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    Abell, F., Krams, M., Ashburner, J., Passingham, R., Friston, K., Frackowiak, R., Happe, F., Frith, C. & Frith, U. The neuroanatomy of autism: a voxel-based whole brain analysis of structural scans {1999} NEUROREPORT
    Vol. {10}({8}), pp. {1647-1651} 
    article  
    Abstract: AUTISM is a biological disorder which affects social cognition, and understanding brain abnormalities of the former will elucidate the brain basis of the latter. We report structural MRI data on 15 high-functioning individuals with autistic disorder. A voxel-based whole brain analysis identified grey matter differences in an amygdala centered system relative to 15 age- and IQ-matched controls. Decreases of grey matter were found in anterior parts of this system (right paracingulate sulcus, left inferior frontal gyrus). Increases were found in posterior parts (amygdala/peri-amygdaloid cortex, middle temporal gyrus, inferior temporal gyrus), and in regions of the cerebellum. These structures are implicated in social cognition by animal, imaging and histopathological studies. This study therefore provides converging evidence of the physiological basis of social cognition. NeuroReport 10:1647-1651 (C) 1999 Lippincott Williams & Wilkins.
    BibTeX:
    @article{Abell1999,
      author = {Abell, F and Krams, M and Ashburner, J and Passingham, R and Friston, K and Frackowiak, R and Happe, F and Frith, C and Frith, U},
      title = {The neuroanatomy of autism: a voxel-based whole brain analysis of structural scans},
      journal = {NEUROREPORT},
      year = {1999},
      volume = {10},
      number = {8},
      pages = {1647-1651}
    }
    
    Adolphs, R. The neurobiology of social cognition {2001} CURRENT OPINION IN NEUROBIOLOGY
    Vol. {11}({2}), pp. {231-239} 
    article  
    Abstract: Recent studies have begun to elucidate the roles played in social cognition by specific neural structures, genes, and neurotransmitter systems. Cortical regions in the temporal robe participate in perceiving socially relevant stimuli, whereas the amygdala, right somatosensory cortices, orbitofrontal cortices, and cingulate cortices all participate in linking perception of such stimuli to motivation, emotion, and cognition. Open questions remain about the domain-specificity of social cognition, about its overlap with emotion and with communication, and about the methods best suited for its investigation.
    BibTeX:
    @article{Adolphs2001,
      author = {Adolphs, R},
      title = {The neurobiology of social cognition},
      journal = {CURRENT OPINION IN NEUROBIOLOGY},
      year = {2001},
      volume = {11},
      number = {2},
      pages = {231-239}
    }
    
    Aghajanian, G. & Marek, G. Serotonin induces excitatory postsynaptic potentials in apical dendrites of neocortical pyramidal cells {1997} NEUROPHARMACOLOGY
    Vol. {36}({4-5}), pp. {589-599} 
    article  
    Abstract: By intracellular and whole cell recording in rat brain slices, it was found that bath-applied serotonin (5-HT) produces an increase in the frequency and amplitude of spontaneous excitatory postsynaptic potentials/currents (EPSPs/EPSCs) in layer V pyramidal cells of neocortex and transitional cortex (e.g. medial prefrontal, cingulate and frontoparietal). The EPSCs were suppressed by LY293558, an antagonist selective for the AMPA subtype of excitatory amino acid receptor, and by two selective 5-HT2A receptor antagonists, MDL 100907 and SR 46349B. In addition, the EPSCs were suppressed by the fast sodium channel blocker tetrodotoxin (TTX) and were dependent upon external calcium. However, despite being TTX-sensitive and calcium dependent, there was no evidence that the EPSPs resulted from an increase in impulse flow in excitatory neuronal afferents to layer V pyramidal cells. The EPSCs could be induced rapidly by the microiontophoresis of 5-HT directly to `'hot spots'' within the apical (but not basilar) dendritic field of recorded neurons, indicating that excitatory amino acids may be released by a TTX-sensitive focal action of 5-HT on a subset of glutamatergic terminals in this region. Consistent with such a presynaptic action, the inhibitory metabotropic glutamate receptor agonist (1S,3S)-aminocyclopentane-1,3-dicarboxylate markedly reduced the induction of EPSPs by 5-HT. Postsynaptically, 5-HT enhanced a subthreshold TTX-sensitive sodium current, potentially contributing to an amplification of EPSC amplitudes. These data suggest 5-HT, via 5-HT2A receptors, enhances spontaneous EPSPs/EPSCs in neocortical layer V pyramidal cells through a TTX-sensitive focal action in the apical dendritic field which may involve both pre- and postsynaptic mechanisms. (C) 1997 Elsevier Science Ltd.
    BibTeX:
    @article{Aghajanian1997,
      author = {Aghajanian, GK and Marek, GJ},
      title = {Serotonin induces excitatory postsynaptic potentials in apical dendrites of neocortical pyramidal cells},
      journal = {NEUROPHARMACOLOGY},
      year = {1997},
      volume = {36},
      number = {4-5},
      pages = {589-599}
    }
    
    Albert, M., Moss, M., Tanzi, R. & Jones, K. Preclinical prediction of AD using neuropsychological tests {2001} JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
    Vol. {7}({5}), pp. {631-639} 
    article  
    Abstract: Normals (N = 42) and patients with mild memory difficulty (N = 123) were given a neuropsychological test battery, and then followed annually for 3 years to determine which individuals developed sufficient functional change that they met clinical criteria for AD. Twenty-three of the 123 participants with mild memory difficulty converted to a diagnosis of probable Alzheimer's disease (AD) within 3 years of follow-up. Four of the 20 neuropsychological measures obtained at baseline, were useful in discriminating the groups on the basis of their status 3 years after the tests were given. The 4 discriminating tests pertained to assessments of memory and executive function. When the controls were compared to the individuals with memory impairments who ultimately developed AD (the converters), the accuracy of discrimination was 89 based on the neuropsychological measures at baseline. The discrimination of the controls from the individuals with mild memory problems who did not progress to the point where they mel clinical criteria for probable AD over the 3 years of follow-up (the Questionables) was 74% and the discrimination of the questionables from the converters was 80 The specific tests that contributed to these discriminations. in conjunction with recent neuropathological and neuroimaging data from preclinical cases, have implications for which brain regions may be affected during the prodromal phase of AD.
    BibTeX:
    @article{Albert2001,
      author = {Albert, MS and Moss, MB and Tanzi, R and Jones, K},
      title = {Preclinical prediction of AD using neuropsychological tests},
      journal = {JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY},
      year = {2001},
      volume = {7},
      number = {5},
      pages = {631-639}
    }
    
    Allman, J., Hakeem, A., Erwin, J., Nimchinsky, E. & Hof, P. The anterior cingulate cortex - The evolution of an interface between emotion and cognition {2001}
    Vol. {935}UNITY OF KNOWLEDGE: THE CONVERGENCE OF NATURAL AND HUMAN SCIENCE, pp. {107-117} 
    inproceedings  
    Abstract: We propose that the anterior cingulate cortex is a specialization of neocortex rather than a more primitive stage of cortical evolution. Functions central to intelligent behavior, that is, emotional self-control, focused problem solving, error recognition, and adaptive response to changing conditions, are juxtaposed with the emotions in this structure. Evidence of an important role for the anterior cingulate cortex in these functions has accumulated through single-neuron recording, electrical stimulation, EEG, PET, fMRI, and lesion studies. The anterior cingulate cortex contains a class of spindle-shaped neurons that are found only in humans and the great apes, and thus are a recent evolutionary specialization probably related to these functions. The spindle cells appear to be widely connected with diverse parts of the brain and may have a role in the coordination that would be essential in developing the capacity to focus on difficult problems. Furthermore, they emerge postnatally and their survival may be enhanced or reduced by environmental conditions of enrichment or stress, thus potentially influencing adult competence or dysfunction in emotional self-control and problem-solving capacity.
    BibTeX:
    @inproceedings{Allman2001,
      author = {Allman, JM and Hakeem, A and Erwin, JM and Nimchinsky, E and Hof, P},
      title = {The anterior cingulate cortex - The evolution of an interface between emotion and cognition},
      booktitle = {UNITY OF KNOWLEDGE: THE CONVERGENCE OF NATURAL AND HUMAN SCIENCE},
      year = {2001},
      volume = {935},
      pages = {107-117},
      note = {Conference on Unity of Knowledge - the Convergence of Natural and Human Science, NEW YORK, NY, JUN 23-25, 2000}
    }
    
    Amodio, D. & Frith, C. Meeting of minds: the medial frontal cortex and social cognition {2006} NATURE REVIEWS NEUROSCIENCE
    Vol. {7}({4}), pp. {268-277} 
    article DOI  
    Abstract: Social interaction is a cornerstone of human life, yet the neural mechanisms underlying social cognition are poorly understood. Recently, research that integrates approaches from neuroscience and social psychology has begun to shed light on these processes, and converging evidence from neuroimaging studies suggests a unique role for the medial frontal cortex. We review the emerging literature that relates social cognition to the medial frontal cortex and, on the basis of anatomical and functional characteristics of this brain region, propose a theoretical model of medial frontal cortical function relevant to different aspects of social cognitive processing.
    BibTeX:
    @article{Amodio2006,
      author = {Amodio, DM and Frith, CD},
      title = {Meeting of minds: the medial frontal cortex and social cognition},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2006},
      volume = {7},
      number = {4},
      pages = {268-277},
      doi = {{10.1038/nrn1884}}
    }
    
    Anderson, M. & Green, C. Suppressing unwanted memories by executive control {2001} NATURE
    Vol. {410}({6826}), pp. {366-369} 
    article  
    Abstract: Freud proposed that unwanted memories can be forgotten by pushing them into the unconscious, a process called repression(1). The existence of repression has remained controversial for more than a century, in part because of its strong coupling with trauma, and the ethical and practical difficulties of studying such processes in controlled experiments. However, behavioural and neurobiological research on memory and attention shows that people have executive control processes directed at minimizing perceptual distraction(2,3), overcoming interference during short and long-term memory tasks(3-7) and stopping strong habitual responses to stimuli(8-13). Here we show that these mechanisms can be recruited to prevent unwanted declarative memories from entering awareness, and that this cognitive act has enduring consequences for the rejected memories. When people encounter cues that remind them of an unwanted memory and they consistently try to prevent awareness of it, the later recall of the rejected memory becomes more difficult. The forgetting increases with the number of times the memory is avoided, resists incentives for accurate recall and is caused by processes that suppress the memory itself. These results show that executive control processes not uniquely tied to trauma may provide a viable model for repression.
    BibTeX:
    @article{Anderson2001,
      author = {Anderson, MC and Green, C},
      title = {Suppressing unwanted memories by executive control},
      journal = {NATURE},
      year = {2001},
      volume = {410},
      number = {6826},
      pages = {366-369}
    }
    
    ANDERSON, T., JENKINS, I., BROOKS, D., HAWKEN, M., FRACKOWIAK, R. & KENNARD, C. CORTICAL CONTROL OF SACCADES AND FIXATION IN MAN - A PET STUDY {1994} BRAIN
    Vol. {117}({Part 5}), pp. {1073-1084} 
    article  
    Abstract: To identify cortical regions activated during saccades and visual fixation, regional cerebral blood flow (rCBF) was measured in eight healthy subjects using (CO2)-O-15 PET during the performance of three tasks: (i) central fixation; (ii) reflexive saccades to random targets; (iii) remembered saccades to locations of recent target appearance. Significant rCBF increases were identified using analysis of covariance and the t statistic (P < 0.001). Compared with central fixation there was activation of striate and extra-striate cortex, posterior parietal cortex (PPC) and frontal eye fields (FEF) during both reflexive and remembered saccades. During remembered saccades there was additional activation of supplementary motor area (SMA), insula, cingulate, thalamus, midbrain, cerebellum and right superior temporal gyrus (Brodmann's area 22). Compared with the individual saccadic tasks, central fixation activated extensive regions of ventromedial (areas 10, 11 and 32) and anterolateral (areas 8, 9, 10, 45 and 46) prefrontal cortex, and foveal visual cortex. We conclude that FEF and PPC are associated with the generation of both reflexive and remembered saccades, with SMA additionally involved during remembered saccades. Sustained voluntary fixation is mediated by prefrontal cortex.
    BibTeX:
    @article{ANDERSON1994,
      author = {ANDERSON, TJ and JENKINS, IH and BROOKS, DJ and HAWKEN, MB and FRACKOWIAK, RSJ and KENNARD, C},
      title = {CORTICAL CONTROL OF SACCADES AND FIXATION IN MAN - A PET STUDY},
      journal = {BRAIN},
      year = {1994},
      volume = {117},
      number = {Part 5},
      pages = {1073-1084}
    }
    
    Andreasen, N., OLeary, D., Cizadlo, T., Arndt, S., Rezai, K., Ponto, L., Watkins, G. & Hichwa, R. Schizophrenia and cognitive dysmetria: A positron-emission tomography study of dysfunctional prefrontal-thalamic-cerebellar circuitry {1996} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {93}({18}), pp. {9985-9990} 
    article  
    Abstract: Patients suffering from schizophrenia display subtle cognitive abnormalities that may reflect a difficulty in rapidly coordinating the steps that occur in a variety of mental activities. Working interactively with the prefrontal cortex, the cerebellum may play a role in coordinating both motor and cognitive performance. This positron-emission tomography study suggests the presence of a prefrontal-thalamic-cerebellar network that is activated when normal subjects recall complex narrative material, but is dysfunctional in schizophrenic patients when they perform the same task. These results support a role for the cerebellum in cognitive functions and suggest that patients with schizophrenia may suffer from a `'cognitive dysmetria'' due to dysfunctional prefrontal-thalamic-cerebellar circuitry.
    BibTeX:
    @article{Andreasen1996,
      author = {Andreasen, NC and OLeary, DS and Cizadlo, T and Arndt, S and Rezai, K and Ponto, LLB and Watkins, GL and Hichwa, RD},
      title = {Schizophrenia and cognitive dysmetria: A positron-emission tomography study of dysfunctional prefrontal-thalamic-cerebellar circuitry},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1996},
      volume = {93},
      number = {18},
      pages = {9985-9990}
    }
    
    ANDREASEN, N., OLEARY, D., CIZADLO, T., ARNDT, S., REZAI, K., WATKINS, L., PONTO, L. & HICHWA, R. REMEMBERING THE PAST - 2 FACETS OF EPISODIC MEMORY EXPLORED WITH POSITRON EMISSION TOMOGRAPHY {1995} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {152}({11}), pp. {1576-1585} 
    article  
    Abstract: Objective: This study used positron emission tomography to examine two kinds of personal memory that are used in psychiatric evaluation: focused episodic memory (recall of past experience, employed in `'taking a history'') and random episodic memory (uncensored thinking about experience, examined during analytic therapy using free association). For comparison, a third memory task was used to tap impersonal memory that represents general information about the world (''semantic memory''). Method: Thirteen subjects were studied using the [O-15]H2O method to obtain quantitative measurements of cerebral blood flow. The three conditions were subtracted and their relative relationships examined. Results: The random episodic condition produced activations in widely distributed association cortex (right and left frontal, parietal, angular/supramarginal, and posterior inferior temporal regions). Focused episodic memory engaged a network that included the medial inferior frontal region, precuneus/retrosplenial cingulate, anterior cingulate, thalamus, and cerebellum. The use of medial frontal regions and the precuneus/retrosplenial cingulate was common to both focused and random episodic memory. The major difference between semantic and episodic memory was activation of Broca's area and the left frontal operculum by semantic memory. Conclusions: These results indicate that free-ranging mental activity (random episodic memory) produces large activations in association cortex and may reflect both active retrieval of past experiences and planning of future experiences. Focused episodic memory shares some components of this circuit (inferior frontal and precuneus), which may reflect the time-linked components of both aspects of episodic memory, and which permit human beings to experience personal identity, consciousness, and self-awareness.
    BibTeX:
    @article{ANDREASEN1995,
      author = {ANDREASEN, NC and OLEARY, DS and CIZADLO, T and ARNDT, S and REZAI, K and WATKINS, L and PONTO, LLB and HICHWA, RD},
      title = {REMEMBERING THE PAST - 2 FACETS OF EPISODIC MEMORY EXPLORED WITH POSITRON EMISSION TOMOGRAPHY},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {1995},
      volume = {152},
      number = {11},
      pages = {1576-1585}
    }
    
    Andreasen, N., OLeary, D., Flaum, M., Nopoulos, P., Watkins, G., Ponto, L. & Hichwa, R. Hypofrontality in schizophrenia: Distributed dysfunctional circuits in neuroleptic-naive patients {1997} LANCET
    Vol. {349}({9067}), pp. {1730-1734} 
    article  
    Abstract: Background There have been reports that patients with schizophrenia have decreased metabolic activity in prefrontal cortex. However, findings have been confounded by medication effects, chronic illness, and difficulties of measurement. We aimed to address these problems by examination of cerebral blood flow with positron emission tomography (PET). Methods We studied 17 neuroleptic-native patients at the early stages of illness by means of image analysis and statistical methods that can detect abnormalities at the gyral level. Findings An initial omnibus test with a randomisation analysis indicated that patients differed from normal controls at the 0.06 level. In the follow-up analysis, three separate prefrontal regions had decreased perfusion (lateral, orbital, medial), as well as regions in inferior temporal and parietal cortex that are known to be anatomically connected. Regions with increased perfusion were also identified (eg, thalamus, cerebellum, retrosplenial cingulate), which suggests an imbalance in distributed cortical and subcortical circuits. Interpretation These distributed dysfunctional circuits may form the neural basis of schizophrenia through cognitive impairment of the brain, which prevents it from processing input efficiently and producing output effectively, thereby leading to symptoms such as hallucinations, delusions, and loss of volition.
    BibTeX:
    @article{Andreasen1997,
      author = {Andreasen, NC and OLeary, DS and Flaum, M and Nopoulos, P and Watkins, GL and Ponto, LLB and Hichwa, RD},
      title = {Hypofrontality in schizophrenia: Distributed dysfunctional circuits in neuroleptic-naive patients},
      journal = {LANCET},
      year = {1997},
      volume = {349},
      number = {9067},
      pages = {1730-1734}
    }
    
    ANDREASEN, N., REZAI, K., ALLIGER, R., SWAYZE, V., FLAUM, M., KIRCHNER, P., COHEN, G. & OLEARY, D. HYPOFRONTALITY IN NEUROLEPTIC-NAIVE PATIENTS AND IN PATIENTS WITH CHRONIC-SCHIZOPHRENIA - ASSESSMENT WITH XE-133 SINGLE-PHOTON EMISSION COMPUTED-TOMOGRAPHY AND THE TOWER OF LONDON {1992} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {49}({12}), pp. {943-958} 
    article  
    Abstract: The ``hypofrontality hypothesis'' has been supported by many neuroimaging studies, but not all, perhaps because of heterogeneity of samples. The present study examined three different samples that permitted assessment of a variety of confounders, such as effects of long-term treatment, chronicity of illness, and presenting phenomenology: (1) 13 neuroleptic-naive schizophrenic patients, (2) 23 nonnaive schizophrenic patients who had been relatively chronically ill but were medication free for at least 3 weeks, and (3) 15 healthy normal volunteers. Regional cerebral blood flow was measured using single-photon emission computed tomography with xenon 133 as the tracer. The control condition consisted of looking at undulating colored shapes on a video monitor, while the experimental task was the Tower of London. We observed the Tower of London to be a relatively specific stimulant of the left mesial frontal cortex (probably including parts of the cingulate gyrus) in healthy normal volunteers. Both the neuroleptic-naive and the nonnaive patients lacked this area of activation, as well as a related one in the right parietal cortex (representing the circuitry specifically activated by the Tower of London). Decreased activation occurred only in the patients with high scores for negative symptoms. These results suggest that hypofrontality is related to negative symptoms and is not a long-term effect of neuroleptic treatment or of chronicity of illness.
    BibTeX:
    @article{ANDREASEN1992,
      author = {ANDREASEN, NC and REZAI, K and ALLIGER, R and SWAYZE, VW and FLAUM, M and KIRCHNER, P and COHEN, G and OLEARY, DS},
      title = {HYPOFRONTALITY IN NEUROLEPTIC-NAIVE PATIENTS AND IN PATIENTS WITH CHRONIC-SCHIZOPHRENIA - ASSESSMENT WITH XE-133 SINGLE-PHOTON EMISSION COMPUTED-TOMOGRAPHY AND THE TOWER OF LONDON},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1992},
      volume = {49},
      number = {12},
      pages = {943-958}
    }
    
    Apkarian, A., Bushnell, M., Treede, R. & Zubieta, J. Human brain mechanisms of pain perception and regulation in health and disease {2005} EUROPEAN JOURNAL OF PAIN
    Vol. {9}({4}), pp. {463-484} 
    article DOI  
    Abstract: Context: The perception of pain due to an acute injury or in clinical pain states undergoes substantial processing at supraspinal levels. Supraspinal, brain mechanisms are increasingly recognized as playing a major role in the representation and modulation of pain experience, These neural mechanisms may then contribute to interindividual variations and disabilities associated with chronic pain conditions. Objective: To systematically review the literature regarding how activity in diverse brain regions creates and modulates the experience of acute and chronic pain states, emphasizing the contribution of various imaging techniques to emerging concepts. Data Sources: MEDLINE and PRE-MEDLINE searches were performed to identify all English-language articles that examine human brain activity during pain, using hemodynamic (PET, fMRI), neuroelectrical (EEG, MEG) and neurochemical methods (MRS, receptor binding and neurotransmitter modulation), from January 1, 1988 to March 1, 2003. Additional studies were identified through bibliographies. Study Selection: Studies were selected based on consensus across all four authors. The criteria included well-designed experimental procedures, as well as landmark studies that have significantly advanced the field. Data Synthesis: Sixty-eight hemodynamic studies of experimental pain in normal subjects, 30 in clinical pain conditions, and 30 using neuroelectrical methods met selection criteria and were used in a meta-analysis. Another 24 articles were identified where brain neurochemistry of pain was examined. Technical issues that may explain differences between studies across laboratories are expounded. The evidence for and the respective incidences of brain areas constituting the brain network for acute pain are presented. The main components of this network are: primary and secondary somatosensory, insular, anterior cingulate, and prefrontal cortices (S1, S2, IC, ACC, PFC) and thalamus (Th). Evidence for somatotopic organization, based on 10 studies, and psychological modulation, based on 20 studies, is discussed, as well as the temporal sequence of the afferent volley to the cortex, based on neuroelectrical studies. A meta-analysis highlights important methodological differences in identifying the brain network underlying acute pain perception. It also shows that the brain network for acute pain perception in normal subjects is at least partially distinct from that seen in chronic clinical pain conditions and that chronic pain engages brain regions critical for cognitive/emotional assessments, implying that this component of pain may be a distinctive feature between chronic and acute pain. The neurochemical studies highlight the role of opiate and catecholamine transmitters and receptors in pain states, and in the modulation of pain with environmental and genetic influences. Conclusions: The nociceptive system is now recognized as a sensory system in its own right, from primary afferents to multiple brain areas. Pain experience is strongly modulated by interactions of ascending and descending pathways. Understanding these modulatory mechanisms in health and in disease is critical for developing fully effective therapies for the treatment of clinical pain conditions. (c) 2004 Published by Elsevier Ltd on behalf of European Federation of Chapters of the International Association for the Study of Pain.
    BibTeX:
    @article{Apkarian2005,
      author = {Apkarian, AV and Bushnell, MC and Treede, RD and Zubieta, JK},
      title = {Human brain mechanisms of pain perception and regulation in health and disease},
      journal = {EUROPEAN JOURNAL OF PAIN},
      year = {2005},
      volume = {9},
      number = {4},
      pages = {463-484},
      doi = {{10.1016/j.ejpain.2004.11.001}}
    }
    
    Arnsten, A. Catecholamine regulation of the prefrontal cortex {1997} JOURNAL OF PSYCHOPHARMACOLOGY
    Vol. {11}({2}), pp. {151-162} 
    article  
    Abstract: The catecholamines dopamine (DA) and norepinephrine provide an essential modulatory influence on the working memory and attentional functions of the prefrontal cortex (PFC). The following critique reviews evidence that (1) either insufficient or excessive DA D-1 receptor stimulation is detrimental to PFC function, while DA stimulation of the D-2 family of receptors may contribute to detrimental actions in PFC and (2) that norepinephrine has an important beneficial influence on PFC function through its actions at post-synaptic, alpha(2A) adrenergic receptors, but impairs PFC function through actions at alpha(1) receptors. Critical levels of catecholamine stimulation may be needed to optimize PFC cognitive function; high levels of catecholamine release during stress may serve to take the PFC `off-line' to allow faster, more habitual responses mediated by the posterior and/or subcortical structures to regulate behavior. These studies have relevance to our understanding and treatment of disorders with prominent symptoms of PFC dysfunction.
    BibTeX:
    @article{Arnsten1997,
      author = {Arnsten, AFT},
      title = {Catecholamine regulation of the prefrontal cortex},
      journal = {JOURNAL OF PSYCHOPHARMACOLOGY},
      year = {1997},
      volume = {11},
      number = {2},
      pages = {151-162}
    }
    
    Ashby, F., Alfonso-Reese, L., Turken, A. & Waldron, E. A neuropsychological theory of multiple systems in category learning {1998} PSYCHOLOGICAL REVIEW
    Vol. {105}({3}), pp. {442-481} 
    article  
    Abstract: A neuropsychological theory is proposed that assumes category learning is a competition between separate verbal and implicit (i.e., procedural-learning-based) categorization systems. The theory assumes that the caudate nucleus is an important component of the implicit system and that the anterior cingulate and prefrontal cortices are critical to the verbal system. In addition to making predictions for normal human adults, the theory makes specific predictions for children, elderly people, and patients suffering from Parkinson's disease, Huntington's disease, major depression, amnesia, or lesions of the prefrontal cortex. Two separate formal descriptions of the theory are also provided. One describes trial-by-trial learning, and the other describes global dynamics. The theory is tested on published neuropsychological data and on category learning data with normal adults.
    BibTeX:
    @article{Ashby1998,
      author = {Ashby, FG and Alfonso-Reese, LA and Turken, AU and Waldron, EM},
      title = {A neuropsychological theory of multiple systems in category learning},
      journal = {PSYCHOLOGICAL REVIEW},
      year = {1998},
      volume = {105},
      number = {3},
      pages = {442-481}
    }
    
    Ashby, F., Isen, A. & Turken, U. A neuropsychological theory of positive affect and its influence on cognition {1999} PSYCHOLOGICAL REVIEW
    Vol. {106}({3}), pp. {529-550} 
    article  
    Abstract: Positive affect systematically influences performance on many cognitive tasks. A new neuropsychological theory is proposed that accounts for many of these effects by assuming that positive affect is associated with increased brain dopamine levels. The theory predicts or accounts for influences of positive affect on olfaction, the consolidation of long-term (i.e., episodic) memories, working memory, and creative problem solving. For example, the theory assumes that creative problem solving is improved, in part, because increased dopamine release in the anterior cingulate improves cognitive flexibility and facilitates the selection of cognitive perspective.
    BibTeX:
    @article{Ashby1999,
      author = {Ashby, FG and Isen, AM and Turken, U},
      title = {A neuropsychological theory of positive affect and its influence on cognition},
      journal = {PSYCHOLOGICAL REVIEW},
      year = {1999},
      volume = {106},
      number = {3},
      pages = {529-550}
    }
    
    Astafiev, S., Shulman, G., Stanley, C., Snyder, A., Van Essen, D. & Corbetta, M. Functional organization of human intraparietal and frontal cortex for attending, looking, and pointing {2003} JOURNAL OF NEUROSCIENCE
    Vol. {23}({11}), pp. {4689-4699} 
    article  
    Abstract: We studied the functional organization of human posterior parietal and frontal cortex using functional magnetic resonance imaging ( fMRI) to map preparatory signals for attending, looking, and pointing to a peripheral visual location. The human frontal eye field and two separate regions in the intraparietal sulcus were similarly recruited in all conditions, suggesting an attentional role that generalizes across response effectors. However, the preparation of a pointing movement selectively activated a different group of regions, suggesting a stronger role in motor planning. These regions were lateralized to the left hemisphere, activated by preparation of movements of either hand, and included the inferior and superior parietal lobule, precuneus, and posterior superior temporal sulcus, plus the dorsal premotor and anterior cingulate cortex anteriorly. Surface-based registration of macaque cortical areas onto the map of fMRI responses suggests a relatively good spatial correspondence between human and macaque parietal areas. In contrast, large interspecies differences were noted in the topography of frontal areas.
    BibTeX:
    @article{Astafiev2003,
      author = {Astafiev, SV and Shulman, GL and Stanley, CM and Snyder, AZ and Van Essen, DC and Corbetta, M},
      title = {Functional organization of human intraparietal and frontal cortex for attending, looking, and pointing},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2003},
      volume = {23},
      number = {11},
      pages = {4689-4699}
    }
    
    Aston-Jones, G. & Cohen, J. An integrative theory of locus coeruleus-norepinephrine function: Adaptive gain and optimal performance {2005} ANNUAL REVIEW OF NEUROSCIENCE
    Vol. {28}, pp. {403-450} 
    article DOI  
    Abstract: Historically, the locus coeruleus-norepinephrine (LC-NE) system has been implicated in arousal, but recent findings suggest that this system plays a more complex and specific role in the control of behavior than investigators previously thought. We review neurophysiological and modeling studies in monkey that support a new theory of LC-NE function. LC neurons exhibit two modes of activity, phasic and tonic. Phasic LC activation is driven by the outcome of task-related decision processes and is proposed to facilitate ensuing behaviors and to help optimize task performance (exploitation). When utility in the task wanes, LC neurons exhibit a tonic activity mode, associated with disengagement from the current task and a search for alternative behaviors (exploration). Monkey LC receives prominent, direct inputs from the anterior cingulate (ACC) and orbitofrontal cortices (OFC), both of which are thought to monitor task-related utility. We propose that these frontal areas produce the above patterns of LC activity to optimize utility on both short and long timescales.
    BibTeX:
    @article{Aston-Jones2005,
      author = {Aston-Jones, G and Cohen, JD},
      title = {An integrative theory of locus coeruleus-norepinephrine function: Adaptive gain and optimal performance},
      journal = {ANNUAL REVIEW OF NEUROSCIENCE},
      year = {2005},
      volume = {28},
      pages = {403-450},
      doi = {{10.1146/annurev.neuro.28.061604.135709}}
    }
    
    Augustine, J. Circuitry and functional aspects of the insular lobe in primates including humans {1996} BRAIN RESEARCH REVIEWS
    Vol. {22}({3}), pp. {229-244} 
    article  
    Abstract: The progress made in understanding the insula in the decade following an earlier review (Augustine, Neurol. Res., 7 (1985) 2-10) is examined in this review. In these ten years, connections have been described between the insula and the orbital cortex, frontal operculum, lateral premotor cortex, ventral granular cortex, and medial area 6 in the frontal lobe. Insular connections between the second somatosensory area and retroinsular area of the parietal lobe have been documented. The insula was found to connect with the temporal pole and the superior temporal sulcus of the temporal lobe. It has an abundance of local intrainsular connections and projections to subdivisions of the cingulate gyrus. The insula has connections with the lateral, lateral basal, central, cortical and medial amygdaloid nuclei. It also connects with nonamygdaloid areas such as the perirhinal cortex, entorhinal, and periamygdaloid cortex. The thalamic taste area, the parvicellular part of the ventral posteromedial nucleus, projects fibers to the ipsilateral insular-opercular cortex. In the past decade, confirmation has been given to the insula as a visceral sensory area, visceral motor area, motor association area, vestibular area, and language area. Recent studies have expanded the role of the insula as a somatosensory area, emphasizing its multifaceted, sensory role. The idea of the insula as limbic integration cortex has been affirmed and its role in Alzheimer's disease suggested.
    BibTeX:
    @article{Augustine1996,
      author = {Augustine, JR},
      title = {Circuitry and functional aspects of the insular lobe in primates including humans},
      journal = {BRAIN RESEARCH REVIEWS},
      year = {1996},
      volume = {22},
      number = {3},
      pages = {229-244}
    }
    
    BAHN, S., VOLK, B. & WISDEN, W. KAINATE RECEPTOR GENE-EXPRESSION IN THE DEVELOPING RAT-BRAIN {1994} JOURNAL OF NEUROSCIENCE
    Vol. {14}({9}), pp. {5525-5547} 
    article  
    Abstract: Kainate-preferring receptors are a subclass of ionotropic glutamate receptors that might play a role in brain development. The expression of the five known genes encoding kainate receptor subunits (GluR-5, -6, -7, KA-1, and KA-2) was studied by in situ hybridization during pre- and postnatal development of the rat brain. We compared the combined expression patterns of these genes with autoradiography using H-3-kainate in the developing brain from embryonic day 12 (E12) through to adult. Although mRNAs for the receptor subunits (except KA-1) can be detected at stage E12, H-3- kainic acid binding (as an index of receptor protein) is not found at this stage. However, by E14 high-affinity kainate sites are found throughout the gray matter, but particularly in spinal cord, primordial cerebellum, and ventral forebrain structures. All genes undergo a peak in their expression in the late embryonic/early postnatal period. GluR-5 expression during development shows the most interesting features because the changes are qualitative. The GluR-5 gene shows peaks of expression around the period of birth in the sensory cortex (layers II, III, and IV), in CA1 hippocampal interneurons in the stratum oriens, in the septum, and in the thalamus. GluR-6 shows a prenatal expression peak in the cingulate gyrus of the neocortex. KA-1 transcripts appear with the development of the hippocampus and remain largely confined to discrete areas such as the CA3 region, the dentate gyrus, and subiculum. KA-2 transcripts are found throughout the CNS from as early as E12 and remain constant until adulthood. The GluR-5 and GluR-6 genes are coexpressed in multiple peripheral ganglia (e.g., cranial nerve ganglia, dorsal root ganglia, and mural ganglia) at E14.
    BibTeX:
    @article{BAHN1994,
      author = {BAHN, S and VOLK, B and WISDEN, W},
      title = {KAINATE RECEPTOR GENE-EXPRESSION IN THE DEVELOPING RAT-BRAIN},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1994},
      volume = {14},
      number = {9},
      pages = {5525-5547}
    }
    
    Baker, S., Rogers, R., Owen, A., Frith, C., Dolan, R., Frackowiak, R. & Robbins, T. Neural systems engaged by planning: A PET study of the Tower of London task {1996} NEUROPSYCHOLOGIA
    Vol. {34}({6}), pp. {515-526} 
    article  
    Abstract: The functional anatomy of planning was investigated using the Tower of London task. Activation was observed in a distributed network of cortical areas incorporating prefrontal, cingulate, premotor, parietal and occipital cortices. Activation in corresponding areas has been observed in visuospatial working memory tasks with the exception of the rostral prefrontal cortex. This area may be identified with the executive components of planning comprising response selection and evaluation. Enhanced neural activity in both this rostral prefrontal area and the visuospatial working memory system was associated with increased task difficulty. Copyright (C) 1996 Elsevier Science Ltd.
    BibTeX:
    @article{Baker1996,
      author = {Baker, SC and Rogers, RD and Owen, AM and Frith, CD and Dolan, RJ and Frackowiak, RSJ and Robbins, TW},
      title = {Neural systems engaged by planning: A PET study of the Tower of London task},
      journal = {NEUROPSYCHOLOGIA},
      year = {1996},
      volume = {34},
      number = {6},
      pages = {515-526}
    }
    
    Bantick, S., Wise, R., Ploghaus, A., Clare, S., Smith, S. & Tracey, I. Imaging how attention modulates pain in humans using functional MRI {2002} BRAIN
    Vol. {125}({Part 2}), pp. {310-319} 
    article  
    Abstract: Current clinical and experimental literature strongly supports the phenomenon of reduced pain perception whilst attention is distracted away from noxious stimuli. This study used functional MRI to elucidate the underlying neural systems and mechanisms involved. An analogue of the Stroop task, the counting Stroop, was used as a cognitive distraction task whilst subjects received intermittent painful thermal stimuli. Pain intensity scores were significantly reduced when subjects took part in the more cognitively demanding interference task of the counting Stroop than in the less demanding neutral task. When subjects were distracted during painful stimulation, brain areas associated with the affective division of the anterior cingulate cortex (ACC) and orbitofrontal regions showed increased activation. In contrast, many areas of the pain matrix (i.e. thalamus, insula, cognitive division of the ACC) displayed reduced activation, supporting the behavioural results of reduced pain perception.
    BibTeX:
    @article{Bantick2002,
      author = {Bantick, SJ and Wise, RG and Ploghaus, A and Clare, S and Smith, SM and Tracey, I},
      title = {Imaging how attention modulates pain in humans using functional MRI},
      journal = {BRAIN},
      year = {2002},
      volume = {125},
      number = {Part 2},
      pages = {310-319}
    }
    
    Barbas, H. Connections underlying the synthesis of cognition, memory, and emotion in primate prefrontal cortices {2000} BRAIN RESEARCH BULLETIN
    Vol. {52}({5}), pp. {319-330} 
    article  
    Abstract: Distinct domains of the prefrontal cortex in primates have a set of connections suggesting that they have different roles in cognition, memory, and emotion. Caudal lateral prefrontal areas (areas 8 and 46) receive projections from cortices representing early stages in visual or auditory processing, and from intraparietal and posterior cingulate areas associated with oculomotor guidance and attentional processes. Cortical input to areas 46 and 8 is complemented by projections from the thalamic multiform and parvicellular sectors of the mediodorsal nucleus associated with oculomotor functions and working memory. In contrast, caudal orbitofrontal areas receive diverse input from cortices representing late stages of processing within every unimodal sensory cortical system. In addition, orbitofrontal and caudal medial(limbic) prefrontal cortices receive robust projections from the amygdala, associated with emotional memory, and from medial temporal and thalamic structures associated with long-term memory. Prefrontal cortices are linked with motor control structures related to their specific roles in central executive functions. Caudal lateral prefrontal areas project to brainstem oculomotor structures, and are connected with premotor cortices effecting head, limb and body movements. In contrast, medial prefrontal and orbitofrontal limbic cortices project to hypothalamic visceromotor centers for the expression of emotions. Lateral, orbitofrontal, and medial prefrontal cortices are robustly interconnected, suggesting that they participate in concert in central executive functions. Prefrontal limbic cortices issue widespread projections through their deep layers and terminate in the upper layers of lateral (eulaminate) cortices, suggesting a predominant role in feedback communication. In contrast, when lateral prefrontal cortices communicate with limbic areas they issue projections from their upper layers and their axons terminate in the deep layers, suggesting a role in feedforward communication. Through their widespread connections, prefrontal limbic cortices may exercise a tonic influence on lateral prefrontal cortices, inextricably linking areas associated with cognitive and emotional processes. The integration of cognitive, mnemonic and emotional processes is likely to be disrupted in psychiatric and neurodegenerative diseases which preferentially affect limbic cortices and consequently disconnect major feedback pathways to the neuraxis, (C) 2000 Elsevier Science Inc.
    BibTeX:
    @article{Barbas2000,
      author = {Barbas, H},
      title = {Connections underlying the synthesis of cognition, memory, and emotion in primate prefrontal cortices},
      journal = {BRAIN RESEARCH BULLETIN},
      year = {2000},
      volume = {52},
      number = {5},
      pages = {319-330},
      note = {Meeting on Human Cerebral Cortex - From Gene to Structure and Function, AMSTERDAM, NETHERLANDS, APR 25, 1998}
    }
    
    Barch, D., Braver, T., Nystrom, L., Forman, S., Noll, D. & Cohen, J. Dissociating working memory from task difficulty in human prefrontal cortex {1997} NEUROPSYCHOLOGIA
    Vol. {35}({10}), pp. {1373-1380} 
    article  
    Abstract: A functional magnetic resonance imaging (fMRI) study was conducted to determine whether prefrontal cortex (PFC) increases activity in working memory (WM) tasks as a specific result of the demands placed on WM, or to other processes affected by the greater difficulty of such tasks. Increased activity in dorsolateral PFC (DLPFC) was observed during task conditions that placed demands on active maintenance (long retention interval) relative to control conditions matched for difficulty. Furthermore, the activity was sustained over the entire retention interval and did not increase when task difficulty was manipulated independently of WM requirements. This contrasted with the transient increases in activity observed in the anterior cingulate, and other regions of frontal cortex, in response to increased task difficulty but not WM demands. Thus, this study established a double-dissociation between regions responsive to WM versus task difficulty, indicating a specific involvement of DLPFC and related structures in WM function. (C) 1997 Elsevier Science Ltd.
    BibTeX:
    @article{Barch1997,
      author = {Barch, DM and Braver, TS and Nystrom, LE and Forman, SD and Noll, DC and Cohen, JD},
      title = {Dissociating working memory from task difficulty in human prefrontal cortex},
      journal = {NEUROPSYCHOLOGIA},
      year = {1997},
      volume = {35},
      number = {10},
      pages = {1373-1380}
    }
    
    Baron, J., Chetelat, G., Desgranges, B., Perchey, G., Landeau, B., de la Sayette, V. & Eustache, F. In vivo mapping of gray matter loss with voxel-based morphometry in mild Alzheimer's disease {2001} NEUROIMAGE
    Vol. {14}({2}), pp. {298-309} 
    article DOI  
    Abstract: Up till now, the study of regional gray matter atrophy in Alzheimer's disease (AD) has been assessed with regions of interest, but this method is time-consuming, observer dependent, and poorly reproducible (especially in terms of cortical regions boundaries) and in addition is not suited to provide a comprehensive assessment of the brain. In this study, we have mapped gray matter density by means of voxel-based morphometry on Tl-weighted MRI volume sets in 19 patients with mild AD and 16 healthy subjects of similar age and gender ratio and report highly significant clusters of gray matter loss with almost symmetrical distribution, affecting mainly and in decreasing order of significance the medial temporal structures, the posterior cingulate gyrus and adjacent precuneus, and the temporoparietal association and perisylvian neocortex, with only little atrophy in the frontal lobe. The findings are discussed in light of previous studies of gray matter atrophy in AD based either on postmortem or neuroimaging data and in relation to PET studies of resting glucose consumption. The limitations of the method are also discussed in some detail, especially with respect to the segmentation and spatial normalization procedures as they apply to pathological brains. Some potential applications of voxel-based morphometry in the study of AD are also mentioned. (C) 2001 Academic Press.
    BibTeX:
    @article{Baron2001,
      author = {Baron, JC and Chetelat, G and Desgranges, B and Perchey, G and Landeau, B and de la Sayette, V and Eustache, F},
      title = {In vivo mapping of gray matter loss with voxel-based morphometry in mild Alzheimer's disease},
      journal = {NEUROIMAGE},
      year = {2001},
      volume = {14},
      number = {2},
      pages = {298-309},
      doi = {{10.1006/nimg.2001.0848}}
    }
    
    Bartels, A. & Zeki, S. The neural basis of romantic love {2000} NEUROREPORT
    Vol. {11}({17}), pp. {3829-3834} 
    article  
    Abstract: The neural correlates of many emotional states have been studied, most recently through the technique of fMRI. However, nothing is known about the neural substrates involved in evoking one of the most overwhelming of all affective states, that of romantic love, about which we report here, The activity in the brains of 17 subjects who were deeply in love was scanned using fMRI, while they viewed pictures of their partners, and compared with the activity produced by viewing pictures of three friends of similar age, sex and duration of friendship as their partners. The activity was restricted to foci in the medial insula and the anterior cingulate cortex and, subcortically, in the caudate nucleus and the putamen, all bilaterally. Deactivations were observed in the posterior cingulate gyrus and in the amygdala and were right-lateralized in the prefrontal, parietal and middle temporal cortices. The combination of these sites differs from those in previous studies of emotion, suggesting that a unique network of areas is responsible for evoking this affective state. This leads us to postulate that the principle of functional specialization in the cortex applies to affective states as well. NeuroReport 11:3829-3834 (C) 2000 Lippincott Williams & Wilkins.
    BibTeX:
    @article{Bartels2000,
      author = {Bartels, A and Zeki, S},
      title = {The neural basis of romantic love},
      journal = {NEUROREPORT},
      year = {2000},
      volume = {11},
      number = {17},
      pages = {3829-3834}
    }
    
    BATES, J. & GOLDMANRAKIC, P. PREFRONTAL CONNECTIONS OF MEDIAL MOTOR AREAS IN THE RHESUS-MONKEY {1993} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {336}({2}), pp. {211-228} 
    article  
    Abstract: Several areas on the medial surface of the frontal lobe in both monkeys and humans, including the supplementary motor area and specific areas within the ventral bank of the cingulate sulcus called the cingulate motor areas, have been implicated in the initiation and execution of skilled movements. These areas project directly to the motor cortex and spinal cord, and, on this basis alone, can be considered premotor areas. The present study investigated whether these premotor areas are specific targets of prefrontal cortical projections in the rhesus monkey and thereby provide links between this association cortex and motor effector pathways. Circumscribed injections of wheat germ agglutinin-conjugated horseradish peroxidase were placed into different cytoarchitectonic subdivisions of prefrontal cortex, and resultant retrograde and anterograde labeling examined with respect to designated premotor targets. Conversely, injections were also made in the supplementary and cingulate motor areas and labeled cells and terminals charted in the prefrontal cortex. A principal finding in this study is the identification of multiple prefrontal regions that project to the supplementary motor area, the cingulate motor areas, or both. Areas 46, 8a, 9, 11, and 12 are reciprocally connected with an area of the superior frontal gyrus in or near the supplementary motor area at its rostral margin. A smaller constellation of prefrontal areas, areas 46, 8a, and 11, is reciprocally connected with portions of cingulate cortex that have been classified as premotor arm and/or leg representations (Hutchins et al., Exp Brain Res 71:667-672, 1988). In accordance with numerous previous reports, prefrontal areas 46, 8a, 9, 10, 11, and 12 are reciprocally connected with `'nonmotor'' subdivisions of cingulate cortex. The results presented here specify the corticocortical connections by which prefrontal cortex may influence motor output. (C) 1993 Wiley-Liss, Inc.
    BibTeX:
    @article{BATES1993,
      author = {BATES, JF and GOLDMANRAKIC, PS},
      title = {PREFRONTAL CONNECTIONS OF MEDIAL MOTOR AREAS IN THE RHESUS-MONKEY},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {1993},
      volume = {336},
      number = {2},
      pages = {211-228}
    }
    
    BAUDENA, P., HALGREN, E., HEIT, G. & CLARKE, J. INTRACEREBRAL POTENTIALS TO RARE TARGET AND DISTRACTER AUDITORY AND VISUAL-STIMULI .3. FRONTAL-CORTEX {1995} ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
    Vol. {94}({4}), pp. {251-264} 
    article  
    Abstract: Evoked potentials (EPs) were recorded from 991 frontal and peri-rolandic sites (106 electrodes) in 36 patients during an auditory discrimination task with target and non-target (distracter) rare stimuli. Variants of this task explored the effects of attention, dishabituation and stimulus characteristics (including modality). Rare stimuli evoked a widespread triphasic waveform with negative, positive and negative peaks at about 210, 280 and 390 msec, respectively. This waveform was identified with the scalp EP complex termed the N2a/P3a/slow wave and associated with orienting. It was evoked by rare target and distracter auditory and visual stimuli, as well as by rare stimulus repetitions or omissions. Across most frontal trajectories, N2a/P3a/SW amplitudes changed only slowly with distance. However, large (120 mu V) P3as with steep voltage gradients were observed laterally, especially near the inferior frontal sulcus, and clear inversions of the P3a were noted in the orbito-frontal and the anterior cingulate cortices. The frontal P3a was earlier to distracter than to target stimuli, but only in some sites and with a latency difference much smaller than that observed at the scalp. Frontal P3a latencies were significantly shorter than those recorded simultaneously at the scalp and often were also shorter than P3a latency in the parietal or temporal lobes. In summary, this study demonstrates an early P3a-like activity that polarity inverts over short distances in the medial frontal lobe, and that it has a significantly shorter latency than similar potentials recorded in the temporal and parietal cortices.
    BibTeX:
    @article{BAUDENA1995,
      author = {BAUDENA, P and HALGREN, E and HEIT, G and CLARKE, JM},
      title = {INTRACEREBRAL POTENTIALS TO RARE TARGET AND DISTRACTER AUDITORY AND VISUAL-STIMULI .3. FRONTAL-CORTEX},
      journal = {ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY},
      year = {1995},
      volume = {94},
      number = {4},
      pages = {251-264}
    }
    
    Beauregard, M., Levesque, J. & Bourgouin, P. Neural correlates of conscious self-regulation of emotion {2001} JOURNAL OF NEUROSCIENCE
    Vol. {21}({18}) 
    article  
    Abstract: A fundamental question about the relationship between cognition and emotion concerns the neural substrate underlying emotional self-regulation. To address this issue, brain activation was measured in normal male subjects while they either responded in a normal manner to erotic film excerpts or voluntarily attempted to inhibit the sexual arousal induced by viewing erotic stimuli. Results demonstrated that the sexual arousal experienced, in response to the erotic film excerpts, was associated with activation in ``limbic'' and paralimbic structures, such as the right amygdala, right anterior temporal pole, and hypothalamus. In addition, the attempted inhibition of the sexual arousal generated by viewing the erotic stimuli was associated with activation of the right superior frontal gyrus and right anterior cingulate gyrus. No activation was found in limbic areas. These findings reinforce the view that emotional self-regulation is normally implemented by a neural circuit comprising various prefrontal regions and subcortical limbic structures. They also suggest that humans have the capacity to influence the electrochemical dynamics of their brains, by voluntarily changing the nature of the mind processes unfolding in the psychological space.
    BibTeX:
    @article{Beauregard2001,
      author = {Beauregard, M and Levesque, J and Bourgouin, P},
      title = {Neural correlates of conscious self-regulation of emotion},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2001},
      volume = {21},
      number = {18}
    }
    
    BECK, C. & FIBIGER, H. CONDITIONED FEAR-INDUCED CHANGES IN BEHAVIOR AND IN THE EXPRESSION OF THE IMMEDIATE-EARLY GENE C-FOS - WITH AND WITHOUT DIAZEPAM PRETREATMENT {1995} JOURNAL OF NEUROSCIENCE
    Vol. {15}({1, Part 2}), pp. {709-720} 
    article  
    Abstract: The synthesis of Fos, the protein product of the immediate early gene c-fos, was used to map metabolically some of the neural substrates of conditioned fear in the rat. analysis of the behaviors emitted by the rats during the test session provided strong evidence that the conditioning procedure was effective. Exposure to the environment in which they had previously received footshock significantly increased the number of Fos-like immunoreactive neurons in nearly 50 brain regions, both cortical and subcortical. Among the structures showing the most dramatic increases in fear-induced c-fos expression were the cingulate, piriform, infralimbic, and retrosplenial cortices, the anterior olfactory nucleus, claustrum, endopiriform nucleus, nucleus accumbens shell, lateral septal nucleus, various amygdalar nuclei, paraventricular thalamic nucleus, ventral lateral geniculate nucleus, the ventromedial, lateral, and dorsal hypothalamic nuclei, the ventral tegmental area, and the supramammillary area. These data demonstrate that a relatively simple classical conditioning procedure activates a large number of widely dispersed cortical and subcortical structures. Some of the structures showing increased c-fos expression have important autonomic functions and may therefore have reflected centrally mediated changes in blood pressure and respiration produced by the anxiogenic stimuli. In a second experiment, the effects of pretreatment with the anxiolytic drug diazepam (2.5, 5.0, or 10 mg/kg) were evaluated. The benzodiazepine produced dose-related decreases in the frequency of crouching (freezing) elicited by the aversively conditioned contextual cues. Diazepam also produced dose-related decreases in conditioned stress-induced c-fos expression in all but one structure, the effects being statistically significant in 38 of 60 sampled structures. Diazepam dose dependently increased fear-induced c-fos expression in the central nucleus of the amygdala. There was considerable regional variability with respect to sensitivity to diazepam, the retrosplenial cortex and the supramammillary area being the only two structures to show decreases after the lowest dose of diazepam. In contrast, the entorhinal cortex, nucleus accumbens core, ventromedial and posterior hypothalamic nuclei, median raphe, and locus coeruleus were particularly resistant to diazepam, all failing to show statistically significant decreases in conditioned fear-induced c-fos expression even at the highest dose. The extent to which diazepam decreased conditioned stress-induced c-fos expression was unrelated to previous estimates of benzodiazepine receptor density in the sampled structures.
    BibTeX:
    @article{BECK1995,
      author = {BECK, CHM and FIBIGER, HC},
      title = {CONDITIONED FEAR-INDUCED CHANGES IN BEHAVIOR AND IN THE EXPRESSION OF THE IMMEDIATE-EARLY GENE C-FOS - WITH AND WITHOUT DIAZEPAM PRETREATMENT},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1995},
      volume = {15},
      number = {1, Part 2},
      pages = {709-720}
    }
    
    BENCH, C., FRACKOWIAK, R. & DOLAN, R. CHANGES IN REGIONAL CEREBRAL BLOOD-FLOW ON RECOVERY FROM DEPRESSION {1995} PSYCHOLOGICAL MEDICINE
    Vol. {25}({2}), pp. {247-261} 
    article  
    Abstract: We have previously described focal abnormalities of regional cerebral blood flow (rCBF) in the left dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex and angular gyrus in 40 patients with major depression. We now report on the patterns of change in rCBF in a subgroup of 25 of the same patients who were rescanned following clinical remission of depression. Fifteen patients were scanned when optimally matched for drug treatment (4) or drug free on both occasions (11). The other 10 patients were fully recovered but could not be matched for drug status for clinical and ethical reasons. In a paired comparison of the same patients when ill and following recovery it was evident that remission was associated with a significant increase in rCBF in the left DLPFC and medial prefrontal cortex including anterior cingulate. Increases in rCBF in the angular gyrus were not seen when the comparison of depressed and recovered scans was matched for medication. The previously described relationship between clinical symptoms and brain perfusion in the depressed state was no longer present in the recovered state; this supports the hypothesis of state relatedness. Thus, recovery from depression is associated with increases in rCBF in the same areas in which focal decreases in rCBF are described in the depressed state in comparison with normal controls.
    BibTeX:
    @article{BENCH1995,
      author = {BENCH, CJ and FRACKOWIAK, RSJ and DOLAN, RJ},
      title = {CHANGES IN REGIONAL CEREBRAL BLOOD-FLOW ON RECOVERY FROM DEPRESSION},
      journal = {PSYCHOLOGICAL MEDICINE},
      year = {1995},
      volume = {25},
      number = {2},
      pages = {247-261}
    }
    
    BENCH, C., FRISTON, K., BROWN, R., FRACKOWIAK, R. & DOLAN, R. REGIONAL CEREBRAL BLOOD-FLOW IN DEPRESSION MEASURED BY POSITRON EMISSION TOMOGRAPHY - THE RELATIONSHIP WITH CLINICAL DIMENSIONS {1993} PSYCHOLOGICAL MEDICINE
    Vol. {23}({3}), pp. {579-590} 
    article  
    Abstract: We have previously reported focal abnormalities of regional cerebral blood flow (rCBF) in a group of 33 patients with major depression. This report, on an extended sample of 40 patients who demonstrated identical regional deficits to those previously described, examines the relationships between depressive symptoms and patterns of rCBF. Patients' symptom ratings were subjected to factor analysis, producing a three-factor solution. The scores for these three factors, which corresponded to recognizable dimensions of depressive illness, were then correlated with rCBF. The first factor had high loadings for anxiety and correlated positively with rCBF in the posterior cingulate cortex and inferior parietal lobule bilaterally. The second factor had high loadings for psychomotor retardation and depressed mood and correlated negatively with rCBF in the left dorsolateral prefrontal cortex and left angular gyrus. The third factor had a high loading for cognitive performance and correlated positively with rCBF in the left medial prefrontal cortex. These data indicate that symptomatic specificity may be ascribed to regional functional deficits in major depressive illness.
    BibTeX:
    @article{BENCH1993a,
      author = {BENCH, CJ and FRISTON, KJ and BROWN, RG and FRACKOWIAK, RSJ and DOLAN, RJ},
      title = {REGIONAL CEREBRAL BLOOD-FLOW IN DEPRESSION MEASURED BY POSITRON EMISSION TOMOGRAPHY - THE RELATIONSHIP WITH CLINICAL DIMENSIONS},
      journal = {PSYCHOLOGICAL MEDICINE},
      year = {1993},
      volume = {23},
      number = {3},
      pages = {579-590}
    }
    
    BENCH, C., FRISTON, K., BROWN, R., SCOTT, L., FRACKOWIAK, R. & DOLAN, R. THE ANATOMY OF MELANCHOLIA - FOCAL ABNORMALITIES OF CEREBRAL BLOOD-FLOW IN MAJOR DEPRESSION {1992} PSYCHOLOGICAL MEDICINE
    Vol. {22}({3}), pp. {607-615} 
    article  
    Abstract: Using positron emission tomography( PET) and Oxygen-15, regional cerebral blood flow (rCBF) was measured in 33 patients with primary depression, 10 of whom had an associated severe cognitive impairment, and 23 age-matched controls. PET scans from these groups were analysed on a pixel-by-pixel basis and significant differences between the groups were identified on Statistical Parametric Maps (SPMs). In the depressed group as a whole rCBF was decreased in the left anterior cingulate and the left dorsolateral prefrontal cortex (P < 0-05 Bonferroni-corrected for multiple comparisons). Comparing patients with and without depression-related cognitive impairment, in the impaired group there were significant decreases in rCBF in the left medial frontal gyrus and increased rCBF in the cerebellar vermis (P < 0.05 Bonferroni-corrected). Therefore an anatomical dissociation has been described between the rCBF profiles associated with depressed mood and depression-related cognitive impairment. The pre-frontal and limbic areas identified in this study constitute a distributed anatomical network that may be functionally abnormal in major depressive disorder.
    BibTeX:
    @article{BENCH1992,
      author = {BENCH, CJ and FRISTON, KJ and BROWN, RG and SCOTT, LC and FRACKOWIAK, RSJ and DOLAN, RJ},
      title = {THE ANATOMY OF MELANCHOLIA - FOCAL ABNORMALITIES OF CEREBRAL BLOOD-FLOW IN MAJOR DEPRESSION},
      journal = {PSYCHOLOGICAL MEDICINE},
      year = {1992},
      volume = {22},
      number = {3},
      pages = {607-615}
    }
    
    BENCH, C., FRITH, C., GRASBY, P., FRISTON, K., PAULESU, E., FRACKOWIAK, R. & DOLAN, R. INVESTIGATIONS OF THE FUNCTIONAL-ANATOMY OF ATTENTION USING THE STROOP TEST {1993} NEUROPSYCHOLOGIA
    Vol. {31}({9}), pp. {907-922} 
    article  
    Abstract: In two separate experiments positron emission tomography (PET) was used to measure changes in regional cerebral blood flow while normal subjects performed the Stroop colour word interference test, a test of selective attention. In the first experiment performance of the Stroop task was associated with activation of right orbito-frontal and bilateral parietal structures, an unexpected result in view of previously reported findings. In addition, there were highly significant time related focal changes in rCBF. A second experiment was therefore carried out which altered the experimental parameters to replicate an earlier study. In this second experiment focal activation of the right anterior cingulate and right frontal polar cortex occurred during the Stroop task. As in the first experiment significant time effects were again apparent. To determine the functionally related brain systems during the performance of the Stroop task a correlation analysis was carried out in relation to blood flow changes induced by experimental manipulation in the right anterior cingulate. This analysis indicated the engagement of a widespread network of anterior brain regions and reciprocal inhibition of posterior brain regions during the performance of the task. The results provide evidence for the involvement of anterior right hemisphere and medial frontal structures in attentional tasks but also indicate that time effects can confound task specific activations. Furthermore subtle experimental treatment parameters, such as stimulus presentation rate, influence the degree and distribution of observed activations.
    BibTeX:
    @article{BENCH1993,
      author = {BENCH, CJ and FRITH, CD and GRASBY, PM and FRISTON, KJ and PAULESU, E and FRACKOWIAK, RSJ and DOLAN, RJ},
      title = {INVESTIGATIONS OF THE FUNCTIONAL-ANATOMY OF ATTENTION USING THE STROOP TEST},
      journal = {NEUROPSYCHOLOGIA},
      year = {1993},
      volume = {31},
      number = {9},
      pages = {907-922}
    }
    
    Benes, F. Emerging principles of altered neural circuitry in schizophrenia {2000} BRAIN RESEARCH REVIEWS
    Vol. {31}({2-3}), pp. {251-269} 
    article  
    Abstract: This paper presents an overview of recent microscopic studies that have sought to define how limbic circuitry may be altered in postmortem schizophrenic brain, The discussion is organized around several basic questions regarding the manner in which interconnections within and between the anterior cingulate cortex and hippocampal formation and involving the glutamate, GABA and dopamine systems may contribute to the pathophysiology of this disorder. The answers to these questions are used to derive several conclusions regarding circuitry changes in schizophrenia: 1) Schizophrenia is not a `typical' degenerative disorder, but rather it is one in which excitotoxicity may contribute to neuronal pathology, whether or not cell death occurs; 2) Three or more neurotransmitter systems may be simultaneously altered within a single microcircuit; 3) Each transmitter system may show circuitry changes in more than one region, but such changes may vary on a region-by-region basis; 4) The pathophysiology of schizophrenia may involve `mis-wirings' in intrinsic circuits (microcircuitry) within a given region, but significant changes are probably also present at the level of interconnections between two or more regions within a network (macrocircuitry); 5) While some microscopic findings appear to be selectively present in schizophrenia and be related to a susceptibility gene for this disorder, others may also be present in patients with bipolar disorder; 6) Although some of the circuitry changes seen in schizophrenia and bipolar disorder seem to be associated with neuroleptic exposure, most are not and may reflect the influence of non-specific environmental factors such as pre- and/or postnatal stress; 7) Normal postnatal changes at the level of both macro- and microcircuitry within the limbic system may serve as `triggers' for the onset of schizophrenia during adolescence. Taken together, these emerging principles can provide a framework for future postmortem studies of schizophrenic brain. (C) 2000 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{Benes2000,
      author = {Benes, FM},
      title = {Emerging principles of altered neural circuitry in schizophrenia},
      journal = {BRAIN RESEARCH REVIEWS},
      year = {2000},
      volume = {31},
      number = {2-3},
      pages = {251-269},
      note = {Nobel Symposium 111: Schizophrenia - Pathophysiological Mechanisms, STOCKHOLM, SWEDEN, OCT 01-03, 1998}
    }
    
    Benes, F. & Berretta, S. GABAergic interneurons: Implications for understanding schizophrenia and bipolar disorder {2001} NEUROPSYCHOPHARMACOLOGY
    Vol. {25}({1}), pp. {1-27} 
    article  
    Abstract: A core component to corticolimbic circuitry is the GABAergic interneuron. Neuroanatomic studies conducted over the past century have demonstrated several subtypes of interneuron defined by characteristic morphological appearances in Golgi-stained preparations, More recently, both cytochemical and electrophysiological techniques have defined various subtypes of GABA neuron according to synaptic connections, electrophysiological properties and neuropeptide content. These cells provide both inhibitory and disinhibitory modulation of cortical and hippocampal circuits and contribute to the generation of oscillatory rhythms, discriminative information processing and gating of sensory information within the corticolimbic system. All of these functions are abnormal in schizophrenia. Recent postmortem studies have provided consistent evidence that a defect of GABAergic neurotransmission probably plays a role in both schizophrenia and bipolar disorder. Many now believe that such a disturbance may be related to a perturbation of early development, one that may result in a disturbance of cell migration and the formation of normal lamination The ingrowth of extrinsic afferents, such as the mesocortical dopamine projections, may ``trigger'' the appearance of a defective GABA system, particularly under stressful conditions when the modulation of the dopamine system is likely to be altered. Based on the regional and subregional distribution of changes in GABA cells in schizophrenia and bipolar disorder, it has been postulated that the basolateral nucleus oft he amygdala may contribute to these abnormalities through an increased flow of excitatory activity. By using ``partial'' modeling, changes in the GABA system remarkably similar to those seen in schizophrenia and bipolar disorder have been induced in mt hippocampus. In the years to come, continued investigations of the GABA system in rodent, primate and human brain and the characterization of changes in specific phenotypic subclasses of interneurons in schizophrenia and bipolar disorder will undoubtedly provide important new insights into how the integration of this transmitter system may be altered in neuropsychiatric disease. [Neuropsychopharmacology 25:1-27, 2001] (C) 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.
    BibTeX:
    @article{Benes2001,
      author = {Benes, FM and Berretta, S},
      title = {GABAergic interneurons: Implications for understanding schizophrenia and bipolar disorder},
      journal = {NEUROPSYCHOPHARMACOLOGY},
      year = {2001},
      volume = {25},
      number = {1},
      pages = {1-27}
    }
    
    BENES, F. & BIRD, E. AN ANALYSIS OF THE ARRANGEMENT OF NEURONS IN THE CINGULATE CORTEX OF SCHIZOPHRENIC-PATIENTS {1987} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {44}({7}), pp. {608-616} 
    article  
    BibTeX:
    @article{BENES1987,
      author = {BENES, FM and BIRD, ED},
      title = {AN ANALYSIS OF THE ARRANGEMENT OF NEURONS IN THE CINGULATE CORTEX OF SCHIZOPHRENIC-PATIENTS},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1987},
      volume = {44},
      number = {7},
      pages = {608-616}
    }
    
    Benes, F., Kwok, E., Vincent, S. & Todtenkopf, M. Reduction of nonpyramidal cells in sector CA2 of schizophrenics and manic depressives {1998} BIOLOGICAL PSYCHIATRY
    Vol. {44}({2}), pp. {88-97} 
    article  
    BibTeX:
    @article{Benes1998,
      author = {Benes, FM and Kwok, EW and Vincent, SL and Todtenkopf, MS},
      title = {Reduction of nonpyramidal cells in sector CA2 of schizophrenics and manic depressives},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {1998},
      volume = {44},
      number = {2},
      pages = {88-97}
    }
    
    BENES, F., MCSPARREN, J., BIRD, E., SANGIOVANNI, J. & VINCENT, S. DEFICITS IN SMALL INTERNEURONS IN PREFRONTAL AND CINGULATE CORTICES OF SCHIZOPHRENIC AND SCHIZOAFFECTIVE PATIENTS {1991} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {48}({11}), pp. {996-1001} 
    article  
    Abstract: A recent report suggested that neurons in the prefrontal, anterior cingulate, and primary motor cortex of the brains of schizophrenic subjects may be less dense than those in the brains of nonschizophrenic subjects. We have determined whether pyramidal neurons and/or interneurons are preferentially reduced in schizophrenic subjects. Twelve control subjects and 18 schizophrenic subjects were studied in a blind, quantitative analysis of the density of pyramidal cells, interneurons, and glial cells in each of the six layers of the anterior cingulate and prefrontal cortex. The results showed that numbers of small neurons (interneurons) were reduced in most layers of the cingulate cortex in schizophrenic subjects compared with nonschizophrenic subjects, with the differences being greatest in layer II. In the prefrontal area, interneuronal density was also lower in layer II and, to a lesser extent, in layer I in schizophrenic subjects compared with control subjects. In most cases, the differences were similar, although more significant, in schizophrenic subjects who had had superimposed mood disturbances than in schizophrenic subjects who had not had such comorbidity. Numbers of pyramidal neurons generally were not different between control and schizophrenic subjects, except in layer V of the prefrontal area, where schizophrenic subjects showed higher densities of these neurons. Glial numbers did not differ between the control and schizophrenic subjects, suggesting that a neurodegenerative process did not cause the reduced interneuronal density observed. Using multiple regression analysis and analysis of covariance, decreases in the density of layer II interneurons could not be adequately explained by the effects of various confounding variables, such as age, postmortem interval, duration of specimen fixation, or administration of neuroleptic agents. Two younger patients who had not received neuroleptic agents also had reduced numbers of small neurons, suggesting that reduction in numbers of small neurons is not due to the effects of antipsychotic medication. Reductions of interneurons, possibly ones that are inhibitory in nature, may occur within intrinsic cortical circuits, and may be an important aspect of the pathophysiology of schizophrenia.
    BibTeX:
    @article{BENES1991,
      author = {BENES, FM and MCSPARREN, J and BIRD, ED and SANGIOVANNI, JP and VINCENT, SL},
      title = {DEFICITS IN SMALL INTERNEURONS IN PREFRONTAL AND CINGULATE CORTICES OF SCHIZOPHRENIC AND SCHIZOAFFECTIVE PATIENTS},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1991},
      volume = {48},
      number = {11},
      pages = {996-1001}
    }
    
    BENES, F., SORENSEN, I. & BIRD, E. REDUCED NEURONAL SIZE IN POSTERIOR HIPPOCAMPUS OF SCHIZOPHRENIC-PATIENTS {1991} SCHIZOPHRENIA BULLETIN
    Vol. {17}({4}), pp. {597-608} 
    article  
    Abstract: The hippocampus, an integral component of the corticolimbic circuitry of the brain, has been recently implicated in the pathophysiology of schizophrenia. This article has employed quantitative morphometric techniques to determine whether abnormalities of posterior hippocampal cross-sectional area, as well as the number, size, and degree of disarray of pyramidal neurons were present in 9 control and 14 schizophrenic subjects. Seven schizophrenic patients showed evidence of superimposed mood disturbance (schizoaffective type), while the remaining seven were a mixture of paranoid, undifferentiated, and catatonic types. All morphometric measurements were conducted under strictly blind conditions; stepwise multiple regression and analyses of covariance were used to evaluate the effects of various confounding variables. There were no differences in the cross-sectional size of the hippocampus or degree of neuronal disarray between the two groups. Similarly, the number of pyramidal neurons was also the same in sectors Cornu Ammonis (CA) 2, CA 3, and CA 4 for the controls and schizophrenic subjects. In CA 1, the schizophrenic subjects without mood disturbances showed a significant reduction (36 of pyramidal neuron numbers when compared with those of both controls and patients with mood disturbance. Pyramidal neurons were smaller in all sectors of the schizophrenic specimens, CA 1 (p less-than-or-equal-to 0.01), CA 2 (p less-than-or-equal-to 0.01), CA 3 (p less-than-or-equal-to 0.01), and CA 4 (p less-than-or-equal-to 0.005), but there were no differences with respect to the presence of mood disturbances. Corrections for the effects of age, postmortem interval, fixation interval, hypoxia, and neuroleptic exposure did not alter the pattern in the data. The significance of a smaller size of hippocampal pyramidal neurons in this group of schizophrenic specimens is unclear, but it is consistent with the suggestions of other laboratories that there may be altered function of this brain region in chronically psychotic individuals.
    BibTeX:
    @article{BENES1991a,
      author = {BENES, FM and SORENSEN, I and BIRD, ED},
      title = {REDUCED NEURONAL SIZE IN POSTERIOR HIPPOCAMPUS OF SCHIZOPHRENIC-PATIENTS},
      journal = {SCHIZOPHRENIA BULLETIN},
      year = {1991},
      volume = {17},
      number = {4},
      pages = {597-608}
    }
    
    BENES, F., TURTLE, M., KHAN, Y. & FAROL, P. MYELINATION OF A KEY RELAY ZONE IN THE HIPPOCAMPAL-FORMATION OCCURS IN THE HUMAN BRAIN DURING CHILDHOOD, ADOLESCENCE, AND ADULTHOOD {1994} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {51}({6}), pp. {477-484} 
    article  
    Abstract: Background: A previous study demonstrated that myelination of the superior medullary lamina along the surface of the parahippocampal gyrus is occurring in human brain during adolescence. To further investigate whether postnatal increases of myelination may continue during the second decade and possibly even longer, the extent of myelination in this region has been analyzed in 164 psychiatrically normal individuals aged newborn to 76 years. Methods: Cross sections of the hippocampal formation with adjoining hippocampal gyrus were analyzed on a blinded basis using either a global rating scale or measurements of the area of myelin staining. Results: A curvilinear increase in the extent of myelination between the first and sixth decades of life (r=.71 and r=.67, respectively) was observed. When the area of myelination was expressed relative to brain weight, there was a twofold increase between the first and second decades and an additional increase of 60% between the fourth and sixth decades. Female subjects showed a significantly greater degree of myelin staining than did male subjects during the interval of ages 6 to 29 years; however, after the third decade, there were no gender differences in the area of myelin staining. Conclusions: The increased staining of myelin during the first and second decades principally occurred in the subicular region and adjacent portions of the presubiculum. During the fourth through sixth decades, however, it extended to progressively more lateral locations along the surface of the presubiculum. The precise origin(s) of the axons showing progressive myelination is unknown; however, the axons in the subiculum may include some perforant path fibers, while those found in the presubiculum may include cingulum bundle projections. Overall, our data are consistent with the idea that both early and late postnatal increases of myelination occur in a key corticolimbic relay area of the human brain and underscore the importance of applying a neurodevelopmental perspective to the study of psychopathology during childhood, adolescence, and even adulthood.
    BibTeX:
    @article{BENES1994,
      author = {BENES, FM and TURTLE, M and KHAN, Y and FAROL, P},
      title = {MYELINATION OF A KEY RELAY ZONE IN THE HIPPOCAMPAL-FORMATION OCCURS IN THE HUMAN BRAIN DURING CHILDHOOD, ADOLESCENCE, AND ADULTHOOD},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1994},
      volume = {51},
      number = {6},
      pages = {477-484}
    }
    
    BENES, F., VINCENT, S., ALSTERBERG, G., BIRD, E. & SANGIOVANNI, J. INCREASED GABA-A RECEPTOR-BINDING IN SUPERFICIAL LAYERS OF CINGULATE CORTEX IN SCHIZOPHRENICS {1992} JOURNAL OF NEUROSCIENCE
    Vol. {12}({3}), pp. {924-929} 
    article  
    Abstract: Recent investigations of postmortem brain from schizophrenic patients have revealed reduced numbers of neurons in several different corticolimbic brain regions. In the prefrontal and anterior cingulate cortices, more specific decreases in the numbers of interneurons, but not pyramidal cells, have been reported to occur preferentially in layer II. Based on this latter finding, a loss of inhibitory basket cells leading to a compensatory upregulation of the GABA(A) receptor has been hypothesized to occur in schizophrenic patients and to be a contributory factor in the pathophysiology of this disorder. We now report the results of a high-resolution quantitation of GABA(A) receptor binding in anterior cingulate cortex of postmortem specimens from normal and schizophrenic cases. The results indicate a preferential increase in bicuculline-sensitive H-3-muscimol binding on neuronal cell bodies of layers II and III, but not layers V and VI, of the schizophrenic cases. There was no difference in the size of neurons in any of the layers examined when the control and schizophrenic groups were compared. The neuropil of layer I also showed significantly greater GABA(A) binding in schizophrenics. The differences seen in the schizophrenic group did not appear to be the result of exposure to antipsychotic medication because one patient who was medication naive and a second who had received minimal exposure to antipsychotic drugs also showed elevated GABA(A) receptor binding. Since information processing depends on corticocortical integration in outer layers I-III, a disturbance of inhibitory activity in these superficial layers of limbic cortex may contribute to the defective associative function seen in schizophrenia.
    BibTeX:
    @article{BENES1992,
      author = {BENES, FM and VINCENT, SL and ALSTERBERG, G and BIRD, ED and SANGIOVANNI, JP},
      title = {INCREASED GABA-A RECEPTOR-BINDING IN SUPERFICIAL LAYERS OF CINGULATE CORTEX IN SCHIZOPHRENICS},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1992},
      volume = {12},
      number = {3},
      pages = {924-929}
    }
    
    Benes, F., Vincent, S., Marie, A. & Khan, Y. Up-regulation of GABA(A) receptor binding on neurons of the prefrontal cortex in schizophrenic subjects {1996} NEUROSCIENCE
    Vol. {75}({4}), pp. {1021-1031} 
    article  
    Abstract: Recent investigations have reported a reduced density of interneurons and an increase of GABA, receptor binding occurring preferentially in layer II of the anterior cingulate cortex of schizophrenic subjects [Benes F. M. et al. (1992) J. Neurosci. 12, 924-929]. Since a reduction in the density of interneurons has also been found in layer II of the prefrontal cortex, this study has sought to determine whether an up-regulation of the GABA, receptor binding activity might also be found in this region of schizophrenics. A high-resolution autoradiographic analysis of bicuculline-sensitive [H-3]muscimol (GABA,) receptor binding on individual neuron cell bodies in layers II, III, IV and VI has been applied to Brodmann area 10 from normal controls (n = 16) and schizophrenic (n = 7) subjects. A computer-assisted technique has been used under strictly blind conditions to determine whether differences in binding occur in the schizophrenic group. A significant increase of GABA, receptor binding activity has been observed in layers II, III, V and VI in the schizophrenic group. When the binding is expressed as a density with respect to neuronal cell, size, there is a gradient of binding across layers II, III, V and VI, with neuronal cell bodies in layer II having the greatest density of grains. When different subpopulations of neurons distinguished according to size criteria are examined separately, large (pyramidal) neurons show significantly higher binding, particularly in layer II, where it was increased by 90% in schizophrenics. Small (non-pyramidal) cells do not show significant differences in binding in schizophrenics, except in layer VI, where there was a 135% increase. Potential confounding effects from age and post mortem interval do not explain the differences between the two groups, because both young and old schizophrenics, as well as schizophrenics with long and short post mortem intervals, showed increased GABA(A) receptor binding activity when compared to control cases distinguished in a corresponding fashion. These data suggest that there may be a preferential reduction of inhibitory GABAergic inputs to pyramidal neurons, particularly in layer II of the prefrontal cortex, in schizophrenia. This change could potentially result in an increased excitatory outflow from the prefrontal area to other cortical regions of the schizophrenic brain. Overall, these results are consistent with the idea that reduced amounts of GABAergic activity in the prefrontal cortex could be related to a perinatal disturbance and could be a potentially important component of the pathophysiology of psychosis. Copyright (C) 1996 IBRO. Published by Elsevier Science Ltd.
    BibTeX:
    @article{Benes1996,
      author = {Benes, FM and Vincent, SL and Marie, A and Khan, Y},
      title = {Up-regulation of GABA(A) receptor binding on neurons of the prefrontal cortex in schizophrenic subjects},
      journal = {NEUROSCIENCE},
      year = {1996},
      volume = {75},
      number = {4},
      pages = {1021-1031}
    }
    
    BERGER, B., GASPAR, P. & VERNEY, C. DOPAMINERGIC INNERVATION OF THE CEREBRAL-CORTEX - UNEXPECTED DIFFERENCES BETWEEN RODENTS AND PRIMATES {1991} TRENDS IN NEUROSCIENCES
    Vol. {14}({1}), pp. {21-27} 
    article  
    Abstract: Until recently, views on the organization and role of the mesotelencephalic dopaminergic (DA) systems were mostly based on studies of rodents, and it was assumed that homology existed across mammalian species. However, recent studies of both human and non-human primates indicate that this might not be so. The mesocortical DA system in primates, which is directly involved in the pathophysiology of severe illnesses such as Parkinson's disease and psychoses, shows substantial differences from that of rodents. These differences include much larger, re-organized terminal fields, a different phenotype for the co-localization neuropeptides and a very early prenatal development.
    BibTeX:
    @article{BERGER1991,
      author = {BERGER, B and GASPAR, P and VERNEY, C},
      title = {DOPAMINERGIC INNERVATION OF THE CEREBRAL-CORTEX - UNEXPECTED DIFFERENCES BETWEEN RODENTS AND PRIMATES},
      journal = {TRENDS IN NEUROSCIENCES},
      year = {1991},
      volume = {14},
      number = {1},
      pages = {21-27}
    }
    
    Binder, J., Frost, J., Hammeke, T., Bellgowan, P., Rao, S. & Cox, R. Conceptual processing during the conscious resting state: A functional MRI study {1999} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {11}({1}), pp. {80-93} 
    article  
    Abstract: Localized, task-induced decreases in cerebral blood flow are a frequent finding in functional brain imaging research but remain poorly understood. One account of these phenomena postulates processes ongoing during conscious, resting states that are interrupted or inhibited by task performance. Psychological evidence suggests that conscious humans are engaged almost continuously in adaptive processes involving semantic knowledge retrieval, representation in awareness, and directed manipulation of represented knowledge for organization, problem-solving, and planning. If interruption of such ``conceptual'' processes accounts for task-induced deactivation, tasks that also engage these conceptual processes should not cause deactivation. Furthermore, comparisons between conceptual and nonconceptual tasks should show activation during conceptual tasks of the same brain areas that are ``deactivated'' relative to rest. To test this model, functional magnetic resonance imaging data were acquired during a resting state, a perceptual task, and a semantic retrieval task. A network of left-hemisphere polymodal cortical regions showed higher signal values during the resting state than during the perceptual task but equal values during the resting and semantic conditions. This result is consistent with the proposal that perceptual tasks interrupt processes ongoing during rest that involve many of the same brain areas engaged during semantic retrieval. As further evidence for this model, the same network of brain areas was activated in two direct comparisons between semantic and perceptual processing tasks. This same ``conceptual processing'' network was also identified in several previous studies that contrasted semantic and perceptual tasks or resting and active states. The model proposed here offers a unified account of these findings and may help to explain several unanticipated results from prior studies of semantic processing.
    BibTeX:
    @article{Binder1999,
      author = {Binder, JR and Frost, JA and Hammeke, TA and Bellgowan, PSF and Rao, SM and Cox, RW},
      title = {Conceptual processing during the conscious resting state: A functional MRI study},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {1999},
      volume = {11},
      number = {1},
      pages = {80-93}
    }
    
    Binkofski, F., Amunts, K., Stephan, K., Posse, S., Schormann, T., Freund, H., Zilles, K. & Seitz, R. Broca's region subserves imagery of motion: A combined cytoarchitectonic and fMRI study {2000} HUMAN BRAIN MAPPING
    Vol. {11}({4}), pp. {273-285} 
    article  
    Abstract: Broca's region in the dominant cerebral hemisphere is known to mediate the production of language but also contributes to comprehension. Here, we report the differential participation of Broca's region in imagery of motion in humans. Healthy volunteers were studied with functional magnetic resonance imaging (fMRI) while they imagined movement trajectories following different instructions. Imagery of right-hand finger movements induced a cortical activation pattern including dorsal and ventral portions of the premotor cortex, frontal medial wall areas, and cortical areas lining the intraparietal sulcus in both cerebral hemispheres. Imagery of movement observation and of a moving target specifically activated the opercular portion of the inferior frontal cortex. A left-hemispheric dominance was found for egocentric movements and a right-hemispheric dominance for movement characteristics in space. To precisely localize these inferior frontal activations, the fMRI data were coregistered with cytoarchitectonic maps of Broca's areas 44 and 45 in a common reference space. It was found that the activation areas in the opercular portion of the inferior frontal cortex were localized to area 44 of Broca's region. These activations of area 44 can be interpreted to possibly demonstrate the location of the human analogue to the so-called mirror neurones found in inferior frontal cortex of nonhuman primates. We suggest that area 44 mediates higher-order forelimb movement control resembling the neuronal mechanisms subserving speech. Hum. Brain Mapping 11:273-285, 2000. (C) 2000 Wiley-Liss, Inc.
    BibTeX:
    @article{Binkofski2000,
      author = {Binkofski, F and Amunts, K and Stephan, KM and Posse, S and Schormann, T and Freund, HJ and Zilles, K and Seitz, RJ},
      title = {Broca's region subserves imagery of motion: A combined cytoarchitectonic and fMRI study},
      journal = {HUMAN BRAIN MAPPING},
      year = {2000},
      volume = {11},
      number = {4},
      pages = {273-285}
    }
    
    Blair, R., Morris, J., Frith, C., Perrett, D. & Dolan, R. Dissociable neural responses to facial expressions of sadness and anger {1999} BRAIN
    Vol. {122}({Part 5}), pp. {883-893} 
    article  
    Abstract: Previous neuroimaging and neuropsychological studies have investigated the neural substrates which mediate responses to fearful, disgusted and happy expressions, No previous studies have investigated the neural substrates which mediate responses to sad and angry expressions. Using functional neuroimaging, we tested two hypotheses. First, we tested whether the amygdala has a neural response to sad and/or angry facial expressions. Secondly, we tested whether the orbitofrontal cortex has a specific neural response to angry facial expressions. Volunteer subjects were scanned, using PET, while they performed a sex discrimination task involving static grey-scale images of faces expressing varying degrees of sadness and anger. We found that increasing intensity of sad facial expression was associated with enhanced activity in the left amygdala and right temporal pole. In addition, we found that increasing intensity of angry facial expression was associated with enhanced activity in the orbitofrontal and anterior cingulate cortex. We found no support for the suggestion that angry expressions generate a signal in the amygdala, The results provide evidence for dissociable, but interlocking, systems for the processing of distinct categories of negative facial expression.
    BibTeX:
    @article{Blair1999,
      author = {Blair, RJR and Morris, JS and Frith, CD and Perrett, DI and Dolan, RJ},
      title = {Dissociable neural responses to facial expressions of sadness and anger},
      journal = {BRAIN},
      year = {1999},
      volume = {122},
      number = {Part 5},
      pages = {883-893}
    }
    
    Blok, B., Willemsen, A. & Holstege, G. A PET study on brain control of micturition in humans {1997} BRAIN
    Vol. {120}({Part 1}), pp. {111-121} 
    article  
    Abstract: Although the brain plays a crucial role in the control of micturition, little is known about the structures involved. Identification of these areas is important because their dysfunction is thought to cause urge incontinence, a major problem in the elderly. In the cat, three areas in the brainstem and diencephalon are specifically implicated in the control of micturition: the dorsomedial pontine tegmentum, the periaqueductal grey, and the preoptic area of the hypothalamus. PET scans were used to test whether these areas are also involved in human micturition. Seventeen right-handed male volunteers were scanned during the following four conditions: (i) 15 min prior to micturition during urine withholding; (ii) during micturition; (iii) 15 min after micturition; (iv) 30 min after micturition. Ten of the 17 volunteers were able to micturate during scanning. Micturition was associated with increased blood flow in the right dorsomedial pontine tegmentum, the periaqueductal grey, the hypothalamus and the right inferior frontal gyrus. Decreased blood flow was found in the right anterior cingulate gyrus when urine was withheld. The other seven volunteers were not able to micturate during scanning, although they had a full bladder and tried vigorously to do so. In this group, during these unsuccessful attempts to micturate, increased blood pow was Sound in the right ventral pontine tegmentum, which corresponds with the hypothesis, formulated from results in cats, that this area controls the motor neurons of the pelvic poor Increased blood pow was also found in the right inferior frontal gyrus during unsuccessful attempts at micturition, and decreased blood pow in the right anterior cingulate gyrus was found during the withholding of urine. The results suggest that, as that of the cat, the human brainstem contains specific nuclei responsible for the control of micturition, and that the cortical and pontine micturition sites are predominantly on the right side.
    BibTeX:
    @article{Blok1997,
      author = {Blok, BFM and Willemsen, ATM and Holstege, G},
      title = {A PET study on brain control of micturition in humans},
      journal = {BRAIN},
      year = {1997},
      volume = {120},
      number = {Part 1},
      pages = {111-121}
    }
    
    Blumberg, H., Leung, H., Skudlarski, P., Lacadie, C., Fredericks, C., Harris, B., Charney, D., Gore, J., Krystal, J. & Peterson, B. A functional magnetic resonance imaging study of bipolar disorder - State- and trait-related dysfunction in ventral prefrontal cortices {2003} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {60}({6}), pp. {601-609} 
    article  
    Abstract: Background: Abnormalities in prefrontal and anterior cingulate cortices are implicated in disturbances of attention, cognition, and impulse regulation in bipolar disorder. Acute episodes have been associated with dysfunction in these brain regions, and more enduring trait-related dysfunction has been implicated by volumetric and cellular abnormalities in these regions. The relative contributions of prefrontal regions to state and trait disturbances in bipolar disorder, however, have not been defined. We sought to characterize state- and trait-related functional impairment in frontal systems in bipolar disorder. Methods: Thirty-six individuals with bipolar disorder 1 (11 with elevated, 10 with depressed, and 15 with euthymic mood states) and 20 healthy control subjects matched for handedness and sex participated in an event-related functional magnetic resonance imaging study of the color-word Stroop to determine mean percentage of regional task-related signal change. Results: Signal increased during the Stroop task similarly across diagnostic groups in a distribution that included dorsal anterior cingulate and prefrontal cortices, consistent with previously reported activations in this task. Signal changes associated with specific mood states in bipolar disorder were detected in ventral prefrontal cortex, with a blunted increase in signal on the right side in the elevated mood group (P=.005) and an exaggerated increase in signal on the left side in the depressed group (P=.02) compared with the euthymic group. Patients (vs healthy controls) demonstrated blunted activation in a spatially distinct, rostral region of left ventral prefrontal cortex that was independent of mood state (P<.005). Conclusions: Bipolar disorder is associated with a trait abnormality in left ventral prefrontal cortex. Additional ventral prefrontal abnormalities may be associated with specific acute mood states. The hemispheric laterality of the abnormality and the directions of signal change may relate to the valence of the mood episode.
    BibTeX:
    @article{Blumberg2003,
      author = {Blumberg, HP and Leung, HC and Skudlarski, P and Lacadie, CM and Fredericks, CA and Harris, BC and Charney, DS and Gore, JC and Krystal, JH and Peterson, BS},
      title = {A functional magnetic resonance imaging study of bipolar disorder - State- and trait-related dysfunction in ventral prefrontal cortices},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {2003},
      volume = {60},
      number = {6},
      pages = {601-609},
      note = {56th Annual Meeting of the Society-of-Biological-Psychiatry, NEW ORLEANS, LOUISIANA, MAY 03-05, 2001}
    }
    
    BOGERTS, B. RECENT ADVANCES IN THE NEUROPATHOLOGY OF SCHIZOPHRENIA {1993} SCHIZOPHRENIA BULLETIN
    Vol. {19}({2}), pp. {431-445} 
    article  
    Abstract: This article reviews some 50 neuroanatomical postmortem studies published in the last 20 years. The majority of these studies demonstrated various types of subtle anomalies in limbic structures, that is, the hippocampus, parahippocampal gyrus, entorhinal cortex, amygdala, cingulate gyrus, and septum of schizophrenia patients. A number of schizophrenic symptoms might be related to structural and functional disturbances of these brain regions. But these studies also reported subtle changes in parts of the basal ganglia, thalamus, cortex, corpus callosum, and brainstem neurotransmitter systems. Many of the studies, however, are based on small sample sizes and, therefore, must be regarded as preliminary. Cytoarchitectonic abnormalities and lack of gliosis in limbic structures as well as the absence of normal structural cerebral asymmetry in a substantial proportion of patients indicate that these structural anomalies may reflect a disorder of prenatal brain development and argue against the notion that schizophrenia is a progressive degenerative brain disorder.
    BibTeX:
    @article{BOGERTS1993,
      author = {BOGERTS, B},
      title = {RECENT ADVANCES IN THE NEUROPATHOLOGY OF SCHIZOPHRENIA},
      journal = {SCHIZOPHRENIA BULLETIN},
      year = {1993},
      volume = {19},
      number = {2},
      pages = {431-445}
    }
    
    BOTTINI, G., CORCORAN, R., STERZI, R., PAULESU, E., SCHENONE, P., SCARPA, P., FRACKOWIAK, R. & FRITH, C. THE ROLE OF THE RIGHT-HEMISPHERE IN THE INTERPRETATION OF FIGURATIVE ASPECTS OF LANGUAGE - A POSITRON EMISSION TOMOGRAPHY ACTIVATION STUDY {1994} BRAIN
    Vol. {117}({Part 6}), pp. {1241-1253} 
    article  
    Abstract: We investigated cerebral activity in six normal volunteers using PET to explore the hypothesis that the right hemisphere has a specific role in the interpretation of figurative aspects of language such as metaphors. WE also mapped the anatomical structures involved in sentence comprehension. During regional cerebral blood flow measurement subjects were asked to perform three different linguistic tasks: (i) metaphorical comprehension; (ii) literal comprehension of sentences; and (iii) a lexical-decision task. We found that comprehension of sentences compared with the lexical-decision task induced extensive activation in several regions of The left hemisphere, including the prefrontal and basal frontal cortex, the middle and inferior temporal gyri and temporal pole, the parietal cortex and the precuneus. Comprehension of metaphors was associated with similar activations in the left hemisphere, but in addition, a number of sites were activated in the right hemisphere: the prefrontal cortex, the middle temporal gyrus, the precuneus and the posterior cingulate. We conclude that the interpretation of language involves widespread distributed systems bilaterally with the right hemisphere having a special role in the appreciation of metaphors.
    BibTeX:
    @article{BOTTINI1994,
      author = {BOTTINI, G and CORCORAN, R and STERZI, R and PAULESU, E and SCHENONE, P and SCARPA, P and FRACKOWIAK, RSJ and FRITH, CD},
      title = {THE ROLE OF THE RIGHT-HEMISPHERE IN THE INTERPRETATION OF FIGURATIVE ASPECTS OF LANGUAGE - A POSITRON EMISSION TOMOGRAPHY ACTIVATION STUDY},
      journal = {BRAIN},
      year = {1994},
      volume = {117},
      number = {Part 6},
      pages = {1241-1253}
    }
    
    BOTTINI, G., STERZI, R., PAULESU, E., VALLAR, G., CAPPA, S., ERMINIO, F., PASSINGHAM, R., FRITH, C. & FRACKOWIAK, R. IDENTIFICATION OF THE CENTRAL VESTIBULAR PROJECTIONS IN MAN - A POSITRON EMISSION TOMOGRAPHY ACTIVATION STUDY {1994} EXPERIMENTAL BRAIN RESEARCH
    Vol. {99}({1}), pp. {164-169} 
    article  
    Abstract: The cerebral representation of space depends on the integration of many different sensory inputs. The vestibular system provides one such input and its dysfunction can cause profound spatial disorientation. Using positron emission tomography (PET), we measured regional cerebral perfusion with various vestibular stimulations to map central vestibular projections and to investigate the cerebral basis of spatial disorientation. We showed that the temporoparietal cortex, the insula, the putamen, and the anterior cingulate cortex are the cerebral projections of the vestibular system in man and that the spatial disorientation caused by unilateral vestibular stimulation is associated with their asymmetric activation.
    BibTeX:
    @article{BOTTINI1994a,
      author = {BOTTINI, G and STERZI, R and PAULESU, E and VALLAR, G and CAPPA, SF and ERMINIO, F and PASSINGHAM, RE and FRITH, CD and FRACKOWIAK, RSJ},
      title = {IDENTIFICATION OF THE CENTRAL VESTIBULAR PROJECTIONS IN MAN - A POSITRON EMISSION TOMOGRAPHY ACTIVATION STUDY},
      journal = {EXPERIMENTAL BRAIN RESEARCH},
      year = {1994},
      volume = {99},
      number = {1},
      pages = {164-169}
    }
    
    Botvinick, M., Braver, T., Barch, D., Carter, C. & Cohen, J. Conflict monitoring and cognitive control {2001} PSYCHOLOGICAL REVIEW
    Vol. {108}({3}), pp. {624-652} 
    article DOI  
    Abstract: A neglected question regarding cognitive control is how control processes might detect situations calling for their involvement. The authors propose here that the demand for control may be evaluated in part by monitoring for conflicts in information processing. This hypothesis is supported by data concerning the anterior cingulate cortex, a brain area involved in cognitive control, which also appears to respond to the occurrence of conflict. The present article reports two computational modeling studies, serving to articulate the conflict monitoring hypothesis and examine its implications. The first study tests the sufficiency of the hypothesis to account for brain activation data, applying a measure of conflict to existing models of tasks shown to engage the anterior cingulate. The second study implements a feedback loop connecting conflict monitoring to cognitive control, using this to simulate a number of important behavioral phenomena.
    BibTeX:
    @article{Botvinick2001,
      author = {Botvinick, MM and Braver, TS and Barch, DM and Carter, CS and Cohen, JD},
      title = {Conflict monitoring and cognitive control},
      journal = {PSYCHOLOGICAL REVIEW},
      year = {2001},
      volume = {108},
      number = {3},
      pages = {624-652},
      doi = {{10.1037//0033-295X.108.3.624}}
    }
    
    Botvinick, M., Nystrom, L., Fissell, K., Carter, C. & Cohen, J. Conflict monitoring versus selection-for-action in anterior cingulate cortex {1999} NATURE
    Vol. {402}({6758}), pp. {179-181} 
    article  
    Abstract: The anterior cingulate cortex (ACC), on the medial surface of the frontal lobes of the brain, is widely believed to be involved in the regulation of attention(1,2), Beyond this, however, its specific contribution to cognition remains uncertain, One influential theory has interpreted activation within the ACC as reflecting `selection-for-action'(3-5), a set of processes that guide the selection of environmental objects as triggers of or targets for action. We have proposed an alternative hypothesis, in which the ACC serves not to exert top-down attentional control but instead to detect and signal the occurrence of conflicts in information processing(6-8). Here, to test this theory against the selection-for-action theory, we used functional magnetic resonance imaging to measure brain activation during performance of a task where, for a particular subset of trials, the strength of selection-for action is inversely related to the degree of response conflict. Activity within the ACC was greater during trials featuring high levels of conflict (and weak selection-for-action) than during trials with low levels of conflict (and strong selection-for-action), providing evidence in favour of the conflict-monitoring account of ACC function.
    BibTeX:
    @article{Botvinick1999,
      author = {Botvinick, M and Nystrom, LE and Fissell, K and Carter, CS and Cohen, JD},
      title = {Conflict monitoring versus selection-for-action in anterior cingulate cortex},
      journal = {NATURE},
      year = {1999},
      volume = {402},
      number = {6758},
      pages = {179-181}
    }
    
    Botvinick, M.M., Cohen, J.D. & Carter, C.S. Conflict monitoring and anterior cingulate cortex: an update {2004} TRENDS IN COGNITIVE SCIENCES
    Vol. {8}({12}), pp. {539-546} 
    article DOI  
    Abstract: One hypothesis concerning the human dorsal anterior cingulate cortex [ACC) is that it functions, in part, to signal the occurrence of conflicts in information processing, thereby triggering compensatory adjustments in cognitive control. Since this idea was first proposed, a great deal of relevant empirical evidence has accrued. This evidence has largely corroborated the conflict-monitoring hypothesis, and some very recent work has provided striking new support for the theory. At the same time, other findings have posed specific challenges, especially concerning the way the theory addresses the processing of errors. Recent research has also begun to shed light on the larger function of the ACC, suggesting some new possibilities concerning how conflict monitoring might fit into the cingulate's overall role in cognition and action.
    BibTeX:
    @article{Botvinick2004,
      author = {Botvinick, Matthew M. and Cohen, Jonathan D. and Carter, Cameron S.},
      title = {Conflict monitoring and anterior cingulate cortex: an update},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      year = {2004},
      volume = {8},
      number = {12},
      pages = {539-546},
      doi = {{10.1016/j.tics.2004.10.003}}
    }
    
    Braver, T., Barch, D., Gray, J., Molfese, D. & Snyder, A. Anterior cingulate cortex and response conflict: Effects of frequency, inhibition and errors {2001} CEREBRAL CORTEX
    Vol. {11}({9}), pp. {825-836} 
    article  
    Abstract: Anterior cingulate cortex (ACC) may play a key role in cognitive control by monitoring for the occurrence of response conflict (i.e. simultaneous activation of incompatible response tendencies). Low-frequency responding might provide a minimal condition for eliciting such conflict, as a result of the need to overcome a prepotent response tendency. We predicted that ACC would be selectively engaged during low-frequency responding, irrespective of the specific task situation. To test this hypothesis, we examined ACC activity during the performance of simple choice-discrimination tasks, using rapid event-related functional magnetic resonance imaging. Subjects were scanned while performing three tasks thought to tap different cognitive processes: `Go/No-go' (response inhibition), `oddball' (target detection), and two-alternative forced-choice (response selection). Separate conditions manipulated the frequency of relevant task events. Consistent with our hypothesis, the same ACC region was equally responsive to low-frequency events across all three tasks, but did not show differential responding when events occurred with equal frequency. Subregions of the ACC were also identified that showed heightened activity during the response inhibition condition, and on trials in which errors were committed. Task-sensitive activity was also found in right prefrontal and parietal cortex (response inhibition), left superior temporal and tempoparietal cortex (target detection), and supplementary motor area (response selection). Taken together, the results are consistent with the hypothesis that the ACC serves as a generic detector of processing conflict arising when low-frequency responses must be executed, but also leave open the possibility that further functional specialization may occur within ACC subregions.
    BibTeX:
    @article{Braver2001,
      author = {Braver, TS and Barch, DM and Gray, JR and Molfese, DL and Snyder, A},
      title = {Anterior cingulate cortex and response conflict: Effects of frequency, inhibition and errors},
      journal = {CEREBRAL CORTEX},
      year = {2001},
      volume = {11},
      number = {9},
      pages = {825-836}
    }
    
    Breiter, H., Gollub, R., Weisskoff, R., Kennedy, D., Makris, N., Berke, J., Goodman, J., Kantor, H., Gastfriend, D., Riorden, J., Mathew, R., Rosen, B. & Hyman, S. Acute effects of cocaine on human brain activity and emotion {1997} NEURON
    Vol. {19}({3}), pp. {591-611} 
    article  
    Abstract: We investigated brain circuitry mediating cocaine-induced euphoria and craving using functional MRI (fMRI). During double-blind cocaine (0.6 mg/kg) and saline infusions in cocaine-dependent subjects, the entire brain was imaged for 5 min before and 13 min after infusion while subjects rated scales for rush, high, low, and craving. Cocaine induced focal signal increases in nucleus accumbens/subcallosal cortex (NAc/SCC), caudate, putamen, basal forebrain, thalamus, insula, hippocampus, parahippocampal gyrus, cingulate, lateral prefrontal and temporal cortices, parietal cortex, striate/extrastriate cortices, Ventral tegmentum, and pens and produced signal decreases in amygdala, temporal pole, and medial frontal cortex. Saline produced few positive or negative activations, which were localized to lateral prefrontal cortex and temporo-occipital cortex. Subjects who underwent repeat studies showed good replication of the regional fMRI activation pattern following cocaine and saline infusions, with activations on saline retest that might reflect expectancy. Brain regions that exhibited early and short duration signal maxima showed a higher correlation with rush ratings. These included the ventral tegmentum, pens, basal forebrain, caudate, cingulate, and most regions of lateral prefrontal cortex. In contrast, regions that demonstrated early but sustained signal maxima were more correlated with craving than with rush ratings; such regions included the NAc/SCC, right parahippocampal gyrus, and some regions of lateral prefrontal cortex. Sustained negative signal change was noted in the amygdala, which correlated with craving ratings. Our data demonstrate the ability of fMRI to map dynamic patterns of brain activation following cocaine infusion in cocaine-dependent subjects and provide evidence of dynamically changing brain networks associated with cocaine-induced euphoria and cocaine-induced craving.
    BibTeX:
    @article{Breiter1997,
      author = {Breiter, HC and Gollub, RL and Weisskoff, RM and Kennedy, DN and Makris, N and Berke, JD and Goodman, JM and Kantor, HL and Gastfriend, DR and Riorden, JP and Mathew, RT and Rosen, BR and Hyman, SE},
      title = {Acute effects of cocaine on human brain activity and emotion},
      journal = {NEURON},
      year = {1997},
      volume = {19},
      number = {3},
      pages = {591-611}
    }
    
    Breiter, H., Rauch, S., Kwong, K., Baker, J., Weisskoff, R., Kennedy, D., Kendrick, A., Davis, T., Jiang, A., Cohen, M., Stern, C., Belliveau, J., Baer, L., OSullivan, R., Savage, C., Jenike, M. & Rosen, B. Functional magnetic resonance imaging of symptom provocation in obsessive-compulsive disorder {1996} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {53}({7}), pp. {595-606} 
    article  
    Abstract: Background: The new technique of functional magnetic resonance imaging was used to investigate the mediating neuroanatomy of obsessive-compulsive disorder symptoms. Methods: Ten patients with obsessive-compulsive disorder and 5 normal subjects were studied via functional magnetic resonance imaging during control and provoked conditions. Data analysis entailed parametric and nonparametric statistical mapping. Results: Statistical maps (nonparametric; P<10(-3)) showed activation for 70% or more of patients with obsessive-compulsive disorder in medial orbitofrontal, lateral frontal, anterior temporal, anterior cingulate, and insular cortex, as well as caudate, lenticulate, and amygdala. No normal subjects exhibited activation in any brain region. Conclusions: Results of functional magnetic resonance imaging were consistent with past studies of obsessive-compulsive disorder that used other functional neuroimaging modalities. However, paralimbic and limbic activations were more prominent in the present study.
    BibTeX:
    @article{Breiter1996,
      author = {Breiter, HC and Rauch, SL and Kwong, KK and Baker, JR and Weisskoff, RM and Kennedy, DN and Kendrick, AD and Davis, TL and Jiang, AP and Cohen, MS and Stern, CE and Belliveau, JW and Baer, L and OSullivan, RL and Savage, CR and Jenike, MA and Rosen, BR},
      title = {Functional magnetic resonance imaging of symptom provocation in obsessive-compulsive disorder},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1996},
      volume = {53},
      number = {7},
      pages = {595-606}
    }
    
    Bremner, J., Narayan, M., Staib, L., Southwick, S., McGlashan, T. & Charney, D. Neural correlates of memories of childhood sexual abuse in women with and without posttraumatic stress disorder {1999} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {156}({11}), pp. {1787-1795} 
    article  
    Abstract: Objective: Childhood sexual abuse is very common in our society, but little is known about the long-term effects of abuse on brain function. The purpose of this study was to measure neural correlates of memories of childhood abuse in sexually abused women with and without the diagnosis of posttraumatic stress disorder (PTSD), Method: Twenty-two women with a history of childhood sexual abuse underwent injection Of [O-15]H2O, followed by positron emission tomography imaging of the brain while they listened to neutral and traumatic (personalized childhood sexual abuse events) scripts. Brain blood flow during exposure to traumatic and neutral scripts was compared for sexually abused women with and without PTSD, Results: Memories of childhood sexual abuse were associated with greater increases in blood flow in portions of anterior prefrontal cortex (superior and middle frontal gyri-areas 6 and 9), posterior cingulate (area 31), and motor cortex in sexually abused women with PTSD than in sexually abused women without PTSD. Abuse memories were associated with alterations in blood flow in medial prefrontal cortex, with decreased blood flow in subcallosal gyrus (area 25), and a failure of activation in anterior cingulate (area 32), There was also decreased blood flow in right hippocampus, fusiform/inferior temporal gyrus, supramarginal gyrus, and visual association cortex in women with PTSD relative to women without PTSD. Conclusions: These findings implicate dysfunction of medial prefrontal cortex (subcallosal gyrus and anterior cingulate), hippocampus, and visual association cortex in pathological memories of childhood abuse in women with PTSD. Increased activation in posterior cingulate and motor cortex was seen in women with PTSD. Dysfunction in these brain areas may underlie PTSD symptoms provoked by traumatic reminders in subjects with PTSD.
    BibTeX:
    @article{Bremner1999a,
      author = {Bremner, JD and Narayan, M and Staib, LH and Southwick, SM and McGlashan, T and Charney, DS},
      title = {Neural correlates of memories of childhood sexual abuse in women with and without posttraumatic stress disorder},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {1999},
      volume = {156},
      number = {11},
      pages = {1787-1795}
    }
    
    Bremner, J., Staib, L., Kaloupek, D., Southwick, S., Soufer, R. & Charney, D. Neural correlates of exposure to traumatic pictures and sound in Vietnam combat veterans with and without posttraumatic stress disorder: A positron emission tomography study {1999} BIOLOGICAL PSYCHIATRY
    Vol. {45}({7}), pp. {806-816} 
    article  
    Abstract: Background: Patients with posttraumatic stress disorder (PTSD) show a reliable increase in PTSD symptoms and physiological reactivity following exposure to traumatic pictures and sounds. In this study neural correlates of exposure to traumatic pictures and sounds were measured in PTSD. Methods: Positron emission tomography and H2[15O] were used to measure cerebral blood flow during exposure to combat-related and neutral pictures and sounds in Vietnam combat veterans with and without PTSD. Results: Exposure to traumatic material in PTSD (but not non-PTSD) subjects resulted in a decrease in blood flow in medial prefrontal cortex (area 25), an area postulated to play a role in emotion through inhibition of amygdala responsiveness. Non-PTSD subjects activated anterior cingulate (area 24) to a greater degree than PTSD patients. There were also differences in cerebral blood flow response in areas involved in memory and visuospatial processing (and by extension response to threat), including posterior cingulate (area 23), precentral (motor) and inferior parietal cortex, and lingual gyrus. There was a pattern of increases in PTSD and decreases in non-PTSD subjects in these areas. Conclusions: The findings suggest that functional alterations in specific cortical and subcortical brain areas involved in memory, visuospatial processing, and emotion underlie the symptoms of patients with PTSD. (C) 1999 Society of Biological Psychiatry.
    BibTeX:
    @article{Bremner1999,
      author = {Bremner, JD and Staib, LH and Kaloupek, D and Southwick, SM and Soufer, R and Charney, DS},
      title = {Neural correlates of exposure to traumatic pictures and sound in Vietnam combat veterans with and without posttraumatic stress disorder: A positron emission tomography study},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {1999},
      volume = {45},
      number = {7},
      pages = {806-816}
    }
    
    Bremner, J., Vythilingam, M., Vermetten, E., Nazeer, A., Adil, J., Khan, S., Staib, L. & Charney, D. Reduced volume of orbitofrontal cortex in major depression {2002} BIOLOGICAL PSYCHIATRY
    Vol. {51}({4}), pp. {273-279} 
    article  
    Abstract: Background: Functional neuroimaging studies have implicated dysfunction of orbitofrontal cortex in the symptoms of depression, and a recent postmortem study of depressed patients found reduced density of neurons and glia in this area. The purpose of this study was to measure volume of orbitofrontal cortex and other frontal cortical subregions in patients with major depression. Methods: Magnetic resonance imaging was used to measure volume of the orbitofrontal cortex and other frontal cortical regions in patients with major depression in remission (n = 15) and comparison subjects (n = 20). Results: Patients with depression had a statistically significant 32% smaller medial orbitofrontal (gyrus rectus) cortical volume, without smaller volumes of other frontal regions including anterior cingulate Brodmann's area 24 (subgenual gyrus), anterior cingulate Brodmann's area 32, subcallosal gyrus (Brodmann's area 25), or whole brain volume. The findings were significant after statistically controlling for brain size. Conclusions: These findings are consistent with smaller orbitofrontal cortical volume in depression. (C) 2002 Society of Biological Psychiatry.
    BibTeX:
    @article{Bremner2002,
      author = {Bremner, JD and Vythilingam, M and Vermetten, E and Nazeer, A and Adil, J and Khan, S and Staib, LH and Charney, DS},
      title = {Reduced volume of orbitofrontal cortex in major depression},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {2002},
      volume = {51},
      number = {4},
      pages = {273-279}
    }
    
    Brody, A., Saxena, S., Stoessel, P., Gillies, L., Fairbanks, L., Alborzian, S., Phelps, M., Huang, S., Wu, H., Ho, M., Ho, M., Au, S., Maidment, K. & Baxter, L. Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy - Preliminary findings {2001} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {58}({7}), pp. {631-640} 
    article  
    Abstract: Background: In functional brain imaging studies of major depressive disorder (MDD), regional abnormalities have been most commonly found in prefrontal cortex, anterior cingulate gyrus, and temporal lobe. We examined baseline regional metabolic abnormalities and metabolic changes from pretreatment to posttreatment in subjects with MDD. We also performed a preliminary comparison of regional changes with 2 distinct forms of treatment (paroxetine and interpersonal psychotherapy). Methods: Twenty-four subjects with unipolar MDD and 16 normal control subjects underwent resting F 18 (F-18) fluorodeoxyglucose positron emission tomography scanning before and after 12 weeks. Between scans, subjects with MDD were treated with either paroxetine or interpersonal psychotherapy (based on patient preference). while controls underwent no treatment. Results: At baseline, subjects with MDD had higher normalized metabolism than controls in the prefrontal cortex land caudate and thalamus), and lower metabolism in the temporal lobe, With treatment, subjects with MDD had metabolic changes in the direction of normalization in these regions. After treatment, paroxetine-treated subjects had a greater mean decrease in Hamilton Depression Raring Scale score (61.4 than did subjects treated with interpersonal psychotherapy (38.0, but both subgroups showed decreases in normalized prefrontal cor tex (paroxetine-treated bilaterally and interpersonal psychotherapy-treated on the right) and left anterior cingulate gyrus metabolism, and increases in normalized left temporal lobe metabolism. Conclusions: Subjects with MDD had regional brain metabolic abnormalities at baseline that tended to normalize with treatment. Regional metabolic changes appeared similar with the Z forms of treatment. These results should be interpreted with caution because of study limitations (small sample size, lack of random assignment to treatment groups, and differential treatment response between treatment subgroups).
    BibTeX:
    @article{Brody2001,
      author = {Brody, AL and Saxena, S and Stoessel, P and Gillies, LA and Fairbanks, LA and Alborzian, S and Phelps, ME and Huang, SC and Wu, HM and Ho, ML and Ho, MK and Au, SC and Maidment, K and Baxter, LR},
      title = {Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy - Preliminary findings},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {2001},
      volume = {58},
      number = {7},
      pages = {631-640},
      note = {38th Annual Meeting of the American-College-of-Neuropsychopharmacology, ACAPULCO, MEXICO, DEC 12-16, 1999}
    }
    
    BROG, J., SALYAPONGSE, A., DEUTCH, A. & ZAHM, D. THE PATTERNS OF AFFERENT INNERVATION OF THE CORE AND SHELL IN THE ACCUMBENS PART OF THE RAT VENTRAL STRIATUM - IMMUNOHISTOCHEMICAL DETECTION OF RETROGRADELY TRANSPORTED FLUOROGOLD {1993} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {338}({2}), pp. {255-278} 
    article  
    Abstract: Recent data have emphasized the neurochemically distinct nature of subterritories in the accumbens part of the rat ventral striatum termed the core, shell, and rostral pole. In order to gain a more comprehensive understanding of how afferents are distributed relative to these subterritories, immunohistochemical detection of retrogradely transported Fluoro-Gold was carried out following iontophoretic injections intended to involve selectively one of the subterritories. The data revealed that a number of cortical afferents of the medial shell and core originate in separate areas, i.e., the dorsal peduncular, infralimbic, and posterior piriform cortices (to medial shell) and the dorsal prelimbic, anterior agranular insular, anterior cingulate, and perirhinal cortices (to core). The lateral shell and rostral pole are innervated by cortical structures that also project either to the medial shell or core. The orbital, posterior agranular insular, and entorhinal cortices, hippocampus, and basal amygdala were observed to innervate the accumbens in a topographic manner. Following core injections, strong bilateral cortical labeling was observed. Few labeled cortical cells were observed contralaterally following injections in the medial shell. Intermediate numbers of labeled neurons were observed in contralateral cortices following lateral shell injections. Robust subcortical labeling in a variety of structures in the ventral forebrain, lateral hypothalamus, deep temporal lobe, and brainstem was observed after shell injections, particularly those that involved the caudal dorsomedial extremity of the shell, i.e., its `'septal pole.'' Selective ipsilateral labeling of subcortical structures in the basal ganglia circuitry was observed following injections in the core and, to a lesser extent, lateral shell. It was concluded that a number of afferent systems exhibit varying degrees of segregation with respect to the accumbal subterritories. (C) 1993 Wiley-Liss, Inc.
    BibTeX:
    @article{BROG1993,
      author = {BROG, JS and SALYAPONGSE, A and DEUTCH, AY and ZAHM, DS},
      title = {THE PATTERNS OF AFFERENT INNERVATION OF THE CORE AND SHELL IN THE ACCUMBENS PART OF THE RAT VENTRAL STRIATUM - IMMUNOHISTOCHEMICAL DETECTION OF RETROGRADELY TRANSPORTED FLUOROGOLD},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {1993},
      volume = {338},
      number = {2},
      pages = {255-278}
    }
    
    BROWN, E., ROBERTSON, G. & FIBIGER, H. EVIDENCE FOR CONDITIONAL NEURONAL ACTIVATION FOLLOWING EXPOSURE TO A COCAINE-PAIRED ENVIRONMENT - ROLE OF FOREBRAIN LIMBIC STRUCTURES {1992} JOURNAL OF NEUROSCIENCE
    Vol. {12}({10}), pp. {4112-4121} 
    article  
    Abstract: The reinforcing properties of cocaine can readily become associated with salient environmental stimuli that acquire secondary reinforcing properties. This form of classical conditioning is of considerable clinical relevance as intense craving can be evoked by the presentation of stimuli previously associated with the effects of cocaine. To understand better the neurobiology of cocaine-induced environment-specific conditioning, Fos expression was examined in the forebrain of rats exposed to an environment in which they had previously received cocaine. These results were compared to those observed following an acute injection of cocaine. Consistent with its stimulant actions, cocaine produced an increase in locomotion that was accompanied by an increase in Fos expression within specific limbic regions (cingulate cortex, claustrum, piriform cortex, lateral septal nucleus, paraventricular nucleus of the thalamus, lateral habenula, and amygdala) as well as the basal ganglia (dorsomedial striatum and nucleus accumbens). Exposure of rats to the cocaine-paired environment also produced an increase in locomotion, as compared to various control groups. In addition to this behavioral effect, conditioned subjects exhibited a significant increase in Fos expression within the cingulate cortex, claustrum, lateral septal nucleus, paraventricular nucleus of the thalamus, lateral habenula, and the amygdala, suggesting increased neuronal activity within these regions. In contrast to the dramatic effects observed within these structures, no conditional activation was observed within the piriform cortex, nucleus accumbens, or dorsal striatum, suggesting that these brain areas are not involved in the conditioned response. The present findings indicate that specific limbic regions exhibit increased neuronal activation during the presentation of cocaine-paired cues and may be involved in the formation of associations between cocaine's stimulant actions and the environment in which the drug administration occurred. Although the nucleus accumbens is necessary for the reinforcing and locomotor effects of cocaine, it does not exhibit a conditional Fos response, suggesting that different neural circuits are involved in the unconditioned and conditioned effects of cocaine.
    BibTeX:
    @article{BROWN1992,
      author = {BROWN, EE and ROBERTSON, GS and FIBIGER, HC},
      title = {EVIDENCE FOR CONDITIONAL NEURONAL ACTIVATION FOLLOWING EXPOSURE TO A COCAINE-PAIRED ENVIRONMENT - ROLE OF FOREBRAIN LIMBIC STRUCTURES},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1992},
      volume = {12},
      number = {10},
      pages = {4112-4121}
    }
    
    Brown, J. & Braver, T. Learned predictions of error likelihood in the anterior cingulate cortex {2005} SCIENCE
    Vol. {307}({5712}), pp. {1118-1121} 
    article DOI  
    Abstract: The anterior cingulate cortex (ACC) and the related medial wall play a critical role in recruiting cognitive control. Although ACC exhibits selective error and conflict responses, it has been unclear how these develop and become context-specific. With use of a modified stop-signal task, we show from integrated computational neural modeling and neuroimaging studies that ACC learns to predict error likelihood in a given context, even for trials in which there is no error or response conflict. These results support a more general error-likelihood theory of ACC function based on reinforcement learning, of which conflict and error detection are special cases.
    BibTeX:
    @article{Brown2005,
      author = {Brown, JW and Braver, TS},
      title = {Learned predictions of error likelihood in the anterior cingulate cortex},
      journal = {SCIENCE},
      year = {2005},
      volume = {307},
      number = {5712},
      pages = {1118-1121},
      doi = {{10.1126/science.1105783}}
    }
    
    Brunet, E., Sarfati, Y., Hardy-Bayle, M. & Decety, J. A PET investigation of the attribution of intentions with a nonverbal task {2000} NEUROIMAGE
    Vol. {11}({2}), pp. {157-166} 
    article  
    Abstract: Several authors have demonstrated that theory of mind is associated with a cerebral pattern of activity involving the medial prefrontal cortex. This study was designed to determine the cerebral regions activated during attribution of intention to others, a task which requires theory-of-mind skills, Eight healthy subjects performed three nonverbal tasks using comic strips while PET scanning was performed. One condition required subjects to attribute intentions to the characters of the comic strips. The other two conditions involved only physical lose and knowledge about objects' properties: one condition involved characters, whereas the other only represented objects, The comparison of the attribution of intention condition with the physical logic with characters condition was associated with rCBF increases in the right middle and medial prefrontal cortex including Brodmann's area (BA) 9, the right inferior prefrontal cortex (BA 47), the right inferior temporal gyrus (BA 20), the left superior temporal gyrus (BA 38), the left cerebellum, the bilateral anterior cingulate, and the middle temporal gyri (EA 21). The comparison of the physical logic with characters condition and the physical logic without characters condition showed the activation of the lingual gyri (BA 17, 18, 19), the fusiform gyri (BA 37), the middle (BA 21) and superior (BA 22, 38) temporal gyri on both sides, and the posterior cingulate, These data suggest that attribution of intentions to others is associated with a complex cerebral activity involving the right medial prefrontal cortex when a nonverbal task is used. The laterality of this function is discussed, (C) 2000 Academic Press.
    BibTeX:
    @article{Brunet2000,
      author = {Brunet, E and Sarfati, Y and Hardy-Bayle, MC and Decety, J},
      title = {A PET investigation of the attribution of intentions with a nonverbal task},
      journal = {NEUROIMAGE},
      year = {2000},
      volume = {11},
      number = {2},
      pages = {157-166}
    }
    
    Buchel, C., Dolan, R., Armony, J. & Friston, K. Amygdala-hippocampal involvement in human aversive trace conditioning revealed through event-related functional magnetic resonance imaging {1999} JOURNAL OF NEUROSCIENCE
    Vol. {19}({24}), pp. {10869-10876} 
    article  
    Abstract: Previous functional neuroimaging studies have characterized brain systems mediating associative learning using classical delay conditioning paradigms. In the present study, we used event-related functional magnetic resonance imaging to characterize neuronal responses mediating aversive trace conditioning. During conditioning, neutral auditory tones were paired with an aversive sound [unconditioned stimulus (US)]. We compared neuronal responses evoked by conditioned (CS+) and nonconditioned (CS-) stimuli in which a 50% pairing of CS+ and the US enabled us to limit our analysis to responses evoked by the CS+ alone. Differential responses (CS+ vs CS-), related to conditioning, were observed in anterior cingulate and anterior insula, regions previously implicated in delay fear conditioning. Differential responses were also observed in the amygdala and hippocampus that were best characterized with a time x stimulus interaction, indicating rapid adaptation of CS+-specific responses in medial temporal lobe. These results are strikingly similar to those obtained with a previous delay conditioning experiment and are in accord with a preferential role for medial temporal lobe structures during the early phase of conditioning. However, an additional activation of anterior hippocampus in the present experiment supports a view that its role in trace conditioning is to maintain a memory trace between the offset of the CS+ and the delayed onset of the US to enable associative learning in trace conditioning.
    BibTeX:
    @article{Buchel1999,
      author = {Buchel, C and Dolan, RJ and Armony, JL and Friston, KJ},
      title = {Amygdala-hippocampal involvement in human aversive trace conditioning revealed through event-related functional magnetic resonance imaging},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1999},
      volume = {19},
      number = {24},
      pages = {10869-10876}
    }
    
    Buckner, R. Memory and executive function in aging and AD: Multiple factors that cause decline and reserve factors that compensate {2004} NEURON
    Vol. {44}({1}), pp. {195-208} 
    article  
    Abstract: Memory decline in aging results from multiple factors that influence both executive function and the medial temporal lobe memory system. In advanced aging, frontal-striatal systems are preferentially vulnerable to white matter change, atrophy, and certain forms of neurotransmitter depletion. Frontal-striatal change may underlie mild memory difficulties in aging that are most apparent on tasks demanding high levels of attention and controlled processing. Through separate mechanisms, Alzheimer's disease preferentially affects the medial temporal lobe and cortical networks, including posterior cingulate and retrosplenial cortex early in its progression, often before clinical symptoms are recognized. Disruption of the medial temporal lobe memory system leads directly to memory impairment. Recent findings further suggest that age-associated change is not received passively. Reliance on reserve is emerging as an important factor that determines who ages gracefully and who declines rapidly. Functional imaging studies, in particular, suggest increased recruitment of brain areas in older adults that may reflect a form of compensation.
    BibTeX:
    @article{Buckner2004,
      author = {Buckner, RL},
      title = {Memory and executive function in aging and AD: Multiple factors that cause decline and reserve factors that compensate},
      journal = {NEURON},
      year = {2004},
      volume = {44},
      number = {1},
      pages = {195-208}
    }
    
    Buckner, R., Raichle, M., Miezin, F. & Petersen, S. Functional anatomic studies of memory retrieval for auditory words and visual pictures {1996} JOURNAL OF NEUROSCIENCE
    Vol. {16}({19}), pp. {6219-6235} 
    article  
    Abstract: Functional neuroimaging with positron emission tomography was used to study brain areas activated during memory retrieval. Subjects (n=15) recalled items from a recent study episode (episodic memory) during two paired-associate recall tasks. The tasks differed in that PICTURE RECALL required pictorial retrieval, whereas AUDITORY WORD RECALL required word retrieval. Word REPETITION and REST served as two reference tasks. Comparing recall with repetition revealed the following observations. (1) Right anterior prefrontal activation (similar to that seen in several previous experiments), in addition to bilateral frontal-opercular and anterior cingulate activations. (2) An anterior subdivision of medial frontal cortex [pre-supplementary motor area (SMA)] was activated, which could be dissociated from a more posterior area (SMA proper). (3) Parietal areas were activated, including a posterior medial area near precuneus, that could be dissociated from an anterior parietal area that was deactivated. (4) Multiple medial and lateral cerebellar areas were activated. Comparing recall with rest revealed similar activations, except right prefrontal activation was minimal and activations related to motor and auditory demands became apparent (e.g., bilateral motor and temporal cortex). Directly comparing picture recall with auditory word recall revealed few notable activations. Taken together, these findings suggest a pathway that is commonly used during the episodic retrieval of picture and word stimuli under these conditions. Many areas in this pathway overlap with areas previously activated by a different set of retrieval tasks using stem-cued recall, demonstrating their generality. Examination of activations within individual subjects in relation to structural magnetic resonance images provided anatomic information about the location of these activations. Such data, when combined with the dissociations between functional areas, provide an increasingly detailed picture of the brain pathways involved in episodic retrieval tasks.
    BibTeX:
    @article{Buckner1996,
      author = {Buckner, RL and Raichle, ME and Miezin, FM and Petersen, SE},
      title = {Functional anatomic studies of memory retrieval for auditory words and visual pictures},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1996},
      volume = {16},
      number = {19},
      pages = {6219-6235}
    }
    
    Buckner, R., Snyder, A., Shannon, B., LaRossa, G., Sachs, R., Fotenos, A., Sheline, Y., Klunk, W., Mathis, C., Morris, J. & Mintun, M. Molecular, structural, and functional characterization of Alzheimer's disease: Evidence for a relationship between default activity, amyloid, and memory {2005} JOURNAL OF NEUROSCIENCE
    Vol. {25}({34}), pp. {7709-7717} 
    article DOI  
    Abstract: Alzheimer's disease ( AD) and antecedent factors associated with AD were explored using amyloid imaging and unbiased measures of longitudinal atrophy in combination with reanalysis of previous metabolic and functional studies. In total, data from 764 participants were compared across five in vivo imaging methods. Convergence of effects was seen in posterior cortical regions, including posterior cingulate, retrosplenial, and lateral parietal cortex. These regions were active in default states in young adults and also showed amyloid deposition in older adults with AD. At early stages of AD progression, prominent atrophy and metabolic abnormalities emerged in these posterior cortical regions; atrophy in medial temporal regions was also observed. Event-related functional magnetic resonance imaging studies further revealed that these cortical regions are active during successful memory retrieval in young adults. One possibility is that lifetime cerebral metabolism associated with regionally specific default activity predisposes cortical regions to AD-related changes, including amyloid deposition, metabolic disruption, and atrophy. These cortical regions may be part of a network with the medial temporal lobe whose disruption contributes to memory impairment.
    BibTeX:
    @article{Buckner2005,
      author = {Buckner, RL and Snyder, AZ and Shannon, BJ and LaRossa, G and Sachs, R and Fotenos, AF and Sheline, YI and Klunk, WE and Mathis, CA and Morris, JC and Mintun, MA},
      title = {Molecular, structural, and functional characterization of Alzheimer's disease: Evidence for a relationship between default activity, amyloid, and memory},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2005},
      volume = {25},
      number = {34},
      pages = {7709-7717},
      doi = {{10.1523/JNEUROSCI.2177-05.2005}}
    }
    
    Buckner, R.L., Andrews-Hanna, J.R. & Schacter, D.L. The brain's default network - Anatomy, function, and relevance to disease {2008}
    Vol. {1124}YEAR IN COGNITIVE NEUROSCIENCE 2008, pp. {1-38} 
    incollection DOI  
    Abstract: Thirty years of brain imaging research has converged to define the brain's default network-a novel and only recently appreciated brain system that participates in internal modes of cognition. Here we synthesize past observations to provide strong evidence that the default network is a specific, anatomically defined brain system preferentially active when individuals are not focused on the external environment. Analysis of connectional anatomy in the monkey supports the presence of an interconnected brain system. Providing insight into function, the default network is active when individuals are engaged in internally focused tasks including autobiographical memory retrieval, envisioning the future, and conceiving the perspectives of others. Probing the functional anatomy of the network in detail reveals that it is best understood as multiple interacting subsystems. The medial temporal lobe subsystem provides information from prior experiences in the form of memories and associations that are the building blocks of mental simulation. The medial prefrontal subsystem facilitates the flexible use of this information during the construction of self-relevant mental simulations. These two subsystems converge on important nodes of integration including the posterior cingulate cortex. The implications of these functional and anatomical observations are discussed in relation to possible adaptive roles of the default network for using past experiences to plan for the future, navigate social interactions, and maximize the utility of moments when we are not otherwise engaged by the external world. We conclude by discussing the relevance of the default network for understanding mental disorders including autism, schizophrenia, and Alzheimer's disease.
    BibTeX:
    @incollection{Buckner2008,
      author = {Buckner, Randy L. and Andrews-Hanna, Jessica R. and Schacter, Daniel L.},
      title = {The brain's default network - Anatomy, function, and relevance to disease},
      booktitle = {YEAR IN COGNITIVE NEUROSCIENCE 2008},
      year = {2008},
      volume = {1124},
      pages = {1-38},
      doi = {{10.1196/annals.1440.011}}
    }
    
    Bunge, S., Hazeltine, E., Scanlon, M., Rosen, A. & Gabrieli, J. Dissociable contributions of prefrontal and parietal cortices to response selection {2002} NEUROIMAGE
    Vol. {17}({3}), pp. {1562-1571} 
    article DOI  
    Abstract: The ability to select between possible responses to a given situation is central to human cognition. The goal of this study was to distinguish between brain areas representing candidate responses and areas selecting between competing response alternatives. Event-related fMRI data were acquired while 10 healthy adults performed a task used to examine response competition: the Eriksen flanker task. Left parietal cortex was activated by either of two manipulations that increased the need to maintain a representation of possible responses. In contrast, lateral prefrontal. and rostral anterior cingulate cortices were specifically engaged by the need to select among competing response alternatives. These findings support the idea that parietal cortex is involved in activating possible responses on the basis of learned stimulus-response associations, and that prefrontal. cortex is recruited when there is a need to select between competing responses. (C) 2002 Elsevier Science (USA).
    BibTeX:
    @article{Bunge2002,
      author = {Bunge, SA and Hazeltine, E and Scanlon, MD and Rosen, AC and Gabrieli, JDE},
      title = {Dissociable contributions of prefrontal and parietal cortices to response selection},
      journal = {NEUROIMAGE},
      year = {2002},
      volume = {17},
      number = {3},
      pages = {1562-1571},
      doi = {{10.1006/nimg.2002.1252}}
    }
    
    Bunge, S., Ochsner, K., Desmond, J., Glover, G. & Gabrieli, J. Prefrontal regions involved in keeping information in and out of mind {2001} BRAIN
    Vol. {124}({Part 10}), pp. {2074-2086} 
    article  
    Abstract: Goal-directed behaviour depends on keeping relevant information in mind (working memory) and irrelevant information out of mind (behavioural inhibition or interference resolution). Prefrontal cortex is essential for working memory and for interference resolution, but it is unknown whether these two mental abilities are mediated by common or distinct prefrontal regions. To address this question, functional MRI was used to identify brain regions activated by separate manipulations of working memory load and interference within a single task (the Sternberg item recognition paradigm). Both load and interference manipulations were associated with performance decrements. Subjects were unaware of the interference manipulation. There was a high degree of overlap between the regions activated by load and interference, which included bilateral ventrolateral and dorsolateral prefrontal cortex, anterior insula, anterior cingulate and parietal cortex. Critically, no region was activated exclusively by interference. Several regions within this common network exhibited a brain-behaviour correlation across subjects for the load or interference manipulation. Activation within the right middle frontal gyrus and left inferior frontal gyrus was correlated with the ability to resolve interference efficiently, but not the ability to manage an increased working memory load efficiently. Conversely, activation of the anterior cingulate was correlated with load susceptibility, but was not correlated with interference susceptibility. These findings suggest that, within the circuitry engaged by this task, some regions are more critically involved in the resolution of interference whereas others are more involved in the resolution of an increase in load. The anterior cingulate was engaged to a greater extent by the load than interference manipulation, suggesting that this region, which is thought to be involved in detecting the need for greater allocation of attentional resources, may be particularly implicated during awareness of the need for cognitive control. In the present study, interference resolution did not involve recruitment of additional inhibitory circuitry, but was instead mediated by a subset of the neural system supporting working memory.
    BibTeX:
    @article{Bunge2001,
      author = {Bunge, SA and Ochsner, KN and Desmond, JE and Glover, GH and Gabrieli, JDE},
      title = {Prefrontal regions involved in keeping information in and out of mind},
      journal = {BRAIN},
      year = {2001},
      volume = {124},
      number = {Part 10},
      pages = {2074-2086}
    }
    
    Burgess, N., Maguire, E., Spiers, H. & O'Keefe, J. A temporoparietal and prefrontal network for retrieving the spatial context of lifelike events {2001} NEUROIMAGE
    Vol. {14}({2}), pp. {439-453} 
    article DOI  
    Abstract: Virtual reality (VR) and event-related functional magnetic resonance imaging were used to study memory for the spatial context of controlled but lifelike events. Subjects received a set of objects from two different people in two different places within a VR environment. Memory for the objects, and for where and from whom they were received was tested by putting the subject back into a place in the company of a person and giving a paired forced choice of objects. In four conditions objects had to be chosen according to different criteria: which was received in that place, which was received from that person, which object was recognized, and which object was widest. Event-related functional magnetic resonance imaging was performed during testing to identify areas involved in retrieval of the spatial context of an event. A network of areas was identified consisting of a temporoparietal pathway running between the precuneus and parahippocampi via retrosplenial cortex and the parieto-occipital sulcus, left hippocampus, bilateral posterior parietal, dorsolateral, ventrolateral and anterior prefrontal cortices, and the anterior cingulate. Of these areas the parahippocampal, right posterior parietal, and posteriodorsal medial parietal areas were specifically involved in retrieval of spatial context compared to retrieval of nonspatial context. The posterior activations are consistent with a model of long-term storage of allocentric representations Mi medial temporal regions with translation to body-centered and head-centered representations computed in right posterior parietal cortex and buffered in the temporoparietal pathway so as to provide an imageable representation in the precuneus. Prefrontal activations are consistent with strategic retrieval processes, including those required to overcome the interference between the highly similar events. (C) 2001 Academic Press.
    BibTeX:
    @article{Burgess2001,
      author = {Burgess, N and Maguire, EA and Spiers, HJ and O'Keefe, J},
      title = {A temporoparietal and prefrontal network for retrieving the spatial context of lifelike events},
      journal = {NEUROIMAGE},
      year = {2001},
      volume = {14},
      number = {2},
      pages = {439-453},
      doi = {{10.1006/nimg.2001.0806}}
    }
    
    Burwell, R. & Amaral, D. Cortical afferents of the perirhinal, postrhinal, and entorhinal cortices of the rat {1998} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {398}({2}), pp. {179-205} 
    article  
    Abstract: We have divided the cortical regions surrounding the rat hippocampus into three cytoarchitectonically discrete cortical regions, the perirhinal, the postrhinal, and the entorhinal cortices. These regions appear to be homologous to the monkey perirhinal, parahippocampal, and entorhinal cortices, respectively. The origin of cortical afferents to these regions is well-documented in the monkey but less is known about them in the rat. The present study investigated the origins of cortical input to the rat perirhinal (areas 35 and 36) and postrhinal cortices and the lateral and medial subdivisions of the entorhinal cortex (LEA and MEA) by placing injections of retrograde tracers at several locations within each region. For each experiment, the total numbers of retrogradely labeled cells (and cell densities) were estimated for 34 cortical regions. We found that the complement of cortical inputs differs for each of the five regions. Area 35 receives its heaviest input from entorhinal, piriform, and insular areas. Area 36 receives its heaviest projections from other temporal cortical regions such as ventral temporal association cortex. Area 36 also receives substantial input from insular and entorhinal areas. Whereas area 36 receives similar magnitudes of input from cortices subserving all sensory modalities, the heaviest projections to the postrhinal cortex originate in visual associational cortex and visuospatial areas such as the posterior parietal cortex. The cortical projections to the LEA are heavier than to the MEA. and differ in origin. The LEA is primarily innervated by the perirhinal, insular, piriform, and postrhinal cortices. The MEA is primarily innervated by the piriform and postrhinal cortices, but also receives minor projections from retrosplenial, posterior parietal, and visual association areas. J. Comp. Neurol. 398:179-205, 1998. (C) 1998 Wiley-Liss, Inc.
    BibTeX:
    @article{Burwell1998,
      author = {Burwell, RD and Amaral, DG},
      title = {Cortical afferents of the perirhinal, postrhinal, and entorhinal cortices of the rat},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {1998},
      volume = {398},
      number = {2},
      pages = {179-205}
    }
    
    Bush, G., Frazier, J., Rauch, S., Seidman, L., Whalen, P., Jenike, M., Rosen, B. & Biederman, J. Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI and the counting stroop {1999} BIOLOGICAL PSYCHIATRY
    Vol. {45}({12}), pp. {1542-1552} 
    article  
    Abstract: Background: The anterior cingulate cognitive division (ACcd) plays a central role in attentional processing by: 1) modulating stimulus selection (i.e,, focusing attention) and/or 2) mediating response selection. We hypothesized that ACcd dysfunction might therefore contribute to producing core features of attention-defcit/hyperactivity disorder (ADHD), namely inattention and impulsivity. ADHD subjects have indeed shown performance deficits on the Color Stroop, an attentional/cognitive interference task known to recuit. the ACcd. Recently, the Counting Stroop, a Stroop-variant specialized for functional magnetic resonance imaging (fMRI), produced ACcd activation in healthy adults. In the present fMRI study, the Counting Stroop was used to examine the functional integrity of the ACcd in ADHD. Methods: Sixteen unmedicated adults from two groups (8 with ADHD and 8 matched control subjects) performed the Counting Stroop during fMRI Results: While both groups showed an interference effect, the ADHD group, in contrast to control subjects, failed to activate the ACcd during the Counting Stroop. Direct comparisons showed ACcd activity was significantly higher in the control group. ADHD subjects did activate a frontostriatal-insular network indicating ACcd hypoactivity was not caused by globally poor nehrronal responsiveness, Conclusions: The data support a hypothesized dysfunction of the ACcd in ADHD.
    BibTeX:
    @article{Bush1999,
      author = {Bush, G and Frazier, JA and Rauch, SL and Seidman, LJ and Whalen, PJ and Jenike, MA and Rosen, BR and Biederman, J},
      title = {Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI and the counting stroop},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {1999},
      volume = {45},
      number = {12},
      pages = {1542-1552}
    }
    
    Bush, G., Luu, P. & Posner, M. Cognitive and emotional influences in anterior cingulate cortex {2000} TRENDS IN COGNITIVE SCIENCES
    Vol. {4}({6}), pp. {215-222} 
    article  
    Abstract: Anterior cingulate cortex (ACC) is a part of the brain's limbic system. Classically, this region has been related to affect on the basis of lesion studies in humans and in animals. In the late 1980s, neuroimaging research indicated that ACC was active in many studies of cognition. The findings from EEG studies of a focal area of negativity in scalp electrodes following an error response led to the idea that ACC might be the brain's error detection and correction device. In this article, these various findings are reviewed in relation to the idea that ACC is a part of a circuit involved in a form of attention that serves to regulate both cognitive and emotional processing. Neuroimaging studies showing that separate areas of ACC are involved in cognition and emotion are discussed and related to results showing that the error negativity is influenced by affect and motivation. In addition, the development of the emotional and cognitive roles of ACC are discussed. and how the success of this regulation in controlling responses might be correlated with cingulate size. Finally, some theories are considered about how the different subdivisions of ACC might interact with other cortical structures as a part of the circuits involved in the regulation or mental and emotional activity.
    BibTeX:
    @article{Bush2000,
      author = {Bush, G and Luu, P and Posner, MI},
      title = {Cognitive and emotional influences in anterior cingulate cortex},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      year = {2000},
      volume = {4},
      number = {6},
      pages = {215-222}
    }
    
    Bush, G., Valera, E. & Seidman, L. Functional neuroimaging of attention-deficit/hyperactivity disorder: A review and suggested future directions {2005} BIOLOGICAL PSYCHIATRY
    Vol. {57}({11}), pp. {1273-1284} 
    article DOI  
    Abstract: Over the past few decades, functional neuroimaging techniques have begun to provide unprecedented windows on the neurobiology of attention-deficient/hyperactivity disorder (ADHD) and the neural effects of medications used to treat the disorder. Convergent data from neuroimaging, neuropsychological, genetics, and neurochemical studies have implicated dysfunction of fronto-strialal structures (lateral prefrontal cortex, dorsal anterior cingulate cortex, caudate, and putamen) as likely contributing to the pathophysiology of ADHD. This review 1) provides an overview of the main imaging techniques being used to study ADHD; 2) discusses their relative strengths and weaknesses, highlighting how they can complement one another; 3) shows how the functional imaging literature, which has built on the structural imaging data, is now being used to test focused hypotheses regarding the neurobiological substrate of ADHD; and 4) suggests guidelines for improving future functional imaging studies. Although at present there are no accepted uses for functional imaging in diagnosing ADHD, this article mentions possible future clinical uses of imaging in ADHD.
    BibTeX:
    @article{Bush2005,
      author = {Bush, G and Valera, EM and Seidman, LJ},
      title = {Functional neuroimaging of attention-deficit/hyperactivity disorder: A review and suggested future directions},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {2005},
      volume = {57},
      number = {11},
      pages = {1273-1284},
      note = {Conference on Advancing the Neuroscience of Attention-Deficit/Hyperactivity Disorder (ADHD), Boston, MA, FEB 28, 2004},
      doi = {{10.1016/j.biopsych.2005.01.034}}
    }
    
    Bush, G., Vogt, B., Holmes, J., Dale, A., Greve, D., Jenike, M. & Rosen, B. Dorsal anterior cingulate cortex: A role in reward-based decision making {2002} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {99}({1}), pp. {523-528} 
    article  
    Abstract: Dorsal anterior cingulate cortex (dACC) is a brain region that subserves cognition and motor control, but the mechanisms of these functions remain unknown. Human neuroimaging and monkey electrophysiology studies have provided valuable insights, but it has been difficult to link the two literatures. Based on monkey single-unit recordings, we hypothesized that human dACC is comprised of a mixture of functionally distinct cells that variously anticipate and detect targets, indicate novelty, influence motor responses, encode reward values, and signal errors. As an initial test of this conceptualization, the current event-related functional MRI study used a reward-based decision-making task to isolate responses from a subpopulation of dACC cells sensitive to reward reduction. As predicted, seven of eight subjects showed significant (p < 10(-4)) dACC activation when contrasting reduced reward (REDrew) trials to fixation (FIX). Confirmatory group analyses then corroborated the predicted ordinal relationships of functional MRI activation expected during each trial type (REDrew > SWITCH > CONrew greater than or equal to FIX). The data support a role for dACC in reward-based decision making, and by linking the human and monkey literatures, provide initial support for the existence of heterogeneity within dACC. These findings should be of interest to those studying reward, cognition, emotion, motivation, and motor control.(parallel to)
    BibTeX:
    @article{Bush2002,
      author = {Bush, G and Vogt, BA and Holmes, J and Dale, AM and Greve, D and Jenike, MA and Rosen, BR},
      title = {Dorsal anterior cingulate cortex: A role in reward-based decision making},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {2002},
      volume = {99},
      number = {1},
      pages = {523-528},
      note = {7th Annual Meeting of the Organization for Human Brain Mapping, BRIGHTON, ENGLAND, JUN 10-14, 2001}
    }
    
    Bush, G., Whalen, P., Rosen, B., Jenike, M., McInerney, S. & Rauch, S. The counting stroop: An interference task specialized for functional neuroimaging - Validation study with functional MRI {1998} HUMAN BRAIN MAPPING
    Vol. {6}({4}), pp. {270-282} 
    article  
    Abstract: The anterior cingulate cortex has been activated by color Stroop tasks, supporting the hypothesis that it is recruited to mediate response selection or allocate attentional resources when confronted with competing information-processing streams. The current study used the newly developed ``Counting Stroop'' to identify the mediating neural substrate of cognitive interference. The Counting Stroop, a Stroop variant allowing on-line response time measurements while obviating speech, was created because speaking produces head movements that can exceed those tolerated by functional magnetic resonance imaging (fMRI), preventing the collection of vital performance data. During this task, subjects report by button-press the number of words (1-4) on the screen, regardless of word meaning. Interference trials contain number words that are incongruent with the correct response (e.g., ``two'' written three times), while neutral trials contain single semantic category common animals (e.g., ``bird''). Nine normal right-handed adult volunteers underwent fMRI while performing the Counting Stroop. Group fMRI data revealed significant (P less than or equal to 10(-4)) activity in the cognitive division of anterior cingulate cortex when contrasting the interference vs. neutral conditions. On-line performance data showed 1) longer reaction times for interference blocks than for neutral ones, and 2) decreasing reaction times with practice during interference trials (diminished interference effects), indicating that learning occurred. The performance data proved to be a useful guide in analyzing the image data. The relative difference in anterior cingulate activity between the interference and neutral conditions decreased as subjects learned the task. These findings have ramifications for attentional, cognitive interference, learning, and motor control mechanism theories. Hum. Brain Mapping 6:270-282, 1998. a 1998 Wiley-Liss, Inc.
    BibTeX:
    @article{Bush1998,
      author = {Bush, G and Whalen, PJ and Rosen, BR and Jenike, MA and McInerney, SC and Rauch, SL},
      title = {The counting stroop: An interference task specialized for functional neuroimaging - Validation study with functional MRI},
      journal = {HUMAN BRAIN MAPPING},
      year = {1998},
      volume = {6},
      number = {4},
      pages = {270-282},
      note = {4th Annual Meeting of the Cognitive-Neuroscience-Society, BOSTON, MASSACHUSETTS, MAR 23-25, 1997}
    }
    
    Bushnell, M., Duncan, G., Hofbauer, R., Ha, B., Chen, J. & Carrier, B. Pain perception: Is there a role for primary somatosensory cortex? {1999} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {96}({14}), pp. {7705-7709} 
    article  
    Abstract: Anatomical, physiological, and lesion data implicate multiple cortical regions in the complex experience of pain. These regions include primary and secondary somatosensory cortices, anterior cingulate cortex, insular cortex, and regions of the frontal cortex. Nevertheless, the role of different cortical areas in pain processing is controversial, particularly that of primary somatosensory cortex (S1). Human brain-imaging studies do not consistently reveal pain-related activation of S1, and older studies of cortical lesions and cortical stimulation in humans did not uncover a clear role of S1 in the pain experience. Whereas studies from a number of laboratories show that S1 is activated during the presentation of noxious stimuli as well as in association with some pathological pain states, others do not report such activation. Several factors may contribute to the different results among studies. First, we have evidence demonstrating that S1 activation is highly modulated by cognitive factors that alter pain perception, including attention and previous experience. Second, the precise somatotopic organization of S1 may lead to small focal activations, which are degraded by sulcal anatomical variability when averaging data across subjects. Third, the probable mixed excitatory and inhibitory effects of nociceptive input to S1 could be disparately represented in different experimental paradigms. Finally, statistical considerations are important in interpreting negative findings in S1. We conclude that, when these factors are taken into account, the bulk of the evidence now strongly supports a prominent and highly modulated role for S1 cortex in the sensory aspects of pain, including localization and discrimination of pain intensity.
    BibTeX:
    @article{Bushnell1999,
      author = {Bushnell, MC and Duncan, GH and Hofbauer, RK and Ha, B and Chen, JI and Carrier, B},
      title = {Pain perception: Is there a role for primary somatosensory cortex?},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1999},
      volume = {96},
      number = {14},
      pages = {7705-7709},
      note = {National-Academy-of-Sciences Colloguium on the Neurobiology of Pain, IRVINE, CALIFORNIA, DEC 11-13, 1998}
    }
    
    Cabeza, R., Grady, C., Nyberg, L., McIntosh, A., Tulving, E., Kapur, S., Jennings, J., Houle, S. & Craik, F. Age-related differences in neural activity during memory encoding and retrieval: A positron emission tomography study {1997} JOURNAL OF NEUROSCIENCE
    Vol. {17}({1}), pp. {391-400} 
    article  
    Abstract: Positron emission tomography (PET) was used to compare regional cerebral blood flow (rCBF) in young (mean 26 years) and old (mean 70 years) subjects while they were encoding, recognizing, and recalling word pairs. A multivariate partial-least-squares (PLS) analysis of the data was used to identify age-related neural changes associated with (1) encoding versus retrieval and (2) recognition versus recall. Young subjects showed higher activation than old subjects (1) in left prefrontal and occipito-temporal regions during encoding and (2) in right prefrontal and parietal regions during retrieval. Old subjects showed relatively higher activation than young subjects in several regions, including insular regions during encoding, cuneus/precuneus regions during recognition, and left prefrontal regions during recall. Frontal activity in young subjects was left-lateralized during encoding and right-lateralized during recall [hemispheric encoding/retrieval asymmetry (HERA)], whereas old adults showed little frontal activity during encoding and a more bilateral pattern of frontal activation during retrieval. In young subjects, activation in recall was higher than that in recognition in cerebellar and cingulate regions, whereas recognition showed higher activity in right temporal and parietal regions. In old subjects, the differences in blood flow between recall and recognition were smaller in these regions, yet more pronounced in other regions. Taken together, the results indicate that advanced age is associated with neural changes in the brain systems underlying encoding, recognition, and recall. These changes take two forms: (1) age-related decreases in local regional activity, which may signal less efficient processing by the old, and (2) age-related increases in activity, which may signal functional compensation.
    BibTeX:
    @article{Cabeza1997,
      author = {Cabeza, R and Grady, CL and Nyberg, L and McIntosh, AR and Tulving, E and Kapur, S and Jennings, JM and Houle, S and Craik, FIM},
      title = {Age-related differences in neural activity during memory encoding and retrieval: A positron emission tomography study},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1997},
      volume = {17},
      number = {1},
      pages = {391-400}
    }
    
    Cabeza, R. & Nyberg, L. Imaging cognition II: An empirical review of 275 PET and fMRI studies {2000} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {12}({1}), pp. {1-47} 
    article  
    Abstract: Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have been extensively used to explore the functional neuroanatomy of cognitive functions. Here we review 275 PET and fMRI studies of attention (sustained, selective, Stroop, orientation, divided), perception (object, face, space/motion, smell), imagery (object, space/motion), language (written/spoken word recognition, spoken/no spoken response), working memory (verbal/numeric, object, spatial, problem solving), semantic memory retrieval (categorization, generation), episodic memory encoding (verbal, object, spatial), episodic memory retrieval (verbal, nonverbal, success, effort, mode, context), priming (perceptual, conceptual), and procedural memory (conditioning, motor, and nonmotor skill learning). To identify consistent activation patterns associated with these cognitive operations, data from 412 contrasts were summarized at the level of cortical Brodmann's areas, insula, thalamus, medial-temporal lobe (including hippocampus), basal ganglia, and cerebellum. For perception and imagery, activation patterns included primary and secondary regions in the dorsal and ventral pathways. For attention and working memory, activations were usually found in prefrontal and parietal regions. For language and semantic memory retrieval, typical regions included left prefrontal and temporal regions. For episodic memory encoding, consistently activated regions included left prefrontal and medial-temporal regions. For episodic memory retrieval, activation patterns included prefrontal, medial-temporal, and posterior midline regions. For priming, deactivations in prefrontal (conceptual) or extrastriate (perceptual) regions were consistently seen. For procedural memory, activations were found in motor as well as in non-motor brain areas. Analysis of regional activations across cognitive domains suggested that several brain regions, including the cerebellum, are engaged by a variety of cognitive challenges. These observations are discussed in relation to functional specialization as well as functional integration.
    BibTeX:
    @article{Cabeza2000,
      author = {Cabeza, R and Nyberg, L},
      title = {Imaging cognition II: An empirical review of 275 PET and fMRI studies},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {2000},
      volume = {12},
      number = {1},
      pages = {1-47}
    }
    
    Cabeza, R. & Nyberg, L. Imaging cognition: An empirical review of PET studies with normal subjects {1997} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {9}({1}), pp. {1-26} 
    article  
    Abstract: We review PET studies of higher-order cognitive processes, including attention (sustained and selective), perception (of objects, faces, and locations), language (word listening, reading, and production), working memory (phonological and visuospatial), semantic memory retrieval (intentional and incidental), episodic memory retrieval (verbal and nonverbal), priming, and procedural memory (conditioning and skill learning). For each process, we identify activation patterns including the most consistently involved regions. These regions constitute important components of the network of brain regions that underlie each function.
    BibTeX:
    @article{Cabeza1997a,
      author = {Cabeza, R and Nyberg, L},
      title = {Imaging cognition: An empirical review of PET studies with normal subjects},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {1997},
      volume = {9},
      number = {1},
      pages = {1-26}
    }
    
    Cagnin, A., Brooks, D., Kennedy, A., Gunn, R., Myers, R., Turkheimer, F., Jones, T. & Banati, R. In-vivo measurement of activated microglia in dementia {2001} LANCET
    Vol. {358}({9280}), pp. {461-467} 
    article  
    Abstract: Background Activated microglia have a key role in the brain's immune response to neuronal degeneration. The transition of microglia from the normal resting state to the activated state is associated with an increased expression of receptors known as peripheral benzodiazepine binding sites, which are abundant on cells of mononuclear phagocyte lineage. We used brain imaging to study expression of these sites in healthy individuals and patients with Alzheimer's disease. Methods We studied 15 normal individuals (age 32-80 years), eight patients with Alzheimer's disease, and one patient with minimal cognitive impairment. Quantitative in-vivo measurements of glial activation were obtained with positron emission tomography (PET) and carbon-11-labelled (R)-PK11195, a specific ligand for the peripheral benzodiazepine binding site. Findings In normal individuals, regional [C-11](R)-PK11195 binding did not significantly change with age, except in the thalamus, where an age-dependent increase was found. By contrast, patients with Alzheimer's disease showed significantly increased regional [C-11](R)-PK11195 binding in the entorhinal, temporoparietal, and cingulate cortex. Interpretation In-vivo detection of increased [C-11](R)-PK11195 binding in Alzheimer-type dementia, including mild and early forms, suggests that microglial activation is an early event in the pathogenesis of the disease.
    BibTeX:
    @article{Cagnin2001,
      author = {Cagnin, A and Brooks, DJ and Kennedy, AM and Gunn, RN and Myers, R and Turkheimer, FE and Jones, T and Banati, RB},
      title = {In-vivo measurement of activated microglia in dementia},
      journal = {LANCET},
      year = {2001},
      volume = {358},
      number = {9280},
      pages = {461-467}
    }
    
    Callicott, J., Bertolino, A., Mattay, V., Langheim, F., Duyn, J., Coppola, R., Goldberg, T. & Weinberger, D. Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited {2000} CEREBRAL CORTEX
    Vol. {10}({11}), pp. {1078-1092} 
    article  
    Abstract: Evidence implicates subtle neuronal pathology of the prefrontal cortex (PFC) in schizophrenia, but how this pathology is reflected in physiological neuroimaging experiments remains controversial. We investigated PFC function in schizophrenia using functional magnetic resonance imaging (fMRI) and a parametric version of the n-back working memory (WM) task. In a group of patients who performed relatively well on this task, there were three fundamental deviations from the `healthy' pattern of PFC fMRI activation to varying WM difficulty. The first characteristic was a greater magnitude of PFC fMRI activation in the context of slightly impaired WM performance (i.e. physiological inefficiency). The second was that the significant correlations between behavioral WM performance and dorsal PFC fMRI activation were in opposite directions in the two groups. Third, the magnitude of the abnormal dorsal PFC fMRI response was predicted by an assay of N-acetylaspartate concentrations (NAA) in dorsal PFC, a measure of neuronal pathology obtained using proton magnetic resonance spectroscopy. Patients had significantly lower dorsal PFC NAA than controls and dorsal PFC NAA inversely predicted the fMRI response in dorsal PFC (areas 9, 46) to varying WM difficulty - supporting the assumption that abnormal PFC responses arose from abnormal PFC neurons. These data suggest that under certain conditions the physiological ramifications of dorsal PFC neuronal pathology in schizophrenia includes exaggerated and inefficient cortical activity, especially of dorsal PFC.
    BibTeX:
    @article{Callicott2000,
      author = {Callicott, JH and Bertolino, A and Mattay, VS and Langheim, FJP and Duyn, J and Coppola, R and Goldberg, TE and Weinberger, DR},
      title = {Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited},
      journal = {CEREBRAL CORTEX},
      year = {2000},
      volume = {10},
      number = {11},
      pages = {1078-1092}
    }
    
    CAMERON, V., NISHIMURA, E., MATHEWS, L., LEWIS, K., SAWCHENKO, P. & VALE, W. HYBRIDIZATION HISTOCHEMICAL-LOCALIZATION OF ACTIVIN RECEPTOR SUBTYPES IN RAT-BRAIN, PITUITARY, OVARY, AND TESTIS {1994} ENDOCRINOLOGY
    Vol. {134}({2}), pp. {799-808} 
    article  
    Abstract: We have studied the distribution of activin receptor gene expression in the brain, pituitary, ovary, and testis of the adult rat by in situ hybridization, using probes complementary to the mRNAs encoding the mouse activin receptor subtypes II and IIB (ActRII and ActRIIB). Throughout the brain, ActRII mRNA expression was stronger than that of ActRIIB, and the patterns of expression were similar, although not identical. The most intense sites of activin receptor gene expression were the hippocampal formation, especially the dentate gyrus (ActRII), taenia tecta, and induseum griseum; the amygdala, particularly the amygdaloid-hippocampal transition zone; and throughout the cortical mantle, including the primary olfactory cortex (piriform cortex and olfactory tubercle); other regions of the cortex showing lesser degrees of hybridization included the cingulate cortex, claustrum, entorhinal cortex, and subiculum. In addition, moderate levels of expression were observed in several hypothalamic areas involved in neuroendocrine regulation, such as the suprachiasmatic, supraoptic, paraventricular, and arcuate nuclei. Moreover, activin receptors were also expressed in regions with inputs to the hypothalamus, both in the forebrain (bed nucleus of the stria terminalis and medial preoptic area) and within the brainstem (nucleus of the solitary tract, dorsal motor nucleus of the vagus, locus coeruleus, and mesencephalic raphe system). ActRII mRNA was observed in the intermediate lobe of the pituitary and, less prominently, in the anterior lobe, whereas ActRIIB appeared to be weakly expressed throughout all three pituitary divisions. In both male and female gonads, activin receptor message was clearly present in germ cells, and ActRII was the predominant form. In the ovary, in addition to an intense signal in the oocyte, activin receptor was expressed in corpus luteum and granulosa cells during diestrous day 1. In the testis, there was a strong ActRII signal in rounded spermatids, and a moderate signal in pachytene spermatocytes. In contrast, ActRIIB was absent within tubules, but weakly expressed in interstitial and Leydig cells. This is the first report of the distribution of activin receptor message in adult mammalian tissues. Although consistent with some previously suggested functional associations of activin-containing pathways in the brain, this pattern of expression suggests a greater role for activin than was previously appreciated in cortical, limbic, and somatosensory pathways and in the maturation of germ cells in the gonads of both male and female rats.
    BibTeX:
    @article{CAMERON1994,
      author = {CAMERON, VA and NISHIMURA, E and MATHEWS, LS and LEWIS, KA and SAWCHENKO, PE and VALE, WW},
      title = {HYBRIDIZATION HISTOCHEMICAL-LOCALIZATION OF ACTIVIN RECEPTOR SUBTYPES IN RAT-BRAIN, PITUITARY, OVARY, AND TESTIS},
      journal = {ENDOCRINOLOGY},
      year = {1994},
      volume = {134},
      number = {2},
      pages = {799-808}
    }
    
    Cardinal, R., Parkinson, J., Hall, J. & Everitt, B. Emotion and motivation: the role of the amygdala, ventral striatum, and prefrontal cortex {2002} NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
    Vol. {26}({3}), pp. {321-352} 
    article  
    Abstract: Emotions are multifaceted, but a key aspect of emotion involves the assessment of the value of environmental stimuli. This article reviews the many psychological representations, including representations of stimulus value, which are formed in the brain during Pavlovian and instrumental conditioning tasks. These representations may be related directly to the functions of cortical and subcortical neural structures. The basolateral amygdala (BLA) appears to be required for a Pavlovian conditioned stimulus (CS) to gain access to the current value of the specific unconditioned stimulus (US) that it predicts, while the central nucleus of the amygdala acts as a controller of brainstem arousal and response systems, and subserves some forms of stimulus-response Pavlovian conditioning. The nucleus accumbens, which appears not to be required for knowledge of the contingency between instrumental actions and their outcomes, nevertheless influences instrumental behaviour strongly by allowing Pavlovian CSs to affect the level of instrumental responding (Pavlovian-instrumental transfer), and is required for the normal ability of animals to choose rewards that are delayed. The prelimbic cortex is required for the detection of instrumental action-outcome contingencies, while insular cortex may allow rats to retrieve the values of specific foods via their sensory properties. The orbitofrontal cortex, like the BLA, may represent aspects of reinforcer value that govern instrumental choice behaviour. Finally, the anterior cingulate cortex, implicated in human disorders of emotion and attention, may have multiple roles in responding to the emotional significance of stimuli and to errors in performance, preventing responding to inappropriate stimuli. (C) 2002 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{Cardinal2002,
      author = {Cardinal, RN and Parkinson, JA and Hall, J and Everitt, BJ},
      title = {Emotion and motivation: the role of the amygdala, ventral striatum, and prefrontal cortex},
      journal = {NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS},
      year = {2002},
      volume = {26},
      number = {3},
      pages = {321-352}
    }
    
    Cardinal, R., Pennicott, D., Sugathapala, C., Robbins, T. & Everitt, B. Impulsive choice induced in rats by lesions of the nucleus accumbens core {2001} SCIENCE
    Vol. {292}({5526}), pp. {2499-2501} 
    article  
    Abstract: Impulsive choice is exemplified by choosing a small or poor reward that is available immediately, in preference to a Larger but delayed reward. Impulsive choice contributes to drug addiction, attention-deficit/hyperactivity disorder, mania, and personality disorders, but its neuroanatomical basis is unclear. Here, we show that selective Lesions of the nucleus accumbens core induce persistent impulsive choice in rats. In contrast, damage to two of its afferents, the anterior cingulate cortex and medial prefrontal cortex, had no effect on this capacity. Thus, dysfunction of the nucleus accumbens core may be a key element in the neuropathology of impulsivity.
    BibTeX:
    @article{Cardinal2001,
      author = {Cardinal, RN and Pennicott, DR and Sugathapala, CL and Robbins, TW and Everitt, BJ},
      title = {Impulsive choice induced in rats by lesions of the nucleus accumbens core},
      journal = {SCIENCE},
      year = {2001},
      volume = {292},
      number = {5526},
      pages = {2499-2501}
    }
    
    Carmichael, S. & Price, J. Limbic connections of the orbital and medial prefrontal cortex in macaque monkeys {1995} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {363}({4}), pp. {615-641} 
    article  
    Abstract: Previous studies have shown that the orbital and medial prefrontal cortex (OMPFC) is extensively connected with medial temporal and cingulate limbic structures. In this study, the organization of these projections was defined in relation to architectonic areas within the OMPFC. All of the limbic structures were substantially connected with the following posterior and medial orbital areas: the posteromedial, medial, intermediate, and lateral agranular insular areas (Iapm, Iam, Iai, and Ial, respectively) and areas 11m, 13a, 13b, 14c, and 14r. In contrast, lateral orbital areas 12o, 12m, and 12l and medial wall areas 24a,b and 32 were primarily connected with the amygdala, the temporal pole, and the cingulate cortex. Data were not obtained on the posteroventral medial wall. Three distinct projections were recognized from the basal amygdaloid nucleus: 1) The dorsal part projected to area 121; 2) the ventromedial part projected to most areas in the posterior and medial orbital cortex except for areas Iai, 12o, 13a, and 14c; and 3) the ventrolateral part projected to orbital areas 120, Iai, 13a, 14c, and to the medial wall areas. The accessory basal and lateral amygdaloid nuclei projected most strongly to areas in the posterior and medial orbital cortex. The medial, anterior cortical, and central amygdaloid nuclei and the periamygdaloid cortex were connected with the posterior orbital areas. The projection from the hippocampus originated from the rostral subiculum and terminated in the medial orbital areas. The same region was reciprocally connected with the anteromedial nucleus of the thalamus, which received input from the rostral subiculum. The parahippocampal cortical areas (including the temporal polar, entorhinal, perirhinal, and posterior parahippocampal cortices) were primarily connected with posterior and medial orbital areas, with some projections to the dorsal part of the medial wall. The rostral cingulate cortex sent fibers to the medial wall, to the medial orbital areas, and to lateral areas 12o, 12r, and Iai. The posterior cingulate gyrus, including the caudomedial lobule, was especially strongly connected with area 11m. (C) 1995 Wiley-Liss, Inc.
    BibTeX:
    @article{Carmichael1995,
      author = {Carmichael, ST and Price, JL},
      title = {Limbic connections of the orbital and medial prefrontal cortex in macaque monkeys},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {1995},
      volume = {363},
      number = {4},
      pages = {615-641}
    }
    
    Carmichael, S. & Price, J. Sensory and premotor connections of the orbital and medial prefrontal cortex of macaque monkeys {1995} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {363}({4}), pp. {642-664} 
    article  
    Abstract: Sensory and premotor inputs to the orbital and medial prefrontal cortex (OMPFC) were studied with retrograde axonal tracers. Restricted areas of the lateral and posterior orbital cortex had specific connections with visual-, somatosensory-, olfactory-, gustatory-, and visceral-related structures. More medial areas received few direct sensory inputs. Within the lateral and posterior orbital cortex, area 12l received a substantial projection from visual areas in the inferior temporal cortex (TE). Area 12m received somatosensory input from face, digit, or forelimb regions in the opercular part of area 1-2, in area 7b, in the second somatosensory area (SII), and in the anterior infraparietal area (AIP). Areas 13m and 13l also received a projection from the opercular part of areas 1-2 and 3b. The posteromedial and lateral agranular insular areas (Iapm and Ial, respectively) received fibers from the ventral part of the parvicellular division of the ventroposterior medial nucleus of the thalamus (VPMpc) that may represent a visceral afferent system. The dorsal part of VPMpc projected to the adjacent gustatory cortex. These restricted inputs from several sensory modalities and the convergent corticocortical connections to orbital areas 13l and 13m suggest a network related to feeding. The OMPFC was also connected to premotor cortex in ventral area 6 (areas 6va and 6vb), in cingulate area 24c, and probably in the supplementary eye field. Area 6va projected to area 12m, whereas a region of area 6vb projected to area 13l. The region of the supplementary eye field projected to areas 12l, 12o, and 12r. Area Ial received fibers from area 24c. Lighter and more diffuse projections also reached wider areas of the OMPFC. For example, injections in several orbital areas labeled a few cells scattered through the anterior part of area TE and the superior temporal gyrus. There was also a projection to the intermediate agranular insular area (Iai) and to areas 13a and 12o from the apparently multimodal areas in the superior temporal sulcus and gyrus. (C) 1995 Wiley-Liss, Inc.
    BibTeX:
    @article{Carmichael1995a,
      author = {Carmichael, ST and Price, JL},
      title = {Sensory and premotor connections of the orbital and medial prefrontal cortex of macaque monkeys},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {1995},
      volume = {363},
      number = {4},
      pages = {642-664}
    }
    
    Carter, C., Botvinick, M. & Cohen, J. The contribution of the anterior cingulate cortex to executive processes in cognition {1999} REVIEWS IN THE NEUROSCIENCES
    Vol. {10}({1}), pp. {49-57} 
    article  
    Abstract: The anterior cingulate cortex (ACC), on the medial surface of the frontal lobes, has frequently been hypothesized to make critical contributions to the function of neural systems involved in the executive control of cognition. Three principal theories have been developed to account for this role. The first, `motivated attention', emphasizes the limbic identity of the ACC and the effects of lesions to this area of the brain. The second,'attention allocation', emphasizes the fact that during functional neuroimaging studies activation of the ACC is seen during tasks that elicit incompatible response tendencies that must be resolved for correct performance. The third theory, `error detection', reflects the observation of a negative scalp potential occurring during incorrect responses which appears to have a medial frontal generator. The first and last theories suggest evaluative functions by the ACC in the service of control, while attention allocation suggests a strategic function. We have proposed that the data supporting all three theories can be reconciled if the ACC were detecting conflicting processes during task performance that might be associated with errors. In support of this hypothesis we describe results using event-related fMRI which confirm that the ACC does show error related activity but that the same region of the brain also shows increased response related activity during correct responses associated with response competition. This suggests a re-conceptualization of the contribution of the ACC to executive processes that support an evaluative role, specifically the on-line detection of processing conflicts that may be associated with deteriorating performance. Unresolved questions related to the contribution of this region to executive processes and potential future directions for research on the function of this region of the brain are discussed.
    BibTeX:
    @article{Carter1999,
      author = {Carter, CS and Botvinick, MM and Cohen, JD},
      title = {The contribution of the anterior cingulate cortex to executive processes in cognition},
      journal = {REVIEWS IN THE NEUROSCIENCES},
      year = {1999},
      volume = {10},
      number = {1},
      pages = {49-57}
    }
    
    Carter, C., Braver, T., Barch, D., Botvinick, M., Noll, D. & Cohen, J. Anterior cingulate cortex, error detection, and the online monitoring of performance {1998} SCIENCE
    Vol. {280}({5364}), pp. {747-749} 
    article  
    Abstract: An unresolved question in neuroscience and psychology is how the brain monitors performance to regulate behavior. It has been proposed that the anterior cingulate cortex (ACC), on the medial surface of the frontal lobe, contributes to performance monitoring by detecting errors. In this study, event-related functional magnetic resonance imaging was used to examine ACC function. Results confirm that this region shows activity during erroneous responses. However, activity was also observed in the same region during correct responses under conditions of increased response competition. This suggests that the ACC detects conditions under which errors are likely to occur rather than errors themselves.
    BibTeX:
    @article{Carter1998,
      author = {Carter, CS and Braver, TS and Barch, DM and Botvinick, MM and Noll, D and Cohen, JD},
      title = {Anterior cingulate cortex, error detection, and the online monitoring of performance},
      journal = {SCIENCE},
      year = {1998},
      volume = {280},
      number = {5364},
      pages = {747-749}
    }
    
    Carter, C., Macdonald, A., Botvinick, M., Ross, L., Stenger, V., Noll, D. & Cohen, J. Parsing executive processes: Strategic vs. evaluative functions of the anterior cingulate cortex {2000} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {97}({4}), pp. {1944-1948} 
    article  
    Abstract: Event-related functional MRI and a version of the stroop color naming task were used to test two conflicting theories of anterior cingulate cortex (ACC) function during executive processes of cognition. A response-related increase in ACC activity was present when strategic processes were less engaged, and conflict high, but not when strategic processes were engaged and conflict reduced. This is inconsistent with the widely held view that the ACC implements strategic processes to reduce cognitive conflicts, such as response competition. Instead, it suggests that the ACC serves an evaluative function, detecting cognitive states such as response competition, which may lead to poor performance, and representing the knowledge that strategic processes need to be engaged.
    BibTeX:
    @article{Carter2000,
      author = {Carter, CS and Macdonald, AM and Botvinick, M and Ross, LL and Stenger, VA and Noll, D and Cohen, JD},
      title = {Parsing executive processes: Strategic vs. evaluative functions of the anterior cingulate cortex},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {2000},
      volume = {97},
      number = {4},
      pages = {1944-1948}
    }
    
    Carter, C., Mintun, M. & Cohen, J. Interference and facilitation effects during selective attention: An (H2O)-O-15 PET study of Stroop task performance {1995} NEUROIMAGE
    Vol. {2}({4}), pp. {264-272} 
    article  
    Abstract: To investigate the functional anatomy of interference and facilitation during selective attention, we studied 15 normal subjects using the (H2O)-O-15 positron emission tomography technique and a computer presented single-trial Stroop task for cognitive activation. Increases in regional cerebral blood flow (rCBF) were observed in a network of structures that have been previously associated with selective attention, including the anterior cingulate gyrus, the frontal polar cortex, the inferior parietal lobule, and the thalamus, as well as the lingual gyrus. Furthermore rCBF decreases (compared to control states) were observed in lateral extra-striate cortex. rCBF changes in prefrontal and extra-striate regions varied with differences in the need to modulate the influence of word and color information while subjects responded to either incongruent or congruent Stroop stimuli. These results indicate the utility of Stroop procedures for investigating the functional anatomy of selective attention, Given recent interest regarding the role of the anterior cingulate gyrus in the pathophysiology of neuropsychiatric disorders, our results also suggest that the Stroop task can serve as a reliable neurobehavioral probe for this region. The significance of these results for understanding processing mechanisms underlying selective attention is discussed within the framework of a parallel distributed processing model of Stroop task performance. (C) 1995 Academic Press, Inc.
    BibTeX:
    @article{Carter1995,
      author = {Carter, CS and Mintun, M and Cohen, JD},
      title = {Interference and facilitation effects during selective attention: An (H2O)-O-15 PET study of Stroop task performance},
      journal = {NEUROIMAGE},
      year = {1995},
      volume = {2},
      number = {4},
      pages = {264-272}
    }
    
    Carter, C., Mintun, M., Nichols, T. & Cohen, J. Anterior cingulate gyrus dysfunction and selective attention deficits in schizophrenia: [O-15]H2O PET study during single-trial Stroop task performance {1997} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {154}({12}), pp. {1670-1675} 
    article  
    Abstract: Objective: Attentional deficits are a prominent aspect of cognitive dysfunction in schizophrenia. The anterior cingulate gyrus is proposed to be an important component of frontal attentional control systems. Structural and functional abnormalities have been reported in this region in schizophrenia, but their relationship to attentional deficits is unknown. The authors investigated the function of the anterior cingulate gyrus and the related neural systems that are associated with selective attention in patients with schizophrenia. Method: While subjects performed multiple blocks of a single-trial Stroop task, [O-15]H2O positron emission tomography scans were obtained. Fourteen patients with schizophrenia were compared with 15 normal subjects matched for age, gender, and parental education. Results: The patients with schizophrenia responded at the same rate but made more errors in color naming during the color-incongruent condition. Consistent with the authors' hypothesis, patients with schizoephrenia showed significantly less anterior cingulate gyrus activation while naming the color of color-incongruent stimuli. Conclusions: Patients with schizophrenia fail to activate the anterior cingulate gyrus during selective attention performance. This finding adds to the understanding of the functional significance of the structural and metabolic abnormalities in schizophrenia that have been previously reported in this region of the brain.
    BibTeX:
    @article{Carter1997,
      author = {Carter, CS and Mintun, M and Nichols, T and Cohen, JD},
      title = {Anterior cingulate gyrus dysfunction and selective attention deficits in schizophrenia: [O-15]H2O PET study during single-trial Stroop task performance},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {1997},
      volume = {154},
      number = {12},
      pages = {1670-1675},
      note = {2nd International Conference on Functional Mapping of the Human Brain, BOSTON, MA, JUN 17-21, 1996}
    }
    
    Casey, B., Trainor, R., Orendi, J., Schubert, A., Nystrom, L., Giedd, J., Castellanos, F., Haxby, J., Noll, D., Cohen, J., Forman, S., Dahl, R. & Rapoport, J. A developmental functional MRI study of prefrontal activation during performance of a Go-No-Go task {1997} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {9}({6}), pp. {835-847} 
    article  
    Abstract: This study examines important developmental differences in patterns of activation in the prefrontal cortex during performance of a Go-No-Go paradigm using functional magnetic resonance imaging (fMRI). Eighteen subjects (9 children and 9 adults) were scanned using gradient echo, echo planar imaging during performance of a response inhibition task. The results suggest four general findings. First, the location of activation in the prefrontal cortex was not different between children and adults, which is similar to our earlier pediatric fMRI results of prefrontal activation during a working memory task (Casey et al., 1995). Second, the volume of activation was significantly greater for children relative to adults. These differences in volume of activation were observed predominantly in the dorsal and lateral prefrontal cortices. Third, although inhibitory processes have typically been associated with more ventral or orbital frontal regions, the current study revealed activation that was distributed across both dorsolateral and orbitofrontal cortices. Finally, consistent with animal and human lesion studies, activity in orbital frontal and anterior cingulate cortices correlated with behavioral performance (i.e., number of false alarms). These results further demonstrate the utility of this methodology in studying pediatric populations.
    BibTeX:
    @article{Casey1997,
      author = {Casey, BJ and Trainor, RJ and Orendi, JL and Schubert, AB and Nystrom, LE and Giedd, JN and Castellanos, FX and Haxby, JV and Noll, DC and Cohen, JD and Forman, SD and Dahl, RE and Rapoport, JL},
      title = {A developmental functional MRI study of prefrontal activation during performance of a Go-No-Go task},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {1997},
      volume = {9},
      number = {6},
      pages = {835-847}
    }
    
    CASEY, K., MINOSHIMA, S., BERGER, K., KOEPPE, R., MORROW, T. & FREY, K. POSITRON EMISSION TOMOGRAPHIC ANALYSIS OF CEREBRAL STRUCTURES ACTIVATED SPECIFICALLY BY REPETITIVE NOXIOUS HEAT STIMULI {1994} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {71}({2}), pp. {802-807} 
    article  
    Abstract: 1. To identify the forebrain and brain stem structures that are active during the perception of acute heat pain in humans, we performed (H2O)-O-15 positron emission tomographic (PET) analyses of cerebral blood flow (CBF) on nine normal volunteers while they received repetitive noxious(50 degrees C) and innocuous(40 degrees C) 5 s heat pulses to the forearm (average resting temperature of 31.8 degrees C). Each subject rated the subjective intensity of each stimulation series according to a magnitude estimation procedure in which 0 = no heat sensation, 7 = barely painful, and 10 = barely tolerable. 2. Three scans were performed at each temperature. Mean CBF images were created for each experimental condition and oriented onto standardized stereotaxic coordinates. Subtraction images were created between conditions for each subject and averaged across subjects. Volumes of interest (VOI) were chosen, based on a priori hypotheses and the results of previously published PET studies. In addition, a separate statistical summation analysis of individual voxels was performed. Statistical thresholds were established with corrections for multiple comparisons. 3. Significant CBF increases to 50 degrees C stimuli were found in the contralateral thalamus, cingulate cortex, S2 and S1 cortex, and insula. The ipsilateral S2 cortex and thalamus, and the medial dorsal midbrain and cerebellar vermis also showed significant CBF increases. All subjects rated the 50 degrees C stimuli as painful (average subjective rating = 8.9 +/- 0.9 SD) and the 40 degrees C stimuli as warm, but not painful (average subjective rating = 2.1 +/- 1.0). 4. To determine whether this result reflected the difference between perceived warmth and heat pain or between stimulus intensities only, an identical PET protocol was used for nine additional subjects except that both forearms were cooled to 21-25 degrees C while thermal pulses of 32 or 42 degrees C were applied during each scan. The subjects easily distinguished between the two stimuli but none was perceived as painful. The average subjective rating of the 32 degrees C stimuli was 1.3 +/- 1.1 and of the 42 degrees C stimuli, 4.0 +/- 1.5. No brain structures were activated significantly in this phase of the study. 5. The results are consistent with the interpretation that the structures showing significant CBF increases are components of the neural mechanisms mediating the sensory, and, possibly, the affective and premotor components of acute, repetitive heat pain.
    BibTeX:
    @article{CASEY1994,
      author = {CASEY, KL and MINOSHIMA, S and BERGER, KL and KOEPPE, RA and MORROW, TJ and FREY, KA},
      title = {POSITRON EMISSION TOMOGRAPHIC ANALYSIS OF CEREBRAL STRUCTURES ACTIVATED SPECIFICALLY BY REPETITIVE NOXIOUS HEAT STIMULI},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1994},
      volume = {71},
      number = {2},
      pages = {802-807}
    }
    
    Casey, K., Minoshima, S., Morrow, T. & Koeppe, R. Comparison of human cerebral activation patterns during cutaneous warmth, heat pain, and deep cold pain {1996} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {76}({1}), pp. {571-581} 
    article  
    Abstract: 1. We wished to determine whether there are differences in the spatial pattern and intensity of synaptic activity within the conscious human forebrain when different forms and intensities of innocuous and noxious thermal stimuli are experienced. Accordingly, positron emission tomography (PET) with intravenous injection of (H2O)-O-15 was used to detect increases in regional cerebral blood flow (rCBF) in normal humans as they discriminated differences in the intensity of noxious and innocuous thermal stimulation applied to the nondominant (left) arm. After stereotactic registration, subtraction images were formed from each subject by subtracting counts of emissions obtained during lower-intensity stimulation from those obtained during stimulation at higher intensities. A statistical summation analysis (Z score) of individual voxels was performed. In addition, volumes of interest were chosen on the basis of a priori hypotheses and the results of previously published PET studies. In both types of analysis, statistical thresholds were established with corrections for multiple comparisons. 2. Twenty-seven subjects were divided into three groups of nine subjects each for the three phases of this investigation. For studies in which repetitive contact heat stimuli were used, each subject was instructed in magnitude estimation on the basis of a scale for which 0 indicated `'no heat sensation,'' 7 `'just barely painful,'' and 10 `'just barely tolerable.'' For the study of pain elicited by immersion of the hand in cold water, subjects were instructed to use a scale in which 0 represented `'no pain'' and 10 represented just barely tolerable pain. 3. In the warm-discrimination study, two intensities of innocuous heat (36 and 43 degrees C) were applied with a thermode as repetitive 5-s contacts to the volar forearm for a total of similar to 100 s, 8 stimuli before and 12 during each scan. Each temperature was applied on alternate scans for a total of four scans per subject. Neither stimulus was rated painful. All subjects discriminated the 43 degrees C stimulus (average rating 5.90 +/- 1.43, mean +/- SD) from the 36 degrees C stimulus (1.96 +/- 1.08, mean +/- SD; t = 13.19, P < 0.0001). Significant increases in rCBF to the 43 degrees C stimuli were found in the contralateral ventral posterior thalamus, lenticular nucleus, medial prefrontal cortex (Brodmann's areas 10 and 32), and cerebellar vermis. 4. The procedure for discriminating between noxious and innocuous heat stimuli was identical to that used for warm discrimination except that the stimulation temperatures were 40 and 50 degrees C. All subjects rated the 50 degrees C stimuli as painful (average rating 8.9 +/- 0.9, mean +/- SD) and the 40 degrees C stimuli as warm, but not painful (2.1 +/- 1.0). Significant rCBF increases to 50 degrees C stimuli were found contralaterally in the thalamus, anterior cingulate cortex, premotor cortex, and secondary somatosensory (S2) and posterior insular cortices. Significant activity also appeared within the region of the contralateral anterior insula and lenticular nucleus. The ipsilateral premotor cortex and thalamus, and the medial dorsal midbrain and cerebellar vermis, also showed significant rCBF increases. Cerebral blood flow (CBF) increases just below the threshold for statistical significance were seen in the contralateral sensorimotor cortex [primary motor cortex (M1)/primary somatosensory cortex (S1)]. 5. For discrimination between tonic innocuous cold and tonic cold pain, the left hand was immersed to the wrist, throughout each of six scans, in water kept at an average temperature of either 20.5 +/- 1.15 degrees C (mean +/- SD) or 6.02 +/- 1.18 degrees C (mean +/- SD) on alternate scans. All subjects rated the intensity of the stimuli on a scale in which 0 indicated no pain and 10 represented barely tolerable pain. Subjects rated the 20 degrees C water immersion as painless (average rating 0.18 +/- 0.48, mean +/- SD), but gave ratings indicating intense pain during immersion in 6 degrees C water (7.89 +/- 1.45). All subjects expressed the perception of the pain as very cold, steady, and deep. Highly significant increases in rCBF were found contralaterally in the sensorimotor cortex (M1/S1), premotor cor tex, anterior cingulate cortex, and the region of the anterior insula and lenticular nucleus. Ipsilateral increases in rCBF were seen in the lateral prefrontal cortex (Brodmann's areas 10 and 46), anterior cingulate cortex, region of the insular and opercular precentral cortices, and thalamus. The cerebellar vermis also showed a significant increase in rCBF. CBF increases just below the threshold for statistical significance were seen in the contralateral thalamus. No significant rCBF response could be found in the medial dorsal midbrain. The analysis of activity within the ipsilateral premotor and S2 cortices was compromised by the presence of markedly increased blood flow in the ipsilateral scalp during the 6 degrees C immersion stimulus. 6. Comparisons of rCBF response magnitude were made among stereotactically concordant brain regions that showed significant responses in two phases of this study. Five regions were responsive in both the heat pain and cold pain conditions: the cerebellar vermis, ipsilateral thalamus, and the contralateral premotor cortex, contralateral anterior cingulate cortex, and region of the contralateral anterior insula and lenticular nucleus. Each of these regions showed a higher increase in rCBF in the cold pain study than in the heat pain study. The average rCBF increase across all subjects and these five regions was 2.85 +/- 0.124% (mean +/- SE) during the heat pain condition and 3.26 +/- 0.061% (mean +/- SE) during deep cold pain. The difference between these means is statistically significant (paired t(4) = 3.60; P < 0.022). 7. The results show that, in conscious humans, two forms of noxious stimulation that are different in temporal pattern, afferent fiber activation, and perceived spatiotemporal and qualitative characteristics produce similar, but not identical, patterns of brain increases in rCBF. These pain-related response patterns are each quite different from the brain responses observed during the discrimination between two intensities of innocuous heat stimuli. Our results suggest that the increased rCBF responses observed during noxious stimulation reflect physiological differences in neuronal activity that are related to nociceptive processing and to the perception of pain. The overlap in the spatial distribution of rCBF increases during noxious cutaneous heat and noxious deep cold stimulation suggests that there may be a reproducible pattern of rCBF responses that is common to the perception of pain produced by different stimuli. Differences in the intensity and spatial pattern of these pain-related rCBF increases may reflect physiological differences in neuronal nociceptive processing related to the perception of these two forms of pain.
    BibTeX:
    @article{Casey1996,
      author = {Casey, KL and Minoshima, S and Morrow, TJ and Koeppe, RA},
      title = {Comparison of human cerebral activation patterns during cutaneous warmth, heat pain, and deep cold pain},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1996},
      volume = {76},
      number = {1},
      pages = {571-581}
    }
    
    Castelli, F., Frith, C., Happe, F. & Frith, U. Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes {2002} BRAIN
    Vol. {125}({Part 8}), pp. {1839-1849} 
    article  
    Abstract: Ten able adults with autism or Asperger syndrome and 10 normal volunteers were PET scanned while watching animated sequences. The animations depicted two triangles moving about on a screen in three different conditions: moving randomly, moving in a goal-directed fashion (chasing, fighting), and moving interactively with implied intentions (coaxing, tricking). The, last condition frequently elicited descriptions in terms of mental states that viewers attributed to the triangles (mentalizing). The autism group gave fewer and less accurate descriptions of these latter animations, but equally accurate descriptions of the other animations compared with controls. While viewing animations that elicited mentalizing, in contrast to randomly moving shapes, the normal group showed increased activation in a previously identified mentalizing network (medial prefrontal cortex, superior temporal sulcus at the temporoparietal junction and temporal poles). The autism group showed less activation than the normal group in all these regions. However, one additional region, extrastriate cortex, which was highly active when watching animations that elicited mentalizing, showed the same amount of increased activation in both groups. In the autism group this extrastriate region showed reduced functional connectivity with the superior temporal sulcus at the temporo-parietal junction, an area associated with the processing of biological motion as well as with mentalizing. This finding suggests a physiological cause for the mentalizing dysfunction in autism: a bottleneck in the interaction between higher order and lower order perceptual processes.
    BibTeX:
    @article{Castelli2002,
      author = {Castelli, Fulvia and Frith, Chris and Happe, Francesca and Frith, Uta},
      title = {Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes},
      journal = {BRAIN},
      year = {2002},
      volume = {125},
      number = {Part 8},
      pages = {1839-1849}
    }
    
    Castelli, F., Happe, F., Frith, U. & Frith, C. Movement and mind: A functional imaging study of perception and interpretation of complex intentional movement patterns {2000} NEUROIMAGE
    Vol. {12}({3}), pp. {314-325} 
    article DOI  
    Abstract: We report a functional neuroimaging study with positron emission tomography (PET) in which six healthy adult volunteers were scanned while watching silent computer-presented animations. The characters in the animations were simple geometrical shapes whose movement patterns selectively evoked mental state attribution or simple action description. Results showed increased activation in association with mental state attribution in four main regions: medial prefrontal cortex, temporoparietal junction (superior temporal sulcus), basal temporal regions (fusiform gyrus and temporal poles adjacent to the amygdala), and extrastriate cortex (occipital gyrus). Previous imaging studies have implicated these regions in self-monitoring, in the perception of biological motion, and in the attribution of mental states using verbal stimuli or visual depictions of the human form. Ne suggest that these regions form a network for processing information about intentions, and speculate that the ability to make inferences about other people's mental states evolved from the ability to make inferences about other creatures' actions. (C) 2000 Academic Press.
    BibTeX:
    @article{Castelli2000,
      author = {Castelli, F and Happe, F and Frith, U and Frith, C},
      title = {Movement and mind: A functional imaging study of perception and interpretation of complex intentional movement patterns},
      journal = {NEUROIMAGE},
      year = {2000},
      volume = {12},
      number = {3},
      pages = {314-325},
      doi = {{10.1006/nimg.2000.0612}}
    }
    
    Cavada, C., Company, T., Tejedor, J., Cruz-Rizzolo, R. & Reinoso-Suarez, F. The anatomical connections of the macaque monkey orbitofrontal cortex. A review {2000} CEREBRAL CORTEX
    Vol. {10}({3}), pp. {220-242} 
    article  
    Abstract: The orbitofrontal cortex (OfC) is a heterogeneous prefrontal sector selectively connected with a wide constellation of other prefrontal. limbic, sensory and promotor areas. Among the limbic cortical connections, the ones with the hippocampus and parahippocampal cortex are particularly salient. Sensory cortices connected with the OfC include areas involved in olfactory, gustatory, somatosensory, auditory and visual processing. Subcortical structures with prominent OfC connections include the amygdala. numerous thalamic nuclei. the striatum, hypothalamus. periaqueductal gray matter, and biochemically specific cell groups in the basal forebrain and brainstem. Architectonic and connectional evidence supports parcellation of the OfC. The rostrally placed isocortical sector is mainly connected with isocortical areas, including sensory areas of the auditory, somatic and visual modalities, whereas the caudal non-isocortical sector is principally connected with non-isocortical areas, and, in the sensory domain, with olfactory and gustatory areas. The connections of the isocortical and non-isocortical orbital sectors with the amygdala, thalamus, striatum, hypothalamus and periaqueductal gray matter are also specific. The medial sector of the OfC is selectively connected with the hippocampus. posterior parahippocampal cortex, posterior cingulate and retrosplenial areas, and area prostriata, while the lateral orbitofrontal sector is the most heavily connected with sensory areas of the gustatory, somatic and visual modalities, with premotor regions, and with the amygdala.
    BibTeX:
    @article{Cavada2000,
      author = {Cavada, C and Company, T and Tejedor, J and Cruz-Rizzolo, RJ and Reinoso-Suarez, F},
      title = {The anatomical connections of the macaque monkey orbitofrontal cortex. A review},
      journal = {CEREBRAL CORTEX},
      year = {2000},
      volume = {10},
      number = {3},
      pages = {220-242}
    }
    
    CEBALLOSBAUMANN, A., PASSINGHAM, R., WARNER, T., PLAYFORD, E., MARSDEN, C. & BROOKS, D. OVERACTIVE PREFRONTAL AND UNDERACTIVE MOTOR CORTICAL AREAS IN IDIOPATHIC DYSTONIA {1995} ANNALS OF NEUROLOGY
    Vol. {37}({3}), pp. {363-372} 
    article  
    Abstract: Regional cerebral blood flow was measured using (H2O)-O-15 and positron emission tomography ina group of 6 patients with idiopathic torsion dystonia and in a group of 6 control subjects. Subjects were scanned while at rest and when performing paced joystick movements in freely chosen directions with the right hand. Patients with idiopathic torsion dystonia showed significant overactivity in the contralateral lateral premotor cortex, rostral supplementary motor area, Brodmann area 8, anterior cingulate area 32, ipsilateral dorsolateral prefrontal cortex, and bilateral lentiform nucleus. Significant underactivity was found in the caudal supplementary motor area, bilateral sensorimotor cortex, posterior cingulate, and mesial parietal cortex. These results are consistent with inappropriate overactivity of striato-frontal projections and impaired activity of motor executive areas in idiopathic torsion dystonia and may explain the simultaneous dystonic posturing and bradykinesia evident in these patients.
    BibTeX:
    @article{CEBALLOSBAUMANN1995,
      author = {CEBALLOSBAUMANN, AO and PASSINGHAM, RE and WARNER, T and PLAYFORD, ED and MARSDEN, CD and BROOKS, DJ},
      title = {OVERACTIVE PREFRONTAL AND UNDERACTIVE MOTOR CORTICAL AREAS IN IDIOPATHIC DYSTONIA},
      journal = {ANNALS OF NEUROLOGY},
      year = {1995},
      volume = {37},
      number = {3},
      pages = {363-372}
    }
    
    Childress, A., Mozley, P., McElgin, W., Fitzgerald, J., Reivich, M. & O'Brien, C. Limbic activation during cue-induced cocaine craving {1999} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {156}({1}), pp. {11-18} 
    article  
    Abstract: Objective: Since signals for cocaine induce limbic brain activation in animals and cocaine craving in humans, the objective of this study was to test whether limbic activation occurs during cue-induced craving in humans. Method: Using positron emission tomography, the researchers measured relative regional cerebral blood flow (CBF) in limbic and comparison brain regions of 14 detoxified male cocaine users and six cocaine-naive comparison subjects during exposure to both non-drug-related and cocaine-related videos and during resting baseline conditions. Results: During the cocaine video, the cocaine users experienced craving and showed a pattern of increases in limbic (amygdala and anterior cingulate) CBF and decreases in basal ganglia CBF relative to their responses to the nondrug video. This pattern did not occur in the cocaine-naive comparison subjects, and the two groups did not differ in their responses in the comparison regions (i.e., the dorsolateral prefrontal cortex, cerebellum, thalamus, and visual cortex). Conclusions: These findings indicate that limbic activation is one component of cue-induced cocaine craving. Limbic activation may be similarly involved in appetitive craving for other drugs and for natural rewards.
    BibTeX:
    @article{Childress1999,
      author = {Childress, AR and Mozley, PD and McElgin, W and Fitzgerald, J and Reivich, M and O'Brien, CP},
      title = {Limbic activation during cue-induced cocaine craving},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {1999},
      volume = {156},
      number = {1},
      pages = {11-18},
      note = {149th Annual Meeting of the American-Psychiatric-Association, NEW YORK, NEW YORK, MAY 04-09, 1996}
    }
    
    Chochon, F., Cohen, L., van de Moortele, P. & Dehaene, S. Differential contributions of the left and right inferior parietal lobules to number processing {1999} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {11}({6}), pp. {617-630} 
    article  
    Abstract: We measured cerebral activation with functional magnetic resonance imaging at 3 Tesla while eight healthy volunteers performed various number processing tasks known to be dissociable in brain-lesioned patients: naming, comparing, multiplying, or subtracting single digits. The results revealed the activation of a circuit comprising bilateral intraparietal, prefrontal, and anterior cingulate components. The extension and lateralization of this circuit was modulated by task demands. The intraparietal and prefrontal activation was more important in the right hemisphere during the comparison task and in the left hemisphere during the multiplication task and was intensely bilateral during the subtraction task. Thus, partially distinct cerebral circuits with the dorsal parietal pathway underlie distinct arithmetic operations.
    BibTeX:
    @article{Chochon1999,
      author = {Chochon, F and Cohen, L and van de Moortele, PF and Dehaene, S},
      title = {Differential contributions of the left and right inferior parietal lobules to number processing},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {1999},
      volume = {11},
      number = {6},
      pages = {617-630}
    }
    
    Ciccocioppo, R., Sanna, P. & Weiss, F. Cocaine-predictive stimulus induces drug-seeking behavior and neural activation in limbic brain regions after multiple months of abstinence: Reversal by D-1 antagonists {2001} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {98}({4}), pp. {1976-1981} 
    article  
    Abstract: The conditioning of cocaine's subjective actions with environmental stimuli may be a critical factor in long-lasting relapse risk associated with cocaine addiction. To study the significance of learning factors in persistent addictive behavior as well as the neurobiological basis of this phenomenon, rats were trained to associate discriminative stimuli (SD) with the availability of i.v. cocaine vs. nonrewarding saline solution, and then placed on extinction conditions during which the i.v. solutions and S(D)s were withheld. The effects of reexposure to the SD on the recovery of responding at the previously cocaine-paired lever and on Fos protein expression then were determined in two groups. One group was tested immediately after extinction, whereas rats in the second group were confined to their home cages for an additional 4 months before testing, In both groups, the cocaine SD, but not the non-reward SD, elicited strong recovery of responding and increased Fos immunoreactivity in the basolateral amygdala and medial prefrontal cortex (areas Cg1/Cg3). The response reinstatement and Fos expression induced by the cocaine SD were both reversed by selective dopamine D-1 receptor antagonists. The undiminished efficacy of the cocaine SD to elicit drug-seeking behavior after 4 months of abstinence parallels the long-lasting nature of conditioned cue reactivity and cue-induced cocaine craving in humans, and confirms a significant role of learning factors in the long-lasting addictive potential of cocaine. Moreover, the results implicate D-1-dependent neural mechanisms within the medial prefrontal cortex and basolateral amygdala as substrates for cocaine-seeking behavior elicited by cocaine-predictive environmental stimuli.
    BibTeX:
    @article{Ciccocioppo2001,
      author = {Ciccocioppo, R and Sanna, PP and Weiss, F},
      title = {Cocaine-predictive stimulus induces drug-seeking behavior and neural activation in limbic brain regions after multiple months of abstinence: Reversal by D-1 antagonists},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {2001},
      volume = {98},
      number = {4},
      pages = {1976-1981}
    }
    
    Coghill, R., Sang, C., Maisog, J. & Iadarola, M. Pain intensity processing within the human brain: A bilateral, distributed mechanism {1999} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {82}({4}), pp. {1934-1943} 
    article  
    Abstract: Functional imaging studies of human subjects have identified a diverse assortment of brain areas that are engaged in the processing of pain. Although many of these brain areas are highly interconnected and are engaged in multiple processing roles, each area has been typically considered in isolation. Accordingly, little attention has been given to the global functional organization of brain mechanisms mediating pain processing. In the present investigation, we have combined positron emission tomography with psychophysical assessment of graded painful stimuli to better characterize the multiregional organization of supraspinal pain processing mechanisms and to identify a brain mechanism subserving the processing of pain intensity. Multiple regression analysis revealed statistically reliable relationships between perceived pain intensity and activation of a functionally diverse group of brain regions, including those important in sensation, motor control, affect, and attention. Pain intensity-related activation occurred bilaterally in the cerebellum, putamen, thalamus, insula, anterior cingulate cortex, and secondary somatosensory cortex, contralaterally in the primary somatosensory cortex and supplementary motor area, and ipsilaterally in the ventral premotor area. These results confirm the existence of a highly distributed, bilateral supraspinal mechanism engaged in the processing of pain intensity. The conservation of pain intensity information across multiple, functionally distinct brain areas contrasts sharply with traditional views that sensory-discriminative processing of pain is confined within the somatosensory cortex and can account for the preservation of conscious awareness of pain intensity after extensive cerebral cortical lesions.
    BibTeX:
    @article{Coghill1999,
      author = {Coghill, RC and Sang, CN and Maisog, JH and Iadarola, MJ},
      title = {Pain intensity processing within the human brain: A bilateral, distributed mechanism},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1999},
      volume = {82},
      number = {4},
      pages = {1934-1943}
    }
    
    COGHILL, R., TALBOT, J., EVANS, A., MEYER, E., GJEDDE, A., BUSHNELL, M. & DUNCAN, G. DISTRIBUTED-PROCESSING OF PAIN AND VIBRATION BY THE HUMAN BRAIN {1994} JOURNAL OF NEUROSCIENCE
    Vol. {14}({7}), pp. {4095-4108} 
    article  
    Abstract: Pain is a diverse sensory and emotional experience that likely involves activation of numerous regions of the brain. Yet, many of these areas are also implicated in the processing of nonpainful somatosensory information. In order to better characterize the processing of pain within the human brain, activation produced by noxious stimuli was compared with that produced by robust innocuous stimuli. Painful heat (47-48 degrees C), nonpainful vibratory (110 Hz), and neutral control (34 degrees C) stimuli were applied to the left forearm of right-handed male subjects. Activation of regions within the diencephalon and telencephalon was evaluated by measuring regional cerebral blood flow using positron emission tomography (O-15-water-bolus method). Painful stimulation produced contralateral activation in primary and secondary somatosensory cortices (SI and SII), anterior cingulate cortex, anterior insula, the supplemental motor area of the frontal cortex, and thalamus. Vibrotactile stimulation produced activation in contralateral SI, and bilaterally in SII and posterior insular cortices. A direct comparison of pain and vibrotactile stimulation revealed that both stimuli produced activation In similar regions of SI and SII, regions long thought to be involved activating the anterior insula, a region heavily linked with both somatosensory and limbic systems. Such connections may provide one route through which nociceptive input may be integrated with memory in order to allow a full appreciation of the meaning and dangers of painful stimuli. These data reveal that pain-related activation, although predominantly contralateral in distribution, is more widely dispersed across both cortical and thalamic regions than that produced during innocuous vibrotactile stimulation. This distributed cerebral activation reflects the complex nature of pain, involving discriminative, affective, autonomic, and motoric components. Furthermore, the high degree of interconnectivity among activated regions may account for the difficulty of eliminating pathological pain with discrete CNS lesions.
    BibTeX:
    @article{COGHILL1994,
      author = {COGHILL, RC and TALBOT, JD and EVANS, AC and MEYER, E and GJEDDE, A and BUSHNELL, MC and DUNCAN, GH},
      title = {DISTRIBUTED-PROCESSING OF PAIN AND VIBRATION BY THE HUMAN BRAIN},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1994},
      volume = {14},
      number = {7},
      pages = {4095-4108}
    }
    
    Cohen, J., Botvinick, M. & Carter, C. Anterior cingulate and prefrontal cortex: who's in control? {2000} NATURE NEUROSCIENCE
    Vol. {3}({5}), pp. {421-423} 
    article  
    Abstract: A sophisticated study of error-related brain potentials in patients with prefrontal lesions addresses how we monitor performance and adjust cognitive control based on task demands.
    BibTeX:
    @article{Cohen2000,
      author = {Cohen, JD and Botvinick, M and Carter, CS},
      title = {Anterior cingulate and prefrontal cortex: who's in control?},
      journal = {NATURE NEUROSCIENCE},
      year = {2000},
      volume = {3},
      number = {5},
      pages = {421-423}
    }
    
    Colcombe, S., Kramer, A., Erickson, K., Scalf, P., McAuley, E., Cohen, N., Webb, A., Jerome, G., Marquez, D. & Elavsky, S. Cardiovascular fitness, cortical plasticity, and aging {2004} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {101}({9}), pp. {3316-3321} 
    article  
    Abstract: Cardiovascular fitness is thought to offset declines in cognitive performance, but little is known about the cortical mechanisms that underlie these changes in humans. Research using animal models shows that aerobic training increases cortical capillary supplies, the number of synaptic connections, and the development of new neurons. The end result is a brain that is more efficient, plastic, and adaptive, which translates into better performance in aging animals. Here, in two separate experiments, we demonstrate for the first time to our knowledge, in humans that increases in cardiovascular fitness results in increased functioning of key aspects of the attentional network of the brain during a cognitively challenging task. Specifically, highly fit (Study 1) or aerobically trained (Study 2) persons show greater task-related activity in regions of the prefrontal and parietal cortices that are involved in spatial selection and inhibitory functioning, when compared with low-fit (Study 1) or nonaerobic control (Study 2) participants. Additionally, in both studies there exist groupwise differences in activation of the anterior cingulate cortex, which is thought to monitor for conflict in the attentional system, and signal the need for adaptation in the attentional network. These data suggest that increased cardiovascular fitness can affect improvements in the plasticity of the aging human brain, and may serve to reduce both biological and cognitive senescence in humans.
    BibTeX:
    @article{Colcombe2004,
      author = {Colcombe, SJ and Kramer, AF and Erickson, KI and Scalf, P and McAuley, E and Cohen, NJ and Webb, A and Jerome, GJ and Marquez, DX and Elavsky, S},
      title = {Cardiovascular fitness, cortical plasticity, and aging},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {2004},
      volume = {101},
      number = {9},
      pages = {3316-3321}
    }
    
    Collette, F. & Van der Linden, M. Brain imaging of the central executive component of working memory {2002} NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
    Vol. {26}({2}), pp. {105-125} 
    article  
    Abstract: This review presents neuroimaging studies which have explored the cerebral substrates of the central executive component of the working memory model proposed by Baddeley and Hitch [working memory (1986); Recent advances in learning and motivation (1974)]. These studies have demonstrated that different executive functions (manipulating and updating of information, dual-task coordination, inhibition and shifting processes) not only recruit various frontal areas, but also depend upon posterior (mainly parietal) regions. Such results are in agreement with the hypothesis that executive functions rely on a distributed cerebral network not restricted to anterior cerebral areas. Moreover, the intervention of similar prefrontal regions in a large number of executive tasks suggests that the central executive functioning must be understood in terms of different interactions between a network of regions rather than in terms of a specific association between one region and one higher-level cognitive process. (C) 2002 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{Collette2002,
      author = {Collette, F and Van der Linden, M},
      title = {Brain imaging of the central executive component of working memory},
      journal = {NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS},
      year = {2002},
      volume = {26},
      number = {2},
      pages = {105-125}
    }
    
    CONDE, F., MAIRELEPOIVRE, E., AUDINAT, E. & CREPEL, F. AFFERENT CONNECTIONS OF THE MEDIAL FRONTAL-CORTEX OF THE RAT .2. CORTICAL AND SUBCORTICAL AFFERENTS {1995} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {352}({4}), pp. {567-593} 
    article  
    Abstract: In order to compare the frontal cortex of rat and macaque monkey, cortical and subcortical afferents to subdivisions of the medial frontal cortex (MFC) in the rat were analyzed with fluorescent retrograde tracers. In addition to afferent inputs common to the whole MFC, each subdivision of the MFC has a specific pattern of afferent connections. The dorsally situated precentral medial area (PrCm) was the only area to receive inputs from the somatosensory cortex. The specific pattern of afferents common to the ventrally situated prelimbic (PL) and infralimbic (IL) areas included projections from the agranular insular cortex, the entorhinal and piriform cortices, the CA1-CA2 fields of the hippocampus, the subiculum, the endopiriform nucleus, the amygdalopiriform transition, the amygdalohippocampal area, the lateral tegmentum, and the parabrachial nucleus. In all these structures, the number of retrogradely labeled cells was larger when the injection site was located in area IL. The dorsal part of the anterior cingulate area (ACd) seemed to be connectionally intermediate between the adjacent areas PrCm and PL; it receives neither the somatosensory inputs characteristic of area PrCm nor the afferents characteristic of areas PL and IL, with the exception of the afferents from the caudal part of the retrosplenial cortex. A comparison of the pattern of afferent and efferent connections of the rat MFC with the pattern of macaque prefrontal cortex suggests that PrCm and ACd areas share some properties with the macaque premotor cortex, whereas PL and IL areas may have characteristics in common with the cingulate or with medial areas 24, 25, and 32 and with orbital areas 12, 13, and 14 of macaques. (C) 1995 Wiley-Liss, Inc.
    BibTeX:
    @article{CONDE1995,
      author = {CONDE, F and MAIRELEPOIVRE, E and AUDINAT, E and CREPEL, F},
      title = {AFFERENT CONNECTIONS OF THE MEDIAL FRONTAL-CORTEX OF THE RAT .2. CORTICAL AND SUBCORTICAL AFFERENTS},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {1995},
      volume = {352},
      number = {4},
      pages = {567-593}
    }
    
    CORBETTA, M., MIEZIN, F., DOBMEYER, S., SHULMAN, G. & PETERSEN, S. SELECTIVE AND DIVIDED ATTENTION DURING VISUAL DISCRIMINATIONS OF SHAPE, COLOR, AND SPEED - FUNCTIONAL-ANATOMY BY POSITRON EMISSION TOMOGRAPHY {1991} JOURNAL OF NEUROSCIENCE
    Vol. {11}({8}), pp. {2383-2402} 
    article  
    Abstract: Positron emission tomography (PET) was used to identify the neural systems involved in discriminating the shape, color, and speed of a visual stimulus under conditions of selective and divided attention. Psychophysical evidence indicated that the sensitivity for discriminating subtle stimulus changes in a same-different matching task was higher when subjects selectively attended to one attribute than when they divided attention among the attributes. PET measurements of brain activity indicated that modulations of extrastriate visual activity were primarily produced by task conditions of selective attention. Attention to speed activated a region in the left inferior parietal lobule. Attention to color activated a region in the collateral sulcus and dorsolateral occipital cortex, while attention to shape activated collateral sulcus (similarly to color), fusiform and parahippocampal gyri, and temporal cortex along the superior temporal sulcus. Outside the visual system, selective and divided attention activated nonoverlapping sets of brain regions. Selective conditions activated globus pallidus, caudate nucleus, lateral orbitofrontal cortex, posterior thalamus/colliculus, and insular-premotor regions, while the divided condition activated the anterior cingulate and dorsolateral prefrontal cortex. The results in the visual system demonstrate that selective attention to different features modulates activity in distinct regions of extrastriate cortex that appear to be specialized for processing the selected feature. The disjoint pattern of activations in extravisual brain regions during selective- and divided-attention conditions also suggests that perceptual judgments involve different neural systems, depending on attentional strategies.
    BibTeX:
    @article{CORBETTA1991,
      author = {CORBETTA, M and MIEZIN, FM and DOBMEYER, S and SHULMAN, GL and PETERSEN, SE},
      title = {SELECTIVE AND DIVIDED ATTENTION DURING VISUAL DISCRIMINATIONS OF SHAPE, COLOR, AND SPEED - FUNCTIONAL-ANATOMY BY POSITRON EMISSION TOMOGRAPHY},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1991},
      volume = {11},
      number = {8},
      pages = {2383-2402}
    }
    
    Cotter, D., Mackay, D., Landau, S., Kerwin, R. & Everall, I. Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder {2001} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {58}({6}), pp. {545-553} 
    article  
    Abstract: Background: Glial cells are more numerous than neurons in the cortex and are crucial to neuronal function. There is evidence for reduced neuronal size in schizophrenia, with suggestive evidence for reduced glial cell density in mood disorders. In this investigation, we have simultaneously assessed glial cell density and neuronal density and size in the anterior cingulate cortex in schizophrenia, major depressive disorder, and bipolar disorder. Methods: We examined tissue from area 24b of the supracallosal anterior cingulate cortex in 69 postmodern brain specimens from 4 groups of 15 subjects, as follows: major depressive disorder, schizophrenia, bipolar disorder, and normal controls. Glial cell density and neuronal size and density were examined in all subjects using the nucleator and the optical disector. Results: Glial cell density (22 (P=.004) and neuronal size (23 (P=.01) were reduced in layer 6 in major depressive disorder compared with controls. There was some evidence for reduced glial density in layer 6 (20 (P=.02) in schizophrenia compared with controls, before adjusting for multiple layerwise comparisons, but there were no significant changes in neuronal size. There was no evidence for differences in glial density or neuronal size in bipolar disorder compared with controls. Neuronal density was similar in all groups to that found in controls. Conclusion: These findings suggest that there is reduced frontal cortical glial cell density and neuronal size in major depressive disorder.
    BibTeX:
    @article{Cotter2001,
      author = {Cotter, D and Mackay, D and Landau, S and Kerwin, R and Everall, I},
      title = {Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {2001},
      volume = {58},
      number = {6},
      pages = {545-553}
    }
    
    Courtney, S., Ungerleider, L., Keil, K. & Haxby, J. Object and spatial visual working memory activate separate neural systems in human cortex {1996} CEREBRAL CORTEX
    Vol. {6}({1}), pp. {39-49} 
    article  
    Abstract: Human and nonhuman primate visual systems are divided into object and spatial information processing pathways, In the macaque, it has been shown that these pathways project to separate areas in the frontal lobe and that the ventral and dorsal frontal areas are, respectively, involved in working memory for objects and spatial locations. A positron emission tomography (PET) study was done to determine if a similar anatomical segregation exists in humans for object and spatial visual working memory. Face working memory demonstrated significant increases in regional cerebral blood flow (rCBF), relative to location working memory, in fusiform, parahippocampal, inferior frontal, and anterior cingulate cortices, and in right thalamus and midline cerebellum. Location working memory demonstrated significant increases in rCBF relative to face working memory, in superior and inferior parietal cortex, and in the superior frontal sulcus. Our results show that the neural systems involved in working memory for faces and for spatial location are functionally segregated, with different areas recruited in both extrastriate and frontal cortices for processing the two types of visual information.
    BibTeX:
    @article{Courtney1996,
      author = {Courtney, SM and Ungerleider, LG and Keil, K and Haxby, JV},
      title = {Object and spatial visual working memory activate separate neural systems in human cortex},
      journal = {CEREBRAL CORTEX},
      year = {1996},
      volume = {6},
      number = {1},
      pages = {39-49}
    }
    
    Craig, A. Interoception: the sense of the physiological condition of the body {2003} CURRENT OPINION IN NEUROBIOLOGY
    Vol. {13}({4}), pp. {500-505} 
    article DOI  
    Abstract: Converging evidence indicates that primates have a distinct cortical image of homeostatic afferent activity that reflects all aspects of the physiological condition of all tissues of the body. This interoceptive system, associated with autonomic motor control, is distinct from the exteroceptive system (cutaneous mechanoreception and proprioception) that guides somatic motor activity. The primary interoceptive representation in the dorsal posterior insula engenders distinct highly resolved feelings from the body that include pain, temperature, itch, sensual touch, muscular and visceral sensations, vasomotor activity, hunger, thirst, and `air hunger'. In humans, a meta-representation of the primary interoceptive activity is engendered in the right anterior insula, which seems to provide the basis for the subjective image of the material self as a feeling (sentient) entity, that is, emotional awareness.
    BibTeX:
    @article{Craig2003,
      author = {Craig, AD},
      title = {Interoception: the sense of the physiological condition of the body},
      journal = {CURRENT OPINION IN NEUROBIOLOGY},
      year = {2003},
      volume = {13},
      number = {4},
      pages = {500-505},
      doi = {{10.1016/S0959-4388(03)0090-4}}
    }
    
    Craig, A. How do you feel? Interoception: the sense of the physiological condition of the body {2002} NATURE REVIEWS NEUROSCIENCE
    Vol. {3}({8}), pp. {655-666} 
    article DOI  
    BibTeX:
    @article{Craig2002,
      author = {Craig, AD},
      title = {How do you feel? Interoception: the sense of the physiological condition of the body},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2002},
      volume = {3},
      number = {8},
      pages = {655-666},
      doi = {{10.1038/nrn894}}
    }
    
    Craig, A., Reiman, E., Evans, A. & Bushnell, M. Functional imaging of an illusion of pain {1996} NATURE
    Vol. {384}({6606}), pp. {258-260} 
    article  
    Abstract: TOUCHING warm and cool bars that are spatially interlaced produces a painful burning sensation resembling that caused by intense, noxious cold. We demonstrated previously that this thermal grill illusion can be explained as an unmasking phenomenon that reveals the central inhibition of pain by thermosensory integration(1). In order to localize this unmasking in the human brain, we have used positron emission tomography (PET) to compare the cortical activation patterns evoked by the thermal grill and by cool, warm, noxious cold and noxious heat stimuli. The thermal grill illusion produces activation in the anterior cingulate cortex, whereas its component warm and cool stimuli do not. This area is also activated bq noxious heat or cold. Thus, increased activity in the anterior cingulate cortex appears to be selectively associated with the perception of thermal pain. Disruption of thermosensory and pain integration may account for the central pain syndrome that can occur after stroke damage.
    BibTeX:
    @article{Craig1996,
      author = {Craig, AD and Reiman, EM and Evans, A and Bushnell, MC},
      title = {Functional imaging of an illusion of pain},
      journal = {NATURE},
      year = {1996},
      volume = {384},
      number = {6606},
      pages = {258-260}
    }
    
    Critchley, H. Neural mechanisms of autonomic, affective, and cognitive integration {2005} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {493}({1}), pp. {154-166} 
    article DOI  
    Abstract: Influential theoretical models propose a central role for afferent information from the body in the expression of emotional feeling states. Feedback representations of changing states of bodily arousal influence learning and facilitate concurrent and prospective decision-making. Functional neuroimaging studies have increased understanding of brain mechanisms that generate changes in autonomic arousal during behavior and those which respond to internal feedback signals to influence subjective feeling states. In particular, anterior cingulate cortex is implicated in generating autonomic changes, while insula and orbitofrontal cortices may be specialized in mapping visceral responses. Independently, ventromedial prefrontal cortex is recognized to support processes of internal (self-) reference that predominate in states of rest and disengagement and which putatively serve as a benchmark for dynamic interactions with the environment. Lesion data further highlight the integrated role of these cortical regions in autonomic and motivational control. In computational models of control, forward (efference copies) and inverse models are proposed to enable prediction and correction of action and, by extension, the interpretation of the behavior of others. It is hypothesized that the neural substrate for these processes during motivational and affective behavior lies within the interactions of anterior cingulate, insula, and orbitofrontal cortices. Generation of visceral autonomic correlates of control reinforce experiential engagement in simulatory models and underpin concepts such as somatic markers to bridge the dualistic divide.
    BibTeX:
    @article{Critchley2005,
      author = {Critchley, HD},
      title = {Neural mechanisms of autonomic, affective, and cognitive integration},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {2005},
      volume = {493},
      number = {1},
      pages = {154-166},
      note = {Neuroscience Conference on Anatomy of the Soul, Ameland, NETHERLANDS, MAY 19-24, 2005},
      doi = {{10.1002/cne.20749}}
    }
    
    Critchley, H., Corfield, D., Chandler, M., Mathias, C. & Dolan, R. Cerebral correlates of autonomic cardiovascular arousal: a functional neuroimaging investigation in humans {2000} JOURNAL OF PHYSIOLOGY-LONDON
    Vol. {523}({1}), pp. {259-270} 
    article  
    Abstract: 1. States of peripheral autonomic arousal accompany emotional behaviour, physical exercise and cognitive effort, and their central representation may influence decision making and the regulation of social and emotional behaviours. However, the cerebral functional neuroanatomy representing and mediating peripheral autonomic responses in humans is poorly understood. 2. Six healthy volunteer subjects underwent (H2O)-O-15 positron emission tomography (PET) scanning while performing isometric exercise and mental arithmetic stressor tasks, and during corresponding control tasks. Mean arterial blood pressure (MAP) and heart rate (HR) were monitored during scanning. 3. Data were analysed using statistical parametric mapping (SPM99). Conjunction analyses were used to determine significant changes in regional cerebral blood flow (rCBF) during states of cardiovascular arousal common to both exercise and mental stressor tasks. 4. Exercise and mental stressor tasks, relative to their control tasks, were associated with significantly (P < 0.001) increased MAP and HR. Significant common activations (increased rCBF) were observed in cerebellar vermis, brainstem and right anterior cingulate. In both exercise and mental stress tasks, increased rCBF in cerebellar vermis, right anterior cingulate and right insula covaried with MAP; rCBF in pens, cerebellum and right insula covaried with HR. Cardiovascular arousal in both categorical and covariance analyses was associated with decreased rCBF in prefrontal and medial temporal regions. 5. Neural responses in discrete brain regions accompany peripheral cardiovascular arousal. We provide evidence for the involvement of areas previously implicated in cognitive and emotional behaviours in the representation of peripheral autonomic states, consistent with a functional organization that produces integrated cardiovascular response patterns in the service of volitional and emotional behaviours.
    BibTeX:
    @article{Critchley2000a,
      author = {Critchley, HD and Corfield, DR and Chandler, MP and Mathias, CJ and Dolan, RJ},
      title = {Cerebral correlates of autonomic cardiovascular arousal: a functional neuroimaging investigation in humans},
      journal = {JOURNAL OF PHYSIOLOGY-LONDON},
      year = {2000},
      volume = {523},
      number = {1},
      pages = {259-270}
    }
    
    Critchley, H., Elliott, R., Mathias, C. & Dolan, R. Neural activity relating to generation and representation of galvanic skin conductance responses: A functional magnetic resonance imaging study {2000} JOURNAL OF NEUROSCIENCE
    Vol. {20}({8}), pp. {3033-3040} 
    article  
    Abstract: Central feedback of peripheral states of arousal influences motivational behavior and decision making. The sympathetic skin conductance response (SCR) is one index of autonomic arousal. The precise functional neuroanatomy underlying generation and representation of SCR during motivational behavior is undetermined, although it is impaired by discrete brain lesions to ventromedial prefrontal cortex, anterior cingulate, and parietal lobe. We used functional magnetic resonance imaging to study brain activity associated with spontaneous fluctuations in amplitude of SCR, and activity corresponding to generation and afferent representation of discrete SCR events. Regions that covaried with increased SCR included right orbitofrontal cortex, right anterior insula, left lingual gyrus, right fusiform gyrus, and left cerebellum. At a less stringent level of significance, predicted areas in bilateral medial prefrontal cortex and right inferior parietal lobule covaried with SCR. Generation of discrete SCR events was associated with significant activity in left medial prefrontal cortex, bilateral extrastriate visual cortices, and cerebellum. Activity in right medial prefrontal cortex related to afferent representation of SCR events. Activity in bilateral medial prefrontal lobe, right orbitofrontal cortex, and bilateral extrastriate visual cortices was common to both generation and afferent representation of discrete SCR events identified in a conjunction analysis. Our results suggest that areas implicated in emotion and attention are differentially involved in generation and representation of peripheral SCR responses. We propose that this functional arrangement enables integration of adaptive bodily responses with ongoing emotional and attentional states of the organism.
    BibTeX:
    @article{Critchley2000,
      author = {Critchley, HD and Elliott, R and Mathias, CJ and Dolan, RJ},
      title = {Neural activity relating to generation and representation of galvanic skin conductance responses: A functional magnetic resonance imaging study},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2000},
      volume = {20},
      number = {8},
      pages = {3033-3040}
    }
    
    Critchley, H., Mathias, C. & Dolan, R. Neural activity in the human brain relating to uncertainty and arousal during anticipation {2001} NEURON
    Vol. {29}({2}), pp. {537-545} 
    article  
    Abstract: We used functional magnetic resonance neuroimaging to measure brain activity during delay between reward-related decisions and their outcomes, and the modulation of this delay activity by uncertainty and arousal. Feedback, indicating financial gain or loss, was given following a fixed delay. Anticipatory arousal was indexed by galvanic skin conductance. Delay-period activity was associated with bilateral activation in orbital and medial prefrontal, temporal, and right parietal cortices. During delay, activity in anterior cingulate and orbitofrontal cortices was modulated by outcome uncertainty, whereas anterior cingulate, dorsolateral prefrontal, and parietal cortices activity was modulated by degree of anticipatory arousal. A distinct region of anterior cingulate was commonly activated by both uncertainty and arousal. Our findings highlight distinct contributions of cognitive uncertainty and autonomic arousal to anticipatory neural activity in prefrontal cortex.
    BibTeX:
    @article{Critchley2001,
      author = {Critchley, HD and Mathias, CJ and Dolan, RJ},
      title = {Neural activity in the human brain relating to uncertainty and arousal during anticipation},
      journal = {NEURON},
      year = {2001},
      volume = {29},
      number = {2},
      pages = {537-545}
    }
    
    Critchley, H., Mathias, C., Josephs, O., O'Doherty, J., Zanini, S., Dewar, B., Cipolotti, L., Shallice, T. & Dolan, R. Human cingulate cortex and autonomic control: converging neuroimaging and clinical evidence {2003} BRAIN
    Vol. {126}({Part 10}), pp. {2139-2152} 
    article DOI  
    Abstract: Human anterior cingulate function has been explained primarily within a cognitive framework. We used functional MRI experiments with simultaneous electrocardiography to examine regional brain activity associated with autonomic cardiovascular control during performance of cognitive and motor tasks. Using indices of heart rate variability, and high- and low-frequency power in the cardiac rhythm, we observed activity in the dorsal anterior cingulate cortex (ACC) related to sympathetic modulation of heart rate that was dissociable from cognitive and motor-related activity. The findings predict that during effortful cognitive and motor behaviour the dorsal ACC supports the generation of associated autonomic states of cardiovascular arousal. We subsequently tested this prediction by studying three patients with focal damage involving the ACC while they performed effortful cognitive and motor tests. Each showed abnormalities in autonomic cardiovascular responses with blunted autonomic arousal to mental stress when compared with 147 normal subjects tested in identical fashion. Thus, converging neuroimaging and clinical findings suggest that ACC function mediates context-driven modulation of bodily arousal states.
    BibTeX:
    @article{Critchley2003,
      author = {Critchley, HD and Mathias, CJ and Josephs, O and O'Doherty, J and Zanini, S and Dewar, BK and Cipolotti, L and Shallice, T and Dolan, RJ},
      title = {Human cingulate cortex and autonomic control: converging neuroimaging and clinical evidence},
      journal = {BRAIN},
      year = {2003},
      volume = {126},
      number = {Part 10},
      pages = {2139-2152},
      doi = {{10.1093/brain/awg216}}
    }
    
    Critchley, H., Wiens, S., Rotshtein, P., Ohman, A. & Dolan, R. Neural systems supporting interoceptive awareness {2004} NATURE NEUROSCIENCE
    Vol. {7}({2}), pp. {189-195} 
    article DOI  
    Abstract: Influential theories of human emotion argue that subjective feeling states involve representation of bodily responses elicited by emotional events. Within this framework, individual differences in intensity of emotional experience reflect variation in sensitivity to internal bodily responses. We measured regional brain activity by functional magnetic resonance imaging (fMRI) during an interoceptive task wherein subjects judged the timing of their own heartbeats. We observed enhanced activity in insula, somatomotor and cingulate cortices. In right anterior insular/opercular cortex, neural activity predicted subjects' accuracy in the heartbeat detection task. Furthermore, local gray matter volume in the same region correlated with both interoceptive accuracy and subjective ratings of visceral awareness. Indices of negative emotional experience correlated with interoceptive accuracy across subjects. These findings indicate that right anterior insula supports a representation of visceral responses accessible to awareness, providing a substrate for subjective feeling states.
    BibTeX:
    @article{Critchley2004,
      author = {Critchley, HD and Wiens, S and Rotshtein, P and Ohman, A and Dolan, RJ},
      title = {Neural systems supporting interoceptive awareness},
      journal = {NATURE NEUROSCIENCE},
      year = {2004},
      volume = {7},
      number = {2},
      pages = {189-195},
      doi = {{10.1038/nn1176}}
    }
    
    Dalley, J., Cardinal, R. & Robbins, T. Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates {2004} NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
    Vol. {28}({7}), pp. {771-784} 
    article DOI  
    Abstract: The prefrontal cortex has been implicated in a variety of cognitive and executive processes, including working memory, decision-making, inhibitory response control, attentional set-shifting and the temporal integration of voluntary behaviour. This article reviews current progress in our understanding of the rodent prefrontal cortex, especially evidence for functional divergence of the anatomically distinct sub-regions of the rat prefrontal cortex. Recent findings suggest clear distinctions between the dorsal (precentral and anterior cingulate) and ventral (prelimbic, infralimbic and medial orbital) sub-divisions of the medial prefrontal cortex, and between the orbitofrontal cortex (ventral orbital, ventrolateral orbital, dorsal and ventral agranular cortices) and the adjacent medial wall of the prefrontal cortex. The dorso-medial prefrontal cortex is implicated in memory for motor responses, including response selection, and the temporal processing of information. Ventral regions of the medial prefrontal cortex are implicated in interrelated `supervisory' attentional functions, including attention to stimulus features and task contingencies (or action-outcome rules), attentional set-shifting, and behavioural flexibility. The orbitofrontal cortex is implicated in lower-order discriminations, including reversal of stimulus-reward associations (reversal learning), and choice involving delayed reinforcement. It is anticipated that a greater understanding of the prefrontal cortex will come from using tasks that load specific cognitive and executive processes, in parallel with discovering new ways of manipulating the different sub-regions and neuromodulatory systems of the prefrontal cortex. (C) 2004 Elsevier Ltd. All rights reserved.
    BibTeX:
    @article{Dalley2004,
      author = {Dalley, JW and Cardinal, RN and Robbins, TW},
      title = {Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates},
      journal = {NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS},
      year = {2004},
      volume = {28},
      number = {7},
      pages = {771-784},
      doi = {{10.1016/j.neubiorev.2004.09.006}}
    }
    
    Davidson, R. Affective style, psychopathology, and resilience: Brain mechanisms and plasticity {2000} AMERICAN PSYCHOLOGIST
    Vol. {55}({11}), pp. {1196-1214} 
    article  
    Abstract: The brain circuitry underlying emotion includes several territories of the prefrontal cortex (PFC), the amygdala, hippocampus, anterior cingulate, and related structures. In general, the PFC represents emotion in the absence of immediately present incentives and thus plays a crucial role in the anticipation of the future affective consequences of action, as well as in the persistence of emotion following the offset of an elicitor. The functions of the other structures in this circuit are also considered. Individual differences in this circuitry are reviewed with an emphasis on asymmetry within the PFC and activation of the amygdala as 2 key components of affective style. These individual differences are related to both behavioral and biological variables associated with affective style and emotion regulation. Plasticity in this circuitry and its implications for transforming emotion and cultivating positive affect and resilience are considered.
    BibTeX:
    @article{Davidson2000a,
      author = {Davidson, RJ},
      title = {Affective style, psychopathology, and resilience: Brain mechanisms and plasticity},
      journal = {AMERICAN PSYCHOLOGIST},
      year = {2000},
      volume = {55},
      number = {11},
      pages = {1196-1214},
      note = {108th Annual Meeting of the APA, WASHINGTON, D.C., AUG 04-08, 2000}
    }
    
    Davidson, R. & Irwin, W. The functional neuroanatomy of emotion and affective style {1999} TRENDS IN COGNITIVE SCIENCES
    Vol. {3}({1}), pp. {11-21} 
    article  
    Abstract: Recently, there has been a convergence in lesion and neuroimaging data in the identification of circuits underlying positive and negative emotion in the human brain. Emphasis is placed on the prefrontal cortex (PFC) and the amygdala as two key components of this circuitry. Emotion guides action and organizes behaviour towards salient goals. To accomplish this, It is essential that the organism have a means of representing affect in the absence of immediate elicitors. It is proposed that the PFC plays a crucial role in affective working memory. The ventromedial sector of the PFC is most directly involved in the representation of elementary positive and negative emotional states while the dorsolateral PFC may be involved in the representation of the goal states towards which these elementary positive and negative states are directed. The amygdala has been consistently identified as playing a crucial role in both the perception of emotional cues and the production of emotional responses, with some evidence suggesting that it is particularly involved with fear-related negative affect. Individual differences in amygdala activation are implicated in dispositional affective styles and increased reactivity to negative incentives. The ventral striatum, anterior cingulate and insular cortex also provide unique contributions to emotional processing.
    BibTeX:
    @article{Davidson1999,
      author = {Davidson, RJ and Irwin, W},
      title = {The functional neuroanatomy of emotion and affective style},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      year = {1999},
      volume = {3},
      number = {1},
      pages = {11-21}
    }
    
    Davidson, R., Pizzagalli, D., Nitschke, J. & Putnam, K. Depression: Perspectives from affective neuroscience {2002} ANNUAL REVIEW OF PSYCHOLOGY
    Vol. {53}, pp. {545-574} 
    article  
    Abstract: Depression is a disorder of the representation and regulation of mood and emotion. The circuitry underlying the representation and regulation of normal emotion and mood is reviewed, including studies at the animal level, human lesion studies, and human brain imaging studies. This corpus of data is used to construct a model of the ways in which affect can become disordered in depression. Research on the prefrontal cortex, anterior cingulate, hippocampus, and amygdala is reviewed and abnormalities in the structure and function of these different regions in depression is considered. The review concludes with proposals for the specific types of processing abnormalities that result from dysfunctions in different parts of this circuitry and offers suggestions for the major themes upon which future research in this area should be focused.
    BibTeX:
    @article{Davidson2002,
      author = {Davidson, RJ and Pizzagalli, D and Nitschke, JB and Putnam, K},
      title = {Depression: Perspectives from affective neuroscience},
      journal = {ANNUAL REVIEW OF PSYCHOLOGY},
      year = {2002},
      volume = {53},
      pages = {545-574}
    }
    
    Davidson, R., Putnam, K. & Larson, C. Dysfunction in the neural circuitry of emotion regulation - A possible prelude to violence {2000} SCIENCE
    Vol. {289}({5479}), pp. {591-594} 
    article  
    Abstract: Emotion is normally regulated in the human brain by a complex circuit consisting of the orbital frontal cortex, amygdala, anterior cingulate cortex, and several other interconnected regions. There are both genetic and environmental contributions to the structure and function of this circuitry. We posit that impulsive aggression and violence arise as a consequence of faulty emotion regulation. Indeed, the prefrontal cortex receives a major serotonergic projection, which is dysfunctional in individuals who show impulsive violence. Individuals vulnerable to faulty regulation of negative emotion are at risk for violence and aggression. Research on the neural circuitry of emotion regulation suggests new avenues of intervention for such at-risk populations.
    BibTeX:
    @article{Davidson2000,
      author = {Davidson, RJ and Putnam, KM and Larson, CL},
      title = {Dysfunction in the neural circuitry of emotion regulation - A possible prelude to violence},
      journal = {SCIENCE},
      year = {2000},
      volume = {289},
      number = {5479},
      pages = {591-594}
    }
    
    Davis, K., Kwan, C., Crawley, A. & Mikulis, D. Functional MRI study of thalamic and cortical activations evoked by cutaneous heat, cold, and tactile stimuli {1998} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {80}({3}), pp. {1533-1546} 
    article  
    Abstract: Positron emission tomography studies have provided evidence for the involvement of the thalamus and cortex in pain and temperature perception. However, the involvement of these structures in pain and temperature perception of individual subjects has not been studied in detail with high spatial resolution imaging. As a first step toward this goal, we have used functional magnetic resonance imaging (fMRI) to locate discrete regions of the thalamus, insula, and second somatosensory cortex (S2) modulated during innocuous and noxious thermal stimulation. Results were compared with those obtained during tactile stimulation of the palm. High resolution functional images were acquired on a 1.5 T echospeed GE MR system with an in-plane resolution of 1.7 mm. A modified peltier-type thermal stimulator was used to deliver innocuous cool and warm and noxious cold and hot stimuli for 40-60 s to the thenar eminence of normal male and female volunteers. Experimental paradigms consisted of four repetitions of interleaved control and task stimuli. A pixel by pixel statistical analysis of images obtained during each task versus control (e.g., noxious heat vs, warm, warm vs. neutral temperature, etc.) was used to determine task-related activations. Painful thermal stimuli activated discrete regions within the lateral and medial thalamus, and insula, predominantly in the anterior insula in most subjects, and the contralateral S2 in 50% of subjects. The innocuous thermal stimuli did not activate the S2 in any of the subjects but activated the thalamus and posterior insula in 50% of subjects. By comparison, innocuous tactile stimulation consistently activated S2 bilaterally and the contralateral lateral thalamus. These data also demonstrate that noxious thermal and innocuous tactile-related activations overlap in S2. The data also suggest that innocuous and noxious-related activations may overlap within the thalamus but may be located in different regions of the insula. Therefore, we provide support for a role of the anterior insula, S2, and thalamus in the perception of pain; whereas the posterior insula appears to be involved in tactile and innocuous temperature perception. These data demonstrate the feasibility of using fMRI for studies of pain, temperature, and mechanical stimuli in individual subjects, even in small regions such as thalamic nuclei. However, the intersubject variability should be considered in future single subject imaging studies and studies that rely on averaged group responses.
    BibTeX:
    @article{Davis1998,
      author = {Davis, KD and Kwan, CL and Crawley, AP and Mikulis, DJ},
      title = {Functional MRI study of thalamic and cortical activations evoked by cutaneous heat, cold, and tactile stimuli},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1998},
      volume = {80},
      number = {3},
      pages = {1533-1546}
    }
    
    Davis, K., Taylor, S., Crawley, A., Wood, M. & Mikulis, D. Functional MRI of pain- and attention-related activations in the human cingulate cortex {1997} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {77}({6}), pp. {3370-3380} 
    article  
    Abstract: The aims of the study were to use functional magnetic resonance imaging (fMRI) to 1) locate pain-related regions in the anterior cingulate cortex (ACC) of normal human subjects and 2) determine whether each subject's pain-related activation is congruent with ACC regions involved in attention-demanding cognitive processes. Ten normal subjects underwent fMRI with a 1.5-T standard commercial MRI scanner. A conventional gradient echo technique was used to obtain data from a single 4-mm sagittal slice of the left ACC, similar to 3.5 mm from midline. For each subject, interleaved sets of 6 images were obtained during a pain task, an attention-demanding task, and al rest, for a total of 36 images per task. Pain of different intensities was evoked via electrical stimulation of the right median nerve. The attention-demanding task consisted of silent word generation (verbal fluency). Additional experiments obtained data from the right ACC. A pixel-by-pixel statistical analysis of task versus rest images was used to determine task-related activated regions. The pain task resulted in a 1.6-4.0% increase in mean signal intensity within a small region of the ACC, The exact location of this activation varied from subject to subject, but was typically in the posterior part of area 24. The signal intensity changes within this region correlated with pain intensity reported by the subject. The attention-demanding tasks increased the mean signal intensity by 1.3-3.3% in a region anterior and/or superior to the pain-related activation in each subject. The activated region was typically larger than the pain-related activation. Ln some cases this activation was at or superior to the ACC border, near the supplementary motor area. These regions did not show any pain-intensity-related activation. In one subject both right and left ACC were imaged, revealing bilateral ACC activation during the attention task but only contralateral pain-related activation. These findings shed Light on pain- and attention-related cognitive processes. The results provide evidence for a region in the posterior part of the ACC that is involved in pain and a more anterior region involved in other attention-demanding cognitive tasks.
    BibTeX:
    @article{Davis1997,
      author = {Davis, KD and Taylor, SJ and Crawley, AP and Wood, ML and Mikulis, DJ},
      title = {Functional MRI of pain- and attention-related activations in the human cingulate cortex},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1997},
      volume = {77},
      number = {6},
      pages = {3370-3380}
    }
    
    Debener, S., Ullsperger, M., Siegel, M., Fiehler, K., von Cramon, D. & Engel, A. Trial-by-trial coupling of concurrent electroencephalogram and functional magnetic resonance imaging identifies the dynamics of performance monitoring {2005} JOURNAL OF NEUROSCIENCE
    Vol. {25}({50}), pp. {11730-11737} 
    article DOI  
    Abstract: Goal-directed behavior requires the continuous monitoring and dynamic adjustment of ongoing actions. Here, we report a direct coupling between the event-related electroencephalogram ( EEG), functional magnetic resonance imaging ( fMRI), and behavioral measures of performance monitoring in humans. By applying independent component analysis to EEG signals recorded simultaneously with fMRI, we found the single- trial error-related negativity of the EEG to be systematically related to behavior in the subsequent trial, thereby reflecting immediate behavioral adjustments of a cognitive performance monitoring system. Moreover, this trial-by-trial EEG measure of performance monitoring predicted the fMRI activity in the rostral cingulate zone, a brain region thought to play a key role in processing of response errors. We conclude that investigations of the dynamic coupling between EEG and fMRI provide a powerful approach for the study of higher order brain functions.
    BibTeX:
    @article{Debener2005,
      author = {Debener, S and Ullsperger, M and Siegel, M and Fiehler, K and von Cramon, DY and Engel, AK},
      title = {Trial-by-trial coupling of concurrent electroencephalogram and functional magnetic resonance imaging identifies the dynamics of performance monitoring},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2005},
      volume = {25},
      number = {50},
      pages = {11730-11737},
      doi = {{10.1523/JNEUROSCI.3286-05.2005}}
    }
    
    DECETY, J., PERANI, D., JEANNEROD, M., BETTINARDI, V., TADARY, B., WOODS, R., MAZZIOTTA, J. & FAZIO, F. MAPPING MOTOR REPRESENTATIONS WITH POSITRON EMISSION TOMOGRAPHY {1994} NATURE
    Vol. {371}({6498}), pp. {600-602} 
    article  
    Abstract: BRAIN activity was mapped in normal subjects during passive observation of the movements of an `alien' hand and while imagining grasping objects with their own hand. None of the tasks required actual movement. Shifting from one mental task to the other greatly changed the pattern of brain activation. During observation of hand movements, activation was mainly found in visual cortical areas, but also in subcortical areas involved in motor behaviour, such as the basal ganglia and the cerebellum. During motor imagery, cortical and subcortical areas related to motor preparation and programming were strongly activated. These data support the notion that motor learning during observation of movements and mental practice involves rehearsal of neural pathways related to cognitive stages of motor control(1-3).
    BibTeX:
    @article{DECETY1994,
      author = {DECETY, J and PERANI, D and JEANNEROD, M and BETTINARDI, V and TADARY, B and WOODS, R and MAZZIOTTA, JC and FAZIO, F},
      title = {MAPPING MOTOR REPRESENTATIONS WITH POSITRON EMISSION TOMOGRAPHY},
      journal = {NATURE},
      year = {1994},
      volume = {371},
      number = {6498},
      pages = {600-602}
    }
    
    Dehaene, S., Kerszberg, M. & Changeux, J. A neuronal model of a global workspace in effortful cognitive tasks {1998} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {95}({24}), pp. {14529-14534} 
    article  
    Abstract: A minimal hypothesis is proposed concerning the brain processes underlying effortful tasks. It distinguishes two main computational spaces: a unique global workspace composed of distributed and heavily interconnected neurons with long-range axons, and a set of specialized and modular perceptual, motor, memory, evaluative, and attentional processors, Workspace neurons are mobilized in effortful tasks for which the specialized processors do not suffice. They selectively mobilize or suppress, through descending connections, the contribution of specific processor neurons. In the course of task performance, workspace neurons become spontaneously coactivated, forming discrete though variable spatio-temporal patterns subject to modulation by vigilance signals and to selection by reward signals. A computer simulation of the Stroop task shows workspace activation to increase during acquisition of a novel task, effortful execution, and after errors. We outline predictions for spatio-temporal activation patterns during brain imaging, particularly about the contribution of dorsolateral prefrontal cortex and anterior cingulate to the workspace.
    BibTeX:
    @article{Dehaene1998,
      author = {Dehaene, S and Kerszberg, M and Changeux, JP},
      title = {A neuronal model of a global workspace in effortful cognitive tasks},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1998},
      volume = {95},
      number = {24},
      pages = {14529-14534}
    }
    
    Dehaene, S. & Naccache, L. Towards a cognitive neuroscience of consciousness: basic evidence and a workspace framework {2001} COGNITION
    Vol. {79}({1-2}), pp. {1-37} 
    article  
    Abstract: This introductory chapter attempts to clarify the philosophical, empirical, and theoretical bases on which a cognitive neuroscience approach to consciousness can be founded. We isolate three major empirical observations that any theory of consciousness should incorporate, namely (1) a considerable amount of processing is possible without consciousness, (2) attention is a prerequisite of consciousness, and (3) consciousness is required for some specific cognitive tasks, including those that require durable information maintenance, novel combinations of operations, or the spontaneous generation of intentional behavior. We then propose a theoretical framework that synthesizes those facts: the hypothesis of a global neuronal workspace. This framework postulates that, at any given time, many modular cerebral networks are active in parallel and process information in an unconscious manner. An information becomes conscious, however, if the neural population that represents it is mobilized by top-down attentional amplification into a brain-scale state of coherent activity that involves many neurons distributed throughout the brain. The long-distance connectivity of these `workspace neurons' can, when they are active for a minimal duration, make the information available to a variety of processes including perceptual categorization, longterm memorization, evaluation, and intentional action. We postulate that this global availability of information through the workspace is what we subjectively experience as a conscious state. A complete theory of consciousness should explain why some cognitive and cerebral representations can be permanently or temporarily inaccessible to consciousness, what is the range of possible conscious contents, how they map onto specific cerebral circuits, and whether a generic neuronal mechanism underlies all of them. We confront the workspace model with those issues and identify novel experimental predictions. Neurophysiological, anatomical, and brain-imaging data strongly argue for a major role of prefrontal cortex, anterior cingulate, and the areas that connect to them, in creating the postulated brain-scale workspace. (C) 2001 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{Dehaene2001,
      author = {Dehaene, S and Naccache, L},
      title = {Towards a cognitive neuroscience of consciousness: basic evidence and a workspace framework},
      journal = {COGNITION},
      year = {2001},
      volume = {79},
      number = {1-2},
      pages = {1-37}
    }
    
    Deiber, M., Honda, M., Ibanez, V., Sadato, N. & Hallett, M. Mesial motor areas in self-initiated versus externally triggered movements examined with fMRI: Effect of movement type and rate {1999} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {81}({6}), pp. {3065-3077} 
    article  
    Abstract: The human frontomesial cortex reportedly contains at least four cortical areas that are involved in motor control: the anterior supplementary motor area (pre-SMA), the posterior SMA (SMA proper, or SMA), and, in the anterior cingulate cortex, the rostral cingulate zone (RCZ) and the caudal cingulate zone (CCZ). We used functional magnetic resonance imaging (fMRI) to examine the role of each of these mesial motor areas in self-initiated and visually triggered movements. Healthy subjects performed self-initiated movements of the right fingers (self-initiated task, SI). Each movement elicited a visual signal that was recorded. The recorded sequence of visual signals was played back, and the subjects moved the right fingers in response to each signal (visually triggered task, VT). There were two types of movements: repetitive (FIXED) or Sequential (SEQUENCE), performed at two different rates: SLOW or FAST. The four regions of interest (pre-SMA, SMA, RCZ, CCZ) were traced on a high-resolution MRI of each subject's brain. Descriptive analysis, consisting of individual assessment of significant activation, revealed a bilateral activation in the four mesial structures for all movement conditions, but SI movements were more efficient than VT movements. The more complex and more rapid the movements, the smaller the difference in activation efficiency between the SI and the VT tasks, which indicated an additional processing role of the mesial motor areas involving both the type and rate of movements. Quantitative analysis was performed on the spatial extent of the area activated and the percentage of change in signal amplitude. In the pre-SMA, activation was more extensive for SI than for VT movements, and for fast than for slow movements; the extent of activation was larger in the ipsilateral pre-SMA. In the SMA, the difference was not significant in the extent and magnitude of activation between SI and VT movements, but activation was more extensive for sequential than for fixed movements. In the RCZ and CCZ, both the extent and magnitude of activation were larger for SI than for VT movements. In the CCZ, both indices of activation were also larger for sequential than for fixed movements, and for fast than for slow movements. These data suggest functional specificities of the frontomesial motor areas with respect not only to the mode of movement initiation (self-initiated or externally triggered) but also to the movement type and rate.
    BibTeX:
    @article{Deiber1999,
      author = {Deiber, MP and Honda, M and Ibanez, V and Sadato, N and Hallett, M},
      title = {Mesial motor areas in self-initiated versus externally triggered movements examined with fMRI: Effect of movement type and rate},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1999},
      volume = {81},
      number = {6},
      pages = {3065-3077}
    }
    
    Deiber, M., Ibanez, V., Sadato, N. & Hallett, M. Cerebral structures participating in motor preparation in humans: A positron emission tomography study {1996} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {75}({1}), pp. {233-247} 
    article  
    Abstract: 1. Using positron emission tomography and measurement of regional cerebral blood flow (rCBF) as an index of cerebral activity, we investigated the central processing of motor preparation in 13 healthy volunteers. 2. We used a motor reaction time paradigm with visual cues as preparatory and response signals. A preparatory stimulus (PS) provided either full, partial, or no information regarding two variables of a forthcoming right finger movement: finger type (index or little finger) and movement direction (abduction or elevation). After a variable delay period, a response stimulus (RS) prompted the movement. A condition was also tested in which the subject could freely select any of the four possible movements during the preparation period (''free'' condition). The timing of events was designed to emphasize the motor preparation phase over the motor execution component during the scanning time of 1 min. 3. Distinct preparatory processes, which depended on the information contained in the PS, were demonstrated by significant differences in reaction time between conditions. The reaction time was shorter in the `'full'' and free conditions, intermediate in the two partial information conditions (''finger'' and `'direction''), and longer when no preparatory information was available (''none'' condition). Conversely, movement time and movement amplitude were similar between conditions, establishing the constancy of the motor executive output. 4. In comparison with a `'rest'' condition, which had matched visual inputs, the different conditions of motor preparation were associated with increased rCBF in a common set of cerebral regions: the contralateral frontal cortex (sensorimotor, premotor, cingulate, and supplementary motor cortex), the contralateral parietal association cortex (anterior and posterior regions), the ipsilateral cerebellum, the contralateral basal ganglia, and the thalamus. This observation substantiates the participation of those cerebral structures in the preparation for movement. Furthermore, the similarity of the activated areas among the different conditions compared with the rest condition suggests a single anatomic substrate for motor preparation, independent of the movement information context. 5. Differing amounts of movement information contained in the PS affected rCBF changes in some cerebral regions. In particular, the rCBF in the anterior parietal cortex (Brodmann's area 40) was significantly larger in each of the full, finger, and direction conditions, individually, compared with the none condition. This observation supports the hypothesis that the anterior parietal association cortex plays a major role in the use of visual instructions contained in the PS for partial or complete preparation to perform a motor act. On the other hand, the posterior parietal association cortex (Brodmann's area 7) was more activated in the finger, direction, and none conditions than in the full condition. This increased activity with restricted advance information suggests that the posterior region of the parietal cortex is concerned with correct movement selection on the basis of enhanced spatial attention to the RS. 6. In contrast with the parietal cortex, the secondary motor areas (i.e, premotor cortex, cingulate cortex, and supplementary motor area) showed similar activity regardless of the degree of preparation allowed by the advance visual information. Thus the parietal cortex may play a more crucial role than the secondary motor areas in integrating visual information in preparation for movement. 7. The effect on brain activity of the internal (self-generated) versus the external (cued) mode of movement selection was assessed by comparing the free and full conditions, the preparatory component being matched in the two conditions. The anterior part of the supplementary motor area was the main area preferentially involved in the internal selection of movement, independently of motor preparation processes.
    BibTeX:
    @article{Deiber1996,
      author = {Deiber, MP and Ibanez, V and Sadato, N and Hallett, M},
      title = {Cerebral structures participating in motor preparation in humans: A positron emission tomography study},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1996},
      volume = {75},
      number = {1},
      pages = {233-247}
    }
    
    DeKosky, S., Ikonomovic, M., Styren, S., Beckett, L., Wisniewski, S., Bennett, D., Cochran, E., Kordower, J. & Mufson, E. Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment {2002} ANNALS OF NEUROLOGY
    Vol. {51}({2}), pp. {145-155} 
    article DOI  
    Abstract: In Alzheimer's disease (AD), loss of cortical and hippocampal choline acetyltransferase (ChAT) activity has been correlated with dementia severity and disease duration, and it forms the basis for current therapies. However, the extent to which reductions in ChAT activity are associated with early cognitive decline has not been well established. We quantified ChAT activity in the hippocampus and four cortical regions (superior frontal, inferior parietal, superior temporal, and anterior cingulate) of 58 individuals diagnosed with no cognitive impairment (NCI; n = 26; mean age 81.4 +/- 7.3 years), mild cognitive impairment (MCI; n = 18; mean age 84.5 +/- 5.7), or mild AD (n = 14; mean age 86.3 +/- 6.6). Inferior parietal cortex ChAT activity was also assessed in 12 subjects with end-stage AD (mean age 81.4 +/- 4.3 years) and compared to inferior parietal cortex ChAT levels of the other three groups. Only the end-stage AD group had ChAT levels reduced below normal. In individuals with MCI and mild AD, ChAT activity was unchanged in the inferior parietal, superior temporal, and anterior cingulate cortices compared to NCI. In contrast, ChAT activity in the superior frontal cortex was significantly elevated above normal controls in MCI subjects, whereas the mild AD group was not different from NCI or MCI. Hippocampal ChAT activity was significantly higher in MCI subjects than in either NCI or AD. Our results suggest that cognitive deficits in MCI and early AD are not associated with the loss of ChAT and occur despite regionally specific upregulation. Thus, the earliest cognitive deficits in AD involve brain changes other than simply cholinergic system loss. Of importance, the cholinergic system is capable of compensatory responses during the early stage of dementia. The upregulation in frontal cortex and hippocampal ChAT activity could be an important factor in preventing the transition of MCI subjects to AD.
    BibTeX:
    @article{DeKosky2002,
      author = {DeKosky, ST and Ikonomovic, MD and Styren, SD and Beckett, L and Wisniewski, S and Bennett, DA and Cochran, EJ and Kordower, JH and Mufson, EJ},
      title = {Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment},
      journal = {ANNALS OF NEUROLOGY},
      year = {2002},
      volume = {51},
      number = {2},
      pages = {145-155},
      doi = {{10.1002/ana.10069}}
    }
    
    DERBYSHIRE, S., JONES, A., DEVANI, P., FRISTON, K., FEINMANN, C., HARRIS, M., PEARCE, S., WATSON, J. & FRACKOWIAK, R. CEREBRAL RESPONSES TO PAIN IN PATIENTS WITH ATYPICAL FACIAL-PAIN MEASURED BY POSITRON EMISSION TOMOGRAPHY {1994} JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
    Vol. {57}({10}), pp. {1166-1172} 
    article  
    Abstract: The localised PET cerebral correlates of the painful experience in the normal human brain have previously been demonstrated. This study examined whether these responses are different in patients with chronic atypical facial pain. The regional cerebral responses to nonpainful and painful thermal stimuli in six female patients with atypical facial pain and six matched female controls were studied by taking serial measurements of regional blood flow by PET. Both groups displayed highly significant differences in responses to painful heat compared with non-painful heat in the thalamus, anterior cingulate cortex (area 24), lentiform nucleus, insula, and prefrontal cortex. These structures are closely related to the `'medial pain system''. The atypical facial pain group had increased blood flow in the anterior cingulate cortex and decreased blood flow in the prefrontal cortex. These findings show the importance of the anterior cingulate cortex and the reciprocal (possibly inhibitory) connections with the prefrontal cortex in the processing of pain in patients with this disorder. A hypothesis is proposed to explain the mechanisms of cognitive and pharmacological manipulation of these pain processes.
    BibTeX:
    @article{DERBYSHIRE1994,
      author = {DERBYSHIRE, SWG and JONES, AKP and DEVANI, P and FRISTON, KJ and FEINMANN, C and HARRIS, M and PEARCE, S and WATSON, JDG and FRACKOWIAK, RSJ},
      title = {CEREBRAL RESPONSES TO PAIN IN PATIENTS WITH ATYPICAL FACIAL-PAIN MEASURED BY POSITRON EMISSION TOMOGRAPHY},
      journal = {JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY},
      year = {1994},
      volume = {57},
      number = {10},
      pages = {1166-1172}
    }
    
    Derbyshire, S., Jones, A., Gyulai, F., Clark, S., Townsend, D. & Firestone, L. Pain processing during three levels of noxious stimulation produces differential patterns of central activity {1997} PAIN
    Vol. {73}({3}), pp. {431-445} 
    article  
    Abstract: Previous functional imaging studies have demonstrated a number of discrete brain structures that increase activity with noxious stimulation. Of the commonly identified central structures, only the anterior cingulate cortex shows a consistent response during the experience of pain. The insula and thalamus demonstrate reasonable consistency while all other regions, including the lentiform nucleus, somatosensory cortex and prefrontal cortex, are active in no more than half the current studies. The reason for such discrepancy is likely to be due in part to methodological variability and in part to individual variability. One aspect of the methodology which is likely to contribute is the stimulus intensity. Studies vary considerably regarding the intensity of the noxious and non-noxious stimuli delivered. This is likely to produce varying activation of central structures coding for the intensity, affective and cognitive components of pain. Using twelve healthy volunteers and positron emission tomography (PET), the regional cerebral blood flow (rCBF) responses to four intensities of stimulation were recorded. The stimulation was delivered by a CO2 laser and was described subjectively as either warm (not painful), pain threshold (just painful), mildly painful or moderately painful. The following group subtractions were made to examine the changing cerebral responses as the stimulus intensity increased: (1) just painful - warm; (2) mild pain - warm; and (3) moderate pain - warm. In addition, rCBF changes were correlated with the subjective stimulus ratings. The results for comparison `1' indicated activity in the contralateral prefrontal (area 10/46/44), bilateral inferior parietal (area 40) and ipsilateral premotor cortices (area 6), possibly reflecting initial orientation and plans for movement. The latter comparisons and correlation analysis indicated a wide range of active regions including bilateral prefrontal, inferior parietal and premotor cortices and thalamic responses, contralateral hippocampus, insula and primary somatosensory cortex and ipsilateral perigenual cingulate cortex (area 24) and medial frontal cortex (area 32). Decreased rCBF was observed in the amygdala region. These responses were interpreted with respect to their contribution to the multidimensional aspects of pain including fear avoidance, affect, sensation and motivation or motor initiation. It is suggested that future studies examine the precise roles of each particular region during the central processing of pain. (C) 1997 International Association for the Study of Pain. Published by Elsevier Science B.V.
    BibTeX:
    @article{Derbyshire1997,
      author = {Derbyshire, SWG and Jones, AKP and Gyulai, F and Clark, S and Townsend, D and Firestone, LL},
      title = {Pain processing during three levels of noxious stimulation produces differential patterns of central activity},
      journal = {PAIN},
      year = {1997},
      volume = {73},
      number = {3},
      pages = {431-445}
    }
    
    Desgranges, B., Baron, J., de la Sayette, V., Petit-Taboue, M., Benali, K., Landeau, B., Lechevalier, B. & Eustache, F. The neural substrates of memory systems impairment in Alzheimer's disease - A PET study of resting brain glucose utilization {1998} BRAIN
    Vol. {121}({Part 4}), pp. {611-631} 
    article  
    Abstract: The aim of this study was to determine the neuronal basis for memory impairment in Alzheimer's disease by taking advantage of the clinical and metabolic heterogeneity of this pathology. To this end, 19 patients satisfying the NINCDS-ADRDA criteria for probable Alzheimer's disease of mild-to-moderate severity underwent a detailed Examination of the five memory systems according to Tulving's model, together with a PET measurement of resting regional cerebral glucose utilization (CMRGlc). Compared with controls, the patients as a group showed the expected memory and metabolic profiles of impairment. Correlations (corrected for the effects of ageing) were calculated between memory scores and CMRGlc (normalized by the vermis CMRGlc) rising two methods: (i) the classic regions-of-interest method based on a priori hypotheses and individual coregistered structural MRI; and (ii) the statistical parametric mapping method which allows a systematic voxel-by-voxel analysis, in a more descriptive and exploratory way. Significant correlations were above chance levels and largely consistent between the two methods. They were almost exclusively positive (i.e. in the neurobiologically expected direction) and their distribution showed striking differences according to each memory system. Thus, verbal episodic memory impairment was related to changes in a large neuronal network including not only the limbic structures (mesial temporal cortex, thalamus and cingulate gyrus, with left side predominance) but also the parietotemporal and frontal association cortices of the right hemisphere, possibly on a compensatory basis. Regardless of modality, short-term memory tests were mainly correlated with bilateral activity in posterior association cortex, and also with activity in left prefrontal cortex for the visuospatial span, possibly indicating essentially uniform strategies for the performance of the different tasks. As predicted, semantic memory scores correlated with activity in temporoparietal and frontal association cortices of the left hemisphere, and also with activity in left cingulate cortex. Thus, for episodic, short-term and semantic memory, many findings fit classical neuropsychology, while most of the less expected ones were consistent with recent results from functional neuro-imaging in healthy subjects, notably with the hemispheric encoding/retrieval asymmetry (HERA) model; only few findings suggested possible reorganization processes and/or recourse to unexpected cognitive strategy. Finally, only negative correlations were found for perceptual priming and procedural memory; although they could arise by chance, some of these unexpected findings give rise to interesting hypotheses about the cognitive relationships between the most and least affected memory systems. This study documents the validity and usefulness of our approach in unravelling the neural substrates of cognitive impairment in brain pathology without focal tissue loss such as that seen in neurodegenerative diseases.
    BibTeX:
    @article{Desgranges1998,
      author = {Desgranges, B and Baron, JC and de la Sayette, V and Petit-Taboue, MC and Benali, K and Landeau, B and Lechevalier, B and Eustache, F},
      title = {The neural substrates of memory systems impairment in Alzheimer's disease - A PET study of resting brain glucose utilization},
      journal = {BRAIN},
      year = {1998},
      volume = {121},
      number = {Part 4},
      pages = {611-631}
    }
    
    DETTMERS, C., FINK, G., LEMON, R., STEPHAN, K., PASSINGHAM, R., SILBERSWEIG, D., HOLMES, A., RIDDING, M., BROOKS, D. & FRACKOWIAK, R. RELATION BETWEEN CEREBRAL-ACTIVITY AND FORCE IN THE MOTOR AREAS OF THE HUMAN BRAIN {1995} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {74}({2}), pp. {802-815} 
    article  
    Abstract: 1. Positron emission tomography (PET) studies were performed in six normal right-handed male volunteers (age 30 +/- 3) to investigate the relationship between cerebral activation as measured by relative regional cerebral blood flow (rCBF) and force peak exerted during right index finger flexion. The purpose was to determine in which central motor structures activity is directly correlated with force for repeatedly executed movements. 2. Twelve PET rCBF measurements were performed in each volunteer with the use of (H2O)-O-15 as a perfusion tracer. Volunteers pressed a Morse-key repetitively with their right index finger for 2 min while lying in a supine position in the PET camera. The device was fitted with strain gauges to measure the force peaks exerted upon it. Scans were collected twice each at five different levels of exerted force peak and in a resting state. Individual and group results were co-registered with anatomic magnetic resonance images (MRT). 3. Group analysis revealed four major regions with a high correlation between rCBF and different degrees of repetitively exerted force peaks. One was located in the arm area of the left lateral surface [primary somatosensory and motor cortex (SI, MI)]. The second area was situated on the left mesial surface of the brain, posterior to the anterior commissure (AC) and encompassing the first gyrus dorsal to the cingulate sulcus. This area is thought to be homologous to the posterior part of the supplementary motor area (SMA) in the monkey. The third area was the dorsal bank of the posterior cingulate sulcus. The fourth area showing a significant correlation between rCBF and force peaks was in the cerebellar vermis. 4. Individual PET data were co-registered with each individual's MRI in order to identify precisely the locations of structures demonstrating a positive correlation between rCBF and force peak. Activated areas on the mesial surface consisted of the same two distinct regions seen in the group data. In three subjects the focus on the lateral surface of the cortex appeared to extend into the caudal premotor area; in two it extended into the rostral part of the superior parietal area. In no subject did blood flow in the anterior cingulate areas and anterior SMA show a correlation with the force exerted. Cerebellar correlations were present in the vermis in all subjects. 5. In addition to the activation in the primary sensorimotor cortex, a comparison of all activated conditions with the resting state revealed a significant activation in the cerebellar Vermis, left putamen/claustrum, bilateral insular cortices, right and left ventrolateral premotor areas, bilateral parietal opercular regions (SII), left ventral posterior SMA, and bilateral dorsal posterior SMA. 6. At the lowest force level exerted by the right index finger, rCBF in the right primary sensorimotor cortex showed a decrease relative to rest of 5.9 At higher force levels, rCBF showed an 8.7% increase. This was associated with electromyographic evidence of contractions of left shoulder muscles. 7. The relationship between relative increase of rCBF and force peaks was logarithmic with an initial steep increase in rCBF reaching a plateau at higher force levels. The initial slope was steepest in MI. This area, together with the posterior cingulate motor area and the ventral part of the posterior SMA constitute an executive motor system responsible for the execution of controlled force pulses by the index finger. This system is a subset of the areas associated with the generation of finger movements and is responsible for all the components that together result in application of the required digital force.
    BibTeX:
    @article{DETTMERS1995,
      author = {DETTMERS, C and FINK, GR and LEMON, RN and STEPHAN, KM and PASSINGHAM, RE and SILBERSWEIG, D and HOLMES, A and RIDDING, MC and BROOKS, DJ and FRACKOWIAK, RSJ},
      title = {RELATION BETWEEN CEREBRAL-ACTIVITY AND FORCE IN THE MOTOR AREAS OF THE HUMAN BRAIN},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1995},
      volume = {74},
      number = {2},
      pages = {802-815}
    }
    
    DEVINSKY, O., MORRELL, M. & VOGT, B. CONTRIBUTIONS OF ANTERIOR CINGULATE CORTEX TO BEHAVIOUR {1995} BRAIN
    Vol. {118}({Part 1}), pp. {279-306} 
    article  
    Abstract: Assessments of anterior cingulate cortex in experimental animals and humans have led to unifying theories of its structural organization and contributions to mammalian behaviour The anterior cingulate cortex forms a large region around the rostrum of the corpus callosum that is termed the anterior executive region. This region has numerous projections into motor systems, however since these projections originate from different parts of anterior cingulate cortex and because functional studies have shown that it does not have a uniform contribution to brain functions, the anterior executive region is further subdivided into `affect' and `cognition' components. The affect division includes areas 25, 33 and rostral area 24, and has extensive connections with the amygdala and periaqueductal grey, and parts of it project to autonomic brainstem motor nuclei. In addition to regulating autonomic and endocrine functions, it is involved in conditioned emotional learning, vocalizations associated with expressing internal states, assessments of motivational content and assigning emotional valence to internal and external stimuli, and maternal-infant interactions. The cognition divi sion includes caudal areas 24' and 32', the cingulate motor areas in the cingulate sulcus and nociceptive cortex. The cingulate motor areas project to the spinal cord and red nucleus and have premotor functions, while the nociceptive area is engaged in both response selection and cognitively demanding information processing. The cingulate epilepsy syndrome provides important support of experimental animal and human functional imaging studies for the role of anterior cingulate cortex in movement affect and social behaviours. Excessive cingulate activity in cases with seizures confirmed in anterior cingulate cortex with subdural electrode recordings, can impair consciousness alter affective stare and expression, and influence skeletomotor and autonomic activity. Interictally, patients with anterior cingulate cortex epilepsy often display psychopathic or sociopathic behaviours. In other clinical examples of elevated anterior cingulate cortex activity it may contribute to ties, obsessive-compulsive behaviours, and aberrent social behaviour. Conversely, reduced cingulate activity following infarcts or surgery can contribute to behavioural disorders including akinetic mutism, diminished self-awareness and depression, motor neglect and impaired motor initiation, reduced responses to pain, and aberrent social behaviour. The role of anterior cingulate cortex in pain responsiveness is suggested by cingulumotomy results and functional imaging studies during noxious somatic stimulation. The affect division of anterior cingulate cortex modulates autonomic activity and internal emotional responses, while the cognition division is engaged in response selection associated with skeletomotor activity and responses to noxious stimuli. Over-all, anterior cingulate cortex appears to play a crucial role in initiation, motivation, and goal-directed behaviours. The anterior cingulate cortex is part of a larger matrix of structures that are engaged in similar functions. These structures from the rostral limbic system and include the amygdala, periaqueductal grey, ventral striatum, orbitofrontal and anterior insular cortices. The system formed by these interconnected areas assesses the motivational content of internal and external stimuli and regulates context-dependent behaviours.
    BibTeX:
    @article{DEVINSKY1995,
      author = {DEVINSKY, O and MORRELL, MJ and VOGT, BA},
      title = {CONTRIBUTIONS OF ANTERIOR CINGULATE CORTEX TO BEHAVIOUR},
      journal = {BRAIN},
      year = {1995},
      volume = {118},
      number = {Part 1},
      pages = {279-306}
    }
    
    DIORIO, D., VIAU, V. & MEANEY, M. THE ROLE OF THE MEDIAL PREFRONTAL CORTEX (CINGULATE GYRUS) IN THE REGULATION OF HYPOTHALAMIC-PITUITARY-ADRENAL RESPONSES TO STRESS {1993} JOURNAL OF NEUROSCIENCE
    Vol. {13}({9}), pp. {3839-3847} 
    article  
    Abstract: In the studies reported here we have examined the role of the medial prefrontal cortex (MpFC) in regulating hypothalamic-pituitary-adrenal (HPA) activity under basal and stressful conditions. In preliminary studies we characterized corticosteroid receptor binding in the rat MpFC. The results revealed high-affinity (K(d) approximately 1 nm) binding with a moderate capacity (42.9 +/- 3 fmol/mg) for H-3-aldosterone (with a 50-fold excess of cold RU28362; mineralocorticoid receptor) and high-affinity (K(d) approximately 0.5-1.0 nm) binding with higher capacity (1 83.2 +/- 22 fmol/mg) for H-3-RU 28362 (glucocorticoid receptor). Lesions of the MpFC (cingulate gyrus) significantly increased plasma levels of both adrenocorticotropin (ACTH) and corticosterone (CORT) in response to a 20 min restraint stress. The same lesions had no effect on hormone levels following a 2.5 min exposure to ether. Implants of crystalline CORT into the same region of the MpFC produced a significant decrease in plasma levels of both ACTH and CORT with restraint stress, but again, there was no effect with ether stress. Neither MpFC lesions nor CORT implants had any consistent effect on A.M. or P.M. levels of plasma ACTH or CORT. Manipulations of MpFC function were not associated with changes in the clearance rate for CORT or in corticosteroid receptor densities in the pituitary, hypothalamus, hippocampus, or amygdala. Taken together, these findings suggest that MpFC is a target site for the negative-feedback effects of glucocorticoids on stress-induced HPA activity, and that this effect is dependent upon the nature of the stress.
    BibTeX:
    @article{DIORIO1993,
      author = {DIORIO, D and VIAU, V and MEANEY, MJ},
      title = {THE ROLE OF THE MEDIAL PREFRONTAL CORTEX (CINGULATE GYRUS) IN THE REGULATION OF HYPOTHALAMIC-PITUITARY-ADRENAL RESPONSES TO STRESS},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1993},
      volume = {13},
      number = {9},
      pages = {3839-3847}
    }
    
    DOLAN, R., FLETCHER, P., FRITH, C., FRISTON, K., FRACKOWIAK, R. & GRASBY, P. DOPAMINERGIC MODULATION OF IMPAIRED COGNITIVE ACTIVATION IN THE ANTERIOR CINGULATE CORTEX IN SCHIZOPHRENIA {1995} NATURE
    Vol. {378}({6553}), pp. {180-182} 
    article  
    Abstract: DOPAMINERGIC dysregulation remains an empirical cornerstone for theories concerning the causation of schizophrenia. Evidence for a dopamine system dysfunction in schizophrenia includes the psychosis-inducing effects of dopaminergic agonists(1,2) and the antipsychotic potency of dopaminergic antagonists(3'4). Here we use positron emission tomography (PET) to examine the regulatory role of dopamine on cortical function in normal subjects and unmedicated schizophrenic patients. Using a factorial experimental design, we compared the effect of dopaminergic manipulation with apomorphine on a neural response to a cognitive task. In the schizophrenic patients, relative to controls, an impaired cognitive activation of the anterior cingulate cortex was significantly modulated by a manipulation of dopaminergic neurotransmission. Thus, after apomorphine, the schizophrenic subjects displayed a significantly enhanced cognitive activation of the anterior cingulate cortex relative to the controls. These data provide in vivo evidence that an impaired cognitive-task-induced activation of the anterior cingulate cortex in schizophrenic patients can be significantly modulated by a dopaminergic manipulation.
    BibTeX:
    @article{DOLAN1995,
      author = {DOLAN, RJ and FLETCHER, P and FRITH, CD and FRISTON, KJ and FRACKOWIAK, RSJ and GRASBY, PM},
      title = {DOPAMINERGIC MODULATION OF IMPAIRED COGNITIVE ACTIVATION IN THE ANTERIOR CINGULATE CORTEX IN SCHIZOPHRENIA},
      journal = {NATURE},
      year = {1995},
      volume = {378},
      number = {6553},
      pages = {180-182}
    }
    
    Downar, J., Crawley, A., Mikulis, D. & Davis, K. A multimodal cortical network for the detection of changes in the sensory environment {2000} NATURE NEUROSCIENCE
    Vol. {3}({3}), pp. {277-283} 
    article  
    Abstract: Sensory stimuli undergoing sudden changes draw attention and preferentially enter our awareness. We used event-related functional magnetic-resonance imaging (fMRI) to identify brain regions responsive to changes in visual, auditory and tactile stimuli. Unimodally responsive areas included visual, auditory and somatosensory association cortex. Multimodally responsive areas comprised a right-lateralized network including the temporoparietal junction, inferior frontal gyrus, insula and left cingulate and supplementary motor areas. These results reveal a distributed, multimodal network for involuntary attention to events in the sensory environment. This network contains areas thought to underlie the P300 event-related potential and closely corresponds to the set of cortical regions damaged in patients with hemineglect syndromes.
    BibTeX:
    @article{Downar2000,
      author = {Downar, J and Crawley, AP and Mikulis, DJ and Davis, KD},
      title = {A multimodal cortical network for the detection of changes in the sensory environment},
      journal = {NATURE NEUROSCIENCE},
      year = {2000},
      volume = {3},
      number = {3},
      pages = {277-283}
    }
    
    Doyon, J., Owen, A., Petrides, M., Sziklas, V. & Evans, A. Functional anatomy of visuomotor skill learning in human subjects examined with positron emission tomography {1996} EUROPEAN JOURNAL OF NEUROSCIENCE
    Vol. {8}({4}), pp. {637-648} 
    article  
    Abstract: The present study was designed to examine patterns of regional cerebral blood flow (CBF) associated with the learning of a repeated visuomotor sequence both in the early and late phases of the acquisition process. In addition, changes in blood Row related to the implicit versus explicit aspects of learning such a skill were investigated. Fourteen normal control subjects were scanned while performing the task (i) in both early and advanced]earning stages of the visuomotor sequence; (ii) after having acquired explicit knowledge of the sequences; and (iii) in two control conditions (perceptual and random sequence), Subtraction of the random condition from the highly learned condition revealed specific areas of activity in the right ventral striatum and dentate nucleus of the cerebellum. Blood flow changes in the right hemisphere were also seen in the medial posterior parietal and prestriate regions, as well as in the anterior cingulate cortex. Finally, once the subjects had acquired explicit knowledge of the embedded sequence that was presented in the highly learned condition, increased CBF activity was observed only in the mid-ventrolateral frontal area in the right hemisphere, These findings confirm that both the striatum and the cerebellum are involved in the implicit acquisition of a visuomotor skill, especially in the advanced stages of the learning process, and furthermore that the ventrolateral prefrontal cortex contributes preferentially to the declarative aspect of this task.
    BibTeX:
    @article{Doyon1996,
      author = {Doyon, J and Owen, AM and Petrides, M and Sziklas, V and Evans, AC},
      title = {Functional anatomy of visuomotor skill learning in human subjects examined with positron emission tomography},
      journal = {EUROPEAN JOURNAL OF NEUROSCIENCE},
      year = {1996},
      volume = {8},
      number = {4},
      pages = {637-648}
    }
    
    Drevets, W. Neuroimaging studies of mood disorders {2000} BIOLOGICAL PSYCHIATRY
    Vol. {48}({8}), pp. {813-829} 
    article  
    Abstract: Neuroimaging studies of major depression have identified neurophysiologic abnormalities in multiple areas of the orbital and medial prefrontal cortex, the amygdala, and related parts of the striatum and thalamus. Some of these abnormalities appear mood state-dependent and are located in regions where cerebral blood flow increases during normal and other pathologic emotional states. These neurophysiologic differences between depressives and control subjects may thus implicate areas where physiologic activity changes to mediate or respond to the emotional, behavioral, and cognitive manifestations of major depressive episodes. Other abnormalities persist following symptom remission, and are found in orbital and medial prefrontal cortex areas where postmortem studies demonstrate reductions in colter volume and histopathologic changes in primary mood disorders. These areas appear to modulate emotional behavior and stress responses, based upon evidence from brain mapping, lesion analysis, and electrophysiologic studies of humans and/or experimental animals. Dysfunction involving these regions is thus hypothesized to play a role in the pathogenesis of depressive symptoms. Taken together, these findings implicate interconnected neural circuits in which pathologic patterns of neurotransmission may result in the emotional, motivational, cognitive, and behavioral manifestations of primary and secondary affective disorders. Biol Psychiatry 2000;48:813-829 (C) 2000 Society of Biological Psychiatry.
    BibTeX:
    @article{Drevets2000,
      author = {Drevets, WC},
      title = {Neuroimaging studies of mood disorders},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {2000},
      volume = {48},
      number = {8},
      pages = {813-829},
      note = {Conference on Depression in the 21st Century: New Insight into Drug Development and Neurobiology, DANA POINT, CA, FEB 02-22, 2000}
    }
    
    Drevets, W. & Raichle, M. Reciprocal suppression of regional cerebral blood flow during emotional versus higher cognitive processes: Implications for interactions between emotion and cognition {1998} COGNITION & EMOTION
    Vol. {12}({3}), pp. {353-385} 
    article  
    Abstract: Brain mapping studies using dynamic imaging methods demonstrate areas where regional cerebral blood flow (rCBF) decreases, as well as areas where flow increases, during performance of various experimental tasks. Task specificity holds for both sets of cerebral blood flow changes (Delta CBF), respectively, providing the opportunity to investigate areas that become ``deactivated'' and ``activated'' in the experimental condition relative to the control state. Such data yield the intriguing observation that in areas implicated in emotional processing, such as the amygdala, the posteromedial orbital cortex, and the ventral anterior cingulate cortex, although flow increases as expected during specific emotion-related tasks, flow decreases during performance of some attentionally demanding, cognitive tasks. Conversely, in some of the areas that appear to subserve cognitive functions, such as the dorsal anterior cingulate and the dorsolateral prefrontal cortices, flow increases while performing attentionally demanding cognitive tasks, but decreases during some experimentally induced and pathological emotional states. Although the specific nature of such reciprocal patterns of regional Delta CBF remains unclear, they may reflect an important cross-modal interaction during mental operations. The possibility that neural activity is less active in areas required in emotional processing during some higher cognitive processes holds implications for the mechanisms underlying interactions between cognition and emotion. Furthermore, the possibility that neural activity in some cognitive-processing areas is suppressed during intense emotional states suggests mechanisms by which extreme fear or severe depression may interfere with cognitive performance.
    BibTeX:
    @article{Drevets1998,
      author = {Drevets, WC and Raichle, ME},
      title = {Reciprocal suppression of regional cerebral blood flow during emotional versus higher cognitive processes: Implications for interactions between emotion and cognition},
      journal = {COGNITION & EMOTION},
      year = {1998},
      volume = {12},
      number = {3},
      pages = {353-385}
    }
    
    Drossman, D. The functional gastrointestinal disorders and the Rome III process {2006} GASTROENTEROLOGY
    Vol. {130}({5}), pp. {1377-1390} 
    article  
    BibTeX:
    @article{Drossman2006,
      author = {Drossman, DA},
      title = {The functional gastrointestinal disorders and the Rome III process},
      journal = {GASTROENTEROLOGY},
      year = {2006},
      volume = {130},
      number = {5},
      pages = {1377-1390}
    }
    
    DUM, R. & STRICK, P. THE ORIGIN OF CORTICOSPINAL PROJECTIONS FROM THE PREMOTOR AREAS IN THE FRONTAL-LOBE {1991} JOURNAL OF NEUROSCIENCE
    Vol. {11}({3}), pp. {667-689} 
    article  
    Abstract: We determined the origin of corticospinal neurons in the frontal lobe. These neurons were labeled by retrograde transport of tracers after injections into either the dorsolateral funiculus at the second cervical segment or the gray matter of the spinal cord throughout the cervical enlargement. Using retrograde transport of tracer from the arm area of the primary motor cortex, we defined the arm representation in each premotor area in another set of animals. We found that corticospinal projections to cervical segments of the spinal cord originate from the primary motor cortex and from the 6 premotor areas in the frontal lobe. These are the same premotor areas that project directly to the arm area of the primary motor cortex. The premotor areas are located in parts of cytoarchitectonic area 6 on the lateral surface and medial wall of the hemisphere, as well as in subfields of areas 23 and 24 in the cingulate sulcus. The total number of corticospinal neurons in the arm representations of the premotor areas equals or exceeds the total number in the arm representation of the primary motor cortex. The premotor areas collectively comprise more than 60% of the cortical area in the frontal lobe that projects to the spinal cord. Like the primary motor cortex, each of the premotor areas contains local regions that have a high density of corticospinal neurons. These observations indicate that a substantial component of the corticospinal system originates from the premotor areas in the frontal lobe. Each of the premotor areas has direct access to the spinal cord, and as a consequence, each has the potential to influence the generation and control of movement independently of the primary motor cortex. These findings raise serious questions about the utility of viewing the primary motor cortex as the ``upper motoneuron'' or ``final common pathway'' for the central control of movement.
    BibTeX:
    @article{DUM1991,
      author = {DUM, RP and STRICK, PL},
      title = {THE ORIGIN OF CORTICOSPINAL PROJECTIONS FROM THE PREMOTOR AREAS IN THE FRONTAL-LOBE},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1991},
      volume = {11},
      number = {3},
      pages = {667-689}
    }
    
    Duncan, G., Knapp, D. & Breese, G. Neuroanatomical characterization of Fos induction in rat behavioral models of anxiety {1996} BRAIN RESEARCH
    Vol. {713}({1-2}), pp. {79-91} 
    article  
    Abstract: Immunohistochemical staining for Fos-like immunoreactivity (Fos-LI) was used to map functional activation in discrete brain regions of rats processed in three empirical models of anxiety: foot shock avoidance responding in a shuttle box, the elevated plus maze, and an air puff-induced ultrasonic vocalization test. The avoidance test and elevated plus maze induced prominent Fos-LI in select brain regions, including the medial prefrontal, cingulate, and ventrolateral orbital cortices, taenia tecta, nucleus accumbens, paraventricular nucleus of the hypothalamus, medial nucleus of the amygdala and lateral septum. Air puff stimuli that produced ultrasonic vocalizations induced Fos-LI to a more limited extent compared to the plus maze and avoidance test, with only the medial prefrontal cortex, medial nucleus of the amygdala, and lateral septum being significantly affected by air-puff. Even though the sensory stimuli and environmental conditions associated with the three anxiety models were markedly different, specific common forebrain regions were affected, i.e. the medial prefrontal cortex, medial amygdala, and lateral septum. It is hypothesized that these regions are components of a circuit in the rat brain related to anxiety or distress. To determine the potential relationship between generalized arousal and the observed induction of Fos-LI in the anxiety models, rats were tested in a non-aversive situation involving marked behavioral activation. Accordingly, after vigorous bar pressing behavior for reinforcement with sweetened condensed milk, induction of Fos-LI was minimal and comparable to that in unhandled control rats. These latter data indicate that the distinctive neuroanatomical patterns of Fos-LI observed in the paradigms related to anxiety were not simply due to generalized behavioral activation. In summary, select common brain regions were identified that express Fos-LI in empirical models of anxiety. These data provide a functional framework to explore neuroanatomical sites of action of psychotherapeutic drugs that influence behavioral responses in these tasks.
    BibTeX:
    @article{Duncan1996,
      author = {Duncan, GE and Knapp, DJ and Breese, GR},
      title = {Neuroanatomical characterization of Fos induction in rat behavioral models of anxiety},
      journal = {BRAIN RESEARCH},
      year = {1996},
      volume = {713},
      number = {1-2},
      pages = {79-91}
    }
    
    Duncan, J. & Owen, A. Common regions of the human frontal lobe recruited by diverse cognitive demands {2000} TRENDS IN NEUROSCIENCES
    Vol. {23}({10}), pp. {475-483} 
    article  
    Abstract: Though many neuroscientific methods have been brought to bear in the search for functional specializations within prefrontal cortex, little consensus has emerged. To assess the contribution of functional neuroimaging, this article reviews patterns of frontal-lobe activation associated with a broad range of different cognitive demands, including aspects of perception, response selection, executive control, working memory, episodic memory and problem solving,The results show a striking regularity: for many demands, there is a similar recruitment of mid-dorsolateral, mid-ventrolateral and dorsal anterior cingulate cortex. Much of the remainder of frontal cortex, including most of the medial and orbital surfaces, is largely insensitive to these demands. Undoubtedly, these results provide strong evidence for regional specialization of function within prefrontal cortex,This specialization, however, takes an unexpected form: a specific frontal-lobe network that is consistently recruited for solution of diverse cognitive problems.
    BibTeX:
    @article{Duncan2000,
      author = {Duncan, J and Owen, AM},
      title = {Common regions of the human frontal lobe recruited by diverse cognitive demands},
      journal = {TRENDS IN NEUROSCIENCES},
      year = {2000},
      volume = {23},
      number = {10},
      pages = {475-483}
    }
    
    Ehrsson, H., Fagergren, A., Jonsson, T., Westling, G., Johansson, R. & Forssberg, H. Cortical activity in precision- versus power-grip tasks: An fMRI study {2000} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {83}({1}), pp. {528-536} 
    article  
    Abstract: Most manual grips can be divided in precision and power grips on the basis of phylogenetic and functional considerations. We used functional magnetic resonance imaging to compare human brain activity during force production by the right hand when subjects used a precision grip and a power grip. During the precision-grip task, subjects applied fine grip forces between the tips of the index finger and the thumb. During the power-grip task, subjects squeezed a cylindrical object using all digits in a palmar opposition grasp. The activity recorded in the primary sensory and motor cortex contralateral to the operating hand was higher when the power grip was applied than when subjects applied force with a precision grip. In contrast, the activity in the ipsilateral ventral pre motor area, the rostral cingulate motor area, and at several locations in the posterior parietal and prefrontal cortices was stronger while making the precision grip than during the power grip. The power grip was associated predominately with contralateral left-sided activity, whereas the precision-grip task involved extensive activations in both hemispheres. Thus our findings indicate that in addition to the primary motor cortex, premotor and parietal areas are important for control of fingertip forces during precision grip. Moreover, the ipsilateral hemisphere appears to be strongly engaged in the control of precision-grip tasks performed with the right hand.
    BibTeX:
    @article{Ehrsson2000,
      author = {Ehrsson, HH and Fagergren, A and Jonsson, T and Westling, G and Johansson, RS and Forssberg, H},
      title = {Cortical activity in precision- versus power-grip tasks: An fMRI study},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {2000},
      volume = {83},
      number = {1},
      pages = {528-536}
    }
    
    Eickhoff, S., Stephan, K., Mohlberg, H., Grefkes, C., Fink, G., Amunts, K. & Zilles, K. A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data {2005} NEUROIMAGE
    Vol. {25}({4}), pp. {1325-1335} 
    article DOI  
    Abstract: Correlating the activation foci identified in functional imaging studies of the human brain with structural (e.g., cytoarchitectonic) information oil the activated areas is a major methodological challenge for neuroscience research. We here present a new approach to make use of three-dimensional probabilistic cytoarchitectonic maps, as obtained from the analysis of human post-mortem brains, for correlating microscopical, anatomical and functional imaging data of the cerebral cortex. We introduce a new, MATLAB based toolbox for the SPM2 software package which enables the integration of probabilistic cytoarchitectonic maps and results of functional imaging studies. The toolbox include the functionality for the construction of summary maps combining probability of several cortical areas by finding the most probable assignment of each vosel to one of these areas. Its main feature is to provide several measures defining the degree of correspondence between architectonic areas and functional foci. The maps, is software, together with the presently available probability available as open source software to the neuroimaging community. This new toolbox provides an easy-to-use tool for the integrated analysis of functional and anatomical data in a common reference space. (c) 2004 Elsevier Inc. All rights reserved.
    BibTeX:
    @article{Eickhoff2005,
      author = {Eickhoff, SB and Stephan, KE and Mohlberg, H and Grefkes, C and Fink, GR and Amunts, K and Zilles, K},
      title = {A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data},
      journal = {NEUROIMAGE},
      year = {2005},
      volume = {25},
      number = {4},
      pages = {1325-1335},
      doi = {{10.1016/j.neuroimage.2004.12.034}}
    }
    
    Eisenberger, N., Lieberman, M. & Williams, K. Does rejection hurt? An fMRI study of social exclusion {2003} SCIENCE
    Vol. {302}({5643}), pp. {290-292} 
    article  
    Abstract: A neuroimaging study examined the neural correlates of social exclusion and tested the hypothesis that the brain bases of social pain are similar to those of physical pain. Participants were scanned while playing a virtual ball-tossing game in which they were ultimately excluded. Paralleling results from physical pain studies, the anterior cingulate cortex (ACC) was more active during exclusion than during inclusion and correlated positively with self-reported distress. Right ventral prefrontal cortex (RVPFC) was active during exclusion and correlated negatively with self-reported distress. ACC changes mediated the RVPFC-distress correlation, suggesting that RVPFC regulates the distress of social exclusion by disrupting ACC activity.
    BibTeX:
    @article{Eisenberger2003,
      author = {Eisenberger, NI and Lieberman, MD and Williams, KD},
      title = {Does rejection hurt? An fMRI study of social exclusion},
      journal = {SCIENCE},
      year = {2003},
      volume = {302},
      number = {5643},
      pages = {290-292}
    }
    
    Elliott, R., Friston, K. & Dolan, R. Dissociable neural responses in human reward systems {2000} JOURNAL OF NEUROSCIENCE
    Vol. {20}({16}), pp. {6159-6165} 
    article  
    Abstract: Reward is one of the most important influences shaping behavior. Single-unit recording and lesion studies in experimental animals have implicated a number of regions in response to reinforcing stimuli, in particular regions of the extended limbic system and the ventral striatum. In this experiment, functional neuroimaging was used to assess neural response within human reward systems under different psychological contexts. Nine healthy volunteers were scanned using functional magnetic resonance imaging during the performance of a gambling task with financial rewards and penalties. We demonstrated neural sensitivity of midbrain and ventral striatal regions to financial rewards and hippocampal sensitivity to financial penalties. Furthermore, we show that neural responses in globus pallidus, thalamus, and subgenual cingulate were specific to high reward levels occurring in the context of increasing reward. Responses to both reward level in the context of increasing reward and penalty level in the context of increasing penalty were seen in caudate, insula, and ventral prefrontal cortex. These results demonstrate dissociable neural responses to rewards and penalties that are dependent on the psychological context in which they are experienced.
    BibTeX:
    @article{Elliott2000,
      author = {Elliott, R and Friston, KJ and Dolan, RJ},
      title = {Dissociable neural responses in human reward systems},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2000},
      volume = {20},
      number = {16},
      pages = {6159-6165}
    }
    
    Ennaceur, A., Neave, N. & Aggleton, J. Spontaneous object recognition and object location memory in rats: The effects of lesions in the cingulate cortices, the medial prefrontal cortex, the cingulum bundle and the fornix {1997} EXPERIMENTAL BRAIN RESEARCH
    Vol. {113}({3}), pp. {509-519} 
    article  
    Abstract: The first experiment assessed the effects of neurotoxic lesions in either the anterior cingulate cortex (ACc) or the retrosplenial cortex (RSc) on a test of object recognition. Neither lesion affected performance on this task, which takes advantage of the rat's normal preference to spend more time investigating novel rather than familiar stimuli. In response to this negative result, a second experiment assessed the effects of much more extensive cingulate lesions (Cg) on both object recognition and object location memory. The latter task also used a preference measure, but in this case it concerned preference for a novel location. For comparison purposes this second study included groups of rats with lesions in closely allied regions: the fornix (Fx), the cingulum bundle (CB) and the medial prefrontal cortex (Pfc). Comparisons with sham-operated control rats showed that none of the four groups (Cg, Fx, CB, Pfc) was impaired on the object recognition task, adding further weight to the view that these structures are not necessary for assessing stimulus familiarity. The Fx and Cg groups were, however, impaired on the object location task, suggesting that these regions are necessary for remembering other attributes of a stimulus (spatial location).
    BibTeX:
    @article{Ennaceur1997,
      author = {Ennaceur, A and Neave, N and Aggleton, JP},
      title = {Spontaneous object recognition and object location memory in rats: The effects of lesions in the cingulate cortices, the medial prefrontal cortex, the cingulum bundle and the fornix},
      journal = {EXPERIMENTAL BRAIN RESEARCH},
      year = {1997},
      volume = {113},
      number = {3},
      pages = {509-519}
    }
    
    Everitt, B., Dickinson, A. & Robbins, T. The neuropsychological basis of addictive behaviour {2001} BRAIN RESEARCH REVIEWS
    Vol. {36}({2-3, Sp. Iss. SI}), pp. {129-138} 
    article  
    Abstract: The argument advanced in this review is that drug addiction can be understood in terms of normal learning and memory systems of the brain which, through the actions of chronically self-administered drugs, are pathologically subverted, thereby leading to the establishment of compulsive drug-seeking habits, strengthened by the motivational impact of drug-associated stimuli and occurring at the expense of other sources of reinforcement. We review data from our studies that have utilized procedures which reveal the various influences of pavlovian stimuli on goal-directed behaviour, namely discriminated approach, pavlovian-to-instrumental transfer and conditioned reinforcement, in order to demonstrate their overlapping and also unique neural bases. These fundamental studies are also reviewed in the context of the neural and psychological mechanisms underlying drug-seeking behaviour that is under the control of drug-associated environmental stimuli. The ways in which such drug-seeking behaviour becomes compulsive and habitual, as well as the propensity for relapse to drug-seeking even after long periods of relapse, are discussed in terms of the aberrant learning set in train by the effects of self-administered drugs on plastic processes in limbic cortical-ventral striatal systems. (C) 2001 Elsevier Science BY All rights reserved.
    BibTeX:
    @article{Everitt2001,
      author = {Everitt, BJ and Dickinson, A and Robbins, TW},
      title = {The neuropsychological basis of addictive behaviour},
      journal = {BRAIN RESEARCH REVIEWS},
      year = {2001},
      volume = {36},
      number = {2-3, Sp. Iss. SI},
      pages = {129-138},
      note = {Symposium of the Swiss-National-Science-Foundation, WARTH, SWITZERLAND, MAR 29-31, 2001}
    }
    
    Everitt, B. & Robbins, T. Central cholinergic systems and cognition {1997} ANNUAL REVIEW OF PSYCHOLOGY
    Vol. {48}, pp. {649-684} 
    article  
    Abstract: The organization and possible functions of basal forebrain and pontine cholinergic systems are reviewed. Whereas the basal forebrain cholinergic neuronal projections likely subserve a common electrophysiological function, e.g. to boost signal-to-noise ratios in cortical target areas, this function has different effects on psychological processes dependent upon the neural network operations within these various cortical domains. Evidence is presented that (a) the nucleus basalis-neocortical cholinergic system contributes greatly to visual attentional function, but not to mnemonic processes per se; (b) the septohippocampal projection is involved in the modulation of short-term spatial (working) memory processes, perhaps by prolonging the neural representation of external stimuli within the hippocampus; and (c) the diagonal band-cingulate cortex cholinergic projection impacts on the ability to utilize response rules through conditional discrimination. We also suggest that nucleus basalis-amygdala cholinergic projections have a role in the retention of affective conditioning while brainstem cholinergic projections to the thalamus and midbrain dopamine neurons affect basic arousal processes (e.g. sleep-wake cycle) and behavioral activation, respectively. The possibilities and limitations of therapeutic interventions with procholinergic drugs in patients with Alzheimer's disease and other neurodegenerative disorders in which basal forebrain cholinergic neurons degenerate are also discussed.
    BibTeX:
    @article{Everitt1997,
      author = {Everitt, BJ and Robbins, TW},
      title = {Central cholinergic systems and cognition},
      journal = {ANNUAL REVIEW OF PSYCHOLOGY},
      year = {1997},
      volume = {48},
      pages = {649-684}
    }
    
    Everitt, B. & Wolf, M. Psychomotor stimulant addiction: A neural systems perspective {2002} JOURNAL OF NEUROSCIENCE
    Vol. {22}({9}), pp. {3312-3320} 
    article  
    BibTeX:
    @article{Everitt2002,
      author = {Everitt, BJ and Wolf, ME},
      title = {Psychomotor stimulant addiction: A neural systems perspective},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2002},
      volume = {22},
      number = {9},
      pages = {3312-3320}
    }
    
    Fan, J., Flombaum, J., McCandliss, B., Thomas, K. & Posner, M. Cognitive and brain consequences of conflict {2003} NEUROIMAGE
    Vol. {18}({1}), pp. {42-57} 
    article DOI  
    Abstract: Tasks involving conflict between stimulus dimensions have been shown to activate dorsal anterior cingulate and prefrontal areas. It has been proposed that the dorsal anterior cingulate is involved a domain general process of monitoring conflict, while prefrontal areas are involved in resolving conflict. We examine three tasks that all require people to respond based on one stimulus dimension while ignoring another con flicting dimension, but which vary in the source of conflict. One of the tasks uses Language stimuli (Stroop effect) and two use nonlanguage spatial conflicts appropriate for children and nonhuman animals In Experiment 1, 12 participants were studied with event-related functional magnetic resonance imaging (fMRI) while performing each of the three tasks. Reaction tunes for each of the three tasks were significantly longer in the incongruent condition compared with the congruent condition, demonstrating that each task elicits a conflict. By studying the same people in the same session, we test the hypothesis that conflict activates a similar brain network in the three tasks. Significant activations were found in the anterior cingulate and left prefrontal cortex for all three conflict tasks. Within these regions, the conflict component demonstrated evidence for significant common activation across the three tasks, although the peak activation point and spatial extent were not identical. Other areas demonstrated activation unique to each task. Experiments 2-4 provide behavioral evidence indicating considerable independence between conflict operations involved in the tasks. The behavioral and fMRI results taken together seem to argue against a single unified network for processing conflict, but instead support either distinct networks for each conflict task or a single network that monitors conflict with different sites used to resolve the conflict. (C) 2002 Elsevier Science (USA).
    BibTeX:
    @article{Fan2003,
      author = {Fan, J and Flombaum, JI and McCandliss, BD and Thomas, KM and Posner, MI},
      title = {Cognitive and brain consequences of conflict},
      journal = {NEUROIMAGE},
      year = {2003},
      volume = {18},
      number = {1},
      pages = {42-57},
      doi = {{10.1006/nimg.2002.1319}}
    }
    
    Fan, J., McCandliss, B., Fossella, J., Flombaum, J. & Posner, M. The activation of attentional networks {2005} NEUROIMAGE
    Vol. {26}({2}), pp. {471-479} 
    article DOI  
    Abstract: Alerting, orienting, and executive control are widely thought to be relatively independent aspects of attention that are linked to separable brain regions. However, neuroimaging studies have yet to examine evidence for the anatomical separability of these three aspects of attention in the same subjects performing the same task. The attention network test (ANT) examines the effects of cues and targets within a single reaction time task to provide a means of exploring the efficiency of the alerting, orienting, and executive control networks involved in attention. It also provides an opportunity to examine the brain activity of these three networks as they operate in a single integrated task. We used event-related functional magnetic resonance imaging (fMRI) to explore the brain areas involved in the three attention systems targeted by the ANT. The alerting contrast showed strong thalamic involvement and activation of anterior and posterior cortical sites. As expected, the orienting contrast activated parietal sites and frontal eye fields. The executive control network contrast showed activation of the anterior cingulate along with several other brain areas. With some exceptions, activation patterns of these three networks within this single task are consistent with previous fMRI studies that have been studied in separate tasks. Overall, the fMRI results suggest that the functional contrasts within this single task differentially activate three separable anatomical networks related to the components of attention. (c) 2005 Elsevier Inc. All rights reserved.
    BibTeX:
    @article{Fan2005,
      author = {Fan, J and McCandliss, BD and Fossella, J and Flombaum, JI and Posner, MI},
      title = {The activation of attentional networks},
      journal = {NEUROIMAGE},
      year = {2005},
      volume = {26},
      number = {2},
      pages = {471-479},
      doi = {{10.1016/j.neuroimage.2005.02.004}}
    }
    
    Fan, J., McCandliss, B., Sommer, T., Raz, A. & Posner, M. Testing the efficiency and independence of attentional networks {2002} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {14}({3}), pp. {340-347} 
    article  
    Abstract: In recent years, three attentional networks have been defined in anatomical and functional terms. These functions involve alerting, orienting, and executive attention. Reaction time measures can be used to quantify the processing efficiency within each of these three networks. The Attention Network Test (ANT) is designed to evaluate alerting, orienting, and executive attention within a single 30-min testing session that can be easily performed by children, patients, and monkeys. A study with 40 normal adult subjects indicates that the ANT produces reliable single Subject estimates of alerting, orienting, and executive function, and further Suggests that the efficiencies of these three networks are uncorrelated. There are, however, some interactions in which alerting and orienting can modulate the degree of interference from flankers, This procedure may prove to be convenient and useful in evaluating attentional abnormalities associated with cases of brain injury, stroke, schizophrenia, and attention-deficit disorder. The ANT may also serve as an activation task for neuroimaging studies and as a phenotype for the study, of the influence of genes on attentional networks.
    BibTeX:
    @article{Fan2002,
      author = {Fan, J and McCandliss, BD and Sommer, T and Raz, A and Posner, MI},
      title = {Testing the efficiency and independence of attentional networks},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {2002},
      volume = {14},
      number = {3},
      pages = {340-347}
    }
    
    Fiez, J. & Petersen, S. Neuroimaging studies of word reading {1998} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {95}({3}), pp. {914-921} 
    article  
    Abstract: This review discusses how neuroimaging can contribute to our understanding of a fundamental aspect of skilled reading: the ability to pronounce a visually presented word, One contribution of neuroimaging is that it provides a tool for localizing brain regions that are active during word reading, To assess the extent to which similar results are obtained across studies, a quantitative review of nine neuroimaging investigations of word reading was conducted, Across these studies, the results converge to reveal a set of areas active during word reading, including left-lateralized regions in occipital and occipitotemporal cortex, the left frontal operculum, bilateral regions within the cerebellum, primary motor cortex, and the superior and middle temporal cortex, and medial regions in the supplementary motor area and anterior cingulate, Beyond localization, the challenge is to use neuroimaging as a tool for understanding how reading is accomplished, Central to this challenge will be the integration of neuroimaging results with information from other methodologies, To illustrate this point, this review will highlight the importance of spelling-to-sound consistency in the transformation from orthographic (word form) to phonological (word sound) representations, and then explore results from three neuroimaging studies in which the spelling-to-sound consistency of the stimuli was deliberately varied, Emphasis is placed on the pattern of activation observed within the left frontal cortex, because the results provide an example of the issues and benefits involved in relating neuroimaging results to behavioral results in normal and brain damaged subjects, and to theoretical models of reading.
    BibTeX:
    @article{Fiez1998,
      author = {Fiez, JA and Petersen, SE},
      title = {Neuroimaging studies of word reading},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1998},
      volume = {95},
      number = {3},
      pages = {914-921},
      note = {Colloquium on Neuroimaging of Human Brain Function, IRVINE, CALIFORNIA, MAY 29-31, 1997}
    }
    
    FIEZ, J., RAICHLE, M., MIEZIN, F., PETERSEN, S., TALLAL, P. & KATZ, W. PET STUDIES OF AUDITORY AND PHONOLOGICAL PROCESSING - EFFECTS OF STIMULUS CHARACTERISTICS AND TASK DEMANDS {1995} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {7}({3}), pp. {357-375} 
    article  
    Abstract: Positron emission tomography (PET) was used to investigate the functional anatomy of auditory and phonological processing. Stimulus sets were designed to determine areas of the brain significantly activated during speech and nonspeech acoustic processing for stimuli with or without rapidly changing acoustic cues. Performance of auditory target detection tasks using these stimulus sets produced increased activation in superior temporal, frontal opercular, and medial frontal (SMA) cortices, relative to a visual fixation control task. While the medial frontal and superior temporal changes are best explained by motor and sensory components of the task, respectively, the frontal opercular changes were dependent upon the task performed upon the auditory input (mere presentation of the stimuli did not result in significant activation). On the left, the frontal opercular increases were larger when subjects performed an auditory detection task upon stimuli that incorporated rapid temporal changes (words, syllables, and tone sequences) than steady-state vowels. A converging study involving performance of orthographic (ascending letter) and phonological (long vowel sound) word discrimination tasks supports anatomical and behavioral evidence suggesting the left frontal opercular region is important for certain types of auditory/temporal analysis, as well as high-level articulatory coding. In addition to the activation increases associated with performance of auditory target detection tasks, decreases in activation were observed bilaterally along the intraparietal sulcus and superior parietal cortex, in the Rolandic sulcus, and the posterior cingulate; these decreases may reflect an attentional shift away from areas involved in the fixation task during the performance of a difficult auditory task. These results demonstrate that focusing more closely on basic neural processing differences (such as temporal integration rates) may lead to a better understanding of the specific neural processes that underlie complex phonological tasks.
    BibTeX:
    @article{FIEZ1995,
      author = {FIEZ, JA and RAICHLE, ME and MIEZIN, FM and PETERSEN, SE and TALLAL, P and KATZ, WF},
      title = {PET STUDIES OF AUDITORY AND PHONOLOGICAL PROCESSING - EFFECTS OF STIMULUS CHARACTERISTICS AND TASK DEMANDS},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {1995},
      volume = {7},
      number = {3},
      pages = {357-375}
    }
    
    Fink, G., Frackowiak, R., Pietrzyk, U. & Passingham, R. Multiple nonprimary motor areas in the human cortex {1997} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {77}({4}), pp. {2164-2174} 
    article  
    Abstract: We measured the distribution of regional cerebral blood flow with positron emission tomography while three subjects moved their hand, shoulder, or leg. The images were coregistered with each individual's anatomic magnetic resonance scans. The data were analyzed for each individual to avoid intersubject averaging and so to preserve individual gyral anatomy. Instead of inspecting all pixels, we prospectively restricted the data analysis to particular areas of interest. These were defined on basis of the anatomic and physiological literature on nonhuman primates. By examining only a subset of areas, we strengthened the power of the statistical analysis and thereby increased the confidence in reporting single subject data. On the lateral convexity, motor related activity was found for all three subjects in the primary motor cortex, lateral premotor cortex, and an opercular area within the premotor cortex. In addition, there was activation of somatosensory cortex (SI), the supplementary somatosensory area (SII) in the Sylvian fissure, and parietal association areas (Brodmann areas 5 and 40). There was also activation in the insula. We suggest that the activation in the dorsal premotor cortex may correspond with dorsal premotor area (PMd) as described in the macaque brain. We propose three hypotheses as to the probable location of vental premotor area (PMv) in the human brain. On the medial surface, motor-related activity was found for all three subjects in the leg areas of the primary motor cortex and somatosensory cortex and also activity for the hand, shoulder, and leg is the supplementary motor area (SMA) on the dorsal medial convexity and in three areas in the cingulate sulcus. We suggest that the three cingulate areas may correspond with rostral cingulate premotor area, dorsal cingulate motor area (CMAd), and ventral cingulate motor area (CMAv) as identified in the macaque brain. Somatotopic mapping was demonstrated in the primary motor and primary somatosensory cortex. In all three subjects, the arm region lay anterior to the leg region in parietal area 5. Also in all three subjects, the arm region lay anterior to the leg region in the supplementary motor cortex.
    BibTeX:
    @article{Fink1997,
      author = {Fink, GR and Frackowiak, RSJ and Pietrzyk, U and Passingham, RE},
      title = {Multiple nonprimary motor areas in the human cortex},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1997},
      volume = {77},
      number = {4},
      pages = {2164-2174}
    }
    
    Fink, G., Markowitsch, H., Reinkemeier, M., Bruckbauer, T., Kessler, J. & Heiss, W. Cerebral representation of one's own past: Neural networks involved in autobiographical memory {1996} JOURNAL OF NEUROSCIENCE
    Vol. {16}({13}), pp. {4275-4282} 
    article  
    Abstract: We studied the functional anatomy of affect-laden autobiographical memory in normal volunteers. Using (H2O)-O-15 positron emission tomography (PET), we measured changes in relative regional cerebral blood flow (rCBF). Four rCBF measurements were obtained during three conditions: REST, i.e., subjects lay at rest (for control); IMPERSONAL, i.e., subjects listened to sentences containing episodic information taken from an autobiography of a person they did not know, but which had been presented to them before PET scanning (nonautobiographical episodic memory ecphory); and PERSONAL, i.e., subjects listened to sentences containing information taken from their own past (autobiographical episodic memory ecphory). Comparing IMPERSONAL with REST (nonautobiographical episodic memory ecphory) resulted in relative rCBF increases symmetrically in both temporal robes including the temporal poles and medial and superior temporal gyri. The same loci, however, with a stronger lateralization to the right hemisphere were activated in the comparison PERSONAL to REST (autobiographical episodic memory ecphory). In addition, the right temporomesial, right dorsal prefrontal, right posterior cingulate areas, and the left cerebellum were activated. A comparison of PERSONAL and IMPERSONAL (autobiographical vs nonautobiographical episodic memory ecphory) demonstrated a preponderantly right hemispheric activation including primarily right temporomesial and temporolateral cortex, right posterior cingulate areas, right insula, and right prefrontal areas. The right temporomesial activation included hippocampus, parahippocampus, and amygdala. These results suggest that a right hemispheric network of temporal, together with posterior, cingulate, and prefrontal, areas is engaged in the ecphory of affect-laden autobiographical information.
    BibTeX:
    @article{Fink1996,
      author = {Fink, GR and Markowitsch, HJ and Reinkemeier, M and Bruckbauer, T and Kessler, J and Heiss, WD},
      title = {Cerebral representation of one's own past: Neural networks involved in autobiographical memory},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1996},
      volume = {16},
      number = {13},
      pages = {4275-4282}
    }
    
    Fink, G., Sumner, B., Rosie, R., Grace, O. & Quinn, J. Estrogen control of central neurotransmission: Effect on mood, mental state, and memory {1996} CELLULAR AND MOLECULAR NEUROBIOLOGY
    Vol. {16}({3}), pp. {325-344} 
    article  
    Abstract: 1. Estrogen exerts profound effects on mood, mental state and memory by acting on both `'classical'' monoamine and neuropeptide transmitter mechanisms in brain. Here we review an example of each type of action. 2. With respect to the effect of estrogen on central monoamine neurotransmission, low levels of estrogen in women are associated with the premenstrual syndrome, postnatal depression and post-menopausal depression. Sex differences in schizophrenia have also been attributed to estrogen. Previous studies have shown that estrogen stimulates a significant increase in dopamine, (D-2) receptors in the striatum. Here we show for the first time that estrogen also stimulates a significant increase in the density of 5-hydroxytryptamine(2A) (5-HT2A) binding sites in anterior frontal, cingulate and primary olfactory cortex and in the nucleus accumbens, areas of the brain concerned with the control of mood, mental state, cognition, emotion and behavior. These findings explain, for example, the efficacy of estrogen therapy or 5-HT uptake blockers such as fluoxetine in treating the depressive symptoms of the premenstrual syndrome, and suggest that the sex differences in schizophrenia may also be due to an action of estrogen mediated bq way of 5-HT2A receptors. 3. With respect to the effect of estrogen on central neuropeptide transmission, estrogen stimulates the expression of the arginine vasopressin (AVP) gene in the bed nucleus of the stria terminalis (BNST) in rodents. This results in a 100-fold increase in AVP mRNA in the BNST and a massive increase in AVP peptide in the BNST and its projections to the lateral septum and lateral habenula. The BNST-AVP system enhances and/or maintains `'social'' or `'olfactory'' memory, and thus provides a powerful model for correlating transcriptional control of neuropeptide gene expression with behavior. Whether similar mechanisms operate in the human remain to be determined. 4. These two examples of the action of estrogen on central neurotransmission are discussed in terms of their immediate clinical importance for the treatment of depressive symptoms, their use as powerful models for investigations on the steroid control of central neurotransmitter mechanisms, and the role of estrogen as `'Nature's'' psychoprotectant.
    BibTeX:
    @article{Fink1996a,
      author = {Fink, G and Sumner, BEH and Rosie, R and Grace, O and Quinn, JP},
      title = {Estrogen control of central neurotransmission: Effect on mood, mental state, and memory},
      journal = {CELLULAR AND MOLECULAR NEUROBIOLOGY},
      year = {1996},
      volume = {16},
      number = {3},
      pages = {325-344}
    }
    
    FLETCHER, P., FRITH, C., GRASBY, P., SHALLICE, T., FRACKOWIAK, R. & DOLAN, R. BRAIN SYSTEMS FOR ENCODING AND RETRIEVAL OF AUDITORY-VERBAL MEMORY - AN IN-VIVO STUDY IN HUMANS {1995} BRAIN
    Vol. {118}({Part 2}), pp. {401-416} 
    article  
    Abstract: Long-term auditory-verbal memory comprises, at a neuropsychological level, a number of distinct cognitive processes. In the present study we determined the brain systems engaged during encoding (experiment 1) and retrieval (experiment 2) of episodic auditory-verbal material. In the separate experiments, PET measurements of regional cerebral blood flow (rCBF), an index of neural activity, were performed in normal volunteers during either the encoding or the retrieval of paired word associates. In experiment 1, a dual task interference paradigm was used to isolate areas involved in episodic encoding from those which would be concurrently activated by other cognitive processes associated with the presentation of paired associates, notably priming. In experiment 2, we used the cued retrieval of paired associates from episodic or from semantic memory in order to isolate the neural correlates of episodic memories. Encoding of episodic memory was associated with activation of the left prefrontal cortex and the retrosplenial area of the cingulate cortex, while retrieval from episodic memory was associated with activation of the precuneus bilaterally and of the right prefrontal cortex. These results are compatible with the patterns of activation reported in a previous PET memory experiment in which encoding and retrieval were studied concurrently. They also indicate that separate brain systems are engaged during the encoding and retrieval phases of episodic auditory-verbal memory. Retrieval from episodic memory engages a different but overlapping, system to that engaged by retrieval from semantic memory, a finding that fends functional anatomical support to this neuropsychological distinction.
    BibTeX:
    @article{FLETCHER1995a,
      author = {FLETCHER, PC and FRITH, CD and GRASBY, PM and SHALLICE, T and FRACKOWIAK, RSJ and DOLAN, RJ},
      title = {BRAIN SYSTEMS FOR ENCODING AND RETRIEVAL OF AUDITORY-VERBAL MEMORY - AN IN-VIVO STUDY IN HUMANS},
      journal = {BRAIN},
      year = {1995},
      volume = {118},
      number = {Part 2},
      pages = {401-416}
    }
    
    FLETCHER, P., HAPPE, F., FRITH, U., BAKER, S., DOLAN, R., FRACKOWIAK, R. & FRITH, C. OTHER MINDS IN THE BRAIN - A FUNCTIONAL IMAGING STUDY OF THEORY OF MIND IN STORY COMPREHENSION {1995} COGNITION
    Vol. {57}({2}), pp. {109-128} 
    article  
    Abstract: The ability of normal children and adults to attribute independent mental states to self and others in order to explain and predict behaviour (''theory of mind'') has been a focus of much recent research. Autism is a biologically based disorder which appears to be characterised by a specific impairment in this `'mentalising'' process. The present paper reports a functional neuroimaging study with positron emission tomography in which we studied brain activity in normal volunteers while they performed story comprehension tasks necessitating the attribution of mental states. The resultant brain activity was compared with that measured in two control tasks: `'physical'' stories which did not require this mental attribution, and passages of unlinked sentences. Both story conditions, when compared to the unlinked sentences, showed significantly increased regional cerebral blood flow in the following regions: the temporal poles bilaterally, the left superior temporal gyrus and the posterior cingulate cortex. Comparison of the `'theory of mind'' stories with `'physical'' stories revealed a specific pattern of activation associated with mental state attribution: it was only this task which produced activation in the medial frontal gyrus on the left (Brodmann's area 8). This comparison also showed significant activation in the posterior cingulate cortex. These surprisingly clear-cut findings are discussed in relation to previous studies of brain activation during story comprehension. The localisation of brain regions involved in normal attribution of mental states and contextual problem solving is feasible and may have implications for the neural basis of autism.
    BibTeX:
    @article{FLETCHER1995,
      author = {FLETCHER, PC and HAPPE, F and FRITH, U and BAKER, SC and DOLAN, RJ and FRACKOWIAK, RSJ and FRITH, CD},
      title = {OTHER MINDS IN THE BRAIN - A FUNCTIONAL IMAGING STUDY OF THEORY OF MIND IN STORY COMPREHENSION},
      journal = {COGNITION},
      year = {1995},
      volume = {57},
      number = {2},
      pages = {109-128}
    }
    
    Fogassi, L., Gallese, V., Fadiga, L., Luppino, G., Matelli, M. & Rizzolatti, G. Coding of peripersonal space in inferior premotor cortex (area F4) {1996} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {76}({1}), pp. {141-157} 
    article  
    Abstract: 1. We studied the functional properties of neurons in the caudal part of inferior area 6 (area F4) in awake monkeys. In agreement with previous reports, we found that the large majority (87 of neurons responded to sensory stimuli. The responsive neurons fell into three categories: somatosensory neurons (30; visual neurons (14; and bimodal, visual and somatosensory neurons (56. Both somatosensory and bimodal neurons typically responded to light touch of the skin. Their RFs were located on the face, neck, trunk, and arms. Approaching objects were the most effective visual stimuli. Visual RFs were mostly located in the space near the monkey (peripersonal space). Typically they extended in the space adjacent to the tactile RFs. 2. The coordinate system in which visual RFs were coded was studied in 110 neurons. In 94 neurons the RF location was independent of eye position, remaining in the same position in the peripersonal space regardless of eye deviation. The RF location with respect to the monkey was not modified by changing monkey position in the recording room. In 10 neurons the RF's location followed the eye movements, remaining in the same retinal position (retinocentric RFs). For the remaining six neurons the RF organization was not clear. We will refer to F4 neurons with RF independent of eye position as somatocentered neurons. 3. In most somatocentered neurons (43 of 60 neurons) the back ground level of activity and the response to visual stimuli were not modified by changes in eye position, whereas they were modulated in the remaining 17. It is important to note that eye deviations were constantly accompanied by a synergic increase of the activity of the ipsilateral neck muscles. It is not clear, therefore, whether the modulation of neuron discharge depended on eye position or was a consequence of changes in neck muscle activity. 4. The effect of stimulus velocity (20-80 cm/s) on neuron response intensity and RF extent in depth was studied in 34 somato-centered neurons. The results showed that in most neurons the increase of stimulus velocity produced an expansion in depth of the RF. 5. We conclude that space is coded differently in areas that control somatic and eye movements. We suggest that space coding in different cortical areas depends on the computational necessity of the effecters they control.
    BibTeX:
    @article{Fogassi1996,
      author = {Fogassi, L and Gallese, V and Fadiga, L and Luppino, G and Matelli, M and Rizzolatti, G},
      title = {Coding of peripersonal space in inferior premotor cortex (area F4)},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1996},
      volume = {76},
      number = {1},
      pages = {141-157}
    }
    
    Frankland, P., Bontempi, B., Talton, L., Kaczmarek, L. & Silva, A. The involvement of the anterior cingulate cortex in remote contextual fear memory {2004} SCIENCE
    Vol. {304}({5672}), pp. {881-883} 
    article  
    Abstract: Although the molecular, cellular, and systems mechanisms required for initial memory processing have been intensively investigated, those underlying permanent memory storage remain elusive. We present neuroanatomical, pharmacological, and genetic results demonstrating that the anterior cingulate cortex plays a critical role in remote memory for contextual fear conditioning. Imaging of activity-dependent genes shows that the anterior cingulate is activated by remote memory and that this activation is impaired by a null alpha-CaMKII mutation that blocks remote memory. Accordingly, reversible inactivation of this structure in normal mice disrupts remote memory without affecting recent memory.
    BibTeX:
    @article{Frankland2004,
      author = {Frankland, PW and Bontempi, B and Talton, LE and Kaczmarek, L and Silva, AJ},
      title = {The involvement of the anterior cingulate cortex in remote contextual fear memory},
      journal = {SCIENCE},
      year = {2004},
      volume = {304},
      number = {5672},
      pages = {881-883}
    }
    
    FRIEDMAN, W., OLSON, L. & PERSSON, H. CELLS THAT EXPRESS BRAIN-DERIVED NEUROTROPHIC FACTOR MESSENGER-RNA IN THE DEVELOPING POSTNATAL RAT-BRAIN {1991} EUROPEAN JOURNAL OF NEUROSCIENCE
    Vol. {3}({7}), pp. {688-697} 
    article  
    Abstract: Brain-derived neurotrophic factor (BDNF) is a member of a family of related neurotrophic proteins which includes nerve growth factor (NGF) and hippocampus-derived neurotrophic factor/neurotrophin-3 (NT-3). To obtain information regarding possible roles for BDNF during postnatal brain development, we have examined the temporal and spatial expression of this trophic factor using in situ hybridization. In specific neocortical regions BDNF mRNA-expressing cells were seen at 2 weeks of age and thereafter. One particular neuronal cell type strikingly labelled was the inverted pyramidal cell population in the deep layers of parietotemporal cortex. In pyriform and cingulate cortices, BDNF mRNA was detected at postnatal day 1 and 1 week of age, respectively, with increasing levels during ontogeny. Several forebrain regions, including the thalamic anterior paraventricular nucleus, hypothalamic ventromedial nucleus as well as the preoptic area, contained moderate levels of BDNF mRNA throughout development. BDNF mRNA was detected transiently in several brainstem structures, notably in the substantia nigra and interpeduncular nucleus. Expression of this trophic factor in hippocampus was relatively low in the early neonatal brain, but attained high levels in the CA3 and CA4 regions as well as in the dentate gyrus by 2 weeks of age. At this early age, which is still during the period of neurogenesis in the dentate gyrus, labelling was restricted to the outer layer, which contained cells with a more mature appearance. However, by 3 weeks of age labelling was distributed throughout the granule cell layer. Our results show both transient and persistent expression of BDNF mRNA in various regions of the developing rat brain and suggest that there is a caudal to rostral gradient of BDNF expression during postnatal brain development, which may be correlated to neuronal maturation.
    BibTeX:
    @article{FRIEDMAN1991,
      author = {FRIEDMAN, WJ and OLSON, L and PERSSON, H},
      title = {CELLS THAT EXPRESS BRAIN-DERIVED NEUROTROPHIC FACTOR MESSENGER-RNA IN THE DEVELOPING POSTNATAL RAT-BRAIN},
      journal = {EUROPEAN JOURNAL OF NEUROSCIENCE},
      year = {1991},
      volume = {3},
      number = {7},
      pages = {688-697}
    }
    
    FRISTON, K., FRITH, C., LIDDLE, P. & FRACKOWIAK, R. FUNCTIONAL CONNECTIVITY - THE PRINCIPAL-COMPONENT ANALYSIS OF LARGE (PET) DATA SETS {1993} JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
    Vol. {13}({1}), pp. {5-14} 
    article  
    Abstract: The distributed brain systems associated with performance of a verbal fluency task were identified in a nondirected correlational analysis of neurophysiological data obtained with positron tomography. This analysis used a recursive principal-component analysis developed specifically for large data sets. This analysis is interpreted in terms of functional connectivity, defined as the temporal correlation of a neurophysiological index measured in different brain areas. The results suggest that the variance in neurophysiological measurements, introduced experimentally, was accounted for by two independent principal components. The first, and considerably larger, highlighted an intentional brain system seen in previous studies of verbal fluency. The second identified a distributed brain system including the anterior cingulate and Wernicke's area that reflected monotonic time effects. We propose that this system has an attentional bias.
    BibTeX:
    @article{FRISTON1993,
      author = {FRISTON, KJ and FRITH, CD and LIDDLE, PF and FRACKOWIAK, RSJ},
      title = {FUNCTIONAL CONNECTIVITY - THE PRINCIPAL-COMPONENT ANALYSIS OF LARGE (PET) DATA SETS},
      journal = {JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM},
      year = {1993},
      volume = {13},
      number = {1},
      pages = {5-14}
    }
    
    Frith, C. & Frith, U. Cognitive psychology - Interacting minds - A biological basis {1999} SCIENCE
    Vol. {286}({5445}), pp. {1692-1695} 
    article  
    Abstract: The ability to ``mentalize,'' that is to understand and manipulate other people's behavior in terms of their mental states, is a major ingredient in successful social interactions. A rudimentary form of this ability may be seen in great apes, but in humans it is developed to a high Level. Specific impairments of mentalizing in both developmental and acquired disorders suggest that this ability depends on a dedicated and circumscribed brain system. Functional imaging studies implicate medial prefrontal cortex and posterior superior temporal sulcus (STS) as components of this system. Clues to the specific function of these components in mentalizing come from single cell recording studies: STS is concerned with representing the actions of others through the detection of biological motion; medial prefrontal regions are concerned with explicit representation of states of the self. These observations suggest that the ability to mentalize has evolved from a system for representing actions.
    BibTeX:
    @article{Frith1999,
      author = {Frith, CD and Frith, U},
      title = {Cognitive psychology - Interacting minds - A biological basis},
      journal = {SCIENCE},
      year = {1999},
      volume = {286},
      number = {5445},
      pages = {1692-1695}
    }
    
    Frith, U. & Frith, C. Development and neurophysiology of mentalizing {2003} PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
    Vol. {358}({1431}), pp. {459-473} 
    article DOI  
    Abstract: The mentalizing (theory of mind) system of the brain is probably in operation from ca. 18 months of age, allowing implicit attribution of intentions and other mental states. Between the ages of 4 and 6 years explicit mentalizing becomes possible, and from this age children are able to explain the misleading reasons that have given rise to a false belief. Neuroimaging studies of mentalizing have so far only been carried out in adults. They reveal a system with three components consistently activated during both implicit and explicit mentalizing tasks: medial prefrontal cortex (MPFC), temporal poles and posterior superior temporal sulcus (STS). The functions of these components can be elucidated, to some extent, from their role in other tasks used in neuroimaging studies. Thus, the MPFC region is probably the basis of the decoupling mechanism that distinguishes mental state representations from physical state representations; the STS region is probably the basis of the detection of agency, and the temporal poles might be involved in access to social knowledge in the form of scripts. The activation of these components in concert appears to be critical to mentalizing.
    BibTeX:
    @article{Frith2003,
      author = {Frith, U and Frith, CD},
      title = {Development and neurophysiology of mentalizing},
      journal = {PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES},
      year = {2003},
      volume = {358},
      number = {1431},
      pages = {459-473},
      doi = {{10.1098/rstb.2002.1218}}
    }
    
    Fu, C., Williams, S., Cleare, A., Brammer, M., Walsh, N., Kim, J., Andrew, C., Pich, E., Williams, P., Reed, L., Mitterschiffthaler, M., Suckling, J. & Bullmore, E. Attenuation of the neural response to sad faces in major depression by antidepressant treatment - A prospective, event-related functional magnetic resonance imaging study {2004} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {61}({9}), pp. {877-889} 
    article  
    Abstract: Background: Depression is associated with interpersonal difficulties related to abnormalities in affective facial processing. Objectives: To map brain systems activated by sad facial affect processing in patients with depression and to identify brain functional correlates of antidepressant treatment and symptomatic response. Design: Two groups underwent scanning twice using functional magnetic resonance imaging (fMRI) during an 8-week period. The event-related fMRI paradigm entailed incidental affect recognition of facial stimuli morphed to express discriminable intensities of sadness. Setting: Participants were recruited by advertisement from the local population; depressed subjects were treated as outpatients. Patients and Other Participants: We matched 19 medication-free, acutely symptomatic patients satisfying DSM-IV criteria for unipolar major depressive disorder by age, sex, and IQ with 19 healthy volunteers. intervention: After the baseline assessment, patients received fluoxetine hydrochloride, 20 mg/d, for 8 weeks. Main Outcome Measures: Average activation (capacity) and differential response to variable affective intensity (dynamic range) were estimated in each fMRI time series. We used analysis of variance to identify brain regions that demonstrated a main effect of group (depressed vs healthy subjects) and a group X time interaction (attributable to antidepressant treatment). Change in brain activation associated with reduction of depressive symptoms in the patient group was identified by means of regression analysis. Permutation tests were used for inference. Results: Over time, depressed subjects showed reduced capacity for activation in the left amygdala, ventral striatum, and frontoparietal cortex and a negatively correlated increase of dynamic range in the prefrontal cortex. Symptomatic improvement was associated with reduction of dynamic range in the pregenual cingulate cortex, ventral striatum, and cerebellum. Conclusions: Antidepressant treatment reduces left limbic, subcortical, and neocortical capacity for activation in depressed subjects and increases the dynamic range of the left prefrontal cortex. Changes in anterior cingulate function associated with symptomatic improvement indicate that fMRI may be a useful surrogate marker of antidepressant treatment response.
    BibTeX:
    @article{Fu2004,
      author = {Fu, CHY and Williams, SCR and Cleare, AJ and Brammer, MJ and Walsh, ND and Kim, J and Andrew, CM and Pich, EM and Williams, PM and Reed, LJ and Mitterschiffthaler, MT and Suckling, J and Bullmore, ET},
      title = {Attenuation of the neural response to sad faces in major depression by antidepressant treatment - A prospective, event-related functional magnetic resonance imaging study},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {2004},
      volume = {61},
      number = {9},
      pages = {877-889}
    }
    
    Gallagher, H. & Frith, C. Functional imaging of `theory of mind' {2003} TRENDS IN COGNITIVE SCIENCES
    Vol. {7}({2}), pp. {77-83} 
    article  
    Abstract: Our ability to explain and predict other people's behaviour by attributing to them independent mental states, such as beliefs and desires, is known as having a `theory of mind'. Interest in this very human ability has engendered a growing body of evidence concerning its evolution and development and the biological basis of the mechanisms underpinning it. Functional imaging has played a key role in seeking to isolate brain regions specific to this ability. Three areas are consistently activated in association with theory of mind. These are the anterior paracingulate cortex, the superior temporal sulci and the temporal poles bilaterally. This review discusses the functional significance of each of these areas within a social cognitive network.
    BibTeX:
    @article{Gallagher2003,
      author = {Gallagher, HL and Frith, CD},
      title = {Functional imaging of `theory of mind'},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      year = {2003},
      volume = {7},
      number = {2},
      pages = {77-83}
    }
    
    Gallagher, H., Jack, A., Roepstorff, A. & Frith, C. Imaging the intentional stance in a competitive game {2002} NEUROIMAGE
    Vol. {16}({3, Part 1}), pp. {814-821} 
    article DOI  
    Abstract: The ``intentional stance'' is the disposition to treat an entity as a rational agent, possessing particular beliefs, desires, and intentions, in order to interpret and predict it's behavior. The intentional stance is a component of a broader social cognitive function, mentalizing. Here we report a study that investigates the neural substrates of ``on-line'' mentalizing, using PET, by asking volunteers to second-guess an opponent. In order to identify brain activity specifically associated with adoption of an intentional stance, we used a paradigm that allowed tight control of other cognitive demands. Volunteers played a computerised version of the children's game ``stone, paper, scissors.'' In the mentalizing condition volunteers believed they were playing against the experimenter. In the comparison condition, volunteers believed they were playing against a computer. In fact, during the actual scanning, the ``opponent'' produced a random sequence in both conditions. The only difference was the attitude, or stance, adopted by the volunteer. Only one region was more active when volunteers adopted the intentional stance. This was in anterior paracingulate cortex (bilaterally). This region has been activated in a number of previous studies involving mentalizing. However, this is the first study suggesting a specific link between activity in this brain region and the adoption of an intentional stance. (C) 2002 Elsevier Science (USA).
    BibTeX:
    @article{Gallagher2002,
      author = {Gallagher, HL and Jack, AI and Roepstorff, A and Frith, CD},
      title = {Imaging the intentional stance in a competitive game},
      journal = {NEUROIMAGE},
      year = {2002},
      volume = {16},
      number = {3, Part 1},
      pages = {814-821},
      doi = {{10.1006/nimg.2002.1117}}
    }
    
    Garavan, H., Pankiewicz, J., Bloom, A., Cho, J., Sperry, L., Ross, T., Salmeron, B., Risinger, R., Kelley, D. & Stein, E. Cue-induced cocaine craving: Neuroanatomical specificity for drug users and drug stimuli {2000} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {157}({11}), pp. {1789-1798} 
    article  
    Abstract: Objective: Cocaine-related cues have been hypothesized to perpetuate drug abuse by inducing a craving response that prompts drug-seeking behavior. However, the mechanisms, underlying neuroanatomy, and specificity of this neuroanatomy are not yet fully understood. Method: To address these issues, experienced cocaine users (N=17) and comparison subjects (N=14) underwent functional magnetic resonance imaging while viewing three separate films that portrayed 1) individuals smoking crack cocaine, 2) outdoor nature scenes, and 3) explicit sexual content. Candidate craving sites were identified as those that showed significant activation in the cocaine users when viewing the cocaine film. These sites were then required to show significantly greater activation when contrasted with comparison subjects viewing the cocaine film (population specificity) and cocaine users viewing the nature film (content specificity). Results: Brain regions that satisfied these criteria were largely left lateralized and included the frontal lobe (medial and middle frontal gyri, bilateral inferior frontal gyrus), parietal lobe (bilateral inferior parietal lobule), insula, and limbic lobe (anterior and posterior cingulate gyrus). Of the 13 regions identified as putative craving sites,just three(anterior cingulate, right inferior parietal lobule, and the caudate/lateral dorsal nucleus) showed significantly greater activation during the cocaine film than during the sex film in the cocaine users, which suggests that cocaine cues activated similar neuroanatomical substrates as naturally evocative stimuli in the cocaine users. Finally, contrary to the effects of the cocaine film, cocaine users showed a smaller response than the comparison subjects to the sex film. Conclusions: These data suggest that cocaine craving is not associated with a dedicated and unique neuroanatomical circuitry; instead, unique to the cocaine user is the ability of learned, drug-related cues to produce brain activation comparable to that seen with nondrug evocative stimuli in healthy comparison subjects.
    BibTeX:
    @article{Garavan2000,
      author = {Garavan, H and Pankiewicz, J and Bloom, A and Cho, JK and Sperry, L and Ross, TJ and Salmeron, BJ and Risinger, R and Kelley, D and Stein, EA},
      title = {Cue-induced cocaine craving: Neuroanatomical specificity for drug users and drug stimuli},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {2000},
      volume = {157},
      number = {11},
      pages = {1789-1798}
    }
    
    Garavan, H., Ross, T., Murphy, K., Roche, R. & Stein, E. Dissociable executive functions in the dynamic control of behavior: Inhibition, error detection, and correction {2002} NEUROIMAGE
    Vol. {17}({4}), pp. {1820-1829} 
    article DOI  
    Abstract: The present study employed event-related fMRI and EEG to investigate the biological basis of the cognitive control of behavior. Using a GO/NOGO task optimized to produce response inhibitions, frequent commission errors, and the opportunity for subsequent behavioral correction, we identified distinct cortical areas associated with each of these specific executive processes. Two cortical systems, one involving right prefrontal and parietal areas and the second regions of the cingulate, underlay inhibitory control. The involvement of these two systems was predicated upon the difficulty or urgency of the inhibition and each was employed to different extents by high- and low-absent-minded subjects. Errors were associated with medial activation incorporating the anterior cingulate and pre-SMA while behavioral alteration subsequent to errors was associated with both the anterior cingulate and the left prefrontal cortex. Furthermore, the EEG data demonstrated that successful response inhibition depended upon the timely activation of cortical areas as predicted by race models of response selection. The results highlight how higher cognitive functions responsible for behavioral control can result from the dynamic interplay of distinct cortical systems. (C) 2002 Elsevier Science (USA).
    BibTeX:
    @article{Garavan2002,
      author = {Garavan, H and Ross, TJ and Murphy, K and Roche, RAP and Stein, EA},
      title = {Dissociable executive functions in the dynamic control of behavior: Inhibition, error detection, and correction},
      journal = {NEUROIMAGE},
      year = {2002},
      volume = {17},
      number = {4},
      pages = {1820-1829},
      doi = {{10.1006/nimg.2002.1326}}
    }
    
    Gehring, W., Himle, J. & Nisenson, L. Action-monitoring dysfunction in obsessive-compulsive disorder {2000} PSYCHOLOGICAL SCIENCE
    Vol. {11}({1}), pp. {1-6} 
    article  
    Abstract: Evidence suggests that a hyperactive frontal-striatal-thalamix-frontal circuit is associated with the symptoms of obsessive-compulsive disorder (OCD), but there is little agreement about the function of the exaggerated activity. We report electrophysiological evidence suggesting that part of this system inonitors events and generates error signals when the events conflict with an individual's internal standards or goals. Nine individuals with OCD and 9 age-sex-, and education -matched participants performed a speeded reaction time task. The error-related negativity, an event-related brain potential component that reflects action-monitoring processes, was enhanced in the individuals with OCD. The magnitude of this enhancement correlated with symptom severity. Dipole modelling suggested that the locus of the enhancement to medial frontal regions, possibly the anterior cingulate cortex.
    BibTeX:
    @article{Gehring2000a,
      author = {Gehring, WJ and Himle, J and Nisenson, LG},
      title = {Action-monitoring dysfunction in obsessive-compulsive disorder},
      journal = {PSYCHOLOGICAL SCIENCE},
      year = {2000},
      volume = {11},
      number = {1},
      pages = {1-6}
    }
    
    Gehring, W. & Knight, R. Prefrontal-cingulate interactions in action monitoring {2000} NATURE NEUROSCIENCE
    Vol. {3}({5}), pp. {516-520} 
    article  
    Abstract: We found that medial frontal cortex activity associated with action monitoring (detecting errors and behavioral conflict) depended on activity in the lateral prefrontal cortex. We recorded the error-related negativity (ERN), an event-related brain potential proposed to reflect anterior cingulate action monitoring, from individuals with lateral prefrontal damage or age-matched or young control participants. In controls, error trials generated greater ERN activity than correct trials. In individuals with lateral prefrontal damage, however, correct-trial ERN activity was equal to error-trial ERN activity. Lateral prefrontal damage also affected corrective behavior. Thus the lateral prefrontal cortex seemed to interact with the anterior cingulate cortex in monitoring behavior and in guiding compensatory systems.
    BibTeX:
    @article{Gehring2000,
      author = {Gehring, WJ and Knight, RT},
      title = {Prefrontal-cingulate interactions in action monitoring},
      journal = {NATURE NEUROSCIENCE},
      year = {2000},
      volume = {3},
      number = {5},
      pages = {516-520}
    }
    
    Gehring, W. & Willoughby, A. The medial frontal cortex and the rapid processing of monetary gains and losses {2002} SCIENCE
    Vol. {295}({5563}), pp. {2279-2282} 
    article  
    Abstract: We report the observation of neural processing that occurs within 265 milliseconds after outcome stimuli that inform human participants about gains and losses in a gambling task. A negative-polarity event-related brain potential, probably generated by a medial-frontal region in or near the anterior cingulate cortex, was greater in amplitude when a participant's choice between two alternatives resulted in a toss than when it resulted in a gain. The sensitivity to losses was not simply a reflection of detecting an error; gains did not elicit the medial-frontal activity when the alternative choice would have yielded a greater gain, and losses elicited the activity even when the alternative choice would have yielded a greater loss. Choices made after losses were riskier and were associated with greater toss-related activity than choices made after gains. It follows that medial-frontal computations may contribute to mental states that participate in higher level decisions, including economic choices.
    BibTeX:
    @article{Gehring2002,
      author = {Gehring, WJ and Willoughby, AR},
      title = {The medial frontal cortex and the rapid processing of monetary gains and losses},
      journal = {SCIENCE},
      year = {2002},
      volume = {295},
      number = {5563},
      pages = {2279-2282}
    }
    
    GEORGE, M., KETTER, T., PAREKH, P., HORWITZ, B., HERSCOVITCH, P. & POST, R. BRAIN ACTIVITY DURING TRANSIENT SADNESS AND HAPPINESS IN HEALTHY WOMEN {1995} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {152}({3}), pp. {341-351} 
    article  
    Abstract: Objective: The specific rain regions involved in the normal emotional states of transient sadness or happiness are poorly understood. The authors therefore sought to determine if (H2O)-O-15 positron emission tomography (PET) might demonstrate changes in regional cerebral blood flow (rCBF) associated with transient sadness or happiness in healthy adult women. Method: Eleven healthy and never mentally ill adult women were scanned, by using PET and (H2O)-O-15, during happy, sad, and neutral states induced by recalling affect-appropriate life events and looking at happy, sad, or neutral human faces. Results: Compared to the neutral condition, transient sadness significantly activated bilateral limbic and paralimbic structures (cingulate, medial prefrontal, and mesial temporal cortex), as well as brainstem, thalamus, and caudate/putamen. In contrast, transient happiness had no areas of significantly increased activity but was associated with significant and widespread reductions in cortical rCBF, especially in the right perfrontal and bilateral temporal-parietal regions. Conclusions: Transient sadness and happiness in healthy volunteer women are accompanied by significant changes in regional brain activity in the limbic system, as well as other brain regions. Transient sadness and happiness affect different brain regions in divergent directions and are not merely opposite activity in identical brain regions. These findings have implications for understanding the neural substrates of both normal and pathological emotion.
    BibTeX:
    @article{GEORGE1995,
      author = {GEORGE, MS and KETTER, TA and PAREKH, PI and HORWITZ, B and HERSCOVITCH, P and POST, RM},
      title = {BRAIN ACTIVITY DURING TRANSIENT SADNESS AND HAPPINESS IN HEALTHY WOMEN},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {1995},
      volume = {152},
      number = {3},
      pages = {341-351},
      note = {Annual Meeting of the Society-for-Biological-Psychiatry, PHILADELPHIA, PA, MAY 18-21, 1994}
    }
    
    Gevins, A., Smith, M., McEvoy, L. & Yu, D. High-resolution EEG mapping of cortical activation related to working memory: Effects of task difficulty, type of processing, and practice {1997} CEREBRAL CORTEX
    Vol. {7}({4}), pp. {374-385} 
    article  
    Abstract: Changes in cortical activity during working memory tasks were examined with electroencephalograms (EEGs) sampled from 115 channels and spatially sharpened with magnetic resonance imaging (MRI)-based finite element deblurring. Eight subjects performed tasks requiring comparison of each stimulus to a preceding one on verbal or spatial attributes. A frontal midline theta rhythm increased in magnitude with increased memory load. Dipole models localized this signal to the region of the anterior cingulate cortex. A slow (low-frequency), parietocentral, alpha signal decreased with increased working memory load. These signals were insensitive to the type of stimulus attribute being processed. A faster (higher-frequency), occipitoparietal, alpha signal was relatively attenuated in the spatial version of the task, especially over the posterior right hemisphere. Theta and alpha signals increased, and overt performance improved, after practice on the tasks. increases in theta with both increased task difficulty and with practice suggests that focusing attention required more effort after an extended test session. Decreased alpha in the difficult tasks indicates that this signal is inversely related to the amount of cortical resources allocated to task performance. Practice-related increases ire alpha suggest that fewer cortical resources are required after skill development. These results serve: (i) to dissociate the effects of task difficulty and practice; (ii) to differentiate the involvement of posterior cortex in spatial versus verbal tasks; (iii) to localize frontal midline theta to the anteromedial cortex; and (iv) to demonstrate the feasibility of using anatomical MRIs to remove the blurring effect of the skull and scalp from the ongoing EEG. The results are discussed with respect to those obtained in a prior study of transient evoked potentials during worsting memory.
    BibTeX:
    @article{Gevins1997,
      author = {Gevins, A and Smith, ME and McEvoy, L and Yu, D},
      title = {High-resolution EEG mapping of cortical activation related to working memory: Effects of task difficulty, type of processing, and practice},
      journal = {CEREBRAL CORTEX},
      year = {1997},
      volume = {7},
      number = {4},
      pages = {374-385}
    }
    
    Gillardon, F., Lenz, C., Waschke, K., Krajewski, S., Reed, J., Zimmermann, M. & Kuschinsky, W. Altered expression of bcl-2, bcl-X, bax, and c-fos colocalizes with DNA fragmentation and ischemic cell damage following middle cerebral artery occlusion in rats {1996} MOLECULAR BRAIN RESEARCH
    Vol. {40}({2}), pp. {254-260} 
    article  
    Abstract: Permanent occlusion of the middle cerebral artery in rats was used to assess the effects of focal ischemia on the expression of members of the bcl-2 family which have been implicated in the regulation of programed cell death. intraluminal occlusion of one middle cerebral artery for 6 h resulted in histologically detectable brain damage within the ipsilateral caudate putamen, basolateral cortex and parts of the thalamus. Zn the infarcted basolateral cortex and thalamus fragmentation of DNA was detected in many nuclei using in-situ end-labeling of DNA breaks by terminal transferase, whereas only scattered labeled nuclei were visible in the infarcted caudate putamen. Immunohistochemical analysis revealed activation of c-Fos in the infarcted cortex and thalamus and in the non-infarcted cingulate cortex as has been shown by others. A decrease in immunoreactivity for Bcl-2, and Bcl-X and an increase in immunostaining for Bax was observed exclusively in neurons within the ischemic cortex and thalamus. Within the infarcted caudate putamen, however, protein levels of all bcl-2 family members declined and c-Fos remained absent. By reverse transcription and polymerase chain reaction it was demonstrated that levels of bcl-2 mRNA markedly decreased in the ipsilateral hemisphere, whereas the amount of bax mRNA was elevated. These findings suggest that a shift in the ratio of cell death repressor Bcl-2 to cell death effector Bax and a concomitant activation of c-Fos may contribute to neuronal apoptosis in the infarcted thalamus and cortex.
    BibTeX:
    @article{Gillardon1996,
      author = {Gillardon, F and Lenz, C and Waschke, KF and Krajewski, S and Reed, JC and Zimmermann, M and Kuschinsky, W},
      title = {Altered expression of bcl-2, bcl-X, bax, and c-fos colocalizes with DNA fragmentation and ischemic cell damage following middle cerebral artery occlusion in rats},
      journal = {MOLECULAR BRAIN RESEARCH},
      year = {1996},
      volume = {40},
      number = {2},
      pages = {254-260}
    }
    
    Gitelman, D., Nobre, A., Parrish, T., LaBar, K., Kim, Y., Meyer, J. & Mesulam, M. A large-scale distributed network for covert spatial attention - Further anatomical delineation based on stringent behavioural and cognitive controls {1999} BRAIN
    Vol. {122}({Part 6}), pp. {1093-1106} 
    article  
    Abstract: Functional MRI was used to examine cerebral activations in 12 subjects while they performed a spatial attention task. This study applied more stringent behavioural and cognitive controls than previously used for similar experiments: (i) subjects were included only if they showed evidence of attentional shifts while performing the task in the magnet; (ii) the experimental task and baseline condition were designed to eliminate the contributions of motor output, visual fixation, inhibition of eye movements, working memory and the conditional (no-go) component of responding, Activations were seen in all three hypothesized cortical epicentres forming a network for spatial attention: the lateral premotor cortex (frontal eye fields), the posterior parietal cortex and the cingulate cortex, Subcortical activations were seen in the basal ganglia and the thalamus, Although the task required attention to be equally shifted to the left and to the right, eight of 10 subjects showed a greater area of activation in the right parietal cortex, consistent with the specialization of the right hemisphere for spatial attention, Other areas of significant activation included the posterior temporo-occipital cortex and the anterior insula, The temporo-occipital activation was within a region broadly defined as MT+ (where MT is the middle temporal area) which contains the human equivalent of area MT in the macaque monkey, This temporo-occipital area appears to constitute a major component of the functional network activated by this spatial attention task, Its activation may reflect the `inferred' shift of the attentional focus across the visual scene.
    BibTeX:
    @article{Gitelman1999,
      author = {Gitelman, DR and Nobre, AC and Parrish, TB and LaBar, KS and Kim, YH and Meyer, JR and Mesulam, MM},
      title = {A large-scale distributed network for covert spatial attention - Further anatomical delineation based on stringent behavioural and cognitive controls},
      journal = {BRAIN},
      year = {1999},
      volume = {122},
      number = {Part 6},
      pages = {1093-1106}
    }
    
    Gold, J.I. & Shadlen, M.N. The neural basis of decision making {2007} ANNUAL REVIEW OF NEUROSCIENCE
    Vol. {30}, pp. {535-574} 
    article DOI  
    Abstract: The study of decision making spans such varied fields as neuroscience, psychology, economics, statistics, political science, and computer science. Despite this diversity of applications, most decisions share common elements including deliberation and commitment. Here we evaluate recent progress in understanding how these basic elements of decision formation are implemented in the brain. We focus on simple decisions that can be studied in the laboratory but emphasize general principles likely to extend to other settings.
    BibTeX:
    @article{Gold2007,
      author = {Gold, Joshua I. and Shadlen, Michael N.},
      title = {The neural basis of decision making},
      journal = {ANNUAL REVIEW OF NEUROSCIENCE},
      year = {2007},
      volume = {30},
      pages = {535-574},
      doi = {{10.1146/annurev.neuro.29.051605.113038}}
    }
    
    Goldapple, K., Segal, Z., Garson, C., Lau, M., Bieling, P., Kennedy, S. & Mayberg, H. Modulation of cortical-limbic pathways in major depression - Treatment-specific effects of cognitive behavior therapy {2004} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {61}({1}), pp. {34-41} 
    article  
    Abstract: Background: Functional imaging studies of major depressive disorder demonstrate response-specific regional changes following various modes of antidepressant treatment. Objective: To examine changes associated with cognitive behavior therapy (CBT). Methods: Brain, changes underlying response to CBT were examined using resting-state fluorine-18-labeled deoxyglucose positron emission tomography. Seventeen unmedicated, unipolar depressed outpatients (mean +/- SD age, 41 9 years; mean SD initial 17-item. Hamilton Depression Rating Scale score, 20 3) were scanned before and after a 15- to 20-session course of outpatient CBT. Whole-brain, voxel-based methods were used to assess response-specific CBT effects. A post hoc comparison to an independent group of 13 paroxetine-treated responders was also performed to interpret the specificity of identified CBT effects. Results: A full course of CBT resulted in significant clinical improvement in the 14 study completers (mean SD posttreatment Hamilton Depression Rating Scale score of 6.7 +/- 4). Treatment response was associated with significant metabolic changes: increases in hippocampus and dorsal cingulate (Brodmann area [BA] 24) and decreases in dorsal (BA 9/46), ventral (BA 47/11), and medial (BA 9/10/11) frontal cortex. This pattern is distinct from that seen with paroxetine-facilitated clinical recovery where prefrontal increases and hippocampal and subgenual cingulate decreases were seen. Conclusions: Like other antidepressant treatments, CBT seems to affect clinical recovery by modulating the functioning of specific sites in limbic and cortical regions. Unique directional changes in frontal cortex, cingulate, and hippocampus with CBT relative to paroxetine may reflect modality-specific effects with implications for understanding mechanisms underlying different treatment strategies.
    BibTeX:
    @article{Goldapple2004,
      author = {Goldapple, K and Segal, Z and Garson, C and Lau, M and Bieling, P and Kennedy, S and Mayberg, H},
      title = {Modulation of cortical-limbic pathways in major depression - Treatment-specific effects of cognitive behavior therapy},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {2004},
      volume = {61},
      number = {1},
      pages = {34-41},
      note = {57th Annual Meeting of the Society-of-Biological-Psychiatry, PHILADELPHIA, PENNSYLVANIA, MAY 16-18, 2002}
    }
    
    Goldman, R., Stern, J., Engel, J. & Cohen, M. Simultaneous EEG and fMRI of the alpha rhythm {2002} NEUROREPORT
    Vol. {13}({18}), pp. {2487-2492} 
    article DOI  
    Abstract: The alpha rhythm in the EEG is 8-12 Hz activity present when a subject is awake with eyes closed. In this study, we used simultaneous EEG and fMRI to make maps of regions whose MRI signal changed reliably with modulation in posterior alpha activity. We scanned II subjects as they rested with eyes closed. We found that increased alpha power was correlated with decreased MRI signal in multiple regions of occipital, superior temporal, inferior frontal, and cingulate cortex, and with increased signal in the thalamus and insula. These results are consistent with animal experiments and point to the alpha rhythm as an index of cortical inactivity that may be generated in part by the thalamus. These results also may have important implications for interpretation of resting baseline in fMRI studies.
    BibTeX:
    @article{Goldman2002,
      author = {Goldman, RI and Stern, JM and Engel, J and Cohen, MS},
      title = {Simultaneous EEG and fMRI of the alpha rhythm},
      journal = {NEUROREPORT},
      year = {2002},
      volume = {13},
      number = {18},
      pages = {2487-2492},
      doi = {{10.1097/01.wnr.0000047685.08940.d0}}
    }
    
    Goldstein, J., Goodman, J., Seidman, L., Kennedy, D., Makris, N., Lee, H., Tourville, J., Caviness, V., Faraone, S. & Tsuang, M. Cortical abnormalities in schizophrenia identified by structural magnetic resonance imaging {1999} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {56}({6}), pp. {537-547} 
    article  
    Abstract: Background: Relatively few magnetic resonance imaging studies of schizophrenia have investigated the entire cerebral cortex. Most focus on only a few areas within a lobe or an entire lobe. To assess expected regional alterations in cortical volumes, we used a new method to segment the entire neocortex into 48 topographically defined brain regions. We hypothesized, based on previous empirical and theoretical work, that dorsolateral prefrontal and paralimbic cortices would be significantly volumetrically reduced in patients with schizophrenia compared with normal controls. Methods: Twenty-nine patients with DSM-III-R schizophrenia were systematically sampled from 3 public outpatient service networks in the Boston, Mass, area. Healthy subjects, recruited from catchment areas from which the patients were drawn, were screened for psychopathologic disorders and proportionately matched to patients by age, sex, ethnicity, parental socioeconomic status, reading ability, and handedness. Analyses of covariance of the volumes of brain regions, adjusted for age- and sex-corrected head size, were used to compare patients and controls. Results: The greatest volumetric reductions and largest effect sizes were in the middle frontal gyrus and paralimbic brain regions, such as the frontomedial and frontoorbital cortices, anterior cingulate and paracingulate gyri, and the insula. In addition, the supramarginal gyrus, which is densely connected to prefrontal and cingulate cortices, was also significantly reduced in patients. Patients also had subtle volumetric increases in other cortical areas with strong reciprocal connections to the paralimbic areas that were volumetrically reduced. Conclusion: Findings using our methods have implications for understanding brain abnormalities in schizophrenia and suggest the importance of the paralimbic areas and their connections with prefrontal brain regions.
    BibTeX:
    @article{Goldstein1999,
      author = {Goldstein, JM and Goodman, JM and Seidman, LJ and Kennedy, DN and Makris, N and Lee, H and Tourville, J and Caviness, VS and Faraone, SV and Tsuang, MT},
      title = {Cortical abnormalities in schizophrenia identified by structural magnetic resonance imaging},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1999},
      volume = {56},
      number = {6},
      pages = {537-547}
    }
    
    Goldstein, R. & Volkow, N. Drug addiction and its underlying neurobiological basis: Neuroimaging evidence for the involvement of the frontal cortex {2002} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {159}({10}), pp. {1642-1652} 
    article  
    Abstract: Objective: Studies of the neurobiological processes underlying drug addiction primarily have focused on limbic subcortical structures. Here the authors evaluated the role of frontal cortical structures in drug addiction. Method: An integrated model of drug addiction that encompasses intoxication, bingeing, withdrawal, and craving is proposed. This model and findings from neuroirnaging studies on the behavioral, cognitive, and emotional processes that are at the core of drug addiction were used to analyze the involvement of frontal structures in drug addiction. Results: The orbitofrontal cortex and the anterior cingulate gyrus, which are regions neuroanatomically connected with limbic structures, are the frontal cortical areas most frequently implicated in drug addiction. They are activated in addicted subjects during intoxication, craving, and bingeing, and they are deactivated during withdrawal. These regions are also involved in higher-order cognitive and motivational functions, such as the ability to track, update, and modulate the salience of a reinforcer as a function of context and expectation and the ability to control and inhibit prepotent responses. Conclusions: These results imply that addiction connotes cortically regulated cognitive and emotional processes, which result in the overvaluing of drug reinforcers, the undervaluing of alternative reinforcers, and deficits in inhibitory control for drug responses. These changes in addiction, which the authors call I-RISA (impaired response inhibition and salience attribution), expand the traditional concepts of drug dependence that emphasize limbic-regulated responses to pleasure and reward.
    BibTeX:
    @article{Goldstein2002,
      author = {Goldstein, RZ and Volkow, ND},
      title = {Drug addiction and its underlying neurobiological basis: Neuroimaging evidence for the involvement of the frontal cortex},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {2002},
      volume = {159},
      number = {10},
      pages = {1642-1652}
    }
    
    GOMEZPINILLA, F., LEE, J. & COTMAN, C. BASIC FGF IN ADULT-RAT BRAIN - CELLULAR-DISTRIBUTION AND RESPONSE TO ENTORHINAL LESION AND FIMBRIA FORNIX TRANSECTION {1992} JOURNAL OF NEUROSCIENCE
    Vol. {12}({1}), pp. {345-355} 
    article  
    Abstract: Basic fibroblast growth factor (bFGF) is a potent trophic factor for neurons and astrocytes and recently has been implicated in the pathology of Alzheimer's disease. In order to better understand the role of bFGF in normal brain function and during pathology, we have analyzed its anatomical distribution and its response to injury in the CNS. Double-staining immunohistochemistry showed that bFGF immunoreactivity was localized in astrocytes, in select neuronal populations, and occasionally in microglial cells throughout the normal rat brain. Neuronal populations that showed bFGF immunoreactivity included septohippocampal nucleus, cingulate cortex, subfield CA2 of the hippocampus, cerebellar Purkinje cells, cerebellar deep nuclei, facial nerve nucleus, and the motor and spinal subdivisions of the trigeminal nucleus and facial nerve nucleus. The pattern of bFGF immunoreactivity in the hippocampus was examined following entorhinal cortex lesion or fimbria-fornix transection. After entorhinal cortex lesion, bFGF immunoreactivity increased in the outer molecular layer of the dentate gyrus ipsilateral to the lesion. The lesion effect on bFGF immunoreactivity was expressed as an increase in the number of bFGF astrocytes, as an increase in the intensity of bFGF immunoreactivity within astrocytes, and as an increase of bFGF immunoreactivity in the surrounding extracellular matrix, relative to the contralateral side. The time course and pattern of reorganization paralleled the sprouting of septal cholinergic terminals in response to the same type of lesion, suggesting that bFGF may play an important role in lesion-induced plasticity. After transection of the fimbria-fornix, chronic infusion of bFGF appeared to preserve NGF receptors on neurons within the medial septal complex and, as previously reported, prevent the death of medial septal neurons. Therefore, it appears that bFGF infusion, which has been shown to increase the synthesis of NGF by astrocytes (Yoshida and Gage, 1991), also helps enable neurons to respond to NGF. This suggests that after injury bFGF may participate in a cascade of neurotrophic events, directly and indirectly facilitating neuronal repair and/or promoting neuronal survival.
    BibTeX:
    @article{GOMEZPINILLA1992,
      author = {GOMEZPINILLA, F and LEE, JWK and COTMAN, CW},
      title = {BASIC FGF IN ADULT-RAT BRAIN - CELLULAR-DISTRIBUTION AND RESPONSE TO ENTORHINAL LESION AND FIMBRIA FORNIX TRANSECTION},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1992},
      volume = {12},
      number = {1},
      pages = {345-355}
    }
    
    Good, C., Johnsrude, I., Ashburner, J., Henson, R., Friston, K. & Frackowiak, R. A voxel-based morphometric study of ageing in 465 normal adult human brains {2001} NEUROIMAGE
    Vol. {14}({1, Part 1}), pp. {21-36} 
    article DOI  
    Abstract: Voxel-based-morphometry (VBM) is a whole-brain, unbiased technique for characterizing regional cerebral volume and tissue concentration differences in structural magnetic resonance images. We describe an optimized method of VBM to examine the effects of age on grey and white matter and CSF in 465 normal adults. Global grey matter volume decreased linearly with age, with a significantly steeper decline in males. Local areas of accelerated loss were observed bilaterally in the insula, superior parietal gyri, central sulci, and cingulate sulci. Areas exhibiting little or no age effect (relative preservation) were noted in the amygdala, hippocampi, and entorhinal cortex. Global white matter did not decline with age, but local areas of relative accelerated loss and preservation were seen. There was no interaction of age with sex for regionally specific effects. These results corroborate previous reports and indicate that VBM is a useful technique for studying structural brain correlates of ageing through life in humans. (C) 2001 Academic Press.
    BibTeX:
    @article{Good2001,
      author = {Good, CD and Johnsrude, IS and Ashburner, J and Henson, RNA and Friston, KJ and Frackowiak, RSJ},
      title = {A voxel-based morphometric study of ageing in 465 normal adult human brains},
      journal = {NEUROIMAGE},
      year = {2001},
      volume = {14},
      number = {1, Part 1},
      pages = {21-36},
      doi = {{10.1006/nimg.2001.0786}}
    }
    
    Good, C., Johnsrude, I., Ashburner, J., Henson, R., Friston, K. & Frackowiak, R. Cerebral asymmetry and the effects of sex and handedness on brain structure: A voxel-based morphometric analysis of 465 normal adult human brains {2001} NEUROIMAGE
    Vol. {14}({3}), pp. {685-700} 
    article  
    Abstract: We used voxel-based morphometry (VBM) to examine human brain asymmetry and the effects of sex and handedness on brain structure in 465 normal adults. We observed significant asymmetry of cerebral grey and white matter in the occipital, frontal, and temporal lobes (petalia), including Heschl's gyrus, planum temporale (PT) and the hippocampal formation. Males demonstrated increased leftward asymmetry within Heschl's gyrus and PT compared to females. There was no significant interaction between asymmetry and handedness and no main effect of handedness. There was a significant main effect of sex on brain morphology, even after accounting for the larger global volumes of grey and white matter in males. Females had increased grey matter volume adjacent to the depths of both central sulci and the left superior temporal sulcus, in right Heschl's gyrus and PT, in right inferior frontal and frontomarginal gyri and in the cingulate gyrus. Females had significantly increased grey matter concentration extensively and relatively symmetrically in the cortical mantle, parahippocampal gyri, and in the banks of the cingulate and calcarine sulci. Males had increased grey matter volume bilaterally in the mesial temporal lobes, entorhinal and perirhinal cortex, and in the anterior lobes of the cerebellum, but no regions of increased grey matter concentration. (C) 2001 Academic Press.
    BibTeX:
    @article{Good2001a,
      author = {Good, CD and Johnsrude, I and Ashburner, J and Henson, RNA and Friston, KJ and Frackowiak, RSJ},
      title = {Cerebral asymmetry and the effects of sex and handedness on brain structure: A voxel-based morphometric analysis of 465 normal adult human brains},
      journal = {NEUROIMAGE},
      year = {2001},
      volume = {14},
      number = {3},
      pages = {685-700}
    }
    
    Gracely, R., Petzke, F., Wolf, J. & Clauw, D. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia {2002} ARTHRITIS AND RHEUMATISM
    Vol. {46}({5}), pp. {1333-1343} 
    article DOI  
    Abstract: Objective. To use functional magnetic resonance imaging (fMRI) to evaluate the pattern of cerebral activation during the application of painful pressure and determine whether this pattern is augmented in patients with fibromyalgia (FM) compared with controls. Methods. Pressure was applied to the left thumbnail beds of 16 right-handed patients with FM and 16 right-handed matched controls. Each FM patient underwent fMRI while moderately painful pressure was being applied. The functional activation patterns in FM patients were compared with those in controls, who were tested under 2 conditions: the ``stimulus pressure control'' condition, during which they received an amount of pressure similar to that delivered to patients, and the ``subjective pain control'' condition, during which the intensity of stimulation was increased to deliver a subjective level of pain similar to that experienced by patients. Results. Stimulation with adequate pressure to cause similar pain in both groups resulted in 19 regions of increased regional cerebral blood flow in healthy controls and 12 significant regions in patients. Increased fMRI signal occurred in 7 regions common to both groups, and decreased signal was observed in 1 common region. In contrast, stimulation of controls with the same amount of pressure that caused pain in patients resulted in only 2 regions of increased signal, neither of which coincided with a region of activation in patients. Statistical comparison of the patient and control groups receiving similar stimulus pressures revealed 13 regions of greater activation in the patient group. In contrast, similar stimulus pressures produced only 1 region of greater activation in the control group. Conclusion. The fact that comparable subjectively painful conditions resulted in activation patterns that were similar in patients and controls, whereas similar pressures resulted in no common regions of activation and greater effects in patients, supports the hypothesis that FM is characterized by cortical or subcortical augmentation of pain processing.
    BibTeX:
    @article{Gracely2002,
      author = {Gracely, RH and Petzke, F and Wolf, JM and Clauw, DJ},
      title = {Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia},
      journal = {ARTHRITIS AND RHEUMATISM},
      year = {2002},
      volume = {46},
      number = {5},
      pages = {1333-1343},
      doi = {{10.1002/art.10225}}
    }
    
    Grafton, S., Arbib, M., Fadiga, L. & Rizzolatti, G. Localization of grasp representations in humans by positron emission tomography .2. Observation compared with imagination {1996} EXPERIMENTAL BRAIN RESEARCH
    Vol. {112}({1}), pp. {103-111} 
    article  
    Abstract: Positron emission tomography imaging of cerebral blood flow was used to localize blain areas involved in the representation of hand grasping movements. Seven normal subjects were scanned under three conditions. In the first, they observed precision grasping of common objects performed by the examiner. In the second, they imagined themselves grasping the objects without actually moving the hand. These two tasks were compared with a control task of object viewing. Grasp observation activated the left rostral superior temporal sulcus, left inferior frontal cortex (area 45), left rostral inferior parietal cortex (area 40), the rostral part of left supplementary motor area (SMA-proper), and the right dorsal premotor cortex. Imagined grasping activated the left inferior frontal (area 44) and middle frontal cortex, left caudal inferior parietal cortex (area 40), a more extensive response in left rostral SMA-proper. and left dorsal premotor cortex. The two conditions activated different areas of the right posterior cerebellar cortex. We propose that the areas active during grasping observation may form a circuit for recognition of hand-object interactions, whereas the areas active during imagined grasping may be a putative human homologue of a circuit for hand grasping movements recently defined in nonhuman primates. The location of responses in SMA-proper confirms the rostrocaudal segregation of this area for imagined and real movement. A similar segregation is also present in the cerebellum, with imagined and observed grasping movements activating different parts of the posterior lobe and real movements activating the anterior lobe.
    BibTeX:
    @article{Grafton1996,
      author = {Grafton, ST and Arbib, MA and Fadiga, L and Rizzolatti, G},
      title = {Localization of grasp representations in humans by positron emission tomography .2. Observation compared with imagination},
      journal = {EXPERIMENTAL BRAIN RESEARCH},
      year = {1996},
      volume = {112},
      number = {1},
      pages = {103-111}
    }
    
    Grafton, S., Fagg, A., Woods, R. & Arbib, M. Functional anatomy of pointing and grasping in humans {1996} CEREBRAL CORTEX
    Vol. {6}({2}), pp. {226-237} 
    article  
    Abstract: The functional anatomy of reaching and grasping simple objects was determined in nine healthy subjects with positron emission tomography imaging of regional cerebral blood Row (rCBF). In a prehension (grasping) task, subjects reached and grasped illuminated cylindrical objects with their right hand. In a pointing task, subjects reached and pointed over the same targets. In a control condition subjects looked at the targets. Both movement tasks increased activity in a distributed set of cortical and subcortical sites: contralateral motor, premotor, ventral supplementary motor area (SMA), cingulate, superior parietal, and dorsal occipital cortex. Cortical areas including cuneate and dorsal occipital cortex were more extensively activated than ventral occipital or temporal pathways. The left parietal operculum (putative SII) was recruited during grasping but not pointing; Blood Row changes were individually localized with respect to local cortical anatomy using sulcal landmarks. Consistent anatomic landmarks from MRI scans could he identified to locate sensorimotor, ventral SMA, and SII blood flow increases. The time required to complete individual movements and the amount of movement made during imaging correlated positively with the magnitude of rCBF increases during grasping in the contralateral inferior sensorimotor, cingulate, and ipsilateral inferior temporal cortex, and bilateral anterior cerebellum. This functional-anatomic study defines a cortical system for `'pragmatic'' manipulation of simple neutral objects.
    BibTeX:
    @article{Grafton1996a,
      author = {Grafton, ST and Fagg, AH and Woods, RP and Arbib, MA},
      title = {Functional anatomy of pointing and grasping in humans},
      journal = {CEREBRAL CORTEX},
      year = {1996},
      volume = {6},
      number = {2},
      pages = {226-237}
    }
    
    GRASBY, P., FRITH, C., FRISTON, K., BENCH, C., FRACKOWIAK, R. & DOLAN, R. FUNCTIONAL MAPPING OF BRAIN-AREAS IMPLICATED IN AUDITORY - VERBAL MEMORY FUNCTION {1993} BRAIN
    Vol. {116}({Part 1}), pp. {1-20} 
    article  
    Abstract: Positron emission tomography measurements of regional cerebral blood flow (rCBF) were performed in normal volunteers during two auditory - verbal memory tasks: a subspan and supraspan task. The difference in rCBF between tasks was used to identify brain areas/systems involved in auditory - verbal long-term memory. Increases in rCBF were observed in the left and right prefrontal cortex, precuneus and the retrosplenial area of the cingulate gyrus. Decreases in blood flow were centred in the superior temporal gyrus bilaterally. Separate comparisons were also made between each span task and a resting state. Brain regions showing increases in rCBF in these comparisons included the thalamus, left anterior cingulate, right parahippocampal gyrus, cerebellum and the superior temporal gyrus. The brain areas identified in these comparisons define a number of the neuroanatomical components of a distributed system for signal processing and storage relevant to auditory - verbal memory function.
    BibTeX:
    @article{GRASBY1993,
      author = {GRASBY, PM and FRITH, CD and FRISTON, KJ and BENCH, C and FRACKOWIAK, RSJ and DOLAN, RJ},
      title = {FUNCTIONAL MAPPING OF BRAIN-AREAS IMPLICATED IN AUDITORY - VERBAL MEMORY FUNCTION},
      journal = {BRAIN},
      year = {1993},
      volume = {116},
      number = {Part 1},
      pages = {1-20}
    }
    
    Gray, J., Chabris, C. & Braver, T. Neural mechanisms of general fluid intelligence {2003} NATURE NEUROSCIENCE
    Vol. {6}({3}), pp. {316-322} 
    article DOI  
    Abstract: We used an individual-differences approach to test whether general fluid intelligence (gF) is mediated by brain regions that support attentional (executive) control, including subregions of the prefrontal cortex. Forty-eight participants first completed a standard measure of gF (Raven's Advanced Progressive Matrices). They then performed verbal and nonverbal versions of a challenging working-memory task (three-back) while their brain activity was measured using functional magnetic resonance imaging (fMRI). Trials within the three-back task varied greatly in the demand for attentional control because of differences in trial-to-trial interference. On high-interference trials specifically, participants with higher gF were more accurate and had greater event-related neural activity in several brain regions. Multiple regression analyses indicated that lateral prefrontal and parietal regions may mediate the relation between ability (gF) and performance (accuracy despite interference), providing constraints on the neural mechanisms that support gF.
    BibTeX:
    @article{Gray2003,
      author = {Gray, JR and Chabris, CF and Braver, TS},
      title = {Neural mechanisms of general fluid intelligence},
      journal = {NATURE NEUROSCIENCE},
      year = {2003},
      volume = {6},
      number = {3},
      pages = {316-322},
      doi = {{10.1038/nn1014}}
    }
    
    Greene, J., Nystrom, L., Engell, A., Darley, J. & Cohen, J. The neural bases of cognitive conflict and control in moral judgment {2004} NEURON
    Vol. {44}({2}), pp. {389-400} 
    article  
    Abstract: Traditional theories of moral psychology emphasize reasoning and ``higher cognition,'' while more recent work emphasizes the role of emotion. The present fMRI data support a theory of moral judgment according to which both ``cognitive'' and emotional processes play crucial and sometimes mutually competitive roles. The present results indicate that brain regions associated with abstract reasoning and cognitive control (including dorsolateral prefrontal cortex and anterior cingulate cortex) are recruited to resolve difficult personal moral dilemmas in which utilitarian values require ``personal'' moral violations, violations that have previously been associated with increased activity in emotion-related brain regions. Several regions of frontal and parietal cortex predict intertrial differences in moral judgment behavior, exhibiting greater activity for utilitarian judgments. We speculate that the controversy surrounding utilitarian moral philosophy reflects an underlying tension between competing subsystems in the brain.
    BibTeX:
    @article{Greene2004,
      author = {Greene, JD and Nystrom, LE and Engell, AD and Darley, JM and Cohen, JD},
      title = {The neural bases of cognitive conflict and control in moral judgment},
      journal = {NEURON},
      year = {2004},
      volume = {44},
      number = {2},
      pages = {389-400}
    }
    
    Greicius, M., Krasnow, B., Reiss, A. & Menon, V. Functional connectivity in the resting brain: A network analysis of the default mode hypothesis {2003} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {100}({1}), pp. {253-258} 
    article DOI  
    Abstract: Functional imaging studies have shown that certain brain regions, including posterior cingulate cortex (PCC) and ventral anterior cingulate cortex (vACC), consistently show greater activity during resting states than during cognitive tasks. This finding led to the hypothesis that these regions constitute a network supporting a default mode of brain function. In this study, we investigate three questions pertaining to this hypothesis: Does such a resting-state network exist in the human brain? Is it modulated during simple sensory processing? How is it modulated during cognitive processing? To address these questions, we defined PCC and vACC regions that showed decreased activity during a cognitive (working memory) task, then examined their functional connectivity during rest. PCC was strongly coupled with vACC and several other brain regions implicated in the default mode network. Next, we examined the functional connectivity of PCC and vACC during a visual processing task and show that the resultant connectivity maps are virtually identical to those obtained during rest. Last, we defined three lateral prefrontal regions showing increased activity during the cognitive task and examined their resting-state connectivity. We report significant inverse correlations among all three lateral prefrontal regions and PCC, suggesting a mechanism for attenuation of default mode network activity during cognitive processing. This study constitutes, to our knowledge, the first resting-state connectivity analysis of the default mode and provides the most compelling evidence to date for the existence of a cohesive default mode network. Our findings also provide insight into how this network is modulated by task demands and what functions it might subserve.
    BibTeX:
    @article{Greicius2003,
      author = {Greicius, MD and Krasnow, B and Reiss, AL and Menon, V},
      title = {Functional connectivity in the resting brain: A network analysis of the default mode hypothesis},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {2003},
      volume = {100},
      number = {1},
      pages = {253-258},
      doi = {{10.1073/pnas.0135058100}}
    }
    
    Greicius, M., Srivastava, G., Reiss, A. & Menon, V. Default-mode network activity distinguishes Alzheimer's disease from healthy aging: Evidence from functional MRI {2004} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {101}({13}), pp. {4637-4642} 
    article DOI  
    Abstract: Recent functional imaging studies have revealed coactivation in a distributed network of cortical regions that characterizes the resting state, or default mode, of the human brain. Among the brain regions implicated in this network, several, including the posterior cingulate cortex and inferior parietal lobes, have also shown decreased metabolism early in the course of Alzheimer's disease (AD). We reasoned that default-mode network activity might therefore be abnormal in AD. To test this hypothesis, we used independent component analysis to isolate the network in a group of 13 subjects with mild AD and in a group of 13 age-matched elderly controls as they performed a simple sensory-motor processing task. Three important findings are reported. Prominent coactivation of the hippocampus, detected in all groups, suggests that the default-mode network is closely involved with episodic memory processing. The AD group showed decreased resting-state activity in the posterior cingulate and hippocampus, suggesting that disrupted connectivity between these two regions accounts for the posterior cingulate hypometabolism commonly detected in positron emission tomography studies of early AD. Finally, a goodness-of-fit analysis applied at the individual subject level suggests that activity in the default-mode network may ultimately prove a sensitive and specific biomarker for incipient AD.
    BibTeX:
    @article{Greicius2004,
      author = {Greicius, MD and Srivastava, G and Reiss, AL and Menon, V},
      title = {Default-mode network activity distinguishes Alzheimer's disease from healthy aging: Evidence from functional MRI},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {2004},
      volume = {101},
      number = {13},
      pages = {4637-4642},
      doi = {{10.1073/pnas.0308627101}}
    }
    
    Gron, G., Wunderlich, A., Spitzer, M., Tomczak, R. & Riepe, M. Brain activation during human navigation: gender-different neural networks as substrate of performance {2000} NATURE NEUROSCIENCE
    Vol. {3}({4}), pp. {404-408} 
    article  
    Abstract: Visuospatial navigation in animals and human subjects is generally studied using maze exploration. We used functional MRI to observe brain activation in male and female subjects as they searched for the way out of a complex, three-dimensional, virtual-reality maze. Navigation activated the medial occipital gyri, lateral and medial parietal regions, posterior cingulate and parahippocampal gyri as well as the right hippocampus proper. Gender-specific group analysis revealed distinct activation of the left hippocampus in males, whereas females consistently recruited right parietal and right prefrontal cortex. Thus we demonstrate a neural substrate of well established human gender differences in spatial-cognition performance.
    BibTeX:
    @article{Gron2000,
      author = {Gron, G and Wunderlich, AP and Spitzer, M and Tomczak, R and Riepe, MW},
      title = {Brain activation during human navigation: gender-different neural networks as substrate of performance},
      journal = {NATURE NEUROSCIENCE},
      year = {2000},
      volume = {3},
      number = {4},
      pages = {404-408}
    }
    
    Gusnard, D., Akbudak, E., Shulman, G. & Raichle, M. Medial prefrontal cortex and self-referential mental activity: Relation to a default mode of brain function {2001} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {98}({7}), pp. {4259-4264} 
    article  
    Abstract: Medial prefrontal cortex (MPFC) is among those brain regions having the highest baseline metabolic activity at rest and one that exhibits decreases from this baseline across a wide variety of goal-directed behaviors in functional imaging studies. This high metabolic rate and this behavior suggest the existence of an organized mode of default brain function, elements of which may be either attenuated or enhanced. Extant data suggest that these MPFC regions may contribute to the neural instantiation of aspects of the multifaceted ``self.'' We explore this important concept by targeting and manipulating elements of MPFC default state activity. In this functional magnetic resonance imaging (fMRI) study, subjects made two judgments, one self-referential, the other not in response to affectively normed pictures: pleasant vs, unpleasant (an internally cued condition, ICC) and indoors vs. outdoors (an externally cued condition, ECC), The ICC was preferentially associated with activity increases along the dorsal MPFC. These increases were accompanied by decreases in both active task conditions in ventral MPFC. These results support the view that dorsal and ventral MPFC are differentially influenced by attention-demanding tasks and explicitly self-referential tasks. The presence of self-referential mental activity appears to be associated with increases from the baseline in dorsal MPFC, Reductions in Ventral MPFC occurred consistent with the fact that attention-demanding tasks attenuate emotional processing. We posit that both self-referential mental activity and emotional processing represent elements of the default state as represented by activity in MPFC. We suggest that a useful way to explore the neurobiology of the self is to explore the nature of default state activity.
    BibTeX:
    @article{Gusnard2001a,
      author = {Gusnard, DA and Akbudak, E and Shulman, GL and Raichle, ME},
      title = {Medial prefrontal cortex and self-referential mental activity: Relation to a default mode of brain function},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {2001},
      volume = {98},
      number = {7},
      pages = {4259-4264}
    }
    
    Gusnard, D. & Raichle, M. Searching for a baseline: Functional imaging and the resting human brain {2001} NATURE REVIEWS NEUROSCIENCE
    Vol. {2}({10}), pp. {685-694} 
    article  
    Abstract: Functional brain Imaging in humans has revealed task-specific increases in brain activity that are associated with various mental activities. In the same studies, mysterious, task-Independent decreases have also frequently been encountered, especially when the tasks of interest have been compared with a passive state, such as simple fixation or eyes closed. These decreases have raised the possibility that there might be a baseline or resting state of brain function involving a specific set of mental operations. We explore this possibility, including the manner in which we might define a baseline and the implications of such a baseline for our understanding of brain function.
    BibTeX:
    @article{Gusnard2001,
      author = {Gusnard, DA and Raichle, ME},
      title = {Searching for a baseline: Functional imaging and the resting human brain},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2001},
      volume = {2},
      number = {10},
      pages = {685-694}
    }
    
    HALGREN, E., BAUDENA, P., CLARKE, J., HEIT, G., LIEGEOIS, C., CHAUVEL, P. & MUSOLINO, A. INTRACEREBRAL POTENTIALS TO RARE TARGET AND DISTRACTER AUDITORY AND VISUAL-STIMULI .1. SUPERIOR TEMPORAL PLANE AND PARIETAL LOBE {1995} ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
    Vol. {94}({3}), pp. {191-220} 
    article  
    Abstract: Event-related potentials were recorded from 537 sites in the superior temporal plane and parietal lobe of 41 patients. Depth electrodes were implanted to localize seizure origin prior to surgical treatment. Subjects received an auditory discrimination task with target and non-target rare stimuli (''standard oddball paradigm''). In some cases, the target, distracting and frequent tones were completely balanced across blocks for pitch and volume. Variants included an analogous visual discrimination task, or auditory tasks where the rare target event was the omission of a tone, or the repetition of a tone within a series of alternating tones. In some subjects, the same auditory stimuli were delivered but the patient ignored them while reading. Three general response patterns could be distinguished on the basis of their wave forms, latencies and task correlates. First, potentials apparently related to rarity per se, as opposed to differences in sensory characteristics, or in habituation, were observed in the posterior superior temporal plane, beginning with a large positivity superimposed on early components. This positivity peaked at 150 msec after stimulus onset and inverted in sites superior to the Sylvian fissure. Subsequent components could be large, focal and/or inverting in polarity, and usually included a positivity at 230 msec and a negativity at 330 msec. All components in this area were specific to the auditory modality. Second, in the posterior cingulate and supramarginal gyri, a sharp triphasic negative-positive-negative wave form with peaks at about 210-300-400 msec was observed. This wave form was of relatively small amplitude and diffuse, and seldom inverted in polarity. It was multimodal but most prominent to auditory stimuli, appeared to remain when the stimuli were ignored, and was not apparent to repeated words and faces. Third, a broad, often monophasic, wave form peaking at about 380 msec was observed in the superior parietal lobe, similar to that which has been recorded in the hippocampus. This wave form could be of large amplitude, often highly focal, and could invert over short distances. It was equal to visual and auditory stimuli and was also evoked by repeating words and faces. The early endogenous activity in auditory cortex may embody activity that is antecedent to the other patterns in multimodal association cortex. The `'triphasic'' pattern may embody a diffuse non-specific orienting response that is also reflected in the scalp P3a. The later broad pattern may embody the cognitive closure that is also reflected in the scalp P3b or late positive component.
    BibTeX:
    @article{HALGREN1995,
      author = {HALGREN, E and BAUDENA, P and CLARKE, JM and HEIT, G and LIEGEOIS, C and CHAUVEL, P and MUSOLINO, A},
      title = {INTRACEREBRAL POTENTIALS TO RARE TARGET AND DISTRACTER AUDITORY AND VISUAL-STIMULI .1. SUPERIOR TEMPORAL PLANE AND PARIETAL LOBE},
      journal = {ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY},
      year = {1995},
      volume = {94},
      number = {3},
      pages = {191-220}
    }
    
    HALGREN, E., BAUDENA, P., HEIT, G., CLARKE, M. & MARINKOVIC, K. SPATIOTEMPORAL STAGES IN FACE AND WORD-PROCESSING .1. DEPTH RECORDED POTENTIALS IN THE HUMAN OCCIPITAL AND PARIETAL LOBES {1994} JOURNAL OF PHYSIOLOGY-PARIS
    Vol. {88}({1}), pp. {1-50} 
    article  
    Abstract: Evoked potentials (EPs) were used to help identify the timing, location, and intensity of the information-processing stages applied to faces and words in humans. EP generators were localized using intracranial recordings in 33 patients with depth electrodes implanted in order to direct surgical treatment of drug-resistant epilepsy. While awaiting spontaneous seizure onset, the patients gave their fully informed consent to perform cognitive tasks. Depth recordings were obtained from 1198 sites in the occipital. temporal and parietal cortices, and in the limbic system (amygdala, hippocampal formation and posterior cingulate gyrus). Twenty-three patients received a declarative memory recognition task in which faces of previously unfamiliar young adults without verbalizable distinguishing features were exposed for 300 ms every 3 s; 25 patients received an analogous task using words. For component identification, some patients also received simple auditory (21 patients) or visual (12 patients) discrimination tasks. Eight successive EP stages preceding the behavioral response (at about 600 ms) could be distinguished by latency, and each of 14 anatomical structures was found to participate in 2-8 of these stages. The earliest response, an N75-P105, focal in the most medial and posterior of the leads implanted in the occipital lobe (lingual g), was probably generated in visual cortical areas 17 and 18. These components were not visible in response to words, presumably because words were presented foveally. A focal evoked alpha rhythm to both words and faces was also noted in the lingual g. This was followed by an N130-P180-N240 focal and polarity-inverting in the basal occipitotemporal cortex (fusiform g, probably areas 19 and 37). In most cases, the P180 was evoked only by faces, and not by words, letters or symbols. Although largest in the fusiform g this sequence of potentials (especially the N240) was also observed in the supramarginal g, posterior superior and middle temporal g, posterior cingulate g, and posterior hippocampal formation. The N130, but not later components of this complex, was observed in the anterior hippocampus and amygdala. Faces only also evoked longer-latency potentials up to 600 ms in the right fusiform g. Words only evoked a series of potentials beginning at 190 ms and extending to 600 ms in the fusiform g and near the angular g (especially left). Both words and faces evoked a N150-P200-PN260 in the lingual g, and posterior inferior and middle temporal g. A N310-N430-P630 sequence to words and faces was largest and polarity-inverted in the hippocampal formation and amygdala, but was also probably locally-generated in many sites including the lingual g, lateral occipitotemporal cortex, middle and superior temporal g, temporal pole, supramarginal g, and posterior cingulate g. The P660 had the same distribution as has been noted for the P3b to rare target simple auditory and visual stimuli in `oddball' tasks, with inversions in the hippocampus. In several sites, the N310 and N430 were smaller to repeated faces, and the P630 was larger. Putative information-processing functions were tentatively assigned to successive EP components based upon their cognitive correlates, as well as the functions and connections of their generating structures. For the N75-P105, this putative function is simple feature detection in primary visual cortex (V1 and V2). The N130-P180-N240 may embody structural face encoding in posterobasal inferotemporal cortex (homologous to V4?), with the results being spread widely to inferotemporal, multimodal and paralimbic cortices. For words, similar visual-form encoding (in fusiform g) or visual-phonemic encoding (in angular g) may occur between 150 and 280 ms. During the N310, faces and words may be multiply encoded for form and identity (inferotemporal), emotional (amygdala), recent declarative mnestic (hippocampal formation), and semantic (supramarginal and superior temporal sulcal supramodal cortices) characteristics. These multiple characteristics may be contextually integrated across inferotemporal, supramodal association, and limbic cortices during the N430, with cognitive closure following in the P630. In sum, visual information arrives at area 17 by about 75 ms, and is structurally-encoded in occipito-temporal cortex during the next 110 ms. By 150-200 ms after stimulus onset, activation has spread to parietal, lateral temporal, and limbic cortices, all of which continue to participate with the more posterior areas for the next 500 ms of event-encoding. Thus, face and word processing is serial in the sense that it can be divided into successive temporal stages, but highly parallel in that (after the initial stages where visual primitives are extracted) multiple anatomical areas with distinct perceptual, mnestic and emotional functions are engaged simultaneously. Consequently, declarative memory and emotional encoding can participate in early stages of perceptual, as well as later stages of cognitive integration. Conversely, occipitotemporal cortex is involved both early in processing (immediately after V1), as well as later, in the N430. That is, most stages of face and word processing appear to take advantage of the rich `upstream' and `downstream' anatomical connections in the ventral visual processing stream to link the more strictly perceptual networks with semantic, emotional, and mnestic networks.
    BibTeX:
    @article{HALGREN1994,
      author = {HALGREN, E and BAUDENA, P and HEIT, G and CLARKE, M and MARINKOVIC, K},
      title = {SPATIOTEMPORAL STAGES IN FACE AND WORD-PROCESSING .1. DEPTH RECORDED POTENTIALS IN THE HUMAN OCCIPITAL AND PARIETAL LOBES},
      journal = {JOURNAL OF PHYSIOLOGY-PARIS},
      year = {1994},
      volume = {88},
      number = {1},
      pages = {1-50}
    }
    
    Hariri, A., Mattay, V., Tessitore, A., Fera, F. & Weinberger, D. Neocortical modulation of the amygdala response to fearful stimuli {2003} BIOLOGICAL PSYCHIATRY
    Vol. {53}({6}), pp. {494-501} 
    article DOI  
    Abstract: Background: The cortical circuitry involved in conscious cognitive processes and the subcortical circuitry involved in fear responses have been extensively studied with neuroimaging, but their interactions remain largely unexplored. A recent functional magnetic resonance imaging (fMRI) study demonstrated that the engagement of the right prefrontal cortex during the cognitive evaluation of angry and fearful facial expressions is associated with an attenuation of the response of the amygdala to these same stimuli, providing evidence for a functional neural network for emotional regulation. Methods: In the current study, we have explored the generalizability of this functional network by using threatening and fearful non-face stimuli derived from the International Affective Picture System (IAPS), as well as the influence of this network on peripheral autonomic responses. Results: Similar to the earlier findings with facial expressions, blood oxygen level dependent fMRI revealed that whereas perceptual processing of IAPS stimuli was associated with a bilateral amygdala response, cognitive evaluation of these same stimuli was associated with attenuation of this amygdala response and a correlated increase in response of the right prefrontal cortex and the anterior cingulate cortex. Moreover, this pattern was reflected in changes in skin conductance. Conclusions: The current results further implicate the importance of neocortical regions, including the prefrontal and anterior cingulate cortices, in regulating emotional responses mediated by the amygdala through conscious evaluation and appraisal. (C) 2003 Society of Biological Psychiatry.
    BibTeX:
    @article{Hariri2003,
      author = {Hariri, AR and Mattay, VS and Tessitore, A and Fera, F and Weinberger, DR},
      title = {Neocortical modulation of the amygdala response to fearful stimuli},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {2003},
      volume = {53},
      number = {6},
      pages = {494-501},
      doi = {{10.1016/S0002-3223(03)01786-9}}
    }
    
    HE, S., DUM, R. & STRICK, P. TOPOGRAPHIC ORGANIZATION OF CORTICOSPINAL PROJECTIONS FROM THE FRONTAL-LOBE - MOTOR AREAS ON THE MEDIAL SURFACE OF THE HEMISPHERE {1995} JOURNAL OF NEUROSCIENCE
    Vol. {15}({5, Part 1}), pp. {3284-3306} 
    article  
    Abstract: We examined the topographic organization of corticospinal neurons in the four premotor areas on the medial wall of the hemisphere of macaques, These motor areas include the supplementary motor area (SMA) and three areas buried within the cingulate sulcus: the caudal cingulate motor area on the dorsal bank (CMAd), the caudal cingulate motor area on the ventral bank (CMAv), and the rostral cingulate motor area (CMAr), In one set of animals, we injected one fluorescent tracer into lower cervical segments of the spinal cord and another fluorescent tracer into lower lumbosacral segments to define the topographic organization of arm and leg representation within each promotor area. Similarly, in another set of animals, we injected different tracers into upper cervical and lower cervical segments to provide an indication of the topographic organization of proximal and distal arm representation within the arm representation of each premotor area. We found that all four of the premotor areas on the medial wall project to cervical and lumbosacral segments of the spinal cord, Three of these areas (SMA, CMAd, and CMAv) are like the primary motor cortex in having distinct arm and leg representations. The arm representation in each of the four motor areas on the medial wall contains separate regions that project densely to upper or to lower cervical segments, This observation suggests that each motor area contains distinct proximal and distal representations of the arm, Surprisingly, the size of the distal representation is comparable to or larger than the size of the proximal representation in each motor area, Thus, contrary to some previous hypotheses, the anatomical substrate exists for the premotor areas on the medial wall to be involved in the control of distal, as well as proximal arm movements, Our results provide a new map for guiding the exploration of the motor functions of the medial wall of the hemisphere, Furthermore, the observations of the present study support our suggestion that each of the premotor areas may be an important source of descending commands for the generation and control of movement.
    BibTeX:
    @article{HE1995,
      author = {HE, SQ and DUM, RP and STRICK, PL},
      title = {TOPOGRAPHIC ORGANIZATION OF CORTICOSPINAL PROJECTIONS FROM THE FRONTAL-LOBE - MOTOR AREAS ON THE MEDIAL SURFACE OF THE HEMISPHERE},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1995},
      volume = {15},
      number = {5, Part 1},
      pages = {3284-3306}
    }
    
    HE, S., DUM, R. & STRICK, P. TOPOGRAPHIC ORGANIZATION OF CORTICOSPINAL PROJECTIONS FROM THE FRONTAL-LOBE - MOTOR AREAS ON THE LATERAL SURFACE OF THE HEMISPHERE {1993} JOURNAL OF NEUROSCIENCE
    Vol. {13}({3}), pp. {952-980} 
    article  
    Abstract: We examined the topographic organization of corticospinal neurons in the primary motor cortex and in the two premotor areas on the lateral surface of the hemisphere [i.e., the dorsal premotor area (PMd) and the ventral premotor area (PMv)]. In two macaques, we labeled corticospinal neurons that project beyond T7 or S2 by placing crystals of HRP into the dorsolateral funiculus at these segmental levels. In another seven macaques, we labeled corticospinal neurons that project to specific segmental levels of the spinal cord by injecting the fluorescent tracers fast blue and diamidino yellow into the gray matter of the cervical and lumbosacral segments. In one set of experiments (n = 2), we defined the representations of the arm and leg in each cortical motor area by injecting one of the two fluorescent tracers into lower cervical segments (C7-T1) and the other fluorescent tracer into lower lumbosacral segments (L6-S1) of the same animal. In another set of experiments (n = 5), we defined the representations of distal and proximal parts of the forelimb in each cortical motor area by injecting one of the two fluorescent tracers into lower cervical segments (C7-T1) and the other tracer into upper cervical segments (C2-C4) of the same animal. In the primary motor cortex and the PMd, cortical regions that project to lower cervical segments were largely separate from those that project to lower lumbosacral segments. In the PMv, few neurons were labeled after tracer injections into lower cervical segments or lower lumbosacral segments. However, corticospinal neurons were labeled in the PMv after tracer injections into upper cervical segments and after HRP placement in the dorsolateral funiculus at T7. The region of the PMv that projects to upper cervical segments was separate from that which projects below T7. Cortical regions that project to upper and lower cervical segments of the spinal cord overlapped considerably in the primary motor cortex and in the PMd. Despite this overlap, we found that the regions of the primary motor cortex and PMd that project most densely to upper cervical segments were largely separate from those that project most densely to lower cervical segments. Furthermore, we found two separate regions within area 4 that send corticospinal projections primarily to the lower cervical segments. One of these regions was located within the classical `'hand'' area of the primary motor cortex. The other was located at the medial edge of arm representation in the primary motor cortex. These results provide new insights into the pattern of body representation in the primary motor cortex, PMd, and PMv. Our findings support the classic distinction between the `'arm'' and `'leg'' representation in the primary motor cortex. However, the demonstration that two regions in the primary motor cortex project densely to lower cervical segments suggests that the organization of distal representation in the `'arm'' area is more complex than previously thought. Our study provides additional support for the existence of separate arm and leg representations in the PMd and possibly in the PMv. Furthermore, we present evidence that the arm area of the PMd contains separate regions of distal and proximal representation. Thus, our results imply that the PMd is involved in the control of both distal and proximal arm movements. Finally, we found some striking differences in the pattern of corticospinal projections from the PMd and PMv. These differences provide additional support for distinguishing between these two premotor areas.
    BibTeX:
    @article{HE1993,
      author = {HE, SQ and DUM, RP and STRICK, PL},
      title = {TOPOGRAPHIC ORGANIZATION OF CORTICOSPINAL PROJECTIONS FROM THE FRONTAL-LOBE - MOTOR AREAS ON THE LATERAL SURFACE OF THE HEMISPHERE},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1993},
      volume = {13},
      number = {3},
      pages = {952-980}
    }
    
    Henson, R., Rugg, M., Shallice, T., Josephs, O. & Dolan, R. Recollection and familiarity in recognition memory: An event-related functional magnetic resonance imaging study {1999} JOURNAL OF NEUROSCIENCE
    Vol. {19}({10}), pp. {3962-3972} 
    article  
    Abstract: The question of whether recognition memory judgments with and without recollection reflect dissociable patterns of brain activity is unresolved. We used event-related, functional magnetic resonance imaging (fMRI) of 12 healthy volunteers to measure hemodynamic responses associated with both studying and recognizing words. Volunteers made one of three judgments to each word during recognition: whether they recollected seeing it during study (R judgments), whether they experienced a feeling of familiarity in the absence of recollection (K judgments), or whether they did not remember seeing it during study (N judgments). Both R and K judgments for studied words were associated with enhanced responses in left prefrontal and left parietal cortices relative to N judgments for unstudied words. The opposite pattern was observed in bilateral temporoccipital regions and amygdalae. R judgments for studied words were associated with enhanced responses in anterior left prefrontal, left parietal, and posterior cingulate regions relative to K judgments. At study, a posterior left prefrontal region exhibited an enhanced response to words subsequently given R versus K judgments, but the response of this region during recognition did not differentiate R and K judgments. K judgments for studied words were associated with enhanced responses in right lateral and medial prefrontal cortex relative to both R judgments for studied words and N judgments for unstudied words, a difference we attribute to greater monitoring demands when memory judgments are less certain. These results suggest that the responses of different brain regions do dissociate according to the phenomenology associated with memory retrieval.
    BibTeX:
    @article{Henson1999,
      author = {Henson, RNA and Rugg, MD and Shallice, T and Josephs, O and Dolan, RJ},
      title = {Recollection and familiarity in recognition memory: An event-related functional magnetic resonance imaging study},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1999},
      volume = {19},
      number = {10},
      pages = {3962-3972}
    }
    
    Herholz, K., Salmon, E., Perani, D., Baron, J., Holthoff, V., Frolich, L., Schonknecht, P., Ito, K., Mielke, R., Kalbe, E., Zundorf, G., Delbeuck, X., Pelati, O., Anchisi, D., Fazio, F., Kerrouche, N., Desgranges, B., Eustache, F., Beuthien-Baumann, B., Menzel, C., Schroder, J., Kato, T., Arahata, Y., Henze, M. & Heiss, W. Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET {2002} NEUROIMAGE
    Vol. {17}({1}), pp. {302-316} 
    article DOI  
    Abstract: A new diagnostic indicator of FDG PET scan abnormality, based on age-adjusted t statistics and an automated voxel-based procedure, is presented and validated in a large data set comprising 110 normal controls and 395 patients with probable Alzheimer's disease (AD) that were studied in eight participating centers. The effect of differences in spatial resolution of PET scanners was minimized effectively by filtering and masking. In controls FDG uptake declined significantly with age in anterior cingulate and frontolateral perisylvian cortex. In patients with probable AD decline of FDG uptake in posterior cingulate, temporoparietal, and prefrontal association cortex was related to dementia severity. These effects were clearly distinct from age effects in controls, suggesting that the disease process of AD is not related to normal aging. Women with probable AD had significantly more frontal metabolic impairment than men. The new indicator of metabolic abnormality in AD-related regions provided 93% sensitivity and specificity for distinction of mild to moderate probable AD from normals, and 84% sensitivity at 93% specificity for detection of very mild probable AD (defined by Mini Mental Score 24 or better). All regions related to AD severity were already affected in very mild AD, suggesting that all vulnerable areas are affected to a similar degree already at disease onset. Ventromedial frontal cortex was also abnormal. In conclusion, automated analysis of multicenter FDG PET is feasible, provides insights into AD pathophysiology, and can be used potentially as a sensitive biomarker for early AD diagnosis. (C) 2002 Elsevier Science (USA).
    BibTeX:
    @article{Herholz2002,
      author = {Herholz, K and Salmon, E and Perani, D and Baron, JC and Holthoff, V and Frolich, L and Schonknecht, P and Ito, K and Mielke, R and Kalbe, E and Zundorf, G and Delbeuck, X and Pelati, O and Anchisi, D and Fazio, F and Kerrouche, N and Desgranges, B and Eustache, F and Beuthien-Baumann, B and Menzel, C and Schroder, J and Kato, T and Arahata, Y and Henze, M and Heiss, WD},
      title = {Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET},
      journal = {NEUROIMAGE},
      year = {2002},
      volume = {17},
      number = {1},
      pages = {302-316},
      doi = {{10.1006/nimg.2002.1208}}
    }
    
    Herman, J., Ostrander, M., Mueller, N. & Figueiredo, H. Limbic system mechanisms of stress regulation: Hypothalamo-pituitary-adrenocortical axis {2005} PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
    Vol. {29}({8}), pp. {1201-1213} 
    article DOI  
    Abstract: Limbic dysfunction and hypothalamo-pituitary-adrenocortical (HPA) axis dysregulation are key features of affective disorders. The following review summarizes our current understanding of the relationship between limbic structures and control of ACTH and glucocorticoid release, focusing on the hippocampus, medial prefrontal cortex and amygdala. In general, the hippocampus and anterior cingulate/prelimbic cortex inhibit stress-induced HPA activation, whereas the amygdala and perhaps the infralimbic cortex may enhance glucocorticoid secretion. Several characteristics of limbic-HPA interaction are notable: first, in all cases, the role of given limbic structures is both region- and stimulus-specific. Second, limbic sites have minimal direct projections to HPA effector neurons of the paraventricular nucleus (PVN); hippocampal, cortical and amygdalar efferents apparently relay with neurons in the bed nucleus of the stria terminalis, hypothalamus and brainstem to access corticotropin releasing hormone neurons. Third, hippocampal, cortical and amygdalar projection pathways show extensive overlap in regions such as the bed nucleus of the stria terminalis, hypothalamus and perhaps brainstem, implying that limbic information may be integrated at subcortical relay sites prior to accessing the PVN. Fourth, these limbic sites also show divergent projections, with the various structures having distinct subcortical targets. Finally, all regions express both glucocorticoid and mineralocorticoid receptors, allowing for glucocorticoid modulation of limbic signaling patterns. Overall, the influence of the limbic system on the HPA axis is likely the end result of the overall patterning of responses to given stimuli and glucocorticoids, with the magnitude of the secretory response determined with respect to the relative contributions of the various structures. (c) 2005 Elsevier Inc. All rights reserved.
    BibTeX:
    @article{Herman2005,
      author = {Herman, JP and Ostrander, MM and Mueller, NK and Figueiredo, H},
      title = {Limbic system mechanisms of stress regulation: Hypothalamo-pituitary-adrenocortical axis},
      journal = {PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY},
      year = {2005},
      volume = {29},
      number = {8},
      pages = {1201-1213},
      doi = {{10.1016/j.pnpbp.2005.08.006}}
    }
    
    HINTON, V., BROWN, W., WISNIEWSKI, K. & RUDELLI, R. ANALYSIS OF NEOCORTEX IN 3 MALES WITH THE FRAGILE-X SYNDROME {1991} AMERICAN JOURNAL OF MEDICAL GENETICS
    Vol. {41}({3}), pp. {289-294} 
    article  
    Abstract: Fragile X [fraX] syndrome is a common hereditary disorder associated with a fragile site marker at Xq27.3 which clinically presents as a form of mental retardation (MR). Postmortem investigation of 3 fraX positive males with mild to moderate MR did not document any gross neuropathological changes. Golgi analysis of neocortical dendritic spine morphology extended our previous observations of immature, long, tortuous spines in one adult case of fraX (Rudelli, et al., Acta Neuropathologica 67:289-295, 1985) to 2 new cases. Evidence for similar dendritic spine abnormalities was found, although Golgi analysis was less than optimal because of incomplete dendritic stain impregnation. Neocortical intra-layer cell density was also investigated in all 3 cases. Cresyl violet stained neurons were counted in 10 randomly selected fields in neocortical layers II-VI of cingulate and temporal association areas (Brodmann's areas 23 and 38). Neuron counts in fraX and control neocortex showed no significant differences. Thus, abnormal dendritic spine morphology with preservation of neuronal density appears to characterize the neocortex in individuals with this common form of mental retardation.
    BibTeX:
    @article{HINTON1991,
      author = {HINTON, VJ and BROWN, WT and WISNIEWSKI, K and RUDELLI, RD},
      title = {ANALYSIS OF NEOCORTEX IN 3 MALES WITH THE FRAGILE-X SYNDROME},
      journal = {AMERICAN JOURNAL OF MEDICAL GENETICS},
      year = {1991},
      volume = {41},
      number = {3},
      pages = {289-294}
    }
    
    Hirayasu, Y., Shenton, M., Salisbury, D., Kwon, J., Wible, C., Fischer, I., Yurgelun-Todd, D., Zarate, C., Kikinis, R., Jolesz, F. & McCarley, R. Subgenual cingulate cortex volume in first-episode psychosis {1999} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {156}({7}), pp. {1091-1093} 
    article  
    Abstract: Objective: Gray matter volume and glucose utilization have been reported to be reduced in the left subgenual cingulate of subjects with familial bipolar or unipolar depression. It is unclear whether these findings are secondary to recurrent illness or are part of a familial/ genetic syndrome. The authors' goal was to clarify these findings. Method: Volumetric analyses were performed by using magnetic resonance imaging in 41 patients experiencing their first episode of affective disorder or schizophrenia and in 20 normal comparison subjects. Results: The left subgenual cingulate volume of the patients with affective disorder who had a family history of affective disorder was smaller than that of patients with affective disorder with no family history of the illness and the normal comparison subjects. Patients with schizophrenia did not differ from comparison subjects in left subgenual cingulate volume. Conclusions: Left subgenual cingulate abnormalities are present at first hospitalization for psychotic affective disorder in patients who have a family history of affective disorder.
    BibTeX:
    @article{Hirayasu1999,
      author = {Hirayasu, Y and Shenton, ME and Salisbury, DF and Kwon, JS and Wible, CG and Fischer, IA and Yurgelun-Todd, D and Zarate, C and Kikinis, R and Jolesz, FA and McCarley, RW},
      title = {Subgenual cingulate cortex volume in first-episode psychosis},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {1999},
      volume = {156},
      number = {7},
      pages = {1091-1093}
    }
    
    Hofbauer, R., Rainville, P., Duncan, G. & Bushnell, M. Cortical representation of the sensory dimension of pain {2001} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {86}({1}), pp. {402-411} 
    article  
    Abstract: It is well accepted that pain is a multidimensional experience, but little is known of how the brain represents these dimensions. We used positron emission tomography (PET) to indirectly measure pain-evoked cerebral activity before and after hypnotic suggestions were given to modulate the perceived intensity of a painful stimulus. These techniques were similar to those of a previous study in which we gave suggestions to modulate the perceived unpleasantness of a noxious stimulus. Ten volunteers were scanned while tonic warm and noxious heat stimuli were presented to the hand during four experimental conditions: alert control, hypnosis control, hypnotic suggestions for increased-pain intensity and hypnotic suggestions for decreased-pain intensity. As shown in previous brain imaging studies, noxious thermal stimuli presented during the alert and hypnosis-control conditions reliably activated contralateral structures, including primary somatosensory cortex (S1), secondary somatosensory cortex (S2), anterior cingulate cortex, and insular cortex. Hypnotic modulation of the intensity of the pain sensation led to significant changes in pain-evoked activity within S1 in contrast to our previous study in which specific modulation of pain unpleasantness (affect), independent of pain intensity, produced specific changes within the ACC. This double dissociation of cortical modulation indicates a relative specialization of the sensory and the classical limbic cortical areas in the processing of the sensory and affective dimensions of pain.
    BibTeX:
    @article{Hofbauer2001,
      author = {Hofbauer, RK and Rainville, P and Duncan, GH and Bushnell, MC},
      title = {Cortical representation of the sensory dimension of pain},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {2001},
      volume = {86},
      number = {1},
      pages = {402-411}
    }
    
    Holroyd, C. & Coles, M. The neural basis. of human error processing: Reinforcement learning, dopamine, and the error-related negativity {2002} PSYCHOLOGICAL REVIEW
    Vol. {109}({4}), pp. {679-709} 
    article DOI  
    Abstract: The authors present a unified account of 2 neural systems concerned with the development and expression of adaptive behaviors: a mesencephalic dopamine system for reinforcement learning and a ``generic'' error-processing system associated with the anterior cingulate cortex. The existence of the error-processing system has been inferred from the error-related negativity (ERN), a component. of the event-related brain potential elicited when human participants commit errors in reaction-time tasks. The authors propose that the ERN is generated when a negative reinforcement learning signal is conveyed to the anterior cingulate cortex via the mesencephalic dopamine system and that this signal is used by the anterior cingulate cortex to modify performance on the task at hand. They provide support for this proposal using both computational modeling and psychophysiological experimentation.
    BibTeX:
    @article{Holroyd2002,
      author = {Holroyd, CB and Coles, MGH},
      title = {The neural basis. of human error processing: Reinforcement learning, dopamine, and the error-related negativity},
      journal = {PSYCHOLOGICAL REVIEW},
      year = {2002},
      volume = {109},
      number = {4},
      pages = {679-709},
      doi = {{10.1037//0033-295X.109.4.679}}
    }
    
    HSIEH, J., BELFRAGE, M., STONEELANDER, S., HANSSON, P. & INGVAR, M. CENTRAL REPRESENTATION OF CHRONIC ONGOING NEUROPATHIC PAIN STUDIED POSITRON EMISSION TOMOGRAPHY {1995} PAIN
    Vol. {63}({2}), pp. {225-236} 
    article  
    Abstract: This study was undertaken to explore whether the neural substrates demonstrated in brain imaging studies on experimentally induced pain are involved in the perception of chronic neuropathic pain. We investigated the cerebral representation of chronic lateralised ongoing pain in patients with painful mononeuropathy (PMN, i.e., pain in the distribution of a nerve, neuralgia) with positron emission tomography (PET), using regional cerebral blood flow (rCBF) as an index for neuronal activity. Eight patients (29-53 years) with PMN in the lower extremity (4 in the right, 4 in the left) were recruited. Paired comparisons of rCBF were made between the patient's habitual pain (HP) state and the pain alleviated (PA) state following a successful regional nerve block (RNB) with lidocaine. The ongoing neuropathic pain resulted in activation of bilateral anterior insula, posterior parietal, lateral inferior prefrontal, and posterior cingulate cortices as well as the posterior sector of the right anterior cingulate cortex (ACC), Brodmann area (BA) 24, regardless of the side of PMN. In addition, a reduction in rCBF was noted in the contralateral posterior thalamus. No significant change of rCBF was detected in the somatosensory areas, i.e., SI and SII. The cerebral activation pattern, while addressing the differences between the HP and PA states, emphasises the affective-motivational dimension in chronic ongoing neuropathic pain. The striking preferential activation of the right ACC (BA 24), regardless of the side of the PMN, not only confirms that the ACC participates in the sensorial/affectional aspect of the pain experience but also suggests a possible right hemispheric lateralisation of the ACC for affective processing in chronic ongoing neuropathic pain. Our data suggests that the brain employs different central mechanisms for chronic neuropathic pain and experimentally induced acute pain, respectively.
    BibTeX:
    @article{HSIEH1995,
      author = {HSIEH, JC and BELFRAGE, M and STONEELANDER, S and HANSSON, P and INGVAR, M},
      title = {CENTRAL REPRESENTATION OF CHRONIC ONGOING NEUROPATHIC PAIN STUDIED POSITRON EMISSION TOMOGRAPHY},
      journal = {PAIN},
      year = {1995},
      volume = {63},
      number = {2},
      pages = {225-236}
    }
    
    HUANG, Q., ZHOU, D., CHASE, K., GUSELLA, J., ARONIN, N. & DIFIGLIA, M. IMMUNOHISTOCHEMICAL LOCALIZATION OF THE D1 DOPAMINE RECEPTOR IN RAT-BRAIN REVEALS ITS AXONAL-TRANSPORT, PRESYNAPTIC AND POSTSYNAPTIC LOCALIZATION, AND PREVALENCE IN THE BASAL GANGLIA, LIMBIC SYSTEM, AND THALAMIC RETICULAR NUCLEUS {1992} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {89}({24}), pp. {11988-11992} 
    article  
    Abstract: D1 dopamine receptor localization was examined by immunohistochemistry using a polyclonal anti-peptide antibody which (i) immunoprecipitated a protein fragment encoded by a D1 receptor cDNA and (ii) on Western blots of solubilized striatal and hippocampal membranes recognized two proteins of approximately 50 kDa and 75 kDa, corresponding to reported sizes of D1 receptor proteins. Immunoreactivity overlapped with dopamine-containing pathways, patterns of D1 receptor binding, and mRNA expression. Staining was concentrated in prefrontal, cingulate, parietal, piriform, entorhinal, and hippocampal cortical areas and subcortically in the basal ganglia, amygdala, septal area, substantia inominata, thalamus, hypothalamus, and neurohypophysis. Prominent labeling was seen in the thalamic reticular nucleus, a region known to integrate ascending basal forebrain inputs with thalamocortical and corticothalamic pathways and in fiber bundles interconnecting limbic areas. In striatal neuropil, staining appeared in spines (heads and necks), at postsynaptic sites in dendrites, and in axon terminals; in the pars reticulata of the substantia nigra, labeling was prevalent in myelinated and unmyelinated axons and dendrites. These data provide direct evidence for the regional and subcellular distribution of D1 receptor protein in the brain and for its pre- and postsynaptic localization in the basal ganglia. The prominent immunoreactivity seen in the limbic system and thalamic reticular nucleus supports an important role for this receptor subtype in mediating integrative processes involved with learning, memory, and cognition.
    BibTeX:
    @article{HUANG1992,
      author = {HUANG, Q and ZHOU, D and CHASE, K and GUSELLA, JF and ARONIN, N and DIFIGLIA, M},
      title = {IMMUNOHISTOCHEMICAL LOCALIZATION OF THE D1 DOPAMINE RECEPTOR IN RAT-BRAIN REVEALS ITS AXONAL-TRANSPORT, PRESYNAPTIC AND POSTSYNAPTIC LOCALIZATION, AND PREVALENCE IN THE BASAL GANGLIA, LIMBIC SYSTEM, AND THALAMIC RETICULAR NUCLEUS},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1992},
      volume = {89},
      number = {24},
      pages = {11988-11992}
    }
    
    Hui, K., Liu, J., Makris, N., Gollub, R., Chen, A., Moore, C., Kennedy, D., Rosen, B. & Kwong, K. Acupuncture modulates the limbic system and subcortical gray structures of the human brain: Evidence from fMRI studies in normal subjects {2000} HUMAN BRAIN MAPPING
    Vol. {9}({1}), pp. {13-25} 
    article  
    Abstract: Acupuncture, an ancient therapeutic technique, is emerging as an important modality of complementary medicine in the United States. The use and efficacy of acupuncture treatment are not yet widely accepted in Western scientific and medical communities. Demonstration of regionally specific, quantifiable acupuncture effects on relevant structures of the human brain would facilitate acceptance and integration of this therapeutic modality into the practice of modem medicine. Research with animal models of acupuncture indicates that many of the beneficial effects may be mediated at the subcortical level in the brain. We used functional magnetic resonance imaging (fMRI) to investigate the effects of acupuncture in normal subjects and to provide a foundation for future studies on mechanisms of acupuncture action in therapeutic interventions. Acupuncture needle manipulation was performed at Large Intestine 4 (LI 4, Hegu) on the hand in 13 subjects [Stux, 1997]. Needle manipulation on either hand produced prominent decreases of fMRI signals in the nucleus accumbens, amygdala, hippocampus, parahippocampus, hypothalamus, ventral tegmental area, anterior cingulate gyrus (BA 24), caudate, putamen, temporal pole, and insula in all 11 subjects who experienced acupuncture sensation. In marked contrast, signal increases were observed primarily in the somatosensory cortex. The two subjects who experienced pain instead of acupuncture sensation exhibited signal increases instead of decreases in the anterior cingulate gyrus (BA 24), caudate, putamen, anterior thalamus, and posterior insula. Superficial tactile stimulation to the same area elicited signal increases in the somatosensory cortex as expected, but no signal decreases in the deep structures. These preliminary results suggest that acupuncture needle manipulation modulates the activity of the limbic system and subcortical structures. We hypothesize that modulation of subcortical structures may be an important mechanism by which acupuncture exerts its complex multisystem effects. (C) 2000 Wiley-Liss, Inc.
    BibTeX:
    @article{Hui2000,
      author = {Hui, KKS and Liu, J and Makris, N and Gollub, RL and Chen, AJW and Moore, CI and Kennedy, DN and Rosen, BR and Kwong, KK},
      title = {Acupuncture modulates the limbic system and subcortical gray structures of the human brain: Evidence from fMRI studies in normal subjects},
      journal = {HUMAN BRAIN MAPPING},
      year = {2000},
      volume = {9},
      number = {1},
      pages = {13-25}
    }
    
    HURLEY, K., HERBERT, H., MOGA, M. & SAPER, C. EFFERENT PROJECTIONS OF THE INFRALIMBIC CORTEX OF THE RAT {1991} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {308}({2}), pp. {249-276} 
    article  
    Abstract: On the basis of stimulation studies, it has been proposed that the infralimbic cortex (ILC), Brodmann area 25, may serve as an autonomic motor cortex. To explore this hypothesis, we have combined anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHA-L) and retrograde tracing with wheat germ aggutinin conjugated to horseradish peroxidase (WGA-HRP) to determine the efferent projections from the ILC. Axons exit the ILC in one of three efferent pathways. The dorsal pathway ascends through layers III and V to innervate the prelimbic and anterior cingulate cortices. The lateral pathway courses through the nucleus accumbens to innervate the insular cortex, the perirhinal cortex, and parts of the piriform cortex. In addition, some fibers from the lateral pathway enter the corticospinal tract. The ventral pathway is by far the largest and innervates the thalamus (including the paraventricular nucleus of the thalamus, the border zone between the paraventricular and medial dorsal nuclei, and the paratenial, reuniens, ventromedial, parafasicular, and subparafasicular nuclei), the hypothalamus (including the lateral hypothalamic and medial preoptic areas, and the suprachiasmatic, dorsomedial, and supramammillary nuclei), the amygdala (including the central, medial, and basomedial nuclei, and the periamygdaloid cortex) and the bed nucleus of the stria terminalis. The ventral efferent pathway also provides descending projections to autonomic cell groups of the brainstem and spinal cord including the periaqueductal gray matter, the parabrachial nucleus, the nucleus of the solitary tract, the dorsal motor vagal nucleus, the nucleus ambiguus, and the ventrolateral medulla, as well as lamina I and the intermediolateral column of the spinal cord. The ILC has extensive projections to central autonomic nuclei that may subserve a role in modulating visceral responses to emotional stimuli, such as stress.
    BibTeX:
    @article{HURLEY1991,
      author = {HURLEY, KM and HERBERT, H and MOGA, MM and SAPER, CB},
      title = {EFFERENT PROJECTIONS OF THE INFRALIMBIC CORTEX OF THE RAT},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {1991},
      volume = {308},
      number = {2},
      pages = {249-276}
    }
    
    Hutchison, W., Davis, K., Lozano, A., Tasker, R. & Dostrovsky, J. Pain-related neurons in the human cingulate cortex {1999} NATURE NEUROSCIENCE
    Vol. {2}({5}), pp. {403-405} 
    article  
    BibTeX:
    @article{Hutchison1999,
      author = {Hutchison, WD and Davis, KD and Lozano, AM and Tasker, RR and Dostrovsky, JO},
      title = {Pain-related neurons in the human cingulate cortex},
      journal = {NATURE NEUROSCIENCE},
      year = {1999},
      volume = {2},
      number = {5},
      pages = {403-405}
    }
    
    Iadarola, M., Berman, K., Zeffiro, T., Byas-Smith, M., Gracely, R., Max, M. & Bennett, G. Neural activation during acute capsaicin-evoked pain and allodynia assessed with PET {1998} BRAIN
    Vol. {121}({Part 5}), pp. {931-947} 
    article  
    Abstract: The PET (H2O)-O-15-bolus method was used to image regional brain activity in normal human subjects during intense pain induced by intradermal injection of capsaicin and during post-capsaicin mechanical allodynia (the perception of pain from a normally non-painful stimulus), Images of regional cerebral blood flow were acquired during six conditions: (i) rest; (ii) light brushing of the forearm; (iii) forearm intradermal injection of capsaicin, (iv) and (v) the waning phases of capsaicin pain; and (vi) allodynia, Allodynia was produced by light brushing adjacent to the capsaicin injection site after ongoing pain from the capsaicin injection had completely subsided. Capsaicin treatment produced activation in many discrete brain regions which we classified as subserving four main functions: sensation-perception (primary somatosensory cortex, thalamus and insula); attention (anterior cingulate cortex); descending pain control (periaqueductal grey); and an extensive network related to sensory-motor integration (supplementary motor cortex, bilateral putamen and insula, anterior lobe and vermis of the cerebellum and superior colliculus), Comparison of the noxious and non-noxious stimuli yielded several new insights into neural organization of pain and tactile sensations. Capsaicin pain, which had no concomitant tactile component, produced little or no activation in secondary somatosensory cortex (SII), whereas light brushing produced a prominent activation of SII, suggesting a differential sensitivity of Sn: to tactile versus painful stimuli. The cerebellar vermis was strongly activated by capsaicin, whereas light brush and experimental allodynia produced little or no activation, suggesting a selective association with C-fibre stimulation and nociceptive second-order spinal neurons. The experimental allodynia activated a network that partially overlapped those activated by both pain and light brush alone. Unlike capsaicin-induced pain, allodynia was characterized by bilateral activation of inferior prefrontal cortex, suggesting that prefrontal responses to pain are context dependent.
    BibTeX:
    @article{Iadarola1998,
      author = {Iadarola, MJ and Berman, KF and Zeffiro, TA and Byas-Smith, MG and Gracely, RH and Max, MB and Bennett, GJ},
      title = {Neural activation during acute capsaicin-evoked pain and allodynia assessed with PET},
      journal = {BRAIN},
      year = {1998},
      volume = {121},
      number = {Part 5},
      pages = {931-947}
    }
    
    Ibanez, V., Pietrini, P., Alexander, G., Furey, M., Teichberg, D., Rajapakse, J., Rapoport, S., Schapiro, M. & Horwitz, B. Regional glucose metabolic abnormalities are not the result of atrophy in Alzheimer's disease {1998} NEUROLOGY
    Vol. {50}({6}), pp. {1585-1593} 
    article  
    Abstract: Objective: To determine whether the hypometabolism observed in PET images of patients with Alzheimer's disease (AD) is due entirely to brain atrophy. Background: Reduced brain glucose metabolism in AD patients measured using PET has been reported by numerous authors. Actual glucose metabolic values in AD may be reduced artificially because of brain atrophy, which accentuates the partial volume effect (PVE) on data collected by PET. Methods: Using segmented MR images, we corrected regional cerebral metabolic rates for glucose for PVEs to evaluate the effect of atrophy on uncorrected values for brain metabolism in AD patients and healthy control subjects. Results: Global glucose metabolism was reduced significantly before and after correction in AD patients compared with controls. Before PVE correction, glucose metabolic values in patients were lower than in control subjects in the inferior parietal, frontal, and lateral temporal cortex; in the posterior cingulate; and in the precuneus. These reductions remained significantly lower after PVE correction, although in the posterior cingulate the difference in metabolism between AD patients and control subjects lessened. Regional glucose metabolism of these areas with PVE correction was lower in moderately-severely demented patients than in mildly demented patients. Conclusion: Reduced glucose metabolism measured by PET in AD is not simply an artifact due to an increase in CSF space induced by atrophy, but reflects a true metabolic reduction per gram of tissue.
    BibTeX:
    @article{Ibanez1998,
      author = {Ibanez, V and Pietrini, P and Alexander, GE and Furey, ML and Teichberg, D and Rajapakse, JC and Rapoport, SI and Schapiro, MB and Horwitz, B},
      title = {Regional glucose metabolic abnormalities are not the result of atrophy in Alzheimer's disease},
      journal = {NEUROLOGY},
      year = {1998},
      volume = {50},
      number = {6},
      pages = {1585-1593}
    }
    
    Insausti, R., Herrero, M. & Witter, M. Entorhinal cortex of the rat: Cytoarchitectonic subdivisions and the origin and distribution of cortical efferents {1997} HIPPOCAMPUS
    Vol. {7}({2}), pp. {146-183} 
    article  
    Abstract: The origins and terminations of entorhinal cortical projections in the rat were analyzed in detail with retrograde and anterograde tracing techniques. Retrograde fluorescent tracers were injected in different portions of olfactory, medial frontal (infralimbic and prelimbic areas), lateral frontal (motor area), temporal (auditory), parietal (somatosensory), occipital (visual), cingulate, retrosplenial, insular, and perirhinal cortices. Anterograde tracer injections were placed in various parts of the rat entorhinal cortex to demonstrate the laminar and topographical distribution of the cortical projections of the entorhinal cortex. The retrograde experiments showed that each cortical area explored receives projections from a specific set of entorhinal neurons, limited in number and distribution. By far the most extensive entorhinal projection was directed to the perirhinal cortex. This projection, which arises from all layers, originates throughout the entorhinal cortex, although its major origin is from the more lateral and caudal parts of the entorhinal cortex. Projections to the medial frontal cortex and olfactory structures originate largely in layers II and III of much of the intermediate and medial portions of the entorhinal cortex, although a modest component arises from neurons in layer V of the more caudal parts of the entorhinal cortex, Neurons in layer V of an extremely laterally located strip of entorhinal cortex, positioned along the rhinal fissure, give rise to the projections to lateral frontal (motor), parietal (somatosensory), temporal (auditory), occipital (visual), anterior insular, and cingulate cortices. Neurons in layer V of the most caudal part of the entorhinal cortex originate projections to the retrosplenial cortex. The anterograde experiments confirmed these findings and showed that in general, the terminal fields of the entorhinal-cortical projections were densest in layers I, II, and III, although particularly in the more densely innervated areas, labeling in layer V was also present. Comparably distributed, but much weaker projections reach the contralateral hemisphere. Our results show that in the rat, hippocampal output can reach widespread portions of the neocortex through a relay in a very restricted part of the entorhinal cortex. However most of the hippocampal-cortical connections will be mediated by way of entorhinal-perirhinal-cortical connections. We conclude that, in contrast to previous notions, the overall organization of the hippocampal-cortical connectivity in the rat is largely comparable to that in the monkey. (C) 1997 Wiley-Liss, Inc.
    BibTeX:
    @article{Insausti1997,
      author = {Insausti, R and Herrero, MT and Witter, MP},
      title = {Entorhinal cortex of the rat: Cytoarchitectonic subdivisions and the origin and distribution of cortical efferents},
      journal = {HIPPOCAMPUS},
      year = {1997},
      volume = {7},
      number = {2},
      pages = {146-183}
    }
    
    Irizarry, M., Soriano, F., McNamara, M., Page, K., Schenk, D., Games, D. & Hyman, B. A beta deposition is associated with neuropil changes, but not with overt neuronal loss in the human amyloid precursor protein V717F (PDAPP) transgenic mouse {1997} JOURNAL OF NEUROSCIENCE
    Vol. {17}({18}), pp. {7053-7059} 
    article  
    Abstract: The PDAPP transgenic mouse overexpresses human amyloid precursor protein V717F (PDAPP minigene) and develops age-related cerebral amyloid-beta protein (A beta) deposits similar to senile plaques in Alzheimer's disease. We find age-related cortical and limbic A beta deposition that begins at 8 months and progresses to cover 20-50% of the neuropil in cingulate cortex, entorhinal cortex, and hippocampus of 18-month-old heterozygotic animals. The regional patterns of transgene expression and amyloid deposition suggest that A beta deposits occur at the terminals of overexpressing neurons. Amyloid deposition is associated with dystrophic neurites and extensive gliosis. However, stereological analysis shows that there is no overt neuronal loss in entorhinal cortex, CAI hippocampal subfield, or cingulate cortex through 18 months of age. In addition, there is no apparent loss of mRNA encoding neuronal synaptic, cytoskeletal, or metabolic proteins. Thus, widespread AP deposition in 18-month-old heterozygotic mice produces neuritic alterations and gliosis without widespread neuronal death.
    BibTeX:
    @article{Irizarry1997,
      author = {Irizarry, MC and Soriano, F and McNamara, M and Page, KJ and Schenk, D and Games, D and Hyman, BT},
      title = {A beta deposition is associated with neuropil changes, but not with overt neuronal loss in the human amyloid precursor protein V717F (PDAPP) transgenic mouse},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1997},
      volume = {17},
      number = {18},
      pages = {7053-7059}
    }
    
    Jackson, P., Meltzoff, A. & Decety, J. How do we perceive the pain of others? A window into the neural processes involved in empathy {2005} NEUROIMAGE
    Vol. {24}({3}), pp. {771-779} 
    article DOI  
    Abstract: To what extent do we share feelings with others? Neuroimaging investigations of the neural mechanisms involved in the perception of pain in others may cast light on one basic component of human empathy, the interpersonal sharing of affect. In this fMRI study, participants were shown a series of still photographs of hands and feet in situations that are likely to cause pain, and a matched set of control photographs without any painful events. They were asked to assess on-line the level of pain experienced by the person in the photographs. The results demonstrated that perceiving and assessing painful situations in others was associated with significant bilateral changes in activity in several regions notably, the anterior cingulate, the anterior insula. the cerebellum, and to a lesser extent the thalamus. These regions are known to play a significant role in pain processing. Finally, the activity in the anterior cingulate was strongly correlated with the participants' ratings of the others' pain, suggesting that the activity of this brain region is modulated according to subjects' reactivity to the pain of others. Our findings suggest that there is a partial cerebral commonality between perceiving pain in another individual and experiencing it oneself. This study adds to our understanding of the neurological mechanisms implicated in intersubjectivity and human empathy. Published by Elsevier Inc.
    BibTeX:
    @article{Jackson2005,
      author = {Jackson, PL and Meltzoff, AN and Decety, J},
      title = {How do we perceive the pain of others? A window into the neural processes involved in empathy},
      journal = {NEUROIMAGE},
      year = {2005},
      volume = {24},
      number = {3},
      pages = {771-779},
      doi = {{10.1016/j.neuroimage.2004.09.006}}
    }
    
    JAHANSHAHI, M., JENKINS, H., BROWN, R., MARSDEN, C., PASSINGHAM, R. & BROOKS, D. SELF-INITIATED VERSUS EXTERNALLY TRIGGERED MOVEMENTS .1. AN INVESTIGATION USING MEASUREMENT OF REGIONAL CEREBRAL BLOOD-FLOW WITH PET AND MOVEMENT-RELATED POTENTIALS IN NORMAL AND PARKINSONS-DISEASE SUBJECTS {1995} BRAIN
    Vol. {118}({Part 4}), pp. {913-933} 
    article  
    Abstract: We investigated the functional anatomy of self-initiated and externally triggered movements. Six patients with Parkinson's disease off medication and six age-matched normals were assessed All subjects had regional cerebral blood pow (rCBF) measurement with PET and recording of movement-related cortical potentials (MRPs) from frontal (F), fronto-central (FC), central (C) and parietal (P) sites to obtain measures of the Bereitschaftspotential (BP). The tasks were (i) self-initiated extension of the right index finger on average once every 3 s, (ii) externally triggered finger extension with the rate yoked to the self-initiated task, and (iii) rest condition with tones presented at a rate yoked with the self-initiated task. For the self-initiated movements, the amplitude of the early and peak BP were lower in Parkinson's disease relative to normals. For the externally triggered movements, the patients and the normals did not differ on any of the measures of cortical negativity prior to movement For both groups, the late and peak BP components, but not the early component, had a lower amplitude in the externally triggered than the self-initiated movements. In normals, the left primary sensorimotor cortex, the supplementary motor area bilaterally anterior cingulate, the lateral premotor cortex bilaterally the insular cortex bilaterally, the left thalamus and the left putamen, parietal area 40 bilaterally and the right dorsolateral prefrontal cortex (DLPFC) were significantly activated during the self-initiated movements relative to rest. For the normals, greater activation of the right DLPFC during the self-initiated movements was the only area that significantly differentiated them from the externally triggered movements. When Parkinson's disease patients and normals were compared for the self-initiated movements relative to rest, normals showed greater activation of the supplementary motor area and anterior cingulate, left putamen, left insular cortex, right DLPFC and right parietal area 40. When the groups were compared for the externally triggered movements relative to rest the global pattern of blood pow and rCBF change in the two groups did not differ, confirming the absence of group differences in BPs for the externally triggered movements. During the self-initiated movements, the lower amplitude of the early BP in patients with Parkinson's disease as well as the underactivation of the supplementary motor area relative to normals support the premises that (i) the supplementary motor area contributes to the early BT: and (ii) the deficit in self-initiated movements in Parkinson's disease is due to supplementary motor area underactivation. The DLPFC is activated in situations requiring non-routine decision making as in the self-initiated movements.
    BibTeX:
    @article{JAHANSHAHI1995,
      author = {JAHANSHAHI, M and JENKINS, H and BROWN, RG and MARSDEN, CD and PASSINGHAM, RE and BROOKS, DJ},
      title = {SELF-INITIATED VERSUS EXTERNALLY TRIGGERED MOVEMENTS .1. AN INVESTIGATION USING MEASUREMENT OF REGIONAL CEREBRAL BLOOD-FLOW WITH PET AND MOVEMENT-RELATED POTENTIALS IN NORMAL AND PARKINSONS-DISEASE SUBJECTS},
      journal = {BRAIN},
      year = {1995},
      volume = {118},
      number = {Part 4},
      pages = {913-933}
    }
    
    JENKINS, I., BROOKS, D., NIXON, P., FRACKOWIAK, R. & PASSINGHAM, R. MOTOR SEQUENCE LEARNING - A STUDY WITH POSITRON EMISSION TOMOGRAPHY {1994} JOURNAL OF NEUROSCIENCE
    Vol. {14}({6}), pp. {3775-3790} 
    article  
    Abstract: We have used positron emission tomography to study the functional anatomy of motor sequence learning. Subjects learned sequences of keypresses by trial and error using auditory feedback. They were scanned with eyes closed under three conditions: at rest, while performing a sequence that was practiced before scanning until overlearned, and while learning new sequences at the same rate of performance. Compared with rest, both sequence tasks activated the contralateral sensorimotor cortex to the same extent. Comparing new learning with performance of the prelearned sequence, differences in activation were identified in other areas. (1) Prefrontal cortex was only activated during new sequence learning. (2) Lateral premotor cortex was significantly more activated during new learning, whereas the supplementary motor area was more activated during performance of the prelearned sequence. (3) Activation of parietal association cortex was present during both motor tasks, but was significantly greater during new learning. (4) The putamen was equally activated by both conditions. (5) The cerebellum was activated by both conditions, but the activation was more extensive and greater in degree during new learning. There was an extensive decrease in the activity of prestriate cortex, inferotemporal cortex, and the hippocampus in both active conditions, when compared with rest. These decreases were significantly greater during new learning. We draw three main conclusions. (1) The cerebellum is involved in the process by which motor tasks become automatic, whereas the putamen is equally activated by sequence learning and retrieval, and may play a similar role in both. (2) When subjects team new sequences of motor actions, prefrontal cortex is activated. This may reflect the need to generate new responses. (3) Reduced activity of areas concerned with visual processing, particularly during new learning, suggests that selective attention may involve depressing the activity of cells in modalities that are not engaged by the task.
    BibTeX:
    @article{JENKINS1994,
      author = {JENKINS, IH and BROOKS, DJ and NIXON, PD and FRACKOWIAK, RSJ and PASSINGHAM, RE},
      title = {MOTOR SEQUENCE LEARNING - A STUDY WITH POSITRON EMISSION TOMOGRAPHY},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1994},
      volume = {14},
      number = {6},
      pages = {3775-3790}
    }
    
    JENKINS, I., FERNANDEZ, W., PLAYFORD, E., LEES, A., FRACKOWIAK, R., PASSINGHAM, R. & BROOKS, D. IMPAIRED ACTIVATION OF THE SUPPLEMENTARY MOTOR AREA IN PARKINSONS-DISEASE IS REVERSED WHEN AKINESIA IS TREATED WITH APOMORPHINE {1992} ANNALS OF NEUROLOGY
    Vol. {32}({6}), pp. {749-757} 
    article  
    Abstract: Using positron emission tomography (PET) we previously showed that activation of the putamen, supplementary motor area, and cingulate cortex is impaired in patients with Parkinson's disease (PD) when they are off treatment and perform volitional motor tasks. Evidence suggests that these areas are involved in the generation of internally cued movements in normal subjects. We have now studied the effect of the dopamine agonist apomorphine on cerebral activation when used to treat the akinesia of PD. Regional cerebral blood flow was measured using (CO2)-O-15 PET in PD patients at rest and when performing paced joystick movements with the right hand in one of four freely chosen directions. All patients used apomorphine regularly, and were studied before treatment, while still ``off `` but receiving a subcutaneous apomorphine infusion, and when switched ``on'' with apomorphine. Significant increases in regional cerebral blood flow were determined using statistical parametric mapping. Under resting conditions apomorphine had no effect on focal or global cerebral blood flow. Seven patients with PD performed the motor task adequately in the ``off'' and ``on'' states. This group of subjects demonstrated impaired activation of the supplementary motor area and contralateral putamen in the ``off `` state. Activation of the supplementary motor area significantly improved when the akinesia was reversed with apomorphine. We conclude that the concomitant improvement of supplementary motor area activation and motor function in apomorphine-treated patients with PD provides further evidence for the role of this structure in generating motor programs.
    BibTeX:
    @article{JENKINS1992,
      author = {JENKINS, IH and FERNANDEZ, W and PLAYFORD, ED and LEES, AJ and FRACKOWIAK, RSJ and PASSINGHAM, RE and BROOKS, DJ},
      title = {IMPAIRED ACTIVATION OF THE SUPPLEMENTARY MOTOR AREA IN PARKINSONS-DISEASE IS REVERSED WHEN AKINESIA IS TREATED WITH APOMORPHINE},
      journal = {ANNALS OF NEUROLOGY},
      year = {1992},
      volume = {32},
      number = {6},
      pages = {749-757}
    }
    
    Jentsch, J., Redmond, D., Elsworth, J., Taylor, J., Youngren, K. & Roth, R. Enduring cognitive deficits and cortical dopamine dysfunction in monkeys after long-term administration of phencyclidine {1997} SCIENCE
    Vol. {277}({5328}), pp. {953-955} 
    article  
    Abstract: The effects of the psychotomimetic drug phencyclidine on the neurochemistry and function of the prefrontal cortex in vervet monkeys were investigated, Monkeys treated with phencyclidine twice a day for 14 days displayed performance deficits on a task that was sensitive to prefrontal cortex function; the deficits were ameliorated by the atypical antipsychotic drug clozapine, Repeated exposure to phencyclidine caused a reduction in both basal and evoked dopamine utilization in the dorsolateral prefrontal cortex, a brain region that has long been associated with cognitive function, Behavioral deficits and decreased dopamine utilization remained after phencyclidine treatment was stopped, an indication that these effects were not simply due to direct drug effects. The data suggest that repeated administration of phencyclidine in monkeys may be useful for studying psychiatric disorders associated with cognitive dysfunction and dopamine hypofunction in the prefrontal cortex, particularly schizophrenia.
    BibTeX:
    @article{Jentsch1997,
      author = {Jentsch, JD and Redmond, DE and Elsworth, JD and Taylor, JR and Youngren, KD and Roth, RH},
      title = {Enduring cognitive deficits and cortical dopamine dysfunction in monkeys after long-term administration of phencyclidine},
      journal = {SCIENCE},
      year = {1997},
      volume = {277},
      number = {5328},
      pages = {953-955}
    }
    
    JERNIGAN, T., ARCHIBALD, S., BERHOW, M., SOWELL, E., FOSTER, D. & HESSELINK, J. CEREBRAL STRUCTURE ON MRI .1. LOCALIZATION OF AGE-RELATED-CHANGES {1991} BIOLOGICAL PSYCHIATRY
    Vol. {29}({1}), pp. {55-67} 
    article  
    Abstract: In this report, earlier findings of age-related changes in brain morphology on magnetic resonance (MR) images are extended to include measurements of individual cerebral grey matter structures and an index of white matter degeneration. Volumes of caudate, lenticular, and diencephalic structures are estimated, as are grey matter volumes in eight separate cortical regions. Results suggest that between 30 and 79 years significant decreases occur in the volume of the caudate nucleus, in anterior diencephalic structures and in the grey matter of most cortical regions. The data suggest that the volumes of the thalamus and the anterior cingulate cortex may be unchanged. Among those cortical regions found to be affected in aging, some evidence is present for greater change in association cortices and mesial temporal lobe structures. There are also dramatic age-related changes in the white matter, manifest as lengthened T2 values on MR images.
    BibTeX:
    @article{JERNIGAN1991,
      author = {JERNIGAN, TL and ARCHIBALD, SL and BERHOW, MT and SOWELL, ER and FOSTER, DS and HESSELINK, JR},
      title = {CEREBRAL STRUCTURE ON MRI .1. LOCALIZATION OF AGE-RELATED-CHANGES},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {1991},
      volume = {29},
      number = {1},
      pages = {55-67}
    }
    
    JERNIGAN, T., ZISOOK, S., HEATON, R., MORANVILLE, J., HESSELINK, J. & BRAFF, D. MAGNETIC-RESONANCE-IMAGING ABNORMALITIES IN LENTICULAR NUCLEI AND CEREBRAL-CORTEX IN SCHIZOPHRENIA {1991} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {48}({10}), pp. {881-890} 
    article  
    Abstract: Neuropathologic and brain imaging studies have produced evidence of brain abnormalities in schizophrenic patients, often within the cerebrum's limbic lobe, and, less frequently, within basal ganglia. In the present study we used magnetic resonance imaging morphometric techniques to estimate volumes of specific cerebral structures in schizophrenic patients and age- and sex-matched normal controls. Estimates of the volume of mesial temporal lobe structures were reduced and estimates of the volume of the lenticular nucleus were increased in the schizophrenic patients. There was also evidence of reduced cranial volume in some schizophrenics. The magnitude of the lenticular abnormality, but not the temporal lobe abnormality, was associated with age at first psychiatric contact; earlier onset was associated with larger lenticular nuclei. The possible relevance of these results to neurodevelopmental hypotheses about the pathogenesis of schizophrenia is discussed.
    BibTeX:
    @article{JERNIGAN1991a,
      author = {JERNIGAN, TL and ZISOOK, S and HEATON, RK and MORANVILLE, JT and HESSELINK, JR and BRAFF, DL},
      title = {MAGNETIC-RESONANCE-IMAGING ABNORMALITIES IN LENTICULAR NUCLEI AND CEREBRAL-CORTEX IN SCHIZOPHRENIA},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1991},
      volume = {48},
      number = {10},
      pages = {881-890}
    }
    
    Johnson, S.C., Baxter, L.C., Wilder, L.S., Pipe, J.G., Heiserman, J.E. & Prigatano, G.P. Neural correlates of self-reflection {2002} BRAIN
    Vol. {125}({Part 8}), pp. {1808-1814} 
    article  
    Abstract: The capacity to reflect on one's sense of self is an important component of self-awareness. In this paper, we investigate some of the neurocognitive processes underlying reflection on the self using functional MRI. Eleven healthy volunteers were scanned with echoplanar imaging using the blood oxygen level-dependent contrast method. The task consisted of aurally delivered statements requiring a yes-no decision. In the,:experimental condition, participants responded to a variety of statements requiring knowledge of and reflection on their own abilities, traits and attitudes (e.g. `I forget important things', `I'm a good friend', `I have a quick temper'). In the control condition, participants responded to statements requiring a basic level of semantic knowledge (e.g. `Ten seconds is more than a minute', `You need water to live'). The latter condition was intended to control for auditory comprehension, attentional demands, decision-making, the motoric response, and any common retrieval processes. Individual analyses revealed consistent anterior medial prefrontal and posterior cingulate activation for all participants. The overall activity for the group, using a random-effects model, occurred in anterior medial prefrontal cortex (t = 13.0, corrected P = 0.05; x, y, z, 0, 54, 8, respectively) and the posterior cingulate (t = 14.7, P = 0.02; x, y, z, -2, -62, 32, respectively; 967 voxel extent). These data are consistent with lesion studies of impaired awareness, and suggest that the medial prefrontal and posterior cingulate cortex are part of a neural system subserving self-reflective thought.
    BibTeX:
    @article{Johnson2002,
      author = {Johnson, Sterling C. and Baxter, Leslie C. and Wilder, Lana S. and Pipe, James G. and Heiserman, Joseph E. and Prigatano, George P.},
      title = {Neural correlates of self-reflection},
      journal = {BRAIN},
      year = {2002},
      volume = {125},
      number = {Part 8},
      pages = {1808-1814}
    }
    
    JONES, A., BROWN, W., FRISTON, K., QI, L. & FRACKOWIAK, R. CORTICAL AND SUBCORTICAL LOCALIZATION OF RESPONSE TO PAIN IN MAN USING POSITRON EMISSION TOMOGRAPHY {1991} PROCEEDINGS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
    Vol. {244}({1309}), pp. {39-44} 
    article  
    Abstract: A quantitative study of the regional cerebral responses to non-painful and painful thermal stimuli in six normal volunteers has been done by monitoring serial measurements of regional blood flow measured by positron emission tomography (PET). In comparison to a baseline of warm stimulation no statistically significant changes in blood flow were seen in relation to increasing non-painful heat. However, highly significant increases in blood flow were seen in response to painful heat in comparison to non-painful heat. These changes were in the contralateral cingulate cortex, thalamus and lenticular nucleus. These findings are discussed in relation to previous physiological observations of responses to nociceptive stimuli in man and primates.
    BibTeX:
    @article{JONES1991,
      author = {JONES, AKP and BROWN, WD and FRISTON, KJ and QI, LY and FRACKOWIAK, RSJ},
      title = {CORTICAL AND SUBCORTICAL LOCALIZATION OF RESPONSE TO PAIN IN MAN USING POSITRON EMISSION TOMOGRAPHY},
      journal = {PROCEEDINGS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES},
      year = {1991},
      volume = {244},
      number = {1309},
      pages = {39-44}
    }
    
    Jonides, J., Schumacher, E., Smith, E., Koeppe, R., Awh, E., Reuter-Lorenz, P., Marshuetz, C. & Willis, C. The role of parietal cortex in verbal working memory {1998} JOURNAL OF NEUROSCIENCE
    Vol. {18}({13}), pp. {5026-5034} 
    article  
    Abstract: Neuroimaging studies of normal subjects and studies of patients with focal lesions implicate regions of parietal cortex in verbal working memory (VWM), yet the precise role of parietal cortex in VWM remains unclear. Some evidence (Paulesu et al., 1993; Awh et al., 1996) suggests that the parietal cortex mediates the storage of verbal information, but these studies and most previous ones included encoding and retrieval processes as well as storage and rehearsal of verbal information. A recent positron emission tomography (PET) study by Fiez et al. (1996) isolated storage and rehearsal from other VWM processes and did not find reliable activation in parietal cortex. This result suggests that parietal cortex may not be involved in VWM storage, contrary to previous proposals. However, we report two behavioral studies indicating that some of the verbal material used by Fiez et al. (1996) may not have required phonological representations in VWM. In addition, we report a PET study that isolated VWM encoding, retrieval, and storage and rehearsal processes in different PET scans and used material likely to require phonological codes in VWM. After subtraction of appropriate controls, the encoding condition revealed no reliable activations; the retrieval condition revealed reliable activations in dorsolateral prefrontal, anterior cingulate, posterior parietal, and extrastriate cortices, and the storage condition revealed reliable activations in dorsolateral prefrontal, inferior frontal, premotor, and posterior parietal cortices, as well as cerebellum. These results suggest that parietal regions are part of a network of brain areas that mediate the short-term storage and retrieval of phonologically coded verbal material.
    BibTeX:
    @article{Jonides1998,
      author = {Jonides, J and Schumacher, EH and Smith, EE and Koeppe, RA and Awh, E and Reuter-Lorenz, PA and Marshuetz, C and Willis, CR},
      title = {The role of parietal cortex in verbal working memory},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1998},
      volume = {18},
      number = {13},
      pages = {5026-5034}
    }
    
    JOYCE, J., SHANE, A., LEXOW, N., WINOKUR, A., CASANOVA, M. & KLEINMAN, J. SEROTONIN UPTAKE SITES AND SEROTONIN RECEPTORS ARE ALTERED IN THE LIMBIC SYSTEM OF SCHIZOPHRENICS {1993} NEUROPSYCHOPHARMACOLOGY
    Vol. {8}({4}), pp. {315-336} 
    article  
    Abstract: Serotonin (5-HT) uptake sites were mapped by autoradiographic means with [H-3]cyano-imipramine ([H-3]CN-IMI), the 5-HT1A receptor with [H-3]8-hydroxy-2-[di-n-propyl-amino]tetralin ([H-3]8-OH-DPAT), and the 5-HT2 receptor with both [H-3]ketanserin and [I-125]lysergic acid diethylamide ([I-125]LSD) in eight nonneurologic controls and 10 cases with a diagnosis of schizophrenia. In the striatum, there was a marked heterogeneous patterning of 5-HT uptake sites that corresponded to the striosomal/matrix compartmentalization of the striatum. This organization was not matched with an equally heterogeneous pattern of either 5-HT2 or 5-HT1A receptors. For the isocortex, a general organizational scheme was observed with the 5-HT1A receptor expression high in the external laminae and deep laminae, but 5-HT2 receptor expression was higher in the internal laminae. There was a laminar distribution of 5-HT uptake sites that approximated the combined distributions of the 5-HT1A receptor and the 5-HT2 receptor. In the parahippocampal gyrus and hippocampus, the distribution of 5-HT uptake sites was complementary to the distribution of 5-HT1A and 5-HT2 receptors. In schizophrenic cases, there was a large increase in the number and altered striosomal/matrix organization of 5-HT uptake sites in the striatum. There was also an increase in the numbers of 5-HT2 receptors in the nucleus accumbens and ventral putamen of the schizophrenics. The number of 5-HT1A receptors was not modified. There was a marked reduction in 5-HT uptake sites in the external and middle laminae of the anterior cingulate, frontal cortex, and posterior cingulate, and no changes were observed in the motor cortex, temporal cortex, or hippocampus. Increased numbers of 5-HT1A receptors were found in the posterior cingulate, motor cortex, and hippocampus. Serotonin2 receptors were substantially elevated in the posterior cingulate, temporal cortex, and hippocampus, but not in the frontal, anterior cingulate, or motor cortices. Examination of the temporal lobe and hippocampus of a group of nonschizophrenic suicides (n = 8) indicated the alterations in 5-HT system in the limbic regions of the striatum, the limbic cortex, and hippocampus of the schizophrenic cases may be disease specific.
    BibTeX:
    @article{JOYCE1993,
      author = {JOYCE, JN and SHANE, A and LEXOW, N and WINOKUR, A and CASANOVA, MF and KLEINMAN, JE},
      title = {SEROTONIN UPTAKE SITES AND SEROTONIN RECEPTORS ARE ALTERED IN THE LIMBIC SYSTEM OF SCHIZOPHRENICS},
      journal = {NEUROPSYCHOPHARMACOLOGY},
      year = {1993},
      volume = {8},
      number = {4},
      pages = {315-336}
    }
    
    Jueptner, M., Stephan, K., Frith, C., Brooks, D., Frackowiak, R. & Passingham, R. Anatomy of motor learning .1. Frontal cortex and attention to action {1997} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {77}({3}), pp. {1313-1324} 
    article  
    Abstract: We used positron emission tomography to study new learning and automatic performance in normal volunteers. Subjects learned sequences of eight finger movements by trial and error. In a previous experiment we showed that the prefrontal cortex was activated during new learning but not during automatic performance. The aim of the present experiment was to see what areas could be reactivated if the subjects performed the prelearned sequence but were required to pay attention to what they were doing. Scans were carried out under four conditions. In the first the subjects performed a prelearned sequence of eight key presses; this sequence was learned before scanning and was practiced until it had become overlearned, so that the subjects were able to perform it automatically. In the second condition the subjects learned a new sequence during scanning. In a third condition the subjects performed the prelearned sequence, but they were required to attend to what they were doing; they were instructed to think about the next movement. The fourth condition was a baseline condition. As in the earlier study, the dorsal prefrontal cortex and anterior cingulate area 32 were activated during new learning, but not during automatic performance. The left dorsal prefrontal cortex and the right anterior cingulate cortex were reactivated when subjects paid attention to the performance of the prelearned sequence compared with automatic performance of the same task. It is suggested that the critical feature was that the subjects were required to attend to the preparation of their responses. However, the dorsal prefrontal cortex and the anterior cingulate cortex were activated more when the subjects learned a new sequence than they were when subjects simply paid attention to a prelearned sequence. New learning differs from the attention condition in that the subjects generated moves, monitored the outcomes, and remembered the responses that had been successful. All these are nonroutine operations to which the subjects must attend. Further analysis is needed to specify which are the nonroutine operations that require the involvement of the dorsal prefrontal and anterior cingulate cortex.
    BibTeX:
    @article{Jueptner1997,
      author = {Jueptner, M and Stephan, KM and Frith, CD and Brooks, DJ and Frackowiak, RSJ and Passingham, RE},
      title = {Anatomy of motor learning .1. Frontal cortex and attention to action},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1997},
      volume = {77},
      number = {3},
      pages = {1313-1324}
    }
    
    Kalivas, P. & McFarland, K. Brain circuitry and the reinstatement of cocaine-seeking behavior {2003} PSYCHOPHARMACOLOGY
    Vol. {168}({1-2}), pp. {44-56} 
    article DOI  
    Abstract: Rationale. Recent studies have attempted to identify the neuroanatomical substrates underlying primed reinstatement of drug-seeking behavior. Identification of neuronal substrates will provide a logical rationale for designing pharmacological interventions in treating drug relapse. Objective. The objective was to identify brain circuitry that is shared between cue-, drug- and stress-primed reinstatement, as well as identifying aspects of brain circuitry that are distinct for each stimulus modality. The resulting circuit offers theoretical interpretations for consideration in future studies. Results. Aspects of the circuitry mediating reinstatement can be identified with reasonable confidence. The role of the basolateral amygdala in cue-primed reinstatement, the role of the ventral tegmental area in drug-primed reinstatement and the role of adrenergic innervation of the extended amygdala in stress-primed reinstatement are well characterized. Also, all three modes for priming reinstatement may converge on the anterior cingulate cortex and have a final common output through the core of the nucleus accumbens. Lacunae in our understanding of the circuit were identified, especially with regard to how stress priming is conveyed from the extended amygdala to the shared anterior cingulate accumbens core circuit. Conclusions. The proposed convergence of priming stimuli into the glutamatergic projection from anterior cingulate to the accumbens core combined with the changes in glutamate transmission and signaling that accompany repeated psychostimulant administration points to the potential value of pharmacological agents that manipulate glutamate release or postsynaptic glutamate receptor signaling and trafficking in treating primed relapse in addicts.
    BibTeX:
    @article{Kalivas2003,
      author = {Kalivas, PW and McFarland, K},
      title = {Brain circuitry and the reinstatement of cocaine-seeking behavior},
      journal = {PSYCHOPHARMACOLOGY},
      year = {2003},
      volume = {168},
      number = {1-2},
      pages = {44-56},
      doi = {{10.1007/s00213-003-1393-2}}
    }
    
    Kalivas, P. & Volkow, N. The neural basis of addiction: A pathology of motivation and choice {2005} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {162}({8}), pp. {1403-1413} 
    article  
    Abstract: Objective: A primary behavioral pathology in drug addiction is the overpowering motivational strength and decreased ability to control the desire to obtain drugs. In this review the authors explore how advances in neurobiology are approaching an understanding of the cellular and circuitry underpinnings of addiction, and they describe the novel pharmacotherapeutic targets emerging from this understanding. Method: Findings from neuroimaging of addicts are integrated with cellular studies in animal models of drug seeking. Results: While dopamine is critical for acute reward and initiation of addiction, end-stage addiction results primarily from cellular adaptations in anterior cingulate and orbitofrontal glutamatergic projections to the nucleus accumbens. Pathophysiological plasticity in excitatory transmission reduces the capacity of the prefrontal cortex to initiate behaviors in response to biological rewards and to provide executive control over drug seeking. Simultaneously, the prefrontal cortex is hyperresponsive to stimuli predicting drug availability, resulting in supraphysiological glutamatergic drive in the nucleus accumbens, where excitatory synapses have a reduced capacity to regulate neurotransmission. Conclusions: Cellular adaptations in prefrontal glutamatergic innervation of the accumbens promote the compulsive character of drug seeking in addicts by decreasing the value of natural rewards, diminishing cognitive control ( choice), and enhancing glutamatergic drive in response to drug-associated stimuli.
    BibTeX:
    @article{Kalivas2005,
      author = {Kalivas, PW and Volkow, ND},
      title = {The neural basis of addiction: A pathology of motivation and choice},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {2005},
      volume = {162},
      number = {8},
      pages = {1403-1413},
      note = {157th Annual Meeting of the American-Psychiatric-Association, New York, NY, MAY 01-06, 2004}
    }
    
    Kane, M. & Engle, R. Working-memory capacity and the control of attention: The contributions of goal neglect, response competition, and task set to Stroop interference {2003} JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL
    Vol. {132}({1}), pp. {47-70} 
    article DOI  
    Abstract: Individual differences in working-memory (WM) capacity predicted performance on the Stroop task in 5 experiments, indicating the importance of executive control and goal maintenance to selective attention. When the Stroop task encouraged goal neglect by including large numbers of congruent trials (RED Presented in red), low WM individuals committed more errors than did high WM individuals on the rare incongruent trials.(BLUE in red) that required maintaining access to the ``ignore-the-word'' goal for accurate responding. In contrast, in tasks with no or few congruent trials, or in high-congruency tasks that followed low-congruency tasks, WM predicted response-time interference. WM was related to latency, not accuracy, in contexts that reinforced the task goal and so minimized the difficulty of actively maintaining it. The data and a literature review suggest that Stroop interference is jointly determined by 2 mechanisms, goal maintenance and competition resolution, and that the dominance of each depends on WM capacity, as well as the task set induced by current and previous contexts.
    BibTeX:
    @article{Kane2003,
      author = {Kane, MJ and Engle, RW},
      title = {Working-memory capacity and the control of attention: The contributions of goal neglect, response competition, and task set to Stroop interference},
      journal = {JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL},
      year = {2003},
      volume = {132},
      number = {1},
      pages = {47-70},
      doi = {{10.1037/0096-3445.132.1.47}}
    }
    
    Kelley, W., Macrae, C., Wyland, C., Caglar, S., Inati, S. & Heatherton, T. Finding the self? An event-related fMRI study {2002} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {14}({5}), pp. {785-794} 
    article  
    Abstract: Researchers have long debated whether knowledge about the self is unique in terms of its functional anatomic representation within the human brain. In the context of memory function, knowledge about the self is typically remembered better than other types of semantic information. But why does this memorial effect emerge? Extending previous research on this topic (see Craik et al., 1999), the present study used event-related functional magnetic resonance imaging to investigate potential neural substrates of self-referential processing. Participants were imaged while making judgments about trait adjectives under three experimental conditions (self-relevance, other-relevance, or case judgment). Relevance judgments, when compared to case judgments, were accompanied by activation of the left inferior frontal cortex and the anterior cingulate. A separate region of the medial prefrontal cortex was selectively engaged during self-referential processing. Collectively, these findings suggest that self-referential processing is functionally dissociable from other forms of semantic processing within the human brain.
    BibTeX:
    @article{Kelley2002,
      author = {Kelley, WM and Macrae, CN and Wyland, CL and Caglar, S and Inati, S and Heatherton, TF},
      title = {Finding the self? An event-related fMRI study},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {2002},
      volume = {14},
      number = {5},
      pages = {785-794}
    }
    
    Kennedy, S., Evans, K., Kruger, S., Mayberg, H., Meyer, J., McCann, S., Arifuzzman, A., Houle, S. & Vaccarino, F. Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression {2001} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {158}({6}), pp. {899-905} 
    article  
    Abstract: Objective: Depression is commonly associated with frontal hypometabolic activity accompanied by hypermetabolism in certain limbic regions. It is unclear whether successful antidepressant treatments reverse these abnormalities or create new resting levels of metabolism. The aim of the present study was to assess the effects of successful paroxetine treatment on regional glucose metabolism in patients with major depression. Method: Positron emission tomography with [F-18]fluorodeoxyglucose was performed on 13 male patients before and after 6 weeks of paroxetine therapy. Resting state scans were also acquired under similar conditions in 24 healthy male subjects for comparison. Results: After successful paroxetine therapy, increased glucose metabolism occurred in dorsolateral. ventrolateral, and medial aspects of the prefrontal cortex (left greater than right), parietal cortex. and dorsal anterior cingulate. Areas of decreased metabolism were noted in both anterior and posterior insular regions (left) as well as right hippocampal and parahippocampal regions, In comparison to metabolism levels in a group of healthy volunteers, the increase in prefrontal metabolic activity represented a normalization of previously reduced metabolic activity, whereas the reduction in pregenual anterior cingulate activity represented a decrease from previously elevated metabolic levels. Conclusions: These results provide further support for a dysfunction in cortical-limbic circuitry in depression, which is at least partly reversed after successful paroxetine treatment.
    BibTeX:
    @article{Kennedy2001,
      author = {Kennedy, SH and Evans, KR and Kruger, S and Mayberg, HS and Meyer, JH and McCann, S and Arifuzzman, AI and Houle, S and Vaccarino, FJ},
      title = {Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {2001},
      volume = {158},
      number = {6},
      pages = {899-905},
      note = {53rd Annual Biological Psychiatry Meeting, TORONTO, CANADA, MAY 26-29, 1998}
    }
    
    Kerns, J., Cohen, J., MacDonald, A., Cho, R., Stenger, V. & Carter, C. Anterior Cingulate conflict monitoring and adjustments in control {2004} SCIENCE
    Vol. {303}({5660}), pp. {1023-1026} 
    article  
    Abstract: Conflict monitoring by the anterior cingulate cortex (ACC) has been posited to signal a need for greater cognitive control, producing neural and behavioral adjustments. However, the very occurrence of behavioral adjustments after conflict has been questioned, along with suggestions that there is no direct evidence of ACC conflict-related activity predicting subsequent neural or behavioral adjustments in control. Using the Stroop color-naming task and controlling for repetition effects, we demonstrate that ACC conflict-related activity predicts both greater prefrontal cortex activity and adjustments in behavior, supporting a role of ACC conflict monitoring in the engagement of cognitive control.
    BibTeX:
    @article{Kerns2004,
      author = {Kerns, JG and Cohen, JD and MacDonald, AW and Cho, RY and Stenger, VA and Carter, CS},
      title = {Anterior Cingulate conflict monitoring and adjustments in control},
      journal = {SCIENCE},
      year = {2004},
      volume = {303},
      number = {5660},
      pages = {1023-1026}
    }
    
    Kiehl, K., Liddle, P. & Hopfinger, J. Error processing and the rostral anterior cingulate: An event-related fMRI study {2000} PSYCHOPHYSIOLOGY
    Vol. {37}({2}), pp. {216-223} 
    article  
    Abstract: The anterior cingulate is believed to play a crucial role in the regulation of thought and action. Recent evidence suggests that the anterior cingulate may play a role in the detection of inappropriate responses. We used event-related functional magnetic resonance imaging techniques to examine the neural responses to appropriate (correct rejects and correct hits) and inappropriate (errors of commission) behavioral responses during a go/no-go task Analyses of the inappropriate responses revealed extensive activation in the rostral anterior cingulate cortex and in the left lateral frontal cortex. These areas were not activated for correctly classified trials (correct rejects and correct hits). These data suggest that the rostral anterior cingulate and left lateral frontal cortex are integral components of the brain's error checking system.
    BibTeX:
    @article{Kiehl2000,
      author = {Kiehl, KA and Liddle, PF and Hopfinger, JB},
      title = {Error processing and the rostral anterior cingulate: An event-related fMRI study},
      journal = {PSYCHOPHYSIOLOGY},
      year = {2000},
      volume = {37},
      number = {2},
      pages = {216-223}
    }
    
    Killiany, R., Gomez-Isla, T., Moss, M., Kikinis, R., Sandor, T., Jolesz, F., Tanzi, R., Jones, K., Hyman, B. & Albert, M. Use of structural magnetic resonance imaging to predict who will get Alzheimer's disease {2000} ANNALS OF NEUROLOGY
    Vol. {47}({4}), pp. {430-439} 
    article  
    Abstract: We used magnetic resonance imaging (MRI) measurements to determine whether persons in the prodromal phase of Alzheimer's disease (AD) could be accurately identified before they developed clinically diagnosed dementia. Normal subjects (n = 24) and those with mild memory difficulty (n = 79) received an MRI scan at baseline and were then followed annually for 3 pears to determine which individuals subsequently met clinical criteria for AD. Patients with mild AD at baseline were also evaluated (n = 16). Nineteen of the 79 subjects with mild memory difficulty ``converted'' to a diagnosis of probable AD after 3 years of follow-up. Baseline MRI measures of the entorhinal cortex, the banks of the superior temporal sulcus, and the anterior cingulate were most useful in discriminating the status of the subjects on follow-up examination. The accuracy of discrimination was related to the clinical similarity between groups. One hundred percent (100 of normal subjects and patients with mild AD could be discriminated from one another based on these MRT measures. When the normals were compared with the individuals with memory impairments who ultimately developed AD (the converters), the accuracy of discrimination was 93 based on the MRI measures at baseline (sensitivity = 0.95; specificity = 0.90). The discrimination of the normal subjects and the individuals with mild memory problems who did not progress to the point where they met clinical criteria for probable AD over the 3 years of follow-up (the ``questionables'') was 85% and the discrimination of the questionables and converters was 75 The apolipoprotein E genotype did not improve the accuracy of discrimination. The specific regions selected for each of these discriminations provides information concerning the hierarchical fashion in which the pathology of AD may affect the brain during its prodromal phase.
    BibTeX:
    @article{Killiany2000,
      author = {Killiany, RJ and Gomez-Isla, T and Moss, M and Kikinis, R and Sandor, T and Jolesz, F and Tanzi, R and Jones, K and Hyman, BT and Albert, MS},
      title = {Use of structural magnetic resonance imaging to predict who will get Alzheimer's disease},
      journal = {ANNALS OF NEUROLOGY},
      year = {2000},
      volume = {47},
      number = {4},
      pages = {430-439}
    }
    
    Kilts, C., Schweitzer, J., Quinn, C., Gross, R., Faber, T., Muhammad, F., Ely, T., Hoffman, J. & Drexler, K. Neural activity related to drug craving in cocaine addiction {2001} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {58}({4}), pp. {334-341} 
    article  
    Abstract: Background: Crack cocaine dependence and addiction is typically associated with frequent and intense drug wanting or craving triggered by internal or environmental cues associated with past drug use. Methods: Water O 15 positron emission tomography (PET) studies were used to localize alterations in synaptic activity related to cue-induced drug craving in 8 crack cocaine-dependent African American men. In a novel approach, script-guided imagery of autobiographical memories were used as individualized cues to internally generate a cocaine craving state and 2 control (ie, anger and neutral episodic memory recall) states during PET image acquisition. Results: The mental imagery of personalized drug use and anger-related scripts was associated with self-ratings of robust drug craving or anger, and comparable alterations in heart rate. Compared with the neutral imagery control condition, imagery-induced drug craving was associated with bilateral (right hemisphere amygdala activation greater than left) activation of the amygdala, the left insula and anterior cingulate gyrus, and the right subcallosal gyrus and nucleus accumbens area. Compared with the anger control condition, internally generated drug craving was associated with bilateral activation of the insula and subcallosal cortex, left hippocampus, and anterior cingulate cortex and brainstem. A brain-wide pixel-by-pixel search indicated significant positive and negative correlations between imagery-induced cocaine craving and regional cerebral blood flow (rCBF) in distributed sites. Conclusions: The collected findings suggest the craving-related activation of a network of limbic, paralimbic, and striatal brain regions, including structures involved in stimulus-reward association (amygdala), incentive motivation (subcallosal gyrus/nucleus accumbens), and anticipation (anterior cingulate cortex).
    BibTeX:
    @article{Kilts2001,
      author = {Kilts, CD and Schweitzer, JB and Quinn, CK and Gross, RE and Faber, TL and Muhammad, F and Ely, TD and Hoffman, JM and Drexler, KPG},
      title = {Neural activity related to drug craving in cocaine addiction},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {2001},
      volume = {58},
      number = {4},
      pages = {334-341}
    }
    
    Kim, Y., Gitelman, D., Nobre, A., Parrish, T., LaBar, K. & Mesulam, M. The large-scale neural network for spatial attention displays multifunctional overlap but differential asymmetry {1999} NEUROIMAGE
    Vol. {9}({3}), pp. {269-277} 
    article  
    Abstract: Functional magnetic resonance imaging (fMRI) was used to determine the brain regions activated by two types of covert visuospatial attentional shifts: one based on exogenous spatial priming and the other on foveally presented cues which endogenously regulated the direction of spatial expectancy. Activations were seen in the cortical and subcortical components of a previously characterized attentional network, namely, the frontal eye fields, posterior parietal cortex, the cingulate gyrus, the putamen, and the thalamus, Additional activations occurred in the anterior insula, dorsolateral prefrontal cortex, temporo-occipital cortex in the middle and inferior temporal gyri, the supplementary motor area, and the cerebellum. Direct comparisons showed a nearly complete overlap in the location of activations resulting from the two tasks. However, the spatial priming task displayed a more pronounced rightward asymmetry of parietal activation, and a conjunction analysis showed that the area of posterior parietal cortex jointly activated by both tasks was more extensive in the right hemisphere. Furthermore, the posterior parietal and temporo-occipital activations were more pronounced in the task of endogenous attentional shifts. The results show that both exogenous (based on spatial priming) and endogenous (based on expectancy cueing) shifts of attention are subserved by a common network of cortical and subcortical regions. However, the differences between the two tasks, especially in the degree of rightward asymmetry, suggests that the pattern of activation within this network may show variations that reflect the specific attributes of the attentional task. (C) 1999 Academic Press.
    BibTeX:
    @article{Kim1999,
      author = {Kim, YH and Gitelman, DR and Nobre, AC and Parrish, TB and LaBar, KS and Mesulam, MM},
      title = {The large-scale neural network for spatial attention displays multifunctional overlap but differential asymmetry},
      journal = {NEUROIMAGE},
      year = {1999},
      volume = {9},
      number = {3},
      pages = {269-277}
    }
    
    Knutson, B., Fong, G., Bennett, S., Adams, C. & Homme, D. A region of mesial prefrontal cortex tracks monetarily rewarding outcomes: characterization with rapid event-related fMRI {2003} NEUROIMAGE
    Vol. {18}({2}), pp. {263-272} 
    article DOI  
    Abstract: The function of the mesial prefrontal cortex (MPFC: including Brodman areas 10/12/32) remains an enigma. Current theories suggest a role in representing internal information, including emotional introspection, autonomic control, and a ``default state'' of semantic processing. Recent evidence also suggests that parts of this region may also play a role in processing reward outcomes. In this study, we investigated the possibility that a region of the MPFC would be preferentially recruited by monetary reward outcomes using a parametric monetary incentive delay (MID) task. Twelve healthy volunteers participated in functional magnetic resonance scans while playing the MID task. Group analyses indicated that while the ventral striatum was recruited by anticipation of monetary reward, a region of the MPFC, instead responded to rewarding monetary outcomes. Specifically, volume-of-interest analyses indicated that when volunteers received 5.00 after anticipating a 5.00 win, MPFC activity increased, whereas when volunteers did not receive 5.00 after anticipating a 5.00 win, MPFC activity decreased, relative to outcomes with no incentive value. These findings suggest that in the context of processing monetary rewards, a region of the MPFC preferentially tracks rewarding outcomes. (C) 2003 Elsevier Science (USA). All rights reserved.
    BibTeX:
    @article{Knutson2003,
      author = {Knutson, B and Fong, GW and Bennett, SM and Adams, CM and Homme, D},
      title = {A region of mesial prefrontal cortex tracks monetarily rewarding outcomes: characterization with rapid event-related fMRI},
      journal = {NEUROIMAGE},
      year = {2003},
      volume = {18},
      number = {2},
      pages = {263-272},
      doi = {{10.1016/S1053-8119(02)00057-5}}
    }
    
    Knutson, B., Westdorp, A., Kaiser, E. & Hommer, D. FMRI visualization of brain activity during a monetary incentive delay task {2000} NEUROIMAGE
    Vol. {12}({1}), pp. {20-27} 
    article  
    Abstract: Comparative studies have implicated striatal and mesial forebrain circuitry in the generation of autonomic, endocrine, and behavioral responses for incentives. Using blood oxygen level-dependent functional magnetic resonance imaging, we sought to visualize functional activation of these regions in 12 normal volunteers as they anticipated and responded for monetary incentives. Both individual and group analyses of time-series data revealed significant activation of striatal and mesial forebrain structures (including insula, caudate, putamen, and mesial prefrontal cortex) during trials involving both monetary rewards and punishments. In addition to these areas, during trials involving punishment, group analysis revealed activation foci in the anterior cingulate and thalamus. These results corroborate comparative studies which implicate striatal and mesial forebrain circuitry in the elaboration of incentive-driven behavior. This report also introduces a new paradigm for probing the functional integrity of this circuitry in humans.
    BibTeX:
    @article{Knutson2000,
      author = {Knutson, B and Westdorp, A and Kaiser, E and Hommer, D},
      title = {FMRI visualization of brain activity during a monetary incentive delay task},
      journal = {NEUROIMAGE},
      year = {2000},
      volume = {12},
      number = {1},
      pages = {20-27}
    }
    
    Kogure, D., Matsuda, H., Ohnishi, T., Asada, T., Uno, M., Kunihiro, T., Nakano, S. & Takasaki, M. Longitudinal evaluation of early Alzheimer's disease using brain perfusion SPECT {2000} JOURNAL OF NUCLEAR MEDICINE
    Vol. {41}({7}), pp. {1155-1162} 
    article  
    Abstract: The aim of this SPECT study was to determine the initial abnormality and longitudinal changes in regional cerebral blood flow (rCBF) in early Alzheimer's disease (AD) using statistical parametric mapping (SPM). Methods: rCBF was noninvasively measured using Tc-99m-ethyl cysteinate dimer SPECT in 32 patients complaining of mild cognitive impairment, with a Mini-Mental State Examination score more than 24 at the initial study, and 45 age-matched healthy volunteers. All patients satisfied the diagnostic criteria of AD during the follow-up period of at least 2 y. Follow-up SPECT studies were performed on the patients at a mean interval of 15 mo. We used the raw data (absolute rCBF parametric maps) and the adjusted rCBF images of relative flow distribution (normalization of global cerebral blood flow [CBF] for each subject to 50 mL/100 g/min with proportional scaling) to compare these groups with SPM. Results: In the baseline study, the adjusted rCBF was significantly and bilaterally decreased in the posterior cingulate gyri and precunei of patients compared with healthy volunteers. in the follow-up study, selected reduction of the adjusted rCBF was observed in the left hippocampus and parahippocampal gyrus. These areas showed the most prominent reduction in absolute rCBF on each occasion. Moreover, further decline of the absolute rCBF was longitudinally observed in extensive areas of the cerebral association cortex. Conclusion: SPM analysis showed the characteristic early-AD rCBF pattern of selective decrease and longitudinal decline, which may be overlooked by a conventional region-of-interest technique with observer a priori choice and hypothesis. This alteration in rCBF may closely relate to the pathophysiologic process of this disease.
    BibTeX:
    @article{Kogure2000,
      author = {Kogure, D and Matsuda, H and Ohnishi, T and Asada, T and Uno, M and Kunihiro, T and Nakano, S and Takasaki, M},
      title = {Longitudinal evaluation of early Alzheimer's disease using brain perfusion SPECT},
      journal = {JOURNAL OF NUCLEAR MEDICINE},
      year = {2000},
      volume = {41},
      number = {7},
      pages = {1155-1162}
    }
    
    KOVES, K., ARIMURA, A., GORCS, T. & SOMOGYVARIVIGH, A. COMPARATIVE DISTRIBUTION OF IMMUNOREACTIVE PITUITARY ADENYLATE-CYCLASE ACTIVATING POLYPEPTIDE AND VASOACTIVE INTESTINAL POLYPEPTIDE IN RAT FOREBRAIN {1991} NEUROENDOCRINOLOGY
    Vol. {54}({2}), pp. {159-169} 
    article  
    Abstract: Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are structurally similar, share the same high affinity site in same peripheral tissues and increase the intracellular content of adenylate cyclase. To establish which neural circuits are signaling with each of these two peptides, we systematically compared the immunohistochemical distribution of PACAP and VIP in selected rat forebrain regions using previously characterized antiserum. The PACAP antiserum recognized both PACAP27 and PACAP38, and PACAP immunoreactivity was unaffected by preincubation with various other peptides. PACAP-immunoreactive perikarya and fibers were observed in both hypothalamic and extrahypothalamic regions. In the hypothalamus PACAP perikarya were located in the supraoptic, paraventricular, anterior commissural, periventricular, and perifornical nuclei. In intact rats PACAP immunolabeled fibers were present in the internal zone of the median eminence and posterior pituitary. One week after hypophysectomy the intensity of staining in the internal zone was enhanced and immunoreactive fibers appeared in the external zone of the median eminence. Two or 3 weeks later a dense fiber network was observed around the portal capillaries in the external zone, and immunoreactive material further accumulated in the fibers of the internal zone. PACAP-immunoreactive perikarya and fibers were also observed in several extrahypothalamic regions including central thalamic nuclei, amygdaloid complex, bed nucleus of stria terminalis, septum, hippocampus and cingulate, and entorhinal cortices. In the lateral septum and entorhinal cortex PACAP fibers surrounded unstained neuronal cell bodies and small blood vessels. In intact rats, VIP-immunoreactive perikarya were present in all regions of the cerebral cortex, hippocampus, amygdaloid complexus and in the suprachiasmatic nucleus, but not in the paraventricular and supraoptic nuclei. In colchicine-treated rats the VIP perikarya appeared in the preoptic area and paraventricular nucleus. The fibers were organized in two main pathways: the stria terminalis and an ascending pathway from the suprachiasmatic nucleus to the paraventricular area. Hypophysectomy induced the appearance of VIP-immunoreactive fibers in the internal zone of the median eminence and perikarya in the supraoptic and paraventricular nuclei in addition to the suprachiasmatic nucleus. The dissimilar distributions of PACAP and VIP suggest that PACAP neural circuits are independent of that of VIP in the rat forebrain. These findings support possible multifunctional roles for PACAP as a posterior pituitary hormone, a hypophysiotrophic factor, and a neurotransmitter/neuromodulator.
    BibTeX:
    @article{KOVES1991,
      author = {KOVES, K and ARIMURA, A and GORCS, TG and SOMOGYVARIVIGH, A},
      title = {COMPARATIVE DISTRIBUTION OF IMMUNOREACTIVE PITUITARY ADENYLATE-CYCLASE ACTIVATING POLYPEPTIDE AND VASOACTIVE INTESTINAL POLYPEPTIDE IN RAT FOREBRAIN},
      journal = {NEUROENDOCRINOLOGY},
      year = {1991},
      volume = {54},
      number = {2},
      pages = {159-169}
    }
    
    Krams, M., Rushworth, M., Deiber, M., Frackowiak, R. & Passingham, R. The preparation, execution and suppression of copied movements in the human brain {1998} EXPERIMENTAL BRAIN RESEARCH
    Vol. {120}({3}), pp. {386-398} 
    article  
    Abstract: We used positron emission tomography (PET) to measure movement set-related changes in regional cerebral blood flow (rCBF) when human subjects were asked to copy hand movements. Movement set-related activity in the brain is thought to reflect the processes of movement selection, preparation and inhibition. Four conditions were used. In the first condition, prepare and execute (PE), the hand stimulus to be copied was shown to subjects 3 a before an auditory ``go''-cue instructed subjects to execute the movement, a large part of the scanning time was therefore spent in preparing to move. In the immediate execution condition (E), the hand stimulus and the go cue were presented simultaneously. The prepare-only condition (P) was similar to PE, except subjects only prepared to make the movement and did not actually execute any movement when they heard the auditory go-cue. The same stimuli were presented in a baseline condition (B), but the subjects were instructed to neither prepare nor execute movements. There were 5 principle findings: (1) In contrast to a previous study of human set-related activity in which movements were instructed by an arbitrary pattern of LEDs, preparing to make a copied movement causes rCBF changes in area 44 in posterior Broca's area; (2) set-related activity can be recorded in the cerebellar hemispheres and midline; (3) we confirmed that the supramarginal gyrus has a general role in preparing movements - there was more rCBF in the P than the E condition; (4) the cerebellar nuclei and the basal ganglia may be particularly involved in the initiation and execution of a planned movement; these regions were more active in the PE condition than the P condition; (5) the ventrolateral prefrontal cortex and a left anterior cingulate area are part of a distributed system involved in the suppression of a motor response; these areas were significantly more active in the P than the PE condition.
    BibTeX:
    @article{Krams1998,
      author = {Krams, M and Rushworth, MFS and Deiber, MP and Frackowiak, RSJ and Passingham, RE},
      title = {The preparation, execution and suppression of copied movements in the human brain},
      journal = {EXPERIMENTAL BRAIN RESEARCH},
      year = {1998},
      volume = {120},
      number = {3},
      pages = {386-398}
    }
    
    LAHTI, A., HOLCOMB, H., MEDOFF, D. & TAMMINGA, C. KETAMINE ACTIVATES PSYCHOSIS AND ALTERS LIMBIC BLOOD-FLOW IN SCHIZOPHRENIA {1995} NEUROREPORT
    Vol. {6}({6}), pp. {869-872} 
    article  
    Abstract: THE non-competitive NMDA antagonist ketamine, given to schizophrenic individuals in subanesthetic doses, produced a short-lived, discrete activation of their psychotic symptoms, which had striking similarities to symptoms of their usual psychotic episodes. To further study this Psychotomimetic property of ketamine, we administered 0.3 mg kg(-1) of the drug to schizophrenic individuals during a [O-15] water cerebral blood flow study. Regional cerebral blood flow (rCBF) was measured using (H2O)-O-15 and positron emission tomography (PET) before and after ketamine administration to identify regions of flow change. rCBF was increased in anterior cingulate cortex and was reduced in the hippocampus and primary visual cortex (lingual and fusiform gyri). These data encourage further consideration of altered glutamatergic transmission in schizophrenic and PCP-induced psychoses.
    BibTeX:
    @article{LAHTI1995,
      author = {LAHTI, AC and HOLCOMB, HH and MEDOFF, DR and TAMMINGA, CA},
      title = {KETAMINE ACTIVATES PSYCHOSIS AND ALTERS LIMBIC BLOOD-FLOW IN SCHIZOPHRENIA},
      journal = {NEUROREPORT},
      year = {1995},
      volume = {6},
      number = {6},
      pages = {869-872}
    }
    
    Lane, R., Fink, G., Chau, P. & Dolan, R. Neural activation during selective attention to subjective emotional responses {1997} NEUROREPORT
    Vol. {8}({18}), pp. {3969-3972} 
    article  
    Abstract: WE examined neural activity associated with selectively attending to subjective emotional responses in a study where subjects viewed emotional picture sets. During picture viewing when subjects attended to their subjective emotional responses, highly significant increased neural activity was elicited in rostral anterior cingulate (BA 32) (Z = 6.87, p < 0.001, corrected). By contrast, under the same stimulus conditions when subjects attended to spatial aspects of identical picture sets activation was observed in the parieto-occipital cortex bilaterally (Z = 5.71, P < 0.001, corrected). The findings indicated a specific role for the anterior cingulate cortex in representing subjective emotional responses and are consistent with a suggested role for associated medial prefrontal structures in representing states of mind.
    BibTeX:
    @article{Lane1997,
      author = {Lane, RD and Fink, GR and Chau, PML and Dolan, RJ},
      title = {Neural activation during selective attention to subjective emotional responses},
      journal = {NEUROREPORT},
      year = {1997},
      volume = {8},
      number = {18},
      pages = {3969-3972}
    }
    
    Lane, R., Reiman, E., Axelrod, B., Yun, L., Holmes, A. & Schwartz, G. Neural correlates of levels of emotional awareness: Evidence of an interaction between emotion and attention in the anterior cingulate cortex {1998} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {10}({4}), pp. {525-535} 
    article  
    Abstract: Recent functional imaging studies have begun to identify the neural correlates of emotion in healthy volunteers. However, studies to date have not differentially addressed the brain areas associated with the perception, experience, or expression of emotion during emotional arousal. To explore the neural correlates of emotional experience, we used positron emission tomography (PET) and O-15-water to measure cerebral blood flow (CBF) in 12 healthy women during film and recall-induced emotion and correlated CBF changes attributable to emotion with subjects' scores on the Levels of Emotional Awareness Scale (LEAS), a measure of individual differences in the capacity to experience emotion in a differentiated and complex way. A conjunction analysis revealed that the correlations between LEAS and CBF during film and recall-induced emotion overlapped significantly (z = 3.74, p < 0.001) in Brodmann's area 24 of the anterior cingulate cortex (ACC). This finding suggests that individual differences in the ability to accurately detect emotional signals interoceptively or exteroceptively may at least in part be a function of the degree to which the ACC participates in the experiential processing and response to emotion cues. To the extent that this finding is consistent with the functions of the ACC involving attention and response selection, it suggests that this neural correlate of conscious emotional experience is not exclusive to emotion.
    BibTeX:
    @article{Lane1998,
      author = {Lane, RD and Reiman, EM and Axelrod, B and Yun, LS and Holmes, A and Schwartz, GE},
      title = {Neural correlates of levels of emotional awareness: Evidence of an interaction between emotion and attention in the anterior cingulate cortex},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {1998},
      volume = {10},
      number = {4},
      pages = {525-535}
    }
    
    Lepage, M., Ghaffar, O., Nyberg, L. & Tulving, E. Prefrontal cortex and episodic memory retrieval mode {2000} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {97}({1}), pp. {506-511} 
    article  
    Abstract: A multistudy analysis of positron emission tomography data identified three right prefrontal and two left prefrontal cortical sites, as well as a region in the anterior cingulate gyrus, where neuronal activity is correlated with the maintenance of episodic memory retrieval mode (REMO), a basic and necessary condition of remembering past experiences. The right prefrontal sites were near the frontal pole [Brodmann's area (BA) 10], frontal operculum (BA 47/45), and lateral dorsal area (BA 8/9). The two left prefrontal sites were homotopical with the right frontal pole and opercular sites. The same kinds of REMO sites were not observed in any other cerebral region. Many previous functional neuroimaging studies of episodic memory retrieval have reported activations near the frontal REMO sites identified here, although their function has not been clear. Many of these, too, probably have signaled their involvement in REMO, We propose that REMO activations largely if not entirety account for the frontal hemispheric asymmetry of retrieval as described by the original hemispheric encoding retrieval asymmetry model.
    BibTeX:
    @article{Lepage2000,
      author = {Lepage, M and Ghaffar, O and Nyberg, L and Tulving, E},
      title = {Prefrontal cortex and episodic memory retrieval mode},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {2000},
      volume = {97},
      number = {1},
      pages = {506-511}
    }
    
    Levesque, J., Eugene, F., Joanette, Y., Paquette, V., Mensour, B., Beaudoin, G., Leroux, J., Bourgouin, P. & Beauregard, M. Neural circuitry underlying voluntary suppression of sadness {2003} BIOLOGICAL PSYCHIATRY
    Vol. {53}({6}), pp. {502-510} 
    article DOI  
    Abstract: Background: The ability to voluntarily self-regulate negative emotion is essential to a healthy psyche. Indeed, a chronic incapacity to suppress negative emotion might be a key factor in the genesis of depression and anxiety. Regarding the neural underpinnings of emotional self-regulation, a recent functional neuroimaging study carried out by our group has revealed that the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex are involved in voluntary suppression of sexual arousal. As few things are known, still, with respect to the neural substrate underlying volitional self-regulation of basic emotions, here we used functional magnetic resonance imaging to identify the neural circuitry associated with the voluntary suppression of sadness. Methods: Twenty healthy female subjects were scanned during a Sad condition and a Suppression condition. In the Sad condition, subjects were instructed to react normally to sad film excerpts whereas, in the Suppression condition, they were asked to voluntarily suppress any emotional reaction in response to comparable stimuli. Results: Transient sadness was associated with significant loci of activation in the anterior temporal pole and the midbrain, bilaterally, as well as in the left amygdala, left insula, and right ventrolateral prefrontal cortex (VLPFC) (Brodmann area [BA] 47). Correlational analyses carried out between self-report ratings of sadness and regional blood oxygen level dependent (BOLD) signal changes revealed the existence of positive correlations in the right VLPFC (BA 47), bilaterally, as well as in the left insula and the affective division of the left anterior cingulate gyrus (BA 24/32). In the Suppression condition, significant loci of activation were noted in the right DLPFC (BA 9) and the right orbitofrontal cortex (OFC) (BA 11), and positive correlations were found between the self-report ratings of sadness and BOLD signal changes in the right OFC (BA 11) and right DLPFC (BA 9). Conclusions: These results confirm the key role played by the DLPFC in emotional self-regulation. They also indicate that the right DLPFC and right OFC are components of a neural circuit implicated in voluntary suppression of sadness. (C) 2003 Society of Biological Psychiatry.
    BibTeX:
    @article{Levesque2003,
      author = {Levesque, J and Eugene, F and Joanette, Y and Paquette, V and Mensour, B and Beaudoin, G and Leroux, JM and Bourgouin, P and Beauregard, M},
      title = {Neural circuitry underlying voluntary suppression of sadness},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {2003},
      volume = {53},
      number = {6},
      pages = {502-510},
      doi = {{10.1016/S0002-3223(03)01817-6}}
    }
    
    Levitt, P., Harvey, J., Friedman, E., Simansky, K. & Murphy, E. New evidence for neurotransmitter influences on brain development {1997} TRENDS IN NEUROSCIENCES
    Vol. {20}({6}), pp. {269-274} 
    article  
    Abstract: The early appearance of monoamine systems in the developing mammalian CNS suggests that they play a role in neural development. We review data from two model systems that provide compelling new evidence of this role. In one model system - in utero exposure to cocaine - specific and robust alterations are seen in dopamine-rich areas of the cerebral cortex, such as the anterior cingulate cortex: D-1 receptor-G protein coupling is greatly reduced, the GABAergic system is altered and pyramidal dendrites undergo excessive growth. In a second model system - a transgenic mouse line in which the gene that encodes monoamine oxidase A (MAOA) is disrupted, resulting in excessively high 5-HT levels - barrels fail to form in the developing somatosensory cortex. Both models reveal the effects of very early manipulation of monoamines on forebrain development, and the long-term anomalies that persist into adulthood.
    BibTeX:
    @article{Levitt1997,
      author = {Levitt, P and Harvey, JA and Friedman, E and Simansky, K and Murphy, EH},
      title = {New evidence for neurotransmitter influences on brain development},
      journal = {TRENDS IN NEUROSCIENCES},
      year = {1997},
      volume = {20},
      number = {6},
      pages = {269-274}
    }
    
    Lewis, D., Hashimoto, T. & Volk, D. Cortical inhibitory neurons and schizophrenia {2005} NATURE REVIEWS NEUROSCIENCE
    Vol. {6}({4}), pp. {312-324} 
    article DOI  
    Abstract: Impairments in certain cognitive functions, such as working memory, are core features of schizophrenia. Convergent findings indicate that a deficiency in signalling through the TrkB neurotrophin receptor leads to reduced GABA (gamma-aminobutyric acid) synthesis in the parvalbumin-containing subpopulation of inhibitory GABA neurons in the dorsolateral prefrontal cortex of individuals with schizophrenia. Despite both pre- and postsynaptic compensatory responses, the resulting alteration in perisomatic inhibition of pyramidal neurons contributes to a diminished capacity for the gamma-frequency synchronized neuronal activity that is required for working memory function. These findings reveal specific targets for therapeutic interventions to improve cognitive function in individuals with schizophrenia.
    BibTeX:
    @article{Lewis2005,
      author = {Lewis, DA and Hashimoto, T and Volk, DW},
      title = {Cortical inhibitory neurons and schizophrenia},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2005},
      volume = {6},
      number = {4},
      pages = {312-324},
      doi = {{10.1038/nrn1648}}
    }
    
    Liberzon, I., Taylor, S., Amdur, R., Jung, T., Chamberlain, K., Minoshima, S., Koeppe, R. & Fig, L. Brain activation in PTSD in response to trauma-related stimuli {1999} BIOLOGICAL PSYCHIATRY
    Vol. {45}({7}), pp. {817-826} 
    article  
    Abstract: Background: Repetitive recall of traumatic memories and chronic intermittent hyperarousal are characteristic of posttraumatic stress disorder (PTSD). Hyperarousal and memory dysfunction implicates ``limbic'' brain regions, including the amygdaloid complex, hippocampal formation, and limbic cortex, such as the orbitofrontal and anterior cingulate areas. To investigate the neurobiologic role of these brain regions in PTSD, we measured regional cerebral blood flow in PTSD with single photon emission computerized tomography (SPECT) during a symptom provocation paradigm. Methods: Fourteen Vietnam veterans with PTSD, 11 combat control subjects, and 14 normal control subjects were studied with [Tc-99m] HMPAO in two sessions 48 hours apart: one session after exposure to white noise and the other following exposure to combat sounds. Skin conductance, heart rate, and subjective experience were recorded at the time of the studies. Results: Activation for all three groups occurred in the anterior cingulate/middle prefrontal gyrus. Activation in the region of the left amygdala/nucleus accumbens was found in PTSD patients only. Deactivation was found in all three groups in the left retrosplenial region. Conclusions: These findings implicate regions of the ``limbic'' brain, which may mediate the response to aversive stimuli in healthy individuals and in patients suffering from PTSD. (C) 1999 Society of Biological Psychiatry.
    BibTeX:
    @article{Liberzon1999,
      author = {Liberzon, I and Taylor, SF and Amdur, R and Jung, TD and Chamberlain, KR and Minoshima, S and Koeppe, RA and Fig, LM},
      title = {Brain activation in PTSD in response to trauma-related stimuli},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {1999},
      volume = {45},
      number = {7},
      pages = {817-826}
    }
    
    Liddle, P., Kiehl, K. & Smith, A. Event-related fMRI study of response inhibition {2001} HUMAN BRAIN MAPPING
    Vol. {12}({2}), pp. {100-109} 
    article  
    Abstract: Event-related functional magnetic resonance imaging (erfMRI) was employed to measure the hemodynamic response during a Go/No-go task in 16 healthy subjects. The task was designed so that Go and No-go events were equally probable, allowing an unbiased comparison of cerebral activity during these two types of trials. Zn accordance with prediction, anterior cingulate was active during both the Go and No-go trials, dorsolateral and ventrolateral prefrontal cortex was more active during the No-go trials, while primary motor cortex, supplementary motor area, pre-motor cortex and cerebellum were more active during Go trials. These findings are consistent with the hypothesis that the anterior cingulate cortex is principally engaged in making and monitoring of decisions, while dorsolateral and ventral lateral prefrontal sites play a specific role in response inhibition. (C) 2001 Wiley-Liss, Inc.
    BibTeX:
    @article{Liddle2001,
      author = {Liddle, PF and Kiehl, KA and Smith, AM},
      title = {Event-related fMRI study of response inhibition},
      journal = {HUMAN BRAIN MAPPING},
      year = {2001},
      volume = {12},
      number = {2},
      pages = {100-109}
    }
    
    LIM, S., DINNER, D., PILLAY, P., LUDERS, H., MORRIS, H., KLEM, G., WYLLIE, E. & AWAD, I. FUNCTIONAL-ANATOMY OF THE HUMAN SUPPLEMENTARY SENSORIMOTOR AREA - RESULTS OF EXTRAOPERATIVE ELECTRICAL-STIMULATION {1994} ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
    Vol. {91}({3}), pp. {179-193} 
    article  
    Abstract: Electrical stimulation studies have demonstrated that a `'supplementary motor area'' (SMA) exists in humans. However, its precise functional organization has not been well defined. We reviewed the extraoperative electrical stimulation studies of 15 patients with intractable epilepsy who were evaluated with chronically implanted interhemispheric subdural electrodes. SMA-type positive motor responses were elicited not only from the mesial portion of the superior frontal gyrus but also from its dorsal convexity, and from the paracentral lobule, cingulate gyrus, and precuneus. Sensory symptoms, that could not be attributed to stimulation of the primary sensory area, were elicited from the superior frontal and cingulate gyri in addition to the precuneus. Therefore, human SMA, as defined by electrical stimulation, is not always confined to the mesial portion of the superior frontal gyrus as described previously. It is also not strictly `'motor'' but `'sensorimotor'' in representation. We propose referring to this region as the `'supplementary sensorimotor area'' (SSMA). We observed a somatotopic organization within the SSMA with an order of lower extremity, upper extremity, and head from posterior to anterior. Sensory representation in an individual was either anterior or posterior to the positive motor representation but never both. There was a supplementary eye field within the head representation. A supplementary negative motor area was noted at the anterior aspect of the SSMA. No language area was demonstrated within the SSMA. The physiologic significance of the SSMA and functional consequences of its resection must be addressed in further studies.
    BibTeX:
    @article{LIM1994,
      author = {LIM, SH and DINNER, DS and PILLAY, PK and LUDERS, H and MORRIS, HH and KLEM, G and WYLLIE, E and AWAD, IA},
      title = {FUNCTIONAL-ANATOMY OF THE HUMAN SUPPLEMENTARY SENSORIMOTOR AREA - RESULTS OF EXTRAOPERATIVE ELECTRICAL-STIMULATION},
      journal = {ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY},
      year = {1994},
      volume = {91},
      number = {3},
      pages = {179-193}
    }
    
    Limousin, P., Greene, J., Pollak, P., Rothwell, J., Benabid, A. & Frackowiak, R. Changes in cerebral activity pattern due to subthalamic nucleus or internal pallidum stimulation in Parkinson's disease {1997} ANNALS OF NEUROLOGY
    Vol. {42}({3}), pp. {283-291} 
    article  
    Abstract: High-frequency electrical stimulation of the internal pallidum (GPi) or the subthalamic nucleus (STN) improves clinical symptoms of Parkinson's disease. In 12 parkinsonian patients, G with STN and G with GPi stimulators, we used (H2O)-O-15 positron emission tomography to evaluate whether changes in movement performance were accompanied by change in regional cerebral blood flow (rCBF). Patients were scanned both at rest and while performing a free-choice joystick movement, under conditions of effective and ineffective electrostimulation. During effective STN stimulation, movement-related increases in rCBF were significantly higher in supplementary motor area, cingulate cortex, and dorsolateral prefrontal cortex (DLPFC) than during ineffective stimulation. No significant change was observed in any of these areas during GPi stimulation. The difference between the effect of STN and GPi stimulation on movement-related activity was mainly localized to DLPFC. These results confirm the dominant role of nonprimary motor areas in the control of movement in parkinsonian patients and demonstrate the importance of STN input in the control of these areas.
    BibTeX:
    @article{Limousin1997,
      author = {Limousin, P and Greene, J and Pollak, P and Rothwell, J and Benabid, AL and Frackowiak, R},
      title = {Changes in cerebral activity pattern due to subthalamic nucleus or internal pallidum stimulation in Parkinson's disease},
      journal = {ANNALS OF NEUROLOGY},
      year = {1997},
      volume = {42},
      number = {3},
      pages = {283-291}
    }
    
    Linden, D., Prvulovic, D., Formisano, E., Vollinger, M., Zanella, F., Goebel, R. & Dierks, T. The functional neuroanatomy of target detection: An fMRI study of visual and auditory oddball tasks {1999} CEREBRAL CORTEX
    Vol. {9}({8}), pp. {815-823} 
    article  
    Abstract: The neuronal response patterns that are required for an adequate behavioural reaction to subjectively relevant changes in the environment are commonly studied by means of oddball paradigms, in which occasional `target' stimuli have to be detected in a train of frequent `non-target' stimuli. The detection of such task-relevant stimuli is accompanied by a parietocentral positive component of the event-related potential, the P300. We performed EEG recordings of visual and auditory event-related potentials and functional magnetic resonance imaging (fMRI) when healthy subjects performed an oddball task. Significant increases in fMRI signal for target versus non-target conditions were observed in the supramarginal gyrus, frontal operculum and insular cortex bilaterally, and in further circumscribed parietal and frontal regions. These effects were consistent over various stimulation and response modalities and can be regarded as specific for target detection in both the auditory and the visual modality. These results therefore contribute to the understanding of the target detection network in human cerebral cortex and impose constraints on attempts at localizing the neuronal P300 generator. This is of importance both from a neurobiological perspective and because of the widespread application of the physiological correlates of target detection in clinical P300 studies.
    BibTeX:
    @article{Linden1999,
      author = {Linden, DEJ and Prvulovic, D and Formisano, E and Vollinger, M and Zanella, FE and Goebel, R and Dierks, T},
      title = {The functional neuroanatomy of target detection: An fMRI study of visual and auditory oddball tasks},
      journal = {CEREBRAL CORTEX},
      year = {1999},
      volume = {9},
      number = {8},
      pages = {815-823}
    }
    
    Liotti, M., Mayberg, H., Brannan, S., McGinnis, S., Jerabek, P. & Fox, P. Differential limbic-cortical correlates of sadness and anxiety in healthy subjects: Implications for affective disorders {2000} BIOLOGICAL PSYCHIATRY
    Vol. {48}({1}), pp. {30-42} 
    article  
    Abstract: Background: Affective disorders are associated with comorbidity of depression and anxiety symptoms, Positron emission tomography resting-state studies in affective disorders have generally failed to isolate specific symptom effects, Emotion provocation studies in healthy volunteers have produced variable results, due to differences in experimental paradigm and instructions. Methods: To better delineate the neural correlates of sad mood and anxiety, this study used autobiographical memory scripts in eight healthy women to generate sadness, anxiety, or a neutral relaxed state in a within-subject design, Results: Sadness and anxiety, when contrasted to a neutral emotional state, engaged a set of distinct pam-limbic-cortical regions, with a limited number of common effects. Sadness,vas accompanied by specific activations of the subgenual cingulate area (BA) 25 and dorsal insula, specific deactivation of the right prefrontal cortex BA 9, and more prominent deactivation of the posterior parietal cortex BAs 40/7. Anxiety was associated with specific activations of the ventral insula, the orbitofrontal and anterior temporal cortices, specific deactivation of parahippocampal gyri, and more prominent deactivation of the inferior temporal cortex BAs 20/37, Conclusions: These findings are interpreted within a model in which sadness and anxiety are represented by segregated corticolimbic pathways, where a major role is played by selective dorsal cortical deactivations during sadness, and ventral cortical deactivations in anxiety, (C) 2000 Society of Biological Psychiatry.
    BibTeX:
    @article{Liotti2000,
      author = {Liotti, M and Mayberg, HS and Brannan, SK and McGinnis, S and Jerabek, P and Fox, PT},
      title = {Differential limbic-cortical correlates of sadness and anxiety in healthy subjects: Implications for affective disorders},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {2000},
      volume = {48},
      number = {1},
      pages = {30-42}
    }
    
    LU, M., PRESTON, J. & STRICK, P. INTERCONNECTIONS BETWEEN THE PREFRONTAL CORTEX AND THE PREMOTOR AREAS IN THE FRONTAL-LOBE {1994} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {341}({3}), pp. {375-392} 
    article  
    Abstract: We examined interconnections between a portion of the prefrontal cortex and the premotor areas in the frontal lobe to provide insights into the routes by which the prefrontal cortex gains access to the primary motor cortex and the central control of movement. We placed multiple injections of one retrograde tracer in the arm area of the primary motor cortex to define the premotor areas in the frontal lobe. Then, in the same animal, we placed multiple injections of another retrograde tracer in and around the principal sulcus (Walker's area 46). This double labeling strategy enabled us to determine which premotor areas are interconnected with the prefrontal cortex.
    BibTeX:
    @article{LU1994,
      author = {LU, MT and PRESTON, JB and STRICK, PL},
      title = {INTERCONNECTIONS BETWEEN THE PREFRONTAL CORTEX AND THE PREMOTOR AREAS IN THE FRONTAL-LOBE},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {1994},
      volume = {341},
      number = {3},
      pages = {375-392}
    }
    
    LUPPINO, G., MATELLI, M., CAMARDA, R., GALLESE, V. & RIZZOLATTI, G. MULTIPLE REPRESENTATIONS OF BODY MOVEMENTS IN MESIAL AREA-6 AND THE ADJACENT CINGULATE CORTEX - AN INTRACORTICAL MICROSTIMULATION STUDY IN THE MACAQUE MONKEY {1991} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {311}({4}), pp. {463-482} 
    article  
    Abstract: The mesial agranular frontal cortex that lies rostral to area 4 (F1) is formed by two distinct cytoarchitectonic areas: F3, located caudally, and F6, located rostrally. In the present experiments we investigated the organization of F3 and F6 by observing the motor responses evoked by their intracortical electrical microstimulation. Our main purpose was to find out whether the cytoarchitectonic subdivision of the mesial agranular frontal cortex into two areas has a physiological counterpart. The result showed that F3 (the caudal area) contains a complete motor representation with hindlimb movements located caudally, forelimb movements located centrally, and orofacial movements located rostrally. The great majority of limb movements involved proximal joints. With respect to F1, F3 showed the following functional characteristics: (1) lack of segregation between proximal and distal movements, (2) larger percentage of complex movements, and (3) higher excitability threshold. Movements were more difficult to elicit from F6 (the rostral area) than from F3. However, by using a longer stimulus train duration (100 ms) 39.3% of tested sites produced body movements. This percentage increased (50.5 when the electrical stimulation was applied during monkey natural movements instead of when the monkey was still in its chair. Most of the evoked movements concerned the forelimb. More rarely, neck and upper face movements were observed. Unlike F1 and F3 where most movements were fast, slow movements were frequently observed with stimulation of F6. Many of them mimicked natural movements of the animal. Eye movements were evoked from F7 (superior area 6) but not from F6. An additional motor representation was found in the dorsocaudal part of area 24 (24d). This area is topographically organized with a forelimb representation located caudally and ventrally and a hindlimb representation located rostrally and dorsally. The excitability threshold of area 24d is higher than that of F1 and F3. Evoked movements were occasionally observed also after stimulation of area 24c. In conclusion, on the mesial cortical wall rostral to F1, there are at least three independent motor representations. On the basis of somatotopic organization and excitability properties, we propose that the term supplementary motor area (SMA-proper) should be reserved to F3.
    BibTeX:
    @article{LUPPINO1991,
      author = {LUPPINO, G and MATELLI, M and CAMARDA, RM and GALLESE, V and RIZZOLATTI, G},
      title = {MULTIPLE REPRESENTATIONS OF BODY MOVEMENTS IN MESIAL AREA-6 AND THE ADJACENT CINGULATE CORTEX - AN INTRACORTICAL MICROSTIMULATION STUDY IN THE MACAQUE MONKEY},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {1991},
      volume = {311},
      number = {4},
      pages = {463-482}
    }
    
    LUPPINO, G., MATELLI, M., CAMARDA, R. & RIZZOLATTI, G. CORTICOCORTICAL CONNECTIONS OF AREA-F3 (SMA-PROPER) AND AREA F6 (PRE-SMA) IN THE MACAQUE MONKEY {1993} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {338}({1}), pp. {114-140} 
    article  
    Abstract: The monkey mesial area 6 comprises two distinct cytoarchitectonic areas: F3 [supplementary motor area properly defined (SMA-proper)], located caudally, and F6 (pre-SMA), located rostrally. The aim of the present study was to describe the corticocortical connections of these two areas. To this purpose restricted injections of neuronal tracers (wheat germ-agglutinin conjugated to horseradish peroxidase, fluorescent tracers) were made in different somatotopic fields of F3, F6, and F1 (area 4) and their transport plotted. The results showed that F3 and F6 differ markedly in their cortical connections. F3 is richly linked with F1 and the posterior premotor and cingulate areas (F2, F4, 24d). Connections with the anterior premotor and cingulate areas (F6, F7, F5, 24c) although present, are relatively modest. There is no input from the prefrontal lobe. F3 is also connected with several postrolandic cortical areas. These connections are with areas PC, PE, and PEa in the superior parietal lobule, cingulate areas 23 and PEci, the opercular parietal areas (PFop, PGop, SII) and the granular insula. F6 receives a rich input from the anterior premotor areas (especially F5) and cingulate area 24c, whereas its input from the posterior premotor and cingulate areas is very weak. A strong input originates from area 46. There are no connections with F1. The connections with the postrolandic areas are extremely meagre. They are with areas PG and PFG in the inferior parietal lobule, the disgranular insula, and the superior temporal sulcus. A further result was the demonstration of a differential connectivity pattern of the cingulate areas 24d and 24c. Area 24d is strongly linked with F1 and F3, whereas area 24c is connected mostly with F6. The present data support the notion that the classical SMA comprises two functionally distinct areas. They suggest that F6 (the rostral area) is responsible for the `'SMA'' so-called high level motor functions, whereas F3 (the caudal area) is more closely related to movement execution. (C) 1993 Wiley-Liss, Inc.
    BibTeX:
    @article{LUPPINO1993,
      author = {LUPPINO, G and MATELLI, M and CAMARDA, R and RIZZOLATTI, G},
      title = {CORTICOCORTICAL CONNECTIONS OF AREA-F3 (SMA-PROPER) AND AREA F6 (PRE-SMA) IN THE MACAQUE MONKEY},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {1993},
      volume = {338},
      number = {1},
      pages = {114-140}
    }
    
    Luu, P., Collins, P. & Tucker, D. Mood, personality, and self-monitoring: Negative affect and emotionality in relation to frontal lobe mechanisms of error monitoring {2000} JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL
    Vol. {129}({1}), pp. {43-60} 
    article DOI  
    Abstract: A fundamental question in frontal lobe function is how motivational and emotional parameters of behavior apply to executive processes. Recent advances in mood and personality research and the technology and methodology of brain research provide opportunities to address this question empirically. Using event-related-potentials to track error monitoring in real time, the authors demonstrated that variability in the amplitude of the error-related negativity (ERN) is dependent on mood and personality variables. College students who are high on negative affect (NA) and negative emotionality (NEM) displayed larger ERN amplitudes early in the experiment than participants who are low on these dimensions. As the high-NA and -NEM participants disengaged from the task, the amplitude of the ERN decreased. These results reveal that affective distress and associated behavioral patterns are closely related with frontal lobe executive functions.
    BibTeX:
    @article{Luu2000,
      author = {Luu, P and Collins, P and Tucker, DM},
      title = {Mood, personality, and self-monitoring: Negative affect and emotionality in relation to frontal lobe mechanisms of error monitoring},
      journal = {JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL},
      year = {2000},
      volume = {129},
      number = {1},
      pages = {43-60},
      doi = {{10.1037//0096-3445.129.1.43}}
    }
    
    Luu, P., Flaisch, T. & Tucker, D. Medial frontal cortex in action monitoring {2000} JOURNAL OF NEUROSCIENCE
    Vol. {20}({1}), pp. {464-469} 
    article  
    Abstract: Effective behavior requires continuous action monitoring. Electrophysiological studies in both monkeys and humans have shown activity in the medial frontal cortex that reflects dynamic control and monitoring of behavioral acts. In humans, the centromedial frontal cortex shows an electrical response within 100 msec of an error, the error-related negativity (ERN). The ERN occurs only when subjects are aware of making an error, suggesting that a critical factor may be self-monitoring of the action process. In the present study, we examined late responses in a deadline reaction time task, in which the subject becomes increasingly aware of making an error as the response becomes increasingly late. We found evidence of response conflict before errors defined by late responses but not before errors defined by incorrect responses. The results also show a linear increase in the amplitude of the ERN with increasingly late responses. These data suggest that frontal networks provide dynamic representations that monitor and evaluate the unfolding action plan.
    BibTeX:
    @article{Luu2000a,
      author = {Luu, P and Flaisch, T and Tucker, DM},
      title = {Medial frontal cortex in action monitoring},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2000},
      volume = {20},
      number = {1},
      pages = {464-469}
    }
    
    Maas, L., Lukas, S., Kaufman, M., Weiss, R., Daniels, S., Rogers, V., Kukes, T. & Renshaw, P. Functional magnetic resonance imaging of human brain activation during cue-induced cocaine craving {1998} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {155}({1}), pp. {124-126} 
    article  
    Abstract: Objective: Functional magnetic resonance Imaging (MRI) was used to test whether brain activation was detectable in regions previously associated with cocaine cue-induced craving. Method: Blood oxygenation level dependent (BOLD) functional activation was measured during presentation of audiovisual stimuli containing alternating intervals of drug-related and neutral scenes to six male subjects with a history of crack cocaine use and six male comparison subjects. Results: Significant activation was detected in the anterior cingulate and left dorsolateral prefrontal cortex in the cocaine-using group. In addition, a correlation between self-reported levels of craving and activation in these regions was found. Conclusions: These results suggest that Junctional MRI may be a useful tool to study the neurobiological basis of cue-induced craving.
    BibTeX:
    @article{Maas1998,
      author = {Maas, LC and Lukas, SE and Kaufman, MJ and Weiss, RD and Daniels, SL and Rogers, VW and Kukes, TJ and Renshaw, PF},
      title = {Functional magnetic resonance imaging of human brain activation during cue-induced cocaine craving},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {1998},
      volume = {155},
      number = {1},
      pages = {124-126}
    }
    
    MacDonald, A., Cohen, J., Stenger, V. & Carter, C. Dissociating the role of the dorsolateral prefrontal and anterior cingulate cortex in cognitive control {2000} SCIENCE
    Vol. {288}({5472}), pp. {1835-1838} 
    article  
    Abstract: Theories of the regulation of cognition suggest a system with two necessary components: one to implement control and another to monitor performance and signal when adjustments in control are needed. Event-related functional magnetic resonance imaging and a task-switching version of the Stroop task were used to examine whether these components of cognitive control have distinct neural bases in the human brain. A double dissociation was found. During task preparation, the left dorsolateral prefrontal cortex (Brodmann's area 9) was more active for color naming than for word reading, consistent with a role in the implementation of control. In contrast, the anterior cingulate cortex (Brodmann's areas 24 and 32) was more active when responding to incongruent stimuli, consistent with a role in performance monitoring.
    BibTeX:
    @article{MacDonald2000,
      author = {MacDonald, AW and Cohen, JD and Stenger, VA and Carter, CS},
      title = {Dissociating the role of the dorsolateral prefrontal and anterior cingulate cortex in cognitive control},
      journal = {SCIENCE},
      year = {2000},
      volume = {288},
      number = {5472},
      pages = {1835-1838}
    }
    
    Maddock, R. The retrosplenial cortex and emotion: new insights from functional neuroimaging of the human brain {1999} TRENDS IN NEUROSCIENCES
    Vol. {22}({7}), pp. {310-316} 
    article  
    Abstract: Little is known about the function of the retrosplenial cortex and until recently, there was no evidence that it had any involvement in emotional processes. Surprisingly, recent: functional neuroimaging studies show that the retrosplenial cortex is consistently activated by emotionally salient words. A review of the functional neuroimaging literature reveals a previously overlooked pattern of observations: the retrosplenial cortex is the cortical region most consistently activated by emotionally salient stimuli. Evidence that this region is also involved in episodic memory suggests that it might have a role in the interaction between emotion and episodic memory. Recognition that the retrosplenial cortex has a prominent role in the processing of emotionally salient stimuli invites further studies to define its specific functions and its interactions with other emotion-related brain regions.
    BibTeX:
    @article{Maddock1999,
      author = {Maddock, RJ},
      title = {The retrosplenial cortex and emotion: new insights from functional neuroimaging of the human brain},
      journal = {TRENDS IN NEUROSCIENCES},
      year = {1999},
      volume = {22},
      number = {7},
      pages = {310-316}
    }
    
    Maguire, E. & Mummery, C. Differential modulation of a common memory retrieval network revealed by positron emission tomography {1999} HIPPOCAMPUS
    Vol. {9}({1}), pp. {54-61} 
    article  
    Abstract: Functional neuroimaging is uniquely placed to examine the dynamic nature of normal human memory, the distributed brain networks that support it, and how they are modulated. Memory has traditionally been classified into context-specific memories personally experienced (''episodic memory'') and impersonal non-context-specific memories (''Semantic memory''). However, we suggest that another useful distinction is whether events are personally relevant or not. Typically the factors of personal relevance and temporal context are confounded, and it is as yet not clear the precise influence of either on how memories are stored or retrieved. Here we focus on the retrieval of real-world memories unconfounding personal relevance and temporal context during positron emission tomography (PET) scanning. Memories differed along two dimensions: They were personally relevant (or not) and had temporal specificity (or not). Recollection of each of the resultant four memory subtypes-autobiographical events, public events, autobiographical facts, and general knowledge-was associated with activation of a common network of brain regions. Within this system, however, enhanced activity was observed for retrieval of personally relevant, time-specific memories in left hippocampus, medial prefrontal cortex, and left temporal pole. Bilateral temporoparietal junctions were activated preferentially for personal memories, regardless of time specificity. Finally, left parahippocampal gyrus, left anterolateral temporal cortex, and posterior cingulate cortex were involved in memory retrieval irrespective of person or time. Our findings suggest that specializations in memory retrieval result from associations between subsets of regions within a common network. We believe that these findings throw new light on an old debate surrounding episodic and declarative theories of memory and the precise involvement of the hippocampus. Hippocampus 1999; 9:54-61. (C) 1999 Wiley-Liss, Inc.
    BibTeX:
    @article{Maguire1999,
      author = {Maguire, EA and Mummery, CJ},
      title = {Differential modulation of a common memory retrieval network revealed by positron emission tomography},
      journal = {HIPPOCAMPUS},
      year = {1999},
      volume = {9},
      number = {1},
      pages = {54-61}
    }
    
    MAILLEUX, P. & VANDERHAEGHEN, J. DISTRIBUTION OF NEURONAL CANNABINOID RECEPTOR IN THE ADULT-RAT BRAIN - A COMPARATIVE RECEPTOR-BINDING AUTORADIOGRAPHY AND INSITU HYBRIDIZATION HISTOCHEMISTRY {1992} NEUROSCIENCE
    Vol. {48}({3}), pp. {655-668} 
    article  
    Abstract: The neuronal distribution of cannabinoid receptor in the adult rat brain is reported, combining receptor binding radioautography using the synthetic psychoative cannabinoid ligand CP55,940 with in situ hybridization histochemistry using oligonucleotide probes complementary to rat cannabinoid receptor cDNA. In the cerebral cortex, especially in the frontal and cingulate cortex, dense binding was found in layers I and VI together with slight mRNA levels in a majority of both pyramidal and non-pyramidal-shaped neurons and of high mRNA levels in a moderate number of non-pyramidal-shaped neurons especially in layers II-III and V-VI. In the hippocampal dentate gyrus, very dense staining was found in the molecular layer together with high mRNA levels in a moderate number of hilar neurons close to the granular layer. In Ammon's horn, especially in the CA3 sector, very dense binding was found in the dendritic layers together with slight mRNA levels in the majority of the pyramidal cells and high mRNA levels in a moderate number of interneurons. In the basal ganglia, binding was very dense in the lateral putamen, substantia nigra pars reticulata, globus pallidus and entopeduncular nucleus, moderate in the medial putamen and caudate; and slight in the accumbens, together with slight to moderate mRNA levels in the striatal medium-sized neurons. Together with slight binding, slight to moderate mRNA levels were found in the majority of the neurons in the subthalamic nucleus. No binding and mRNA were found in the substantia nigra pars compacta and ventral tegmental area. Slight to moderate binding was found together with slight to moderate mRNA levels in the majority of neurons in the anterior olfactory nucleus; septum, especially medial septum and diagonal band of Broca; amygdala, especially basolateral amygdala; lateral habenula; ventromedial hypothalamic nucleus; lateral interpenduncular nucleus; central gray, dorsal cochlear nucleus; parabrachial nucleus; dorsal pontine tegmentum; pontine nuclei; commissural part of the nucleus tractus solitarius; inferior olive and dorsal horn of the spinal cord. In the cerebellum, very dense binding was found in the molecular layer together with slight mRNA levels in the majority of the granule cells and moderate mRNA levels in the basket and stellate cells. In conclusion, this study provides, for the first time, indirect assessment of the neurons containing cannabinoid receptor in the entire adult rat brain and will serve as a basis for future direct morphological confirmation using receptor immunohistochemistry and for functional studies.
    BibTeX:
    @article{MAILLEUX1992,
      author = {MAILLEUX, P and VANDERHAEGHEN, JJ},
      title = {DISTRIBUTION OF NEURONAL CANNABINOID RECEPTOR IN THE ADULT-RAT BRAIN - A COMPARATIVE RECEPTOR-BINDING AUTORADIOGRAPHY AND INSITU HYBRIDIZATION HISTOCHEMISTRY},
      journal = {NEUROSCIENCE},
      year = {1992},
      volume = {48},
      number = {3},
      pages = {655-668}
    }
    
    Manji, H., Quiroz, J., Sporn, J., Payne, J., Denicoff, K., Gray, N., Zarate, C. & Charney, D. Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depression {2003} BIOLOGICAL PSYCHIATRY
    Vol. {53}({8}), pp. {707-742} 
    article DOI  
    Abstract: There is growing evidence from neuroimaging and postmortem studies that severe mood disorders, which have traditionally been conceptualized as neurochemical disorders, are associated with impairments of structural plasticity and cellular resilience. It is thus noteworthy that recent preclinical studies have shown that critical molecules in neurotrophic signaling cascades (most notably cyclic adenosine monophosphate [CAMP] response element binding protein, brain-derived neurotrophic factor, bcl-2, and mitogen activated protein [MAP] kinases) are long-term targets for antidepressant agents and antidepressant potentiating modalities. This suggests that effective treatments provide both trophic and neurochemical support, which serves to enhance and maintain normal synaptic connectivity, thereby allowing the chemical signal to reinstate the optimal functioning of critical circuits necessary for normal affective functioning. For many refractory patients; drugs mimicking ``traditional'' strategies, which directly or indirectly alter monoaminergic levels, may be of limited benefit. Newer ``plasticity enhancing'' strategies that may have utility in the treatment of refractory depression include N-methyl-D-aspartate antagonists, alpha-amino-3-hydroxy-5-methylisoxazole propionate (AMPA) potentiators, CAMP phosphodiesterase inhibitors, and glucocorticoid receptor antagonists. Small-molecule agents that regulate the activity of growth factors, MAP kinases cascades, and the bcl-2 family of proteins are also promising future avenues. The development of novel, nonaminergic-based therapeutics holds much promise for improved treatment of severe, refractory mood disorders.
    BibTeX:
    @article{Manji2003,
      author = {Manji, HK and Quiroz, JA and Sporn, J and Payne, JL and Denicoff, K and Gray, NA and Zarate, CA and Charney, DS},
      title = {Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depression},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {2003},
      volume = {53},
      number = {8},
      pages = {707-742},
      note = {Conference on Difficult-to-Treat Depression, SAN FRANCISCO, CALIFORNIA, APR 21-22, 2002},
      doi = {{10.1016/S0006-3223(03)00117-3}}
    }
    
    MANSOUR, A., FOX, C., BURKE, S., AKIL, H. & WATSON, S. IMMUNOHISTOCHEMICAL LOCALIZATION OF THE CLONED MU-OPIOID RECEPTOR IN THE RAT CNS {1995} JOURNAL OF CHEMICAL NEUROANATOMY
    Vol. {8}({4}), pp. {283-305} 
    article  
    Abstract: Three opioid receptor types have recently been cloned that correspond to the pharmacologically defined mu, delta and K-1 receptors. In situ hybridization studies suggest that the opioid receptor mRNAs that encode these receptors have distinct distributions in the central nervous system that correlate well with their known functions. In the present study polyclonal antibodies were generated to the C terminal 63 amino acids of the cloned mu receptor (335-398) to examine the distribution of the mu receptor-like protein with immunohistochemical techniques. mu receptor-like immunoreactivity is widely distributed in the rat central nervous system with immunoreactive fibers and/or perikarya in such regions as the neocortex, the striatal patches and subcallosal streak, nucleus accumbens, lateral and medial septum, endopiriform nucleus, globus pallidus and ventral pallidum, amygdala, hippocampus, presubiculum, thalamic and hypothalamic nuclei, superior and inferior colliculi, central grey, substantia nigra, ventral tegmental area, interpeduncular nucleus, medial terminal nucleus of the accessory optic tract, raphe nuclei, nucleus of the solitary tract, spinal trigeminal nucleus, dorsal motor nucleus of vagus, the spinal cord and dorsal root ganglia. In addition, two major neuronal pathways, the fasciculus retroflexus and the stria terminalis, exhibit densely stained axonal fibers. While this distribution is in excellent agreement with the known mu receptor binding localization, a few regions, such as neocortex and cingulate cortex, basolateral amygdala, medial geniculate nucleus and the medial preoptic area fail to show a good correspondence. Several explanations are provided to interpret these results, and the anatomical and functional implications of these findings are discussed.
    BibTeX:
    @article{MANSOUR1995,
      author = {MANSOUR, A and FOX, CA and BURKE, S and AKIL, H and WATSON, SJ},
      title = {IMMUNOHISTOCHEMICAL LOCALIZATION OF THE CLONED MU-OPIOID RECEPTOR IN THE RAT CNS},
      journal = {JOURNAL OF CHEMICAL NEUROANATOMY},
      year = {1995},
      volume = {8},
      number = {4},
      pages = {283-305}
    }
    
    Maquet, P. Functional neuroimaging of normal human sleep by positron emission tomography {2000} JOURNAL OF SLEEP RESEARCH
    Vol. {9}({3}), pp. {207-231} 
    article  
    Abstract: Functional neuroimaging using positron emission tomography has recently yielded original data on the functional neuroanatomy of human sleep. This paper attempts to describe the possibilities and limitations of the technique and clarify its usefulness in sleep research. A short overview of the methods of acquisition and statistical analysis (statistical parametric mapping, SPM) is presented before the results of PET sleep studies are reviewed. The discussion attempts to integrate the functional neuroimaging data into the body of knowledge already acquired on sleep in animals and humans using various other techniques (intracellular recordings, in situ neurophysiology, lesional and pharmacological trials, scalp EEG recordings, behavioural or psychological description). The published PET data describe a very reproducible functional neuroanatomy in sleep. The core characteristics of this `canonical' sleep may be summarized as follows. In slow-wave sleep, most deactivated areas are located in the dorsal pons and mesencephalon, cerebellum, thalami, basal ganglia, basal forebrain/hypothalamus, prefrontal cortex, anterior cingulate cortex, precuneus and in the mesial aspect of the temporal lobe. During rapid-eye movement sleep, significant activations were found in the pontine tegmentum, thalamic nuclei, limbic areas (amygdaloid complexes, hippocampal formation, anterior cingulate cortex) and in the posterior cortices (temporo-occipital areas). In contrast, the dorso-lateral prefrontal cortex, parietal cortex, as well as the posterior cingulate cortex and precuneus, were the least active brain regions. These preliminary studies open up a whole field in sleep research. More detailed explorations of sleep in humans are now accessible to experimental challenges using PET and other neuroimaging techniques. These new methods will contribute to a better understanding of sleep functions.
    BibTeX:
    @article{Maquet2000,
      author = {Maquet, P},
      title = {Functional neuroimaging of normal human sleep by positron emission tomography},
      journal = {JOURNAL OF SLEEP RESEARCH},
      year = {2000},
      volume = {9},
      number = {3},
      pages = {207-231}
    }
    
    Maquet, P., Peters, J., Aerts, J., Delfiore, G., Degueldre, C., Luxen, A. & Franck, G. Functional neuroanatomy of human rapid-eye-movement sleep and dreaming {1996} NATURE
    Vol. {383}({6596}), pp. {163-166} 
    article  
    Abstract: RAPID-EYE-MOVEMENT (REM) sleep is associated with intense neuronal activity, ocular saccades, muscular atonia and dreaming(1,2). The function of REM sleep remains elusive and its neural correlates have not been characterized precisely in man. Here we use positron emission tomography and statistical parametric mapping to study the brain state associated with REM sleep in humans. We report a group study of seven subjects who maintained steady REM sleep during brain scanning and recalled dreams upon awakening. The results show that regional cerebral blood flow is positively correlated with REM sleep in pontine tegmentum, left thalamus, both amygdaloid complexes, anterior cingulate cortex and right parietal operculum. Negative correlations between regional cerebral blood flow and REM sleep are observed bilaterally, in a vast area of dorsolateral prefrontal cortex, in parietal cortex (supramarginal gyrus) as well as in posterior cingulate cortex and precuneus. Given the role of the amygdaloid complexes in the acquisition of emotionally influenced memories, the pattern of activation in the amygdala and the cortical areas provides a biological basis for the processing of some types of memory during REM sleep.
    BibTeX:
    @article{Maquet1996,
      author = {Maquet, P and Peters, JM and Aerts, J and Delfiore, G and Degueldre, C and Luxen, A and Franck, G},
      title = {Functional neuroanatomy of human rapid-eye-movement sleep and dreaming},
      journal = {NATURE},
      year = {1996},
      volume = {383},
      number = {6596},
      pages = {163-166}
    }
    
    MATELLI, M., LUPPINO, G. & RIZZOLATTI, G. ARCHITECTURE OF SUPERIOR AND MESIAL AREA-6 AND THE ADJACENT CINGULATE CORTEX IN THE MACAQUE MONKEY {1991} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {311}({4}), pp. {445-462} 
    article  
    Abstract: The agranular frontal cortex is formed by several distinct functional areas. There is no agreement, however, on its cytoarchitectonic organization. The aim of this study was to redefine the cytoarchitectonic organization of superior and mesial area 6 and the adjacent cingulate cortex in the macaque monkey. A particular goal was to find out whether the so-called supplementary motor area (SMA) is cytoarchitectonically different from the rest of area 6 and whether it can be considered as a single, independent cytoarchitectonic area. The results showed that, rostral to F1 (area 4), four architectonic areas can be recognized in the superior (dorsal) and mesial area 6. Two of them are located on mesial cortical surface (F3 caudally and F6 rostrally) and two on superior cortical convexity (F2 caudally and F7 rostrally). The main cytoarchitectonic features of the five identified areas can be summarized as follows. F1: (1) giant pyramidal cells organized in multiple rows, (2) columnar pattern extending from the white matter to the superficial layers, (3) low cellular density in the lower part of layer III. F3: (1) high cellular density in the lower part of layer III, which fuses with a dense Va, (2) columnar pattern present only in the deepest layer, (3) occasional presence of giant pyramidal cells in layer Vb. F6: (1) prominent layer V, (2) absence of sublayer Vb, (3) homogeneous cell density in superficial layers. F2: (1) thin row of medium-size pyramids in the lowest part of layer III, (2) columnar pattern extending to the superficial layers, (3) dense layer Va, (4) few, scattered giant pyramids in layer Vb. F7: (1) prominent layer V, (2) bipartite layer VI. Areas F1, F2, and F3, as defined cytoarchitectonically, coincided with the homonymous histochemical areas. The present data showed also that area 24 is formed by four subareas: 24a, b, c and d. Areas 24a and b occupy the ventral part of area 24, whereas its dorsal part is formed by area 24c, located rostrally, and area 24d, located caudally. The following features distinguish area 24d from area 24c: (1) larger pyramidal cells in layer V, (2) presence of medium-size pyramidal cells in the lower part of layer III, (3) more prominent columnar pattern, (4) higher myelinization with the presence of an evident horizontal plexus. Mesial area 6 is usually considered as a single functional entity (SMA). Our findings show that this cortical region is formed by two distinct cytoarchitectonic areas. In the following article (Luppino et al. `91: J. Comp. Neurol 311:463-482) physiological evidence is presented that the SMA, as classically defined, corresponds to F3, whereas F6 is an independent functional area.
    BibTeX:
    @article{MATELLI1991,
      author = {MATELLI, M and LUPPINO, G and RIZZOLATTI, G},
      title = {ARCHITECTURE OF SUPERIOR AND MESIAL AREA-6 AND THE ADJACENT CINGULATE CORTEX IN THE MACAQUE MONKEY},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {1991},
      volume = {311},
      number = {4},
      pages = {445-462}
    }
    
    MATSUZAKA, Y., AIZAWA, H. & TANJI, J. A MOTOR AREA ROSTRAL TO THE SUPPLEMENTARY MOTOR AREA (PRESUPPLEMENTARY MOTOR AREA) IN THE MONKEY - NEURONAL-ACTIVITY DURING A LEARNED MOTOR TASK {1992} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {68}({3}), pp. {653-662} 
    article  
    Abstract: 1. The rostromesial agranular frontal cortex of macaque monkey (Macaca fuscata), traditionally defined as the supplementary motor area (SMA), was studied using various physiological techniques to delineate two different areas rostrocaudally. 2. Field and unitary responses to electrical stimulation of the primary motor cortex were distinct in the caudal part, but minimal or absent in the rostral part. Intracortical microstimulation readily evoked limb or orofacial movements in the caudal part, but only infrequently in the rostral part. Neuronal responses to visual stimuli prevailed in the rostral part, but somatosensory responses were rare. The opposite was true in the caudal part. 3. The rostral part, roughly corresponding to area 6abeta, was operationally defined as the presupplementary motor area (pre-SMA). The caudal part was redefined as the SMA proper. 4. Single-cell activity in the pre-SMA was quantitatively compared with that in the SMA proper in relation to a trained motor task. 5. Phasic responses to visual cue signals indicating the direction of forthcoming arm-reaching movement were more abundant in the pre-SMA. 6. Activity changes during the preparatory period, which lasted until the occurrence of the trigger signal for the reaching movement, were more frequent in the pre-SMA. 7. Phasic, movement-related activity was more frequent in the SMA, and its onset was often time locked to the movement onset. In the pre-SMA, the occurrences of response time locked to the movement-trigger signal were more frequent than in the SMA. 8. Among neurons in both areas, directional selectivity was found in all the cue, preparatory, and movement-related responses.
    BibTeX:
    @article{MATSUZAKA1992,
      author = {MATSUZAKA, Y and AIZAWA, H and TANJI, J},
      title = {A MOTOR AREA ROSTRAL TO THE SUPPLEMENTARY MOTOR AREA (PRESUPPLEMENTARY MOTOR AREA) IN THE MONKEY - NEURONAL-ACTIVITY DURING A LEARNED MOTOR TASK},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1992},
      volume = {68},
      number = {3},
      pages = {653-662}
    }
    
    May, A., Bahra, A., Buchel, C., Frackowiak, R. & Goadsby, P. Hypothalamic activation in cluster headache attacks {1998} LANCET
    Vol. {352}({9124}), pp. {275-278} 
    article  
    Abstract: Background Cluster headache, one of the most severe pain syndromes in human beings, is usually described as a vascular headache. However, the striking circadian rhythmicity of this strictly half-sided pain syndrome cannot be readily explained by the vascular hypothesis. We aimed to assess changes in regional cerebral blood flow (rCBF) in patients with cluster headache. Methods We used positron emission tomography (PET) to assess the changes in rCBF, as an index of synaptic activity, during nitroglycerin-induced cluster headache attacks in nine patients who had chronic cluster headache. Eight patients who had cluster headache but were not in the bout acted as a control group. Findings In the acute pain slate, activation was seen in the ipsilateral inferior hypothalamic grey matter, the contralateral ventroposterior thalamus, the anterior cingulate cortex, and bilaterally in the insulae. Activation in the hypothalamus was seen solely in the pain state and was not seen in patients who have cluster headache but were out of the bout. Interpretation Our findings establish central nervous system dysfunction in the region of the hypothalamus as the primum movens in the pathophysiology of cluster headache. We suggest that a radical reappraisal of this type of headache is needed and that it should in general terms, be regarded as a neurovascular headache, to give equal weight to the pathological and physiological mechanisms that are at work.
    BibTeX:
    @article{May1998,
      author = {May, A and Bahra, A and Buchel, C and Frackowiak, RSJ and Goadsby, PJ},
      title = {Hypothalamic activation in cluster headache attacks},
      journal = {LANCET},
      year = {1998},
      volume = {352},
      number = {9124},
      pages = {275-278}
    }
    
    Mayberg, H. Limbic-cortical dysregulation: A proposed model of depression {1997} JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES
    Vol. {9}({3}), pp. {471-481} 
    article  
    Abstract: A working model of depression implicating failure of the coordinated interactions of a distributed network of limbic-cortical pathways is proposed. Resting state patterns of regional glucose metabolism in idiopathic depressed patients, changes in metabolism with antidepressant treatment, and bloodflow changes with induced sadness in healthy subjects were used to test and refine this hypothesis. Dorsal neocortical decreases and ventral paralimbic increases characterize both healthy sadness and depressive illness; concurrent inhibition of overactive paralimbic regions and normalization of hypofunctioning dorsal cortical sites characterize disease remission. Normal functioning of the rostral anterior cingulate, with its direct connections to these dorsal and ventral areas, is postulated to be additionally required for the observed reciprocal compensatory changes, since pretreatment metabolism in this region uniquely predicts antidepressant treatment response. This model is offered as an adaptable framework to facilitate continued integration of clinical imaging findings with complementary neuroanatomical, neurochemical, and electrophysiological studies in the investigation of the pathogenesis of affective disorders.
    BibTeX:
    @article{Mayberg1997a,
      author = {Mayberg, HS},
      title = {Limbic-cortical dysregulation: A proposed model of depression},
      journal = {JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES},
      year = {1997},
      volume = {9},
      number = {3},
      pages = {471-481}
    }
    
    Mayberg, H., Brannan, S., Mahurin, R., Jerabek, P., Brickman, J., Tekell, J., Silva, J., McGinnis, S., Glass, T., Martin, C. & Fox, P. Cingulate function in depression: A potential predictor of treatment response {1997} NEUROREPORT
    Vol. {8}({4}), pp. {1057-1061} 
    article  
    Abstract: THE relationship between pretreatment regional cerebral glucose metabolism and eventual antidepressant drug response was measured using positron emission tomography (PET) in hospitalized patients with unipolar depression. Rostral anterior cingulate metabolism uniquely differentiated eventual treatment responders from non-responders. Hypometabolism characterized non-responders when compared with controls, in contrast to responders who were hypermetabolic. Metabolism in no other region discriminated the two groups, nor did associated demographic, clinical or behavioral measures, including motor speed, cognitive performance, depression severity or illness chronicity. Cingulate hypermetabolism may represent an important adaptive response to depression and failure of this response may underlie poor outcome. A critical role for rostral cingulate area 24a/b in the limbic-cortical network involved in abnormal mood states is proposed.
    BibTeX:
    @article{Mayberg1997,
      author = {Mayberg, HS and Brannan, SK and Mahurin, RK and Jerabek, PA and Brickman, JS and Tekell, JL and Silva, JA and McGinnis, S and Glass, TG and Martin, CC and Fox, PT},
      title = {Cingulate function in depression: A potential predictor of treatment response},
      journal = {NEUROREPORT},
      year = {1997},
      volume = {8},
      number = {4},
      pages = {1057-1061}
    }
    
    Mayberg, H., Brannan, S., Tekell, J., Silva, J., Mahurin, R., McGinnis, S. & Jerabek, P. Regional metabolic effects of fluoxetine in major depression: Serial changes and relationship to clinical response {2000} BIOLOGICAL PSYCHIATRY
    Vol. {48}({8}), pp. {830-843} 
    article  
    Abstract: Background: Treatment of major depression with antidepressants is generally associated with a delay in onset of clinical response. Functional brain correlates of this phenomenon have not been previously characterized Methods: Time course of changes in brain glucose metabolism were measured using positron emission tomography in hospitalized unipolar depressed patients treated with fluoxetine. Time-specific and response-specific effects were examined at 1 and 6 weeks of treatment. Results: Changes were seen over time, and characterized by three distinct patterns: 1) common changes at I and 6 weeks, 21 reversal of the 1-week pattern at 6 weeks, and 3) unique changes seen only after chronic treatment. Fluoxetine responders and nonresponders, similar at 1 week, were differentiated by their 6-week pattern. Clinical improvement was uniquely associated with limbic and striatal decreases (subgenual cingulate, hippocampus, insula, and pallidum) and brain stem and dorsal cortical increases (prefrontal, parietal, anterior, and posterior cingulate). Failed response was associated with a persistent I-week pattern and absence of either subgenual cingulate or prefrontal changes. Conclusions: Chronic treatment and clinical response to fluoxetine was associated with a reciprocal pattern of subcortical and limbic decreases and cortical increases. Reversal irt the week-1 pattern at 6 weeks suggests a process of adaptation in specific brain regions over time in response to sustained serotonin reuptake inhibition. The inverse patterns in responders and nonresponders also suggests that failure to induce these adaptive changes may underlie treatment nonresponse. Biol Psychiatry 2000; 48:830-843 (C) 2000 Society of Biological Psychiatry.
    BibTeX:
    @article{Mayberg2000,
      author = {Mayberg, HS and Brannan, SK and Tekell, JL and Silva, JA and Mahurin, RK and McGinnis, S and Jerabek, PA},
      title = {Regional metabolic effects of fluoxetine in major depression: Serial changes and relationship to clinical response},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {2000},
      volume = {48},
      number = {8},
      pages = {830-843},
      note = {Conference on Depression in the 21st Century: New Insight into Drug Development and Neurobiology, DANA POINT, CALIFORNIA, FEB 02-22, 2000}
    }
    
    MAYBERG, H., LEWIS, P., REGENOLD, W. & WAGNER, H. PARALIMBIC HYPOPERFUSION IN UNIPOLAR DEPRESSION {1994} JOURNAL OF NUCLEAR MEDICINE
    Vol. {35}({6}), pp. {929-934} 
    article  
    Abstract: Methods: Relative regional cerebral blood Row was measured with SPECT using Tc-99m-hexamethylpropyleneamine oxime in 13 patients with severe unipolar depression that was nonresponsive to drug therapy and 11 age-matched nondepressed controls. Results: All patients were clinically depressed and taking antidepressant drugs at the time of the study. The relative blood flow was significantly decreased bilaterally in the frontal cortex, anterior temporal cortex, anterior cingulate gyrus and caudate in the depressed patients compared with the nondepressed healthy controls. The greatest decreases were seen in the paralimbic regions, specifically, the inferior frontal and cingulate cortex. No significant changes were seen in the parietal cortex, occipital cortex or thalami. Psychiatric rating scales correlated poorly with regional blood flow, except for the degree of psychomotor slowing, which was negatively correlated with frontal and cingulate perfusion. Conclusion: These findings implicate selective dysfunction of paralimbic brain regions in clinically depressed patients, independent of their medication use, and support the concept of specific neural systems that regulate mood. Recognition of these regional abnormalities may have clinical utility in both the diagnosis and treatment of depression.
    BibTeX:
    @article{MAYBERG1994,
      author = {MAYBERG, HS and LEWIS, PJ and REGENOLD, W and WAGNER, HN},
      title = {PARALIMBIC HYPOPERFUSION IN UNIPOLAR DEPRESSION},
      journal = {JOURNAL OF NUCLEAR MEDICINE},
      year = {1994},
      volume = {35},
      number = {6},
      pages = {929-934}
    }
    
    Mayberg, H., Liotti, M., Brannan, S., McGinnis, S., Mahurin, R., Jerabek, P., Silva, J., Tekell, J., Martin, C., Lancaster, J. & Fox, P. Reciprocal limbic-cortical function and negative mood: Converging PET findings in depression and normal sadness {1999} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {156}({5}), pp. {675-682} 
    article  
    Abstract: Objective: Theories of human behavior from Plate to Freud have repeatedly emphasized links between emotion and reason, a relationship now commonly attributed to pathways connecting phylogenetically ``old'' and ``new'' brain regions. Expanding on this theory, this study examined functional interactions between specific limbic and neocortical regions accompanying normal and disease-associated shifts in negative mood state. Method: Regions of concordant functional change accompanying provocation of transient sadness in healthy volunteers and resolution of chronic dysphoric symptoms in depressed patients were examined with two positron emission tomography techniques: [O-15]water and [F-18]fluorodeoxyglucose, respectively. Results: With sadness, increases in limbic-paralimbic blood flow (subgenual cingulate, anterior insula) and decreases in neocortical regions (right dorsolateral prefrontal, inferior parietal) were identified. With recovery from depression, the reverse pattern, involving the same regions, was seen-limbic metabolic decreases and neocortical increases. A significant inverse correlation between subgenual cingulate and right dorsolateral prefrontal activity was also demonstrated in both conditions. Conclusions: Reciprocal changes involving subgenual cingulate and right prefrontal cortex occur with both transient and chronic changes in negative mood. The presence and maintenance of functional reciprocity between these regions with shifts in mood in either direction suggests that these regional interactions are obligatory and probably mediate the well-recognized relationships between mood and attention seen in both normal and pathological conditions. The bidirectional nature of this limbic-cortical reciprocity provides additional evidence of potential mechanisms mediating cognitive (''top-down''), pharmacological (mixed), and surgical (''bottom-up'') treatments of mood disorders such as depression.
    BibTeX:
    @article{Mayberg1999,
      author = {Mayberg, HS and Liotti, M and Brannan, SK and McGinnis, S and Mahurin, RK and Jerabek, PA and Silva, JA and Tekell, JL and Martin, CC and Lancaster, JL and Fox, PT},
      title = {Reciprocal limbic-cortical function and negative mood: Converging PET findings in depression and normal sadness},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {1999},
      volume = {156},
      number = {5},
      pages = {675-682},
      note = {3rd International Conference on Functional Mapping of the Human Brain, COPENHAGEN, DENMARK, MAY 19-23, 1997}
    }
    
    Mayberg, H., Lozano, A., Voon, V., McNeely, H., Seminowicz, D., Hamani, C., Schwalb, J. & Kennedy, S. Deep brain stimulation for treatment-resistant depression {2005} NEURON
    Vol. {45}({5}), pp. {651-660} 
    article DOI  
    Abstract: Treatment-resistant depression is a severely disabling disorder with no proven treatment options once multiple medications, psychotherapy, and electroconvulsive therapy have failed. Based on our preliminary observation that the subgenual cingulate region (Brodmann area 25) is metabolically overactive in treatment resistant depression, we studied whether the application of chronic deep brain stimulation to modulate BA25 could reduce this elevated activity and produce clinical benefit in six patients with refractory depression. Chronic stimulation of white matter tracts adjacent to the subgenual cingulate gyrus was associated with a striking and sustained remission of depression in four of six patients. Antidepressant effects were associated with a marked reduction in local cerebral blood flow as well as changes in downstream limbic and cortical sites, measured using positron emission tomography. These results suggest that disrupting focal pathological activity in limbic-cortical circuits using electrical stimulation of the subgenual cingulate white matter can effectively reverse symptoms in otherwise treatment-resistant depression.
    BibTeX:
    @article{Mayberg2005,
      author = {Mayberg, HS and Lozano, AM and Voon, V and McNeely, HE and Seminowicz, D and Hamani, C and Schwalb, JM and Kennedy, SH},
      title = {Deep brain stimulation for treatment-resistant depression},
      journal = {NEURON},
      year = {2005},
      volume = {45},
      number = {5},
      pages = {651-660},
      doi = {{10.1016/j.neuron.2005.02.014}}
    }
    
    Mayberg, H., Silva, J., Brannan, S., Tekell, J., Mahurin, R., McGinnis, S. & Jerabek, P. The functional neuroanatomy of the placebo effect {2002} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {159}({5}), pp. {728-737} 
    article  
    Abstract: Objective: Administration of placebo can result in a clinical response indistinguishable from that seen with active antidepressant treatment. Functional brain correlates of this phenomenon have not been fully characterized. Method: Changes in brain glucose metabolism were measured by using positron emission tomography in hospitalized men with unipolar depression who were administered placebo as part of an inpatient imaging study of fluoxetine. Common and unique response effects to administration of placebo or fluoxetine were assessed after a 6-week, double-blind trial. Results: Placebo response was associated with regional metabolic increases involving the prefrontal, anterior cingulate, premotor, parietal, posterior insula, and posterior cingulate and metabolic decreases involving the subgenual cingulate, para-hippocampus, and thalamus, Regions of change overlapped those seen in responders administered active fluoxetine. Fluoxetine response, however, was associated with additional subcortical and limbic changes in the brainstem, striatum, anterior insula, and hippocampus, sources of efferent input to the response-specific regions identified with both agents. Conclusions: The common pattern of cortical glucose metabolism increases and limbic-paralimbic metabolism decreases in placebo and fluoxetine responders suggests that facilitation of these changes may be necessary for depression remission, regardless of treatment modality. Clinical improvement in the group receiving placebo as part of an inpatient study is consistent with the well-recognized effect that altering the therapeutic environment may significantly contribute to reducing clinical symptoms. The additional subcortical and limbic metabolism decreases seen uniquely in fluoxetine responders may convey additional advantage in maintaining long-term clinical response and in relapse prevention.
    BibTeX:
    @article{Mayberg2002,
      author = {Mayberg, HS and Silva, JA and Brannan, SK and Tekell, JL and Mahurin, RK and McGinnis, S and Jerabek, PA},
      title = {The functional neuroanatomy of the placebo effect},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {2002},
      volume = {159},
      number = {5},
      pages = {728-737},
      note = {56th Annual Meeting of the Society-of-Biological-Psychiatry, NEW ORLEANS, LOUISIANA, MAY 03-05, 2001}
    }
    
    Mazoyer, B., Zago, L., Mellet, E., Bricogne, S., Etard, O., Houde, O., Crivello, F., Joliot, M., Petit, L. & Tzourio-Mazoyer, N. Cortical networks for working memory and executive functions sustain the conscious resting state in man {2001} BRAIN RESEARCH BULLETIN
    Vol. {54}({3}), pp. {287-298} 
    article  
    Abstract: The cortical anatomy of the conscious resting state (REST) was investigated using a meta-analysis of nine positron emission tomography (PET) activation protocols that dealt with different cognitive tasks but shared REST as a common control state. During REST, subjects were in darkness and silence, and were instructed to relax, refrain from moving, and avoid systematic thoughts. Each protocol contrasted REST to a different cognitive task consisting either of language, mental imagery, mental calculation, reasoning, finger movement, or spatial working memory, using either auditory, visual car no stimulus delivery, and requiring either vocal, motor or no output. A total of 63 subjects and 370 spatially normalized PET scans were entered in the meta-analysis. Conjunction analysis revealed a network of brain areas jointly activated during conscious REST as compared to the nine cognitive tasks, including the bilateral angular gyrus, the left anterior precuneus and posterior cingulate cortex, the left medial frontal and anterior cingulate cortex, the left superior and medial frontal sulcus, and the left inferior frontal cortex. These results suggest that brain activity during conscious REST is sustained by a large scale network of heteromodal associative parietal and frontal cortical areas, that can be further hierarchically organized in an episodic working memory parieto-frontal network, driven in part by emotions, working under the supervision of an executive left prefrontal network. (C) 2001 Elsevier Science Inc.
    BibTeX:
    @article{Mazoyer2001,
      author = {Mazoyer, B and Zago, L and Mellet, E and Bricogne, S and Etard, O and Houde, O and Crivello, F and Joliot, M and Petit, L and Tzourio-Mazoyer, N},
      title = {Cortical networks for working memory and executive functions sustain the conscious resting state in man},
      journal = {BRAIN RESEARCH BULLETIN},
      year = {2001},
      volume = {54},
      number = {3},
      pages = {287-298}
    }
    
    MCCARLEY, R., SHENTON, M., ODONNELL, B., FAUX, S., KIKINIS, R., NESTOR, P. & JOLESZ, F. AUDITORY P300 ABNORMALITIES AND LEFT POSTERIOR SUPERIOR TEMPORAL GYRUS VOLUME REDUCTION IN SCHIZOPHRENIA {1993} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {50}({3}), pp. {190-197} 
    article  
    Abstract: Abnormalities in the auditory P300 event-related potential are one of the most robust findings in schizophrenia. To investigate the brain source(s) of this major functional abnormality, we combined P300 recordings with the use of a new generation of magnetic resonance imaging (MRI) technology to examine specific temporal lobe gray matter regions of interest in schizophrenics and normal controls. In schizophrenics, gray matter volume reductions in the left posterior superior temporal gyrus (STG), which includes Heschl's gyrus and the planum temporale, were highly and specifically associated with both P300 amplitude reduction and left
    BibTeX:
    @article{MCCARLEY1993,
      author = {MCCARLEY, RW and SHENTON, ME and ODONNELL, BF and FAUX, SF and KIKINIS, R and NESTOR, PG and JOLESZ, FA},
      title = {AUDITORY P300 ABNORMALITIES AND LEFT POSTERIOR SUPERIOR TEMPORAL GYRUS VOLUME REDUCTION IN SCHIZOPHRENIA},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1993},
      volume = {50},
      number = {3},
      pages = {190-197}
    }
    
    McCarthy, G., Luby, M., Gore, J. & GoldmanRakic, P. Infrequent events transiently activate human prefrontal and parietal cortex as measured by functional MRI {1997} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {77}({3}), pp. {1630-1634} 
    article  
    Abstract: P300 is an event-related potential elicited by infrequent target events whose amplitude is dependent on the context provided by the immediately preceding sequence of stimuli, suggesting its dependence on working memory. We employed magnetic resonance imaging sequences sensitive to blood oxygenation level to identify regional changes evoked by infrequent visual target stimuli presented in a task typically used to elicit P300. Targets evoked transient event-related activation bilaterally in the middle frontal gyrus, in the inferior parietal lobe, and near the inferior aspect of the posterior cingulate gyrus beginning within 1.5 s of target onset and peaking between 1.5 and 6 s. These regions have been identified in previous neuroimaging studies in humans, and in single-unit recordings in monkeys. as components of a neural system mediating working memory, which suggests that this system may be activated by the same events that evoke P300.
    BibTeX:
    @article{McCarthy1997,
      author = {McCarthy, G and Luby, M and Gore, J and GoldmanRakic, P},
      title = {Infrequent events transiently activate human prefrontal and parietal cortex as measured by functional MRI},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1997},
      volume = {77},
      number = {3},
      pages = {1630-1634}
    }
    
    McCarthy, G., Puce, A., Constable, R., Krystal, J., Gore, J. & GoldmanRakic, P. Activation of human prefrontal cortex during spatial and nonspatial working memory tasks measured by functional MRI {1996} CEREBRAL CORTEX
    Vol. {6}({4}), pp. {600-611} 
    article  
    Abstract: Separate working memory domains for spatial location, and for objects, faces, and patterns, have been identified in the prefrontal cortex (PFC) of nonhuman primates. We have used functional magnetic resonance imaging to examine whether spatial and nonspatial visual working memory processes are similarly dissociable in human PFC. Subjects performed tasks which required them to remember either the location or shape of successive visual stimuli. We found that the mnemonic component of the working memory tasks affected the hemispheric pattern of PFC activation. The spatial (LOCATION) working memory task preferentially activated the middle frontal gyrus (MFG) in the right hemisphere, while the nonspatial (SHAPE) working memory task activated the MFG in both hemispheres. Furthermore, the area of activation in the left hemisphere extended into the inferior frontal gyrus for the nonspatial SHAPE task. A perceptual target (DOT) detection task also activated the MFG bilaterally, but at a level approximately half that of the working memory tasks. The activation in the MFG occurred within 3-6 s of task onset and declined following task offset. Time-course analysis revealed a different pattern for the cingulate gyrus, in which activation occurred upon task completion. Cingulate activation was greatest following the SHAPE task and was greater in the left hemisphere. The present results support the prominent role of the PFC and, specifically, the MFG in working memory, and indicate that the mnemonic content of the task affects the relative weighting of hemispheric activation.
    BibTeX:
    @article{McCarthy1996,
      author = {McCarthy, G and Puce, A and Constable, RT and Krystal, JH and Gore, JC and GoldmanRakic, P},
      title = {Activation of human prefrontal cortex during spatial and nonspatial working memory tasks measured by functional MRI},
      journal = {CEREBRAL CORTEX},
      year = {1996},
      volume = {6},
      number = {4},
      pages = {600-611}
    }
    
    McGaughy, J., Kaiser, T. & Sarter, M. Behavioral vigilance following infusions of 192 IgG-saporin into the basal forebrain: Selectivity of the behavioral impairment and relation to cortical AChE-positive fiber density {1996} BEHAVIORAL NEUROSCIENCE
    Vol. {110}({2}), pp. {247-265} 
    article  
    Abstract: Rats were trained in a previously validated behavioral vigilance task that required them to detect visual signals of variable length and to discriminate signal from nonsignal events. Baseline performance was characterized by a signal length-dependent ability to score hits, a decline in hits over time, and a correct rejection rate of approximately 70 After the rats reached criterion performance in this task, the immunotoxin 192 IgG-saporin or its vehicle was infused into the area of the nucleus basalis/substantia innominata of the basal forebrain. Postoperative performance in lesioned rats was characterized by a decrease in their ability to detect signals while their ability to correctly reject nonsignals remained unaffected. The effect of the lesion did not recover in the course of over 180 sessions of postlesion testing. The overall performance of the rats correlated with acetylcholinesterase (AChE)-positive fiber density in all cortical areas measured except the cingulate and pyriform cortex. These findings help to elucidate the nature of the attentional impairments resulting from the loss of cortical cholinergic inputs.
    BibTeX:
    @article{McGaughy1996,
      author = {McGaughy, J and Kaiser, T and Sarter, M},
      title = {Behavioral vigilance following infusions of 192 IgG-saporin into the basal forebrain: Selectivity of the behavioral impairment and relation to cortical AChE-positive fiber density},
      journal = {BEHAVIORAL NEUROSCIENCE},
      year = {1996},
      volume = {110},
      number = {2},
      pages = {247-265}
    }
    
    MCGUIRE, P., BENCH, C., FRITH, C., MARKS, I., FRACKOWIAK, R. & DOLAN, R. FUNCTIONAL-ANATOMY OF OBSESSIVE-COMPULSIVE PHENOMENA {1994} BRITISH JOURNAL OF PSYCHIATRY
    Vol. {164}, pp. {459-468} 
    article  
    Abstract: Regional cerebral blood flow was measured with (H2O)-O-15 positron emission tomography in four patients with obsessive-compulsive disorder. Patients were scanned on 12 occasions in the same session, with each scan paired with brief exposure to one of a hierarchy of contaminants that elicited increasingly intense urges to ritualise. The relationship between symptom intensity and regional cerebral blood flow (rCBF; an index of neural activity) was subsequently examined in the group and in individual patients. The group showed significant positive correlations between symptom intensity and blood flow in the right inferior frontal gyrus, caudate nucleus, putamen, globus pallidus and thalamus, and the left hippocampus and posterior cingulate gyrus. Negative correlations were evident in the right superior prefrontal cortex, and the temporoparietal junction, particularly on the right side. The pattern in single subjects was broadly similar, although individual differences in neural response were also observed. A graded relationship between symptom intensity and regional brain activity can thus be identified in obsessive-compulsive disorder. It is hypothesised that the increases in rCBF in the orbitofrontal cortex, neostriatum, global pallidus and thalamus were related to urges to perform compulsive movements, while those in the hippocampus and posterior cingulate cortex corresponded to the anxiety that accompanied them.
    BibTeX:
    @article{MCGUIRE1994,
      author = {MCGUIRE, PK and BENCH, CJ and FRITH, CD and MARKS, IM and FRACKOWIAK, RSJ and DOLAN, RJ},
      title = {FUNCTIONAL-ANATOMY OF OBSESSIVE-COMPULSIVE PHENOMENA},
      journal = {BRITISH JOURNAL OF PSYCHIATRY},
      year = {1994},
      volume = {164},
      pages = {459-468}
    }
    
    MCGUIRE, P., SHAH, G. & MURRAY, R. INCREASED BLOOD-FLOW IN BROCA AREA DURING AUDITORY HALLUCINATIONS IN SCHIZOPHRENIA {1993} LANCET
    Vol. {342}({8873}), pp. {703-706} 
    article  
    Abstract: Verbal auditory hallucinations are common in schizophrenia but little is known about how they arise. We have used single photon emission tomography (SPET) to measure regional cerebral blood flow with the aim of identifying brain areas that are especially active during auditory hallucinations. We scanned twelve men with schizophrenia while they were experiencing hallucinations. The subjects were rescanned under identical conditions when their hallucinations had resolved (mean 19 weeks later). Blood flow was significantly greater during hallucinations than in the non-hallucinating state in Broca's area (mean count density on SPET 1.18 [SD 0.04] vs 1.13 [0.06]; p<0.001); flow was also higher during hallucinations in the left anterior cingulate cortex and regions in the left temporal lobe, but these differences did not achieve significance. The increased flow in Broca's area was not accounted for by changes in other clinical variables nor by changes in the dose of neuroleptic drugs. These findings suggest that the production of auditory hallucinations in schizophrenia is associated with increased activity in a network of cortical areas specialised for language.
    BibTeX:
    @article{MCGUIRE1993,
      author = {MCGUIRE, PK and SHAH, GMS and MURRAY, RM},
      title = {INCREASED BLOOD-FLOW IN BROCA AREA DURING AUDITORY HALLUCINATIONS IN SCHIZOPHRENIA},
      journal = {LANCET},
      year = {1993},
      volume = {342},
      number = {8873},
      pages = {703-706}
    }
    
    McKiernan, K., Kaufman, J., Kucera-Thompson, J. & Binder, J. A parametric manipulation of factors affecting task-induced deactivation in functional neuroimaging {2003} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {15}({3}), pp. {394-408} 
    article  
    Abstract: Task-induced deactivation (TID) refers to a regional decrease in blood flow during an active task relative to a ``resting'' or ``passive'' baseline. We tested the hypothesis that TID results from a reallocation of Processing resources by parametrically manipulating task difficulty within three factors : target discriminability, stimulus presentation rate, and short-term memory load. Subjects performed all auditory target detection task during functional magnetic resonance imaging (fMRI), responding to a single target tone or, in the short-term memory load conditions, to target sequences. Seven task conditions (a common version and two additional levels for each of the three factors) were each alternated with ``rest'' ill a block design. Analysis of covariance identified brain regions in which TID occurred. Analyses of variance identified seven regions (left anterior cingulate/superior frontal gyrus, left middle frontal gyrus, right anterior cingulate gyrus, left and right posterior cingulate gyrus, left posterior parieto-occipital cortex, and right precuneus) in which TID magnitude varied across task levels within a factor. Follow-up tests indicated that for each of the three factors, TID magnitude increased with task difficulty. These results suggest that TID represents reallocation of processing resources from areas in which TID occurs to areas involved in task performance. Short-term memory load and stimulus rate also predict suppression of spontaneous thought, and many of the brain areas showing TID have been linked with semantic processing, supporting claims that TID may be due in part to suspension of spontaneous semantic processes that occur during ``rest'' (Binder et al. 1999). The concept that the typical ``resting state'' is actually a condition characterized by rich cognitive activity has important implications for the design and analysis of neuroimaging studies.
    BibTeX:
    @article{McKiernan2003,
      author = {McKiernan, KA and Kaufman, JN and Kucera-Thompson, J and Binder, JR},
      title = {A parametric manipulation of factors affecting task-induced deactivation in functional neuroimaging},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {2003},
      volume = {15},
      number = {3},
      pages = {394-408}
    }
    
    McNaughton, N. & Corr, P. A two-dimensional neuropsychology of defense: fear/anxiety and defensive distance {2004} NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
    Vol. {28}({3}), pp. {285-305} 
    article DOI  
    Abstract: We present in this paper a picture of the neural systems controlling defense that updates and simplifies Gray's ``Neuropsychology of Anxiety''. It is based on two behavioural dimensions: `defensive distance' as defined by the Blanchards and `defensive direction'. Defensive direction is a categorical dimension with avoidance of threat corresponding to fear and approach to threat corresponding to anxiety. These two psychological dimensions are mapped to underlying neural dimensions. Defensive distance is mapped to neural level, with the shortest defensive distances involving the lowest neural level (periaqueductal grey) and the largest defensive distances the highest neural level (prefrontal cortex). Defensive direction is mapped to separate parallel streams that run across these levels. A significant departure from prior models is the proposal that both fear and anxiety are represented at all levels. The theory is presented in a simplified form that does not incorporate the interactions that must occur between non-adjacent levels of the system. It also requires expansion to include the dimension of escapability of threat. Our current development and these proposed future extensions do not change the core concepts originally proposed by Gray and, we argue, demonstrate their enduring value. (C) 2004 Elsevier Ltd. All rights reserved.
    BibTeX:
    @article{McNaughton2004,
      author = {McNaughton, N and Corr, PJ},
      title = {A two-dimensional neuropsychology of defense: fear/anxiety and defensive distance},
      journal = {NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS},
      year = {2004},
      volume = {28},
      number = {3},
      pages = {285-305},
      doi = {{10.1016/j.neubiorev.2004.03.005}}
    }
    
    MEGA, M. & CUMMINGS, J. FRONTAL-SUBCORTICAL CIRCUITS AND NEUROPSYCHIATRIC DISORDERS {1994} JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES
    Vol. {6}({4}), pp. {358-370} 
    article  
    Abstract: Five parallel anatomic circuits link regions of the frontal cortex to the striatum, globus pallidus/substantia nigra, and thalamus. The circuits originate in the supplmentary motor area, frontal eye fields, dorsolateral prefrontal region, lateral orbitofrontal area, and anterior cingulate cortex. Open loop structures that provide input to or receive output from specific circuits share functions, cytoarchitectural features, and phylogenetic histories with the relevant circuits. The circuits mediate motor and oculomotor function as well as executive functions, socially responsive behavior, and motivation. Neuropsychiatric disorders of frontal-subcortical circuits include impaired executive function, disinhibition, and apathy; indicative mood disorders include depression, mania, and lability. Transmitters, modulators, receptor subtypes, and second messengers within the circuits provide a chemoarchitecture that can inform pharmacotherapy.
    BibTeX:
    @article{MEGA1994,
      author = {MEGA, MS and CUMMINGS, JL},
      title = {FRONTAL-SUBCORTICAL CIRCUITS AND NEUROPSYCHIATRIC DISORDERS},
      journal = {JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES},
      year = {1994},
      volume = {6},
      number = {4},
      pages = {358-370}
    }
    
    Menon, V., Adleman, N., White, C., Glover, G. & Reiss, A. Error-related brain activation during a Go/NoGo response inhibition task {2001} HUMAN BRAIN MAPPING
    Vol. {12}({3}), pp. {131-143} 
    article  
    Abstract: Inhibitory control and performance monitoring are critical executive functions of the human brain. Lesion and imaging studies have shown that the inferior frontal cortex plays an important role in inhibition of inappropriate response. In contrast, specific brain areas involved in error processing and their relation to those implicated in inhibitory control processes are unknown. In this study, we used a random effects model to investigate error-related brain activity associated with failure to inhibit response during a Go/NoGo task. Error-related brain activation was observed in the rostral aspect of the right anterior cingulate (BA 24/32) and adjoining medial prefrontal cortex, the left and right insular cortex and adjoining frontal operculum (BA 47) and left precuneus/posterior cingulate (BA 7/31/29). Brain activation related to response inhibition and competition was observed bilaterally in the dorsolateral prefrontal cortex (BA 9/46), pars triangularis region of the inferior frontal cortex (BA 45/47), premotor cortex (BA 6), inferior parietal lobule (BA 39), lingual gyrus and the caudate, as well as in the right dorsal anterior cingulate cortex (BA 24). These findings provide evidence for a distributed error processing system in the human brain that overlaps partially, but not completely, with brain regions involved in response inhibition and competition. In particular, the rostal anterior cingulate and posterior cingulate/precuneus as well as the left and right anterior insular cortex were activated only during error processing, but not during response competition, inhibition, selection, or execution. Our results also suggest that the brain regions involved in the error processing system overlap with brain areas implicated in the formulation and execution of articulatory plans. Hum. Brain Mapping 12:131-143, 2001. (C) 2001 Wiley-Liss, Inc.
    BibTeX:
    @article{Menon2001,
      author = {Menon, V and Adleman, NE and White, CD and Glover, GH and Reiss, AL},
      title = {Error-related brain activation during a Go/NoGo response inhibition task},
      journal = {HUMAN BRAIN MAPPING},
      year = {2001},
      volume = {12},
      number = {3},
      pages = {131-143}
    }
    
    Menon, V., Ford, J., Lim, K., Glover, G. & Pfefferbaum, A. Combined event-related fMRI and EEG evidence for temporal-parietal cortex activation during target detection {1997} NEUROREPORT
    Vol. {8}({14}), pp. {3029-3037} 
    article  
    Abstract: TARGET detection is the process of bringing a salient stimulus into conscious awareness. Target detection evokes a prominent event-related potential (ERP) component (P3) in the electroencephalogram (EEG). We combined the high spatial resolution of functional magnetic resonance imaging (fMRI) with the high temporal resolution of EEG to investigate the generators of the P3. Event-related brain activation (ERBA) and ERPs were computed by time-locked averaging of fMRI and EEG, respectively, recorded using the same paradigm in the same subjects. Target detection elicited significantly greater ERBAs bilaterally in the temporal-parietal cortex, thalamus and anterior cingulate. Spatio-temporal modelling of ERPs based on dipole locations derived from the ERBAs indicated that bilateral sources in the temporal-parietal cortex are the main generators of the P3. The findings provide convergent fMRI and EEG evidence for significant activation of the temporal-parietal cortex 285-610 ms after stimulus onset during target detection. The methods developed here provide a novel multimodal neuroimaging technique to investigate the spatio-temporal aspects of processes underlying brain function.
    BibTeX:
    @article{Menon1997,
      author = {Menon, V and Ford, JM and Lim, KO and Glover, GH and Pfefferbaum, A},
      title = {Combined event-related fMRI and EEG evidence for temporal-parietal cortex activation during target detection},
      journal = {NEUROREPORT},
      year = {1997},
      volume = {8},
      number = {14},
      pages = {3029-3037}
    }
    
    Mertz, H., Morgan, V., Tanner, G., Pickens, D., Price, R., Shyr, Y. & Kessler, R. Regional cerebral activation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distention {2000} GASTROENTEROLOGY
    Vol. {118}({5}), pp. {842-848} 
    article  
    Abstract: Background & Aims: Irritable bowel syndrome (IBS) is characterized by visceral hypersensitivity, possibly related to abnormal brain-gut communication, Positron emission tomography imaging has suggested specific central nervous system (CNS) abnormalities in visceral pain processing in IBS, This study aimed to determine (1) if functional magnetic resonance imaging (fMRI) detects CNS activity during painful and nonpainful visceral stimulation; and (2) if CNS pain centers in IBS respond abnormally. Methods: fMRI was performed during nonpainful and painful rectal distention in 18 patients with IBS and 16 controls. Results: Rectal stimulation increased the activity of anterior cingulate (33/34), prefrontal (32/34), insular cortices (33/34), and thalamus (32/34) in most subjects. In IBS subjects, but not controls, pain led to greater activation of the anterior cingulate cortex (ACC) than did nonpainful stimuli. IBS patients had a greater number of pixels activated in the ACC and reported greater intensity of pain at 55-mm Hg distention than controls, Conclusions: IBS patients activate the ACC, a critical CNS pain center, to a greater extent than controls in response to a painful rectal stimulus. Contrary to previous reports, these data suggest heightened pain sensitivity of the brain-gut axis in IBS, with a normal pattern of activation.
    BibTeX:
    @article{Mertz2000,
      author = {Mertz, H and Morgan, V and Tanner, G and Pickens, D and Price, R and Shyr, Y and Kessler, R},
      title = {Regional cerebral activation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distention},
      journal = {GASTROENTEROLOGY},
      year = {2000},
      volume = {118},
      number = {5},
      pages = {842-848}
    }
    
    Mesulam, M. Spatial attention and neglect: parietal, frontal and cingulate contributions to the mental representation and attentional targeting of salient extrapersonal events {1999} PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
    Vol. {354}({1387}), pp. {1325-1346} 
    article  
    Abstract: The syndrome of contralesional neglect reflects a lateralized disruption of spatial attention. In the human, the left hemisphere shifts attention predominantly in the contralateral hemispace and in a contraversive direction whereas the right hemisphere distributes attention more evenly, in both hemispaces and both directions. As a consequence of this asymmetry severe contralesional neglect occurs almost exclusively after right hemisphere lesions. Patients with left neglect experience a loss of salience in the mental representation and conscious perception of the left side and display a reluctance to direct orientating and exploratory behaviours to the left. Neglect is distributed according to egocentric, allocentric, world-centred, and object-centred frames of reference. Neglected events can continue to exert an implicit influence on behaviour, indicating that the attentional filtering occurs at the level of an internalized representation rather than at the level of peripheral sensory input. The unilateral neglect syndrome is caused by a dysfunction of a large-scale neurocognitive network, the cortical epicentres of which are located in posterior parietal cortex, the frontal eye fields, and the cingulate gyrus. This network coordinates all aspects of spatial attention, regardless of the modality of input or output. It helps to compile a mental representation of extrapersonal events in terms of their motivational salience, and to generate `kinetic strategies' so that the attentional focus can shift from one target to another.
    BibTeX:
    @article{Mesulam1999,
      author = {Mesulam, MM},
      title = {Spatial attention and neglect: parietal, frontal and cingulate contributions to the mental representation and attentional targeting of salient extrapersonal events},
      journal = {PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES},
      year = {1999},
      volume = {354},
      number = {1387},
      pages = {1325-1346}
    }
    
    Meunier, M., Bachevalier, J. & Mishkin, M. Effects of orbital frontal and anterior cingulate lesions on object and spatial memory in rhesus monkeys {1997} NEUROPSYCHOLOGIA
    Vol. {35}({7}), pp. {999-1015} 
    article  
    Abstract: Object memory processes, evaluated in rhesus monkeys by delayed nonmatching-to-sample with trial-unique stimuli and object reversal learning, were more severely impaired by orbital frontal than by anterior cingulate lesions. Spatial memory processes, assessed by spatial delayed response and spatial reversal learning, showed a weak trend in the opposite direction, though on these tasks neither lesion produced a serious loss. Comparison of the present results with those of earlier studies on the effects of various limbic system lesions suggests that object memory processes, including object recognition and object-reward association, are served by a circuit consisting mainly of the rhinal cortex, orbitofrontal cortex, and the magnocellular division of the medial dorsal thalamic nucleus. Although both the rhinal and orbitofrontal components of this circuit appear to participate in both functions, evidence from the present and earlier studies suggests that the orbitofrontal component is the more important one for associative memory, i.e. the formation across trials of associations between particular objects or classes of objects and reward, whereas the rhinal component is the more critical one for recognition memory, i.e. the storage and retrieval within trials of the representations of particular objects. Published by Elsevier Science Ltd.
    BibTeX:
    @article{Meunier1997,
      author = {Meunier, M and Bachevalier, J and Mishkin, M},
      title = {Effects of orbital frontal and anterior cingulate lesions on object and spatial memory in rhesus monkeys},
      journal = {NEUROPSYCHOLOGIA},
      year = {1997},
      volume = {35},
      number = {7},
      pages = {999-1015}
    }
    
    Meyer-Lindenberg, A., Buckholtz, J., Kolachana, B., Hariri, A., Pezawas, L., Blasi, G., Wabnitz, A., Honea, R., Verchinski, B., Callicott, J., Egan, M., Mattay, V. & Weinberger, D. Neural mechanisms of genetic risk for impulsivity and violence in humans {2006} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {103}({16}), pp. {6269-6274} 
    article DOI  
    Abstract: Neurobiological factors contributing to violence in humans remain poorly understood. One approach to this question is examining allelic variation in the X-linked monoamine oxidase A (MAOA) gene, previously associated with impulsive aggression in animals and humans. Here, we have studied the impact of a common functional polymorphism in MAOA on brain structure and function assessed with MRI in a large sample of healthy human volunteers. We show that the low expression variant, associated with increased risk of violent behavior, predicted pronounced limbic volume reductions and hyperresponsive amygdala during emotional arousal, with diminished reactivity of regulatory prefrontal regions, compared with the high expression allele. In men, the low expression allele is also associated with changes in orbitofrontal volume, amygdala and hippocampus hyperreactivity during aversive recall, and impaired cingulate activation during cognitive inhibition. Our data identify differences in limbic circuitry for emotion regulation and cognitive control that may be involved in the association of MAOA with impulsive aggression, suggest neural systems-level effects of X-inactivation in human brain, and point toward potential targets for a biological approach toward violence.
    BibTeX:
    @article{Meyer-Lindenberg2006,
      author = {Meyer-Lindenberg, A and Buckholtz, JW and Kolachana, B and Hariri, AR and Pezawas, L and Blasi, G and Wabnitz, A and Honea, R and Verchinski, B and Callicott, JH and Egan, M and Mattay, V and Weinberger, DR},
      title = {Neural mechanisms of genetic risk for impulsivity and violence in humans},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {2006},
      volume = {103},
      number = {16},
      pages = {6269-6274},
      doi = {{10.1073/pnas.0511311103}}
    }
    
    Meyer-Lindenberg, A., Poline, J., Kohn, P., Holt, J., Egan, M., Weinberger, D. & Berman, K. Evidence for abnormal cortical functional connectivity during working memory in schizophrenia {2001} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {158}({11}), pp. {1809-1817} 
    article  
    Abstract: Objective: Disturbed neuronal interactions may be involved in schizophrenia because it is without clear regional pathology. Aberrant connectivity is further suggested by theoretical formulations and neurochemical and neuroanatomical data. The authors applied to schizophrenia a recently available functional neuroimaging analytic method that permits characterization of cooperative action on the systems level. Method: Thirteen medication-free patients and 13 matched healthy comparison subjects performed a working memory (n-back) task and sensorimotor baseline task during positron emission tomography. ``Functional connectivity'' patterns, reflecting distributed correlated activity that differed most between groups, were extracted by a canonical variates analysis. Results: More than half the variance was explained by a single pattern showing inferotemporal, (para-)hippocampal, and cerebellar loadings for patients versus dorsolateral prefrontal and anterior cingulate activity for comparison subjects. Expression of this pattern perfectly separated all patient scans from comparison scans, thus showing promise as a trait marker. This result was validated prospectively by successfully classifying unrelated scans from the same patients and data from a new cohort. An additional 19% of variance corresponded to the pattern activated by the working memory task. Expression of this pattern was more variable in patients during working memory but not the control condition, suggesting inability to sustain a task-adequate neural network, consistent with the disconnection hypothesis. Conclusions: Pronounced disruptions of distributed cooperative activity in schizophrenia were found. A pattern showing disturbed frontotemporal interactions showed promise as a trait marker and may be useful for future investigations.
    BibTeX:
    @article{Meyer-Lindenberg2001,
      author = {Meyer-Lindenberg, A and Poline, JB and Kohn, PD and Holt, JL and Egan, MF and Weinberger, DR and Berman, KF},
      title = {Evidence for abnormal cortical functional connectivity during working memory in schizophrenia},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {2001},
      volume = {158},
      number = {11},
      pages = {1809-1817}
    }
    
    Miller, E. & Cohen, J. An integrative theory of prefrontal cortex function {2001} ANNUAL REVIEW OF NEUROSCIENCE
    Vol. {24}, pp. {167-202} 
    article  
    Abstract: The prefrontal cortex has long been suspected to play an important role in cognitive control, in the ability to orchestrate thought and action in accordance with internal goals. Its neural basis, however, has remained a mystery. Here, we propose that cognitive control stems from the active maintenance of patterns of activity in the prefrontal cortex that represent goals and the means to achieve them. They provide bias signals to other brain structures whose net effect is to guide the flow of activity along neural pathways that establish the proper mappings between inputs, internal states, and outputs needed to perform a given task. We review neurophysiological, neurobiological, neuroimaging, and computational studies that support this theory and discuss its implications as well as further issues to be addressed.
    BibTeX:
    @article{Miller2001,
      author = {Miller, EK and Cohen, JD},
      title = {An integrative theory of prefrontal cortex function},
      journal = {ANNUAL REVIEW OF NEUROSCIENCE},
      year = {2001},
      volume = {24},
      pages = {167-202}
    }
    
    Miltner, W., Braun, C. & Coles, M. Event-related brain potentials following incorrect feedback in a time-estimation task: Evidence for a ``generic'' neural system for error detection {1997} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {9}({6}), pp. {788-798} 
    article  
    Abstract: We examined scalp-recorded event-related potentials following feedback stimuli in a time-estimation task. Six hundred msec after indicating the end of a 1 sec interval, subjects received a visual, auditory, or somatosensory stimulus that indicated whether the interval their had produced was correct. Following feedback indicating incorrect performance, a negative deflection occurred, whose characteristics corresponded closely to those of the component (the error-related negativity) that accompanies errors in choice reaction time tasks. Furthermore, equivalent dipole analysis suggested that, for all three modalities, the distribution of the scalp potential was consistent with a local source in the anterior cingulate cortex or a more distributed source in the supplementary motor areas. These loci correspond closely to those described previously Tor the error-related negativity. We conclude that the error-related negativity is the manifestation of the activity of a ``genetic'' neural system involved in error detection.
    BibTeX:
    @article{Miltner1997,
      author = {Miltner, WHR and Braun, CH and Coles, MGH},
      title = {Event-related brain potentials following incorrect feedback in a time-estimation task: Evidence for a ``generic'' neural system for error detection},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {1997},
      volume = {9},
      number = {6},
      pages = {788-798}
    }
    
    Minoshima, S., Giordani, B., Berent, S., Frey, K., Foster, N. & Kuhl, D. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease {1997} ANNALS OF NEUROLOGY
    Vol. {42}({1}), pp. {85-94} 
    article  
    Abstract: This study investigated cerebral glucose metabolism in very early Alzheimer's disease, before a clinical diagnosis of probable Alzheimer's disease is possible, using [F-18] fluorodeoxyglucose positron emission tomography. First, 66 patients with probable Alzheimer's disease with a spectrum of dementia severity (Mini-Mental State Examination score, 0-23) were recruited and studied. Cortical metabolic activity was analyzed topographically using three-dimensional stereotactic surface projections. Regression analysis was performed for each brain pixel to predict metabolic patterns of very early disease. Predictions were tested prospectively in a group of 8 patients who complained only of memory impairment without general cognitive decline (Mini-Mental State Examination score, 25 +/- 1) at the time of scanning but whose condition later progressed to probable Alzheimer's disease. Both results were compared to cerebral metabolic activity in 22 age-similar normal control subjects. Prediction and analysis of actual patients consistently indicated marked metabolic reduction (21-22 in the posterior cingulate cortex and cinguloparietal transitional area in patients with very early Alzheimer's disease. Mean metabolic reduction in the posterior cingulate cortex was significantly greater than that in the lateral neocortices or parahippocampal cortex. The result suggests a functional importance for the posterior cingulate cortex in impairment of learning and memory, which is a feature of very early Alzheimer's disease.
    BibTeX:
    @article{Minoshima1997,
      author = {Minoshima, S and Giordani, B and Berent, S and Frey, KA and Foster, NL and Kuhl, DE},
      title = {Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease},
      journal = {ANNALS OF NEUROLOGY},
      year = {1997},
      volume = {42},
      number = {1},
      pages = {85-94}
    }
    
    Monchi, O., Petrides, M., Petre, V., Worsley, K. & Dagher, A. Wisconsin card sorting revisited: Distinct neural circuits participating in different stages of the task identified by event-related functional magnetic resonance imaging {2001} JOURNAL OF NEUROSCIENCE
    Vol. {21}({19}), pp. {7733-7741} 
    article  
    Abstract: The Wisconsin Card Sorting Task (WCST) has been used to assess dysfunction of the prefrontal cortex and basal ganglia. Previous brain imaging studies have focused on identifying activity related to the set-shifting requirement of the WCST The present study used event-related functional magnetic resonance imaging (fMRI) to study the pattern of activation during four distinct stages in the performance of this task. Eleven subjects were scanned while performing the WCST and a control task involving matching two identical cards. The results demonstrated specific involvement of different prefrontal areas during different stages of task performance. The mid-dorsolateral prefrontal cortex (area 9/46) increased activity while subjects received either positive or negative feedback, that is at the point when the current information must be related to earlier events stored in working memory. This is consistent with the proposed role of the mid-dorsolateral prefrontal cortex in the monitoring of events in working memory. By contrast, a cortical basal ganglia loop involving the mid-ventrolateral prefrontal cortex (area 47/12), caudate nucleus, and mediodorsal thalamus increased activity specifically during the reception of negative feedback, which signals the need for a mental shift to a new response set. The posterior prefrontal cortex response was less specific; increases in activity occurred during both the reception of feedback and the response period, indicating a role in the association of specific actions to stimuli. The putamen exhibited increased activity while matching after negative feedback but not while matching after positive feedback, implying greater involvement during novel than routine actions.
    BibTeX:
    @article{Monchi2001,
      author = {Monchi, O and Petrides, M and Petre, V and Worsley, K and Dagher, A},
      title = {Wisconsin card sorting revisited: Distinct neural circuits participating in different stages of the task identified by event-related functional magnetic resonance imaging},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2001},
      volume = {21},
      number = {19},
      pages = {7733-7741}
    }
    
    MORECRAFT, R., GEULA, C. & MESULAM, M. CYTOARCHITECTURE AND NEURAL AFFERENTS OF ORBITOFRONTAL CORTEX IN THE BRAIN OF THE MONKEY {1992} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {323}({3}), pp. {341-358} 
    article  
    Abstract: The orbitofrontal cortex of the monkey can be subdivided into a caudal agranular sector, a transitional dysgranular sector, and an anterior granular sector. The neural input into these sectors was investigated with the help of large horseradish peroxidase injections that covered the different sectors of orbitofrontal cortex. The distribution of retrograde labeling showed that the majority of the cortical projections to orbitofrontal cortex arises from a restricted set of telencephalic sources, which include prefrontal cortex, lateral, and inferomedial temporal cortex, the temporal pole, cingulate gyrus, insula, entorhinal cortex, hippocampus, amygdala, and claustrum. The posterior portion of the orbitofrontal cortex receives additional input from the piriform cortex and the anterolateral portion from gustatory, somatosensory, and premotor areas. Thalamic projections to the orbitofrontal cortex arise from midline and intralaminar nuclei, from the anteromedial nucleus, the medial dorsal nucleus, and the pulvinar nucleus. Orbitofrontal cortex also receives projections from the hypothalamus, nucleus basalis, ventral tegmental area, the raphe nuclei, the nucleus locus coeruleus, and scattered neurons of the pontomesencephalic tegmentum. The non-isocortical (agranular-dysgranular) sectors of orbitofrontal cortex receive more intense projections from the non-isocortical sectors of paralimbic areas, the hippocampus, amygdala, and midline thalamic nuclei, whereas the isocortical (granular) sector receives more intense projections from the dorsolateral prefrontal area, the granular insula, granular temporopolar cortex, posterolateral temporal cortex, and from the medial dorsal and pulvinar thalamic nuclei. Retrograde labeling within cingulate, entorhinal, and hippocampal cortices was most pronounced when the injection site extended medially into the dysgranular paraolfactory cortex of the gyrus rectus, an area that can be conceptualized as an orbitofrontal extension of the cingulate complex. These observations demonstrate that the orbitofrontal cortex has cytoarchitectonically organized projections and that it provides a convergence zone for afferents from heteromodal association and limbic areas. The diverse connections of orbitofrontal cortex are in keeping with the participation of this region in visceral, gustatory, and olfactory functions and with its importance in memory, motivation, and epileptogenesis.
    BibTeX:
    @article{MORECRAFT1992,
      author = {MORECRAFT, RJ and GEULA, C and MESULAM, MM},
      title = {CYTOARCHITECTURE AND NEURAL AFFERENTS OF ORBITOFRONTAL CORTEX IN THE BRAIN OF THE MONKEY},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {1992},
      volume = {323},
      number = {3},
      pages = {341-358}
    }
    
    Morris, J., Friston, K., Buchel, C., Frith, C., Young, A., Calder, A. & Dolan, R. A neuromodulatory role for the human amygdala in processing emotional facial expressions {1998} BRAIN
    Vol. {121}({Part 1}), pp. {47-57} 
    article  
    Abstract: Localized amygdalar lesions in humans produce deficits in the recognition of fearful facial expressions. We used functional neuroimaging to test two hypotheses: (i) that the amygdala and some of its functionally connected structures mediate specific neural responses to fearful expressions; (ii) that the early visual processing of emotional faces can be influenced by amygdalar activity. Normal subjects were scanned using PET while they performed a gender discrimination task involving static grey-scale images of faces expressing varying degrees of fear or happiness. In support of the first hypothesis, enhanced activity in the left amygdala, left pulvinar, left anterior insula and bilateral anterior cingulate gyri was observed during the processing of fearful faces. Evidence consistent with the second hypothesis was obtained by a demonstration that amygdalar responses predict expression specific neural activity in extrastriate cortex.
    BibTeX:
    @article{Morris1998,
      author = {Morris, JS and Friston, KJ and Buchel, C and Frith, CD and Young, AW and Calder, AJ and Dolan, RJ},
      title = {A neuromodulatory role for the human amygdala in processing emotional facial expressions},
      journal = {BRAIN},
      year = {1998},
      volume = {121},
      number = {Part 1},
      pages = {47-57}
    }
    
    Muir, J., Everitt, B. & Robbins, T. The cerebral cortex of the rat and visual attentional function: Dissociable effects of mediofrontal, cingulate, anterior dorsolateral, and parietal cortex lesions on a five-choice serial reaction time task {1996} CEREBRAL CORTEX
    Vol. {6}({3}), pp. {470-481} 
    article  
    Abstract: Dissociable effects of bilateral excitotoxic lesions of different regions of the rat neocortex, including medial prefrontal and anterior cingulate cortices, were investigated in a five-choice serial reaction time task that provides several indices of the accuracy and speed of attentional function. Whereas medial prefrontal cortical lesions impaired performance of the task as revealed by a reduction in choice accuracy, an increase in the latency to respond correctly to the visual target and enhanced perseverative responding, lesions of the anterior cingulate cortex specifically increased premature responding. By contrast, lateral frontal cortical lesions did not significantly disrupt baseline performance of the task, but rather increased the latency to respond correctly to the visual target during various behavioral manipulations, for example, when the length of the intertrial interval was varied unpredictably and during interpolation of distracting bursts of white noise. Lesions of the parietal cortex failed to disrupt any aspect of task performance investigated. These behavioral effects in the five-choice task were compared with the effect of these same lesions on acquisition and retention of a one-trial passive avoidance task. The main finding from this paradigm was that lesions of the lateral frontal cortex produced a significant disruption to the retention of passive avoidance, which stands in marked contrast to the successful retention observed by animals of the other lesion groups. In addition, this pattern of results reveals that the `'disinhibitory'' effect of cingulate cortex lesions are relatively specific to the five-choice attentional task. Finally, the results of the present study are compared with the findings of previous experiments using the five-choice task, which have examined the effect of selective manipulations of the ascending noradrenergic, cholinergic, dopaminergic, and serotonergic projections. In particular, the deficits in attentional function observed following cholinergic lesions of the nucleus basalis magnocellularis appear to be attributable to cholinergic denervation of the medial frontal cortex. These results are discussed in terms of the role of parallel distributed neural systems within the neocortex that mediate continuous attentional performance in the rat.
    BibTeX:
    @article{Muir1996,
      author = {Muir, JL and Everitt, BJ and Robbins, TW},
      title = {The cerebral cortex of the rat and visual attentional function: Dissociable effects of mediofrontal, cingulate, anterior dorsolateral, and parietal cortex lesions on a five-choice serial reaction time task},
      journal = {CEREBRAL CORTEX},
      year = {1996},
      volume = {6},
      number = {3},
      pages = {470-481}
    }
    
    Neisewander, J., Baker, D., Fuchs, R., Tran-Nguyen, L., Palmer, A. & Marshall, J. Fos protein expression and cocaine-seeking behavior in rats after exposure to a cocaine self-administration environment {2000} JOURNAL OF NEUROSCIENCE
    Vol. {20}({2}), pp. {798-805} 
    article  
    Abstract: To examine neuronal activation associated with incentive motivation for cocaine, cocaine-seeking behavior (operant responding without cocaine reinforcement) and Fos expression were examined in rats exposed to saline and cocaine priming injections and/or a self-administration environment. Rats were first trained to self-administer cocaine or received yoked saline administration (''control''). They then received 21 daily exposures to either the self-administration environment (''extinction'') or a different environment (''no extinction'') without cocaine available. Extinction training, used to decrease incentive motivation for cocaine elicited by the self-administration environment, decreased cocaine-seeking behavior elicited by both the environment and the cocaine priming injection. Exposure to the self-administration environment enhanced Fos expression in the no extinction group relative to control and extinction groups in the anterior cingulate, basolateral amygdala, hippocampal CA1 region, dentate gyrus, nucleus accumbens shell and core, and central gray area, regardless of whether or not priming injections were given. The priming injections enhanced Fos expression in the ventral tegmental area, caudate putamen, substantia nigra pars reticulata, entorhinal cortex, central amygdala, lateral amygdala, arcuate nucleus, and central gray area, regardless of group. Thus, these changes likely reflect an unconditioned effect from either cocaine or injection stress. The priming injections also enhanced Fos expression in the anterior cingulate, but only in cocaine-experienced groups, suggesting that this enhancement reflects an experience-dependent motivational effect of the priming injections. The results suggest that different neural circuits may be involved in the incentive motivational effects of cocaine-paired environmental stimuli versus priming injections and that the anterior cingulate may be part of a common pathway for both.
    BibTeX:
    @article{Neisewander2000,
      author = {Neisewander, JL and Baker, DA and Fuchs, RA and Tran-Nguyen, LTL and Palmer, A and Marshall, JF},
      title = {Fos protein expression and cocaine-seeking behavior in rats after exposure to a cocaine self-administration environment},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2000},
      volume = {20},
      number = {2},
      pages = {798-805}
    }
    
    Nieuwenhuis, S., Ridderinkhof, K., Blow, J., Band, G. & Kok, A. Error-related brain potentials are differentially related to awareness of response errors: Evidence from an antisaccade task {2001} PSYCHOPHYSIOLOGY
    Vol. {38}({5}), pp. {752-760} 
    article  
    Abstract: The error negativity (Ne/ERN) and error positivity (Pe) are two components of the event-related brain potential (ERP) that are associated with action monitoring and error detection. To investigate the relation between error processing and conscious self-monitoring of behavior, the present experiment examined whether an Ne and Pe are observed after response errors of which participants are unaware. Ne and Pe measures, behavioral accuracy, and trial-to-trial subjective accuracy judgments were obtained from participants performing an antisaccade task. which elicits Many unperceived, incorrect reflex-like saccades. Consistent with previous research, subjectively unperceived saccade errors were almost always immediately corrected, and were associated with faster correction times and smaller saccade sizes than perceived errors. Importantly, irrespective of whether the participant was aware of the error or not, erroneous saccades were followed by a sizable Ne. In contrast, the Pe was much more pronounced for perceived than for unperceived errors. Unperceived errors were characterized by the absence of posterror slowing. These and other results are consistent with the view that the Ne and Pe reflect the activity of two separate error monitoring processes, of which only the later process, reflected by the Pe, is associated with conscious error recognition and remedial action.
    BibTeX:
    @article{Nieuwenhuis2001,
      author = {Nieuwenhuis, S and Ridderinkhof, KR and Blow, J and Band, GPH and Kok, A},
      title = {Error-related brain potentials are differentially related to awareness of response errors: Evidence from an antisaccade task},
      journal = {PSYCHOPHYSIOLOGY},
      year = {2001},
      volume = {38},
      number = {5},
      pages = {752-760}
    }
    
    Nimchinsky, E., Gilissen, E., Allman, J., Perl, D., Erwin, J. & Hof, P. A neuronal morphologic type unique to humans and great apes {1999} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {96}({9}), pp. {5268-5273} 
    article  
    Abstract: We report the existence and distribution of an unusual type of projection neuron, a large, spindle-shaped cell, in layer Vb of the anterior cingulate cortex of pongids and hominids. These spindle cells were not observed in any other primate species or any other mammalian taxa, and their volume was correlated with brain volume residuals, a measure of encephalization in higher primates. These observations are of particular interest when considering primate neocortical evolution, as they reveal possible adaptive changes and functional modifications over the last 15-20 million years in the anterior cingulate cortex, a region that plays a major role in the regulation of many aspects of autonomic function and of certain cognitive processes. That in humans these unique neurons have been shown previously to be severely affected in the degenerative process of Alzheimer's disease suggests that some of the differential neuronal susceptibility that occurs in the human brain in the course of age-related dementing illnesses may have appeared only recently during primate evolution.
    BibTeX:
    @article{Nimchinsky1999,
      author = {Nimchinsky, EA and Gilissen, E and Allman, JM and Perl, DP and Erwin, JM and Hof, PR},
      title = {A neuronal morphologic type unique to humans and great apes},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1999},
      volume = {96},
      number = {9},
      pages = {5268-5273}
    }
    
    Nobre, A., Sebestyen, G., Gitelman, D., Mesulam, M., Frackowiak, R. & Frith, C. Functional localization of the system for visuospatial attention using positron emission tomography {1997} BRAIN
    Vol. {120}({Part 3}), pp. {515-533} 
    article  
    Abstract: PET was used to image the neural system underlying visuospatial attention. Analysis of data at both the group and individual-subject level provided anatomical resolution superior to that described to date. Six right-handed male subjects were selected from a pilot behavioural study in which behavioural responses and eye movements were recorded. The attention tasks involved covert shifts of attention, where peripheral cues indicated the location of subsequent target stimuli to be discriminated. One attention condition emphasized reflexive aspects of spatial orientation, while the other required controlled shifts of attention. PET activations agreed closely with the cortical regions recently proposed to form the core of a neural network for spatial attention. The two attention tasks evoked largely overlapping patterns of neural activation, supporting the existence of a general neural system for visuospatial attention with regional functional specialization. Specifically, neocortical activations were observed in the right anterior cingulate gyrus (Brodmann area 24), in the intraparietal sulcus of right posterior parietal cortex, and in the mesial and lateral premotor cortices (Brodmann area 6).
    BibTeX:
    @article{Nobre1997,
      author = {Nobre, AC and Sebestyen, GN and Gitelman, DR and Mesulam, MM and Frackowiak, RSJ and Frith, CD},
      title = {Functional localization of the system for visuospatial attention using positron emission tomography},
      journal = {BRAIN},
      year = {1997},
      volume = {120},
      number = {Part 3},
      pages = {515-533}
    }
    
    Northoff, G. & Bermpohl, F. Cortical midline structures and the self {2004} TRENDS IN COGNITIVE SCIENCES
    Vol. {8}({3}), pp. {102-107} 
    article DOI  
    Abstract: For a long time philosophers and psychologists have been intrigued by the question of the self. More recently, this has become a topic of discussion in neuroscience. In this article, we suggest that the processing of self-referential stimuli in cortical midline structures (CMS) is a fundamental component in generating a model of the self. Drawing from neuroimaging studies, we distinguish between representation, monitoring, evaluation and integration of self-referential stimuli. All of these subfunctions are related to distinct regions within the CMS. This relationship between self-referential processing and CMS might provide novel insight into the neural correlates underlying the constitution of the self.
    BibTeX:
    @article{Northoff2004,
      author = {Northoff, G and Bermpohl, F},
      title = {Cortical midline structures and the self},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      year = {2004},
      volume = {8},
      number = {3},
      pages = {102-107},
      doi = {{10.1016/j.tics.2004.01.004}}
    }
    
    Nyberg, L., McIntosh, A., Cabeza, R., Habib, R., Houle, S. & Tulving, E. General and specific brain regions involved in encoding and retrieval of events: What, where, and when {1996} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {93}({20}), pp. {11280-11285} 
    article  
    Abstract: Remembering an event involves not only what happened, but also where and when it occurred, We measured regional cerebral blood flow by positron emission tomography during initial encoding and subsequent retrieval of item, location, and time information. Multivariate image analysis showed that left frontal brain regions were always activated during encoding, and right superior frontal regions were always activated at retrieval. Pairwise image subtraction analyses revealed information-specific activations at (i) encoding, item information in left hippocampal, location information in right parietal, and time information in left fusiform regions; and (ii) retrieval, item in right inferior frontal and temporal, location in left frontal, and time in anterior cingulate cortices. These results point to the existence of general encoding and retrieval networks of episodic memory whose operations are augmented by unique brain areas recruited for processing specific aspects of remembered events.
    BibTeX:
    @article{Nyberg1996,
      author = {Nyberg, L and McIntosh, AR and Cabeza, R and Habib, R and Houle, S and Tulving, E},
      title = {General and specific brain regions involved in encoding and retrieval of events: What, where, and when},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1996},
      volume = {93},
      number = {20},
      pages = {11280-11285}
    }
    
    Nyberg, L., Tulving, E., Habib, R., Nilsson, L., Kapur, S., Houle, S., Cabeza, R. & McIntosh, A. Functional brain maps of retrieval mode and recovery of episodic information {1995} NEUROREPORT
    Vol. {7}({1}), pp. {249-252} 
    article  
    Abstract: POSITRON emission tomography (PET) was used to identify brain regions associated with two component processes of episodic retrieval; those related to thinking back in subjective time (retrieval mode) and those related to actual recovery of stored information (ecphory). Healthy young subjects recognized words that: had been encoded with respect to meaning or the speaker's voice. Regardless of how the information had been encoded, recognition was associated with increased activation in regions in right prefrontal cortex, left anterior cingulate, and cerebellum. These activations reflect retrieval mode. Recognition following meaning encoding was specifically associated with increased activation in left temporal cortex, and recognition following voice encoding involved regions in right orbital frontal and parahippocampal cortex. These activations reflect ecphory of differentially encoded information.
    BibTeX:
    @article{Nyberg1995,
      author = {Nyberg, L and Tulving, E and Habib, R and Nilsson, LG and Kapur, S and Houle, S and Cabeza, R and McIntosh, AR},
      title = {Functional brain maps of retrieval mode and recovery of episodic information},
      journal = {NEUROREPORT},
      year = {1995},
      volume = {7},
      number = {1},
      pages = {249-252}
    }
    
    O'Doherty, J. Reward representations and reward-related learning in the human brain: insights from neuroimaging {2004} CURRENT OPINION IN NEUROBIOLOGY
    Vol. {14}({6}), pp. {769-776} 
    article DOI  
    Abstract: This review outlines recent findings from human neuroimaging concerning the role of a highly interconnected network of brain areas including orbital and medial prefrontal cortex, amygdala, striatum and dopaminergic mid-brain in reward processing. Distinct reward-related functions can be attributed to different components of this network. Orbitofrontal cortex is involved in coding stimulus reward value and in concert with the amygdala and ventral striatum is implicated in representing predicted future reward. Such representations can be used to guide action selection for reward, a process that depends, at least in part, on orbital and medial prefrontal cortex as well as dorsal striatum.
    BibTeX:
    @article{O'Doherty2004,
      author = {O'Doherty, JP},
      title = {Reward representations and reward-related learning in the human brain: insights from neuroimaging},
      journal = {CURRENT OPINION IN NEUROBIOLOGY},
      year = {2004},
      volume = {14},
      number = {6},
      pages = {769-776},
      doi = {{10.1016/j.conb.2004.10.016}}
    }
    
    Ochsner, K., Bunge, S., Gross, J. & Gabrieli, J. Rethinking feelings: An fMRI study of the cognitive regulation of emotion {2002} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {14}({8}), pp. {1215-1229} 
    article  
    Abstract: The ability to cognitively regulate emotional responses to aversive events is important for mental and physical health. Little is known, however, about neural bases of the cognitive control of emotion. The present study employed functional magnetic resonance imaging to examine the neural systems used to reappraise highly negative scenes in unemotional terms. Reappraisal of highly negative scenes reduced subjective experience of negative affect. Neural correlates of reappraisal were increased activation of the lateral and medial prefrontal regions and decreased activation of the amygdala and medial orbito-frontal cortex. These findings support the hypothesis that prefrontal cortex is involved in constructing reappraisal strategies that can modulate activity in multiple emotion-processing systems.
    BibTeX:
    @article{Ochsner2002,
      author = {Ochsner, KN and Bunge, SA and Gross, JJ and Gabrieli, JDE},
      title = {Rethinking feelings: An fMRI study of the cognitive regulation of emotion},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {2002},
      volume = {14},
      number = {8},
      pages = {1215-1229}
    }
    
    Ochsner, K., Knierim, K., Ludlow, D., Hanelin, J., Ramachandran, T., Glover, G. & Mackey, S. Reflecting upon feelings: an fMRI study of neural systems supporting the attribution of emotion to self and other {2004} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {16}({10}), pp. {1746-1772} 
    article  
    Abstract: Understanding one's own and other individual's emotional states is essential for maintaining emotional equilibrium and strong social bonds. Although the neural substrates supporting reflection upon one's own feelings have been investigated, no studies have directly examined attributions about the internal emotional states of others to determine whether common or distinct neural systems support these abilities. The present study sought to directly compare brain regions involved in judging one's own, as compared to another individual's, emotional state. Thirteen participants viewed mixed valence blocks of photos drawn from the International Affective Picture System while whole-brain fMRI data were collected. Preblock cues instructed participants to evaluate either their emotional response to each photo, the emotional state of the central figure in each photo, or (in a baseline condition) whether the photo was taken indoors or outdoors. Contrasts indicated (1) that both self and other judgments activated the medial prefrontal cortex (MPFC), the superior temporal gyrus, and the posterior cingulate/precuneus, (2) that self judgments selectively activated subregions of the MPFC and the left temporal cortex, whereas (3) other judgments selectively activated the left lateral prefrontal cortex (including Broca's area) and the medial occipital cortex. These results suggest (1) that self and other evaluation of emotion rely on a network of common mechanisms centered on the MPFC, which has been hypothesized to support mental state attributions in general, and (2) that medial and lateral PFC regions selectively recruited by self or other judgments may be involved in attention to, and elaboration of, internally as opposed to externally generated information.
    BibTeX:
    @article{Ochsner2004a,
      author = {Ochsner, KN and Knierim, K and Ludlow, DH and Hanelin, J and Ramachandran, T and Glover, G and Mackey, SC},
      title = {Reflecting upon feelings: an fMRI study of neural systems supporting the attribution of emotion to self and other},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {2004},
      volume = {16},
      number = {10},
      pages = {1746-1772}
    }
    
    Ochsner, K., Ray, R., Cooper, J., Robertson, E., Chopra, S., Gabrieli, J. & Gross, J. For better or for worse: neural systems supporting the cognitive down- and up-regulation of negative emotion {2004} NEUROIMAGE
    Vol. {23}({2}), pp. {483-499} 
    article DOI  
    Abstract: Functional neuroimaging studies examining the neural bases of the cognitive control of emotion have found increased prefrontal and decreased amygdala activation for the reduction or down-regulation of negative emotion. It is unknown, however, (1) whether the same neural systems underlie the enhancement or tip-regulation of emotion, and (2) whether altering the nature of the regulatory strategy alters the neural systems mediating the regulation. To address these questions using functional magnetic resonance imaging (fMRI), participants up- and down-regulated negative emotion either by focusing internally on the self-relevance of aversive scenes or by focusing externally on alternative meanings for pictured actions and their situational contexts Results indicated (1a) that both up- and down-regulating negative emotion recruited prefrontal and anterior cingulate regions implicated in cognitive control, (1b) that amygdala activation was modulated up or down in accord with the regulatory goal, and (1c) that up-regulation uniquely recruited regions of left rostromedial PFC implicated in the retrieval of emotion knowledge, whereas down-regulation uniquely recruited regions of right lateral and orbital PFC implicated in behavioral inhibition. Results also indicated that (2) self-focused regulation recruited medial prefrontal regions implicated in internally focused processing, whereas situation-focused regulation recruited lateral prefrontal regions implicated in externally focused processing. These data suggest that both common and distinct neural systems support various forms of reappraisal and that which particular prefrontal systems modulate the amygdala in different ways depends on the regulatory goal and strategy employed. (C) 2004 Elsevier Inc. All rights reserved.
    BibTeX:
    @article{Ochsner2004,
      author = {Ochsner, KN and Ray, RD and Cooper, JC and Robertson, ER and Chopra, S and Gabrieli, JDE and Gross, JJ},
      title = {For better or for worse: neural systems supporting the cognitive down- and up-regulation of negative emotion},
      journal = {NEUROIMAGE},
      year = {2004},
      volume = {23},
      number = {2},
      pages = {483-499},
      doi = {{10.1016/j.neuroimage.2004.06.030}}
    }
    
    OHISHI, H., AKAZAWA, C., SHIGEMOTO, R., NAKANISHI, S. & MIZUNO, N. DISTRIBUTIONS OF THE MESSENGER-RNAS FOR L-2-AMINO-4-PHOSPHONOBUTYRATE-SENSITIVE METABOTROPIC GLUTAMATE RECEPTORS, MGLUR4 AND MGLUR7, IN THE RAT-BRAIN {1995} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {360}({4}), pp. {555-570} 
    article  
    Abstract: The distribution of mRNAs for metabotropic glutamate receptors, mGluR4 and mGluR7, which are highly sensitive for L-2-amino-4-phosphonobutyrate (L-AP4), was examined in the central nervous system of the rat by in situ hybridization. In general, the hybridization signals of mGluR7 mRNA were more widely distributed than those of mGluR4 mRNA, and differential expression of mGluR4 mRNA and mGluR7 mRNA was clearly indicated in some brain regions. Intense or moderate expression of mGluR4 mRNA was detected in the granule cells of the olfactory bulb and cerebellum, whereas no significant expression of mGluR7 mRNA was found in these cells. In other neurons or regions where mGluR7 mRNA was intensely or moderately expressed, no significant expression of mGluR4 mRNA was observed. Such were the mitral and tufted cells of the olfactory bulb; anterior olfactory nucleus; neocortical regions; cingulate cortex; retrosplenial cortex; piriform cortex; perirhinal cortex; CA1; CA3; granule cells of the dentate gyrus; superficial layers of the subicular cortex; deep layers of the entorhinal, parasubicular, and presubicular cortices; ventral part of the lateral septal nucleus; septohippocampal nucleus; triangular septal nucleus; nuclei of the diagonal band; bed nucleus of the stria terminalis; ventral pallidum; claustrum; amygdaloid nuclei other than the intercalated nuclei; preoptic region; hypothalamic nuclei other than the medial mammillary nucleus; ventral lateral geniculate nucleus; locus coeruleus; Purkinje cells; many nuclei of the lower brainstem other than the superior colliculus, periaqueductal gray, interpeduncular nucleus, pontine nuclei, and dorsal cochlear nucleus; and dorsal horn of the spinal cord. Both mGluR4 mRNA and mGluR7 mRNA were moderately or intensely expressed in the olfactory tubercle, superficial layers of the entorhinal cortex, CA4, septofimbrial nucleus, intercalated nuclei of the amygdala, medial mammillary nucleus, many thalamic nuclei, and pontine nuclei. Intense expression of both mGluR4 mRNA and mGluR7 mRNA was further detected in the trigeminal ganglion and dorsal root ganglia, whereas no significant expression of them was found in the pterygopalatine ganglion and superior cervical ganglion. The results indicate differential roles of the L-AP4-sensitive metabotropic glutamate receptors in the glutamatergic nervous system. (C) 1995 Wiley-Liss, Inc.
    BibTeX:
    @article{OHISHI1995,
      author = {OHISHI, H and AKAZAWA, C and SHIGEMOTO, R and NAKANISHI, S and MIZUNO, N},
      title = {DISTRIBUTIONS OF THE MESSENGER-RNAS FOR L-2-AMINO-4-PHOSPHONOBUTYRATE-SENSITIVE METABOTROPIC GLUTAMATE RECEPTORS, MGLUR4 AND MGLUR7, IN THE RAT-BRAIN},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {1995},
      volume = {360},
      number = {4},
      pages = {555-570}
    }
    
    Olney, J., Newcomer, J. & Farber, N. NMDA receptor hypofunction model of schizophrenia {1999} JOURNAL OF PSYCHIATRIC RESEARCH
    Vol. {33}({6}), pp. {523-533} 
    article  
    Abstract: Several decades of research attempting to explain schizophrenia in terms of the dopamine hyperactivity hypothesis have produced disappointing results. A new hypothesis focusing on hypofunction of the NMDA glutamate transmitter system is emerging as a potentially more promising concept. In this article, we present a version of the NMDA receptor hypofunction hypothesis that has evolved from our recent studies pertaining to the neurotoxic and psychotomimetic effects of PCP and related NMDA antagonist drugs. In this article, we examine this hypothesis in terms of its strengths and weaknesses, its therapeutic implications and ways in which it can be further tested. (C) 1999 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{Olney1999,
      author = {Olney, JW and Newcomer, JW and Farber, NB},
      title = {NMDA receptor hypofunction model of schizophrenia},
      journal = {JOURNAL OF PSYCHIATRIC RESEARCH},
      year = {1999},
      volume = {33},
      number = {6},
      pages = {523-533}
    }
    
    Ongur, D., An, X. & Price, J. Prefrontal cortical projections to the hypothalamus in macaque monkeys {1998} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {401}({4}), pp. {480-505} 
    article  
    Abstract: The organization of projections from the macaque orbital and medial prefrontal cortex (OMPFC) to the hypothalamus and related regions of the diencephalon and midbrain was studied with retrograde and anterograde tracing techniques. Almost all of the prefrontal cortical projections to the hypothalamus arise from areas within the ``medial prefrontal network,'' as defined previously by Carmichael and Price ([1996] J. Comp. Neurol. 371:179-207). Outside of the OMPFC, only a few neurons in the temporal Dole, anterior cingulate and insular cortex project to the hypothalamus. Axons from the OMPFC also innervate the basal forebrain, zona incerta, and ventral midbrain. Within the medial prefrontal network, different regions project to distinct parts of the hypothalamus. The medial wall areas 25 and 32 send the heaviest projections to the hypothalamus; axons from these areas are especially concentrated in the anterior hypothalamic area and the ventromedial hypothalamic nucleus. Orbital areas 13a, 12o, and Iai, which are related to the medial prefrontal network, selectively innervate the lateral hypothalamic area, especially its posterior part. The cellular regions of the paraventricular, supraoptic, suprachiasmatic, arcuate, and mammillary nuclei are conspicuously devoid of cortical axons, but many axons abut the borders of these nuclei and may contact dendrites that extend from them. Areas within the orbital prefrontal network on the posterior orbital surface and agranular insula send only weak projections to the posterior lateral hypothalamic area. The rostral orbital surface does not contribute to the cortico-hypothalamic projection. (C) 1998 Wiley-Liss, Inc.
    BibTeX:
    @article{Ongur1998,
      author = {Ongur, D and An, X and Price, JL},
      title = {Prefrontal cortical projections to the hypothalamus in macaque monkeys},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {1998},
      volume = {401},
      number = {4},
      pages = {480-505}
    }
    
    Ongur, D., Ferry, A. & Price, J. Architectonic subdivision of the human orbital and medial prefrontal cortex {2003} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {460}({3}), pp. {425-449} 
    article DOI  
    Abstract: The structure of the human orbital and medial prefrontal cortex (OMPFC) was investigated using five histological and immunohistochemical stains and was correlated with a previous analysis in macaque monkeys [Carmichael and Price (1994) J. Comp. Neurol. 346:366-402]. A cortical area was recognized if it was distinct with at least two stains and was found in similar locations in different brains. All of the areas recognized in the macaque OMPFC have counterparts in humans. Areas 11, 13, and 14 were subdivided into areas 11m, 111, 13a, 13b, 13m, 131, 14r, and 14c. Within area 10, the region corresponding to area 10m in monkeys was divided into 10m and 10r, and area 10o (orbital) was renamed area 10p (polar). Areas 47/12r, 47/12m, 47/12l, and 47/12s occupy the lateral orbital cortex, corresponding to monkey areas 12r, 12m, 121, and 12o. The agranular insula (areas lam, Iapm, Iai, and Ial) extends onto the caudal orbital surface and into the horizontal ramus of the lateral sulcus. The growth of the frontal pole in humans has pushed area 25 and area 32pl, which corresponds to the prelimbic area 32 in Brodmann's monkey brain map, caudal and ventral to the genu of the corpus callosum. Anterior cingulate areas 24a and 24b also extend ventral to the genu of the corpus callosum. Area 32ac, corresponding to the dorsal anterior cingulate area 32 in Brodmann's human brain map, is anterior and dorsal to the genu. The parallel organization of the OMPFC in monkeys and humans allows experimental data from monkeys to be applied to studies of the human cortex. (C) 2003 Wiley-Liss, Inc.
    BibTeX:
    @article{Ongur2003,
      author = {Ongur, D and Ferry, AT and Price, JL},
      title = {Architectonic subdivision of the human orbital and medial prefrontal cortex},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {2003},
      volume = {460},
      number = {3},
      pages = {425-449},
      doi = {{10.1002/cne.10609}}
    }
    
    Owen, A., McMillan, K., Laird, A. & Bullmore, E. N-back working memory paradigm: A meta-analysis of normative functional neuroimaging {2005} HUMAN BRAIN MAPPING
    Vol. {25}({1}), pp. {46-59} 
    article DOI  
    Abstract: One of the most popular experimental paradigms for functional neuroimaging studies of working memory has been the n-back task, in which subjects are asked to monitor the identity or location of a series of verbal or nonverbal stimuli and to indicate when the currently presented stimulus is the same as the one presented n trials previously. We conducted a quantitative meta-analysis of 668 sets of activation coordinates in Talairach space reported in 24 primary studies of n-back task variants manipulating process (location vs. identity monitoring) and content (verbal or nonverbal) of working memory. We found the following cortical regions were activated robustly (voxelwise false discovery rate = 1: lateral premotor cortex; dorsal cingulate and medial premotor cortex; dorsolateral and ventrolateral prefrontal cortex; frontal poles; and medial and lateral posterior parietal cortex. Subsidiary meta-analyses based on appropriate subsets of the primary data demonstrated broadly similar activation patterns for identity monitoring of verbal stimuli and both location and identity monitoring of nonverbal stimuli. There was also some evidence for distinct frontoparietal activation patterns in response to different task variants. The functional specializations of each of the major cortical components in the generic large-scale frontoparietal system are discussed. We conclude that quantitative meta-analysis can be a powerful too] for combining results of multiple primary studies reported in Talairach space. Here, it provides evidence both for broadly consistent activation of frontal and parietal cortical regions by various versions of the n-back working memory paradigm, and for process- and content-specific frontoparietal activation by working memory. (c) 2005 Wiley-Liss, Inc.
    BibTeX:
    @article{Owen2005,
      author = {Owen, AM and McMillan, KM and Laird, AR and Bullmore, E},
      title = {N-back working memory paradigm: A meta-analysis of normative functional neuroimaging},
      journal = {HUMAN BRAIN MAPPING},
      year = {2005},
      volume = {25},
      number = {1},
      pages = {46-59},
      doi = {{10.1002/hbm.20131}}
    }
    
    Padoa-Schioppa, C. & Assad, J. Neurons in the orbitofrontal cortex encode economic value {2006} NATURE
    Vol. {441}({7090}), pp. {223-226} 
    article DOI  
    Abstract: Economic choice is the behaviour observed when individuals select one among many available options. There is no intrinsically `correct' answer: economic choice depends on subjective preferences. This behaviour is traditionally the object of economic analysis(1) and is also of primary interest in psychology(2). However, the underlying mental processes and neuronal mechanisms are not well understood. Theories of human and animal choice(1-3) have a cornerstone in the concept of `value'. Consider, for example, a monkey offered one raisin versus one piece of apple: behavioural evidence suggests that the animal chooses by assigning values to the two options(4). But where and how values are represented in the brain is unclear. Here we show that, during economic choice, neurons in the orbitofrontal cortex(5-18) (OFC) encode the value of offered and chosen goods. Notably, OFC neurons encode value independently of visuospatial factors and motor responses. If a monkey chooses between A and B, neurons in the OFC encode the value of the two goods independently of whether A is presented on the right and B on the left, or vice versa. This trait distinguishes the OFC from other brain areas in which value modulates activity related to sensory or motor processes(19-25). Our results have broad implications for possible psychological models, suggesting that economic choice is essentially choice between goods rather than choice between actions. In this framework, neurons in the OFC seem to be a good candidate network for value assignment underlying economic choice.
    BibTeX:
    @article{Padoa-Schioppa2006,
      author = {Padoa-Schioppa, C and Assad, JA},
      title = {Neurons in the orbitofrontal cortex encode economic value},
      journal = {NATURE},
      year = {2006},
      volume = {441},
      number = {7090},
      pages = {223-226},
      doi = {{10.1038/nature04676}}
    }
    
    Pantelis, C., Velakoulis, D., McGorry, P., Wood, S., Suckling, J., Phillips, L., Yung, A., Bullmore, E., Brewer, W., Soulsby, B., Desmond, P. & McGuire, P. Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison {2003} LANCET
    Vol. {361}({9354}), pp. {281-288} 
    article  
    Abstract: Background Psychotic disorders, such as schizophrenia, are associated with neuroanatomical abnormalities, but whether these predate the onset of symptoms or develop progressively over the course of illness is unclear. We investigated this issue with MRI to study people with prodromal symptoms who are at ultra high-risk for the development of psychosis. Methods We did two comparisons, cross-sectional and longitudinal. For the cross-sectional comparison, 75 people with prodromal signs of psychosis were scanned with MRI. After at least 12 months of follow-up, 23 (31 had developed psychosis and 52 (69 had not. Baseline MRI data from these two subgroups were compared. For the longitudinal comparison, 21 of the ultra high-risk individuals were scanned again with MRI after at least 12 months. Ten of these had developed psychosis and 11 had not. MRI data from baseline and follow-up were compared within each group of people. Findings In the cross-sectional comparison, compared with people who did not develop psychosis, those who did develop the disorder had less grey matter in the right medial temporal, lateral temporal, and inferior frontal cortex, and in the cingulate cortex bilaterally. In the longitudinal comparison, when re-scanned, individuals who had developed psychosis showed a reduction in grey matter in the left parahippocampal, fusiform, orbitofrontal and cerebellar cortices, and the cingulate gyri. In those who had not become psychotic, longitudinal changes were restricted to the cerebellum. Interpretation Some of the grey-matter abnormalities associated with psychotic disorders predate the onset of frank symptoms, whereas others appear in association with their first expression.
    BibTeX:
    @article{Pantelis2003,
      author = {Pantelis, C and Velakoulis, D and McGorry, PD and Wood, SJ and Suckling, J and Phillips, LJ and Yung, AR and Bullmore, ET and Brewer, W and Soulsby, B and Desmond, P and McGuire, PK},
      title = {Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison},
      journal = {LANCET},
      year = {2003},
      volume = {361},
      number = {9354},
      pages = {281-288}
    }
    
    PARDO, J., FOX, P. & RAICHLE, M. LOCALIZATION OF A HUMAN SYSTEM FOR SUSTAINED ATTENTION BY POSITRON EMISSION TOMOGRAPHY {1991} NATURE
    Vol. {349}({6304}), pp. {61-64} 
    article  
    Abstract: POSITRON emission tomographic (PET) studies of human attention have begun to dissect isolable components of this complex higher brain function, including a midline attentional system in a region of the anterior cingulate cortex1-3. The right hemisphere may play a special part in human attention4; neglect, an important phenomenon associated with damage to attentional systems, is more severe, extensive and long-lasting after lesions to the right hemisphere. Here we use PET measurements of brain flood flow in healthy subjects to identify changes in regional brain activity during simple visual and somatosensory tasks of sustained attention or vigilance. We find localized increases in blood flow in the prefrontal and superior parietal cortex primarily in the right hemisphere, regardless of the modality or laterality of sensory input. The anterior cingulate was not activated during either task. These data localize the vigilance aspects of normal human attention to sensory stimuli, thereby clarifying the biology underlying asymmetries of attention to such stimuli that have been reported in clinical lesions.
    BibTeX:
    @article{PARDO1991,
      author = {PARDO, JV and FOX, PT and RAICHLE, ME},
      title = {LOCALIZATION OF A HUMAN SYSTEM FOR SUSTAINED ATTENTION BY POSITRON EMISSION TOMOGRAPHY},
      journal = {NATURE},
      year = {1991},
      volume = {349},
      number = {6304},
      pages = {61-64}
    }
    
    PARDO, J., PARDO, P., JANER, K. & RAICHLE, M. THE ANTERIOR CINGULATE CORTEX MEDIATES PROCESSING SELECTION IN THE STROOP ATTENTIONAL CONFLICT PARADIGM {1990} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {87}({1}), pp. {256-259} 
    article  
    BibTeX:
    @article{PARDO1990,
      author = {PARDO, JV and PARDO, PJ and JANER, KW and RAICHLE, ME},
      title = {THE ANTERIOR CINGULATE CORTEX MEDIATES PROCESSING SELECTION IN THE STROOP ATTENTIONAL CONFLICT PARADIGM},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1990},
      volume = {87},
      number = {1},
      pages = {256-259}
    }
    
    Paus, T. Primate anterior cingulate cortex: Where motor control, drive and cognition interface {2001} NATURE REVIEWS NEUROSCIENCE
    Vol. {2}({6}), pp. {417-424} 
    article  
    Abstract: Controversy surrounds the function of the anterior cingulate cortex. Recent discussions about its role in behavioural control have centred on three main issues: its involvement in motor control, its proposed role in cognition and its relationship with the arousal/drive state of the organism. I argue that the overlap of these three domains is key to distinguishing the anterior cingulate cortex from other frontal regions, placing it in a unique position to translate intentions to actions.
    BibTeX:
    @article{Paus2001,
      author = {Paus, T},
      title = {Primate anterior cingulate cortex: Where motor control, drive and cognition interface},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2001},
      volume = {2},
      number = {6},
      pages = {417-424}
    }
    
    Paus, T. Location and function of the human frontal eye-field: A selective review {1996} NEUROPSYCHOLOGIA
    Vol. {34}({6}), pp. {475-483} 
    article  
    Abstract: The location and possible function of the human frontal eye-field (FEF) were evaluated by reviewing results of cerebral blood-flow (CBF) and lesion studies. A remarkable consistency was found regarding the rostro-caudal (Y: from -6 to 1 mm) and dorso-ventral (Z: from 44 to 51 mm) location of the FEF, as defined by the CBF method within a standardized stereotaxic system (the zero point for all X, Y and Z coordinates coinciding with the anterior commissure, Talairach and Tournoux [Go-planar Stereotactic Atlas of the Human Brain, Georg Thieme, Stuttgart, 1988]. In contrast, there was a marked variability along the mediolateral axis (X: from -24 to -40 mm for the left hemisphere and from 21 to 40 mm for the right hemisphere). The human FEF is thus located either in the vicinity of the precentral sulcus and/or in the depth of the caudalmost part of the superior frontal sulcus. In either case, this location challenges the commonly held view of the FEF being located in Brodmann's area 8. With regard to FEF function, the results of CBF studies failed to support a role for the FEF in the cognitive aspects of oculomotor control, such as the execution of anti-saccades. Blood-flow activation data are consistent in this respect with the results of lesion studies. It is proposed that future research on FEF function in human subjects may benefit from focusing on the visuomotor rather than the cognitive aspects of oculomotor control. Copyright (C) 1996 Elsevier Science Ltd.
    BibTeX:
    @article{Paus1996,
      author = {Paus, T},
      title = {Location and function of the human frontal eye-field: A selective review},
      journal = {NEUROPSYCHOLOGIA},
      year = {1996},
      volume = {34},
      number = {6},
      pages = {475-483}
    }
    
    PAUS, T., PETRIDES, M., EVANS, A. & MEYER, E. ROLE OF THE HUMAN ANTERIOR CINGULATE CORTEX IN THE CONTROL OF OCULOMOTOR, MANUAL, AND SPEECH RESPONSES - A POSITRON EMISSION TOMOGRAPHY STUDY {1993} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {70}({2}), pp. {453-469} 
    article  
    Abstract: 1. Two experiments were aimed at investigating the functional organization of the human anterior cingulate cortex (ACC) in relation to higher-order motor control. 2. The O-15-labeled H2O bolus method was used to measure relative changes of regional cerebral blood flow (rCBF) in 18 healthy human subjects as they performed oculomotor, manual, or speech tasks. 3. Task-specific rCBF changes were obtained in distinct subregions of the ACC, depending on the output system employed. The oculomotor and the manual task-related foci were found in the rostral and caudal regions of the ACC, respectively, whereas the speech foci were localized within two cingulate subregions, the intermediate dorsal and the rostral ACC. 4. In the manual tasks, two groups of activation foci could be distinguished, one just behind and the other just in front of the vertical plane traversing the anterior commissure. 5. The above pattern of rCBF changes was observed only if there was concomitant activation within the lateral prefrontal cortex (except for the posterior group of foci obtained in the manual tasks). 6. The localization of output-specific rCBF changes within the human ACC is consistent with the known somatotopic organization of the cingulate cortex in the monkey. 7. It is tentatively proposed that the ACC participates in motor control by facilitating the execution of the appropriate responses and/or suppressing the execution of the inappropriate ones. Such a modulatory effect would be of particular importance when behavior has to be modified in new and challenging situations.
    BibTeX:
    @article{PAUS1993,
      author = {PAUS, T and PETRIDES, M and EVANS, AC and MEYER, E},
      title = {ROLE OF THE HUMAN ANTERIOR CINGULATE CORTEX IN THE CONTROL OF OCULOMOTOR, MANUAL, AND SPEECH RESPONSES - A POSITRON EMISSION TOMOGRAPHY STUDY},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1993},
      volume = {70},
      number = {2},
      pages = {453-469}
    }
    
    Paus, T., Zatorre, R., Hofle, N., Caramanos, Z., Gotman, J., Petrides, M. & Evans, A. Time-related changes in neural systems underlying attention and arousal during the performance of an auditory vigilance task {1997} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {9}({3}), pp. {392-408} 
    article  
    Abstract: Vigilance behavior. or watch keeping, involves the focusing of attention on the detection of subtle changes in the environment that occur over a long period of time. We investigated the time course of changes in brain activity during the continuous performance of a 60-min auditory vigilance task. The task required the detection of an intensity drop that occurred in 5% of the auditory stimuli. Six 1-min samples of cerebral blood flow (CBF) and electroencephalographic (EEG) activity were obtained at 10-min intervals during the vigilance performance. Changes in CBF were measured by means of positron emission tomography (PET). Performance data (hits, false alarms, reaction time) were analyzed across six 10-min blocks. Eight healthy male volunteers participated in the study. During the 60-min test, the number of correct detections (hits) did not change, but both the reaction time and EEG activity in the theta (4 to 7 Hz) range progressively increased across testing. CBF in several subcortical structures (thalamus, substantia innominata, and putamen) and cortical areas (ventrolateral, dorsolateral, and orbital frontal cortex: parietal cortex: and temporal cortex) decreased as a function of time-on-task; changes in the cortical regions were limited to the right hemisphere. Blood flow also decreased in the temporalis muscles. At the same time, CBF increased in several visual cortical areas including the left and right fusiform gyri. Furthermore, the thalamic blood-flew response co-varied with that in the substantia innominata, the ponto-mesencephalic tegmentum, and the anterior cingulate cortex. The right ventrolateral-frontal blood-flow response co-varied with that in the right parietal, orbitofrontal, and dorsolateral frontal cortex. Two main conclusions are drawn from the obtained data. First, we suggest that the observed time-related changes in reaction time, EEG activity, and blood flow in the temporalis muscles are related to changes in the level of arousal (alertness) and that CBF changes in the thalamus-related neural circuitry represent a brain correlate of such changes. Second, we speculate that time-related CBF decreases in cortical regions of the right hemisphere underlie a shift from controlled to automatic attentional processing of the auditory stimuli.
    BibTeX:
    @article{Paus1997,
      author = {Paus, T and Zatorre, RJ and Hofle, N and Caramanos, Z and Gotman, J and Petrides, M and Evans, AC},
      title = {Time-related changes in neural systems underlying attention and arousal during the performance of an auditory vigilance task},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {1997},
      volume = {9},
      number = {3},
      pages = {392-408}
    }
    
    Petersen, S., van Mier, H., Fiez, J. & Raichle, M. The effects of practice on the functional anatomy of task performance {1998} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {95}({3}), pp. {853-860} 
    article  
    Abstract: The effects of practice on the functional anatomy observed in two different tasks, a verbal and a motor task, are reviewed in this paper, In the first, people practiced a verbal production task, generating an appropriate verb in response to a visually presented noun, Both practiced and unpracticed conditions utilized common regions such as visual and motor cortex, However, there was a set of regions that was affected by practice, Practice produced a shift in activity from left frontal, anterior cingulate, and right cerebellar hemisphere to activity in Sylvian-insular cortex, Similar changes were also observed in the second task, a task in a very different domain, namely the tracing of a maze. Some areas were significantly more activated during initial unskilled performance (right premotor and parietal cortex and left cerebellar hemisphere); a different region (medial frontal cortex, ``supplementary motor area'') showed greater activity during skilled performance conditions, Activations were also found in regions that most likely control movement execution irrespective of skill level (e.g., primary motor cortex was related to velocity of movement), One way of interpreting these results is in a ``scaffolding-storage'' framework. For unskilled, effortful performance, a scaffolding set of regions is used to cope with novel task demands, Following practice, a different set of regions is used, possibly representing storage of particular associations or capabilities that allow for skilled performance, The specific regions used for scaffolding and storage appear to be task dependent.
    BibTeX:
    @article{Petersen1998,
      author = {Petersen, SE and van Mier, H and Fiez, JA and Raichle, ME},
      title = {The effects of practice on the functional anatomy of task performance},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1998},
      volume = {95},
      number = {3},
      pages = {853-860},
      note = {Colloquium on Neuroimaging of Human Brain Function, IRVINE, CALIFORNIA, MAY 29-31, 1997}
    }
    
    Peterson, B., Skudlarski, P., Gatenby, J., Zhang, H., Anderson, A. & Gore, J. An fMRI study of Stroop word-color interference: Evidence for cingulate subregions subserving multiple distributed attentional systems {1999} BIOLOGICAL PSYCHIATRY
    Vol. {45}({10}), pp. {1237-1258} 
    article  
    Abstract: Background: The goal of this study was to model the functional connectivity of the neural systems that subserve attention and impulse control. Proper performance of the Stroop Word-Color Interference Task requires both attention and impulse control. Methods: Word-color interference was studied in 34 normal adult subjects using functional magnetic resonance imaging. Results: inter-regional correlation analyses suggested that the anterior cingulate is coupled functionally with multiple regions throughout the cerebrum. A factor analysis of the significant regional activations further emphasized this functional coupling. The cingulate or related mesial frontal cortices loaded on each of the seven factors identified in the factor analysis. Other regions that loaded significantly on on these factors have been described previously as belonging to anatomically connected circuits believed to subserve sensory tuning, receptive language, vigilance, working memory, response selection motor planning, and motor response functions. These seven factors appeared to be oriented topographically within the anterior cingulate, with sensory, working memory, and vigilance functions planning, and motor response positioned progressively more caudally. Conclusions: These findings support a parallel distributed processing model for word-color interference in which portions of the anterior cingulate cortex modify the strengths of multiple neural pathways used to read and name colors. Allocation of attentional resources is thought to modify pathway strengths by reducing cross-talk between information processing modules that subserve the competing demands of reading and color naming. The functional topography of these neural systems observed within the cingulate argues for the presence of multiple attentional subsystems, each contributing to improved task performance. The topography also suggests a role for the cingulate in coordinating and integrating the activity of these multiple attentional subsystems. Biol Psychiatry 1999;45:1237-1258 (C) 1999 Society of Biological Psychiatry.
    BibTeX:
    @article{Peterson1999,
      author = {Peterson, BS and Skudlarski, P and Gatenby, JC and Zhang, HP and Anderson, AW and Gore, JC},
      title = {An fMRI study of Stroop word-color interference: Evidence for cingulate subregions subserving multiple distributed attentional systems},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {1999},
      volume = {45},
      number = {10},
      pages = {1237-1258}
    }
    
    PETIT, L., ORSSAUD, C., TZOURIO, N., SALAMON, G., MAZOYER, B. & BERTHOZ, A. PET STUDY OF VOLUNTARY SACCADIC EYE-MOVEMENTS IN HUMANS - BASAL GANGLIA-THALAMOCORTICAL SYSTEM AND CINGULATE CORTEX INVOLVEMENT {1993} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {69}({4}), pp. {1009-1016} 
    article  
    Abstract: 1. The purpose of this work was to explore the cortical and subcortical mechanisms underlying the execution of voluntary saccadic eye movements in humans. 2. Normalized regional cerebral blood flow (NrCBF) was measured using positron emission tomography (PET) and (H2O)-O-15 bolus intravenous injections in four right-handed healthy volunteers at rest and while performing self-paced voluntary horizontal saccadic eye movements in total darkness. 3. Magnetic resonance imaging of each subject's brain was matched to PET images, allowing the detection of activation in individually defined anatomic regions of interest. Cortical regions were drawn according to gyri limits; subcortical structures were also defined. 4. Self-paced saccadic eye movements elicited bilateral NrCBF increases in the lenticular nuclei, including putamen and globus pallidus, and in the thalamus. At the cortical level, we found bilateral NrCBF increases in the precentral gyrus, the superior part of the median frontal gyrus that corresponds to the supplementary motor area. There was also a significant NrCBF increase in the cerebellar vermis. 5. Right fusiform and lingual gyri, right insula, and left cingulate gyrus were also activated during the execution of saccades. 6. These results indicate that the classical basal ganglia-thalamocortical motor loop previously described for skeletal movements may also be involved in simple saccadic eye movements in humans.
    BibTeX:
    @article{PETIT1993,
      author = {PETIT, L and ORSSAUD, C and TZOURIO, N and SALAMON, G and MAZOYER, B and BERTHOZ, A},
      title = {PET STUDY OF VOLUNTARY SACCADIC EYE-MOVEMENTS IN HUMANS - BASAL GANGLIA-THALAMOCORTICAL SYSTEM AND CINGULATE CORTEX INVOLVEMENT},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1993},
      volume = {69},
      number = {4},
      pages = {1009-1016}
    }
    
    Petrovic, P., Kalso, E., Petersson, K. & Ingvar, M. Placebo and opioid analgesia - Imaging a shared neuronal network {2002} SCIENCE
    Vol. {295}({5560}), pp. {1737-1740} 
    article  
    Abstract: It has been suggested that placebo analgesia involves both higher order cognitive networks and endogenous opioid systems. The rostral anterior cingulate cortex (rACC) and the brainstem are implicated in opioid analgesia, suggesting a similar role for these structures in placebo analgesia. Using positron emission tomography, we confirmed that both opioid and placebo analgesia are associated with increased activity in the rACC. We also observed a covariation between the activity in the rACC and the brainstem during both opioid and placebo analgesia, but not during the pain-only condition. These findings indicate a related neural mechanism in placebo and opioid analgesia.
    BibTeX:
    @article{Petrovic2002,
      author = {Petrovic, P and Kalso, E and Petersson, KM and Ingvar, M},
      title = {Placebo and opioid analgesia - Imaging a shared neuronal network},
      journal = {SCIENCE},
      year = {2002},
      volume = {295},
      number = {5560},
      pages = {1737-1740}
    }
    
    Petrovic, P., Petersson, K., Ghatan, P., Stone-Elander, S. & Ingvar, M. Pain-related cerebral activation is altered by a distracting cognitive task {2000} PAIN
    Vol. {85}({1-2}), pp. {19-30} 
    article  
    Abstract: It has previously been suggested that the activity in sensory regions of the brain can be modulated by attentional mechanisms during parallel cognitive processing. To investigate whether such attention-related modulations are present in the processing of pain, the regional cerebral blood flow was measured using [O-15]butanol and positron emission tomography in conditions involving both pain and parallel cognitive demands. The painful stimulus consisted of the standard cold presser test and the cognitive task was a computerised perceptual maze test. The activations during the maze test reproduced findings in previous studies of the same cognitive task. The cold presser test evoked significant activity in the contralateral S1, and bilaterally in the somatosensory association areas (including S2), the ACC and the mid-insula. The activity in the somatosensory association areas and periaqueductal gray/midbrain were significantly modified, i.e. relatively decreased, when the subjects also were performing the maze task. The altered activity was accompanied with significantly lower ratings of pain during the cognitive task. In contrast, lateral orbitofrontal regions showed a relative increase of activity during pain combined with the maze task as compared to only pain, which suggests the possibility of the involvement of frontal cortex in modulation of regions processing pain. (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{Petrovic2000,
      author = {Petrovic, P and Petersson, KM and Ghatan, PH and Stone-Elander, S and Ingvar, M},
      title = {Pain-related cerebral activation is altered by a distracting cognitive task},
      journal = {PAIN},
      year = {2000},
      volume = {85},
      number = {1-2},
      pages = {19-30}
    }
    
    Peyron, C., Petit, J., Rampon, C., Jouvet, M. & Luppi, P. Forebrain afferents to the rat dorsal raphe nucleus demonstrated by retrograde and anterograde tracing methods {1998} NEUROSCIENCE
    Vol. {82}({2}), pp. {443-468} 
    article  
    Abstract: The dorsal raphe nucleus through its extensive efferents has been implicated in a great variety of physiological and behavioural functions. However, little is know about its afferents. Therefore, to identify the systems likely to influence the activity of serotonergic neurons of the dorsal raphe nucleus, we re-examined the forebrain afferents to the dorsal raphe nucleus using cholera toxin b subunit and Phaseolus vulgaris-leucoagglutinin as retrograde or anterograde tracers. With small cholera toxin b subunit injection sites, we further determined the specific afferents to the ventral and dorsal parts of the central dorsal raphe nucleus, the rostral dorsal raphe nucleus and the lateral wings. In agreement with previous studies, we observed a large number of retrogradely-labelled cells in the lateral habenula following injections in all subdivisions of the dorsal raphe nucleus. In addition, depending on the subdivision of the dorsal raphe nucleus injected, we observed a small to large number of retrogradely-labelled cells in the orbital, cingulate, infralimbic, dorsal peduncular, and insular cortice, a moderate or substantial number in the ventral pallidum and a small to substantial number in the claustrum. In addition, we observed a substantial to large number of cells in the medial and lateral preoptic areas and the medial preoptic nucleus after cholera toxin b subunit injections in the dorsal raphe nucleus excepting for those located in the ventral part of the central dorsal raphe nucleus, after which we found a moderate number of retrogradely-labelled cells. Following cholera toxin b subunit injections in the dorsal part of the central dorsal raphe nucleus, a large number of retrogradely-labelled cells was seen in the lateral, ventral and medial parts of the bed nucleus of the stria terminalis whereas only a small to moderate number was visualized after injections in the other dorsal raphe nucleus subdivisions. In addition, respectively, a substantial and a moderate number of retrogradely-labelled cells was distributed in the zona incerta and the subincertal nucleus following all tracer injections in the dorsal raphe nucleus. A large number of retrogradely-labelled cells was also visualized in the lateral, dorsal and posterior hypothalamic areas and the perifornical nucleus after cholera toxin b subunit injections in the dorsal part of the central raphe nucleus and to a lesser extent following injections in the other subdivisions. We further observed a substantial to large number of retrogradely-labelled cells in the tuber cinereum and the medial tuberal nucleus following cholera toxin b subunit injections in the dorsal part of the central dorsal raphe nucleus or the lateral wings and a small to moderate number after injections in the two other dorsal raphe nucleus subdivisions. A moderate or substantial number of labelled cells was also seen in the ventromedial hypothalamic area and the arcuate nucleus following cholera toxin injections in the dorsal part of the central dorsal raphe nucleus and the lateral wings and an occasional or small number with injection sites located in the other subdivisions. Finally, we observed, respectively, a moderate and a substantial number of retrogradely-labelled cells in the central nucleus of the amygdala following tracer injections in the ventral or dorsal parts of the central dorsal raphe nucleus and a small number after injections in the other subnuclei. In agreement with these retrograde data, we visualized anterogradely-labelled fibres heterogeneously distributed in the dorsal raphe nucleus following Phaseolus vulgaris-leucoagglutinin injections in the lateral orbital or infralimbic cortice, the lateral preoptic area, the perifornical nucleus, the lateral or posterior hypothalamic areas, the zona incerta, the subincertal nucleus or the medial tuberal nucleus. Altogether our retrograde and anterograde results clearly indicate, in contrast to previous studies, that each dorsal raphe nucleus subdivision receives a differential distribution of afferents from numerous forebrain structures. (C) 1997 IBRO. Published by Elsevier Science Ltd.
    BibTeX:
    @article{Peyron1998,
      author = {Peyron, C and Petit, JM and Rampon, C and Jouvet, M and Luppi, PH},
      title = {Forebrain afferents to the rat dorsal raphe nucleus demonstrated by retrograde and anterograde tracing methods},
      journal = {NEUROSCIENCE},
      year = {1998},
      volume = {82},
      number = {2},
      pages = {443-468}
    }
    
    Peyron, R., Garcia-Larrea, L., Gregoire, M., Costes, N., Convers, P., Lavenne, F., Mauguiere, F., Michel, D. & Laurent, B. Haemodynamic brain responses to acute pain in humans - Sensory and attentional networks {1999} BRAIN
    Vol. {122}({Part 9}), pp. {1765-1779} 
    article  
    Abstract: Turning attention towards or away from a painful heat stimulus is known to modify both the subjective intensity of pain and the cortical evoked potentials to noxious stimuli. Using PET, we investigated in 12 volunteers whether pain-related regional cerebral blood flow (rCBF) changes were also modulated by attention. High (mean 46.6 degrees C) or low (mean 39 degrees C) intensity thermal stimuli were applied to the hand under three attentional conditions: (i) attention directed towards the stimuli, (ii) attention diverted from the stimuli, and (iii) no task. Only the insular/second somatosensory cortices were found to respond whatever the attentional context and might, therefore, subserve the sensory-discriminative dimension of pain (intensity coding). In parallel, other rCBF changes previously described as `pain-related' appeared to depend essentially on the attentional context. Attention to the thermal stimulus involved a large network which was primarily right-sided, including prefrontal, posterior parietal, anterior cingulate cortices and thalamus. Anterior cingulate activity was not found to pertain to the intensity coding network but rather to the attentional neural activity triggered by pain. The attentional network disclosed in this study could be further subdivided into a non-specific arousal component, involving thalamic and upper brainstem regions, and a selective attention and orientating component including prefrontal, posterior parietal and cingulate cortices. A further effect observed in response to high intensity stimuli was a rCBF decrease within the somatosensory cortex ipsilateral to stimulation, which was considered to reflect contrast enhancing and/or anticipation processes. Attentional processes could possibly explain part of the variability observed in previous PET reports and should therefore be considered in further studies on pain in both normal subjects and patients with chronic pain.
    BibTeX:
    @article{Peyron1999,
      author = {Peyron, R and Garcia-Larrea, L and Gregoire, MC and Costes, N and Convers, P and Lavenne, F and Mauguiere, F and Michel, D and Laurent, B},
      title = {Haemodynamic brain responses to acute pain in humans - Sensory and attentional networks},
      journal = {BRAIN},
      year = {1999},
      volume = {122},
      number = {Part 9},
      pages = {1765-1779}
    }
    
    Peyron, R., Laurent, B. & Garcia-Larrea, L. Functional imaging of brain responses to pain. A review and meta-analysis (2000) {2000} NEUROPHYSIOLOGIE CLINIQUE-CLINICAL NEUROPHYSIOLOGY
    Vol. {30}({5}), pp. {263-288} 
    article  
    Abstract: Brain responses to pain, assessed through positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) are reviewed. Functional activation of brain regions are thought to be reflected by increases in the regional cerebral blood flow (rCBF) in PET studies, and in the blood oxygen level dependent (BOLD) signal in fMRI. rCBF increases to noxious stimuli are almost constantly observed in second somatic (SII) and insular regions, and in the anterior cingulate cortex (ACC), and with slightly less consistency in the contralateral thalamus and the primary somatic area (SI). Activation of the lateral thalamus, SI, SII and insula are thought to be related to the sensory-discriminative aspects of pain processing. SI is activated in roughly half of the studies, and the probability of obtaining SI activation appears related to the total amount of body surface stimulated (spatial summation) and probably also by temporal summation and attention to the stimulus. In a number of studies, the thalamic response was bilateral, probably reflecting generalised arousal in reaction to pain. ACC does not seem to be involved in coding stimulus intensity or location but appears to participate in both the affective and attentional concomitants of pain sensation, as well as in response selection. ACC subdivisions activated by painful stimuli partially overlap those activated in orienting and target detection tasks, but are distinct from those activated in tests involving sustained attention (Stroop, etc.). In addition to ACC, increased blood flow in the posterior parietal and prefrontal cortices is thought to reflect attentional and memory networks activated by noxious stimulation. Less noted but frequent activation concerns motor-related areas such as the striatum, cerebellum and supplementary motor area, as well as regions involved in pain control such as the periaqueductal grey. In patients, chronic spontaneous pain is associated with decreased resting rCBF in contralateral thalamus, which may be reverted by analgesic procedures. Abnormal pain evoked by innocuous stimuli (allodynia) has been associated with amplification of the thalamic, insular and SII responses, concomitant to a paradoxical CBF decrease in ACC. It is argued that imaging studies of allodynia should be encouraged in order to understand central reorganisations leading to abnormal cortical pain processing. A number of brain areas activated by acute pain, particularly the thalamus and anterior cingulate, also show increases in rCBF during analgesic procedures. Taken together, these data suggest that hemodynamic responses to pain reflect simultaneously the sensory, cognitive and affective dimensions of pain, and that the same structure may both respond to pain and participate in pain control. The precise biochemical nature of these mechanisms remains to be investigated. (C) 2000 Editions scientifiques et medicales Elsevier SAS.
    BibTeX:
    @article{Peyron2000,
      author = {Peyron, R and Laurent, B and Garcia-Larrea, L},
      title = {Functional imaging of brain responses to pain. A review and meta-analysis (2000)},
      journal = {NEUROPHYSIOLOGIE CLINIQUE-CLINICAL NEUROPHYSIOLOGY},
      year = {2000},
      volume = {30},
      number = {5},
      pages = {263-288}
    }
    
    Pezawas, L., Meyer-Lindenberg, A., Drabant, E., Verchinski, B., Munoz, K., Kolachana, B., Egan, M., Mattay, V., Hariri, A. & Weinberger, D. 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression {2005} NATURE NEUROSCIENCE
    Vol. {8}({6}), pp. {828-834} 
    article DOI  
    Abstract: Carriers of the short allele of a functional 5' promoter polymorphism of the serotonin transporter gene have increased anxiety-related temperamental traits, increased amygdala reactivity and elevated risk of depression. Here, we used multimodal neuroimaging in a large sample of healthy human subjects to elucidate neural mechanisms underlying this complex genetic association. Morphometrical analyses showed reduced gray matter volume in short-allele carriers in limbic regions critical for processing of negative emotion, particularly perigenual cingulate and amygdala. Functional analysis of those regions during perceptual processing of fearful stimuli demonstrated tight coupling as a feedback circuit implicated in the extinction of negative affect. Short-allele carriers showed relative uncoupling of this circuit. Furthermore, the magnitude of coupling inversely predicted almost 30% of variation in temperamental anxiety. These genotype-related alterations in anatomy and function of an amygdala-cingulate feedback circuit critical for emotion regulation implicate a developmental, systems- level mechanism underlying normal emotional reactivity and genetic susceptibility for depression.
    BibTeX:
    @article{Pezawas2005,
      author = {Pezawas, L and Meyer-Lindenberg, A and Drabant, EM and Verchinski, BA and Munoz, KE and Kolachana, BS and Egan, MF and Mattay, VS and Hariri, AR and Weinberger, DR},
      title = {5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression},
      journal = {NATURE NEUROSCIENCE},
      year = {2005},
      volume = {8},
      number = {6},
      pages = {828-834},
      doi = {{10.1038/nn1463}}
    }
    
    Phan, K., Wager, T., Taylor, S. & Liberzon, I. Functional neuroanatomy of emotion: A meta-analysis of emotion activation studies in PET and fMRI {2002} NEUROIMAGE
    Vol. {16}({2}), pp. {331-348} 
    article DOI  
    Abstract: Neuroimaging studies with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have begun to describe the functional neuroanatomy of emotion. Taken separately, specific studies vary in task dimensions and in type(s) of emotion studied and are limited by statistical power and sensitivity. By examining findings across studies, we sought to determine if common or segregated patterns of activations exist across various emotional tasks. We reviewed 55 PET and fMRI activation studies (yielding 761 individual peaks) which investigated emotion in healthy subjects. Peak activation coordinates were transformed into a standard space and plotted onto canonical 3-D brain renderings. We divided the brain into 20 non-overlapping regions, and characterized each region by its responsiveness across individual emotions (positive, negative, happiness, fear, anger, sadness, disgust), to different induction methods (visual, auditory, recall/imagery), and in emotional tasks with and without cognitive demand. Our review yielded the following summary observations: (1) The medial prefrontal cortex had a general role in emotional processing; (2) fear specifically engaged the amygdala; (3) sadness was associated with activity in the subcallosal cingulate; (4) emotional induction by visual stimuli activated the occipital cortex and the amygdala; (5) induction by emotional recall/imagery recruited the anterior cingulate and insula; (6) emotional tasks with cognitive demand also involved the anterior cingulate and insula. This review provides a critical comparison of findings across individual studies and suggests that separate brain regions are involved in different aspects of emotion. (C) 2002 Elsevier Science (USA).
    BibTeX:
    @article{Phan2002,
      author = {Phan, KL and Wager, T and Taylor, SF and Liberzon, I},
      title = {Functional neuroanatomy of emotion: A meta-analysis of emotion activation studies in PET and fMRI},
      journal = {NEUROIMAGE},
      year = {2002},
      volume = {16},
      number = {2},
      pages = {331-348},
      doi = {{10.1006/nimg.2002.1087}}
    }
    
    Phelps, E., Delgado, M., Nearing, K. & LeDoux, J. Extinction learning in humans: Role of the amygdala and vmPFC {2004} NEURON
    Vol. {43}({6}), pp. {897-905} 
    article  
    Abstract: Understanding how fears are acquired is an important step in translating basic research to the treatment of fear-related disorders. However, understanding how learned fears are diminished may be even more valuable. We explored the neural mechanisms of fear extinction in humans. Studies of extinction in nonhuman animals have focused on two interconnected brain regions: the amygdala and the ventral medial prefrontal cortex (vmPFC). Consistent with animal models suggesting that the amygdala is important for both the acquisition and extinction of conditioned fear, amygdala activation was correlated across subjects with the conditioned response in both acquisition and early extinction. Activation in the vmPFC (subgenual anterior cingulate) was primarily linked to the expression of fear learning during a delayed test of extinction, as might have been expected from studies demonstrating this region is critical for the retention of extinction. These results provide evidence that the mechanisms of extinction learning may be preserved across species.
    BibTeX:
    @article{Phelps2004,
      author = {Phelps, EA and Delgado, MR and Nearing, KI and LeDoux, JE},
      title = {Extinction learning in humans: Role of the amygdala and vmPFC},
      journal = {NEURON},
      year = {2004},
      volume = {43},
      number = {6},
      pages = {897-905}
    }
    
    Phillips, M., Drevets, W., Rauch, S. & Lane, R. Neurobiology of emotion perception I: The neural basis of normal emotion perception {2003} BIOLOGICAL PSYCHIATRY
    Vol. {54}({5}), pp. {504-514} 
    article DOI  
    Abstract: There is at present limited understanding of the neurobiological basis of the different processes underlying emotion perception. We have aimed to identify potential neural correlates of three processes suggested by appraisalist theories as important for emotion perception: 1) the identification of the emotional significance of a stimulus; 2) the production of an affective state in response to 1; and 3) the regulation of the affective state. In a critical review, we have examined findings from recent animal, human lesion, and functional neuroimaging studies. Findings from these studies indicate that these processes may be dependent upon the functioning of two neural systems: a ventral system, including the amygdala, insula, ventral striatum, and ventral regions of the anterior cingulate gyrus and prefrontal cortex, predominantly important for processes 1 and 2 and automatic regulation of emotional responses; and a dorsal system, including the hippocampus and dorsal regions of anterior cingulate gyrus and prefrontal cortex, predominantly important for process 3. We suggest that the extent to which a stimulus is identified as emotive and is associated with the production of an affective state may be dependent upon levels of activity within these two neural systems.
    BibTeX:
    @article{Phillips2003,
      author = {Phillips, ML and Drevets, WC and Rauch, SL and Lane, R},
      title = {Neurobiology of emotion perception I: The neural basis of normal emotion perception},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {2003},
      volume = {54},
      number = {5},
      pages = {504-514},
      doi = {{10.1016/S0006-3223(03)00168-9}}
    }
    
    Phillips, M., Drevets, W., Rauch, S. & Lane, R. Neurobiology of emotion perception II: Implications for major psychiatric disorders {2003} BIOLOGICAL PSYCHIATRY
    Vol. {54}({5}), pp. {515-528} 
    article DOI  
    Abstract: To date, there has been little investigation of the neurobiological basis of emotion processing abnormalities in psychiatric populations. We have previously discussed two neural systems: 1) a ventral system, including the amygdala, insula, ventral striatum, ventral anterior cingulate gyrus, and prefrontal cortex, for identification of the emotional significance of a stimulus, production of affective states, and automatic regulation of emotional responses; and 2) a dorsal system, including the hippocampus, dorsal anterior cingulate gyrus, and prefrontal cortex, for the effortful regulation of affective states and subsequent behavior. In this critical review, we have examined evidence from studies employing a variety of techniques for distinct patterns of structural and Junctional abnormalities in these neural systems in schizophrenia, bipolar disorder, and major depressive disorder. In each psychiatric disorder, the pattern of abnormalities may be associated with specific symptoms, including emotional flattening, anhedonia, and persecutory delusions in schizophrenia, prominent mood swings, emotional lability and distractibility in bipolar disorder during depression and mania, and with depressed mood and anhedonia in major depressive disorder. We suggest that distinct patterns of structural and functional abnormalities in neural systems important for emotion processing are associated with specific symptoms of schizophrenia and bipolar and major depressive disorder.
    BibTeX:
    @article{Phillips2003a,
      author = {Phillips, ML and Drevets, WC and Rauch, SL and Lane, R},
      title = {Neurobiology of emotion perception II: Implications for major psychiatric disorders},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {2003},
      volume = {54},
      number = {5},
      pages = {515-528},
      doi = {{10.1016/S0006-3223(03)00171-9}}
    }
    
    Picard, N. & Strick, P. Imaging the premotor areas {2001} CURRENT OPINION IN NEUROBIOLOGY
    Vol. {11}({6}), pp. {663-672} 
    article  
    Abstract: Recent imaging studies of motor function provide new insights into the organization of the premotor areas of the frontal lobe. The pre-supplementary motor area and the rostral portion of the dorsal premotor cortex, the `pre-PMd, are, in many respects, more like prefrontal areas than motor areas. Recent data also suggest the existence of separate functional divisions in the rostral cingulate zone.
    BibTeX:
    @article{Picard2001,
      author = {Picard, N and Strick, PL},
      title = {Imaging the premotor areas},
      journal = {CURRENT OPINION IN NEUROBIOLOGY},
      year = {2001},
      volume = {11},
      number = {6},
      pages = {663-672}
    }
    
    Picard, N. & Strick, P. Motor areas of the medial wall: A review of their location and functional activation {1996} CEREBRAL CORTEX
    Vol. {6}({3}), pp. {342-353} 
    article  
    Abstract: Our goal in this review is to provide an anatomical framework for the analysis of the motor functions of the medial wall of the hemisphere in humans and laboratory primates. Converging evidence indicates that this region of the frontal robe contains multiple areas involved in motor control. In the monkey, the medial wall contains four premotor areas that project directly to both the primary motor cortex and the spinal cord. These are the supplementary motor area (SMA) on the superior frontal gyrus and three motor areas buried within the cingulate sulcus. In addition, there is evidence that a fifth motor field, the pre-SMA, lies rostral to the SMA proper. Recent physiological observations provide evidence for functional differences among these motor fields. In the human, no consensus exists on the number of distinct motor fields on the medial wall. In this review, we summarize the results of positron emission tomography (PET) studies that examined functional activation on the medial wall of humans. Our analysis suggests that it is possible to identify at least four separate cortical areas on the medial wall. Each area appears to be relatively more involved in some aspects of motor behavior than others. These cortical areas in the human appear to be analogous to the pre-SMA, the SMA proper, and two of the cingulate motor areas of the monkey. We believe that these correspondences and the anatomical framework we describe will be important for unraveling the motor functions of the medial wall of the hemisphere.
    BibTeX:
    @article{Picard1996,
      author = {Picard, N and Strick, PL},
      title = {Motor areas of the medial wall: A review of their location and functional activation},
      journal = {CEREBRAL CORTEX},
      year = {1996},
      volume = {6},
      number = {3},
      pages = {342-353}
    }
    
    Pinel, P., Dehaene, S., Riviere, D. & LeBihan, D. Modulation of parietal activation by semantic distance in a number comparison task {2001} NEUROIMAGE
    Vol. {14}({5}), pp. {1013-1026} 
    article  
    Abstract: The time to compare two numbers shows additive effects of number notation and. of semantic distance, suggesting that the comparison task can be decomposed into distinct stages of identification and semantic processing. Using event-related fMRI and high-density ERPs, we isolated cerebral areas where activation was influenced by input notation (verbal or Arabic notation). The bilateral extrastriate cortices and a left precentral. region were more activated during verbal than during Arabic stimulation, while the right fusiform gyrus and a set of bilateral inferoparietal and frontal regions were more activated during Arabic than during verbal stimulation. We also identified areas that were influenced solely by the semantic content of the stimuli (numerical distance between numbers to be compared) independent of the input notation. Activation tightly con-elated with numerical distance was observed mainly in a group of parietal areas distributed bilaterally along the intraparietal sulci and in the precuneus, as well as in the left middle temporal gyrus and posterior cingulate. Our results! support the assumption of a central semantic representation of numerical quantity that relies on a common parietal network shared among notations, (C) 2001 Academic Press.
    BibTeX:
    @article{Pinel2001,
      author = {Pinel, P and Dehaene, S and Riviere, D and LeBihan, D},
      title = {Modulation of parietal activation by semantic distance in a number comparison task},
      journal = {NEUROIMAGE},
      year = {2001},
      volume = {14},
      number = {5},
      pages = {1013-1026}
    }
    
    Pizzagalli, D., Pascual-Marqui, R., Nitschke, J., Oakes, T., Larson, C., Abercrombie, H., Schaefer, S., Koger, J., Benca, R. & Davidson, R. Anterior cingulate activity as a predictor of degree of treatment response in major depression: Evidence from brain electrical tomography analysis {2001} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {158}({3}), pp. {405-415} 
    article  
    Abstract: Objective: The anterior cingulate cortex has been implicated in depression. Results are best interpreted by considering anatomic and cytoarchitectonic subdivisions. Evidence suggests depression is characterized by hypoactivity in the dorsal anterior cingulate, whereas hyperactivity in the rostral anterior cingulate is associated with good response to treatment. The authors tested the hypothesis that activity in the rostral anterior cingulate during the depressed state has prognostic value for the degree of eventual response to treatment. Whereas prior studies used hemodynamic imaging, this investigation used EEC. Method: The authors recorded 28-channel EEC data for 18 unmedicated patients with major depression and 18 matched comparison subjects. Clinical outcome was assessed after nortriptyline treatment. Of the 18 depressed patients, 16 were considered responders 4-6 months after initial assessment. A median split was used to classify response, and the pretreatment EEG data of patients showing better (N=9) and worse (N=9) responses were analyzed with low-resolution electromagnetic tomography, a new method to compute three-dimensional cortical current density for given EEG frequency bands according to a Talairach brain atlas. Results: The patients with better responses showed hyperactivity (higher theta activity) in the rostral anterior cingulate (Brodmann's area 24/32). Follow-up analyses demonstrated the specificity of this finding, which was not confounded by age or pretreatment depression severity. Conclusions: These results, based on electrophysiological imaging, not only support hemodynamic findings implicating activation of the anterior cingulate as a predictor of response in depression, but they also suggest that differential activity in the rostral anterior cingulate is associated with gradations of response.
    BibTeX:
    @article{Pizzagalli2001,
      author = {Pizzagalli, D and Pascual-Marqui, RD and Nitschke, JB and Oakes, TR and Larson, CL and Abercrombie, HC and Schaefer, SM and Koger, JV and Benca, RM and Davidson, RJ},
      title = {Anterior cingulate activity as a predictor of degree of treatment response in major depression: Evidence from brain electrical tomography analysis},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {2001},
      volume = {158},
      number = {3},
      pages = {405-415}
    }
    
    PLAYFORD, E., JENKINS, I., PASSINGHAM, R., NUTT, J., FRACKOWIAK, R. & BROOKS, D. IMPAIRED MESIAL FRONTAL AND PUTAMEN ACTIVATION IN PARKINSONS-DISEASE - A POSITRON EMISSION TOMOGRAPHY STUDY {1992} ANNALS OF NEUROLOGY
    Vol. {32}({2}), pp. {151-161} 
    article  
    Abstract: Selection of movement in normal subjects has been shown to involve the premotor, supplementary motor, anterior cingulate, posterior parietal, and dorsolateral prefrontal areas. In Parkinson's disease (PD), the primary pathological change is degeneration of the nigrostriatal dopaminergic projections, and this is associated with difficulty in initiating actions. We wished to investigate the effect of the nigral abnormality in PD on cortical activation during movement. Using (CO2)-O-15 and positron emission tomography (PET), we studied regional cerebral blood flow in 6 patients with PD and 6 control subjects while they performed motor tasks. Subjects were scanned while at rest, while repeatedly moving a joystick forward, and while freely choosing which of four possible directions to move the joystick. Significant increases in regional cerebral blood flow were determined with covariance analysis. In normal subjects, compared to the rest condition, the free-choice task activated the left primary sensorimotor cortex, left premotor, cortex, left putamen, right dorsolateral prefrontal cortex and supplementary motor area, anterior cingulate area, and parietal association areas bilaterally. In the patients with PD, for the free-choice task, compared with the rest condition, there was significant activation in the left sensorimotor and premotor cortices but there was impaired activation of the contralateral putamen, the anterior cingulate, supplementary motor area, and dorsolateral prefrontal cortex. Impaired activation of the medial frontal areas may account for the difficulties PD patients have in initiating movements.
    BibTeX:
    @article{PLAYFORD1992,
      author = {PLAYFORD, ED and JENKINS, IH and PASSINGHAM, RE and NUTT, J and FRACKOWIAK, RSJ and BROOKS, DJ},
      title = {IMPAIRED MESIAL FRONTAL AND PUTAMEN ACTIVATION IN PARKINSONS-DISEASE - A POSITRON EMISSION TOMOGRAPHY STUDY},
      journal = {ANNALS OF NEUROLOGY},
      year = {1992},
      volume = {32},
      number = {2},
      pages = {151-161}
    }
    
    Ploghaus, A., Narain, C., Beckmann, C., Clare, S., Bantick, S., Wise, R., Matthews, P., Rawlins, J. & Tracey, I. Exacerbation of pain by anxiety is associated with activity in a hippocampal network {2001} JOURNAL OF NEUROSCIENCE
    Vol. {21}({24}), pp. {9896-9903} 
    article  
    Abstract: It is common clinical experience that anxiety about pain can exacerbate the pain sensation. Using event-related functional magnetic resonance imaging (FMRI), we compared activation responses to noxious thermal stimulation while perceived pain intensity was manipulated by changes in either physical intensity or induced anxiety. One visual signal, which reliably predicted noxious stimulation of moderate intensity, came to evoke low anxiety about the impending pain. Another visual signal was followed by the same, moderate-intensity stimulation on most of the trials, but occasionally by discriminably stronger noxious stimuli, and came to evoke higher anxiety. We found that the entorhinal cortex of the hippocampal formation responded differentially to identical noxious stimuli, dependent on whether the perceived pain intensity was enhanced by pain-relevant anxiety. During this emotional pain modulation, entorhinal responses predicted activity in closely connected, affective (perigenual cingulate), and intensity coding (mid-insula) areas. Our finding suggests that accurate preparatory information during medical and dental procedures alleviates pain by disengaging the hippocampus. It supports the proposal that during anxiety, the hippocampal formation amplifies aversive events to prime behavioral responses that are adaptive to the worst possible outcome.
    BibTeX:
    @article{Ploghaus2001,
      author = {Ploghaus, A and Narain, C and Beckmann, CF and Clare, S and Bantick, S and Wise, R and Matthews, PM and Rawlins, JNP and Tracey, I},
      title = {Exacerbation of pain by anxiety is associated with activity in a hippocampal network},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2001},
      volume = {21},
      number = {24},
      pages = {9896-9903}
    }
    
    Ploghaus, A., Tracey, I., Gati, J., Clare, S., Menon, R., Matthews, P. & Rawlins, J. Dissociating pain from its anticipation in the human brain {1999} SCIENCE
    Vol. {284}({5422}), pp. {1979-1981} 
    article  
    Abstract: The experience of pain is subjectively different from the fear and anxiety caused by threats of pain. Functional magnetic resonance imaging in healthy humans was applied to dissociate neural activation patterns associated with acute pain and its anticipation. Expectation of pain activated sites within the medial frontal lobe, insular cortex, and cerebellum distinct from, but close to, locations mediating pain experience itself. Anticipation of pain can in its own right cause mood changes and behavioral adaptations that exacerbate the suffering experienced by chronic pain patients. Selective manipulations of activity at these sites may offer therapeutic possibilities for treating chronic pain.
    BibTeX:
    @article{Ploghaus1999,
      author = {Ploghaus, A and Tracey, I and Gati, JS and Clare, S and Menon, RS and Matthews, PM and Rawlins, JNP},
      title = {Dissociating pain from its anticipation in the human brain},
      journal = {SCIENCE},
      year = {1999},
      volume = {284},
      number = {5422},
      pages = {1979-1981}
    }
    
    PORRINO, L. & GOLDMANRAKIC, P. BRAIN-STEM INNERVATION OF PREFRONTAL AND ANTERIOR CINGULATE CORTEX IN THE RHESUS-MONKEY REVEALED BY RETROGRADE TRANSPORT OF HRP {1982} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {205}({1}), pp. {63-76} 
    article  
    BibTeX:
    @article{PORRINO1982,
      author = {PORRINO, LJ and GOLDMANRAKIC, PS},
      title = {BRAIN-STEM INNERVATION OF PREFRONTAL AND ANTERIOR CINGULATE CORTEX IN THE RHESUS-MONKEY REVEALED BY RETROGRADE TRANSPORT OF HRP},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {1982},
      volume = {205},
      number = {1},
      pages = {63-76}
    }
    
    POSNER, M. & DEHAENE, S. ATTENTIONAL NETWORKS {1994} TRENDS IN NEUROSCIENCES
    Vol. {17}({2}), pp. {75-79} 
    article  
    Abstract: Recent brain-imaging and neurophysiological data indicate that attention is neither a property of a single brain area, nor of the entire brain. While attentional effects seem mediated by a relative amplification of blood flow and electrical activity in the cortical areas processing the attended computation, the details of how this is done through enhancement of attended or suppression of unattended items, or both, appear to depend on the task and brain-area studied. The origins of these amplification effects are to be found in specialized cortical areas of the frontal and parietal lobes that have been described as the anterior and posterior attention systems. These results represent substantial progress in the effort to determine how brain activity is regulated through attention. While many philosophical and practical issues remain in developing an understanding of attentional regulation, the new tools available should provide the basis for progress.
    BibTeX:
    @article{POSNER1994,
      author = {POSNER, MI and DEHAENE, S},
      title = {ATTENTIONAL NETWORKS},
      journal = {TRENDS IN NEUROSCIENCES},
      year = {1994},
      volume = {17},
      number = {2},
      pages = {75-79}
    }
    
    Posner, M. & Rothbart, M. Developing mechanisms of self-regulation {2000} DEVELOPMENT AND PSYCHOPATHOLOGY
    Vol. {12}({3}), pp. {427-441} 
    article  
    Abstract: Child development involves both reactive and self-regulatory mechanisms that children develop in conjunction with social norms. A half-century of research has uncovered aspects of the physical basis of attentional networks that produce regulation, and has given us some knowledge of how the social environment may alter them. In this paper, we discuss six Forms of developmental plasticity related to aspects of attention. We then focus on effortful or executive aspects of attention, reviewing research on temperamental individual differences and important pathways to normal and pathological development. Pathologies of development may arise when regulatory and reactive systems fail to reach the balance that allows for both self-expression and socially acceptable behavior. It remains a challenge for our society during the next millennium to obtain the information necessary to design systems that allow a successful balance to be realized by the largest possible number of children.
    BibTeX:
    @article{Posner2000,
      author = {Posner, MI and Rothbart, MK},
      title = {Developing mechanisms of self-regulation},
      journal = {DEVELOPMENT AND PSYCHOPATHOLOGY},
      year = {2000},
      volume = {12},
      number = {3},
      pages = {427-441}
    }
    
    Posner, M. & Rothbart, M. Attention, self-regulation and consciousness {1998} PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
    Vol. {353}({1377}), pp. {1915-1927} 
    article  
    Abstract: Consciousness has many aspects. These include awareness of the world, feelings of control over one's behaviour and mental state (volition), and the notion of a continuing self. Focal (executive) attention is used to control details of our awareness and is thus closely related to volition. Experiments suggest an integrated network of neural areas involved in executive attention. This network is associated with our voluntary ability to select among competing items, to correct error and to regulate our emotions. Recent neuroimaging studies suggest that these Various functions involve separate areas of the anterior cingulate. We have adopted a strategy of using marker tasks, shown to activate the brain area by imaging studies, as a means of tracing the development of attentional networks. Executive attention appears to develop first to regulate distress during the first year of life. During later childhood the ability to regulate conflict among competing stimuli builds upon the earlier cingulate anatomy to provide a means of cognitive control. During childhood the activation of cingulate structures relates both to the child's success on laboratory tasks involving conflict and to parental reports of self-regulation and emotional control. These studies indicate a start in understanding the anatomy, circuitry and development of executive attention networks that serve to regulate both cognition and emotion.
    BibTeX:
    @article{Posner1998,
      author = {Posner, MI and Rothbart, MK},
      title = {Attention, self-regulation and consciousness},
      journal = {PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES},
      year = {1998},
      volume = {353},
      number = {1377},
      pages = {1915-1927},
      note = {Annual Meeting of the Association-for-Research-in-Nervous-and-Mental-Disease on the Conscious Brain - Normal and Abnormal, NEW YORK, NY, DEC 05-06, 1997}
    }
    
    PREUSS, T. DO RATS HAVE PREFRONTAL CORTEX - THE ROSE-WOOLSEY-AKERT PROGRAM RECONSIDERED {1995} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {7}({1}), pp. {1-24} 
    article  
    Abstract: Primates are unique among mammals in possessing a region of dorsolateral prefrontal cortex with a well-developed internal granular layer. This region is commonly implicated in higher cognitive functions. Despite the histological distinctiveness of primate dorsolateral prefrontal cortex, the work of Rose, Woolsey, and Akert produced a broad consensus among neuroscientists that homologues of primate granular frontal cortex exist in nonprimates and can be recognized by their dense innervation from the mediodorsal thalamic nucleus (MD). Additional characteristics have come to be identified with dorsolateral prefrontal cortex, including rich dopaminergic innervation and involvement in spatial delayed-reaction tasks. However, recent studies reveal that these characteristics are not distinctive of the dorsolateral prefrontal region in primates: MD and dopaminergic projections are widespread in the frontal lobe, and medial and orbital frontal areas may play a role in delay tasks. A reevaluation of rat frontal cortex suggests that the medial frontal cortex, usually considered to be homologous to the dorsolateral prefrontal cortex of primates, actually consists of cortex homologous to primate premotor and anterior cingulate cortex. The lateral MD-projection cortex of rats resembles portions of primate orbital cortex. If prefrontal cortex is construed broadly enough to include orbital and cingulate cortex, rats can be said to have prefrontal cortex. However, they evidently lack homologues of the dorsolateral prefrontal areas of primates. This assessment suggests that rats probably do not provide useful models of human dorsolateral frontal lobe function and dysfunction, although they might prove valuable for understanding other regions of frontal cortex.
    BibTeX:
    @article{PREUSS1995,
      author = {PREUSS, TM},
      title = {DO RATS HAVE PREFRONTAL CORTEX - THE ROSE-WOOLSEY-AKERT PROGRAM RECONSIDERED},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {1995},
      volume = {7},
      number = {1},
      pages = {1-24}
    }
    
    Price, D. Neuroscience - Psychological and neural mechanisms of the affective dimension of pain {2000} SCIENCE
    Vol. {288}({5472}), pp. {1769-1772} 
    article  
    Abstract: The affective dimension of pain is made up of feelings of unpleasantness and emotions associated with future implications, termed secondary affect. Experimental and clinical studies show serial interactions between pain sensation intensity, pain unpleasantness, and secondary affect. These pain dimensions and their interactions relate to a central network of brain structures that processes nociceptive information both in a parallel and in series. Spinal pathways to limbic structures and medial thalamic nuclei provide direct inputs to brain areas involved in affect. Another source is from spinal pathways to somatosensory thalamic and cortical areas and then through a cortico-limbic pathway. The latter integrates nociceptive input with contextual information and memory to provide cognitive mediation of pain affect. Both direct and cortical-limbic pathways converge on the same anterior cingulate cortical and subcortical structures whose function may be to establish emotional valence and response priorities.
    BibTeX:
    @article{Price2000,
      author = {Price, DD},
      title = {Neuroscience - Psychological and neural mechanisms of the affective dimension of pain},
      journal = {SCIENCE},
      year = {2000},
      volume = {288},
      number = {5472},
      pages = {1769-1772}
    }
    
    Ragozzino, M., Detrick, S. & Kesner, R. Involvement of the prelimbic-infralimbic areas of the rodent prefrontal cortex in behavioral flexibility for place and response learning {1999} JOURNAL OF NEUROSCIENCE
    Vol. {19}({11}), pp. {4585-4594} 
    article  
    Abstract: The present experiments investigated the role of the prelimbic-infralimbic areas in behavioral flexibility using a place-response learning paradigm. All rats received a bilateral cannula implant aimed at the prelimbic-infralimbic areas. To examine the role of the prelimbic-infralimbic areas in shifting strategies, rats were tested on a place and a response discrimination in a cross-maze. Some rats were tested on the place version first followed by the response version. The procedure for the other rats was reversed. Infusions of 2% tetracaine into the prelimbic-infralimbic areas did not impair acquisition of the place or response discriminations. Prelimbic-infralimbic inactivation did impair learning when rats were switched from one discrimination to the other (cross-modal shift). To investigate the role of the prelimbic-infralimbic areas in intramodal shifts (reversal learning), one group of rats was tested on a place reversal and another group tested on a response reversal. Prelimbic-infralimbic inactivation did not impair place or response intramodal shifts. Some rats that completed testing on a particular version in the cross-modal and intramodal experiments were tested on the same version in a new room for 3 d. The transfer tests revealed that rats use a spatial strategy on the place version and an egocentric response strategy on the response version. Overall, these results suggest that the prelimbic-infralimbic areas are important for behavioral flexibility involving crossmodal but not intramodal shifts.
    BibTeX:
    @article{Ragozzino1999,
      author = {Ragozzino, ME and Detrick, S and Kesner, RP},
      title = {Involvement of the prelimbic-infralimbic areas of the rodent prefrontal cortex in behavioral flexibility for place and response learning},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1999},
      volume = {19},
      number = {11},
      pages = {4585-4594}
    }
    
    RAICHLE, M., FIEZ, J., VIDEEN, T., MACLEOD, A., PARDO, J., FOX, P. & PETERSEN, S. PRACTICE-RELATED CHANGES IN HUMAN BRAIN FUNCTIONAL-ANATOMY DURING NONMOTOR LEARNING {1994} CEREBRAL CORTEX
    Vol. {4}({1}), pp. {8-26} 
    article  
    Abstract: Practice of a novel task leads to improved performance. The brain mechanisms associated with practice-induced improvement in performance are largely unknown. To address this question we have examined the functional anatomy of the human brain with positron emission tomography (PET) during the naive and practiced performance of a simple verbal response selection task (saying an appropriate verb for a visually presented noun). As a control state, subjects were asked to repeat the visually presented nouns. Areas of the brain most active during naive performance (anterior cingulate, left prefrontal and left posterior temporal cortices, and the right cerebellar hemisphere), compared to repeating the visually presented nouns, were all significantly less active during practiced performance. These changes were accompanied by changes in the opposite direction in sylvian-insular cortex bilaterally and left medial extrastriate cortex. In effect, brief practice made the cortical circuitry used for verbal response selection indistinguishable from simple word repetition. Introduction of a novel list of words reversed the learning-related effects. These results indicate that two distinct circuits can he used for verbal response selection and normal subjects can change the brain circuits used during task performance following less than 15 min of practice. One critical factor in determining the circuitry used appears to be the degree to which a task is learned or automatic.
    BibTeX:
    @article{RAICHLE1994,
      author = {RAICHLE, ME and FIEZ, JA and VIDEEN, TO and MACLEOD, AMK and PARDO, JV and FOX, PT and PETERSEN, SE},
      title = {PRACTICE-RELATED CHANGES IN HUMAN BRAIN FUNCTIONAL-ANATOMY DURING NONMOTOR LEARNING},
      journal = {CEREBRAL CORTEX},
      year = {1994},
      volume = {4},
      number = {1},
      pages = {8-26}
    }
    
    Raichle, M., MacLeod, A., Snyder, A., Powers, W., Gusnard, D. & Shulman, G. A default mode of brain function {2001} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {98}({2}), pp. {676-682} 
    article  
    Abstract: A baseline or control state is fundamental to the understanding of most complex systems. Defining a baseline state in the human brain, arguably our most complex system, poses a particular challenge, Many suspect that left unconstrained, its activity will vary unpredictably. Despite this prediction we identify a baseline state of the normal adult human brain in terms of the brain oxygen extraction fraction or OEF, The OEF is defined as the ratio of oxygen used by the brain to oxygen delivered by flowing blood and is remarkably uniform in the awake but resting state (e.g., lying quietly with eyes closed). Local deviations in the OEF represent the physiological basis of signals of changes in neuronal activity obtained with functional MRI during a wide variety of human behaviors. We used quantitative metabolic and circulatory measurements from positron-emission tomography to obtain the OEF regionally throughout the brain. Areas of activation were conspicuous by their absence. All significant deviations from the mean hemisphere OEF were increases, signifying deactivations, and resided almost exclusively in the visual system. Defining the baseline state of an area in this manner attaches meaning to a group of areas that consistently exhibit decreases from this baseline, during a wide variety of goal-directed behaviors monitored with positron-emission tomography and functional MRI. These decreases suggest the existence of an organized, baseline default mode of brain function that is suspended during specific goal-directed behaviors.
    BibTeX:
    @article{Raichle2001,
      author = {Raichle, ME and MacLeod, AM and Snyder, AZ and Powers, WJ and Gusnard, DA and Shulman, GL},
      title = {A default mode of brain function},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {2001},
      volume = {98},
      number = {2},
      pages = {676-682}
    }
    
    Rainville, P., Duncan, G., Price, D., Carrier, B. & Bushnell, M. Pain affect encoded in human anterior cingulate but not somatosensory cortex {1997} SCIENCE
    Vol. {277}({5328}), pp. {968-971} 
    article  
    Abstract: Recent evidence demonstrating multiple regions of human cerebral cortex activated by pain has prompted speculation about their individual contributions to this complex experience. To differentiate cortical areas involved in pain affect, hypnotic suggestions were used to alter selectively the unpleasantness of noxious stimuli, without changing the perceived intensity. Positron emission tomography revealed significant changes in pain-evoked activity within anterior cingulate cortex, consistent with the encoding of perceived unpleasantness, whereas primary somatosensory cortex activation was unaltered. These findings provide direct experimental evidence in humans linking frontal-lobe limbic activity with pain affect, as originally suggested by early clinical lesion studies.
    BibTeX:
    @article{Rainville1997,
      author = {Rainville, P and Duncan, GH and Price, DD and Carrier, B and Bushnell, MC},
      title = {Pain affect encoded in human anterior cingulate but not somatosensory cortex},
      journal = {SCIENCE},
      year = {1997},
      volume = {277},
      number = {5328},
      pages = {968-971}
    }
    
    Rajkowska, G., Selemon, L. & Goldman-Rakic, P. Neuronal and glial somal size in the prefrontal cortex - A postmortem morphometric study of schizophrenia and Huntington disease {1998} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {55}({3}), pp. {215-224} 
    article  
    Abstract: Background: The cortex of patients with schizophrenia exhibits a deficit in neuropil, but the nature and extent of cellular abnormalities remain unclear. To gain further insight into this abnormality, neuronal and glial somal size were analyzed in postmortem brains from 9 patients with schizophrenia, 10 normal (control) patients, and 7 patients with Huntington disease, the latter representing a known neurodegenerative disorder. Methods: A 3-dimensional image analyzer was used to measure the perimeters of 10722 neuronal and 19913 glial profiles in Brodmann areas 9 and 17. Neurons and glia were classified by size and layer to assess specific vulnerabilities with respect to cortical architecture and circuitry. Results: The schizophrenic prefrontal cortex was characterized by a downward shift in neuronal sizes accompanied by 70% to 140% per layer increases in the density of small neurons. In layer III only, a significant reduction in mean neuronal size was associated with a significant decrease in the density of very large neurons in sublayer IIIc. Neither neuronal size in occipital area 17 nor glial size in prefrontal or occipital cortexes were reduced. In cortex with Huntington disease, neuronal degeneration was evidenced by concurrence of reduced neuronal size, decreased density of large neurons, and dramatic elevation in density of large glia. Conclusions: Distinct cytometric abnormalities support the hypothesis that neuronal degeneration in the prefrontal Sorter is not a prominent feature of the neuropathological changes in schizophrenia, although an ongoing process in Huntington disease. Rather, schizophrenia appears to involve more subtle abnormalities, with the largest corticocortical projection neurons of layer IIIc expressing the greatest somal reduction.
    BibTeX:
    @article{Rajkowska1998,
      author = {Rajkowska, G and Selemon, LD and Goldman-Rakic, PS},
      title = {Neuronal and glial somal size in the prefrontal cortex - A postmortem morphometric study of schizophrenia and Huntington disease},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1998},
      volume = {55},
      number = {3},
      pages = {215-224},
      note = {5th International Congress of Schizophrenia Research, HOT SPRINGS, VIRGINIA, APR 06-12, 1995}
    }
    
    RAUCH, S., JENIKE, M., ALPERT, N., BAER, L., BREITER, H., SAVAGE, C. & FISCHMAN, A. REGIONAL CEREBRAL BLOOD-FLOW MEASURED DURING SYMPTOM PROVOCATION IN OBSESSIVE-COMPULSIVE DISORDER USING OXYGEN 15-LABELED CARBON-DIOXIDE AND POSITRON EMISSION TOMOGRAPHY {1994} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {51}({1}), pp. {62-70} 
    article  
    Abstract: Background: The study was designed to determine the mediating neuroanatomy of obsessive-compulsive disorder (OCD). Methods: The short half-life tracer oxygen 15-labeled carbon dioxide was used to allow for repeated positron emission tomographic determinations of regional cerebral blood flow on each of eight patients with OCD during a resting and a provoked (symptomatic) state. Results: Individually tailored provocative stimuli were successful in provoking OCD symptoms, in comparison with paired innocuous stimuli, as measured by self-report on OCD analogue scales (P=.002). Omnibus subtraction images demonstrated a statistically significant increase in relative regional cerebral blood now during the OCD symptomatic state vs the resting state in right caudate nucleus (P<.006), left anterior cingulate cortex (P<.045), and bilateral orbitofrontal cortex (P<.008); increases in the left thalamus approached but did not reach statistical significance (P=.07). Conclusions: These findings are consistent with results of previous functional neuroimaging studies and contemporary neurocircuitry models of OCD. The data further implicate orbitofrontal cortex, caudate nucleus, and anterior cigulate cortex in the pathophysiology of OCD and in mediating OCD symptoms.
    BibTeX:
    @article{RAUCH1994,
      author = {RAUCH, SL and JENIKE, MA and ALPERT, NM and BAER, L and BREITER, HCR and SAVAGE, CR and FISCHMAN, AJ},
      title = {REGIONAL CEREBRAL BLOOD-FLOW MEASURED DURING SYMPTOM PROVOCATION IN OBSESSIVE-COMPULSIVE DISORDER USING OXYGEN 15-LABELED CARBON-DIOXIDE AND POSITRON EMISSION TOMOGRAPHY},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1994},
      volume = {51},
      number = {1},
      pages = {62-70}
    }
    
    RAUCH, S., SAVAGE, C., ALPERT, N., MIGUEL, E., BAER, L., BREITER, H., FISCHMAN, A., MANZO, P., MORETTI, C. & JENIKE, M. A POSITRON EMISSION TOMOGRAPHIC STUDY OF SIMPLE PHOBIC SYMPTOM PROVOCATION {1995} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {52}({1}), pp. {20-28} 
    article  
    Abstract: Background: The goal of this study was to determine the mediating neuroanatomy of simple phobic symptoms. Methods: Positron emission tomography and oxygen 15 were used to measure normalized regional cerebral blood flow in seven subjects with simple phobia during control and provoked states. Stereotactic transformation and statistical parametric mapping techniques were employed to determine the locations of significant activation. Results: Statistical parametric maps demonstrated significant increases in normalized regional blood flow for the symptomatic state compared with the control state in the anterior cingulate cortex, the insular cortex, the anterior temporal cortex, the somatosensory cortex, the posterior medial orbitofrontal cortex, and the thalamus. Conclusions: The results suggest that anxiety associated with the simple phobic symptomatic state is mediated by paralimbic structures. Moreover, activation of somatosensory cortex may reflect tactile imagery as one component of the phobic symptomatic condition.
    BibTeX:
    @article{RAUCH1995,
      author = {RAUCH, SL and SAVAGE, CR and ALPERT, NM and MIGUEL, EC and BAER, L and BREITER, HC and FISCHMAN, AJ and MANZO, PA and MORETTI, C and JENIKE, MA},
      title = {A POSITRON EMISSION TOMOGRAPHIC STUDY OF SIMPLE PHOBIC SYMPTOM PROVOCATION},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1995},
      volume = {52},
      number = {1},
      pages = {20-28}
    }
    
    Rauch, S., Whalen, P., Shin, L., McInerney, S., Macklin, M., Lasko, N., Orr, S. & Pitman, R. Exaggerated amygdala response to masked facial stimuli in posttraumatic stress disorder: A functional MRI study {2000} BIOLOGICAL PSYCHIATRY
    Vol. {47}({9}), pp. {769-776} 
    article  
    Abstract: Background: Converging lines of evidence have implicated the amygdala in the pathophysiology of posttraumatic stress disorder (PTSD). We previously developed a method for measuring automatic amygdala responses to general threat-related stimuli; in conjunction with functional magnetic resonance imaging, we used a passive viewing task involving masked presentations of human facial stimuli. Methods: We applied this method to study veterans with PTSD and a comparison cohort of combat-exposed veterans without PTSD. Results: The findings indicate that patients with PTSD exhibit exaggerated amygdala responses to masked-fearful versus masked-happy faces. Conclusions: Although some previous neuroimaging studies of PTSD have demonstrated amygdala recruitment in response to reminders of traumatic events, this represents the first evidence for exaggerated amygdala responses to general negative stimuli in PTSD. Furthermore, by using a probe that emphasizes automaticity, we provide initial evidence of amygdala hyperresponsivity dissociated from the ``top-down `` influences of medial frontal cortex. Biol Psychiatry 2000;47:769-776 (C) 2000 Society of Biological Psychiatry.
    BibTeX:
    @article{Rauch2000,
      author = {Rauch, SL and Whalen, PJ and Shin, LM and McInerney, SC and Macklin, ML and Lasko, NB and Orr, SP and Pitman, RK},
      title = {Exaggerated amygdala response to masked facial stimuli in posttraumatic stress disorder: A functional MRI study},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {2000},
      volume = {47},
      number = {9},
      pages = {769-776}
    }
    
    Raz, N., Gunning, F., Head, D., Dupuis, J., McQuain, J., Briggs, S., Loken, W., Thornton, A. & Acker, J. Selective aging of the human cerebral cortex observed in vivo: Differential vulnerability of the prefrontal gray matter {1997} CEREBRAL CORTEX
    Vol. {7}({3}), pp. {268-282} 
    article  
    Abstract: In a prospective cross sectional study, we used computerized volumetry of magnetic resonance images to examine the patterns of brain aging in 148 healthy volunteers. The most substantial age related decline was found in the volume of the prefrontal gray matter. Smaller age-related differences were observed in the volume of the fusiform, inferior temporal and superior parietal cortices. The effects of age on the hippocampal formation, the postcentral gyrus, prefrontal white matter and superior parietal white matter were even weaker. No significant age-related differences were observed in the parahippocampal and anterior cingulate gyri, inferior parietal lobule, pericalcarine gray matter, the precentral gray and white matter, postcentral white matter and inferior parietal white matter. The volume of the total brain volume and the hippocampal formation was larger in men than in women even after adjustment for height. Inferior temporal cortex showed steeper aging trend in men. Small but consistent rightward asymmetry was found in the whole cerebral hemispheres, superior parietal, fusiform and orbito-frontal cortices, postcentral and prefrontal white matter. The left side was larger than the right in the dorsolateral prefrontal, parahippocampal, inferior parietal and pericalcarine cortices, and in the parietal white matter. However, there were no significant differences in age trends between the hemispheres.
    BibTeX:
    @article{Raz1997,
      author = {Raz, N and Gunning, FM and Head, D and Dupuis, JH and McQuain, J and Briggs, SD and Loken, WJ and Thornton, AE and Acker, JD},
      title = {Selective aging of the human cerebral cortex observed in vivo: Differential vulnerability of the prefrontal gray matter},
      journal = {CEREBRAL CORTEX},
      year = {1997},
      volume = {7},
      number = {3},
      pages = {268-282},
      note = {25th Annual Meeting of the Society-for-Neuroscience, SAN DIEGO, CA, NOV 11-16, 1995}
    }
    
    Rees, G., Friston, K. & Koch, C. A direct quantitative relationship between the functional properties of human and macaque V5 {2000} NATURE NEUROSCIENCE
    Vol. {3}({7}), pp. {716-723} 
    article  
    Abstract: The nature of the quantitative relationship between single-neuron recordings in monkeys and functional magnetic resonance imaging (fMRI) measurements in humans is crucial to understanding how experiments in these different species are related, yet it remains undetermined. We measured brain activity in humans attending to moving visual stimuli, using blood oxygenation level-dependent (BOLD) fMRI. Responses in Vs showed a strong and highly linear dependence on increasing strength of motion signal (coherence). These population responses in human Vs had a remarkably simple mathematical relationship to previously observed single-cell responses in macaque Vs. We provided an explicit quantitative estimate for the interspecies comparison of single-neuron activity and BOLD population responses. Our data show previously unknown dissociations between the functional properties of human Vs and other human motion-sensitive areas, thus predicting similar dissociations for the properties of single neurons in homologous areas of macaque cortex.
    BibTeX:
    @article{Rees2000,
      author = {Rees, G and Friston, K and Koch, C},
      title = {A direct quantitative relationship between the functional properties of human and macaque V5},
      journal = {NATURE NEUROSCIENCE},
      year = {2000},
      volume = {3},
      number = {7},
      pages = {716-723}
    }
    
    Reiman, E., Caselli, R., Chen, K., Alexander, G., Bandy, D. & Frost, J. Declining brain activity in cognitively normal apolipoprotein E epsilon 4 heterozygotes: A foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease {2001} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {98}({6}), pp. {3334-3339} 
    article  
    Abstract: Cross-sectional positron emission tomography (PET) studies find that cognitively normal carriers of the apolipoprotein E (APOE) epsilon4 allele, a common Alzheimer's susceptibility gene, have abnormally low measurements of the cerebral metabolic rate for glucose (CMRgI) in the same regions as patients with Alzheimer's dementia. In this article, we characterize longitudinal CMRgI declines in cognitively normal epsilon4 heterozygotes, estimate the power of PET to test the efficacy of treatments to attenuate these declines in 2 years, and consider how this paradigm could be used to efficiently test the potential of candidate therapies for the prevention of Alzheimer's disease. We studied 10 cognitively normal epsilon4 heterozygotes and 15 epsilon4 noncarriers 50-63 years of age with a reported family history of Alzheimer's dementia before and after an interval of approximately 2 years. The epsilon4 heterozygotes had significant CMRgI declines in the vicinity of temporal, posterior cingulate, and prefrontal cortex, basal forebrain, parahippocampal gyrus, and thalamus, and these declines were significantly greater than those in the epsilon4 noncarriers. In testing candidate primary prevention therapies, we estimate that between 50 and 115 cognitively normal epsilon4 heterozygotes are needed per active and placebo treatment group to detect a 25% attenuation in these CMRgI declines with 80% power and P = 0.005 in 2 years. Assuming these CMRgI declines are related to the predisposition to Alzheimer's dementia, this study provides a paradigm for testing the potential of treatments to prevent the disorder without having to study thousands of research subjects or wait many years to determine whether or when treated individuals develop symptoms.
    BibTeX:
    @article{Reiman2001,
      author = {Reiman, EM and Caselli, RJ and Chen, KW and Alexander, GE and Bandy, D and Frost, J},
      title = {Declining brain activity in cognitively normal apolipoprotein E epsilon 4 heterozygotes: A foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {2001},
      volume = {98},
      number = {6},
      pages = {3334-3339}
    }
    
    Reiman, E., Chen, K., Alexander, G., Caselli, R., Bandy, D., Osborne, D., Saunders, A. & Hardy, J. Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia {2004} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {101}({1}), pp. {284-289} 
    article DOI  
    Abstract: Fluorodeoxyglucose positron emission tomography (PET) studies have found that patients with Alzheimer's dementia (AD) have abnormally low rates of cerebral glucose metabolism in posterior cingulate, parietal, temporal, and prefrontal cortex. We previously found that cognitively normal, late-middle-aged carriers of the apolipoprotein E epsilon4 allele, a common susceptibility gene for late-onset Alzheimer's dementia, have abnormally low rates of glucose metabolism in the same brain regions as patients with probable AD. We now consider whether e4 carriers have these regional brain abnormalities as relatively young adults. Apolipoprotein E genotypes were established in normal volunteers 20-39 years of age. Clinical ratings, neuropsychological tests, magnetic resonance imaging, and PET were performed in 12 epsilon4 heterozygotes, all with the epsilon3/epsilon4 genotype, and 15 noncarriers of the epsilon4 allele, 12 of whom were individually matched for sex, age, and educational level. An automated algorithm was used to generate an aggregate surf ace-projection map that compared regional PET measurements in the two groups. The young adult epsilon4 carriers and noncarriers did not differ significantly in their sex, age, educational level, clinical ratings, or neuropsychological test scores. Like previously studied patients with probable AD and late-middle-aged epsilon4 carriers, the young epsilon4 carriers had abnormally low rates of glucose metabolism bilaterally in the posterior cingulate, parietal, temporal, and prefrontal cortex. Carriers of a common Alzheimer's susceptibility gene have functional brain abnormalities in young adulthood, several decades before the possible onset of dementia.
    BibTeX:
    @article{Reiman2004,
      author = {Reiman, EM and Chen, KW and Alexander, GE and Caselli, RJ and Bandy, D and Osborne, D and Saunders, AM and Hardy, J},
      title = {Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {2004},
      volume = {101},
      number = {1},
      pages = {284-289},
      doi = {{10.1073/pnas.2635903100}}
    }
    
    Ridderinkhof, K., Ullsperger, M., Crone, E. & Nieuwenhuiss, S. The role of the medial frontal cortex in cognitive control {2004} SCIENCE
    Vol. {306}({5695}), pp. {443-447} 
    article  
    Abstract: Adaptive goal-directed behavior involves monitoring of ongoing actions and performance outcomes, and subsequent adjustments of behavior and learning. We evaluate new findings in cognitive neuroscience concerning cortical interactions that subserve the recruitment and implementation of such cognitive control. A review of primate and human studies, along with a meta-analysis of the human functional neuroimaging literature, suggest that the detection of unfavorable outcomes, response errors, response conflict, and decision uncertainty elicits largely overlapping clusters of activation foci in an extensive part of the posterior medial. frontal cortex (pMFC). A direct link is delineated between activity in this area and subsequent adjustments in performance. Emerging evidence points to functional interactions between the pMFC and the lateral prefrontal cortex (LPFC), so that monitoring-related pMFC activity serves as a signal that engages regulatory processes in the LPFC to implement performance adjustments.
    BibTeX:
    @article{Ridderinkhof2004,
      author = {Ridderinkhof, KR and Ullsperger, M and Crone, EA and Nieuwenhuiss, S},
      title = {The role of the medial frontal cortex in cognitive control},
      journal = {SCIENCE},
      year = {2004},
      volume = {306},
      number = {5695},
      pages = {443-447}
    }
    
    Ridderinkhof, K., van den Wildenberg, W., Segalowitz, S. & Carter, C. Neurocognitive mechanisms of cognitive control: The role of prefrontal cortex in action selection, response inhibition, performance monitoring, and reward-based learning {2004} BRAIN AND COGNITION
    Vol. {56}({2}), pp. {129-140} 
    article DOI  
    Abstract: Convergent evidence highlights the differential contributions of various regions of the prefrontal cortex in the service of cognitive control, but little is understood about how the brain determines and communicates the need to recruit cognitive control, and how such signals instigate the implementation of appropriate performance adjustments. Here we review recent progress from cognitive neuroscience in examining some of the main constituent processes of cognitive control as involved in dynamic decision making: goal-directed action selection, response activation and inhibition, performance monitoring, and reward-based learning. Medial frontal cortex is found to be involved in performance monitoring: evaluating outcome vis-A-vis expectancy, and detecting performance errors or conflicting response tendencies. Lateral and orbitofrontal divisions of prefrontal cortex are involved in subsequently implementing appropriate adjustments. (C) 2004 Elsevier Inc. All rights reserved.
    BibTeX:
    @article{Ridderinkhof2004a,
      author = {Ridderinkhof, KR and van den Wildenberg, WPM and Segalowitz, SJ and Carter, CS},
      title = {Neurocognitive mechanisms of cognitive control: The role of prefrontal cortex in action selection, response inhibition, performance monitoring, and reward-based learning},
      journal = {BRAIN AND COGNITION},
      year = {2004},
      volume = {56},
      number = {2},
      pages = {129-140},
      doi = {{10.1016/j.bandc.2004.09.016}}
    }
    
    Rilling, J., Gutman, D., Zeh, T., Pagnoni, G., Berns, G. & Kilts, C. A neural basis for social cooperation {2002} NEURON
    Vol. {35}({2}), pp. {395-405} 
    article  
    Abstract: Cooperation based on reciprocal altruism has evolved in only a small number of species, yet it constitutes the core behavioral principle of human social life. The iterated Prisoner's Dilemma Game has been used to model this form of cooperation. We used fMRI to scan 36 women as they played an iterated Prisoner's Dilemma Game with another woman to investigate the neurobiological basis of cooperative social behavior. Mutual cooperation was associated with consistent activation in brain areas that have been linked with reward processing: nucleus accumbens, the caudate nucleus, ventromedial frontal/orbitofrontal cortex, and rostral anterior cingulate cortex. We propose that activation of this neural network positively reinforces reciprocal altruism, thereby motivating subjects to resist the temptation to selfishly accept but not reciprocate favors.
    BibTeX:
    @article{Rilling2002,
      author = {Rilling, JK and Gutman, DA and Zeh, TR and Pagnoni, G and Berns, GS and Kilts, CD},
      title = {A neural basis for social cooperation},
      journal = {NEURON},
      year = {2002},
      volume = {35},
      number = {2},
      pages = {395-405}
    }
    
    Rizzolatti, G., Luppino, G. & Matelli, M. The organization of the cortical motor system: new concepts {1998} ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
    Vol. {106}({4}), pp. {283-296} 
    article  
    Abstract: A series of recent anatomical and functional data has radically changed our view on the organization of the motor cortex in primates. In the present article we present this view and discuss its fundamental principles. The basic principles are the following: (a) the motor cortex, defined as the agranular frontal cortex, is formed by a mosaic of separate areas, each of which contains an independent body movement representation, (b) each motor area plays a specific role in motor control, based on the specificity of its cortical afferents and descending projections, (c) in analogy to the motor cortex, the posterior parietal cortex is formed by a multiplicity of areas, each of which is involved in the analysis of particular aspects of sensory information. There are no such things as multipurpose areas for space or body schema and (d) the parieto-frontal connections form a series of segregated anatomical circuits devoted to specific sensorimotor transformations. These circuits transform sensory information into action. They represent the basic functional units of the motor system. Although these conclusions mostly derive from monkey experiments, anatomical and brain-imaging evidence suggest that the organization of human motor cortex is based on the same principles. Possible homologies between the motor cortices of humans and non-human primates are discussed. (C) 1998 Elsevier Science Ireland Ltd.
    BibTeX:
    @article{Rizzolatti1998,
      author = {Rizzolatti, G and Luppino, G and Matelli, M},
      title = {The organization of the cortical motor system: new concepts},
      journal = {ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY},
      year = {1998},
      volume = {106},
      number = {4},
      pages = {283-296}
    }
    
    Robbins, T. The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry {2002} PSYCHOPHARMACOLOGY
    Vol. {163}({3-4}), pp. {362-380} 
    article DOI  
    Abstract: Rationale: The developmental history and application of the 5-choice serial reaction time task (5CSRTT) for measuring effects of drugs and other manipulations on attentional performance (and stimulus control) in rats is reviewed. Objectives: The 5CSRTT has been used for measuring effects of systemic drug treatments and also central manipulations such as neurochemical lesions on various aspects of attentional control, including sustained, selective and divided attention - and is relevant to the definition of neural systems of attention and applications to human disorders such as attention deficit/hyperactivity disorder (ADHD) and Alzheimer's disease. Methods: The 5CSRTT is implemented in a specially designed operant chamber with multiple response locations ('nine-hole box') using food reinforcers to maintain performance on baseline sessions (about 100 trials) at criterion levels of accuracy and trials completed. The 5CSRTT can be used for measuring various aspects of attentional control over performance with its main measures of accuracy, premature responding, correct response latencies and latency to collect earned food pellets. Results: The data reviewed include studies mainly of systemic and intra-cerebral effects of adrenoceptor, dopamine receptor, serotoninergic receptor and cholinergic receptor agents. These are compared with investigations of effects of selective chemical neurotoxins and excitotoxins applied to discrete parts of the forebrain, in order to define the neural and neurochemical substrates of attentional function. Furthermore, these results are integrated with findings from in vivo microdialysis in freely moving rats or metabolic studies. Conclusions: The monoaminergic and cholinergic systems appear to play separable roles in different aspects of performance controlled by the 5CSRTT, in neural systems centred on the prefrontal cortex, cingulate cortex and striatum. These conclusions are considered in the methodological and theoretical context of other psychopharmacological studies of attention in animals and humans.
    BibTeX:
    @article{Robbins2002,
      author = {Robbins, TW},
      title = {The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry},
      journal = {PSYCHOPHARMACOLOGY},
      year = {2002},
      volume = {163},
      number = {3-4},
      pages = {362-380},
      doi = {{10.1107/s00213-002-1154-7}}
    }
    
    Rogers, R., Owen, A., Middleton, H., Williams, E., Pickard, J., Sahakian, B. & Robbins, T. Choosing between small, likely rewards and large, unlikely rewards activates inferior and orbital prefrontal cortex {1999} JOURNAL OF NEUROSCIENCE
    Vol. {19}({20}), pp. {9029-9038} 
    article  
    Abstract: Patients sustaining lesions of the orbital prefrontal cortex (PFC) exhibit marked impairments in the performance of laboratory-based gambling, or risk-taking, tasks, suggesting that this part of the human PFC contributes to decision-making cognition. However, to date, little is known about the particular regions of the orbital cortex that participate in this function. In the present study, eight healthy volunteers were scanned, using H-2 O-15 PET technology, while performing a novel computerized risk-taking task. The task involved predicting which of two mutually exclusive outcomes would occur, but critically, the larger reward (and penalty) was associated with choice of the least likely outcome, whereas the smallest reward (and penalty) was associated with choice of the most likely outcome. Resolving these ``conflicting'' decisions was associated with three distinct foci of regional cerebral blood flow increase within the right inferior and orbital PFC: laterally, in the anterior part of the middle frontal gyrus [Brodmann area 10 (BA 10)], medially, in the orbital gyrus (BA 11), and posteriorly, in the anterior portion of the inferior frontal gyrus (BA 47). By contrast, increases in the degree of conflict inherent in these decisions was associated with only limited changes in activity within orbital PFC and the anterior cingulate cortex. These results suggest that decision making recruits neural activity from multiple regions of the inferior PFC that receive information from a diverse set of cortical and limbic inputs, and that the contribution of the orbitofrontal regions may involve processing changes in reward-related information.
    BibTeX:
    @article{Rogers1999,
      author = {Rogers, RD and Owen, AM and Middleton, HC and Williams, EJ and Pickard, JD and Sahakian, BJ and Robbins, TW},
      title = {Choosing between small, likely rewards and large, unlikely rewards activates inferior and orbital prefrontal cortex},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1999},
      volume = {19},
      number = {20},
      pages = {9029-9038}
    }
    
    ROLAND, P. & GULYAS, B. VISUAL MEMORY, VISUAL-IMAGERY, AND VISUAL RECOGNITION OF LARGE FIELD PATTERNS BY THE HUMAN BRAIN - FUNCTIONAL-ANATOMY BY POSITRON EMISSION TOMOGRAPHY {1995} CEREBRAL CORTEX
    Vol. {5}({1}), pp. {79-93} 
    article  
    Abstract: We measured the regional cerebral blood flow (rCBF) in 11 healthy volunteers with PET (positron emission tomography). The main purpose was to map the areas of the human brain that changed rCBF during (1) the storage, (2) retrieval from long-term memory, and (3) recognition of complex visual geometrical patterns. A control measurement was done with subjects at rest. Perception and learning of the patterns increased rCBF in V1 and in 17 cortical fields located in the cuneus, the lingual, fusiform, inferior temporal, occipital, and angular gyri, the precuneus, and the posterior part of superior parietal lobules. In addition, rCBF increased in the anterior hippocampus, anterior cingulate gyrus, and in several fields in the prefrontal cortex. Recognition of the patterns increased rCBF in 18 identically located fields overlapping those activated in learning. In addition, recognition provoked differentially localized increases in the pulvinar, posterior hippocampus, and prefrontal cortex. Learning and recognition of the patterns thus activated identical visual regions, but different extravisual regions. A surprising finding was that the hippocampus was also active in recognition. Recall of the patterns from long-term memory was associated with rCBF increases in yet different fields in the prefrontal cortex, and the anterior cingulate cortex. In addition, the posterior inferior temporal lobe, the precuneus, the angular gyrus, and the posterior superior parietal lobule were activated, but not any spot within the occipital cortex. Activation of V1 or immediate visual association areas is not a prerequisite for visual imagery for the patterns. The only four fields activated in storage recall and recognition were those in the posterior inferior temporal robe, the precuneus, the angular gyrus, and the posterior superior parietal lobule. These might be the storage sites for such visual patterns. If this is true, storage, retrieval, and recognition of complex visual patterns are mediated by higher-level visual areas. Thus, visual learning and recognition of the same patterns make use of identical visual areas, whereas retrieval of this material from the storage sites activates only a subset of the visual areas. The extravisual networks mediating storage, retrieval, and recognition differ, indicating that the ways by which the brain accesses the storage sites are different.
    BibTeX:
    @article{ROLAND1995,
      author = {ROLAND, PE and GULYAS, B},
      title = {VISUAL MEMORY, VISUAL-IMAGERY, AND VISUAL RECOGNITION OF LARGE FIELD PATTERNS BY THE HUMAN BRAIN - FUNCTIONAL-ANATOMY BY POSITRON EMISSION TOMOGRAPHY},
      journal = {CEREBRAL CORTEX},
      year = {1995},
      volume = {5},
      number = {1},
      pages = {79-93}
    }
    
    Rolls, E. The orbitofrontal cortex and reward {2000} CEREBRAL CORTEX
    Vol. {10}({3}), pp. {284-294} 
    article  
    Abstract: The primate orbitofrontal cortex contains the secondary taste cortex, in which the reward value of taste is represented. It also contains the secondary and tertiary olfactory cortical areas, in which information about the identity and also about the reward value of odors is represented. The orbitofrontal cortex also receives information about the sight of objects and faces from the temporal lobe cortical visual areas, and neurons in it learn and reverse the visual stimulus to which they respond when the association of the visual stimulus with a primary reinforcing stimulus (such as a taste reward) is reversed. However, the orbitofrontal cortex is involved in representing negative reinforcers (punishers) too, such as aversive taste, and in rapid stimulus-reinforcement association learning for both positive and negative primary reinforcers. In complementary neuroimaging studies in humans it is being found that areas of the orbitofrontal cortex (land connected subgenual cingulate cortex) are activated by pleasant touch, by painful touch, by rewarding and aversive taste, and by odor. Damage to the orbitofrontal cortex in humans can impair the learning and reversal of stimulus-reinforcement associations, and thus the correction of behavioral responses when these are no longer appropriate because previous reinforcement contingencies change. This evidence thus shows that the orbitofrontal cortex is involved in decoding and representing some primary reinforcers such as taste and touch: in learning and reversing associations of visual and other stimuli to these primary reinforcers: and in controlling and correcting reward-related and punishment-related behavior, and thus in emotion.
    BibTeX:
    @article{Rolls2000,
      author = {Rolls, ET},
      title = {The orbitofrontal cortex and reward},
      journal = {CEREBRAL CORTEX},
      year = {2000},
      volume = {10},
      number = {3},
      pages = {284-294}
    }
    
    Rosen, H., Gorno-Tempini, M., Goldman, W., Perry, R., Schuff, N., Weiner, M., Feiwell, R., Kramer, J. & Miller, B. Patterns of brain atrophy in frontotemporal dementia and semantic dementia {2002} NEUROLOGY
    Vol. {58}({2}), pp. {198-208} 
    article  
    Abstract: Objective: To identify and compare the patterns of cerebral atrophy associated with two clinical variants of frontotemporal lobar degeneration (FTLD): frontotemporal dementia (FTD) and semantic dementia (SemD). Methods: Twenty patients with FTLD were classified as having FTD (N = 8) or SemD) (N = 12) based on current clinical criteria. Both groups showed a similar spectrum of behavioral abnormalities, as indicated by the neuropsychiatric inventory. T1-weighted MRI was obtained for each patient and 20 control subjects. The regions of focal gray matter tissue loss associated with both FTD and SemD, as well as those differing between the two groups were examined using voxel-based morphometry. Results: Regions of significant atrophy seen in both groups were located in the ventromedial frontal cortex, the posterior orbital frontal regions bilaterally, the insula bilaterally, and the left anterior cingulate cortex. The FTD, but not the SemD, g-roup showed atrophy in the right dorsolateral frontal cortex and the left premotor cortex. The SemD, but not the FTD, group showed tissue loss in the anterior temporal cortex and the amygdala/anterior hippocampal region bilaterally. Conclusions: Although FTD and SemD are associated with different overall patterns of brain atrophy, regions of gray matter tissue loss in the orbital frontal, insular, and anterior cingulate regions are present in both groups. The authors suggest that pathology in the areas of atrophy associated with both FTD and SemD) may underlie some the behavioral symptoms seen in the two disorders.
    BibTeX:
    @article{Rosen2002,
      author = {Rosen, HJ and Gorno-Tempini, ML and Goldman, WP and Perry, RJ and Schuff, N and Weiner, M and Feiwell, R and Kramer, JH and Miller, BL},
      title = {Patterns of brain atrophy in frontotemporal dementia and semantic dementia},
      journal = {NEUROLOGY},
      year = {2002},
      volume = {58},
      number = {2},
      pages = {198-208}
    }
    
    ROUILLER, E., BABALIAN, A., KAZENNIKOV, O., MORET, V., YU, X. & WIESENDANGER, M. TRANSCALLOSAL CONNECTIONS OF THE DISTAL FORELIMB REPRESENTATIONS OF THE PRIMARY AND SUPPLEMENTARY MOTOR CORTICAL AREAS IN MACAQUE MONKEYS {1994} EXPERIMENTAL BRAIN RESEARCH
    Vol. {102}({2}), pp. {227-243} 
    article  
    Abstract: The goal of the present neuroanatomical study in macaque monkeys was twofold: (1) to clarify whether the hand representation of the primary motor cortex (M1) has a transcallosal projection to M1 of the opposite hemisphere; (2) to compare the topography and density of transcallosal connections for the hand representations of M1 and the supplementary motor area (SMA). The hand areas of M1 and the SMA were identified by intracortical microstimulation and then injected either with retrograde tracer substances in order to label the neurons of origin in the contralateral motor cortical areas (four monkeys) or, with an anterograde tracer, to establish the regional distribution and density of terminal fields in the opposite motor cortical areas (two monkeys). The main results were: (I) The hand representation of M1 exhibited a modest homotopic callosal projection, as judged by the small number of labeled neurons within the region corresponding to the contralateral injection. A modest heterotopic callosal projection originated from the opposite supplementary, premotor, and cingulate motor areas. (2) In contrast, the SMA hand representation showed a dense callosal projection to the opposite SMA. The SMA was found to receive also dense heterotopic callosal projections from the contralateral rostral and caudal cingulate motor areas, moderate projections from the lateral premotor cortex, and sparse projections from M1. (3) After injection of an anterograde tracer (biotinylated dextran amine) in the hand representation of MI, only a few small patches of axonal label were found in the corresponding region of M1, as well as in the lateral premotor cortex; virtually no label was found in the SMA or in cingulate motor areas. Injections of the same anterograde tracer in the hand representation of the SMA, however, resulted in dense and widely distributed axonal terminal fields in the opposite SMA, premotor cortex, and cingulate motor areas, while labeled terminals were clearly less dense in M1. It is concluded that the hand representations of the SMA and M1 strongly differ with respect to the strength and distribution of callosal connectivity with the former having more powerful and widespread callosal connections with a number of motor fields of the opposite cortex than the latter. These anatomical results support the proposition of the SMA being a bilaterally organized system, possibly contributing to bimanual coordination.
    BibTeX:
    @article{ROUILLER1994,
      author = {ROUILLER, EM and BABALIAN, A and KAZENNIKOV, O and MORET, V and YU, XH and WIESENDANGER, M},
      title = {TRANSCALLOSAL CONNECTIONS OF THE DISTAL FORELIMB REPRESENTATIONS OF THE PRIMARY AND SUPPLEMENTARY MOTOR CORTICAL AREAS IN MACAQUE MONKEYS},
      journal = {EXPERIMENTAL BRAIN RESEARCH},
      year = {1994},
      volume = {102},
      number = {2},
      pages = {227-243}
    }
    
    Rowe, C.C., Ng, S., Ackermann, U., Gong, S.J., Pike, K., Savage, G., Cowie, T.F., Dickinson, K.L., Maruff, P., Darby, D., Smith, C., Woodward, M., Merory, J., Tochon-Danguy, H., O'Keefe, G., Klunk, W.E., Mathis, C.A., Price, J.C., Masters, C.L. & Villemagne, V.L. Imaging beta-amyloid burden in aging and dementia {2007} NEUROLOGY
    Vol. {68}({20}), pp. {1718-1725} 
    article  
    Abstract: Objective: To compare brain beta-amyloid (A beta) burden measured with [C-11] Pittsburgh Compound B (PIB) PET in normal aging, Alzheimer disease (AD), and other dementias. Methods: Thirty-three subjects with dementia (17 AD, 10 dementia with Lewy bodies [DLB], 6 frontotemporal dementia [FTD]), 9 subjects with mild cognitive impairment (MCI), and 27 age- matched healthy control subjects (HCs) were studied. A beta burden was quantified using PIB distribution volume ratio. Results: Cortical PIB binding was markedly elevated in every AD subject regardless of disease severity, generally lower and more variable in DLB, and absent in FTD, whereas subjects with MCI presented either an ``AD-like'' (60 or normal pattern. Binding was greatest in the precuneus/posterior cingulate, frontal cortex, and caudate nuclei, followed by lateral temporal and parietal cortex. Six HCs (22 showed cortical uptake despite normal neuropsychological scores. PIB binding did not correlate with dementia severity in AD or DLB but was higher in subjects with an APOE-epsilon 4 allele. In DLB, binding correlated inversely with the interval from onset of cognitive impairment to diagnosis. Conclusions: Pittsburgh Compound B PET findings match histopathologic reports of beta-amyloid (A beta) distribution in aging and dementia. Noninvasive longitudinal studies to better understand the role of amyloid deposition in the course of neurodegeneration and to determine if A beta deposition in nondemented subjects is preclinical AD are now feasible. Our findings also suggest that A beta may influence the development of dementia with Lewy bodies, and therefore strategies to reduce A beta may benefit this condition.
    BibTeX:
    @article{Rowe2007,
      author = {Rowe, C. C. and Ng, S. and Ackermann, U. and Gong, S. J. and Pike, K. and Savage, G. and Cowie, T. F. and Dickinson, K. L. and Maruff, P. and Darby, D. and Smith, C. and Woodward, M. and Merory, J. and Tochon-Danguy, H. and O'Keefe, G. and Klunk, W. E. and Mathis, C. A. and Price, J. C. and Masters, C. L. and Villemagne, V. L.},
      title = {Imaging beta-amyloid burden in aging and dementia},
      journal = {NEUROLOGY},
      year = {2007},
      volume = {68},
      number = {20},
      pages = {1718-1725}
    }
    
    Royall, D., Lauterbach, E., Cummings, J., Reeve, A., Rummans, T., Kaufer, D., LaFrance, W. & Coffey, C. Executive control function: A review of its promise and challenges for clinical research - A report from the Committee on Research of the American Neuropsychiatric Association {2002} JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES
    Vol. {14}({4}), pp. {377-405} 
    article  
    Abstract: This report reviews the state of the literature and opportunities for research related to ``executive control function'' (ECF). ECF has recently been separated from the specific cognitive domains (memory, language, and praxis) traditionally used to assess patients. ECF impairment has been associated with lesions to the frontal cortex and its basal ganglia-thalamic connections. No single putative ECF measure can yet serve as a ``gold standard.'' This and other obstacles to assessment of ECF are reviewed. ECF impairment and related frontal system lesions and metabolic disturbances have been detected in many psychiatric and medical disorders and are strongly associated with functional outcomes, disability, and specific problem behaviors. The prevalence and severity of ECF deficits in many disorders remain to be determined, and treatment has been attempted in only a few disorders. Much more research in these areas is necessary.
    BibTeX:
    @article{Royall2002,
      author = {Royall, DR and Lauterbach, EC and Cummings, JL and Reeve, A and Rummans, TA and Kaufer, DI and LaFrance, WC and Coffey, CE},
      title = {Executive control function: A review of its promise and challenges for clinical research - A report from the Committee on Research of the American Neuropsychiatric Association},
      journal = {JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES},
      year = {2002},
      volume = {14},
      number = {4},
      pages = {377-405}
    }
    
    Rubia, K., Overmeyer, S., Taylor, E., Brammer, M., Williams, S., Simmons, A. & Bullmore, E. Hypofrontality in attention deficit hyperactivity disorder during higher-order motor control: A study with functional MRI {1999} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {156}({6}), pp. {891-896} 
    article  
    Abstract: Objective: Functional magnetic resonance imaging (MRI) was used to investigate the hypothesis that attention deficit hyperactivity disorder (ADHD) is associated with a dysfunction of prefrontal brain regions during motor response inhibition and motor timing. Method: Generic brain activation of seven adolescent boys with ADHD was compared to that of nine comparison subjects equivalent in sex, age, and IQ while they were performing a stop task, requiring inhibition of a planned motor response, and a motor timing task, requiring timing of a motor response to a sensory cue. Results: The hyperactive adolescents showed lower power of response in the right mesial prefrontal cortex during both tasks and in the right inferior prefrontal cortex and left caudate during the stop task. Conclusions: ADHD is associated with subnormal activation of the prefrontal systems responsible for higher-order motor control. Functional MRI is a feasible technique for investigation of neural correlates of ADHD.
    BibTeX:
    @article{Rubia1999,
      author = {Rubia, K and Overmeyer, S and Taylor, E and Brammer, M and Williams, SCR and Simmons, A and Bullmore, ET},
      title = {Hypofrontality in attention deficit hyperactivity disorder during higher-order motor control: A study with functional MRI},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {1999},
      volume = {156},
      number = {6},
      pages = {891-896},
      note = {6th Annual Meeting of the International-Society-for-Magnetic-Resonance-in-Medicine, SYDNEY, AUSTRALIA, APR 18-24, 1998}
    }
    
    Rubia, K., Russell, T., Overmeyer, S., Brammer, M., Bullmore, E., Sharma, T., Simmons, A., Williams, S., Giampietro, V., Andrew, C. & Taylor, E. Mapping motor inhibition: Conjunctive brain activations across different versions of go/no-go and stop tasks {2001} NEUROIMAGE
    Vol. {13}({2}), pp. {250-261} 
    article DOI  
    Abstract: Conjunction analysis methods were used in functional magnetic resonance imaging to investigate brain regions commonly activated in subjects performing different versions of go/no-go and stop tasks, differing in probability of inhibitory signals and/or contrast conditions. Generic brain activation maps highlighted brain regions commonly activated in (a) two different go/no-go task versions, (b) three different stop task versions, and (c) all 5 inhibition task versions. Comparison between the generic activation maps of stop and go/no-go task versions revealed inhibitory mechanisms specific to go/no-go or stop task performance in 15 healthy, right-handed, male adults. In the go/no-go task a motor response had to be selectively executed or inhibited in either 50% or 30% of trials. In the stop task, the motor response to a go-stimulus had to be retracted on either 50 or 30% of trials, indicated by a stop signal, shortly (250 ms) following the go-stimulus. The shared ``inhibitory'' neurocognitive network by all inhibition tasks comprised mesial, medial, and inferior frontal and parietal cortices, Generic activation of the go/no-go task versions identified bilateral, but more predominantly left hemispheric mesial, medial, and inferior frontal and parietal cortices, Common activation to all stop task versions was in predominantly right hemispheric anterior cingulate, supplementary motor area, inferior prefrontal, and parietal cortices, On direct comparison between generic stop and go/no-go activation maps increased BOLD signal was observed in left hemispheric dorsolateral prefrontal, medial, and parietal cortices during the go/no-go task, presumably reflecting a left frontoparietal specialization for response selection. (C) 2001 Academic Press.
    BibTeX:
    @article{Rubia2001,
      author = {Rubia, K and Russell, T and Overmeyer, S and Brammer, MJ and Bullmore, ET and Sharma, T and Simmons, A and Williams, SCR and Giampietro, V and Andrew, CM and Taylor, E},
      title = {Mapping motor inhibition: Conjunctive brain activations across different versions of go/no-go and stop tasks},
      journal = {NEUROIMAGE},
      year = {2001},
      volume = {13},
      number = {2},
      pages = {250-261},
      doi = {{10.1006/nimg.2000.0685}}
    }
    
    Rubia, K., Smith, A., Brammer, M. & Taylor, E. Right inferior prefrontal cortex mediates response inhibition while mesial prefrontal cortex is responsible for error detection {2003} NEUROIMAGE
    Vol. {20}({1}), pp. {351-358} 
    article DOI  
    Abstract: Inhibitory control and error detection are among the highest evolved human self-monitoring functions. Attempts in functional neuroimaging to effectively isolate inhibitory motor control from other cognitive functions have met with limited success. Different brain regions in inferior, mesial, and dorsolateral prefrontal cortices and parietal and temporal lobes have been related to inhibitory control in go/no-go and stop tasks. The widespread activation reflects the fact that the designs used so far have comeasured additional noninhibitory cognitive functions such as selective attention, response competition, decision making, target detection, and inhibition failure. Here we use rapid, mixed trial, event-related functional magnetic resonance imaging to correlate brain activation with an extremely difficult situation of inhibitory control in a challenging stop task that controls for noninhibitory functions. The difficulty of the stop task, requiring withholding of a triggered motor response, was assured by an algorithm that adjusted the task individually so that each subject only succeeded on half of all stop trials, failing on the other half. This design allowed to elegantly separate brain activation related to successful motor response inhibition and to inhibition failure or error detection. Brain activation correlating with successful inhibitory control in 20 healthy volunteers could be isolated in right inferior prefrontal cortex. Failure to inhibit was associated with activation in mesial frontopolar and bilateral inferior parietal cortices, presumably reflecting an attention network for error detection. (C) 2003 Elsevier Inc. All rights reserved.
    BibTeX:
    @article{Rubia2003,
      author = {Rubia, K and Smith, AB and Brammer, MJ and Taylor, E},
      title = {Right inferior prefrontal cortex mediates response inhibition while mesial prefrontal cortex is responsible for error detection},
      journal = {NEUROIMAGE},
      year = {2003},
      volume = {20},
      number = {1},
      pages = {351-358},
      doi = {{10.1016/S1053-8119(03)00275-1}}
    }
    
    Ruby, P. & Decety, J. Effect of subjective perspective taking during simulation of action: a PET investigation of agency {2001} NATURE NEUROSCIENCE
    Vol. {4}({5}), pp. {546-550} 
    article  
    Abstract: Perspective taking is an essential component in the mechanisms that account for intersubjectivity and agency. Mental simulation of action can be used as a natural protocol to explore the cognitive and neural processing involved in agency. Here we took PET measurements while subjects simulated actions with either a first-person or a third-person perspective. Both conditions were associated with common activation in the SMA, the precentral gyrus, the precuneus and the MT/VS complex. When compared to the first-person perspective, the third-person perspective recruited right inferior parietal, precuneus, posterior cingulate and frontopolar cortex. The opposite contrast revealed activation in left inferior parietal and somatosensory cortex. We suggest that the right inferior parietal, precuneus and somatosensory cortex are specifically involved in distinguishing self-produced actions from those generated by others.
    BibTeX:
    @article{Ruby2001,
      author = {Ruby, P and Decety, J},
      title = {Effect of subjective perspective taking during simulation of action: a PET investigation of agency},
      journal = {NATURE NEUROSCIENCE},
      year = {2001},
      volume = {4},
      number = {5},
      pages = {546-550}
    }
    
    Rumsey, J., Horwitz, B., Donohue, B., Nace, K., Maisog, J. & Andreason, P. Phonological and orthographic components of word recognition - A PET-rCBF study {1997} BRAIN
    Vol. {120}({Part 5}), pp. {739-759} 
    article  
    Abstract: Pronunciation (of irregular/inconsistent words and of pseudowords) and lexical decision-making tasks were used with O-15 PET to examine the neural correlates of phonological and orthographic processing in 14 healthy right-handed men (aged 18-40 years). Relative to a visual-fixation control task, all four experimental tasks elicited a left-lateralized stream of activation involving the lingual and fusiform gyri, perirolandic cortex, thalamus and anterior cingulate. Both pronunciation tasks activated the left superior temporal gyrus, with significantly greater activation seen there during phonological (pseudoword) than during orthographic (real word) pronunciation. The left inferior frontal cortex was activated by both decision-making tasks; more intense and widespread activation was seen there during phonological, than during orthographic, decision making, with the activation during phonological decision-making extending into the left insula. Correlations of reference voxels in the left superior temporal gyrus and left inferior frontal region with the rest of the brain were highly similar for the phonological and orthographic versions of each task type. These results are consistent with connectionist models of reading, which hypothesize that both real words and pseudowords are processed within a common neural network.
    BibTeX:
    @article{Rumsey1997,
      author = {Rumsey, JM and Horwitz, B and Donohue, BC and Nace, K and Maisog, JM and Andreason, P},
      title = {Phonological and orthographic components of word recognition - A PET-rCBF study},
      journal = {BRAIN},
      year = {1997},
      volume = {120},
      number = {Part 5},
      pages = {739-759}
    }
    
    Rushworth, M., Walton, M., Kennerley, S. & Bannerman, D. Action sets and decisions in the medial frontal cortex {2004} TRENDS IN COGNITIVE SCIENCES
    Vol. {8}({9}), pp. {410-417} 
    article DOI  
    Abstract: Activations in human dorsomedial frontal and cingulate cortices are often present in neuroimaging studies of decision making and action selection. Interpretations have emphasized executive control, movement sequencing, error detection and conflict monitoring. Recently, however, experimental approaches, using lesions, inactivation, and cell recording, have suggested that these are just components of the areas' functions. Here we review these results and integrate them with those from neuroimaging. A medial superior frontal gyrus (SFG) region centred on the pre-supplementary motor area (pre-SMA) is involved in the selection of action sets whereas the anterior cingulate cortex (ACC) has a fundamental role in relating actions to their consequences, both positive reinforcement outcomes and errors, and in guiding decisions about which actions are worth making.
    BibTeX:
    @article{Rushworth2004,
      author = {Rushworth, MFS and Walton, ME and Kennerley, SW and Bannerman, DM},
      title = {Action sets and decisions in the medial frontal cortex},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      year = {2004},
      volume = {8},
      number = {9},
      pages = {410-417},
      doi = {{10.1016/j.tics.2004.07.009}}
    }
    
    Saarelainen, T., Hendolin, P., Lucas, G., Koponen, E., Sairanen, M., MacDonald, E., Agerman, K., Haapasalo, A., Nawa, H., Aloyz, R., Ernfors, P. & Castren, E. Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects {2003} JOURNAL OF NEUROSCIENCE
    Vol. {23}({1}), pp. {349-357} 
    article  
    Abstract: Recent studies have indicated that exogenously administered neurotrophins produce antidepressant-like behavioral effects. We have here investigated the role of endogenous brain-derived neurotrophic factor (BDNF) and its receptor trkB in the mechanism of action of antidepressant drugs. We found that trkB.T1-overexpressing transgenic mice, which show reduced trkB activation in brain, as well as heterozygous BDNF null (BDNF+/-) mice, were resistant to the effects of antidepressants in the forced swim test, indicating that normal trkB signaling is required for the behavioral effects typically produced by antidepressants. In contrast, neurotrophin-3(+/-) mice showed a normal behavioral response to antidepressants. Furthermore, acute as well as chronic antidepressant treatment induced autophosphorylation and activation of trkB in cerebral cortex, particularly in the prefrontal and anterior cingulate cortex and hippocampus. Tyrosines in the trkB autophosphorylation site were phosphorylated in response to antidepressants, but phosphorylation of the shc binding site was not observed. Nevertheless, phosphorylation of cAMP response element-binding protein was increased by antidepressants in the prefrontal cortex concomitantly with trkB phosphorylation and this response was reduced in trkB.T1-overexpressing mice. Our data suggest that antidepressants acutely increase trkB signaling in a BDNF-dependent manner in cerebral cortex and that this signaling is required for the behavioral effects typical of antidepressant drugs. Neurotrophin signaling increased by antidepressants may induce formation and stabilization of synaptic connectivity, which gradually leads to the clinical antidepressive effects and mood recovery.
    BibTeX:
    @article{Saarelainen2003,
      author = {Saarelainen, T and Hendolin, P and Lucas, G and Koponen, E and Sairanen, M and MacDonald, E and Agerman, K and Haapasalo, A and Nawa, H and Aloyz, R and Ernfors, P and Castren, E},
      title = {Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2003},
      volume = {23},
      number = {1},
      pages = {349-357}
    }
    
    Sabatini, U., Boulanouar, K., Fabre, N., Martin, F., Carel, C., Colonnese, C., Bozzao, L., Berry, I., Montastruc, J., Chollet, F. & Rascol, O. Cortical motor reorganization in akinetic patients with Parkinson's disease - A functional MRI study {2000} BRAIN
    Vol. {123}({Part 2}), pp. {394-403} 
    article  
    Abstract: Using functional MRI (fMRI), we have studied the changes induced by the performance of a complex sequential motor task in the cortical areas of six akinetic patients with Parkinson's disease and six normal subjects. Compared with the normal subjects, the patients with Parkinson's disease exhibited a relatively decreased fMRI signal in the rostral part of the supplementary motor area (SMA) and in the right dorsolateral prefrontal cortex, as previously shown in PET studies. Concomitantly, the same patients exhibited a significant bilateral relative increase in fMRI signal in the primary sensorimotor cortex, lateral premotor cortex, inferior parietal cortex, caudal part of the SMA and anterior cingulate cortex. These fMRI data confirm that the frontal hypoactivation observed in patients with Parkinson's dis