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    ABELES, M., BERGMAN, H., MARGALIT, E. & VAADIA, E. SPATIOTEMPORAL FIRING PATTERNS IN THE FRONTAL-CORTEX OF BEHAVING MONKEYS {1993} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {70}({4}), pp. {1629-1638} 
    article  
    Abstract: 1. Activity of up to 10 single units was recorded in parallel from frontal areas of behaving monkeys. 2. Spatiotemporal firing patterns were revealed by a method that detects all excessively repeating patterns regardless of their complexity or single-unit composition. 3. Excess of repeating patterns was found in 30-60% of the cases examined when timing jitter of 1-3 ms was allowed. 4. An independent test refuted the hypothesis that these patterns represented chance events. 5. In a given behavioral condition there were usually many different patterns, each repeating several times, and not one (or a few) pattern repeating many times. 6. In 13 out of 20 cases, when a single unit elevated its firing rate in association with an external event beyond 40/s, most of the spikes within that period were associated with excessively repeating spatiotemporal patterns. 7. Of 157 types of patterns whose excess was most marked, 107 were composed of spikes from one single unit, 45 of the patterns contained spikes from two single units, and only one was composed of spikes from three different single units. 8. These properties suggest that the patterns were generated by reverberations in a synfire mode within self-exciting cell assemblies.
    BibTeX:
    @article{ABELES1993,
      author = {ABELES, M and BERGMAN, H and MARGALIT, E and VAADIA, E},
      title = {SPATIOTEMPORAL FIRING PATTERNS IN THE FRONTAL-CORTEX OF BEHAVING MONKEYS},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1993},
      volume = {70},
      number = {4},
      pages = {1629-1638}
    }
    
    Abeliovich, A., Schmitz, Y., Farinas, I., Choi-Lundberg, D., Ho, W., Castillo, P., Shinsky, N., Verdugo, J., Armanini, M., Ryan, A., Hynes, M., Phillips, H., Sulzer, D. & Rosenthal, A. Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system {2000} NEURON
    Vol. {25}({1}), pp. {239-252} 
    article  
    Abstract: alpha-Synuclein (alpha-Syn) is a 14 kDa protein of unknown function that has been implicated in the pathophysiology of Parkinson's disease (PD). Here, we show that alpha-Syn(-/-) mice are viable and fertile, exhibit intact brain architecture, and possess a normal complement of dopaminergic cell bodies, fibers, and synapses. Nigrostriatal terminals of alpha-Syn(-/-) mice display a standard pattern of dopamine (DA) discharge and reuptake in response to simple electrical stimulation. However, they exhibit an increased release with paired stimuli that can be mimicked by elevated Ca2+. Concurrent with the altered DA release, alpha-Syn(-/-) mice display a reduction in striatal DA and an attenuation of DA-dependent locomotor response to amphetamine. These findings support the hypothesis that alpha-Syn is an essential presynaptic, activity-dependent negative regulator of DA neurotransmission.
    BibTeX:
    @article{Abeliovich2000,
      author = {Abeliovich, A and Schmitz, Y and Farinas, I and Choi-Lundberg, D and Ho, WH and Castillo, PE and Shinsky, N and Verdugo, JMG and Armanini, M and Ryan, A and Hynes, M and Phillips, H and Sulzer, D and Rosenthal, A},
      title = {Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system},
      journal = {NEURON},
      year = {2000},
      volume = {25},
      number = {1},
      pages = {239-252}
    }
    
    Adolphs, R. Cognitive neuroscience of human social behaviour {2003} NATURE REVIEWS NEUROSCIENCE
    Vol. {4}({3}), pp. {165-178} 
    article DOI  
    Abstract: We are an intensely social species - it has been argued that our social nature defines what makes us human, what makes us conscious or what gave us our large brains. As a new field, the social brain sciences are probing the neural underpinnings of social behaviour and have produced a banquet of data that are both tantalizing and deeply puzzling. We are finding new links between emotion and reason, between action and perception, and between representations of other people and ourselves. No less important are the links that are also being established across disciplines to understand social behaviour, as neuroscientists, social psychologists, anthropologists, ethologists and philosophers forge new collaborations.
    BibTeX:
    @article{Adolphs2003,
      author = {Adolphs, R},
      title = {Cognitive neuroscience of human social behaviour},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2003},
      volume = {4},
      number = {3},
      pages = {165-178},
      doi = {{10.1038/nrn1056}}
    }
    
    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}
    }
    
    AKBARIAN, S., BUNNEY, W., POTKIN, S., WIGAL, S., HAGMAN, J., SANDMAN, C. & JONES, E. ALTERED DISTRIBUTION OF NICOTINAMIDE-ADENINE DINUCLEOTIDE PHOSPHATE DIAPHORASE CELLS IN FRONTAL-LOBE OF SCHIZOPHRENICS IMPLIES DISTURBANCES OF CORTICAL DEVELOPMENT {1993} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {50}({3}), pp. {169-177} 
    article  
    Abstract: Epidemiological and anatomical studies support the theory that disturbances of brain development may play a contributory role in the etiology of schizophrenia. Anatomical findings suggest that the normal pattern of neuronal migration during development of the cerebral cortex may be affected in the brains of schizophrenics, with the implication that cortical connectivity and associative function will be disrupted. In the present investigation in matched schizophrenic and control brains, we examined a particular population of neurons found in the prefrontal cortex and underlying white matter and characterized by histochemical staining for the enzyme nicotinamide-adenine dinucleotide phosphate-diaphorase. In normal brains, these neurons are found in highest numbers in the white matter immediately deep to layer VI of the cortex where they remain from the subplate, an early formed, but transitory structure that plays a key role in cortical development and connection formation. The dorsolateral prefrontal area of schizophrenics showed a significant decline in nicotinamide-adenine dinucleotide phosphate-diaphorase neurons in the superficial white matter and in the overlying cortex but a significant increase in these neurons in white matter deeper than 3 mm from the cortex. These findings are consistent with a disturbance of the subplate during development in which the normal pattern of programmed cell death is compromised and accompanied by a defect in the normal orderly migration of neurons toward the cortical plate. These are likely to have serious consequences for the establishment of a normal pattern of cortical connections leading to a potential breakdown of frontal lobe function in schizophrenics.
    BibTeX:
    @article{AKBARIAN1993,
      author = {AKBARIAN, S and BUNNEY, WE and POTKIN, SG and WIGAL, SB and HAGMAN, JO and SANDMAN, CA and JONES, EG},
      title = {ALTERED DISTRIBUTION OF NICOTINAMIDE-ADENINE DINUCLEOTIDE PHOSPHATE DIAPHORASE CELLS IN FRONTAL-LOBE OF SCHIZOPHRENICS IMPLIES DISTURBANCES OF CORTICAL DEVELOPMENT},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1993},
      volume = {50},
      number = {3},
      pages = {169-177}
    }
    
    AKBARIAN, S., KIM, J., POTKIN, S., HAGMAN, J., TAFAZZOLI, A., BUNNEY, W. & JONES, E. GENE-EXPRESSION FOR GLUTAMIC-ACID DECARBOXYLASE IS REDUCED WITHOUT LOSS OF NEURONS IN PREFRONTAL CORTEX OF SCHIZOPHRENICS {1995} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {52}({4}), pp. {258-266} 
    article  
    Abstract: Background: Up-regulation of gamma-aminobutyric acid(A) (GABA(A)) receptors and decreased GABA uptake in the cerebral cortex of schizophrenics suggest altered GABAergic transmission, which could be caused by primary disturbance of GABA synapses or by decreased production of the transmitter. Decreased production could be due to a shutdown in GABA production or to loss of GABA neurons caused by cell death or their failure to migrate to the cortex during brain development. Methods: To discriminate between these possibilities, we quantified levels of messenger RNA (mRNA) for the 67-kd isoform of glutamic acid decarboxylase (GAD), the key enzyme in GABA synthesis, and the number and laminar distribution of GAD mRNA-expressing neurons in the dorsolateral prefrontal cortex (DLPFC) of schizophrenics and matched controls, using in situ hybridization-histochemistry, densitometry, and cell-counting methods. These data were compared with the total number of neurons, the number of small, round or ovoid neurons 8 to 15 mu m in diameter, and overall frontal lobe volume. As a control, mRNA levels for type II calcium-calmodulin-dependent protein kinase (CamIIK) were quantified. Results: Schizophrenics showed a pronounced decrease in GAD mRNA levels in neurons of layer I (40 and layer II (48 and an overall 30% decrease in layers III to VI. There were also strong overall reductions in GAD mRNA levels. The CamIIK mRNA levels showed no significant differences between samples. No differences were found in the total number of neurons nor in small, round or ovoid neurons, which should include a majority of the GABA cells. Prefrontal gray and white matter volume did not differ significantly between controls and schizophrenics. Conclusions: The prefrontal cortex of schizophrenics shows reduced expression for GAD in the absence of significant cell loss. This may be brought about by an activity-dependent. down-regulation associated with the functional hypoactivity of the DLPFC. The lack of significant alterations in cell numbers in the DLPFC and frontal lobe volume in schizophrenics also implies that overall cortical neuronal migration had not been compromised in development. Previous reports of altered neuronal distribution in the subcortical white matter of schizophrenic brains in comparison with that of controls may indicate disturbances of migration or programmed cell death in the cortical subplate, leading to altered connection formation in the overlying cortex of schizophrenics and activity-dependent down-regulation of neurotransmitter-related gene expression.
    BibTeX:
    @article{AKBARIAN1995,
      author = {AKBARIAN, S and KIM, JJ and POTKIN, SG and HAGMAN, JO and TAFAZZOLI, A and BUNNEY, WE and JONES, EG},
      title = {GENE-EXPRESSION FOR GLUTAMIC-ACID DECARBOXYLASE IS REDUCED WITHOUT LOSS OF NEURONS IN PREFRONTAL CORTEX OF SCHIZOPHRENICS},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1995},
      volume = {52},
      number = {4},
      pages = {258-266}
    }
    
    AKBARIAN, S., VINUELA, A., KIM, J., POTKIN, S., BUNNEY, W. & JONES, E. DISTORTED DISTRIBUTION OF NICOTINAMIDE-ADENINE DINUCLEOTIDE PHOSPHATE DIAPHORASE NEURONS IN TEMPORAL-LOBE OF SCHIZOPHRENICS IMPLIES ANOMALOUS CORTICAL DEVELOPMENT {1993} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {50}({3}), pp. {178-187} 
    article  
    Abstract: The distribution of neurons expressing the enzyme nicotinamide-adenine dinucleotide phosphate-diaphorase (NADPH-d) in the lateral and medial temporal lobes of schizophrenic and matched control brains was investigated in a systematic blind analysis. Schizophrenics had significantly lower numbers of NADPH-d neurons in the hippocampal formation and in the neocortex of the lateral temporal lobe but significantly greater numbers of NADPH-d neurons in the white matter of the lateral temporal lobe and a tendency toward greater numbers in parts of the parahippocampal white matter. The distorted distribution of NADPH-d neurons in the lateral temporal lobe, which may be explained by developmental disturbances, such as impaired neuronal migration or an alteration in the death cycle of transitory subcortical neurons, is similar to that found in the prefrontal cortex of schizophrenics. Alterations of cortical ontogenesis, as reflected in the distribution of NADPH-d neurons, appear to be widespread among neocortical association fields in schizophrenics and may provide a clue to the cause of the disease.
    BibTeX:
    @article{AKBARIAN1993a,
      author = {AKBARIAN, S and VINUELA, A and KIM, JJ and POTKIN, SG and BUNNEY, WE and JONES, EG},
      title = {DISTORTED DISTRIBUTION OF NICOTINAMIDE-ADENINE DINUCLEOTIDE PHOSPHATE DIAPHORASE NEURONS IN TEMPORAL-LOBE OF SCHIZOPHRENICS IMPLIES ANOMALOUS CORTICAL DEVELOPMENT},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1993},
      volume = {50},
      number = {3},
      pages = {178-187}
    }
    
    ALBIN, R., MAKOWIEC, R., HOLLINGSWORTH, Z., DURE, L., PENNEY, J. & YOUNG, A. EXCITATORY AMINO-ACID BINDING-SITES IN THE BASAL GANGLIA OF THE RAT - A QUANTITATIVE AUTORADIOGRAPHIC STUDY {1992} NEUROSCIENCE
    Vol. {46}({1}), pp. {35-48} 
    article  
    Abstract: Quantitative receptor autoradiography was used to determine the distribution of excitatory amino acid binding sites in the basal ganglia of rat brain. alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid, N-methyl-D-aspartate, kainate, quisqualate-sensitive etabotropic and non-N-methyl-D-aspartate, non-kainate, non-quisqualate glutamate binding sites had their highest density in striatum, nucleus accumbens, and olfactory tubercle. Kainate binding was higher in the lateral striatum but there was no medial-lateral striatal gradient for other binding sites. N-Methyl-D-aspartate and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid binding sites were most dense in the nucleus accumbens and olfactory tubercle. There was no dorsal-ventral gradient within the striatal complex for the other binding sites. Other regions of the basal ganglia had lower densities of ligand binding. To compare binding site density within non-striatal regions, binding for each ligand was normalized to the striatal binding density. When compared to the striatal complex, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and metabotropic binding sites had higher relative density in the globus pallidus, ventral pallidum, and subthalamic nucleus than other binding sites. Metabotropic binding also had a high relative density in the substantia nigra. Non-N-methyl-D-aspartate, non-kainate, non-quisqualate glutamate binding sites had a high relative density in globus pallidus, ventral pallidum, and substantia nigra. N-Methyl-D-aspartate binding sites had a low relative density in pallidum, subthalamic nucleus, substantia nigra and ventral tegmental area. Our data indicate heterogeneous distribution of excitatory amino acid binding sites within rat basal ganglia and suggest that the character of excitatory amino acid-mediated neurotransmission within the basal ganglia is also heterogeneous.
    BibTeX:
    @article{ALBIN1992,
      author = {ALBIN, RL and MAKOWIEC, RL and HOLLINGSWORTH, ZR and DURE, LS and PENNEY, JB and YOUNG, AB},
      title = {EXCITATORY AMINO-ACID BINDING-SITES IN THE BASAL GANGLIA OF THE RAT - A QUANTITATIVE AUTORADIOGRAPHIC STUDY},
      journal = {NEUROSCIENCE},
      year = {1992},
      volume = {46},
      number = {1},
      pages = {35-48}
    }
    
    Allison, T., Puce, A., Spencer, D. & McCarthy, G. Electrophysiological studies of human face perception. I: Potentials generated in occipitotemporal cortex by face and non-face stimuli {1999} CEREBRAL CORTEX
    Vol. {9}({5}), pp. {415-430} 
    article  
    Abstract: This and the following two papers describe event-related potentials (ERPs) evoked by visual stimuli in 98 patients in whom electrodes were placed directly upon the cortical surface to monitor medically intractable seizures. Patients viewed pictures of faces, scrambled faces, letter-strings, number-strings, and animate and inanimate objects. This paper describes ERPs generated in striate and peri striate cortex, evoked by faces, and evoked by sinusoidal gratings, objects and letter-strings. Short-latency ERPs generated in striate and peristriate cortex were sensitive to elementary stimulus features such as luminance. Three types of face-specific ERPs were found: (i) a surface negative potential with a peak latency of similar to 200 ms (N200) recorded from ventral occipitotemporal cortex, (ii) a lateral surface N200 recorded primarily from the middle temporal gyrus, and (iii) a late positive potential (P350) recorded from posterior ventral occipitotemporal, posterior lateral temporal and anterior ventral temporal cortex. Face specific N200s were preceded by P150 and followed by P290 and N700 ERPs. N200 reflects initial face-specific processing, while P290, N700 and P350 reflect later face processing at or near N200 sites and in anterior ventral temporal cortex. Face specific N200 amplitude was not significantly different in males and females, in the normal and abnormal hemisphere, or in the right and left hemisphere. However, cortical patches generating ventral face-specific N200s were larger in the right hemisphere. Other cortical patches in the same region of extrastriate cortex generated grating sensitive N180s and object-specific or letter-string specific N200s, suggesting that the human ventral object recognition system is segregated into functionally discrete regions.
    BibTeX:
    @article{Allison1999,
      author = {Allison, T and Puce, A and Spencer, DD and McCarthy, G},
      title = {Electrophysiological studies of human face perception. I: Potentials generated in occipitotemporal cortex by face and non-face stimuli},
      journal = {CEREBRAL CORTEX},
      year = {1999},
      volume = {9},
      number = {5},
      pages = {415-430}
    }
    
    Amit, D. & Brunel, N. Model of global spontaneous activity and local structured activity during delay periods in the cerebral cortex {1997} CEREBRAL CORTEX
    Vol. {7}({3}), pp. {237-252} 
    article  
    Abstract: We investigate self-sustaining stable states (attractors) in networks of integrate-and-fire neurons. First, we study the stability of spontaneous activity in an unstructured network. It is shown that the stochastic background activity, of 1-5 spikes/s, is unstable if all neurons are excitatory. On the other hand, spontaneous activity becomes self-stabilizing in presence of local inhibition, given reasonable values of the parameters of the network. Second, in a network sustaining physiological spontaneous rates, we study the effect of learning in a local module, expressed in synaptic modifications in specific populations of synapses. We find that if the average synaptic potentiation (LTP) is too low, no stimulus specific activity manifests itself in the delay period. Instead, following the presentation and removal of any stimulus there is, in the local module, a delay activity in which all neurons selective (responding visually) to any of the stimuli presented for learning have rates which gradually increase with the amplitude of synaptic potentiation; When the average LTP increases beyond a critical value, specific local attractors (stable states) appear abruptly against the background of the global uniform spontaneous attractor. In this case the local module has two available types of collective delay activity: if the stimulus is unfamiliar, the activity is spontaneous; if it is similar to a learned stimulus, delay activity is selective. These new attractors reflect the synaptic structure developed during learning. In each of them a small population of neurons have elevated rates, which depend on the strength of LTP. The remaining neurons of the module have their activity at spontaneous rates. The predictions made in this paper could be checked by single unit recordings in delayed reponse experiments.
    BibTeX:
    @article{Amit1997,
      author = {Amit, DJ and Brunel, N},
      title = {Model of global spontaneous activity and local structured activity during delay periods in the cerebral cortex},
      journal = {CEREBRAL CORTEX},
      year = {1997},
      volume = {7},
      number = {3},
      pages = {237-252}
    }
    
    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}}
    }
    
    Andersen, R. & Buneo, C. Intentional maps in posterior parietal cortex {2002} ANNUAL REVIEW OF NEUROSCIENCE
    Vol. {25}, pp. {189-220} 
    article DOI  
    Abstract: The posterior parietal cortex (PPC), historically believed to be a sensory structure, is now viewed as an area important for sensory-motor integration. Among its functions is the forming of intentions, that is, high-level cognitive plans for movement. There is a map of intentions within the PPC, with different subregions dedicated to the planning of eye movements, reaching movements, and grasping movements. These areas appear to be specialized for the multisensory integration and coordinate transformations required to convert sensory input to motor output. In several subregions of the PPC, these operations are facilitated by the use of a common distributed space representation that is independent of both sensory input and motor output. Attention and learning effects are also evident in the PPC. However, these effects may be general to cortex and operate in the PPC in the context of sensory-motor transformations.
    BibTeX:
    @article{Andersen2002,
      author = {Andersen, RA and Buneo, CA},
      title = {Intentional maps in posterior parietal cortex},
      journal = {ANNUAL REVIEW OF NEUROSCIENCE},
      year = {2002},
      volume = {25},
      pages = {189-220},
      doi = {{10.1146/annurev.neuro.25.112701.142922}}
    }
    
    Anderson, A., Christoff, K., Stappen, I., Panitz, D., Ghahremani, D., Glover, G., Gabrieli, J. & Sobel, N. Dissociated neural representations of intensity and valence in human olfaction {2003} NATURE NEUROSCIENCE
    Vol. {6}({2}), pp. {196-202} 
    article DOI  
    Abstract: Affective experience has been described in terms of two primary dimensions: intensity and valence. In the human brain, it is intrinsically difficult to dissociate the neural coding of these affective dimensions for visual and auditory stimuli, but such dissociation is more readily achieved in olfaction, where intensity and valence can be manipulated independently. Using event-related functional magnetic resonance imaging (fMRI), we found amygdala activation to be associated with intensity, and not valence, of odors. Activity in regions of orbitofrontal cortex, in contrast, were associated with valence independent of intensity. These findings show that distinct olfactory regions subserve the analysis of the degree and quality of olfactory stimulation, suggesting that the affective representations of intensity and valence draw upon dissociable neural substrates.
    BibTeX:
    @article{Anderson2003,
      author = {Anderson, AK and Christoff, K and Stappen, I and Panitz, D and Ghahremani, DG and Glover, G and Gabrieli, JDE and Sobel, N},
      title = {Dissociated neural representations of intensity and valence in human olfaction},
      journal = {NATURE NEUROSCIENCE},
      year = {2003},
      volume = {6},
      number = {2},
      pages = {196-202},
      doi = {{10.1038/nn1001}}
    }
    
    Anderson, S., Bechara, A., Damasio, H., Tranel, D. & Damasio, A. Impairment of social and moral behavior related to early damage in human prefrontal cortex {1999} NATURE NEUROSCIENCE
    Vol. {2}({11}), pp. {1032-1037} 
    article  
    Abstract: The long-term consequences of early prefrontal cortex lesions occurring before 16 months were investigated in two adults. As is the case when such damage occurs in adulthood, the two early-onset patients had severely impaired social behavior despite normal basic cognitive abilities, and showed insensitivity to future consequences of decisions, defective autonomic responses to punishment contingencies and failure to respond to behavioral interventions. Unlike adult-onset patients, however, the two patients had defective social and moral reasoning, suggesting that the acquisition of complex social conventions and moral rules had been impaired. Thus early-onset prefrontal damage resulted in a syndrome resembling psychopathy.
    BibTeX:
    @article{Anderson1999,
      author = {Anderson, SW and Bechara, A and Damasio, H and Tranel, D and Damasio, AR},
      title = {Impairment of social and moral behavior related to early damage in human prefrontal cortex},
      journal = {NATURE NEUROSCIENCE},
      year = {1999},
      volume = {2},
      number = {11},
      pages = {1032-1037}
    }
    
    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., 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., Paradiso, S. & O'Leary, D. ``Cognitive dysmetria'' as an integrative theory of schizophrenia: A dysfunction in cortical subcortical-cerebellar circuitry? {1998} SCHIZOPHRENIA BULLETIN
    Vol. {24}({2}), pp. {203-218} 
    article  
    Abstract: Earlier efforts to localize the symptoms of schizophrenia in a single brain region have been replaced by models that postulate a disruption in parallel distributed or dynamic circuits. Based on empirical data derived from both magnetic resonance and positron emission tomography, we have developed a model that implicates connectivity among nodes located in prefrontal regions, the thalamic nuclei, and the cerebellum, A disruption in this circuitry produces ``cognitive dysmetria,'' difficulty in prioritizing, processing, coordinating, and responding to information. This ``poor mental coordination'' is a fundamental cognitive deficit in schizophrenia and can account for its broad diversity of symptoms.
    BibTeX:
    @article{Andreasen1998,
      author = {Andreasen, NC and Paradiso, S and O'Leary, DS},
      title = {``Cognitive dysmetria'' as an integrative theory of schizophrenia: A dysfunction in cortical subcortical-cerebellar circuitry?},
      journal = {SCHIZOPHRENIA BULLETIN},
      year = {1998},
      volume = {24},
      number = {2},
      pages = {203-218}
    }
    
    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}}
    }
    
    ARANEDA, R. & ANDRADE, R. 5-HYDROXYTRYPTAMINE2 AND 5-HYDROXYTRYPTAMINE1A RECEPTORS MEDIATE OPPOSING RESPONSES ON MEMBRANE EXCITABILITY IN RAT-ASSOCIATION CORTEX {1991} NEUROSCIENCE
    Vol. {40}({2}), pp. {399-412} 
    article  
    Abstract: The effects of serotonin on pyramidal cells of layer V of the medial prefrontal cortex were examined using intracellular recording techniques in rat brain slices in vitro. Bath administration of serotonin (0.3-100-mu-M) produced two distinct responses which could be differentiated physiologically and pharmacologically. The first of these responses was a membrane hyperpolarization. This effect of serotonin was associated with a decrease in input resistance and was independent of the transmembrane chloride gradient, suggesting that it was mediated by an increase in potassium conductance. The ability of serotonin to induce a hyperpolarization was mimicked by (+/-)-8-hydroxy-dipropylaminotetralin hydrobromide and was blocked by BMY 7378 and spiperone but not by ketanserin, indicating that it was mediated by the activation of receptors of the 5-hydroxytryptamine1A subtype. The second response to serotonin involved a membrane depolarization, the replacement of the afterhyperpolarization that follows a burst of spikes in these cells by a slow depolarizing afterpotential, and a decrease in spike frequency accommodation. These effects were mimicked by 4-bromo-2,5-dimethoxyphenyl-isopropylamine and antagonized by ketanserin and by low concentrations of spiperone, indicating that they were mediated by the activation of 5-hydroxytryptamine2 receptors. Interestingly, qualitatively identical responses could be elicited in these cells by activation of muscarinic and alpha-1-adrenergic receptors suggesting that 5-hydroxytryptamine2, muscarinic and alpha-1-adrenergic receptors converge onto a common set of membrane mechanisms to increase cellular excitability. Although 5-hydroxytryptamine1A and 5-hydroxytryptamine2 receptors mediated opposing effects on membrane excitability, most pyramidal neurons appeared to express both receptor subtypes on their membrane surface. The coactivation of both receptor subtypes resulted in a selective enhancement of responsiveness to strong excitatory stimuli with little effect on weaker stimuli. The paradoxical presence of two serotonin receptors mediating opposite effects on membrane excitability in the same cell provides a flexible mechanism by which serotonin might regulate how pyramidal neurons encode incoming excitatory stimuli onto firing activity.
    BibTeX:
    @article{ARANEDA1991,
      author = {ARANEDA, R and ANDRADE, R},
      title = {5-HYDROXYTRYPTAMINE2 AND 5-HYDROXYTRYPTAMINE1A RECEPTORS MEDIATE OPPOSING RESPONSES ON MEMBRANE EXCITABILITY IN RAT-ASSOCIATION CORTEX},
      journal = {NEUROSCIENCE},
      year = {1991},
      volume = {40},
      number = {2},
      pages = {399-412}
    }
    
    ARNOLD, S., HYMAN, B., VANHOESEN, G. & DAMASIO, A. SOME CYTOARCHITECTURAL ABNORMALITIES OF THE ENTORHINAL CORTEX IN SCHIZOPHRENIA {1991} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {48}({7}), pp. {625-632} 
    article  
    Abstract: The cytoarchitecture of the entorhinal cortex was examined in the brains of six patients with a diagnosis of schizophrenia and in 16 controls. All six brains of schizophrenic patients showed abnormalities of the rostral and intermediate portions of the entorhinal cortex. The abnormalities included aberrant invaginations of the surface, disruption of cortical layers, heterotopic displacement of neurons, and paucity of neurons in superficial layers. These changes suggest disturbed development. Because the entorhinal cortex is pivotal for neural systems that mediate corticohippocampal interactions, early disruption of its structure could lead to important neuropsychological changes during development and in adult life and could contribute to the symptomatology of schizophrenia.
    BibTeX:
    @article{ARNOLD1991,
      author = {ARNOLD, SE and HYMAN, BT and VANHOESEN, GW and DAMASIO, AR},
      title = {SOME CYTOARCHITECTURAL ABNORMALITIES OF THE ENTORHINAL CORTEX IN SCHIZOPHRENIA},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1991},
      volume = {48},
      number = {7},
      pages = {625-632}
    }
    
    ARNSTEN, A. & GOLDMANRAKIC, P. ALPHA-2-ADRENERGIC MECHANISMS IN PREFRONTAL CORTEX ASSOCIATED WITH COGNITIVE DECLINE IN AGED NONHUMAN-PRIMATES {1985} SCIENCE
    Vol. {230}({4731}), pp. {1273-1276} 
    article  
    BibTeX:
    @article{ARNSTEN1985,
      author = {ARNSTEN, AFT and GOLDMANRAKIC, PS},
      title = {ALPHA-2-ADRENERGIC MECHANISMS IN PREFRONTAL CORTEX ASSOCIATED WITH COGNITIVE DECLINE IN AGED NONHUMAN-PRIMATES},
      journal = {SCIENCE},
      year = {1985},
      volume = {230},
      number = {4731},
      pages = {1273-1276}
    }
    
    Arnt, J. & Skarsfeldt, T. Do novel antipsychotics have similar pharmacological characteristics? A review of the evidence {1998} NEUROPSYCHOPHARMACOLOGY
    Vol. {18}({2}), pp. {63-101} 
    article  
    Abstract: The pharmacological properties of the novel antipsychotic drugs (APDs) risperidone, sertindole, olanzapine, quetiapine, ziprasidone, remoxipride, and amperozide are reviewed and compared with haloperidol and clozapine. Focus is made on their receptor profiles, their effects in animal models used for evaluation of antipsychotic activity, and extrapyramidal side effects (EPS). In addition, the contrasting actions of these compounds on animal models of cognition, anxiety, and depression are briefly reviewed. The available evidence indicates that novel APDs and clozapine can be differentiated from haloperidol, particularly in models of EPS and cognitive side effects. However, among the group of novel APDs there are many individual differences in models reflecting limbic versus striatal inhibition of dopamine function: clozapine and sertindole show the largest limbic selectivity, following by quetiapine, ziprasidone, olanzapine and remoxipride, whereas risperidone in many respects hits a profile that resembles haloperidol. To date, the results of clinical studies have confirmed the predictions of lower incidence or absence of EPS after administration of novel APDs in doses which demonstrate antipsychotic efficacy. (C) 1998 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.
    BibTeX:
    @article{Arnt1998,
      author = {Arnt, J and Skarsfeldt, T},
      title = {Do novel antipsychotics have similar pharmacological characteristics? A review of the evidence},
      journal = {NEUROPSYCHOPHARMACOLOGY},
      year = {1998},
      volume = {18},
      number = {2},
      pages = {63-101}
    }
    
    Aron, A., Robbins, T. & Poldrack, R. Inhibition and the right inferior frontal cortex {2004} TRENDS IN COGNITIVE SCIENCES
    Vol. {8}({4}), pp. {170-177} 
    article DOI  
    Abstract: It is controversial whether different cognitive functions can be mapped to discrete regions of the prefrontal cortex (PFC). The localisationist tradition has associated one cognitive function - inhibition - by turns with dorsolateral prefrontal cortex (DLPFC), inferior frontal cortex (IFC), or orbital frontal cortex (OFC). Inhibition is postulated to be a mechanism by which PFC exerts its effects on subcortical and posterior-cortical regions to implement executive control. We review evidence concerning inhibition of responses and task-sets. Whereas neuroimaging implicates diverse PFC foci, advances in human lesion-mapping support the functional localization of such inhibition to right IFC alone. Future research should investigate the generality of this proposed inhibitory function to other task domains, and its interaction within a wider network.
    BibTeX:
    @article{Aron2004,
      author = {Aron, AR and Robbins, TW and Poldrack, RA},
      title = {Inhibition and the right inferior frontal cortex},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      year = {2004},
      volume = {8},
      number = {4},
      pages = {170-177},
      doi = {{10.1016/j.tics.2004.02.010}}
    }
    
    ARTOLA, A. & SINGER, W. LONG-TERM DEPRESSION OF EXCITATORY SYNAPTIC TRANSMISSION AND ITS RELATIONSHIP TO LONG-TERM POTENTIATION {1993} TRENDS IN NEUROSCIENCES
    Vol. {16}({11}), pp. {480-487} 
    article  
    Abstract: In many brain areas, including the cerebellar cortex, neocortex, hippocampus, striatum and nucleus accumbens, brief activation of an excitatory pathway can produce long-term depression (LTD) of synaptic transmission. In most preparations, induction of LTD has been shown to require a minimum level of postsynaptic depolarization and a rise in the intracellular Ca2+ concentration [Ca2+]i in the postsynaptic neurone. Thus, induction conditions resemble those described for the initiation of associative long-term potentiation (LTP). However, data from structures susceptible to both LTD and LTP suggest that a stronger depolarization and a greater increase in [Ca2+]i are required to induce LTP than to initiate LTD. The source of Ca2+ appears to be less critical for the differential induction of LTP and LTD than the amplitude of the Ca2+ surge, since the activation of voltage- and ligand-gated Ca2+ conductances as well as the release from intracellular stores have all been shown to contribute to both LTD and LTP induction. LTD is induceable even at inactive synapses if [Ca2+]i is raised to the appropriate level by antidromic or heterosynaptic activation, or by raising the extracellular Ca2+ concentration [Ca2+]o. These conditions suggest a rule (called here the ABS rule) for activity-dependent synaptic modifications that differs from the classical Hebb rule and that can account for both homosynaptic LTD and LTP as well as for heterosynaptic competition and associativity.
    BibTeX:
    @article{ARTOLA1993,
      author = {ARTOLA, A and SINGER, W},
      title = {LONG-TERM DEPRESSION OF EXCITATORY SYNAPTIC TRANSMISSION AND ITS RELATIONSHIP TO LONG-TERM POTENTIATION},
      journal = {TRENDS IN NEUROSCIENCES},
      year = {1993},
      volume = {16},
      number = {11},
      pages = {480-487}
    }
    
    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}
    }
    
    ASTONJONES, G., CHIANG, C. & ALEXINSKY, T. DISCHARGE OF NORADRENERGIC LOCUS-CERULEUS NEURONS IN BEHAVING RATS AND MONKEYS SUGGESTS A ROLE IN VIGILANCE {1991} PROGRESS IN BRAIN RESEARCH
    Vol. {88}, pp. {501-520} 
    article  
    Abstract: Recordings from noradrenergic locus coeruleus (LC) neurons in behaving rats and monkeys revealed that these cells decrease tonic discharge during sleep and also during certain high arousal behaviors (grooming and consumption) when attention (vigilance) was low. Sensory stimuli of many modalities phasically activated LC neurons. Response magnitudes varied with vigilance, similar to results for tonic activity. The most effective and reliable stimuli for eliciting LC responses were those that disrupted behavior and evoked orienting responses. Similar results were observed in behaving monkeys except that more intense stimuli were required for LC responses. Our more recent studies have examined LC activity in monkeys performing an ``oddball'' visual discrimination task. Monkeys were trained to release a lever after a target cue light that occurred randomly on 10% of trials; animals had to withhold responding during non-target cues. LC neurons selectively responded to the target cues during this task. During reversal training, LC neurons lost their response to the previous target cue and began responding to the new target light in parallel with behavioral reversal. Cortical event-related potentials were elicited in this task selectively by the same stimuli that evoked LC responses. Injections of lidocaine, GABA, or a synaptic decoupling solution into the nucleus paragigantocellularis in the rostral ventrolateral medulla, the major afferent to LC, eliminated responses of LC neurons to sciatic nerve stimulation or foot- or tail-pinch. This indicates that certain sensory information is relayed to LC through the excitatory amino acid (EAA) input from the ventrolateral medulla. The effect of prefrontal cortex (PFC) activation on LC neurons was examined in anesthetized rats. Single pulse PFC stimulation had no pronounced effect on LC neurons, consistent with our findings that this area does not innervate the LC nucleus. However, trains of PFC stimulation substantially activated most LC neurons. Thus, projections from the PFC may activate LC indirectly or through distal dendrites, suggesting a circuit whereby complex stimuli may influence LC neurons. The above results, in view of previous findings for postsynaptic effects of norepinephrine, are interpreted to reveal a role for the LC system in regulating attentional state or vigilance. The roles of major inputs to LC from the ventrolateral and dorsomedial medulla in sympathetic control and behavioral orienting responses, respectively, are integrated into this view of the LC system. It is proposed that the LC provides the cognitive complement to sympathetic function.
    BibTeX:
    @article{ASTONJONES1991,
      author = {ASTONJONES, G and CHIANG, C and ALEXINSKY, T},
      title = {DISCHARGE OF NORADRENERGIC LOCUS-CERULEUS NEURONS IN BEHAVING RATS AND MONKEYS SUGGESTS A ROLE IN VIGILANCE},
      journal = {PROGRESS IN BRAIN RESEARCH},
      year = {1991},
      volume = {88},
      pages = {501-520}
    }
    
    Baddeley, A. Working memory: Looking back and looking forward {2003} NATURE REVIEWS NEUROSCIENCE
    Vol. {4}({10}), pp. {829-839} 
    article DOI  
    Abstract: The concept of working memory proposes that a dedicated system maintains and stores information in the short term, and that this system underlies human thought processes. Current views of working memory involve a central executive and two storage systems: the phonological loop and the visuospatial sketchpad. Although this basic model was first proposed 30 years ago, it has continued to develop and to stimulate research and debate. The model and the most recent results are reviewed in this article.
    BibTeX:
    @article{Baddeley2003,
      author = {Baddeley, A},
      title = {Working memory: Looking back and looking forward},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2003},
      volume = {4},
      number = {10},
      pages = {829-839},
      doi = {{10.1038/nrn1201}}
    }
    
    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}
    }
    
    BARBAS, H. & PANDYA, D. ARCHITECTURE AND INTRINSIC CONNECTIONS OF THE PREFRONTAL CORTEX IN THE RHESUS-MONKEY {1989} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {286}({3}), pp. {353-375} 
    article  
    BibTeX:
    @article{BARBAS1989,
      author = {BARBAS, H and PANDYA, DN},
      title = {ARCHITECTURE AND INTRINSIC CONNECTIONS OF THE PREFRONTAL CORTEX IN THE RHESUS-MONKEY},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {1989},
      volume = {286},
      number = {3},
      pages = {353-375}
    }
    
    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-Cohen, S., Ring, H., Wheelwright, S., Bullmore, E., Brammer, M., Simmons, A. & Williams, S. Social intelligence in the normal and autistic brain: an fMRI study {1999} EUROPEAN JOURNAL OF NEUROSCIENCE
    Vol. {11}({6}), pp. {1891-1898} 
    article  
    Abstract: There is increasing support for the existence of `social intelligence' [Humphrey (1984) Consciousness Regained], independent of general intelligence. Brothers [(1990) J. Cog. Neurosci., 4, 107-118] proposed a network of neural regions that comprise the `social brain': the orbito-frontal cortex (OFC), superior temporal gyrus (STG) and amygdala. We tested Brothers' theory by examining both normal subjects as well as patients with high-functioning autism or Asperger syndrome (AS), who are well known to have deficits in social intelligence, and perhaps deficits in amygdala function [Bauman & Kemper (1988) J, Neuropath. Exp. Neurol,, 47, 369], We used a test of judging from the expressions of another person's eyes what that other person might be thinking or feeling. Using functional magnetic resonance imaging (fMRI) we confirmed Brothers' prediction that the STG and amygdala show increased activation when using social intelligence. Some areas of the prefrontal cortex also showed activation. In contrast, patients with autism or AS activated the fronto-temporal regions but not the amygdala when making mentalistic inferences from the eyes. These results provide support for the social brain theory of normal function, and the amygdala theory of autism.
    BibTeX:
    @article{Baron-Cohen1999,
      author = {Baron-Cohen, S and Ring, HA and Wheelwright, S and Bullmore, ET and Brammer, MJ and Simmons, A and Williams, SCR},
      title = {Social intelligence in the normal and autistic brain: an fMRI study},
      journal = {EUROPEAN JOURNAL OF NEUROSCIENCE},
      year = {1999},
      volume = {11},
      number = {6},
      pages = {1891-1898}
    }
    
    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}
    }
    
    BAXTER, L., SCHWARTZ, J., PHELPS, M., MAZZIOTTA, J., GUZE, B., SELIN, C., GERNER, R. & SUMIDA, R. REDUCTION OF PREFRONTAL CORTEX GLUCOSE-METABOLISM COMMON TO 3 TYPES OF DEPRESSION {1989} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {46}({3}), pp. {243-250} 
    article  
    BibTeX:
    @article{BAXTER1989,
      author = {BAXTER, LR and SCHWARTZ, JM and PHELPS, ME and MAZZIOTTA, JC and GUZE, BH and SELIN, CE and GERNER, RH and SUMIDA, RM},
      title = {REDUCTION OF PREFRONTAL CORTEX GLUCOSE-METABOLISM COMMON TO 3 TYPES OF DEPRESSION},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1989},
      volume = {46},
      number = {3},
      pages = {243-250}
    }
    
    Baxter, M. & Murray, E. The amygdala and reward {2002} NATURE REVIEWS NEUROSCIENCE
    Vol. {3}({7}), pp. {563-573} 
    article DOI  
    Abstract: The amygdala - an almond-shaped group of nuclei at the heart of the telencephalon has been associated with a range of cognitive functions, including emotion, learning, memory, attention and perception. Most current views of amygdala function emphasize its role in negative emotions, such as fear, and in linking negative emotions with other aspects of cognition, such as learning and memory. However, recent evidence supports a role for the amygdala in processing positive emotions as well as negative ones, including learning about the beneficial biological value of stimuli. Indeed, the amygdala's role in stimulus-reward learning might be just as important as its role in processing negative affect and fear conditioning.
    BibTeX:
    @article{Baxter2002,
      author = {Baxter, MG and Murray, EA},
      title = {The amygdala and reward},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2002},
      volume = {3},
      number = {7},
      pages = {563-573},
      doi = {{10.1038/nrn875}}
    }
    
    BECHARA, A., DAMASIO, A., DAMASIO, H. & ANDERSON, S. INSENSITIVITY TO FUTURE CONSEQUENCES FOLLOWING DAMAGE TO HUMAN PREFRONTAL CORTEX {1994} COGNITION
    Vol. {50}({1-3}), pp. {7-15} 
    article  
    Abstract: Following damage to the ventromedial prefrontal cortex, humans develop a defect in real-life decision-making, which contrasts with otherwise normal intellectual functions. Currently, there is no neuropsychological probe to detect in the laboratory, and the cognitive and neural mechanisms responsible for this defect have resisted explanation. Here, using a novel task which simulates real-life decision-making in the way it factors uncertainty of premises and outcomes, as well as reward and punishment, we find that prefrontal patients, unlike controls, are oblivious to the future consequences of their actions, and seem to be guided by immediate prospects only. This finding offers, for the first time, the possibility of detecting these patients' elusive impairment in the laboratory, measuring it, and investigating its possible causes.
    BibTeX:
    @article{BECHARA1994,
      author = {BECHARA, A and DAMASIO, AR and DAMASIO, H and ANDERSON, SW},
      title = {INSENSITIVITY TO FUTURE CONSEQUENCES FOLLOWING DAMAGE TO HUMAN PREFRONTAL CORTEX},
      journal = {COGNITION},
      year = {1994},
      volume = {50},
      number = {1-3},
      pages = {7-15}
    }
    
    Bechara, A., Damasio, H. & Damasio, A. Emotion, decision making and the orbitofrontal cortex {2000} CEREBRAL CORTEX
    Vol. {10}({3}), pp. {295-307} 
    article  
    Abstract: The somatic marker hypothesis provides a systems-level neuroanatomical and cognitive framework for decision making and the influence on it by emotion. The key idea of this hypothesis is that decision making is a process that is influenced by marker signals that arise in bioregulatory processes, including those that express themselves in emotions and feelings. This influence can occur at multiple levels of operation, some of which occur consciously and some of which occur non-consciously. Here we review studies that confirm various predictions from the hypothesis. The orbitofrontal cortex represents one critical structure in a neural system subserving decision making. Decision making is not mediated by the orbitofrontal cortex alone, hut arises from large-scale systems that include other cortical and subcortical components. Such structures include the amygdala, the somatosensory/insular cortices and the peripheral nervous system. Here we focus only on the role of the orbitofrontal cortex in decision making and emotional processing, and the relationship between emotion, decision making and other cognitive functions of the frontal lobe. namely working memory.
    BibTeX:
    @article{Bechara2000,
      author = {Bechara, A and Damasio, H and Damasio, AR},
      title = {Emotion, decision making and the orbitofrontal cortex},
      journal = {CEREBRAL CORTEX},
      year = {2000},
      volume = {10},
      number = {3},
      pages = {295-307}
    }
    
    Bechara, A., Damasio, H., Damasio, A. & Lee, G. Different contributions of the human amygdala and ventromedial prefrontal cortex to decision-making {1999} JOURNAL OF NEUROSCIENCE
    Vol. {19}({13}), pp. {5473-5481} 
    article  
    Abstract: The somatic marker hypothesis proposes that decision-making is a process that depends on emotion. Studies have shown that damage of the ventromedial prefrontal (VMF) cortex precludes the ability to use somatic (emotional) signals that are necessary for guiding decisions in the advantageous direction. However, given the role of the amygdala in emotional processing, we asked whether amygdala damage also would interfere with decision-making. Furthermore, we asked whether there might be a difference between the roles that the amygdala and VMF cortex play in decision-making. To address these two questions, we studied a group of patients with bilateral amygdala, but not VMF, damage and a group of patients with bilateral VMF, but not amygdala, damage. We used the ``gambling task'' to measure decision-making performance and electrodermal activity (skin conductance responses, SCR) as an index of somatic state activation. All patients, those with amygdala damage as well as those with VMF damage, were (1) impaired on the gambling task and (2) unable to develop anticipatory SCRs while they pondered risky choices. However, VMF patients were able to generate SCRs when they received a reward or a punishment (play money), whereas amygdala patients failed to do so. in a Pavlovian conditioning experiment the VMF patients acquired a conditioned SCR to visual stimuli paired with an aversive loud sound, whereas amygdala patients failed to do so. The results suggest that amygdala damage is associated with impairment in decision-making and that the roles played by the amygdala and VMF in decision-making are different.
    BibTeX:
    @article{Bechara1999,
      author = {Bechara, A and Damasio, H and Damasio, AR and Lee, GP},
      title = {Different contributions of the human amygdala and ventromedial prefrontal cortex to decision-making},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1999},
      volume = {19},
      number = {13},
      pages = {5473-5481}
    }
    
    Bechara, A., Damasio, H., Tranel, D. & Anderson, S. Dissociation of working memory from decision making within the human prefrontal cortex {1998} JOURNAL OF NEUROSCIENCE
    Vol. {18}({1}), pp. {428-437} 
    article  
    Abstract: We tested the hypothesis that cognitive functions related to working memory (assessed with delay tasks) are distinct from those related to decision making (assessed with a gambling task), and that working memory and decision making depend in part on separate anatomical substrates. Normal controls (n = 21), subjects with lesions in the ventromedial (VM) (n = 9) or dorsolateral/high mesial (DL/M) prefrontal cortices (n = 10), performed on (1) modified delay tasks that assess working memory and (2) a gambling task designed to measure decision making. VM subjects with more anterior lesions (n = 4) performed defectively on the gambling but not the delay task. VM subjects with more posterior lesions (n = 5) were impaired on both tasks. Right DL/M subjects were impaired on the delay task but not the gambling task. Left DUM subjects were not impaired on either task. The findings reveal a cognitive and anatomic double dissociation between deficits in decision making (anterior VM) and working memory (right DL/M). This presents the first direct evidence of such effects in humans using the lesion method and underscores the special importance of the VM prefrontal region in decision making, independent of a direct role in working memory.
    BibTeX:
    @article{Bechara1998,
      author = {Bechara, A and Damasio, H and Tranel, D and Anderson, SW},
      title = {Dissociation of working memory from decision making within the human prefrontal cortex},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1998},
      volume = {18},
      number = {1},
      pages = {428-437}
    }
    
    Bechara, A., Dolan, S., Denburg, N., Hindes, A., Anderson, S. & Nathan, P. Decision-malting deficits, linked to a dysfunctional ventromedial prefrontal cortex, revealed in alcohol and stimulant abusers {2001} NEUROPSYCHOLOGIA
    Vol. {39}({4}), pp. {376-389} 
    article  
    Abstract: A decision-making instrument known as the `gambling task' was used, which has been shown to be sensitive to the decision-making impairment of patients with bilateral lesions of the ventromedial prefrontal cortex (VM). Three groups of subjects were tested, substance dependent individuals (SD) (n = 41), normal controls (n = 40), and VM patients (n = 5). All SD met the DSM-IV criteria for dependence, with either alcohol or stimulants (metamphetamine or cocaine) as the primary substance of choice. The results revealed a significant impairment in the performance of SD relative to normal controls. A significantly high proportion of SD (61 vs. only 32.5% of normal controls) performed within the range of the VM patients, while the rest performed within the range of normal controls. General demographic Factors such as age, sex, and level of education could not explain these differences in performance. As well, differences in performance were not explained by intelligence (IQ), memory, or performance on standard executive function/frontal lobe tests. Performance on the gambling task was best predicted by a combination of factors; including duration of abstinence, years of abuse, relapses and limes in treatment, and the ability to hold gainful employment. The results support the hypothesis that impairment in decision-making linked to a dysfunctional VM cortex is associated with at least a sub-group of SD. (C) 2001 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{Bechara2001,
      author = {Bechara, A and Dolan, S and Denburg, N and Hindes, A and Anderson, SW and Nathan, PE},
      title = {Decision-malting deficits, linked to a dysfunctional ventromedial prefrontal cortex, revealed in alcohol and stimulant abusers},
      journal = {NEUROPSYCHOLOGIA},
      year = {2001},
      volume = {39},
      number = {4},
      pages = {376-389},
      note = {29th Annual Meeting of the Society-for-Neuroscience, MIAMI BEACH, FLORIDA, OCT 23-28, 1999}
    }
    
    Bechara, A., Tranel, D. & Damasio, H. Characterization of the decision-making deficit of patients with ventromedial prefrontal cortex lesions {2000} BRAIN
    Vol. {123}({Part 11}), pp. {2189-2202} 
    article  
    Abstract: On a gambling task that models real-life decisions, patients with bilateral lesions of the ventromedial prefrontal cortex (VM) opt for choices that yield high immediate gains in spite of higher future losses, In this study, we addressed three possibilities that may account for this behaviour: (i) hypersensitivity to reward; (ii) insensitivity to punishment; and (iii) insensitivity to future consequences, such that behaviour is always guided by immediate prospects. For this purpose, we designed a variant of the original gambling task in which the advantageous decks yielded high immediate punishment but even higher future reward. The disadvantageous decks yielded low immediate punishment but even lower future reward. We measured the skin conductance responses (SCRs) of subjects after they had received a reward or punishment. Patients with VM lesions opted for the disadvantageous decks in both the original and variant versions of the gambling task. The SCRs of VM lesion patients after they had received a reward or punishment were not significantly different from those of controls. In a second experiment, we investigated whether increasing the delayed punishment in the disadvantageous decks of the original task or decreasing the delayed reward in time disadvantageous decks of the variant task would shift the behaviour of VM lesion patients towards an advantageous strategy, Both manipulations failed to shift the behaviour of VM lesion patients away from the disadvantageous decks. These results suggest that patients with VM lesions are insensitive to future consequences, positive or negative, and are primarily guided by immediate prospects. This `myopia for the future' in VM lesion patients persists in the face of severe adverse consequences, i.e. rising future punishment or declining future reward.
    BibTeX:
    @article{Bechara2000a,
      author = {Bechara, A and Tranel, D and Damasio, H},
      title = {Characterization of the decision-making deficit of patients with ventromedial prefrontal cortex lesions},
      journal = {BRAIN},
      year = {2000},
      volume = {123},
      number = {Part 11},
      pages = {2189-2202}
    }
    
    Bechara, A., Tranel, D., Damasio, H. & Damasio, A. Failure to respond autonomically to anticipated future outcomes following damage to prefrontal cortex {1996} CEREBRAL CORTEX
    Vol. {6}({2}), pp. {215-225} 
    article  
    Abstract: Following damage to specific sectors of the prefrontal cortex, humans develop a defect in real-life decision making, in spite of otherwise normal intellectual performance. The patients so affected may even realize the consequences of their actions but fail to act accordingly, thus appearing oblivious to the future. The neural basis of this defect has resisted explanation. Here we identify a physiological correlate for the defect and discuss its possible significance. We measured the skin conductance responses (SCRs) of 7 patients with prefrontal damage, and 12 normal controls, during the performance of a novel task, a card game that simulates real-life decision making in the way it factors uncertainty, rewards, and penalties. Both patients and controls generated SCRs after selecting cards that were followed by penalties or by reward. However, after a number of trials, controls also began to generate SCRs prior to their selection of a card, while they pondered from which deck to choose, but no patients showed such anticipatory SCRs. The absence of anticipatory SCRs in patients with prefrontal damage is a correlate of their insensitivity to future outcomes. It is compatible with the idea that these patients fail to activate biasing signals that would serve as value markers in the distinction between choices with good or bad future outcomes; that these signals also participate in the enhancement of attention and working memory relative to representations pertinent to the decision process; and that the signals hail from the bioregulatory machinery that sustains somatic homeostasis and can be expressed in emotion and feeling.
    BibTeX:
    @article{Bechara1996,
      author = {Bechara, A and Tranel, D and Damasio, H and Damasio, AR},
      title = {Failure to respond autonomically to anticipated future outcomes following damage to prefrontal cortex},
      journal = {CEREBRAL CORTEX},
      year = {1996},
      volume = {6},
      number = {2},
      pages = {215-225}
    }
    
    BECKSTEAD, R. AUTORADIOGRAPHIC EXAMINATION OF CORTICO-CORTICAL AND SUB-CORTICAL PROJECTIONS OF THE MEDIODORSAL-PROJECTION (PREFRONTAL) CORTEX IN THE RAT {1979} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {184}({1}), pp. {43-62} 
    article  
    BibTeX:
    @article{BECKSTEAD1979,
      author = {BECKSTEAD, RM},
      title = {AUTORADIOGRAPHIC EXAMINATION OF CORTICO-CORTICAL AND SUB-CORTICAL PROJECTIONS OF THE MEDIODORSAL-PROJECTION (PREFRONTAL) CORTEX IN THE RAT},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {1979},
      volume = {184},
      number = {1},
      pages = {43-62}
    }
    
    Behrens, T., Johansen-Berg, H., Woolrich, M., Smith, S., Wheeler-Kingshott, C., Boulby, P., Barker, G., Sillery, E., Sheehan, K., Ciccarelli, O., Thompson, A., Brady, J. & Matthews, P. Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging {2003} NATURE NEUROSCIENCE
    Vol. {6}({7}), pp. {750-757} 
    article DOI  
    Abstract: Evidence concerning anatomical connectivities in the human brain is sparse and based largely on limited post-mortem observations. Diffusion tensor imaging has previously been used to define large white-matter tracts in the living human brain, but this technique has had limited success in tracing pathways into gray matter. Here we identified specific connections between human thalamus and cortex using a novel probabilistic tractography algorithm with diffusion imaging data. Classification of thalamic gray matter based on cortical connectivity patterns revealed distinct subregions whose locations correspond to nuclei described previously in histological studies. The connections that we found between thalamus and cortex were similar to those reported for non-human primates and were reproducible between individuals. Our results provide the first quantitative demonstration of reliable inference of anatomical connectivity between human gray matter structures using diffusion data and the first connectivity-based segmentation of gray matter.
    BibTeX:
    @article{Behrens2003,
      author = {Behrens, TEJ and Johansen-Berg, H and Woolrich, MW and Smith, SM and Wheeler-Kingshott, CAM and Boulby, PA and Barker, GJ and Sillery, EL and Sheehan, K and Ciccarelli, O and Thompson, AJ and Brady, JM and Matthews, PM},
      title = {Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging},
      journal = {NATURE NEUROSCIENCE},
      year = {2003},
      volume = {6},
      number = {7},
      pages = {750-757},
      doi = {{10.1038/nn1075}}
    }
    
    Behrens, T., Woolrich, M., Jenkinson, M., Johansen-Berg, H., Nunes, R., Clare, S., Matthews, P., Brady, J. & Smith, S. Characterization and propagation of uncertainty in diffusion-weighted MR imaging {2003} MAGNETIC RESONANCE IN MEDICINE
    Vol. {50}({5}), pp. {1077-1088} 
    article DOI  
    Abstract: A fully probabilistic framework is presented for estimating local probability density functions on parameters of interest in a model of diffusion. This technique is applied to the estimation of parameters in the diffusion tensor model, and also to a simple partial volume model of diffusion. In both cases the parameters of interest include parameters defining local fiber direction. A technique is then presented for using these density functions to estimate global connectivity (i.e., the probability of the existence of a connection through the data field, between any two distant points), allowing for the quantification of belief in tractography results. This technique is then applied to the estimation of the cortical connectivity of the human thalamus. The resulting connectivity distributions correspond well with predictions from invasive tracer methods in nonhuman primate. Magn Reson Med 50:1077-1088, 2003. (C) 2003 Wiley-Liss, Inc.
    BibTeX:
    @article{Behrens2003a,
      author = {Behrens, TEJ and Woolrich, MW and Jenkinson, M and Johansen-Berg, H and Nunes, RG and Clare, S and Matthews, PM and Brady, JM and Smith, SM},
      title = {Characterization and propagation of uncertainty in diffusion-weighted MR imaging},
      journal = {MAGNETIC RESONANCE IN MEDICINE},
      year = {2003},
      volume = {50},
      number = {5},
      pages = {1077-1088},
      doi = {{10.1002/mrm.10609}}
    }
    
    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{BENCH1993,
      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}
    }
    
    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., 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., 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}
    }
    
    Berardelli, A., Rothwell, J., Hallett, M., Thompson, P., Manfredi, M. & Marsden, C. The pathophysiology of primary dystonia {1998} BRAIN
    Vol. {121}({Part 7}), pp. {1195-1212} 
    article  
    Abstract: Go-contraction and overflow of EMG activity of inappropriate muscles are typical features of all dystonic movements whether voluntary or involuntary. Voluntary movements are slow and more variable than normal, and there is particular difficultly switching between component movements of a complex task, Reduced spinal cord and brainstem inhibition is common to many reflex studies (long-latency reflexes, cranial reflexes and reciprocal inhibition), These reflex abnormalities may contribute to the difficulties in voluntary movements but cannot be causal as they can occur outside the clinically involved territory, Clinical and neurophysiological studies have emphasized the possible role of sensory feedback in the generation of dystonic movements, Abnormalities of cortical and basal ganglia function have been described in functional imaging and neurophysiological studies of patients with dystonia and in animal models of primary dystonia, Studies of cortical function have shown reduced preparatory activity in the EEG before the onset of voluntary movements, whilst magnetic brain stimulation has revealed changes in motor cortical excitability, Functional imaging of the brain in primary dystonia has suggested reduced pallidal inhibition of the thalamus with consequent overactivity of medial and prefrontal cortical areas and underactivity of the primary motor cortex during movements. These findings are supported by preliminary neuronal recordings from the globus pallidus and the thalamus at the time of stereotaxic surgery in patients with dystonia, All this evidence suggests that primary dystonia results from a functional disturbance of the basal ganglia, particularly in the striatal control of the globus pallidus (and substantia nigra pars reticulata), This causes altered thalamic control of cortical motor planning and executive areas, and abnormal regulation of brainstem and spinal cord inhibitory interneuronal mechanisms.
    BibTeX:
    @article{Berardelli1998,
      author = {Berardelli, A and Rothwell, JC and Hallett, M and Thompson, PD and Manfredi, M and Marsden, CD},
      title = {The pathophysiology of primary dystonia},
      journal = {BRAIN},
      year = {1998},
      volume = {121},
      number = {Part 7},
      pages = {1195-1212}
    }
    
    BERENDSE, H., GALISDEGRAAF, Y. & GROENEWEGEN, H. TOPOGRAPHICAL ORGANIZATION AND RELATIONSHIP WITH VENTRAL STRIATAL COMPARTMENTS OF PREFRONTAL CORTICOSTRIATAL PROJECTIONS IN THE RAT {1992} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {316}({3}), pp. {314-347} 
    article  
    Abstract: The anterograde tracer Phaseolus vulgaris-leucoagglutinin was used to examine the topographical organization of the projections to the striatum arising from the various cytoarchitectonic subdivisions of the prefrontal cortex in the rat. The relationship of the prefrontal cortical fibres with the compartmental organization of the ventral striatum was assessed by combining PHA-L tracing and enkephalin-immunohistochemistry. The prefrontal cortex projects bilaterally with an ipsilateral predominance to the striatum, sparing only the lateral part of the caudate-putamen complex. Each of the cytoarchitectonic subfields of the prefrontal cortex has a longitudinally oriented striatal terminal field that overlaps slightly with those of adjacent prefrontal areas. The projections of the medial subdivision of the prefrontal cortex distribute to rostral and medial parts of the striatum, whereas the lateral prefrontal subdivision projects to more caudal and lateral striatal areas. The terminal fields of the orbital prefrontal areas involve midventral and ventromedial parts of the caudate-putamen complex. The projection of the ventral orbital area overlaps with that of the prelimbic area in the ventromedial part of the caudate-putamen. In the ``shell'' region of the nucleus accumbens, fibres arising from the prelimbic area concentrate in areas of high cell density that are weakly enkephalin-immunoreactive, whereas fibres from the infralimbic area avoid such areas. Rostrolaterally in the ``core'' region of the nucleus accumbens, fibres from deep layer V and layer VI of the dorsal part of the prelimbic area avoid the enkephalin-positive areas surrounding the anterior commissure and distribute in an inhomogeneous way over the intervening moderately enkephalin-immunoreactive compartment. The other prefrontal afferents show only a preference for, but are not restricted to, the latter compartment. In the border region between the nucleus accumbens and the ventromedial part of the caudate-putamen complex, patches of strong enkephalin immunoreactivity receive prefrontal cortical input from deep layer V and layer VI, whereas fibres from more superficial cortical layers project to the surrounding matrix. Individual eytoarchitectonic subfields of the prefrontal cortex thus have circumscribed terminal domains in the striatum. In combination with data on the organization of the midline and intralaminar thalamostriatal and thalamoprefrontal projections, the present results establish that the projections of the prefrontal cortical subfields converge in the striatum with those of their midline and intralaminar afferent nuclei. The present findings further demonstrate that the relationship of the prefrontal corticostriatal fibres with the neurochemical compartments of the ventral striatum can be influenced by both the areal and the laminar origin of the cortical afferents, depending on the particular ventral striatal region under consideration.
    BibTeX:
    @article{BERENDSE1992,
      author = {BERENDSE, HW and GALISDEGRAAF, Y and GROENEWEGEN, HJ},
      title = {TOPOGRAPHICAL ORGANIZATION AND RELATIONSHIP WITH VENTRAL STRIATAL COMPARTMENTS OF PREFRONTAL CORTICOSTRIATAL PROJECTIONS IN THE RAT},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {1992},
      volume = {316},
      number = {3},
      pages = {314-347}
    }
    
    BERGER, B., THIERRY, A., TASSIN, J. & MOYNE, M. DOPAMINERGIC INNERVATION OF RAT PREFRONTAL CORTEX - FLUORESCENCE HISTOCHEMICAL STUDY {1976} BRAIN RESEARCH
    Vol. {106}({1}), pp. {133-145} 
    article  
    BibTeX:
    @article{BERGER1976,
      author = {BERGER, B and THIERRY, AM and TASSIN, JP and MOYNE, MA},
      title = {DOPAMINERGIC INNERVATION OF RAT PREFRONTAL CORTEX - FLUORESCENCE HISTOCHEMICAL STUDY},
      journal = {BRAIN RESEARCH},
      year = {1976},
      volume = {106},
      number = {1},
      pages = {133-145}
    }
    
    BERMAN, K., OSTREM, J., RANDOLPH, C., GOLD, J., GOLDBERG, T., COPPOLA, R., CARSON, R., HERSCOVITCH, P. & WEINBERGER, D. PHYSIOLOGICAL ACTIVATION OF A CORTICAL NETWORK DURING PERFORMANCE OF THE WISCONSIN CARD SORTING TEST - A POSITRON EMISSION TOMOGRAPHY STUDY {1995} NEUROPSYCHOLOGIA
    Vol. {33}({8}), pp. {1027-1046} 
    article  
    Abstract: To determine the neural circuitry engaged by performance of the Wisconsin Card Sorting Test (WCST), a neuropsychological test traditionally considered to be sensitive to prefrontal lesions, regional cerebral blood flow was measured with oxygen-15 water and positron emission tomography (PET) while young normal subjects performed the test as well as while they performed a specially designed sensorimotor control task. To consider which of the various cognitive operations and other experiential phenomena involved in the WCST PET scan are critical for the pattern of physiological activation and to focus on the working memory component of the test, repeat WCST scans were also performed on nine of the subjects after instruction on the test and practice to criteria. We confirmed that performance of the WCST engages the frontal cortex and also produces activation of a complex network of regions consistently including the inferior parietal lobule but also involving the visual association and inferior temporal cortices as well as portions of the cerebellum. The WCST activation in the dorsolateral prefrontal cortex (DLPFC) remained significant even after training and practice on the test, suggesting that working memory may be largely responsible for the physiological response in DLPFC during the WCST and, conversely, that the DLPFC plays a major role in modulating working memory.
    BibTeX:
    @article{BERMAN1995,
      author = {BERMAN, KF and OSTREM, JL and RANDOLPH, C and GOLD, J and GOLDBERG, TE and COPPOLA, R and CARSON, RE and HERSCOVITCH, P and WEINBERGER, DR},
      title = {PHYSIOLOGICAL ACTIVATION OF A CORTICAL NETWORK DURING PERFORMANCE OF THE WISCONSIN CARD SORTING TEST - A POSITRON EMISSION TOMOGRAPHY STUDY},
      journal = {NEUROPSYCHOLOGIA},
      year = {1995},
      volume = {33},
      number = {8},
      pages = {1027-1046}
    }
    
    BERMAN, K., ZEC, R. & WEINBERGER, D. PHYSIOLOGICAL DYSFUNCTION OF DORSOLATERAL PREFRONTAL CORTEX IN SCHIZOPHRENIA .2. ROLE OF NEUROLEPTIC TREATMENT, ATTENTION, AND MENTAL EFFORT {1986} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {43}({2}), pp. {126-135} 
    article  
    BibTeX:
    @article{BERMAN1986,
      author = {BERMAN, KF and ZEC, RF and WEINBERGER, DR},
      title = {PHYSIOLOGICAL DYSFUNCTION OF DORSOLATERAL PREFRONTAL CORTEX IN SCHIZOPHRENIA .2. ROLE OF NEUROLEPTIC TREATMENT, ATTENTION, AND MENTAL EFFORT},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1986},
      volume = {43},
      number = {2},
      pages = {126-135}
    }
    
    Berridge, K. & Robinson, T. Parsing reward {2003} TRENDS IN NEUROSCIENCES
    Vol. {26}({9}), pp. {507-513} 
    article DOI  
    Abstract: Advances in neurobiology permit neuroscientists to manipulate specific brain molecules, neurons and systems. This has lead to major advances in the neuroscience of reward. Here, it is argued that further advances will require equal sophistication in parsing reward into its specific psychological components: (1) learning (including explicit and implicit knowledge produced by associative conditioning and cognitive processes); (2) affect or emotion (implicit `liking' and conscious pleasure) and (3) motivation (implicit incentive salience `wanting' and cognitive incentive goals). The challenge is to identify how different brain circuits mediate different psychological components of reward, and how these components interact.
    BibTeX:
    @article{Berridge2003,
      author = {Berridge, KC and Robinson, TE},
      title = {Parsing reward},
      journal = {TRENDS IN NEUROSCIENCES},
      year = {2003},
      volume = {26},
      number = {9},
      pages = {507-513},
      doi = {{10.1016/S0166-2236(03)00233-9}}
    }
    
    Binder, J., Frost, J., Hammeke, T., Bellgowan, P., Springer, J., Kaufman, J. & Possing, E. Human temporal lobe activation by speech and nonspeech sounds {2000} CEREBRAL CORTEX
    Vol. {10}({5}), pp. {512-528} 
    article  
    Abstract: Functional organization of the lateral temporal cortex in humans is not well understood. We recorded blood oxygenation signals from the temporal lobes of normal volunteers using functional magnetic resonance imaging during stimulation with unstructured noise, frequency-modulated (FM) tones, reversed speech, pseudowords and words. For all conditions, subjects performed a material-nonspecific detection response when a train of stimuli began or ceased. Dorsal areas surrounding Heschl's gyrus bilaterally, particularly the planum temporale and dorsolateral superior temporal gyrus, were more strongly activated by FM tones than by noise, suggesting a role in processing simple temporally encoded auditory information. Distinct from these dorsolateral areas, regions centered in the superior temporal sulcus bilaterally were more activated by speech stimuli than by FM tones. Identical results were obtained in this region using words, pseudowords and reversed speech, suggesting that the speech-tones activation difference is due to acoustic rather than linguistic factors. In contrast, previous comparisons between word and nonword speech sounds showed left lateralized activation differences in more ventral temporal and temporoparietal regions that are likely involved in processing lexical-semantic or syntactic information associated with words. The results indicate functional subdivision of the human lateral temporal cortex and provide a preliminary framework for understanding the cortical processing of speech sounds.
    BibTeX:
    @article{Binder2000,
      author = {Binder, JR and Frost, JA and Hammeke, TA and Bellgowan, PSF and Springer, JA and Kaufman, JN and Possing, ET},
      title = {Human temporal lobe activation by speech and nonspeech sounds},
      journal = {CEREBRAL CORTEX},
      year = {2000},
      volume = {10},
      number = {5},
      pages = {512-528}
    }
    
    Binder, J., Frost, J., Hammeke, T., Cox, R., Rao, S. & Prieto, T. Human brain language areas identified by functional magnetic resonance imaging {1997} JOURNAL OF NEUROSCIENCE
    Vol. {17}({1}), pp. {353-362} 
    article  
    Abstract: Functional magnetic resonance imaging (FMRI) was used to identify candidate language processing areas in the intact human brain. Language was defined broadly to include both phonological and lexical-semantic functions and to exclude sensory, motor, and general executive functions. The language activation task required phonetic and semantic analysis of aurally presented words and was compared with a control task involving perceptual analysis of nonlinguistic sounds. Functional maps of the entire brain were obtained from 30 right-handed subjects. These maps were averaged in standard stereotaxic space to produce a robust `'average activation map'' that proved reliable in a split-half analysis. As predicted from classical models of language organization based on lesion data, cortical activation associated with language processing was strongly lateralized to the left cerebral hemisphere and involved a network of regions in the frontal, temporal, and parietal robes. Less consistent with classical models were (1) the existence of left hemisphere temporoparietal language areas outside the traditional `'Wernicke area,'' namely, in the middle temporal, inferior temporal, fusiform, and angular gyri; (2) extensive left prefrontal language areas outside the classical `'Broca area''; and (3) clear participation of these left frontal areas in a task emphasizing `'receptive'' language functions. Although partly in conflict with the classical model of language localization, these findings are generally compatible with reported lesion data and provide additional support for ongoing efforts to refine and extend the classical model.
    BibTeX:
    @article{Binder1997,
      author = {Binder, JR and Frost, JA and Hammeke, TA and Cox, RW and Rao, SM and Prieto, T},
      title = {Human brain language areas identified by functional magnetic resonance imaging},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1997},
      volume = {17},
      number = {1},
      pages = {353-362}
    }
    
    Birrell, J. & Brown, V. Medial frontal cortex mediates perceptual attentional set shifting in the rat {2000} JOURNAL OF NEUROSCIENCE
    Vol. {20}({11}), pp. {4320-4324} 
    article  
    Abstract: If rodents do not display the behavioral complexity that is subserved in primates by prefrontal cortex, then evolution of prefrontal cortex in the rat should be doubted. Primate prefrontal cortex has been shown to mediate shifts in attention between perceptual dimensions of complex stimuli. This study examined the possibility that medial frontal cortex of the rat is involved in the shifting of perceptual attentional set. We trained rats to perform an attentional set-shifting task that is formally the same as a task used in monkeys and humans. Rats were trained to dig in bowls for a food reward. The bowls were presented in pairs, only one of which was baited. The rat had to select the bowl in which to dig by its odor, the medium that filled the bowl, or the texture that covered its surface. In a single session, rats performed a series of discriminations, including reversals, an intradimensional shift, and an extradimensional shift. Bilateral lesions by injection of ibotenic acid in medial frontal cortex resulted in impairment in neither initial acquisition nor reversal learning. We report here the same selective impairment in shifting of attentional set in the rat as seen in primates with lesions of prefrontal cortex. We conclude that medial frontal cortex of the rat has functional similarity to primate lateral prefrontal cortex.
    BibTeX:
    @article{Birrell2000,
      author = {Birrell, JM and Brown, VJ},
      title = {Medial frontal cortex mediates perceptual attentional set shifting in the rat},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2000},
      volume = {20},
      number = {11},
      pages = {4320-4324}
    }
    
    Blair, R. & Cipolotti, L. Impaired social response reversal - A case of `acquired sociopathy' {2000} BRAIN
    Vol. {123}({Part 6}), pp. {1122-1141} 
    article  
    Abstract: In this study, we report a patient (J.S.) who, following trauma to the right frontal region, including the orbitofrontal cortex, presented with `acquired sociopathy'. His behaviour was notably aberrant and marked by high levels of aggression and a callous disregard for others. A series of experimental investigations were conducted to address the cognitive dysfunction that might underpin his profoundly aberrant behaviour. His performance was contrasted with that of a second patient (C.L.A.), who also presented with a grave dysexecutive syndrome but no socially aberrant behaviour, and five inmates of Wormwood Scrubs prison with developmental psychopathy. While J.S. showed no reversal learning impairment, he presented with severe difficulty in emotional expression recognition, autonomic responding and social cognition. Unlike the comparison populations, J.S. showed impairment in: the recognition of, and autonomic responding to, angry and disgusted expressions; attributing the emotions of fear, anger and embarrassment to story protagonists; and the identification of violations of social behaviour. The findings are discussed with reference to models regarding the role of the orbitofrontal cortex in the control of aggression. It is suggested that J.S.'s impairment is due to a reduced ability to generate expectations of others' negative emotional reactions, in particular anger. In healthy individuals, these representations act to suppress behaviour that is inappropriate in specific social contexts. Moreover, it is proposed that the orbitofrontal cortex may be implicated specifically either in the generation of these expectations or the use of these expectations to suppress inappropriate behaviour.
    BibTeX:
    @article{Blair2000,
      author = {Blair, RJR and Cipolotti, L},
      title = {Impaired social response reversal - A case of `acquired sociopathy'},
      journal = {BRAIN},
      year = {2000},
      volume = {123},
      number = {Part 6},
      pages = {1122-1141}
    }
    
    Blood, A. & Zatorre, R. Intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion {2001} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {98}({20}), pp. {11818-11823} 
    article  
    Abstract: We used positron emission tomography to study neural mechanisms underlying intensely pleasant emotional responses to music. Cerebral blood flow changes were measured in response to subject-selected music that elicited the highly pleasurable experience of ``shivers-down-the-spine'' or ``chills.'' Subjective reports of chills were accompanied by changes in heart rate, electromyogram, and respiration. As intensity of these chills increased, cerebral blood flow increases and decreases were observed in brain regions thought to be involved in reward/motivation, emotion, and arousal, including ventral striatum, midbrain, amygdala, orbitofrontal cortex, and ventral medial prefrontal cortex. These brain structures are known to be active in response to other euphoria-inducing stimuli, such as food, sex, and drugs of abuse. This finding links music with biologically relevant, survival-related stimuli via their common recruitment of brain circuitry involved in pleasure and reward.
    BibTeX:
    @article{Blood2001,
      author = {Blood, AJ and Zatorre, RJ},
      title = {Intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {2001},
      volume = {98},
      number = {20},
      pages = {11818-11823}
    }
    
    Bookheimer, S. Functional MRI of language: New approaches to understanding the cortical organization of semantic processing {2002} ANNUAL REVIEW OF NEUROSCIENCE
    Vol. {25}, pp. {151-188} 
    article DOI  
    Abstract: Until recently, our understanding of how language is organized in the brain depended on analysis of behavioral deficits in patients with fortuitously placed lesions. The availability of functional magnetic resonance imaging (fMRI) for in vivo analysis of the normal brain has revolutionized the study of language. This review discusses three lines of fMRI research into how the semantic system is organized in the adult brain. These are (a) the role of the left inferior frontal lobe in semantic processing and dissociations from other frontal lobe language functions, (b) the organization of categories of objects and concepts in the temporal lobe, and (c) the role of the right hemisphere in comprehending contextual and figurative meaning. Together, these lines of research broaden our understanding of how the brain stores, retrieves, and makes sense of semantic information, and they challenge some commonly held notions of functional modularity in the language system.
    BibTeX:
    @article{Bookheimer2002,
      author = {Bookheimer, S},
      title = {Functional MRI of language: New approaches to understanding the cortical organization of semantic processing},
      journal = {ANNUAL REVIEW OF NEUROSCIENCE},
      year = {2002},
      volume = {25},
      pages = {151-188},
      doi = {{10.1146/annurev.neuro.25.112701.142946}}
    }
    
    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}}
    }
    
    BRAFF, D., HEATON, R., KUCK, J., CULLUM, M., MORANVILLE, J., GRANT, I. & ZISOOK, S. THE GENERALIZED PATTERN OF NEUROPSYCHOLOGICAL DEFICITS IN OUTPATIENTS WITH CHRONIC-SCHIZOPHRENIA WITH HETEROGENEOUS WISCONSIN CARD SORTING TEST-RESULTS {1991} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {48}({10}), pp. {891-898} 
    article  
    Abstract: Forty schizophrenic outpatients and 40 normal subjects were assessed using extensive clinical (eg, Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms and Scale for the Assessment of Positive Symptoms) and neuropsychological (extended Halstead-Reitan Battery) measures. The schizophrenic patients had multiple neuropsychological deficits on tests of complex conceptual reasoning, psychomotor speed, new learning and incidental memory, and both motor and sensory-perceptual abilities. Neuropsychological impairment correlated more strongly with negative than positive symptoms. Overall, the schizophrenic outpatients showed relatively modest increases in the number of perseverative responses on the Wisconsin Card Sorting Test of abstraction flexibility. A subgroup of these schizophrenic patients seemed to be particularly impaired on the Wisconsin Card Sorting Test. This pattern of results, in conjunction with previous studies, supports the idea that, while some schizophrenic patients may have fixed, frontally based dysfunctions, these dysfunctions may be most prominent, and even fixed, in deteriorated, kraepelinian patients. These data provide evidence for diffuse and far-reaching deficits in a majority of outpatients with chronic schizophrenia.
    BibTeX:
    @article{BRAFF1991,
      author = {BRAFF, DL and HEATON, R and KUCK, J and CULLUM, M and MORANVILLE, J and GRANT, I and ZISOOK, S},
      title = {THE GENERALIZED PATTERN OF NEUROPSYCHOLOGICAL DEFICITS IN OUTPATIENTS WITH CHRONIC-SCHIZOPHRENIA WITH HETEROGENEOUS WISCONSIN CARD SORTING TEST-RESULTS},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1991},
      volume = {48},
      number = {10},
      pages = {891-898}
    }
    
    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}
    }
    
    Braver, T., Cohen, J., Nystrom, L., Jonides, J., Smith, E. & Noll, D. A parametric study of prefrontal cortex involvement in human working memory {1997} NEUROIMAGE
    Vol. {5}({1}), pp. {49-62} 
    article  
    Abstract: Although recent neuroimaging studies suggest that prefrontal cortex (PBC) is involved in working memory (WM), the relationship between PFC activity and memory load has not yet been well-described in humans. Here we use functional magnetic resonance imaging (fMRI) to probe PFC activity during a sequential letter task in which memory load was varied in an incremental fashion. In all nine subjects studied, dorsolateral and left inferior regions of PFC were identified that exhibited a linear relationship between activity and WM load. Furthermore, these same regions were independently identified through direct correlations of the fMRI signal with a behavioral measure that indexes WM function during task performance. A second experiment, using whole-brain imaging techniques, both replicated these findings and identified additional brain regions showing a Linear relationship with load, suggesting a distributed circuit that participates with PFC in subserving WM. Taken together, these results provide a `'dose-response curve'' describing the involvement of both PFC and related brain regions in WM function, and highlight the benefits of using graded, parametric designs in neuroimaging research. (C) 1997 Academic Press.
    BibTeX:
    @article{Braver1997,
      author = {Braver, TS and Cohen, JD and Nystrom, LE and Jonides, J and Smith, EE and Noll, DC},
      title = {A parametric study of prefrontal cortex involvement in human working memory},
      journal = {NEUROIMAGE},
      year = {1997},
      volume = {5},
      number = {1},
      pages = {49-62}
    }
    
    BREIER, A., BUCHANAN, R., ELKASHEF, A., MUNSON, R., KIRKPATRICK, B. & GELLAD, F. BRAIN MORPHOLOGY AND SCHIZOPHRENIA - A MAGNETIC-RESONANCE-IMAGING STUDY OF LIMBIC, PREFRONTAL CORTEX, AND CAUDATE STRUCTURES {1992} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {49}({12}), pp. {921-926} 
    article  
    Abstract: We used magnetic resonance imaging to examine the morphologic characteristics of the amygdala/hippocampus, prefrontal cortex, and caudate nucleus in 29 healthy volunteers matched for age, gender, and head of household socioeconomic status and 44 patients with chronic schizophrenia. Total volumes of these structures were determined from 3-mm contiguous coronal sections. Schizophrenic patients, compared with healthy controls, had significantly smaller right and left amygdala/hippocampal complex volumes, smaller right and left prefrontal volumes, and larger left caudate volumes. A secondary analysis revealed reductions in the right and left amygdala and the left hippocampus. In addition, prefrontal white matter, but not gray matter, was reduced in the schizophrenic patients. Moreover, the right white matter volume in schizophrenic patients was significantly related to right amygdala/hippocampal volume (r=.39), data that provide preliminary support for a hypothesis of abnormal limbic-cortical connection in schizophrenia. We studied the implications of these data for the pathophysiology of schizophrenia.
    BibTeX:
    @article{BREIER1992,
      author = {BREIER, A and BUCHANAN, RW and ELKASHEF, A and MUNSON, RC and KIRKPATRICK, B and GELLAD, F},
      title = {BRAIN MORPHOLOGY AND SCHIZOPHRENIA - A MAGNETIC-RESONANCE-IMAGING STUDY OF LIMBIC, PREFRONTAL CORTEX, AND CAUDATE STRUCTURES},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1992},
      volume = {49},
      number = {12},
      pages = {921-926}
    }
    
    Breiter, H., Aharon, I., Kahneman, D., Dale, A. & Shizgal, P. Functional imaging of neural responses to expectancy and experience of monetary gains and losses {2001} NEURON
    Vol. {30}({2}), pp. {619-639} 
    article  
    Abstract: Neural responses accompanying anticipation and experience of monetary gains and losses were monitored by functional magnetic resonance imaging. Trials comprised an initial ``prospect'' (expectancy) phase, when a set of three monetary amounts was displayed, and a subsequent ``outcome'' phase, when one of these amounts was awarded. Hemodynamic responses in the sublenticular extended amygdala (SLEA) and orbital gyrus tracked the expected values of the prospects, and responses to the highest value set of outcomes increased monotonically with monetary value in the nucleus accumbens, SLEA, and hypothalamus. Responses to prospects and outcomes were generally, but not always, seen in the same regions. The overlap of the observed activations with those seen previously in response to tactile stimuli, gustatory stimuli, and euphoria-inducing drugs is consistent with a contribution of common circuitry to the processing of diverse rewards.
    BibTeX:
    @article{Breiter2001,
      author = {Breiter, HC and Aharon, I and Kahneman, D and Dale, A and Shizgal, P},
      title = {Functional imaging of neural responses to expectancy and experience of monetary gains and losses},
      journal = {NEURON},
      year = {2001},
      volume = {30},
      number = {2},
      pages = {619-639}
    }
    
    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}
    }
    
    BREMNER, J., RANDALL, P., SCOTT, T., BRONEN, R., SEIBYL, J., SOUTHWICK, S., DELANEY, R., MCCARTHY, G., CHARNEY, D. & INNIS, R. MRI-BASED MEASUREMENT OF HIPPOCAMPAL VOLUME IN PATIENTS WITH COMBAT-RELATED POSTTRAUMATIC-STRESS-DISORDER {1995} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {152}({7}), pp. {973-981} 
    article  
    Abstract: Objective: Studies in nonhuman primates suggest that high levels of cortisol associated with stress have neurotoxic effects on the hippocampus, a brain structure involved in memory. The authors previously showed that patients with combat-related posttraumatic stress disorder (PTSD) had deficits in short-term memory. The purpose of this study was to compare the hippocampal volume of patients with PTSD to that of subjects without psychiatric disorder. Method: Magnetic resonance imaging was used to measure the volume of the hippocampus in 26 Vietnam combat veterans with PTSD and 22 comparison subjects selected to be similar to the patients in age, sex, race, years of education, socioeconomic status, body size, and years of alcohol abuse. Results: The PTSD patients had a statistically significant 8% smaller right hippocampal volume relative to that of the comparison subjects, but there was no difference in the volume of other brain regions (caudate and temporal lobe). Deficits in short-term verbal memory as measured with the Wechsler Memory Scale were associated with smaller right hippocampal volume in the PTSD patients only. Conclusions: These findings are consistent with a smaller right hippocampal volume in PTSD that is associated with functional deficits in verbal memory.
    BibTeX:
    @article{BREMNER1995,
      author = {BREMNER, JD and RANDALL, P and SCOTT, TM and BRONEN, RA and SEIBYL, JP and SOUTHWICK, SM and DELANEY, RC and MCCARTHY, G and CHARNEY, DS and INNIS, RB},
      title = {MRI-BASED MEASUREMENT OF HIPPOCAMPAL VOLUME IN PATIENTS WITH COMBAT-RELATED POSTTRAUMATIC-STRESS-DISORDER},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {1995},
      volume = {152},
      number = {7},
      pages = {973-981}
    }
    
    Brewer, J., Zhao, Z., Desmond, J., Glover, G. & Gabrieli, J. Making memories: Brain activity that predicts how well visual experience will be remembered {1998} SCIENCE
    Vol. {281}({5380}), pp. {1185-1187} 
    article  
    Abstract: Experiences are remembered or forgotten, but the neural determinants for the mnemonic fate of experience are unknown. Event-related functional magnetic resonance imaging was used to identify specific brain activations that differentiated between visual experiences that were later remembered well, remembered less well, or forgotten. During scanning of medial temporal lobe and frontal lobe regions, subjects viewed complex, color photographs. Subjects later received a test of memory for the photographs. The magnitudes of focal activations in right prefrontal cortex and in bilateral parahippocampal cortex predicted which photographs were later remembered well, remembered less well, or forgotten.
    BibTeX:
    @article{Brewer1998,
      author = {Brewer, JB and Zhao, Z and Desmond, JE and Glover, GH and Gabrieli, JDE},
      title = {Making memories: Brain activity that predicts how well visual experience will be remembered},
      journal = {SCIENCE},
      year = {1998},
      volume = {281},
      number = {5380},
      pages = {1185-1187}
    }
    
    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}
    }
    
    BROZOSKI, T., BROWN, R., ROSVOLD, H. & GOLDMAN, P. COGNITIVE DEFICIT CAUSED BY REGIONAL DEPLETION OF DOPAMINE IN PREFRONTAL CORTEX OF RHESUS-MONKEY {1979} SCIENCE
    Vol. {205}({4409}), pp. {929-932} 
    article  
    BibTeX:
    @article{BROZOSKI1979,
      author = {BROZOSKI, TJ and BROWN, RM and ROSVOLD, HE and GOLDMAN, PS},
      title = {COGNITIVE DEFICIT CAUSED BY REGIONAL DEPLETION OF DOPAMINE IN PREFRONTAL CORTEX OF RHESUS-MONKEY},
      journal = {SCIENCE},
      year = {1979},
      volume = {205},
      number = {4409},
      pages = {929-932}
    }
    
    Buchel, C. & Friston, K. Modulation of connectivity in visual pathways by attention: Cortical interactions evaluated with structural equation modelling and fMRI {1997} CEREBRAL CORTEX
    Vol. {7}({8}), pp. {768-778} 
    article  
    Abstract: Electrophysiological and neuroimaging studies have shown that attention to visual motion can increase the responsiveness of the motion-selective cortical area V5 and the posterior parietal cortex (PP). Increased or decreased activation in a cortical area is often attributed to attentional modulation of the cortical projections to that area. This leads to the notion that attention is associated with changes in connectivity. We have addressed attentional modulation of effective connectivity using functional magnetic resonance imaging (fMRI). Three subjects were scanned under identical stimulus conditions (visual motion) while varying only the attentional component of the task. Haemodynamic responses defined an occipito-parieto-frontal network, including the, primary visual cortex (V1), V5 and PP. A structural equation model of the interactions among these dorsal visual pathway areas revealed increased connectivity between V5 and PP related to attention. On the basis of our analysis and the neuroanatomical pattern of projections from the prefrontal cortex to PR we attributed the source of modulatory influences, on the posterior visual pathway, to the prefrontal cortex (PFC). To test this hypothesis we included the PFC in our model as a `modulator' of the pathway between V5 and PR using interaction terms in the structural equation model. This analysis revealed a significant modulatory effect of prefrontal regions on V5 afferents to posterior parietal cortex.
    BibTeX:
    @article{Buchel1997,
      author = {Buchel, C and Friston, KJ},
      title = {Modulation of connectivity in visual pathways by attention: Cortical interactions evaluated with structural equation modelling and fMRI},
      journal = {CEREBRAL CORTEX},
      year = {1997},
      volume = {7},
      number = {8},
      pages = {768-778}
    }
    
    BUCHSBAUM, M., HAIER, R., POTKIN, S., NUECHTERLEIN, K., BRACHA, H., KATZ, M., LOHR, J., WU, J., LOTTENBERG, S., JERABEK, P., TRENARY, M., TAFALLA, R., REYNOLDS, C. & BUNNEY, W. FRONTOSTRIATAL DISORDER OF CEREBRAL METABOLISM IN NEVER-MEDICATED SCHIZOPHRENICS {1992} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {49}({12}), pp. {935-942} 
    article  
    Abstract: We scanned 18 patients with schizophrenia who had never received neuroleptic medication and 20 age- and sex-matched controls by positron emission tomography with 18-F-fluorodeoxyglucose (fludeoxyglucose F 18) as a tracer of glucose metabolism. Subjects performed the Continuous Performance Test during 18-F-fluorodeoxyglucose uptake. Scan results were converted to metabolic rates, and computer algorithms were used to identify cortical regions. Pervious reports of relative hypofrontality in schizophrenia were confirmed, indicating that this finding is not an artifact of previous treatment. Significantly reduced ratios of inferior and medial frontal regions to occipital cortex were found, together with diminished metabolism in the basal ganglia. This suggests the presence of a combined fronto-striatal dysfunction in schizophrenia.
    BibTeX:
    @article{BUCHSBAUM1992,
      author = {BUCHSBAUM, MS and HAIER, RJ and POTKIN, SG and NUECHTERLEIN, K and BRACHA, HS and KATZ, M and LOHR, J and WU, J and LOTTENBERG, S and JERABEK, PA and TRENARY, M and TAFALLA, R and REYNOLDS, C and BUNNEY, WE},
      title = {FRONTOSTRIATAL DISORDER OF CEREBRAL METABOLISM IN NEVER-MEDICATED SCHIZOPHRENICS},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1992},
      volume = {49},
      number = {12},
      pages = {935-942}
    }
    
    Buckner, R., Goodman, J., Burock, M., Rotte, M., Koutstaal, W., Schacter, D., Rosen, B. & Dale, A. Functional-anatomic correlates of object priming in humans revealed by rapid presentation event-related fMRI {1998} NEURON
    Vol. {20}({2}), pp. {285-296} 
    article  
    Abstract: Human functional-anatomic correlates of object repetition were explored in a cohort of 20 subjects using fMRI. Subjects performed an object classification task where the target objects were either novel or repeated. Objects appeared rapidly, one every 2 s, in a randomly intermixed task design similar to traditional behavioral, event-related potential (ERP), and single-unit physiological studies. Recently developed event-related fMRI methods were used to analyze the data. Clear effects of repetition were observed. Brain areas in mid-levels of the processing hierarchy, including extrastriate visual cortex extending into inferotemporal cortex and left dorsal prefrontal cortex, showed reductions in the amount of activation after repetition. By contrast, early visual areas and output motor areas were activated equally by both novel and repeated objects and did not show effects of repetition, suggesting that the observed correlates of repetition were anatomically selective. We discuss these findings in relation to previous positron emission tomography (PET) and fMRI studies of item repetition and single-unit physiological studies; we also address the broad impact that rapid event-related fMRI is likely to have on functional neuroimaging.
    BibTeX:
    @article{Buckner1998,
      author = {Buckner, RL and Goodman, J and Burock, M and Rotte, M and Koutstaal, W and Schacter, D and Rosen, B and Dale, AM},
      title = {Functional-anatomic correlates of object priming in humans revealed by rapid presentation event-related fMRI},
      journal = {NEURON},
      year = {1998},
      volume = {20},
      number = {2},
      pages = {285-296}
    }
    
    BUCKNER, R., PETERSEN, S., OJEMANN, J., MIEZIN, F., SQUIRE, L. & RAICHLE, M. FUNCTIONAL ANATOMICAL STUDIES OF EXPLICIT AND IMPLICIT MEMORY RETRIEVAL TASKS {1995} JOURNAL OF NEUROSCIENCE
    Vol. {15}({1, Part 1}), pp. {12-29} 
    article  
    Abstract: Across three experiments, PET scans were obtained while subjects performed different word-stem completion and FIXATION control tasks designed to study the functional anatomy of memory retrieval. During each of three different word-stem completion scans, word-stem cues were visually presented in uppercase letters. The RECALL task required explicit retrieval of study words presented prior to the PET scan. The PRIMING task addressed the implicit effects of the prior study words without requiring intentional recall. The BASELINE task encouraged retrieval of information from a general knowledge store. Across experiments, the similarity between study words and word stems was manipulated by presenting prescan study words in either uppercase letters identical to the stems, in lowercase letters, or auditorily. The PRIMING task was not studied with auditory presentation. Many activations were consistent across experiments. The BASELINE task activated several regions in response to the reading and verbal-response demands of the task (visual, motor, and premotor cortices, cerebellum), as well as a left prefrontal region. The RECALL task additionally activated regions in anterior right prefrontal cortex. Bilateral occipitotemporal regions showed blood flow reductions during the PRIMING task as compared to the BASELINE task. Activation in the right hippocampal/parahippocampal region was observed only in one experiment, and no experiment showed activation in the left medial temporal lobe. These experiments suggest that areas of frontal cortex play a role in explicit recall and that an effect of priming may be to require less activation of perceptual regions for the processing of recently presented information.
    BibTeX:
    @article{BUCKNER1995,
      author = {BUCKNER, RL and PETERSEN, SE and OJEMANN, JG and MIEZIN, FM and SQUIRE, LR and RAICHLE, ME},
      title = {FUNCTIONAL ANATOMICAL STUDIES OF EXPLICIT AND IMPLICIT MEMORY RETRIEVAL TASKS},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1995},
      volume = {15},
      number = {1, Part 1},
      pages = {12-29}
    }
    
    Bunge, S., Dudukovic, N., Thomason, M., Vaidya, C. & Gabrieli, J. Immature frontal lobe contributions to cognitive control in children: Evidence from fMRI {2002} NEURON
    Vol. {33}({2}), pp. {301-311} 
    article  
    Abstract: Event-related fMRI was employed to characterize differences in brain activation between children ages 8-12 and adults related to two forms of cognitive control: interference suppression and response inhibition. Children were more susceptible to interference and less able to inhibit inappropriate responses than were adults. Effective interference suppression in children was associated with prefrontal activation in the opposite hemisphere relative to adults. In contrast, effective response inhibition in children was associated with activation of posterior, but not prefrontal, regions activated by adults. Children failed to activate a region in right ventrolateral prefrontal cortex that was recruited for both types of cognitive control by adults. Thus, children exhibited immature prefrontal activation that varied according to the type of cognitive control required.
    BibTeX:
    @article{Bunge2002,
      author = {Bunge, SA and Dudukovic, NM and Thomason, ME and Vaidya, CJ and Gabrieli, JDE},
      title = {Immature frontal lobe contributions to cognitive control in children: Evidence from fMRI},
      journal = {NEURON},
      year = {2002},
      volume = {33},
      number = {2},
      pages = {301-311}
    }
    
    Bymaster, F., Katner, J., Nelson, D., Hemrick-Luecke, S., Threlkeld, P., Heiligenstein, J., Morin, S., Gehlert, D. & Perry, K. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: A potential mechanism for efficacy in Attention Deficit/Hyperactivity Disorder {2002} NEUROPSYCHOPHARMACOLOGY
    Vol. {27}({5}), pp. {699-711} 
    article  
    Abstract: The selective norepinephrine (NE) transporter inhibitor atomoxetine (formerly called tomoxetine or LY139603) has been shown to alleviate symptoms in Attention Deficit/Hyperactivity Disorder (ADHD). We investigated the mechanism of action of atomoxetine in ADHD by evaluating the interaction of atomoxetine with monoamine transporters, the effects on extracellular levels of monoamines, and the expression of the neuronal activity marker Fos in brain regions. Atomoxetine inhibited binding of radioligands to clonal cell lines transfected with human NE, serotonin (5-HT) and dopamine (DA) transporters with dissociation constants (K-i) values of 5, 77 and 1451 nM, respectively, demonstrating selectivity for NE transporters. In microdialysis studies, atomoxetine increased extracellular (EX) levels of NE in prefrontal cortex (PFC) 3-fold, but did not alter 5-HTEX levels. Atomoxetine also increased DA(EX) concentrations in PFC 3-fold, but did not alter DA(EX) in striatum or nucleus accumbens. In contrast, the psychostimulant methylphenidate, which is used in ADHD therapy, increased NEEX and DA(EX) equally in PFC, but also increased DA(EX) in the striatum and nucleus accumbens to the same level. The expression of the neuronal activity marker Fos was increased 3.7-fold in PFC by atomoxetine administration, but was not increased in the striatum or nucleus accumbens, consistent with the regional distribution of increased DA(EX). We hypothesize that the atomoxetine-induced increase of catecholamines in PFC, a region involved in attention and memory, mediates the therapeutic effects of atomoxetine in ADHD. In contrast to methylphenidate, atomoxetine did not increase DA in striatum or nucleus accumbens, suggesting it would not have motoric or drug abuse liabilities. (C) 2002 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.
    BibTeX:
    @article{Bymaster2002,
      author = {Bymaster, FP and Katner, JS and Nelson, DL and Hemrick-Luecke, SK and Threlkeld, PG and Heiligenstein, JH and Morin, SM and Gehlert, DR and Perry, KW},
      title = {Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: A potential mechanism for efficacy in Attention Deficit/Hyperactivity Disorder},
      journal = {NEUROPSYCHOPHARMACOLOGY},
      year = {2002},
      volume = {27},
      number = {5},
      pages = {699-711}
    }
    
    Cabeza, R., Anderson, N., Locantore, J. & McIntosh, A. Aging gracefully: Compensatory brain activity in high-performing older adults {2002} NEUROIMAGE
    Vol. {17}({3}), pp. {1394-1402} 
    article DOI  
    Abstract: Whereas some older adults show significant cognitive deficits, others perform as well as young adults. We investigated the neural basis of these different aging patterns using positron emission tomography (PET). In PET and functional MRI (fMRI) studies, prefrontal cortex (PFC) activity tends to be less asymmetric in older than in younger adults (Hemispheric Asymmetry Reduction in Old Adults or HAROLD). This change may help counteract age-related neuro-cognitive decline (compensation hypothesis) or it may reflect an age-related difficulty in recruiting specialized neural mechanisms (dedifferentiation hypothesis). To compare these two hypotheses, we measured PFC activity in younger adults, low-performing older adults, and high-performing older adults during recall and source memory of recently studied words. Compared to recall, source memory was associated with right PFC activations in younger adults. Low-performing older adults recruited similar right PFC regions as young adults, but high-performing older adults engaged PFC regions bilaterally. Thus, consistent with the compensation hypothesis and inconsistent with the dedifferentiation hypothesis, a hemispheric asymmetry reduction was found in high-performing but not in low-performing older adults. The results suggest that low-performing older adults recruited a similar network as young adults but used it inefficiently, whereas high-performing older adults counteracted age-related neural decline through a plastic reorganization of neurocognitive networks.(C) 2002 Elsevier Science (USA).
    BibTeX:
    @article{Cabeza2002,
      author = {Cabeza, R and Anderson, ND and Locantore, JK and McIntosh, AR},
      title = {Aging gracefully: Compensatory brain activity in high-performing older adults},
      journal = {NEUROIMAGE},
      year = {2002},
      volume = {17},
      number = {3},
      pages = {1394-1402},
      doi = {{10.1006/nimg.2002.1280}}
    }
    
    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}
    }
    
    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}
    }
    
    Callicott, J., Mattay, V., Bertolino, A., Finn, K., Coppola, R., Frank, J., Goldberg, T. & Weinberger, D. Physiological characteristics of capacity constraints in working memory as revealed by functional MRI {1999} CEREBRAL CORTEX
    Vol. {9}({1}), pp. {20-26} 
    article  
    Abstract: A fundamental characteristic of working memory is that its capacity to handle information is limited. While there have been many brain mapping studies of working memory, the physiological basis of its capacity limitation has not been explained. We identified characteristics of Corking memory capacity using functional magnetic resonance imaging (fMRI) in healthy subjects. Working memory capacity was studied using a parametric `n-back' working memory task involving increasing cognitive load and ultimately decreasing task performance. Loci within dorsolateral prefrontal cortex (DLPFC) evinced exclusively an `inverted-U' shaped neurophysiological response from lowest to highest toad, consistent with a capacity-constrained response. Regions outside of DLPFC, in contrast, were more heterogeneous in response and often showed early plateau or continuously increasing responses, which did not reflect capacity constraints. However, sporadic loci, including in the premotor cortex, thalamus and superior parietal lobule, also demonstrated putative capacity-constrained responses, perhaps arising as an upstream effect of DLPFC limitations or as part of a broader network-wide capacity limitation. These results demonstrate that regionally specific nodes within the working memory network are capacity-constrained in the physiological domain, providing a missing link in current explorations of the capacity characteristics of working memory.
    BibTeX:
    @article{Callicott1999,
      author = {Callicott, JH and Mattay, VS and Bertolino, A and Finn, K and Coppola, R and Frank, JA and Goldberg, TE and Weinberger, DR},
      title = {Physiological characteristics of capacity constraints in working memory as revealed by functional MRI},
      journal = {CEREBRAL CORTEX},
      year = {1999},
      volume = {9},
      number = {1},
      pages = {20-26}
    }
    
    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}
    }
    
    Carr, D. & Sesack, S. Projections from the rat prefrontal cortex to the ventral tegmental area: Target specificity in the synaptic associations with mesoaccumbens and mesocortical neurons {2000} JOURNAL OF NEUROSCIENCE
    Vol. {20}({10}), pp. {3864-3873} 
    article  
    Abstract: Excitatory projections from the prefrontal cortex (PFC) to the ventral tegmental area (VTA) play an important role in regulating the activity of VTA neurons and the extracellular levels of dopamine (DA) within forebrain regions. Previous investigations have demonstrated that PFC terminals synapse on the dendrites of DA and non-DA neurons in the VTA. However, the projection targets of these cells are not known. To address whether PFC afferents innervate different populations of VTA neurons that project to the nucleus accumbens (NAc) or to the PFC, a triple labeling method was used that combined peroxidase markers for anterograde and retrograde tract-tracing with pre-embedding immunogold-silver labeling for either tyrosine hydroxylase (TH) or GABA. Within the VTA, PFC terminals formed asymmetric synapses onto dendritic shafts that were immunoreactive for either TH or GABA. PFC terminals also synapsed on VTA dendrites that were retrogradely labeled from the NAc or the PFC. Dendrites retrogradely labeled from the NAc and postsynaptic to PFC afferents were sometimes immunoreactive for GABA but were never TH-labeled. Conversely, dendrites retrogradely labeled from the PFC and postsynaptic to PFC afferents were sometimes immunoreactive for TH but were never GABA-labeled. These results provide the first demonstration of PFC afferents synapsing on identified cell populations in the VTA and indicate a considerable degree of specificity in the targets of the PFC projection. The unexpected finding of selective PFC synaptic input to GABA-containing mesoaccumbens neurons and DA-containing mesocortical neurons suggests novel mechanisms through which the PFC can influence the activity of ascending DA and GABA projections.
    BibTeX:
    @article{Carr2000,
      author = {Carr, DB and Sesack, SR},
      title = {Projections from the rat prefrontal cortex to the ventral tegmental area: Target specificity in the synaptic associations with mesoaccumbens and mesocortical neurons},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2000},
      volume = {20},
      number = {10},
      pages = {3864-3873}
    }
    
    Casey, B., Castellanos, F., Giedd, J., Marsh, W., Hamburger, S., Schubert, A., Vauss, Y., Vaituzis, A., Dickstein, D., Sarfatti, S. & Rapoport, J. Implication of right frontostriatal circuitry in response inhibition and attention-deficit/hyperactivity disorder {1997} JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
    Vol. {36}({3}), pp. {374-383} 
    article  
    Abstract: Objective: To examine the relation between specific frontostriatal structures (prefrontal cortex and basal ganglia) and response inhibition deficits observed in attention-deficit/hyperactivity disorder (ADHD). Method: Children with ADHD and age-matched normal controls were scanned using magnetic resonance imaging (MRI) and tested on three response inhibition tasks. Behavioral performance was correlated with MRI-based anatomical measures of frontostriatal circuitry (prefrontal cortex and basal ganglia) implicated in ADHD. Results: First, significant differences in performance by children with ADHD and normal volunteers were observed on all three response inhibition tasks. Second, performance on these tasks correlated only with those anatomical measures of frontostriatal circuitry observed to be abnormal in children with ADHD (e.g., the region of the prefrontal cortex, caudate, and globus pallidus, but not the putamen) in the authors' previous study. Third, significant correlations between task performance and anatomical measures of the prefrontal cortex and caudate nuclei were predominantly in the right hemisphere, supporting a role of right frontostriatal circuitry in response inhibition and ADHD. Conclusion: The data suggest a role of the right prefrontal cortex in suppressing responses to salient, but otherwise irrelevant events while the basal ganglia appear to be involved in executing these behavioral responses.
    BibTeX:
    @article{Casey1997,
      author = {Casey, BJ and Castellanos, FX and Giedd, JN and Marsh, WL and Hamburger, SD and Schubert, AB and Vauss, YC and Vaituzis, AC and Dickstein, DP and Sarfatti, SE and Rapoport, JL},
      title = {Implication of right frontostriatal circuitry in response inhibition and attention-deficit/hyperactivity disorder},
      journal = {JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY},
      year = {1997},
      volume = {36},
      number = {3},
      pages = {374-383}
    }
    
    Casey, B., Giedd, J. & Thomas, K. Structural and functional brain development and its relation to cognitive development {2000} BIOLOGICAL PSYCHOLOGY
    Vol. {54}({1-3}), pp. {241-257} 
    article  
    Abstract: Despite significant gains in the fields of pediatric neuroimaging and developmental neurobiology, surprisingly little is known about the developing human brain or the neural bases of cognitive development. This paper addresses MRI studies of structural and functional changes in the developing human brain and their relation to changes in cognitive processes over the first few decades of human life. Based on post-mortem and pediatric neuroimaging studies published to date, the prefrontal cortex appears to be one of the last brain regions to mature. Given the prolonged physiological development and organization of the prefrontal cortex during childhood, tasks believed to involve this region are ideal for investigating the neural bases of cognitive development. A number of normative pediatric fMRI studies examining prefrontal cortical activity in children during memory and attention tasks are reported. These studies, while largely limited to the domain of prefrontal functioning and its development, lend support for continued development of attention and memory both behaviorally and physiologically throughout childhood and adolescence. Specifically, the magnitude of activity observed in these studies was greater and more diffuse in children relative to adults. These findings are consistent with the view that increasing cognitive capacity during childhood may coincide with a gradual loss rather than formation of new synapses and presumably a strengthening of remaining synaptic connections. It is clear that innovative methods like fMRI together with MRI-based morphometry and nonhuman primate studies will transform our current understanding of human brain development and its relation to behavioral development. (C) 2000 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{Casey2000,
      author = {Casey, BJ and Giedd, JN and Thomas, KM},
      title = {Structural and functional brain development and its relation to cognitive development},
      journal = {BIOLOGICAL PSYCHOLOGY},
      year = {2000},
      volume = {54},
      number = {1-3},
      pages = {241-257}
    }
    
    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{Casey1997a,
      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}
    }
    
    Castellanos, F., Giedd, J., Marsh, W., Hamburger, S., Vaituzis, A., Dickstein, D., Sarfatti, S., Vauss, Y., Snell, J., Lange, N., Kaysen, D., Krain, A., Ritchie, G., Rajapakse, J. & Rapoport, J. Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder {1996} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {53}({7}), pp. {607-616} 
    article  
    Abstract: Background: Anatomic magnetic resonance imaging (MRI) studies of attention-deficit hyperactivity disorder (ADHD) have been limited by small samples or measurement of single brain regions. Since the neuropsychological deficits in ADHD implicate a network linking basal ganglia and frontal regions, 12 subcortical and cortical regions and their symmetries were measured to determine if these structures best distinguished ADHD. Method: Anatomic brain MRIs for 57 boys with ADHD and 55 healthy matched controls, aged 5 to 18 years, were obtained using a 1.5-T scanner with contiguous 2-mm sections. Volumetric measures of the cerebrum, caudate nucleus, putamen, globus pallidus, amygdala, hippocampus, temporal lobe, cerebellum; a measure of prefrontal cortex; and related right-left asymmetries were examined along with midsagittal area measures of the cerebellum and corpus callosum. Interrater reliabilities were .82 or greater for all MRI measures. Conclusion: This first comprehensive morphometric analysis is consistent with hypothesized dysfunction of right-sided prefrontal-striatal systems in ADHD.
    BibTeX:
    @article{Castellanos1996,
      author = {Castellanos, FX and Giedd, JN and Marsh, WL and Hamburger, SD and Vaituzis, AC and Dickstein, DP and Sarfatti, SE and Vauss, YC and Snell, JW and Lange, N and Kaysen, D and Krain, AL and Ritchie, GF and Rajapakse, JC and Rapoport, JL},
      title = {Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1996},
      volume = {53},
      number = {7},
      pages = {607-616}
    }
    
    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}
    }
    
    Cavanna, A. & Trimble, M. The precuneus: a review of its functional anatomy and behavioural correlates {2006} BRAIN
    Vol. {129}({Part 3}), pp. {564-583} 
    article DOI  
    Abstract: Functional neuroimaging studies have started unravelling unexpected functional attributes for the posteromedial portion of the parietal lobe, the precuneus. This cortical area has traditionally received little attention, mainly because of its hidden location and the virtual absence of focal lesion studies. However, recent functional imaging findings in healthy subjects suggest a central role for the precuneus in a wide spectrum of highly integrated tasks, including visuo-spatial imagery, episodic memory retrieval and self-processing operations, namely first-person perspective taking and an experience of agency. Furthermore, precuneus and surrounding posteromedial areas are amongst the brain structures displaying the highest resting metabolic rates (hot spots) and are characterized by transient decreases in the tonic activity during engagement in non-self-referential goal-directed actions (default mode of brain function). Therefore, it has recently been proposed that precuneus is involved in the interwoven network of the neural correlates of self-consciousness, engaged in self-related mental representations during rest. This hypothesis is consistent with the selective hypometabolism in the posteromedial cortex reported in a wide range of altered conscious states, such as sleep, drug-induced anaesthesia and vegetative states. This review summarizes the current knowledge about the macroscopic and microscopic anatomy of precuneus, together with its wide-spread connectivity with both cortical and subcortical structures, as shown by connectional and neurophysiological findings in non-human primates, and links these notions with the multifaceted spectrum of its behavioural correlates. By means of a critical analysis of precuneus activation patterns in response to different mental tasks, this paper provides a useful conceptual framework for matching the functional imaging findings with the specific role(s) played by this structure in the higher-order cognitive functions in which it has been implicated. Specifically, activation patterns appear to converge with anatomical and connectivity data in providing preliminary evidence for a functional subdivision within the precuneus into an anterior region, involved in self-centred mental imagery strategies, and a posterior region, subserving successful episodic memory retrieval.
    BibTeX:
    @article{Cavanna2006,
      author = {Cavanna, AE and Trimble, MR},
      title = {The precuneus: a review of its functional anatomy and behavioural correlates},
      journal = {BRAIN},
      year = {2006},
      volume = {129},
      number = {Part 3},
      pages = {564-583},
      doi = {{10.1093/brain/awl004}}
    }
    
    Chafee, M. & Goldman-Rakic, P. Matching patterns of activity in primate prefrontal area 8a and parietal area 7ip neurons during a spatial working memory task {1998} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {79}({6}), pp. {2919-2940} 
    article  
    Abstract: Single-unit recording studies of posterior parietal neurons have indicated a similarity of neuronal activation to that observed in the dorsolateral prefrontal cortex in relation to performance of delayed saccade tasks. A key issue addressed in the present study is whether the different classes of neuronal activity observed in these tasks are encountered more frequently in one or the other area or otherwise exhibit region-specific properties. The present study is the first to directly compare these patterns of neuronal activity by alternately recording from parietal area 7ip and prefrontal area 8a, under the identical behavioral conditions, within the same hemisphere of two monkeys performing an oculomotor delayed response task. The firing rate of 222 posterior parietal and 235 prefrontal neurons significantly changed during the cue, delay, and/or saccade periods of the task. Neuronal responses in the two areas could be distinguished only by subtle differences in their incidence and timing. Thus neurons responding to the cue appeared earliest and were more frequent among the task-related neurons within parietal cortex, whereas neurons exhibiting delay-period activity accounted for a larger proportion of task-related neurons in prefrontal cortex. Otherwise, the task-related neuronal activities were remarkably similar. Cue period activity in prefrontal and parietal cortex exhibited comparable spatial tuning and temporal duration characteristics, taking the form of phasic, tonic, or combined phasic/tonic excitation in both cortical. populations. Neurons in both cortical areas exhibited sustained activity during the delay period with nearly identical spatial tuning. The various patterns of delay-period activity-tonic, increasing or decreasing, alone or in combination with greater activation during cue and/or saccade periods-likewise were distributed to both cortical areas. Finally, similarities in the two populations extended to the proportion and spatial tuning of presaccadic and postsaccadic neuronal activity occurring in relation to the memory-guided saccade. The present findings support and extend evidence for a faithful duplication of receptive held properties and virtually every other dimension of task-related activity observed when parietal and prefrontal cortex are recruited to a common task. This striking similarity attests to the principal that information shared by a prefrontal region and a sensory association area with which it is connected is domain specific and not subject to hierarchical elaboration, as is evident at earlier stages of visuospatial processing.
    BibTeX:
    @article{Chafee1998,
      author = {Chafee, MV and Goldman-Rakic, PS},
      title = {Matching patterns of activity in primate prefrontal area 8a and parietal area 7ip neurons during a spatial working memory task},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1998},
      volume = {79},
      number = {6},
      pages = {2919-2940}
    }
    
    Chambers, R., Taylor, J. & Potenza, M. Developmental neurocircuitry of motivation in adolescence: A critical period of addiction vulnerability {2003} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {160}({6}), pp. {1041-1052} 
    article  
    Abstract: Objective: Epidemiological studies indicate that experimentation with addictive drugs and onset of addictive disorders is primarily concentrated in adolescence and young adulthood. The authors describe basic and clinical data supporting adolescent neurodevelopment as a biologically critical period of greater vulnerability for experimentation with substances and acquisition of substance use disorders. Method: The authors reviewed recent literature regarding neurocircuitry underlying motivation, impulsivity, and addiction, with a focus on studies investigating adolescent neurodevelopment. Results: Adolescent neurodevelopment occurs in brain regions associated with motivation, impulsivity, and addiction. Adolescent impulsivity and/or novelty seeking as a transitional trait behavior can be explained in part by maturational changes in frontal cortical and subcortical monoaminergic systems. These developmental processes may advantageously promote learning drives for adaptation to adult roles but may also confer greater vulnerability to the addictive actions of drugs. Conclusions: An exploration of developmental changes in neurocircuitry involved in impulse control has significant implications for understanding adolescent behavior, addiction vulnerability, and the prevention of addiction in adolescence and adulthood.
    BibTeX:
    @article{Chambers2003,
      author = {Chambers, RA and Taylor, JR and Potenza, MN},
      title = {Developmental neurocircuitry of motivation in adolescence: A critical period of addiction vulnerability},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {2003},
      volume = {160},
      number = {6},
      pages = {1041-1052}
    }
    
    Chao, L. & Martin, A. Representation of manipulable man-made objects in the dorsal stream {2000} NEUROIMAGE
    Vol. {12}({4}), pp. {478-484} 
    article  
    Abstract: We used fMRI to examine the neural response in frontal and parietal cortices associated with viewing and naming pictures of different categories of objects. Because tools are commonly associated with specific hand movements, we predicted that pictures of tools, but not other categories of objects, would elicit activity in regions of the brain that store information about motor-based properties. We found that viewing and naming pictures of tools selectively activated the left ventral premotor cortex (BA 6). Single-unit recording studies in monkeys have shown that neurons in the rostral part of the ventral premotor cortex (canonical F5 neurons) respond to the visual presentation of graspable objects, even in the absence of any subsequent motor activity. Thus, the left ventral premotor region that responded selectively to tools in the current study may be the human homolog of the monkey canonical F5 area. Viewing and naming tools also selectively activated the left posterior parietal cortex (BA 40). This response is similar to the firing of monkey anterior intraparietal neurons to the visual presentation of graspable objects. In humans and monkeys, there appears to be a close link between manipulable objects and information about the actions associated with their use. The selective activation of the left posterior parietal and left ventral premotor cortices by pictures of tools suggests that the ability to recognize and identify at least one category of objects (tools) may depend on activity in specific sites of the ventral and dorsal visual processing streams.
    BibTeX:
    @article{Chao2000,
      author = {Chao, LL and Martin, A},
      title = {Representation of manipulable man-made objects in the dorsal stream},
      journal = {NEUROIMAGE},
      year = {2000},
      volume = {12},
      number = {4},
      pages = {478-484}
    }
    
    Chen, J., Lipska, B., Halim, N., Ma, Q., Matsumoto, M., Melhem, S., Kolachana, B., Hyde, T., Herman, M., Apud, J., Egan, M., Kleinman, J. & Weinberger, D. Functional analysis of genetic variation in catechol-o-methyltransferase (COMT): Effects on mRNA, protein, and enzyme activity in postmortem human brain {2004} AMERICAN JOURNAL OF HUMAN GENETICS
    Vol. {75}({5}), pp. {807-821} 
    article  
    Abstract: Catechol-O-methyltransferase (COMT) is a key enzyme in the elimination of dopamine in the prefrontal cortex of the human brain. Genetic variation in the COMT gene (MIM 116790) has been associated with altered prefrontal cortex function and higher risk for schizophrenia, but the specific alleles and their functional implications have been controversial. We analyzed the effects of several single-nucleotide polymorphisms (SNPs) within COMT on mRNA expression levels (using reverse-transcriptase polymerase chain reaction analysis), protein levels (using Western blot analysis), and enzyme activity (using catechol methylation) in a large sample (n = 108) of postmortem human prefrontal cortex tissue, which predominantly expresses the -membrane-bound isoform. A common coding SNP, Val158Met (rs4680), significantly affected protein abundance and enzyme activity but not mRNA expression levels, suggesting that differences in protein integrity account for the difference in enzyme activity between alleles. A SNP in intron 1 (rs737865) and a SNP in the 3' flanking region (rs165599) - both of which have been reported to contribute to allelic expression differences and to be associated with schizophrenia as part of a haplotype with Val - had no effect on mRNA expression levels, protein immunoreactivity, or enzyme activity. In lymphocytes from 47 subjects, we confirmed a similar effect on enzyme activity in samples with the Val/Met genotype but no effect in samples with the intron 1 or 3 a SNPs. Separate analyses revealed that the subject's sex, as well as the presence of a SNP in the P2 promoter region (rs2097603), had small effects on COMT enzyme activity. Using site-directed mutagenesis of mouse COMT cDNA, followed by in vitro translation, we found that the conversion of Leu at the homologous position into Met or Val progressively and significantly diminished enzyme activity. Thus, although we cannot exclude a more complex genetic basis for functional effects of COMT, Val is a predominant factor that determines higher COMT activity in the prefrontal cortex, which presumably leads to lower synaptic dopamine levels and relatively deleterious prefrontal function.
    BibTeX:
    @article{Chen2004,
      author = {Chen, JS and Lipska, BK and Halim, N and Ma, QD and Matsumoto, M and Melhem, S and Kolachana, BS and Hyde, TM and Herman, MM and Apud, J and Egan, MF and Kleinman, JE and Weinberger, DR},
      title = {Functional analysis of genetic variation in catechol-o-methyltransferase (COMT): Effects on mRNA, protein, and enzyme activity in postmortem human brain},
      journal = {AMERICAN JOURNAL OF HUMAN GENETICS},
      year = {2004},
      volume = {75},
      number = {5},
      pages = {807-821}
    }
    
    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}
    }
    
    Cohen, J., Perlstein, W., Braver, T., Nystrom, L., Noll, D., Jonides, J. & Smith, E. Temporal dynamics of brain activation during a working memory task {1997} NATURE
    Vol. {386}({6625}), pp. {604-608} 
    article  
    Abstract: Working memory is responsible for the short-term storage and online manipulation of information necessary for higher cognitive functions, such as language, planning and problem-solving(1,2). Traditionally, working memory has been divided into two types of processes: executive control (governing the encoding manipulation and retrieval of information in working memory) and active maintenance (keeping information available `online'). It has also been proposed that these two types of processes may be subserved by distinct cortical structures, with the prefrontal cortex housing the executive control processes, and more posterior regions housing the content-specific buffers (for example verbal versus visuospatial) responsible for active maintenance(3,4). However, studies in non-human primates suggest that dorsolateral regions of the prefrontal cortex may alsb be involved in active maintenance(5-8). We have used functional magnetic resonance imaging to examine brain activation in human subjects during performance of a working memory task. We used the temporal resolution of this technique to examine the dynamics of regional activation, and to show that prefrontal cortex along with parietal cortex appears to play a role in active maintenance.
    BibTeX:
    @article{Cohen1997,
      author = {Cohen, JD and Perlstein, WM and Braver, TS and Nystrom, LE and Noll, DC and Jonides, J and Smith, EE},
      title = {Temporal dynamics of brain activation during a working memory task},
      journal = {NATURE},
      year = {1997},
      volume = {386},
      number = {6625},
      pages = {604-608}
    }
    
    COHEN, J. & SERVANSCHREIBER, D. CONTEXT, CORTEX, AND DOPAMINE - A CONNECTIONIST APPROACH TO BEHAVIOR AND BIOLOGY IN SCHIZOPHRENIA {1992} PSYCHOLOGICAL REVIEW
    Vol. {99}({1}), pp. {45-77} 
    article  
    Abstract: Connectionist models are used to explore the relationship between cognitive deficits and biological abnormalities in schizophrenia. Schizophrenic deficits in tasks that tap attention and language processing are reviewed, as are biological disturbances involving prefrontal cortex and the mesocortical dopamine system. Three computer models are then presented that simulate normal and schizophrenic performance in the Stroop task, the continuous performance test, and a lexical disambiguation task. They demonstrate that a disturbance in the internal representation of contextual information can provide a common explanation for schizophrenic deficits in several attention- and language-related tasks. The models also show that these behavioral deficits may arise from a disturbance in a model parameter (gain) corresponding to the neuromodulatory effects of dopamine, in a model component corresponding to the function of prefrontal cortex.
    BibTeX:
    @article{COHEN1992,
      author = {COHEN, JD and SERVANSCHREIBER, D},
      title = {CONTEXT, CORTEX, AND DOPAMINE - A CONNECTIONIST APPROACH TO BEHAVIOR AND BIOLOGY IN SCHIZOPHRENIA},
      journal = {PSYCHOLOGICAL REVIEW},
      year = {1992},
      volume = {99},
      number = {1},
      pages = {45-77}
    }
    
    Cohen, M., Kosslyn, S., Breiter, H., DiGirolamo, G., Thompson, W., Anderson, A., Bookheimer, S., Rosen, B. & Belliveau, J. Changes in cortical activity during mental rotation - A mapping study using functional MRI {1996} BRAIN
    Vol. {119}({Part 1}), pp. {89-100} 
    article  
    Abstract: Mental imagery is an important cognitive method for problem solving, and the mental rotation of complex objects, as originally described by Shepard and Metzler (1971), is among the best studied of mental imagery tasks. Functional MRI was used to observe focal changes in blood flow in the brains of 10 healthy volunteers performing a mental rotation task On each trial, subjects viewed a pair of perspective drawings of three-dimensional shapes, mentally rotated one into congruence with the other and then determined whether the two forms were identical or mirror-images. The control task, which rye have called the `comparison' condition, was identical except that both members of each pair appeared at the same orientation, and hence the same encoding, comparison and decision processes were used but mental rotation was not required. These tasks were interleaved with a baseline `fixation' condition, in which the subjects viewed a crosshair. Technically adequate studies were obtained in eight of the 10 subjects. Areas of increased signal were identified according to sulcal landmarks and are described in terms of the Brodmann's area (BA) definitions that correspond according to the atlas of Talaraich and Tournoux. When the rotation task was contrasted with the comparison condition, all subjects showed consistent foci of activation in BAs 7a and 7b (sometimes spreading to BA 40); 88% had increased signal in middle frontal gyrus (BA 8) and 75% showed extrastriate activation including particularly BAs 39 and 19, in a position consistent with area V5/human MT as localized by functional and histological assays. In move than half of the subjects, hand somatosensory cortex (3-1-2) was engaged, and in 50% of subjects there was elevated signal in BA 18. In frontal cortex activation was above threshold in half the subjects in BAs 9 and/or 46 (dorsolateral prefrontal cortex). Some (four out of eight) subjects also showed signal increases in BAs 44 and/or 46. Premotor cortex (BA 6) was active in half of the subjects during the rotation task. There was little evidence for lateralization of the cortical activity or of engagement of motor cortex. These data are consistent with the hypothesis that mental rotation engages cortical areas involved in tracking moving objects and encoding spatial relations, as well as the more general understanding that mental imagery engages the same, or similar, neural imagery as direct perception.
    BibTeX:
    @article{Cohen1996,
      author = {Cohen, MS and Kosslyn, SM and Breiter, HC and DiGirolamo, GJ and Thompson, WL and Anderson, AK and Bookheimer, SY and Rosen, BR and Belliveau, JW},
      title = {Changes in cortical activity during mental rotation - A mapping study using functional MRI},
      journal = {BRAIN},
      year = {1996},
      volume = {119},
      number = {Part 1},
      pages = {89-100}
    }
    
    Corbetta, M. Frontoparietal cortical networks for directing attention and the eye to visual locations: Identical, independent, or overlapping neural systems? {1998} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {95}({3}), pp. {831-838} 
    article  
    Abstract: Functional anatomical and single-unit recording studies indicate that a set of neural signals in parietal and frontal cortex mediates the covert allocation of attention to visual locations, as originally proposed by psychological studies, This frontoparietal network is the source of a location bias that interacts with extrastriate regions of the ventral visual system during object analysis to enhance visual processing, The frontoparietal network is not exclusively related to visual attention, but may coincide or overlap with regions involved in oculomotor processing, The relationship between attention and eye movement processes is discussed at the psychological, functional anatomical, and cellular level of analysis.
    BibTeX:
    @article{Corbetta1998,
      author = {Corbetta, M},
      title = {Frontoparietal cortical networks for directing attention and the eye to visual locations: Identical, independent, or overlapping neural systems?},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1998},
      volume = {95},
      number = {3},
      pages = {831-838},
      note = {Colloquium on Neuroimaging of Human Brain Function, IRVINE, CALIFORNIA, MAY 29-31, 1997}
    }
    
    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}
    }
    
    Corbetta, M. & Shulman, G. Control of goal-directed and stimulus-driven attention in the brain {2002} NATURE REVIEWS NEUROSCIENCE
    Vol. {3}({3}), pp. {201-215} 
    article DOI  
    Abstract: We review evidence for partially segregated networks of brain areas that carry out different attentional functions. One system, which includes parts of the intraparietal cortex and superior frontal cortex, is involved in preparing and applying goal-directed (top-down) selection for stimuli and responses. This system is also modulated by the detection of stimuli. The other system, which includes the temporoparietal cortex and inferior frontal cortex, and is largely lateralized to the right hemisphere, is not involved in top-down selection. Instead, this system is specialized for the detection of behaviourally relevant stimuli, particularly when they are salient or unexpected. This ventral frontoparietal network works as a `circuit breaker' for the dorsal system, directing attention to salient events. Both attentional systems interact during normal vision, and both are disrupted in unilateral spatial neglect.
    BibTeX:
    @article{Corbetta2002,
      author = {Corbetta, M and Shulman, GL},
      title = {Control of goal-directed and stimulus-driven attention in the brain},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2002},
      volume = {3},
      number = {3},
      pages = {201-215},
      doi = {{10.1038/nrn755}}
    }
    
    Coull, J. Neural correlates of attention and arousal: Insights from electrophysiology, functional neuroimaging and psychopharmacology {1998} PROGRESS IN NEUROBIOLOGY
    Vol. {55}({4}), pp. {343-361} 
    article  
    Abstract: Attention and arousal are multi-dimensional psychological processes, which interact closely with one another. The neural substrates of attention, as well as the interaction between arousal and attention, are discussed in this review. After a brief discussion of psychological and neuropsychological theories of attention, event-related potential correlates of attention are discussed. Essentially, attention acts to modulate stimulus-induced electrical potentials (N100/P100, P300, N400), rather than generating any unique potentials of its own. Functional neuroimaging studies of attentional orienting, selective attention, divided attention and sustained attention land its inter-dependance on underlying levels of arousal) are then reviewed. A distinction is drawn between the brain areas which are crucially involved in the top-down modulation of attention (the `sources' of attention) and those sensory-association areas whose activity is modulated by attention (the `sites' of attentional expression). Frontal and parietal (usually right-lateralised) cortices and thalamus are most often associated with the source of attentional modulation. Also, the use of functional neuroimaging to test explicit hypotheses about psychological theories of attention is emphasised. These experimental paradigms form the basis for a `new generation' of functional imaging studies which exploit the dynamic aspect of imaging and demonstrate how it can be used as more than just a `brain mapping' device. Finally, a review of psychopharmacological studies in healthy human volunteers outlines the contributions of the noradrenergic, cholinergic and dopaminergic neurotransmitter systems to the neurochemical modulation of human attention and arousal. While, noradrenergic and cholinergic systems are involved in `low-level' aspects of attention (e.g. attentional orienting), the dopaminergic system is associated with more `executive' aspects of attention such as attentional set-shifting or working memory. (C) 1998 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{Coull1998,
      author = {Coull, JT},
      title = {Neural correlates of attention and arousal: Insights from electrophysiology, functional neuroimaging and psychopharmacology},
      journal = {PROGRESS IN NEUROBIOLOGY},
      year = {1998},
      volume = {55},
      number = {4},
      pages = {343-361}
    }
    
    Courtney, S., Petit, L., Maisog, J., Ungerleider, L. & Haxby, J. An area specialized for spatial working memory in human frontal cortex {1998} SCIENCE
    Vol. {279}({5355}), pp. {1347-1351} 
    article  
    Abstract: Working memory is the proc!ss of maintaining an active representation of information so that it is available for use. In monkeys, a prefrontal cortical region important for spatial working memory lies in and around the principal sulcus, but in humans the location, and even the existence, of a region for spatial working memory is in dispute. By using functional magnetic resonance imaging in humans, an area in the superior frontal sulcus was identified that is specialized for spatial working memory. This area is located more superiorly and posteriorly in the human than in the monkey brain, which may explain why it was not recognized previously.
    BibTeX:
    @article{Courtney1998,
      author = {Courtney, SM and Petit, L and Maisog, JM and Ungerleider, LG and Haxby, JV},
      title = {An area specialized for spatial working memory in human frontal cortex},
      journal = {SCIENCE},
      year = {1998},
      volume = {279},
      number = {5355},
      pages = {1347-1351}
    }
    
    Courtney, S., Ungerleider, B., Keil, K. & Haxby, J. Transient and sustained activity in a distributed neural system for human working memory {1997} NATURE
    Vol. {386}({6625}), pp. {608-611} 
    article  
    Abstract: Working memory involves the short-term maintenance of an active representation of information so that it is available for further processing. Visual working memory tasks, in which subjects retain the memory of a stimulus over brief delays, require both the perceptual encoding of the stimulus and the subsequent maintenance of its representation after the stimulus is removed from view. Such tasks activate multiple areas in visual and prefrontal cortices(1-9). To delineate the roles these areas play in perception and working memory maintenance, we used functional magnetic resonance imaging (fMRI) to obtain dynamic measures of neural activity related to different components of a face working memory task-non-selective transient responses to visual stimuli, selective transient responses to faces, and sustained responses over memory delays. Three occipitotemporal areas in the ventral object vision pathway had mostly transient responses to stimuli, indicating their predominant role in perceptual processing, whereas three prefrontal areas demonstrated sustained activity over memory delays, indicating their predominant role in working memory. This distinction, however, was not absolute. Additionally, the visual areas demonstrated different degrees of selectivity, and the prefrontal areas demonstrated different strengths of sustained activity, revealing a continuum of functional specialization, from occipital through multiple prefrontal areas, regarding each area's relative contribution to perceptual and mnemonic processing.
    BibTeX:
    @article{Courtney1997,
      author = {Courtney, SM and Ungerleider, BG and Keil, K and Haxby, JV},
      title = {Transient and sustained activity in a distributed neural system for human working memory},
      journal = {NATURE},
      year = {1997},
      volume = {386},
      number = {6625},
      pages = {608-611}
    }
    
    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. 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}}
    }
    
    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}}
    }
    
    D'Esposito, M., Aguirre, G., Zarahn, E., Ballard, D., Shin, R. & Lease, J. Functional MRI studies of spatial and nonspatial working memory {1998} COGNITIVE BRAIN RESEARCH
    Vol. {7}({1}), pp. {1-13} 
    article  
    Abstract: Single-unit recordings in monkeys have revealed neurons in the lateral prefrontal cortex that increase their firing during a delay between the presentation of information and its later use in behavior. Based on monkey lesion and neurophysiology studies, it has been proposed that a dorsal region of lateral prefrontal cortex is necessary for temporary storage of spatial information whereas a more ventral region is necessary for the maintenance of nonspatial information. Functional neuroimaging studies, however, have not clearly demonstrated such a division in humans. We present here an analysis of all reported human functional neuroimaging studies plotted onto a standardized brain. This analysis did not find evidence for a dorsal/ventral subdivision of prefrontal cortex depending on the type of material held in working memory, but a hemispheric organization was suggested (i.e., left-nonspatial; right-spatial). We also performed functional MRT studies in 16 normal subjects during two tasks designed to probe either nonspatial or spatial working memory, respectively. A group and subgroup analysis revealed similarly located activation in right middle frontal gyrus (Brodmann's area 46) in both spatial and nonspatial [working memory-control] subtractions. Based on another model of prefrontal organization [M. Petrides, Frontal lobes and behavior, Cur. Opin. Neurobiol., 4 (1994) 207-211], a reconsideration of the previous imaging Literature data suggested that a dorsal/ventral subdivision of prefrontal cortex may depend upon the type of processing performed upon the information held in working memory. (C) 1998 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{D'Esposito1998,
      author = {D'Esposito, M and Aguirre, GK and Zarahn, E and Ballard, D and Shin, RK and Lease, J},
      title = {Functional MRI studies of spatial and nonspatial working memory},
      journal = {COGNITIVE BRAIN RESEARCH},
      year = {1998},
      volume = {7},
      number = {1},
      pages = {1-13}
    }
    
    D'Esposito, M., Postle, B., Ballard, D. & Lease, J. Maintenance versus manipulation of information held in working memory: An event-related fMRI study {1999} BRAIN AND COGNITION
    Vol. {41}({1}), pp. {66-86} 
    article  
    Abstract: One model of the functional organization of lateral prefrontal cortex (PFC) in primates posits that this region is organized in a dorsal/ventral fashion subserving spatial and object working memory, respectively. Alternatively, it has been proposed that a dorsal/ventral subdivision of lateral PFC instead reflects the type of processing performed upon information held in working memory. We tested this hypothesis using an event-related fMRI method that can discriminate among functional changes occurring during temporally separated behavioral subcomponents of a single trial. Subjects performed a delayed-response task with two types of trials in which they were required to: (1) retain a sequence of letters across the delay period (maintenance) or (2) reorder the sequence into alphabetical order across the delay period (manipulation). In each subject, activity during the delay period was found in both dorsolateral and ventrolateral PFC in both types of trials. However, dorsolateral PFC activity was greater in manipulation trials. These findings are consistent with the processing model of the functional organization of working memory in PFC. (C) 1999 Academic Press.
    BibTeX:
    @article{D'Esposito1999,
      author = {D'Esposito, M and Postle, BR and Ballard, D and Lease, J},
      title = {Maintenance versus manipulation of information held in working memory: An event-related fMRI study},
      journal = {BRAIN AND COGNITION},
      year = {1999},
      volume = {41},
      number = {1},
      pages = {66-86}
    }
    
    Damasio, A. The somatic marker hypothesis and the possible functions of the prefrontal cortex {1996} PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
    Vol. {351}({1346}), pp. {1413-1420} 
    article  
    Abstract: In this article I discuss a hypothesis, known as the somatic marker hypothesis, which I believe is relevant to the understanding of processes of human reasoning and decision making. The ventromedial sector of the prefrontal cortices is critical to the operations postulated here, but the hypothesis does not necessarily apply to prefrontal cortex as a whole and should not be seen as an attempt to unify frontal lobe functions under a single mechanism. The key idea in the hypothesis is that `marker' signals influence the processes of response to stimuli, at multiple levels of operation, some of which occur overtly (consciously, `in mind') and some of which occur covertly (non-consciously, in a non-minded manner). The marker signals arise in bioregulatory processes, including those which express themselves in emotions and feelings, but are not necessarily confined to those alone. This is the reason why the markers are termed somatic: they relate to body-state structure and regulation even when they do not arise in the body proper but rather in the brain's representation of the body. Examples of the covert action of `marker' signals are the undeliberated inhibition of a response learned previously; the introduction of a bias in the selection of an aversive or appetitive mode of behaviour, or in the otherwise deliberate evaluation of varied option-outcome scenarios. Examples of overt action include the conscious `qualifying' of certain option-outcome scenarios as dangerous or advantageous. The hypothesis rejects attempts to limit human reasoning and decision making to mechanisms relying, in an exclusive and unrelated manner, on either conditioning alone or cognition alone.
    BibTeX:
    @article{Damasio1996,
      author = {Damasio, AR},
      title = {The somatic marker hypothesis and the possible functions of the prefrontal cortex},
      journal = {PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES},
      year = {1996},
      volume = {351},
      number = {1346},
      pages = {1413-1420}
    }
    
    Damoiseaux, J.S., Rombouts, S.A.R.B., Barkhof, F., Scheltens, P., Stam, C.J., Smith, S.M. & Beckmann, C.F. Consistent resting-state networks across healthy subjects {2006} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {103}({37}), pp. {13848-13853} 
    article DOI  
    Abstract: Functional MRI (fMRI) can be applied to study the functional connectivity of the human brain. It has been suggested that fluctuations in the blood oxygenation level-dependent (BOLD) signal during rest reflect the neuronal baseline activity of the brain, representing the state of the human brain in the absence of goal-directed neuronal action and external input, and that these slow fluctuations correspond to functionally relevant resting-state networks. Several studies on resting fMRI have been conducted, reporting an apparent similarity between the identified patterns. The spatial consistency of these resting patterns, however, has not yet been evaluated and quantified. In this study, we apply a data analysis approach called tensor probabilistic independent component analysis to resting-state fMRI data to find coherencies that are consistent across subjects and sessions. We characterize and quantify the consistency of these effects by using a bootstrapping approach, and we estimate the BOLD amplitude modulation as well as the voxel-wise cross-subject variation. The analysis found 10 patterns with potential functional relevance, consisting of regions known to be involved in motor function, visual processing, executive functioning, auditory processing, memory, and the so-called default-mode network, each with BOLD signal changes up to 3 In general, areas with a high mean percentage BOLD signal are consistent and show the least variation around the mean. These findings show that the baseline activity of the brain is consistent across subjects exhibiting significant temporal dynamics, with percentage BOLD signal change comparable with the signal changes found in task-related experiments.
    BibTeX:
    @article{Damoiseaux2006,
      author = {Damoiseaux, J. S. and Rombouts, S. A. R. B. and Barkhof, F. and Scheltens, P. and Stam, C. J. and Smith, S. M. and Beckmann, C. F.},
      title = {Consistent resting-state networks across healthy subjects},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {2006},
      volume = {103},
      number = {37},
      pages = {13848-13853},
      doi = {{10.1073/pnas.0601417103}}
    }
    
    Davachi, L., Mitchell, J. & Wagner, A. Multiple routes to memory: Distinct medial temporal lobe processes build item and source memories {2003} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {100}({4}), pp. {2157-2162} 
    article DOI  
    Abstract: A central function of memory is to permit an organism to distinguish between stimuli that have been previously encountered and those that are novel. Although the medial temporal lobe (which includes the hippocampus and surrounding perirhinal, parahippocampal, and entorhinal cortices) is known to be crucial for recognition memory, controversy remains regarding how the specific subregions within the medial temporal lobe contribute to recognition. We used event-related functional MRI to examine the relation between activation in distinct medial temporal lobe subregions during memory formation and the ability (i) to later recognize an item as previously encountered (item recognition) and (it) to later recollect specific contextual details about the prior encounter (source recollection). Encoding activation in hippocampus and in posterior parahippocampal cortex predicted later source recollection, but was uncorrelated with item recognition. In contrast, encoding activation in perirhinal cortex predicted later item recognition, but not subsequent source recollection. These outcomes suggest that the subregions within the medial temporal lobe subserve distinct, but complementary, learning mechanisms.
    BibTeX:
    @article{Davachi2003,
      author = {Davachi, L and Mitchell, JP and Wagner, AD},
      title = {Multiple routes to memory: Distinct medial temporal lobe processes build item and source memories},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {2003},
      volume = {100},
      number = {4},
      pages = {2157-2162},
      doi = {{10.1073/pnas.0337195100}}
    }
    
    Davidson, R. Affective style and affective disorders: Perspectives from affective neuroscience {1998} COGNITION & EMOTION
    Vol. {12}({3}), pp. {307-330} 
    article  
    Abstract: Individual differences in emotional reactivity or affective style can be fruitfully decomposed into more elementary constituents. Several separable features of affective style are identified such as the threshold for reactivity, the peak amplitude of response, the rise time to peak and the recovery time. The latter two characteristics constitute components of affective chronometry. The circuitry that underlies two fundamental forms of motivation and emotion-approach and withdrawal related processes-is described. Data on individual differences in functional activity in certain components of these circuits are next reviewed, with an emphasis on the nomological network of associations surrounding individual differences in asymmetric prefrontal activation. The relevance of such differences for understanding the nature of the affective dysfunction in affective disorders is then considered. The article ends by considering what the prefrontal cortex ``does'' in certain components of affective style and highlights some of the important questions for future research.
    BibTeX:
    @article{Davidson1998,
      author = {Davidson, RJ},
      title = {Affective style and affective disorders: Perspectives from affective neuroscience},
      journal = {COGNITION & EMOTION},
      year = {1998},
      volume = {12},
      number = {3},
      pages = {307-330}
    }
    
    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., Jackson, D. & Kalin, N. Emotion, plasticity, context, and regulation: Perspectives from affective neuroscience {2000} PSYCHOLOGICAL BULLETIN
    Vol. {126}({6, Sp. Iss. SI}), pp. {890-909} 
    article DOI  
    Abstract: The authors present an overview of the neural bases of emotion. They underscore the role of the prefrontal cortex (PFC) and amygdala in 2 brood approach- and withdrawal-related emotion systems. Components and measures of affective style are identified. Emphasis is given to affective chronometry and a role for the PFC in this process is proposed. Plasticity in the central circuitry of emotion is considered, and implications of data showing experience-induced changes in the hippocampus for understanding psychopathology and stress-related symptoms are discussed. Two key forms of affective plasticity are described-context and regulation. A role for the hippocampus in context-dependent normal and dysfunctional emotional responding is proposed. Finally, implications of these data for understanding the impact on neural circuitry of interventions to promote positive affect and on mechanisms that govern health and disease are considered.
    BibTeX:
    @article{Davidson2000a,
      author = {Davidson, RJ and Jackson, DC and Kalin, NH},
      title = {Emotion, plasticity, context, and regulation: Perspectives from affective neuroscience},
      journal = {PSYCHOLOGICAL BULLETIN},
      year = {2000},
      volume = {126},
      number = {6, Sp. Iss. SI},
      pages = {890-909},
      doi = {{10.1037//0033-2909.126.6.890}}
    }
    
    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., KAHN, R., KO, G. & DAVIDSON, M. DOPAMINE IN SCHIZOPHRENIA - A REVIEW AND RECONCEPTUALIZATION {1991} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {148}({11}), pp. {1474-1486} 
    article  
    Abstract: Objective: The initial hypothesis that schizophrenia is a manifestation of hyperdopaminergia has recently been faulted. However, several new findings suggest that abnormal, although not necessarily excessive, dopamine activity is an important factor in schizophrenia. The authors discuss these findings and their implications. Method: All published studies regarding dopamine and schizophrenia and all studies on the role of dopamine in cognition were reviewed. Attention has focused on post-mortem studies, positron emission tomography, neuroleptic drug actions, plasma levels of the dopamine metabolite homovanillic acid (HVA), and cerebral blood flow. Results: Evidence, particularly from intracellular recording studies in animals and plasma HVA measurements, suggests that neuroleptics act by reducing dopamine activity in mesolimbic dopamine neurons. Post-mortem studies have shown high dopamine and HVA concentrations in various subcortical brain regions and greater than normal dopamine receptor densities in the brains of schizophrenic patients. On the other hand, the negative/deficit symptom complex of schizophrenia may be associated with low dopamine activity in the prefrontal cortex. Recent animal and human studies suggest that prefrontal dopamine neurons inhibit subcortical dopamine activity. The authors hypothesize that schizophrenia is characterized by abnormally low prefrontal dopamine activity (causing deficit symptoms) leading to excessive dopamine activity in mesolimbic dopamine neurons (causing positive symptoms). Conclusions: The possible co-occurrence of high and low dopamine activity in schizophrenia has implications for the conceptualization of dopamine's role in schizophrenia. It would explain the concurrent presence of negative and positive symptoms. This hypothesis is testable and has important implications for treatment of schizophrenia and schizophrenia spectrum disorders.
    BibTeX:
    @article{DAVIS1991,
      author = {DAVIS, KL and KAHN, RS and KO, G and DAVIDSON, M},
      title = {DOPAMINE IN SCHIZOPHRENIA - A REVIEW AND RECONCEPTUALIZATION},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {1991},
      volume = {148},
      number = {11},
      pages = {1474-1486}
    }
    
    De Bellis, M., Keshavan, M., Clark, D., Casey, B., Giedd, J., Boring, A., Frustaci, K. & Ryan, N. Developmental traumatology Part II: Brain development {1999} BIOLOGICAL PSYCHIATRY
    Vol. {45}({10}), pp. {1271-1284} 
    article  
    Abstract: Background: Previous investigations suggest that maltreated children with a diagnosis of posttraumatic stress disorder (PTSD) evidence alterations of biological stress systems. Increased levels of catecholaminergic neurotransmitters and steroid hormones during traumatic experiences in childhood could conceivably adversely affect brain development. Methods: In this study, 44 maltreated children and adolescents with PTSD and 61 matched controls underwent comprehensive psychiatric and neuropsychological assessments and an anatomical magnetic resonance imaging (MRI) brain scan. Results: PTSD subjects had smaller intracranial and cerebral volumes than marched controls, The total midsagittal area of corpus callosum and middle and posterior regions remained smaller; while right, left, and total lateral ventricles were proportionally larger than controls, after adjustment for intracranial volume. Brain volume robustly and positively correlated with age of onset of PTSD trauma and negatively correlated with duration of abuse. Symptoms of intrusive thoughts, avoidance, hyperarousal or dissociation correlated positively with ventricular volume, and negatively with brain volume and total corpus callosum and regional measures, Significant gender by diagnosis effect revealed greater corpus callosum al-ea reduction in maltreated males with PTSD and a trend for greater cerebral volume reduction than maltreated females with PTSD. The predicted decrease in hippocampal volume seen in adult PTSD was not seen in these subjects. Conclusions: These data suggest that the overwhelming stress of maltreatment experiences in childhood is associated with adverse brain development. Biol Psychiatry 1999;45:1271-1284 (C) 1999 Society of Biological Psychiatry.
    BibTeX:
    @article{DeBellis1999,
      author = {De Bellis, MD and Keshavan, MS and Clark, DB and Casey, BJ and Giedd, JN and Boring, AM and Frustaci, K and Ryan, ND},
      title = {Developmental traumatology Part II: Brain development},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {1999},
      volume = {45},
      number = {10},
      pages = {1271-1284}
    }
    
    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{Dehaene2001a,
      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}
    }
    
    Dehaene, S., Naccache, L., Cohen, L., Le Bihan, D., Mangin, J., Poline, J. & Riviere, D. Cerebral mechanisms of word masking and unconscious repetition priming {2001} NATURE NEUROSCIENCE
    Vol. {4}({7}), pp. {752-758} 
    article  
    Abstract: We used functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs) to visualize the cerebral processing of unseen masked words. Within the areas associated with conscious reading, masked words activated left extrastriate, fusiform and precentral areas. Furthermore, masked words reduced the amount of activation evoked by a subsequent conscious presentation of the same word. In the left fusiform gyrus, this repetition suppression phenomenon was independent of whether the prime and target shared the same case, indicating that case-independent information about letter strings was extracted unconsciously. In comparison to an unmasked situation, however, the activation evoked by masked words was drastically reduced and was undetectable in prefrontal and parietal areas, correlating with participants' inability to report the masked words.
    BibTeX:
    @article{Dehaene2001,
      author = {Dehaene, S and Naccache, L and Cohen, L and Le Bihan, D and Mangin, JF and Poline, JB and Riviere, D},
      title = {Cerebral mechanisms of word masking and unconscious repetition priming},
      journal = {NATURE NEUROSCIENCE},
      year = {2001},
      volume = {4},
      number = {7},
      pages = {752-758}
    }
    
    Delacourte, A., David, J., Sergeant, N., Buee, L., Wattez, A., Vermersch, P., Ghozali, F., Fallet-Bianco, C., Pasquier, F., Lebert, F., Petit, H. & Di Menza, C. The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer's disease {1999} NEUROLOGY
    Vol. {52}({6}), pp. {1158-1165} 
    article  
    Abstract: Objective: To determine the spatiotemperal mapping of neurofibrillary: degeneration (NFD) in normal aging and the different stages of AD. Background: The pathophysiologic significance of AD lesions, namely amyloid plaques and neurofibrillary tangles, is still unclear, especially their intel relationship and their link with cognitive impairment, Methods: The study included 130 patients of various ages and different cognitive statuses, from nondemented control subjects (n = 60, prospective study) to patients with severe definite,AD. Paired helical filaments (PHF)-tau and A beta were used as biochemical and histologic markers of NFD and amyloid plaques, respectively. Results: NFD with PHF-tau was systematically? present in variable amounts in the hippocampal region of nondemented patients age >75 years. When NFD was found in other brain areas, it was always along a stereotyped, sequential, hierarchical pathway. The progression was categorized into 10 stages according to the brain regions affected: transentorhinal cortex (SI), entorhinal (S2), hippocampus (S3), anterior temporal cortex (S4), inferior temporal cortex (S5), medium temporal cortex (S6), polymodal association areas (prefrontal, parietal inferior? temporal superior) (S7), unimodal areas (S8), primary motor (S9a) or sensory (S9b, S9c) areas, and all neocortical areas (S10). Up to stage 6? the disease could be asymptomatic. In all cases studied here, stage 7 individuals with two polymodal association areas affected by tau pathologic states were cognitively impaired. Conclusions: The relationship between NFD and Alzheimer-type dementia, and the criteria for a biochemical diagnosis of AD, are documented, and an association between AD and the extent of NFD in defined brain areas is shown.
    BibTeX:
    @article{Delacourte1999,
      author = {Delacourte, A and David, JP and Sergeant, N and Buee, L and Wattez, A and Vermersch, P and Ghozali, F and Fallet-Bianco, C and Pasquier, F and Lebert, F and Petit, H and Di Menza, C},
      title = {The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer's disease},
      journal = {NEUROLOGY},
      year = {1999},
      volume = {52},
      number = {6},
      pages = {1158-1165}
    }
    
    DEMB, J., DESMOND, J., WAGNER, A., VAIDYA, C., GLOVER, G. & GABRIELI, J. SEMANTIC ENCODING AND RETRIEVAL IN THE LEFT INFERIOR PREFRONTAL CORTEX - A FUNCTIONAL MRI STUDY OF TASK-DIFFICULTY AND PROCESS SPECIFICITY {1995} JOURNAL OF NEUROSCIENCE
    Vol. {15}({9}), pp. {5870-5878} 
    article  
    Abstract: Prefrontal cortical function was examined during semantic encoding and repetition priming using functional magnetic resonance imaging (fMRI), a noninvasive technique for localizing regional changes in blood oxygenation, a correlate of neural activity. Words studied in a semantic (deep) encoding condition were better remembered than words studied in both easier and more difficult nonsemantic (shallow) encoding conditions, with difficulty indexed by response time. The left inferior prefrontal cortex (LIPC) (Brodmann's areas 45, 46, 47) showed increased activation during semantic encoding relative to nonsemantic encoding regardless of the relative difficulty of the nonsemantic encoding task. Therefore, LIPC activation appears to be related to semantic encoding and not task difficulty. Semantic encoding decisions are performed faster the second time words are presented. This represents semantic repetition priming, a facilitation in semantic processing for previously encoded words that is not dependent on intentional recollection. The same LIPC area activated during semantic encoding showed decreased activation during repeated semantic encoding relative to initial semantic encoding of the same words. This decrease in activation during repeated encoding was process specific; it occurred when words were semantically reprocessed but not when words were nonsemantically reprocessed. The results were apparent in both individual and averaged functional maps. These findings suggest that the LIPC is part of a semantic executive system that contributes to the on-line retrieval of semantic information.
    BibTeX:
    @article{DEMB1995,
      author = {DEMB, JB and DESMOND, JE and WAGNER, AD and VAIDYA, CJ and GLOVER, GH and GABRIELI, JDE},
      title = {SEMANTIC ENCODING AND RETRIEVAL IN THE LEFT INFERIOR PREFRONTAL CORTEX - A FUNCTIONAL MRI STUDY OF TASK-DIFFICULTY AND PROCESS SPECIFICITY},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1995},
      volume = {15},
      number = {9},
      pages = {5870-5878}
    }
    
    Depue, R. & Collins, P. Neurobiology of the structure of personality: Dopamine, facilitation of incentive motivation, and extraversion {1999} BEHAVIORAL AND BRAIN SCIENCES
    Vol. {22}({3}), pp. {491+} 
    article  
    Abstract: Extraversion has two central characteristics: (1) interpersonal engagement, which consists of affiliation (enjoying and valuing close interpersonal bonds, being warm and affectionate) and agency (being socially dominant, enjoying leadership roles, being assertive, being exhibitionistic, and having a sense of potency in accomplishing goals) and (2) impulsivity, which emerges from the interaction of extraversion and a second, independent trait (constraint). Agency is a more general motivational disposition that includes dominance, ambition, mastery, efficacy, and achievement. Positive affect (a combination of positive feelings and motivation) is closely associated with extraversion. Extraversion is accordingly based on positive incentive motivation. Parallels between extraversion (particularly its agency component) and a mammalian behavioral approach system based on positive incentive motivation implicate a neuroanatomical network and modulatory neurotransmitters in the processing of incentive motivation. A corticolimbic-striatal-thalamic network (1) integrates the salient incentive context in the medial orbital cortex, amygdala, and hippocampus; (2) encodes the intensity of incentive stimuli in a motive circuit composed of the nucleus accumbens, ventral pallidum, and ventral tegmental area dopamine projection system; and (3) creates an incentive motivational state that can be transmitted to the motor system. Individual differences in the functioning of this network arise from functional variation in the Ventral tegmental area dopamine projections, which are directly involved in coding the intensity of incentive motivation. The animal evidence suggests that there are three neurodevelopmental sources of individual differences in dopamine: genetic, ``experience-expectant,'' and ``experience-dependent.'' Individual differences in dopamine promote variation in the heterosynaptic plasticity that enhances the connection between incentive con text and incentive motivation and behavior. Our psychobiological threshold model explains the effects of individual differences in dopamine transmission on behavior, and their relation to personality traits is discussed.
    BibTeX:
    @article{Depue1999,
      author = {Depue, RA and Collins, PF},
      title = {Neurobiology of the structure of personality: Dopamine, facilitation of incentive motivation, and extraversion},
      journal = {BEHAVIORAL AND BRAIN SCIENCES},
      year = {1999},
      volume = {22},
      number = {3},
      pages = {491+}
    }
    
    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}
    }
    
    Desimone, R. Neural mechanisms for visual memory and their role in attention {1996} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {93}({24}), pp. {13494-13499} 
    article  
    Abstract: Recent studies show that neuronal mechanisms for learning and memory both dynamically modulate and permanently alter the representations of visual stimuli in the adult monkey cortex, Three commonly observed neuronal effects in memory-demanding tasks are repetition suppression, enhancement, and delay activity, In repetition suppression, repeated experience with the same visual stimulus leads to both short- and long-term suppression of neuronal responses in subpopulations of visual neurons, Enhancement works in an opposite fashion, in that neuronal responses are enhanced for objects with learned behavioral relevance, Delay activity is found in tasks in which animals are required to actively hold specific information `'on-line'' for short periods, Repetition suppression appears to he an intrinsic property of visual cortical areas such as inferior temporal cortex and is thought to be important for perceptual learning and priming, By contrast, enhancement and delay activity mag depend on feedback to temporal cortex from prefrontal cortex and are thought to be important for working memory, All of these mnemonic effects on neuronal responses bias the competitive interactions that take place between stimulus representations in the cortex when there is more than one stimulus in the visual field, As a result, memory will often determine the winner of these competitions and, thus, will determine which stimulus is attended.
    BibTeX:
    @article{Desimone1996,
      author = {Desimone, R},
      title = {Neural mechanisms for visual memory and their role in attention},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1996},
      volume = {93},
      number = {24},
      pages = {13494-13499},
      note = {Colloquium on Memory - Recording Experience in Cells and Circuits, IRVINE, CA, FEB 17-20, 1996}
    }
    
    DESIMONE, R. & DUNCAN, J. NEURAL MECHANISMS OF SELECTIVE VISUAL-ATTENTION {1995} ANNUAL REVIEW OF NEUROSCIENCE
    Vol. {18}, pp. {193-222} 
    article  
    BibTeX:
    @article{DESIMONE1995,
      author = {DESIMONE, R and DUNCAN, J},
      title = {NEURAL MECHANISMS OF SELECTIVE VISUAL-ATTENTION},
      journal = {ANNUAL REVIEW OF NEUROSCIENCE},
      year = {1995},
      volume = {18},
      pages = {193-222}
    }
    
    DESPOSITO, M., DETRE, J., ALSOP, D., SHIN, R., ATLAS, S. & GROSSMAN, M. THE NEURAL BASIS OF THE CENTRAL EXECUTIVE SYSTEM OF WORKING-MEMORY {1995} NATURE
    Vol. {378}({6554}), pp. {279-281} 
    article  
    Abstract: Working memory refers to a system for temporary storage and manipulation of information in the brain, a function critical for a wide range of cognitive operations. It has been proposed that working memory includes a central executive system (CES) to control attention and information flow to and from verbal and spatial short-term memory buffers(1). Although the prefrontal cortex is activated during both verbal and spatial passive working memory tasks(2-8), the brain regions involved in the CES component of working memory have not been identified. We have used functional magnetic resonance imaging (fMRI) to examine brain activation during the concurrent performance of two tasks, which is expected to engage the CES. Activation of the prefrontal cortex was observed when both tasks are performed together, but not when they are performed separately. These results support the view that the prefrontal cortex is involved in human working memory.
    BibTeX:
    @article{DESPOSITO1995,
      author = {DESPOSITO, M and DETRE, JA and ALSOP, DC and SHIN, RK and ATLAS, S and GROSSMAN, M},
      title = {THE NEURAL BASIS OF THE CENTRAL EXECUTIVE SYSTEM OF WORKING-MEMORY},
      journal = {NATURE},
      year = {1995},
      volume = {378},
      number = {6554},
      pages = {279-281}
    }
    
    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}
    }
    
    Di Chiara, G. Nucleus accumbens shell and core dopamine: differential role in behavior and addiction {2002} BEHAVIOURAL BRAIN RESEARCH
    Vol. {137}({1-2}), pp. {75-114} 
    article  
    Abstract: Drug addiction can be conceptualized as a disturbance of behavior motivated by drug-conditioned incentives. This abnormality has been explained by Incentive-Sensitization and Allostatic-Counteradaptive theories as the result of non-associative mechanisms acting at the stage of the expression of incentive motivation and responding for drug reinforcement. Each one of these theories, however, does not account per se for two basic properties of the motivational disturbance of drug addiction: (1) focussing on drug-at the expenses of non-drug-incentives; (2) virtual irreversibility. To account for the above aspects we have proposed an associative learning hypothesis. According to this hypothesis the basic disturbance of drug addiction takes place at the stage of acquisition of motivation and in particular of Pavlovian incentive learning. Drugs share with non-drug rewards the property of stimulating dopamine (DA) transmission in the nucleus accumbens shell but this effect does not undergo habituation upon repeated drug exposure, as instead is the case of non-drug rewards. Repetitive, non-decremental stimulation of DA transmission by drugs in the nucleus accumbens septi (NAc) shell abnormally strenghtens stimulus-drug associations. Thus, stimuli contingent upon drug reward acquire powerful incentive properties after a relatively limited number of predictive associations with the drug and become particularly resistant to extinction. Non-contingent occurrence of drug-conditioned incentive cues or contexts strongly facilitates and eventually reinstates drug self-administration. Repeated drug exposure also induces a process of sensitization of drug-induced stimulation of DA transmission in the NAc core. The precise significance of this adaptive change for the mechanism of drug addiction is unclear given the complexity and uncertainties surrounding the role of NAc core DA in responding but might be more directly related to instrumental performance. (C) 2002 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{DiChiara2002,
      author = {Di Chiara, G},
      title = {Nucleus accumbens shell and core dopamine: differential role in behavior and addiction},
      journal = {BEHAVIOURAL BRAIN RESEARCH},
      year = {2002},
      volume = {137},
      number = {1-2},
      pages = {75-114}
    }
    
    Di Chiara, G. Role of dopamine in the behavioural actions of nicotine related to addiction {2000} EUROPEAN JOURNAL OF PHARMACOLOGY
    Vol. {393}({1-3, Sp. Iss. SI}), pp. {295-314} 
    article  
    Abstract: Experimental impairment of dopamine function by 6-hydroxydopamine lesions or by dopamine receptor antagonists shows that dopamine is involved in nicotine's discriminative stimulus properties, nicotine-induced facilitation of intracranial self-stimulation, intravenous nicotine self-administration, nicotine conditioned place-preference and nicotine-induced disruption of latent inhibition. Therefore, nicotine depends on dopamine for those behavioural effects that are most relevant for its reinforcing properties and are likely to be the basis of the abuse liability of tobacco smoke. On the other hand, in vivo monitoring studies show that nicotine stimulates dopamine transmission in specific brain areas and in particular, in the shell of the nucleus accumbens and in areas of the extended amygdala. These effects of nicotine resemble those of a reward like food except that nicotine-induced release of dopamine does not undergo single-trial, long-lasting habituation. It is speculated that repeated non-habituating stimulation of dopamine release by nicotine in the nucleus accumbens shell abnormally facilitates associative stimulus-reward learning. Acute effects of nicotine on dopamine transmission undergo acute and chronic tolerance; with repeated, discontinuous exposure, sensitization of nicotine-induced stimulation of dopamine release in the nucleus accumbens core takes place while the response in the shell is reduced. It is speculated that these adaptive changes are the substrate of a switch from abnormal incentive responding controlled by consequences (action-outcome responding) into abnormal habit responding, triggered by conditional stimuli and automatically driven by action schemata relatively independent from nicotine reward. These two modalities might coexist, being utilized alternatively in relation to the availability of tobacco. Unavailability of tobacco disrupts the automatic, implicit modality of abnormal habit responding switching responding into the explicit, conscious modality of incentive drug-seeking and craving. (C) 2000 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{DiChiara2000,
      author = {Di Chiara, G},
      title = {Role of dopamine in the behavioural actions of nicotine related to addiction},
      journal = {EUROPEAN JOURNAL OF PHARMACOLOGY},
      year = {2000},
      volume = {393},
      number = {1-3, Sp. Iss. SI},
      pages = {295-314},
      note = {Congress on Neuronal Nicotinic Receptors - From Stucture to Therapeutics, VENICE, ITALY, OCT 01-04, 1999}
    }
    
    Dias, R., Robbins, T. & Roberts, A. Dissociation in prefrontal cortex of affective and attentional shifts {1996} NATURE
    Vol. {380}({6569}), pp. {69-72} 
    article  
    Abstract: The prefrontal cortex is implicated in such human characteristics as volition, planning, abstract reasoning and affect(1-6). Frontal-lobe damage can cause disinhibition such that the behaviour of a subject is guided by previously acquired responses that are inappropriate to the current situation(7-9). Here we demonstrate that disinhibition, or a loss of inhibitory control, can be selective for particular cognitive functions and that different regions of the prefrontal cortex provide inhibitory control in different aspects of cognitive processing. Thus, whereas damage to the lateral prefrontal cortex (Brodmann's area 9) in monkeys causes a loss of inhibitory control in attentional selection, damage to the orbito-frontal cortex in monkeys causes a loss of inhibitory control in `affective' processing, thereby impairing the ability to alter behaviour in response to fluctuations in the emotional significance of stimuli. These findings not only support the view that the prefrontal cortex has multiple functions, but also provide evidence for the distribution of different cognitive functions within specific regions of prefrontal cortex.
    BibTeX:
    @article{Dias1996,
      author = {Dias, R and Robbins, TW and Roberts, AC},
      title = {Dissociation in prefrontal cortex of affective and attentional shifts},
      journal = {NATURE},
      year = {1996},
      volume = {380},
      number = {6569},
      pages = {69-72}
    }
    
    DICHIARA, G. THE ROLE OF DOPAMINE IN DRUG-ABUSE VIEWED FROM THE PERSPECTIVE OF ITS ROLE IN MOTIVATION {1995} DRUG AND ALCOHOL DEPENDENCE
    Vol. {38}({2}), pp. {95-137} 
    article  
    Abstract: Drugs of abuse share with conventional reinforcers the activation of specific neural pathways in the CNS that are the substrate of their motivational properties. Dopamine is recognized as the transmitter of one such neural pathway, being involved in at least three major aspects of motivation: modulation of motivational state, acquisition (incentive learning) and expression of incentive properties by motivational stimuli. Drugs of abuse of different pharmacological classes stimulate in the low dose range dopamine transmission particularly in the ventral striatum. Apart from psychostimulants, the evidence that stimulation of dopamine transmission by drugs of abuse provides the primary motivational stimulus for drug self-administration is either unconvincing or negative. However, stimulation of dopamine transmission is essential for the activational properties of drugs of abuse and might be instrumental for the acquisition of responding to drug-related incentive stimuli (incentive learning). Dopamine is involved in the induction and in the expression of behavioural sensitization by repeated exposure to various drugs of abuse. Sensitization to the dopamine-stimulant properties of specific drug classes leading to facilitation of incentive learning of drug-related stimuli might account for the strong control over behaviour exerted by these stimuli in the addiction state. Withdrawal from drugs of abuse results in a reduction in basal dopamine transmission in vivo and in reduced responding for conventional reinforcers. Although these changes are likely to be the expression of a state of dependence of the dopamine system their contribution to the motivational state of drug addiction is unclear.
    BibTeX:
    @article{DICHIARA1995,
      author = {DICHIARA, G},
      title = {THE ROLE OF DOPAMINE IN DRUG-ABUSE VIEWED FROM THE PERSPECTIVE OF ITS ROLE IN MOTIVATION},
      journal = {DRUG AND ALCOHOL DEPENDENCE},
      year = {1995},
      volume = {38},
      number = {2},
      pages = {95-137}
    }
    
    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. Emotion, cognition, and behavior {2002} SCIENCE
    Vol. {298}({5596}), pp. {1191-1194} 
    article  
    Abstract: Emotion is central to the quality and range of everyday human experience. The neurobiological substrates of human emotion are now attracting increasing interest within the neurosciences motivated, to a considerable extent, by advances in functional neuroimaging techniques. An emerging theme is the question of how emotion interacts with and influences other domains of cognition, in particular attention, memory, and reasoning. The psychological consequences and mechanisms underlying the emotional modulation of cognition provide the focus of this article.
    BibTeX:
    @article{Dolan2002,
      author = {Dolan, RJ},
      title = {Emotion, cognition, and behavior},
      journal = {SCIENCE},
      year = {2002},
      volume = {298},
      number = {5596},
      pages = {1191-1194}
    }
    
    Drevets, W. Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders {2001} CURRENT OPINION IN NEUROBIOLOGY
    Vol. {11}({2}), pp. {240-249} 
    article  
    Abstract: Neuroimaging technology has provided unprecedented opportunities for elucidating the anatomical correlates of major depression. The knowledge gained from imaging research and from the postmortem studies that have been guided by imaging data is catalyzing a paradigm shift in which primary mood disorders are conceptualized as illnesses that involve abnormalities of brain structure, as well as of brain function. These data suggest specific hypotheses regarding the neural mechanisms underlying pathological emotional processing in mood disorders. They particularly support a role for dysfunction within the prefrontal cortical and striatal systems that normally modulate limbic and brainstem structures involved in mediating emotional behavior in the pathogenesis of depressive symptoms.
    BibTeX:
    @article{Drevets2001,
      author = {Drevets, WC},
      title = {Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders},
      journal = {CURRENT OPINION IN NEUROBIOLOGY},
      year = {2001},
      volume = {11},
      number = {2},
      pages = {240-249}
    }
    
    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., Price, J., Simpson, J., Todd, R., Reich, T., Vannier, M. & Raichle, M. Subgenual prefrontal cortex abnormalities in mood disorders {1997} NATURE
    Vol. {386}({6627}), pp. {824-827} 
    article  
    Abstract: Pathological disturbances of mood may follow a `bipolar' course, in which normal moods alternate with both depression and mania, or a `unipolar' course, in which only depression occurs(1-3). Both bipolar and unipolar disorders can be heritable illnesses associated with neurochemical, neuroendocrine and autonomic abnormalities. The neurobiological basis for these abnormalities has not been established(2,3). Using positron emission tomographic (PET) images of cerebral blood flow and rate of glucose metabolism to measure brain activity, we have now localized an area of abnormally decreased activity in the pre-frontal cortex ventral to the germ of the corpus callosum in both familial bipolar depressives and familial unipolar depressives. This decrement in activity was at least partly explained by a corresponding reduction in cortical volume(4) as magnetic resonance imaging (MRI) demonstrated reductions in the mean grey matter volume in the same area of 39 and 48% in the bipolar and unipolar samples, respectively. This region has previously been implicated in the mediation of emotional and autonomic responses to socially significant or provocative stimuli, and in the modulation of the neurotransmitter systems targeted by antidepressant drugs(3,5-10).
    BibTeX:
    @article{Drevets1997,
      author = {Drevets, WC and Price, JL and Simpson, JR and Todd, RD and Reich, T and Vannier, M and Raichle, ME},
      title = {Subgenual prefrontal cortex abnormalities in mood disorders},
      journal = {NATURE},
      year = {1997},
      volume = {386},
      number = {6627},
      pages = {824-827}
    }
    
    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}
    }
    
    DREVETS, W., VIDEEN, T., PRICE, J., PRESKORN, S., CARMICHAEL, S. & RAICHLE, M. A FUNCTIONAL ANATOMICAL STUDY OF UNIPOLAR DEPRESSION {1992} JOURNAL OF NEUROSCIENCE
    Vol. {12}({9}), pp. {3628-3641} 
    article  
    Abstract: The functional neuroanatomy of unipolar major depression was investigated using positron emission tomography to measure differences in regional cerebral blood flow (BF). A relatively homogeneous subject group was obtained using criteria for familial pure depressive disease (FPDD), which are based upon family history as well as upon symptoms and course. Because of the absence of certain knowledge about the pathophysiology of mood disorders and their underlying functional neuroanatomy, we used data obtained from the subtraction of composite images from one-half of depressed and control subjects to identify candidate regions of interest. The major cortical region defined in this manner was statistically tested on a second set of subjects. Using this strategy, we found increased BF in an area that extended from the left ventrolateral prefrontal cortex onto the medial prefrontal cortical surface. Based upon the connectivity between these portions of the prefrontal cortex and the amygdala and evidence that the amygdala is involved in emotional modulation, activity was measured in the left amygdala and found to be significantly increased in the depressed group. A separate group of subjects with FPDD who were currently asymptomatic were also imaged to determine whether these findings represented abnormalities associated with the depressed state, or with a trait difference that might underlie the tendency to become depressed. Only the depressed group had increased activity in the left prefrontal cortex, suggesting that this abnormality represents a state marker of FPDD. Both the depressed and the remitted groups demonstrated increased activity in the left amygdala, though this difference achieved significance only in the depressed group. This suggests that the abnormality involving the left amygdala may represent a trait marker of FPDD, though further assessment in a larger sample size is necessary to establish this. These data along with other evidence suggest that a circuit involving the prefrontal cortex, amygdala, and related parts of the striatum, pallidum, and medial thalamus is involved in the functional neuroanatomy of depression.
    BibTeX:
    @article{DREVETS1992,
      author = {DREVETS, WC and VIDEEN, TO and PRICE, JL and PRESKORN, SH and CARMICHAEL, ST and RAICHLE, ME},
      title = {A FUNCTIONAL ANATOMICAL STUDY OF UNIPOLAR DEPRESSION},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1992},
      volume = {12},
      number = {9},
      pages = {3628-3641}
    }
    
    Dubois, B. & Pillon, B. Cognitive deficits in Parkinson's disease {1997} JOURNAL OF NEUROLOGY
    Vol. {244}({1}), pp. {2-8} 
    article  
    Abstract: Neuropsychological investigations of patients with Parkinson's disease have shown specific impairments even in the early stages of the disease, which include deficit of behavioural regulation in sorting or planning tasks, defective use oi memory stores, and impaired manipulation of internal representation of visuospatial stimuli. These deficits, reported in a disease which predominantly involves subcortical structures, have drawn attention to a potential role of the basal ganglia in cognitive processes. Given the modulatory role of the basal ganglia. these disorders might result from more fundamental deficits concerning the allocation of attentional resources. the temporal organization of behaviour, the maintenance of representations in working memory of the self-elaboration of internal strategies, ail of which resemble dysfunctions of processes that are commonly considered to be controlled by the frontal lobes. This suggests a functional continuity or complementarity between the basal ganglia and association areas of the prefrontal cortex. The recent description in primates of segregated loops that interconnect discrete regions of the caudate nucleus to the dorsolateral and orbitofrontal regions of the prefrontal cortex via the thalamus may give some support to this hypothesis. Alternatively, degeneration of the ascending cholinergic and catecholaminergic neuronal systems may contribute, at least in part, It, the occurrence of this frontal-lobe-like symptomatology associated with Parkinson's disease.
    BibTeX:
    @article{Dubois1997,
      author = {Dubois, B and Pillon, B},
      title = {Cognitive deficits in Parkinson's disease},
      journal = {JOURNAL OF NEUROLOGY},
      year = {1997},
      volume = {244},
      number = {1},
      pages = {2-8}
    }
    
    Dubois, B., Slachevsky, A., Litvan, I. & Pillon, B. The FAB - A frontal assessment battery at bedside {2000} NEUROLOGY
    Vol. {55}({11}), pp. {1621-1626} 
    article  
    Abstract: Objective: To devise a short bedside cognitive and behavioral battery to assess frontal lobe functions. Methods: The designed battery consists of six subtests exploring the following: conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy. It takes approximately 10 minutes to administer. The authors studied 42 normal subjects and 121 patients with various degrees of frontal lobe dysfunction (PD, n = 24; multiple system atrophy, n = 6; corticobasal degeneration, n = 21; progressive supranuclear palsy, n = 47; frontotemporal dementia, n = 25). Results: The Frontal Assessment Battery scores correlated with the Mattis Dementia Rating Scale scores (rho = 0.82, p < 0.01) and with the number of criteria (rho = 0.77, p < 0.01) and perseverative errors (rho = 0.68, p < 0.01) of the Wisconsin Card Sorting Test. These variables accounted for 79% of the variance in a stepwise multiple regression, whereas age or Mini-Mental State Examination scores had no significant influence. There was good interrater reliability ( = 0.87, p < 0.001), internal consistency (Cronbach's coefficient alpha 0.78), and discriminant validity (89.1% of eases correctly identified in a discriminant analysis of patients and controls). Conclusion: The Frontal Assessment Battery is easy to administer at bedside and is sensitive to frontal lobe dysfunction.
    BibTeX:
    @article{Dubois2000,
      author = {Dubois, B and Slachevsky, A and Litvan, I and Pillon, B},
      title = {The FAB - A frontal assessment battery at bedside},
      journal = {NEUROLOGY},
      year = {2000},
      volume = {55},
      number = {11},
      pages = {1621-1626}
    }
    
    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}
    }
    
    Duman, R., Malberg, J. & Thome, J. Neural plasticity to stress and antidepressant treatment {1999} BIOLOGICAL PSYCHIATRY
    Vol. {46}({9}), pp. {1181-1191} 
    article  
    Abstract: Adaptations at the cellular and molecular levels in response to stress and antidepressant treatment could represent a form of neural plasticity that contributes to the pathophysiology and treatment of depression. At the cellular level, atrophy and death of stress-vulnerable neurons in the hippocampus, as well as decreased neurogenesis of hippocampal neurons, has been reported in preclinical studies. Clinical studies also provide evidence for atrophy and cell death in the hippocampus, as well as the prefrontal cortex. It is possible that antidepressant treatment could oppose these adverse cellular effects, which may be regarded as a loss of neural plasticity, by blocking or reversing the atrophy of hippocampal neurons and by increasing cell survival and function. The molecular mechanisms underlying these effects are discussed, including the role of the cAMP signal transduction cascade and neurotrophic factors. (C) 1999 Society of Biological Psychiatry.
    BibTeX:
    @article{Duman1999,
      author = {Duman, RS and Malberg, J and Thome, J},
      title = {Neural plasticity to stress and antidepressant treatment},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {1999},
      volume = {46},
      number = {9},
      pages = {1181-1191},
      note = {Conference on Norepinephrine - New Vistas for and Old Neurotransmitter, KEY WEST, FLORIDA, MAR, 1999}
    }
    
    Duman, R. & Monteggia, L. A neurotrophic model for stress-related mood disorders {2006} BIOLOGICAL PSYCHIATRY
    Vol. {59}({12}), pp. {1116-1127} 
    article DOI  
    Abstract: There is a growing body of evidence demonstrating that stress decreases the expression of brain-derived neurotrophic factor (BDNF) in limbic structures that control mood and that antidepressant treatment reverses or blocks the effects of stress. Decreased levels of BDNF, as well as other neruotropbic factors, could contribute to the atrophy of certain limbic structures, including the hippocampus and prefrontal cortex that has been observed in depressed subjects, Conversely, the neurotrophic actions of antidepressants could reverse neuronal atrophy and cell loss and thereby contribute to the therapeutic actions of these treatments. This review provides a critical examination of the neurotropbic hypothesis of depression that has evolved from this work, including analysis of preclinical cellular (adult neurogenesis) and behavioral models of depression and antidepressant actions, as well as clinical neuroimaging and postmortem studies. Although there are some limitations, the results of these studies are consistent with the hypothesis that decreased expression of BDNF and possibly other growth factors contributes to depression and that upregulation of BDNF plays a role in the actions of antidepressant treatment.
    BibTeX:
    @article{Duman2006,
      author = {Duman, RS and Monteggia, LM},
      title = {A neurotrophic model for stress-related mood disorders},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {2006},
      volume = {59},
      number = {12},
      pages = {1116-1127},
      doi = {{10.1016/j.biopsych.2006.02.013}}
    }
    
    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}
    }
    
    Egan, M., Goldberg, T., Kolachana, B., Callicott, J., Mazzanti, C., Straub, R., Goldman, D. & Weinberger, D. Effect of COMT Val(108/158) Met genotype on frontal lobe function and risk for schizophrenia {2001} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {98}({12}), pp. {6917-6922} 
    article  
    Abstract: Abnormalities of prefrontal cortical function are prominent features of schizophrenia and have been associated with genetic risk, suggesting that susceptibility genes for schizophrenia may impact on the molecular mechanisms of prefrontal function. A potential susceptibility mechanism involves regulation of prefrontal dopamine, which modulates the response of prefrontal neurons during working memory. We examined the relationship of a common functional polymorphism (Va(108/158) Met) in the catechol-O-methyltransferase (COMT) gene, which accounts for a 4-fold variation in enzyme activity and dopamine catabolism, with both prefrontally mediated cognition and prefrontal cortical physiology. In 175 patients with schizophrenia, 219 unaffected siblings, and 55 controls, COMT genotype was related in allele dosage fashion to performance on the Wisconsin Card Sorting Test of executive cognition and explained 4% of variance (P = 0.001) in frequency of perseverative errors. Consistent with other evidence that dopamine enhances prefrontal neuronal function, the load of the low-activity Met allele predicted enhanced cognitive performance. We then examined the effect of COMT genotype on prefrontal physiology during a working memory task in three separate subgroups(n = 11-16) assayed with functional MRI, Met allele load consistently predicted a more efficient physiological response in prefrontal cortex. Finally, in a family-based association analysis of 104 trios, we found a significant increase in transmission of the Val allele to the schizophrenic offspring. These data suggest that the COMT Val allele, because it increases prefrontal dopamine catabolism, impairs prefrontal cognition and physiology. and by this mechanism slightly increases risk for schizophrenia.
    BibTeX:
    @article{Egan2001,
      author = {Egan, MF and Goldberg, TE and Kolachana, BS and Callicott, JH and Mazzanti, CM and Straub, RE and Goldman, D and Weinberger, DR},
      title = {Effect of COMT Val(108/158) Met genotype on frontal lobe function and risk for schizophrenia},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {2001},
      volume = {98},
      number = {12},
      pages = {6917-6922}
    }
    
    Eichenbaum, H. A cortical-hippocampal system for declarative memory {2000} NATURE REVIEWS NEUROSCIENCE
    Vol. {1}({1}), pp. {41-50} 
    article  
    Abstract: Recent neurobiological studies have begun to reveal the cognitive and neural coding mechanisms that underlie declarative memory - our ability to recollect everyday events and factual knowledge. These studies indicate that the critical circuitry involves bidirectional connections between the neocortex, the parahippocampal region and the hippocampus. Each of these areas makes a unique contribution to memory processing. Widespread high-order neocortical areas provide dedicated processors for perceptual, motor or cognitive information that is influenced by other components of the system. The parahippocampal region mediates convergence of this information and extends the persistence of neocortical memory representations. The hippocampus encodes the sequences of places and events that compose episodic memories, and links them together through their common elements. Here describe how these mechanisms work together to create and re-create fully networked representations of previous experiences and knowledge about the world.
    BibTeX:
    @article{Eichenbaum2000,
      author = {Eichenbaum, H},
      title = {A cortical-hippocampal system for declarative memory},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2000},
      volume = {1},
      number = {1},
      pages = {41-50}
    }
    
    Eichenbaum, H., Dudchenko, P., Wood, E., Shapiro, M. & Tanila, H. The hippocampus, memory, and place cells: Is it spatial memory or a memory space? {1999} NEURON
    Vol. {23}({2}), pp. {209-226} 
    article  
    BibTeX:
    @article{Eichenbaum1999,
      author = {Eichenbaum, H and Dudchenko, P and Wood, E and Shapiro, M and Tanila, H},
      title = {The hippocampus, memory, and place cells: Is it spatial memory or a memory space?},
      journal = {NEURON},
      year = {1999},
      volume = {23},
      number = {2},
      pages = {209-226}
    }
    
    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., Dolan, R. & Frith, C. Dissociable functions in the medial and lateral orbitofrontal cortex: Evidence from human neuroimaging studies {2000} CEREBRAL CORTEX
    Vol. {10}({3}), pp. {308-317} 
    article  
    Abstract: Recent imaging studies show that the orbitofrontal cortex (OFC) is activated during a wide variety of paradigms, including guessing tasks, simple delayed matching tasks and sentence completion. We suggest that, as with other regions of the prefrontal cortex, activity in the OFC is most likely to be observed when there is insufficient information available to determine the appropriate course of action. In these circumstances the OFC, rather than other prefrontal regions, is more likely to be activated when the problem of what to do next is best solved by taking into account the likely reward value of stimuli and responses, rather than their identity or location. We suggest that selection of stimuli on the basis of their familiarity and responses on the basis of a feeling of `rightness' are also examples of selection on the basis of reward value. Within the OFC, the lateral regions are more likely to be involved when the action selected requires the suppression of previously rewarded responses.
    BibTeX:
    @article{Elliott2000a,
      author = {Elliott, R and Dolan, RJ and Frith, CD},
      title = {Dissociable functions in the medial and lateral orbitofrontal cortex: Evidence from human neuroimaging studies},
      journal = {CEREBRAL CORTEX},
      year = {2000},
      volume = {10},
      number = {3},
      pages = {308-317}
    }
    
    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}
    }
    
    Engel, A., Fries, P. & Singer, W. Dynamic predictions: Oscillations and synchrony in top-down processing {2001} NATURE REVIEWS NEUROSCIENCE
    Vol. {2}({10}), pp. {704-716} 
    article  
    Abstract: Classical theories of sensory processing view the brain as a passive, stimulus-driven device. By contrast, more recent approaches emphasize the constructive nature of perception, viewing it as an active and highly selective process. Indeed, there is ample evidence that the processing of stimuli is controlled by top-down influences that strongly shape the intrinsic dynamics of thalamocortical networks and constantly create predictions about forthcoming sensory events. We discuss recent experiments indicating that such predictions might be embodied in the temporal structure of both stimulus-evoked and ongoing activity, and that synchronous oscillations are particularly important in this process. Coherence among subthreshold membrane potential fluctuations could be exploited to express selective functional relationships during states of expectancy or attention, and these dynamic patterns could allow the grouping and selection of distributed neuronal responses for further processing.
    BibTeX:
    @article{Engel2001,
      author = {Engel, AK and Fries, P and Singer, W},
      title = {Dynamic predictions: Oscillations and synchrony in top-down processing},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2001},
      volume = {2},
      number = {10},
      pages = {704-716}
    }
    
    Engle, R., Tuholski, S., Laughlin, J. & Conway, A. Working memory, short-term memory, and general fluid intelligence: A latent-variable approach {1999} JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL
    Vol. {128}({3}), pp. {309-331} 
    article  
    Abstract: A study was conducted in which 133 participants performed 11 memory tasks (some thought to reflect working memory and some thought to reflect short-term memory), 2 tests of general fluid intelligence, and the Verbal and Quantitative Scholastic Aptitude Tests. Structural equation modeling suggested that short-term and working memories reflect separate but highly related constructs and that many of the tasks used in the literature as working memory tasks reflect a common construct. Working memory shows a strong connection to fluid intelligence, but short-term memory does not. A theory of working memory capacity and general fluid intelligence is proposed: The authors argue that working memory capacity and fluid intelligence reflect the ability to keep a representation active, particularly in the face of interference and distraction. The authors also discuss the relationship of this capability to controlled attention, and the functions of the prefrontal cortex.
    BibTeX:
    @article{Engle1999,
      author = {Engle, RW and Tuholski, SW and Laughlin, JE and Conway, ARA},
      title = {Working memory, short-term memory, and general fluid intelligence: A latent-variable approach},
      journal = {JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL},
      year = {1999},
      volume = {128},
      number = {3},
      pages = {309-331}
    }
    
    Everitt, B., Parkinson, J., Olmstead, M., Arroyo, M., Robledo, P. & Robbins, T. Associative processes in addiction and reward - The role of amygdala-ventral striatal subsystems {1999}
    Vol. {877}ADVANCING FROM THE VENTRAL STRIATUM TO THE EXTENDED AMYGDALA - IMPLICATIONS FOR NEUROPSYCHIATRY AND DRUG ABUSE: IN HONOR OF LENNART HEIMER , pp. {412-438} 
    inproceedings  
    Abstract: Only recently have the functional implications of the organization of the ventral striatum, amygdala, and related limbic-cortical structures, and their neuroanatomical interactions begun to be clarified. Processes of activation and reward have long been associated with the NAcc and its dopamine innervation, but the precise relationships between these constructs have remained elusive. We have sought to enrich our understanding of the special role of the ventral striatum in coordinating the contribution of different functional subsystems to confer flexibility, as well as coherence and vigor, to goal-directed behavior, through different forms of associative learning. Such appetitive behavior comprises many subcomponents, some of which we have isolated in these experiments to reveal that, not surprisingly, the mechanisms by which an animal sequences responding to reach a goal are complex. The data reveal how the different components, pavlovian approach (or sign-tracking), conditioned reinforcement (whereby pavlovian stimuli control goal-directed action), and also more general response-invigorating processes (often called ``activation,'' ``stress,'' or ``drive'') may be integrated within the ventral striatum through convergent interactions of the amygdala, other limbic cortical structures, and the mesolimbic dopamine system to produce coherent behavior. The position is probably not far different when considering aversively motivated behavior. Although it may be necessary to employ simplified, even abstract, paradigms for isolating these mechanisms, their concerted action can readily be appreciated in an adaptive, functional setting, such as the responding by rats for intravenous cocaine under a second-order schedule of reinforcement. Here, the interactions of primary reinforcement, psychomotor activation, pavlovian conditioning, and the control that drug cues exert over the integrated drug-seeking response can be seen to operate both serially and concurrently. The power of our analytic techniques for understanding complex motivated behavior has been evident for some time. However, the crucial point is that we are now able to map these components with increasing certainty onto discrete amygdaloid, and other Limbic cortical-ventral striatal subsystems. The neural dissection of these mechanisms also serves an important theoretical purpose in helping to validate the various hypothetical constructs and further developing theory. Major challenges remain, not the least of which is an understanding of the operation of the ventral striatum together with its dopaminergic innervation and its interactions with the basolateral amygdala, hippocampal formation, and prefrontal cortex at a more mechanistic, neuronal level.
    BibTeX:
    @inproceedings{Everitt1999,
      author = {Everitt, BJ and Parkinson, JA and Olmstead, MC and Arroyo, M and Robledo, P and Robbins, TW},
      title = {Associative processes in addiction and reward - The role of amygdala-ventral striatal subsystems},
      booktitle = {ADVANCING FROM THE VENTRAL STRIATUM TO THE EXTENDED AMYGDALA - IMPLICATIONS FOR NEUROPSYCHIATRY AND DRUG ABUSE: IN HONOR OF LENNART HEIMER },
      year = {1999},
      volume = {877},
      pages = {412-438},
      note = {Conference on Advancing from the Ventral Striatum to the Extended Amygdala - Implications for Neuropsychiatry and Drug Abuse-In Honor of Lennart Heimer, CHARLOTTESVILLE, VIRGINIA, OCT 18-21, 1998}
    }
    
    Everitt, B. & Robbins, T. Neural systems of reinforcement for drug addiction: from actions to habits to compulsion {2005} NATURE NEUROSCIENCE
    Vol. {8}({11}), pp. {1481-1489} 
    article DOI  
    Abstract: Drug addiction is increasingly viewed as the endpoint of a series of transitions from initial drug use-when a drug is voluntarily taken because it has reinforcing, often hedonic, effects-through loss of control over this behavior, such that it becomes habitual and ultimately compulsive. Here we discuss evidence that these transitions depend on interactions between pavlovian and instrumental learning processes. We hypothesize that the change from voluntary drug use to more habitual and compulsive drug use represents a transition at the neural level from prefrontal cortical to striatal control over drug seeking and drug taking behavior as well as a progression from ventral to more dorsal domains of the striatum, involving its dopaminergic innervation. These neural transitions may themselves depend on the neuroplasticity in both cortical and striatal structures that is induced by chronic self-administration of drugs.
    BibTeX:
    @article{Everitt2005,
      author = {Everitt, BJ and Robbins, TW},
      title = {Neural systems of reinforcement for drug addiction: from actions to habits to compulsion},
      journal = {NATURE NEUROSCIENCE},
      year = {2005},
      volume = {8},
      number = {11},
      pages = {1481-1489},
      doi = {{10.1038/nn1579}}
    }
    
    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}
    }
    
    Fiez, J. Phonology, semantics, and the role of the left inferior prefrontal cortex {1997} HUMAN BRAIN MAPPING
    Vol. {5}({2}), pp. {79-83} 
    article  
    BibTeX:
    @article{Fiez1997,
      author = {Fiez, JA},
      title = {Phonology, semantics, and the role of the left inferior prefrontal cortex},
      journal = {HUMAN BRAIN MAPPING},
      year = {1997},
      volume = {5},
      number = {2},
      pages = {79-83}
    }
    
    Fiez, J., Raife, E., Balota, D., Schwarz, J., Raichle, M. & Petersen, S. A positron emission tomography study of the short-term maintenance of verbal information {1996} JOURNAL OF NEUROSCIENCE
    Vol. {16}({2}), pp. {808-822} 
    article  
    Abstract: Positron emission tomography (PET) was used to investigate the functional brain anatomy associated with the short-term maintenance of linguistic information. Subjects were asked to retain five related words, unrelated words, or pseudowords silently for the duration of a 40 sec PET scan. When brain activity during these short-term maintenance tasks was compared with a visual fixation control task, increases were found bilaterally in the dorsolateral prefrontal cortex and cerebellum, and medially in the supplementary motor area. Furthermore, effects of stimulus condition and recall performance were found in the left frontal operculum. To investigate the role of articulatory systems in the maintenance of verbal information, regional activation was compared across the maintenance tasks and a covert articulation task (silent counting). The cerebellum was active in both task conditions, whereas activation in prefrontal regions was specific to the maintenance condition. Conversely, greater activation was found in a left middle insular region in the silent counting than in the maintenance tasks. Based on converging results in this and previous studies, dorsolateral prefrontal cortical areas appear to contribute to the maintenance of both verbal and nonverbal information, whereas left frontal opercular regions appear to be involved specifically in the rehearsal of verbal material. Contrary to results found in other studies of working memory, activation was not found in the inferior parietal cortex, suggesting that this area is involved in aspects of stimulus encoding and retrieval, which were minimized in the present study.
    BibTeX:
    @article{Fiez1996,
      author = {Fiez, JA and Raife, EA and Balota, DA and Schwarz, JP and Raichle, ME and Petersen, SE},
      title = {A positron emission tomography study of the short-term maintenance of verbal information},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1996},
      volume = {16},
      number = {2},
      pages = {808-822}
    }
    
    Filipek, P., SemrudClikeman, M., Steingard, R., Renshaw, P., Kennedy, D. & Biederman, J. Volumetric MRI analysis comparing subjects having attention-deficit hyperactivity disorder with normal controls {1997} NEUROLOGY
    Vol. {48}({3}), pp. {589-601} 
    article  
    Abstract: Objective: To test by MRI-based morphometry the a priori hypotheses that developmental anomalies exist in attention-deficit hyperactivity disorder (ADHD) in left caudate and right prefrontal/frontal/ and/or posterior parietal hemispheric regions, in accord with neurochemical, neuronal circuitry and attentional network hypotheses, and prior imaging studies. Design: Case-control study. Setting: Academic medical center, Participants: Fifteen male subjects with ADHD without comorbid diagnoses (aged 12.4 +/- 3.4 years) and 15 male normal controls (aged 14.4 +/- 3.4), group-matched for age, IQ, and handedness. Main outcome measures: Global and hemispheric regional volumes (in cm(3)) of cerebral hemispheres, cortex, white matter, ventricles, caudate, lenticulate, central gray nuclei, insula, amygdala, and hippocampus. Results: Despite similar hemispheric volumes, ADHD subjects had smaller volumes of (1) left total caudate and caudate head (p < 0.04), with reversed asymmetry (p < 0.03); (2) right anterior-superior (frontal) region en bloc(p < 0.03) and white matter (p < 0.01); (3) bilateral anterior-inferior region en bloc(p < 0.04); and (4) bilateral retrocallosal (parietal-occipital) region white matter (p < 0.03). Possible structural correlates of ADHD response to stimulants were noted in an exploratory analysis, with the smallest and symmetric caudate, and smallest left anterior-superior cortex volumes found in the responders, but reversed caudate asymmetry and the smallest retrocallosal white matter volumes noted in the nonresponders, Conclusions, This study is the first to report localized hemispheric structural anomalies in ADHD, which are concordant with theoretical models of abnormal frontal-striatal and parietal function, and with possible differing morphologic substrates of response to stimulant medication.
    BibTeX:
    @article{Filipek1997,
      author = {Filipek, PA and SemrudClikeman, M and Steingard, RJ and Renshaw, PF and Kennedy, DN and Biederman, J},
      title = {Volumetric MRI analysis comparing subjects having attention-deficit hyperactivity disorder with normal controls},
      journal = {NEUROLOGY},
      year = {1997},
      volume = {48},
      number = {3},
      pages = {589-601}
    }
    
    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}
    }
    
    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{FLETCHER1995,
      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. & Henson, R. Frontal lobes and human memory - Insights from functional neuroimaging {2001} BRAIN
    Vol. {124}({Part 5}), pp. {849-881} 
    article  
    Abstract: The new functional neuroimaging techniques, PET and functional MRI (fMRI), offer sufficient experimental flexibility and spatial resolution to explore the functional neuroanatomical bases of different memory stages and processes. They have had a particular impact on our understanding of the role of the frontal cortex in memory processing. We review the insights that have been gained, and attempt a synthesis of the findings from functional imaging studies of working memory, encoding in episodic memory and retrieval from episodic memory. Though these different aspects of memory have usually been studied in isolation, we suggest that there is sufficient convergence with respect to frontal activations to make such a synthesis worthwhile. We concentrate in particular on three regions of the lateral frontal cortex-ventro-lateral, dorsolateral and anterior-that are consistently activated in these studies, and attribute these activations to the updating/maintenance of information, the selection/manipulation/monitoring of that information, and the selection of processes/subgoals, respectively. We also acknowledge a number of empirical inconsistencies associated with this synthesis, and suggest possible reasons for these. More generally, we predict that the resolution of questions concerning the functional neuroanatomical subdivisions of the frontal cortex will ultimately depend on a fuller cognitive psychological fractionation of memory control processes, an enterprise that will be guided and tested by experimentation. We expect that the neuroimaging techniques will provide an important part of this enterprise.
    BibTeX:
    @article{Fletcher2001,
      author = {Fletcher, PC and Henson, RNA},
      title = {Frontal lobes and human memory - Insights from functional neuroimaging},
      journal = {BRAIN},
      year = {2001},
      volume = {124},
      number = {Part 5},
      pages = {849-881}
    }
    
    Floresco, S., Seamans, J. & Phillips, A. Selective roles for hippocampal, prefrontal cortical, and ventral striatal circuits in radial-arm maze tasks with or without a delay {1997} JOURNAL OF NEUROSCIENCE
    Vol. {17}({5}), pp. {1880-1890} 
    article  
    Abstract: The hippocampus, the prefrontal cortex, and the ventral striatum form interconnected neural circuits that may underlie aspects of spatial cognition and memory. In the present series of experiments, we investigated functional interactions between these areas in rats during the performance of delayed and nondelayed spatially cued radial-arm maze tasks. The two-phase delayed task consisted of a training phase that provided rats with information about where food would be located on the maze 30 min later during a test phase. The single-phase nondelayed task was identical to the test phase of the delayed task, but in the absence of a training phase rats lacked previous knowledge of the location of food on the maze. Transient inactivation of the ventral CA1/subiculum (vSub) by a bilateral injection of lidocaine disrupted performance on both tasks. Lidocaine injections into the vSub on one side of the brain and the prefrontal cortex on the other transiently disconnected these two brain regions and significantly impaired foraging during the delayed task but not the nondelayed task. Transient disconnections between the vSub and the nucleus accumbens produced the opposite effect, disrupting foraging during the nondelayed task but not during the delayed task. These data suggest that serial transmission of information between the vSub and the prefrontal cortex is required when trial-unique, short-term memory is used to guide prospective search behavior. In contrast, exploratory goal-directed locomotion in a novel situation not requiring previously acquired information about the location of food is dependent on serial transmission between the hippocampus and the nucleus accumbens. These results indicate that different aspects of spatially mediated behavior are subserved by separate, distributed limbic-cortical-striatal networks.
    BibTeX:
    @article{Floresco1997,
      author = {Floresco, SB and Seamans, JK and Phillips, AG},
      title = {Selective roles for hippocampal, prefrontal cortical, and ventral striatal circuits in radial-arm maze tasks with or without a delay},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1997},
      volume = {17},
      number = {5},
      pages = {1880-1890}
    }
    
    Fox, M., Snyder, A., Vincent, J., Corbetta, M., Van Essen, D. & Raichle, M. The human brain is intrinsically organized into dynamic, anticorrelated functional networks {2005} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {102}({27}), pp. {9673-9678} 
    article DOI  
    Abstract: During performance of attention-demanding cognitive tasks, certain regions of the brain routinely increase activity, whereas others routinely decrease activity. In this study, we investigate the extent to which this task-related dichotomy is represented intrinsically in the resting human brain through examination of spontaneous fluctuations in the functional MRI blood oxygen level-dependent signal. We identify two diametrically opposed, widely distributed brain networks on the basis of both spontaneous correlations within each network and anticorrelations between networks. One network consists of regions routinely exhibiting task-related activations and the other of regions routinely exhibiting task-related deactivations. This intrinsic organization, featuring the presence of anticorrelated networks in the absence of overt task performance, provides a critical context in which to understand brain function. We suggest that both task-driven neuronal responses and behavior are reflections of this dynamic, ongoing, functional organization of the brain.
    BibTeX:
    @article{Fox2005,
      author = {Fox, MD and Snyder, AZ and Vincent, JL and Corbetta, M and Van Essen, DC and Raichle, ME},
      title = {The human brain is intrinsically organized into dynamic, anticorrelated functional networks},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {2005},
      volume = {102},
      number = {27},
      pages = {9673-9678},
      doi = {{10.1073/pnas.0504136102}}
    }
    
    Freedman, D., Riesenhuber, M., Poggio, T. & Miller, E. Categorical representation of visual stimuli in the primate prefrontal cortex {2001} SCIENCE
    Vol. {291}({5502}), pp. {312-316} 
    article  
    Abstract: The ability to group stimuli into meaningful categories is a fundamental cognitive process. To explore its neural basis. we trained monkeys to categorize computer-generated stimuli as ``cats'' and ``dogs.'' A morphing system was used to systematically vary stimulus shape and precisely define the category boundary. Neural activity in the Lateral prefrontal cortex reflected the category of visual stimuli, even when a monkey was retrained with the stimuli assigned to new categories.
    BibTeX:
    @article{Freedman2001,
      author = {Freedman, DJ and Riesenhuber, M and Poggio, T and Miller, EK},
      title = {Categorical representation of visual stimuli in the primate prefrontal cortex},
      journal = {SCIENCE},
      year = {2001},
      volume = {291},
      number = {5502},
      pages = {312-316}
    }
    
    Friederici, A. Towards a neural basis of auditory sentence processing {2002} TRENDS IN COGNITIVE SCIENCES
    Vol. {6}({2}), pp. {78-84} 
    article  
    Abstract: Functional dissociations within the neural basis of auditory sentence processing are difficult to specify because phonological, syntactic and semantic information are all involved when sentences are perceived. In this review I argue that sentence processing is supported by a temporo-frontal network. Within this network, temporal regions subserve aspects of identification and frontal regions the building of syntactic and semantic relations. Temporal analyses of brain activation within this network support syntax-first models because they reveal that building of syntactic structure precedes semantic processes and that these interact only during a later stage.
    BibTeX:
    @article{Friederici2002,
      author = {Friederici, AD},
      title = {Towards a neural basis of auditory sentence processing},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      year = {2002},
      volume = {6},
      number = {2},
      pages = {78-84}
    }
    
    FRISTON, K. & FRITH, C. SCHIZOPHRENIA - A DISCONNECTION SYNDROME {1995} CLINICAL NEUROSCIENCE
    Vol. {3}({2}), pp. {89-97} 
    article  
    Abstract: We review the evidence of pathophysiological changes in the prefrontal and temporal cortices of schizophrenic subjects and of abnormal integration of the physiological dynamics in these two regions. The argument we develop is that some schizophrenic phenomena are best understood in terms of abnormal interactions between different areas, not only at the levels of physiology and functional anatomy, but at the level of cognitive and sensorimotor functioning. We discuss recent functional imaging evidence suggesting abnormal prefronto-temporal interactions in relation to a psychological analysis of experiential; symptoms in schizophrenia. Cortico-cortical interactions have been assessed in terms of functional connectivity and eigenimages, using time series of neurophysiological data obtained with positron emission tomography. The results of these analyses suggest that there is a profound disruption of large-scale prefronto-temporal interactions in schizophrenia. These disruptions are particularly relevant if one considers that many positive symptoms of schizophrenia reflect a failure to integrate intrinsically generated behaviour and concurrent perception. (C) 1995 Wiley-Liss, Inc.
    BibTeX:
    @article{FRISTON1995,
      author = {FRISTON, KJ and FRITH, CD},
      title = {SCHIZOPHRENIA - A DISCONNECTION SYNDROME},
      journal = {CLINICAL NEUROSCIENCE},
      year = {1995},
      volume = {3},
      number = {2},
      pages = {89-97}
    }
    
    FRITH, C., FRISTON, K., LIDDLE, P. & FRACKOWIAK, R. WILLED ACTION AND THE PREFRONTAL CORTEX IN MAN - A STUDY WITH PET {1991} PROCEEDINGS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
    Vol. {244}({1311}), pp. {241-246} 
    article  
    Abstract: We used positron emission tomography to contrast changes in cerebral blood flow associated with willed and routine acts. In the six tasks used, volunteers had to make a series of responses to a sequence of stimuli. For the routine acts, each response was completely specified by the stimulus. For the willed acts, the response was open-ended and therefore volunteers had to make a deliberate choice. Willed acts in the two response modalities studied (speaking a word, or lifting a finger) were associated with increased blood flow in the dorsolateral prefrontal cortex (Brodmann area 46). Willed acts were also associated with decreases in blood flow, but the location of these decreases was modality dependent.
    BibTeX:
    @article{FRITH1991,
      author = {FRITH, CD and FRISTON, K and LIDDLE, PF and FRACKOWIAK, RSJ},
      title = {WILLED ACTION AND THE PREFRONTAL CORTEX IN MAN - A STUDY WITH PET},
      journal = {PROCEEDINGS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES},
      year = {1991},
      volume = {244},
      number = {1311},
      pages = {241-246}
    }
    
    FRITH, C., FRISTON, K., LIDDLE, P. & FRACKOWIAK, R. A PET STUDY OF WORD FINDING {1991} NEUROPSYCHOLOGIA
    Vol. {29}({12}), pp. {1137-1148} 
    article  
    Abstract: We have used PET in conjunction with psychological activations to identify cortical areas involved in the intrinsic activation of word representations. In four normal subjects intrinsic generation of a word (verbal fluency) was associated with an increase in left dorsolateral prefrontal cortical activity (BA 46) and a bilateral decrease in activity in auditory and superior temporal cortices. Conversely, when subjects made lexical decisions about words that were heard, there was an increase in superior temporal activity with no change in area 46. We suggest that the superior temporal regions are the site of stored word representations and that inhibitory modulation of these areas by the left prefrontal cortex is the basis of intrinsic word generation.
    BibTeX:
    @article{FRITH1991a,
      author = {FRITH, CD and FRISTON, KJ and LIDDLE, PF and FRACKOWIAK, RSJ},
      title = {A PET STUDY OF WORD FINDING},
      journal = {NEUROPSYCHOLOGIA},
      year = {1991},
      volume = {29},
      number = {12},
      pages = {1137-1148}
    }
    
    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}}
    }
    
    FUNAHASHI, S., BRUCE, C. & GOLDMANRAKIC, P. DORSOLATERAL PREFRONTAL LESIONS AND OCULOMOTOR DELAYED-RESPONSE PERFORMANCE - EVIDENCE FOR MNEMONIC SCOTOMAS {1993} JOURNAL OF NEUROSCIENCE
    Vol. {13}({4}), pp. {1479-1497} 
    article  
    Abstract: The spatial memory functions of the monkey's prefrontal cortex were examined with oculomotor delayed-response (ODR) paradigms that required the animal to remember the spatial location of peripheral visual cues, while maintaining fixation on a central visual target during the presentation of each cue and during a subsequent 1.5-8 sec delay period. Four rhesus monkeys received unilateral or serial prefrontal lesions in and around the principal sulcus after they reached criterion performance on the ODR tasks. Unilateral lesions disrupted the performance of memory-guided eye movements to spatial cues in the visual field contralateral to the hemisphere in which the lesion was placed. Memory-guided eye movements to ipsilateral cues were mildly affected by unilateral lesions, and these lesions had little or no effect on performance in visually guided control tasks. With addition of a second lesion in the opposite hemisphere, the deficit was extended to include the opposite hemifield. The impairment was characterized by eye movements of inappropriate direction, and, excepting the one lesion that extended into the frontal eye field region of the arcuate sulcus, saccadic reaction times and velocities were the same before and after the lesions. The effect of the lesions was delay dependent: performance was rarely altered at the shortest (1.5 sec) delay but became progressively worse as the delay period was lengthened. The present results strengthen the evidence that the delayed-response deficits of monkeys with prefrontal lesions are caused by failure to maintain a transient memory `'trace'' in working memory, and indicate for the first time that working memory mechanisms are lateralized: memories for visuo-spatial coordinates in each hemifield are processed primarily in the contralateral prefrontal cortex. These findings provide evidence for the concept of mnemonic hemianopias and mnemonic scotomas, that is, memory deficits for particular hemifields or visual field locations, unaccompanied by simple sensory or motor deficits.
    BibTeX:
    @article{FUNAHASHI1993a,
      author = {FUNAHASHI, S and BRUCE, CJ and GOLDMANRAKIC, PS},
      title = {DORSOLATERAL PREFRONTAL LESIONS AND OCULOMOTOR DELAYED-RESPONSE PERFORMANCE - EVIDENCE FOR MNEMONIC SCOTOMAS},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1993},
      volume = {13},
      number = {4},
      pages = {1479-1497}
    }
    
    FUNAHASHI, S., BRUCE, C. & GOLDMANRAKIC, P. MNEMONIC CODING OF VISUAL SPACE IN THE MONKEYS DORSOLATERAL PREFRONTAL CORTEX {1989} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {61}({2}), pp. {331-349} 
    article  
    BibTeX:
    @article{FUNAHASHI1989,
      author = {FUNAHASHI, S and BRUCE, CJ and GOLDMANRAKIC, PS},
      title = {MNEMONIC CODING OF VISUAL SPACE IN THE MONKEYS DORSOLATERAL PREFRONTAL CORTEX},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1989},
      volume = {61},
      number = {2},
      pages = {331-349}
    }
    
    FUNAHASHI, S., CHAFEE, M. & GOLDMANRAKIC, P. PREFRONTAL NEURONAL-ACTIVITY IN RHESUS-MONKEYS PERFORMING A DELAYED ANTI-SACCADE TASK {1993} NATURE
    Vol. {365}({6448}), pp. {753-756} 
    article  
    Abstract: PATIENTS with damage to the dorsolateral prefrontal cortex are impaired on cognitive tasks such as the Wisconsin Card Sort Test1, the Stroop Test2 and an anti-saccade paradigm3, in which sensory-guided habitual responses must be suppressed in favour of conceptually or memory-guided responses. We report here recordings from prefrontal neurons in rhesus monkeys trained to perform a delayed anti-saccade task based on tests that have been used with humans3. Activity in the same prefrontal neurons was recorded across conditions when saccades were made toward a remembered target, and also when this prepotent response was suppressed and a saccade in the opposite direction required. Our findings show that most prefrontal neurons code the location of the visual stimulus in working memory, and that this memory can be engaged to suppress as well as prescribe a response. These results establish, in a subset of prefrontal neurons, the iconic nature of the memory code, and suggest a role for visual memory in response suppression.
    BibTeX:
    @article{FUNAHASHI1993,
      author = {FUNAHASHI, S and CHAFEE, MV and GOLDMANRAKIC, PS},
      title = {PREFRONTAL NEURONAL-ACTIVITY IN RHESUS-MONKEYS PERFORMING A DELAYED ANTI-SACCADE TASK},
      journal = {NATURE},
      year = {1993},
      volume = {365},
      number = {6448},
      pages = {753-756}
    }
    
    Fuster, J. The prefrontal cortex - An update: time is of the essence {2001} NEURON
    Vol. {30}({2}), pp. {319-333} 
    article  
    BibTeX:
    @article{Fuster2001,
      author = {Fuster, JM},
      title = {The prefrontal cortex - An update: time is of the essence},
      journal = {NEURON},
      year = {2001},
      volume = {30},
      number = {2},
      pages = {319-333}
    }
    
    FUSTER, J. UNIT-ACTIVITY IN PREFRONTAL CORTEX DURING DELAYED-RESPONSE PERFORMANCE - NEURONAL CORRELATES OF TRANSIENT MEMORY {1973} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {36}({1}), pp. {61-78} 
    article  
    BibTeX:
    @article{FUSTER1973,
      author = {FUSTER, JM},
      title = {UNIT-ACTIVITY IN PREFRONTAL CORTEX DURING DELAYED-RESPONSE PERFORMANCE - NEURONAL CORRELATES OF TRANSIENT MEMORY},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1973},
      volume = {36},
      number = {1},
      pages = {61-78}
    }
    
    Gabrieli, J., Poldrack, R. & Desmond, J. The role of left prefrontal cortex in language and memory {1998} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {95}({3}), pp. {906-913} 
    article  
    Abstract: This article reviews attempts to characterize the mental operations mediated by left inferior prefrontal cortex, especially the anterior and inferior portion of the gyrus, with the functional neuroimaging techniques of positron emission tomography and functional magnetic resonance imaging, Activations in this region occur during semantic, relative to nonsemantic, tasks for the generation of words to semantic cues or the classification of words or pictures into semantic categories, This activation appears in the right prefrontal cortex of people known to be atypically right-hemisphere dominant for language. In this region, activations are associated with meaningful encoding that leads to superior explicit memory for stimuli and deactivations with implicit semantic memory (repetition priming) for words and pictures, New findings are reported showing that patients with global amnesia show deactivations in the same region associated with repetition priming, that activation in this region reflects selection of a response from among numerous relative to few alternatives, and that activations in a portion of this region are associated specifically with semantic relative to phonological processing, It is hypothesized that activations in left inferior prefrontal cortex reflect a domain-specific semantic working memory capacity that is invoked more for semantic than nonsemantic analyses regardless of stimulus modality, more for initial than for repeated semantic analysis of a word or picture, more when a response must be selected from among many than few legitimate alternatives, and that yields superior later explicit memory for experiences.
    BibTeX:
    @article{Gabrieli1998,
      author = {Gabrieli, JDE and Poldrack, RA and Desmond, JE},
      title = {The role of left prefrontal cortex in language and memory},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1998},
      volume = {95},
      number = {3},
      pages = {906-913},
      note = {Colloquium on Neuroimaging of Human Brain Function, IRVINE, CALIFORNIA, MAY 29-31, 1997}
    }
    
    Gallagher, H., Happe, F., Brunswick, N., Fletcher, P., Frith, U. & Frith, C. Reading the mind in cartoons and stories: an fMRI study of `theory of mind' in verbal and nonverbal tasks {2000} NEUROPSYCHOLOGIA
    Vol. {38}({1}), pp. {11-21} 
    article  
    Abstract: Previous functional imaging studies have explored the brain regions activated by tasks requiring `theory of mind'-the attribution of mental states. Tasks used have been primarily verbal, and it has been unclear to what extent different results have reflected different tasks, scanning techniques, or genuinely distinct regions of activation. Here we report results from a functional magnetic resonance imaging study (fMRI) involving two rather different tasks both designed to tap theory of mind, Brain activation during the theory of mind condition of a story task and a cartoon task showed considerable overlap, specifically in the medial prefrontal cortex (paracingulate cortex). These results are discussed in relation to the cognitive mechanisms underpinning our everyday ability to `mind-read'. (C) 1999 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{Gallagher2000,
      author = {Gallagher, HL and Happe, F and Brunswick, N and Fletcher, PC and Frith, U and Frith, CD},
      title = {Reading the mind in cartoons and stories: an fMRI study of `theory of mind' in verbal and nonverbal tasks},
      journal = {NEUROPSYCHOLOGIA},
      year = {2000},
      volume = {38},
      number = {1},
      pages = {11-21}
    }
    
    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}}
    }
    
    Garavan, H., Ross, T. & Stein, E. Right hemispheric dominance of inhibitory control: An event-related functional MRI study {1999} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {96}({14}), pp. {8301-8306} 
    article  
    Abstract: Normal human behavior and cognition are reliant on a person's ability to inhibit inappropriate thoughts, impulses, and actions. The temporal and spatial advantages of event-related functional MRI (fMRI) were exploited to identify cortical regions that showed a transient change in fMRI signal after the withholding of a prepotent motor response. The temporal specificity of the event-related fMRI design also minimized possible contamination from response inhibition errors (i. e., commission errors) and other extraneous processes. Regions identified were strongly lateralized to the right hemisphere and included the middle and inferior frontal gyri, frontal limbic area, anterior insula, and inferior parietal lobe. Contrary to the prominence traditionally given to ventral frontal regions for response inhibition, the results suggest that response inhibition is accomplished by a distributed cortical network.
    BibTeX:
    @article{Garavan1999,
      author = {Garavan, H and Ross, TJ and Stein, EA},
      title = {Right hemispheric dominance of inhibitory control: An event-related functional MRI study},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1999},
      volume = {96},
      number = {14},
      pages = {8301-8306}
    }
    
    GEHRING, W., GOSS, B., COLES, M., MEYER, D. & DONCHIN, E. A NEURAL SYSTEM FOR ERROR-DETECTION AND COMPENSATION {1993} PSYCHOLOGICAL SCIENCE
    Vol. {4}({6}), pp. {385-390} 
    article  
    Abstract: Humans can monitor actions and compensate for errors. Analysis of the human event-related brain potentials (ERPs) accompanying errors provides evidence for a neural process whose activity is specifically associated with monitoring and compensating for erroneous behavior. This error-related activity is enhanced when subjects strive for accurate performance but is diminished when response speed is emphasized at the expense of accuracy. The activity is also related to attempts to compensate for the erroneous behavior.
    BibTeX:
    @article{GEHRING1993,
      author = {GEHRING, WJ and GOSS, B and COLES, MGH and MEYER, DE and DONCHIN, E},
      title = {A NEURAL SYSTEM FOR ERROR-DETECTION AND COMPENSATION},
      journal = {PSYCHOLOGICAL SCIENCE},
      year = {1993},
      volume = {4},
      number = {6},
      pages = {385-390}
    }
    
    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}
    }
    
    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}
    }
    
    George, M., Wassermann, E., Kimbrell, T., Little, J., Williams, W., Danielson, A., Greenberg, B., Hallett, M. & Post, R. Mood improvement following daily left prefrontal repetitive transcranial magnetic stimulation in patients with depression: A placebo-controlled crossover trial {1997} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {154}({12}), pp. {1752-1756} 
    article  
    Abstract: Objective: Preliminary studies have indicated that daily left prefrontal repetitive transcranial magnetic stimulation might have antidepressant activity. The authors sought to confirm this finding by using a double-blind crossover design. Method: Twelve depressed adults received in random order 2 weeks of active treatment (repetitive transcranial magnetic stimulation, 20 Hz at 80% motor threshold) and 2 weeks of sham treatment. Results: Changes from the relevant phase baseline in scores on the 21-item Hamilton depression scale showed that repetitive transcranial magnetic stimulation significantly improved mood over sham treatment. During the active-treatment phase, Hamilton depression scale scores decreased 5 points, while during sham treatment the scores increased or worsened by 3 points. No adverse effects were noted. Conclusions: These placebo-controlled results suggest that daily left prefrontal repetitive transcranial magnetic stimulation has antidepressant activity when administered at these parameters. Further controlled studies are indicated to explore optimal stimulation characteristics and location, potential clinical applications, and possible mechanisms of action.
    BibTeX:
    @article{George1997,
      author = {George, MS and Wassermann, EM and Kimbrell, TA and Little, JT and Williams, WE and Danielson, AL and Greenberg, BD and Hallett, M and Post, RM},
      title = {Mood improvement following daily left prefrontal repetitive transcranial magnetic stimulation in patients with depression: A placebo-controlled crossover trial},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {1997},
      volume = {154},
      number = {12},
      pages = {1752-1756},
      note = {149th Annual Meeting of the American-Psychiatric-Association, NEW YORK, NY, MAY 04-09, 1996}
    }
    
    GEORGE, M., WASSERMANN, E., WILLIAMS, W., CALLAHAN, A., KETTER, T., BASSER, P., HALLETT, M. & POST, R. DAILY REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION (RTMS) IMPROVES MOOD IN DEPRESSION {1995} NEUROREPORT
    Vol. {6}({14}), pp. {1853-1856} 
    article  
    Abstract: CONVERGING evidence points to hypofunction of the left prefrontal cortex in depression. Repetitive transcranial magnetic stimulation (rTMS) activates neurons near the surface of the brain. We questioned whether daily left prefrontal rTMS might improve mood in depressed subjects and report a pilot study of such treatment in six highly medication-resistant depressed inpatients. Depression scores significantly improved for the group as a whole (Hamilton Depression Scores decreased from 23.8 +/- 4.2 (s.d.) at baseline to 17.5 +/- 8.4 after treatment; t = 3.03, 5DF, p = 0.02, two-tailed paired t-test). Two subjects showed robust mood improvement which occurred progressively over the course of several weeks. In one subject, depression symptoms completely remitted for the first time in 3 years. Daily left prefrontal rTMS appears to be safe, well tolerated and may alleviate depression.
    BibTeX:
    @article{GEORGE1995a,
      author = {GEORGE, MS and WASSERMANN, EM and WILLIAMS, WA and CALLAHAN, A and KETTER, TA and BASSER, P and HALLETT, M and POST, RM},
      title = {DAILY REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION (RTMS) IMPROVES MOOD IN DEPRESSION},
      journal = {NEUROREPORT},
      year = {1995},
      volume = {6},
      number = {14},
      pages = {1853-1856}
    }
    
    Gerardin, E., Sirigu, A., Lehericy, S., Poline, J., Gaymard, B., Marsault, C., Agid, Y. & Le Bihan, D. Partially overlapping neural networks for real and imagined hand movements {2000} CEREBRAL CORTEX
    Vol. {10}({11}), pp. {1093-1104} 
    article  
    Abstract: Neuroimagery findings have shown similar cerebral networks associated with imagination and execution of a movement. On the other hand, neuropsychological studies of parietal-lesioned patients suggest that these networks may be at least partly distinct. In the present study, normal subjects were asked to either imagine or execute auditory-cued hand movements. Compared with rest, imagination and execution showed overlapping networks, including bilateral premotor and parietal areas, basal ganglia and cerebellum. However, direct comparison between the two experimental conditions showed that specific cortico-subcortical areas were more engaged in mental simulation, including bilateral premotor, prefrontal, supplementary motor and left posterior parietal areas, and the caudate nuclei. These results suggest that a specific neuronal substrate is involved in the processing of hand motor representations.
    BibTeX:
    @article{Gerardin2000,
      author = {Gerardin, E and Sirigu, A and Lehericy, S and Poline, JB and Gaymard, B and Marsault, C and Agid, Y and Le Bihan, D},
      title = {Partially overlapping neural networks for real and imagined hand movements},
      journal = {CEREBRAL CORTEX},
      year = {2000},
      volume = {10},
      number = {11},
      pages = {1093-1104}
    }
    
    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}
    }
    
    Glantz, L. & Lewis, D. Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia {2000} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {57}({1}), pp. {65-73} 
    article  
    Abstract: Background: The pathophysiological characteristics of schizophrenia appear to involve altered synaptic connectivity in the dorsolateral prefrontal cortex. Given the central role that layer 3 pyramidal neurons play in corticocortical and thalamocortical connectivity, we hypothesized that the excitatory inputs to these neurons are altered in subjects with schizophrenia. Methods: To test this hypothesis, we determined the density of dendritic spines, markers of excitatory inputs, on the basilar dendrites of Golgi-impregnated pyramidal neurons in the superficial and deep portions of layer 3 in the dorsolateral prefrontal cortex (area 46) and in layer 3 of the primary visual cortex (area 17) of 15 schizophrenic subjects, 15 normal control subjects, and 15 nonschizophrenic subjects with a psychiatric illness (referred to as psychiatric subjects). Results: There was a significant effect of diagnosis on spine density only for deep layer 3 pyramidal neurons in area 46 (P = .006). In the schizophrenic subjects, spine density on these neurons was decreased by 23% and 16% compared with the normal control (P = .004) and psychiatric (P = .08) subjects, respectively. In contrast, spine density on neurons in superficial layer 3 in area 46 (P = .09) or in area 17 (P = .08) did not significantly differ across the 3 subject groups. Furthermore, spine density on deep layer 3 neurons in area 46 did not significantly (P = .81) differ between psychiatric subjects treated with antipsychotic agents and normal controls. Conclusion: This region- and disease-specific decrease in dendritic spine density on dorsolateral prefrontal cortex layer 3 pyramidal cells is consistent with the hypothesis that the number of cortical and/or thalamic excitatory inputs to these neurons is altered in subjects with schizophrenia.
    BibTeX:
    @article{Glantz2000,
      author = {Glantz, LA and Lewis, DA},
      title = {Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {2000},
      volume = {57},
      number = {1},
      pages = {65-73}
    }
    
    GLASSMAN, A. CIGARETTE-SMOKING - IMPLICATIONS FOR PSYCHIATRIC-ILLNESS {1993} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {150}({4}), pp. {546-553} 
    article  
    Abstract: Psychiatry has been essentially uninterested in cigarette smoking and nicotine. However, it is the view of this author that both cigarette smoking and smoking cessation are highly relevant to the clinical psychiatrist in the care of patients and that they are potentially a source of important insights into psychopathology. To support that view, the author reviews the evidence that both major depression and depressive symptoms are associated with a high rate of cigarette smoking and that lifetime history of major depression has an adverse impact on smoking cessation. He also reviews the data available on the influence of cigarette smoking cessation on the course of major depression, the relationship between cigarette smoking and other psychiatric diagnoses, particularly schizophrenia, and the neuropharmacology that might underlie these associations. Finally, the implications of these relationships for psychiatry are discussed.
    BibTeX:
    @article{GLASSMAN1993,
      author = {GLASSMAN, AH},
      title = {CIGARETTE-SMOKING - IMPLICATIONS FOR PSYCHIATRIC-ILLNESS},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {1993},
      volume = {150},
      number = {4},
      pages = {546-553}
    }
    
    Gold, J., Carpenter, C., Randolph, C., Goldberg, T. & Weinberger, D. Auditory working memory and Wisconsin Card Sorting Test performance in schizophrenia {1997} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {54}({2}), pp. {159-165} 
    article  
    Abstract: Background: Impaired Wisconsin Card Sorting Test (WCST) performance has been one critical piece of evidence suggesting frontal lobe dysfunction in schizophrenia. However, the specific cognitive processes underlying impaired performance have not been identified. Impaired WCST performance in schizophrenia might in part reflect a fundamental working memory deficit. Method: We examined the performance of 30 normal subjects and 36 patients with schizophrenia on a neuropsychological battery including a novel measure of working memory-letter-number (IN) span. Results: Patients with schizophrenia were impaired on LN span performance, which was also highly correlated with WCST performance (r=0.74). Between-group WCST differences were eliminated when we covaried LN span. Regression analyses suggested that LN span performance predicted the WCST category achieved score, whereas measures of set shifting, verbal fluency, and attention were predictive of perseveration. Conclusion: Working memory may be a critical determinant of one aspect of WCST performance in schizophrenia.
    BibTeX:
    @article{Gold1997,
      author = {Gold, JM and Carpenter, C and Randolph, C and Goldberg, TE and Weinberger, DR},
      title = {Auditory working memory and Wisconsin Card Sorting Test performance in schizophrenia},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1997},
      volume = {54},
      number = {2},
      pages = {159-165}
    }
    
    Gold, P. & Chrousos, G. Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states {2002} MOLECULAR PSYCHIATRY
    Vol. {7}({3}), pp. {254-275} 
    article DOI  
    Abstract: Stress precipitates depression and alters its natural history. Major depression and the stress response share similar phenomena, mediators and circuitries. Thus, many of the features of major depression potentially reflect dysregulations of the stress response. The stress response itself consists of alterations in levels of anxiety, a loss of cognitive and affective flexibility, activation of the hypothalamic-pituitary-ad renal (HPA) axis and autonomic nervous system, and inhibition of vegetative processes that are likely to Impede survival during a life-threatening situation (eg sleep, sexual activity, and endocrine programs for growth and reproduction). Because depression is a heterogeneous illness, we studied two diagnostic sub-types, melancholic and atypical depression. In melancholia, the stress response seems hyperactive, and patients are anxious, dread the future, lose responsiveness to the environment, have insomnia, lose their appetite, and a diurnal variation with depression at its worst in the morning. They also have an activated CRH system and may have diminished activities of the growth hormone and reproductive axes. Patients with atypical depression present with a syndrome that seems the antithesis of melancholia. They are lethargic, fatigued, hyperphagic, hypersomnic, reactive to the environment, and show diurnal variation of depression that is at its best in the morning. In contrast to melancholia, we have advanced several lines of evidence of a down-regulated hypothalamic-pituitary adrenal axis and CRH deficiency In atypical depression, and our data show us that these are of central origin. Given the diversity of effects exerted by CRH and cortisol, the differences in melancholic and atypical depression suggest that studies of depression should examine each subtype separately. In the present paper, we shall first review the mediators and circuitries of the stress system to lay the groundwork for placing in context physiologic and structural alterations in depression that may occur as part of stress system dysfunction.
    BibTeX:
    @article{Gold2002,
      author = {Gold, PW and Chrousos, GP},
      title = {Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states},
      journal = {MOLECULAR PSYCHIATRY},
      year = {2002},
      volume = {7},
      number = {3},
      pages = {254-275},
      doi = {{10.1038/sj/mp/4001032}}
    }
    
    GOLDMAN, P. & ROSVOLD, H. LOCALIZATION OF FUNCTION WITHIN DORSOLATERAL PREFRONTAL CORTEX OF RHESUS MONKEY {1970} EXPERIMENTAL NEUROLOGY
    Vol. {27}({2}), pp. {291-\&} 
    article  
    BibTeX:
    @article{GOLDMAN1970,
      author = {GOLDMAN, PS and ROSVOLD, HE},
      title = {LOCALIZATION OF FUNCTION WITHIN DORSOLATERAL PREFRONTAL CORTEX OF RHESUS MONKEY},
      journal = {EXPERIMENTAL NEUROLOGY},
      year = {1970},
      volume = {27},
      number = {2},
      pages = {291-&}
    }
    
    Goldman-Rakic, P., Muly, E. & Williams, G. D-1 receptors in prefrontal cells and circuits {2000} BRAIN RESEARCH REVIEWS
    Vol. {31}({2-3}), pp. {295-301} 
    article  
    BibTeX:
    @article{Goldman-Rakic2000,
      author = {Goldman-Rakic, PS and Muly, EC and Williams, GV},
      title = {D-1 receptors in prefrontal cells and circuits},
      journal = {BRAIN RESEARCH REVIEWS},
      year = {2000},
      volume = {31},
      number = {2-3},
      pages = {295-301},
      note = {Nobel Symposium 111: Schizophrenia - Pathophysiological Mechanisms, STOCKHOLM, SWEDEN, OCT 01-03, 1998}
    }
    
    GoldmanRakic, P. Regional and cellular fractionation of working memory {1996} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {93}({24}), pp. {13473-13480} 
    article  
    Abstract: This chapter recounts efforts to dissect the cellular and circuit basis of a memory system in the primate cortex with the goal of extending the insights gained from the study of normal brain organization in animal models to an understanding of human cognition and related memory disorders. Primates and humans have developed an extraordinary capacity to process information `'on line,'' a capacity that is widely considered to underlay comprehension, thinking, and so-called executive functions. Understanding the interactions between the major cellular constituents of cortical circuits-pyramidal and nonpyramidal cells-is considered a necessary step in unraveling the cellular mechanisms subserving working memory mechanisms and, ultimately, cognitive processes. Evidence from a variety of sources is accumulating to indicate that dopamine has a major role in regulating the excitability of the cortical circuitry upon which the working memory function of prefrontal cortex depends. Here, I describe several direct and indirect intercellular mechanisms for modulating working memory function in prefrontal cortex based on the localization of dopamine receptors on the distal dendrites and spines of pyramidal cells and on interneurons in the prefrontal cortex. Interactions between monoamines and a compromised cortical circuitry may hold the key to understanding the variety of memory disorders associated with aging and disease.
    BibTeX:
    @article{GoldmanRakic1996,
      author = {GoldmanRakic, PS},
      title = {Regional and cellular fractionation of working memory},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1996},
      volume = {93},
      number = {24},
      pages = {13473-13480},
      note = {Colloquium on Memory - Recording Experience in Cells and Circuits, IRVINE, CA, FEB 17-20, 1996}
    }
    
    GoldmanRakic, P. The prefrontal landscape: Implications of functional architecture for understanding human mentation and the central executive {1996} PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
    Vol. {351}({1346}), pp. {1445-1453} 
    article  
    Abstract: The functional architecture of prefrontal cortex is central to our understanding of human mentation and cognitive prowess. This region of the brain is often treated as an undifferentiated structure, on the one hand, or as a mosaic of psychological faculties, on the other. This paper focuses on the working memory processor as a specialization of prefrontal cortex and argues that the different areas within prefrontal cortex represent iterations of this function for different information domains, including spatial cognition, object cognition and additionally, in humans, semantic processing. According to this parallel processing architecture, the `central executive' could be considered an emergent property of multiple domain-specific processors operating interactively. These processors are specializations of different prefrontal cortical areas, each interconnected both with the domain-relevant long-term storage sites in posterior regions of the cortex and with appropriate output pathways.
    BibTeX:
    @article{GoldmanRakic1996a,
      author = {GoldmanRakic, PS},
      title = {The prefrontal landscape: Implications of functional architecture for understanding human mentation and the central executive},
      journal = {PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES},
      year = {1996},
      volume = {351},
      number = {1346},
      pages = {1445-1453}
    }
    
    GOLDMANRAKIC, P. CELLULAR BASIS OF WORKING-MEMORY {1995} NEURON
    Vol. {14}({3}), pp. {477-485} 
    article  
    BibTeX:
    @article{GOLDMANRAKIC1995,
      author = {GOLDMANRAKIC, PS},
      title = {CELLULAR BASIS OF WORKING-MEMORY},
      journal = {NEURON},
      year = {1995},
      volume = {14},
      number = {3},
      pages = {477-485}
    }
    
    GOLDMANRAKIC, P. WORKING-MEMORY DYSFUNCTION IN SCHIZOPHRENIA {1994} JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES
    Vol. {6}({4}), pp. {348-357} 
    article  
    Abstract: Recent advances in anatomical, behavioral, and physiological techniques have produced new information about the nature of prefrontal function, its cellular basis, and its anatomical underpinnings in nonhuman primates. These findings are changing our views of prefrontal function and providing insight into possible bases for human mental disorder. A major advance is the recognition that various prefrontal areas are engaged in holding information `'on line'' and updating past and current information on a moment-to-moment basis. Studies of animals and of cognitive function in normal, brain-injured, and schizophrenic subjects support the theory that a defect in working memory-the ability to guide behavior by representations-may be the fundamental impairment leading to schizophrenic thought disorder.
    BibTeX:
    @article{GOLDMANRAKIC1994,
      author = {GOLDMANRAKIC, PS},
      title = {WORKING-MEMORY DYSFUNCTION IN SCHIZOPHRENIA},
      journal = {JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES},
      year = {1994},
      volume = {6},
      number = {4},
      pages = {348-357}
    }
    
    GoldmanRakic, P. & Selemon, L. Functional and anatomical aspects of prefrontal pathology in schizophrenia {1997} SCHIZOPHRENIA BULLETIN
    Vol. {23}({3}), pp. {437-458} 
    article  
    Abstract: Clinical and experimental research have provided anatomical, pharmacological, and behavioral evidence for a prominent prefrontal dysfunction in schizophrenia. Negative symptoms and behavioral disorganization in the disorder can be understood as a failure in the working memory functions of the prefrontal cortex by which information is updated on a moment-to-moment basis or retrieved from long-term stores, held in mind, and used to guide behavior by ideas, concepts, and stored knowledge, This article recounts efforts to dissect the cellular and circuit basis of working memory with the goal of extending the insights gained from the study of normal brain organization in animal models to an understanding of the clinical disorder; it includes recent neuropathological findings that indicate that neural dystrophy rather than cell loss predominates in schizophrenia, Evidence from a variety of studies is accumulating to indicate that dopamine has a major role in regulating the excitability of the cortical neurons upon which the working memory function of the prefrontal cortex depends, Interactions between monoamines and a compromised cortical circuitry may hold the key to the salience of frontal lobe symptoms in schizophrenia, in spite of widespread pathological changes, We outline several direct and indirect intercellular mechanisms for modulating working memory function in the prefrontal cortex based on the localization of dopamine receptors on the distal dendrites and spines of glutamatergic pyramidal cells and on gamma-aminobutyric acid (GABA)ergic interneurons in the prefrontal cortex, Understanding the interactions between the major cellular constituents of cortical circuits-pyramidal and nonpyramidal cells-is a necessary step in unraveling the receptor mechanisms, which could lead to an effective pharmacological treatment of negative and cognitive symptoms, as well as improved insight into the pathophysiological basis of the disorder.
    BibTeX:
    @article{GoldmanRakic1997,
      author = {GoldmanRakic, PS and Selemon, LD},
      title = {Functional and anatomical aspects of prefrontal pathology in schizophrenia},
      journal = {SCHIZOPHRENIA BULLETIN},
      year = {1997},
      volume = {23},
      number = {3},
      pages = {437-458}
    }
    
    GOLDMANRAKIC, P., SELEMON, L. & SCHWARTZ, M. DUAL PATHWAYS CONNECTING THE DORSOLATERAL PREFRONTAL CORTEX WITH THE HIPPOCAMPAL-FORMATION AND PARAHIPPOCAMPAL CORTEX IN THE RHESUS-MONKEY {1984} NEUROSCIENCE
    Vol. {12}({3}), pp. {719-743} 
    article  
    BibTeX:
    @article{GOLDMANRAKIC1984,
      author = {GOLDMANRAKIC, PS and SELEMON, LD and SCHWARTZ, ML},
      title = {DUAL PATHWAYS CONNECTING THE DORSOLATERAL PREFRONTAL CORTEX WITH THE HIPPOCAMPAL-FORMATION AND PARAHIPPOCAMPAL CORTEX IN THE RHESUS-MONKEY},
      journal = {NEUROSCIENCE},
      year = {1984},
      volume = {12},
      number = {3},
      pages = {719-743}
    }
    
    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}
    }
    
    Gorman, J., Kent, J., Sullivan, G. & Coplan, J. Neuroanatomical hypothesis of panic disorder, revised {2000} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {157}({4}), pp. {493-505} 
    article  
    Abstract: Objective: In a 1989 article, the authors provided a hypothesis for the neuroanatomical basis of panic disorder that attempted to explain why both medication and cognitive behavioral psychotherapy are effective treatments. Here they revise that hypothesis to consider developments in the preclinical understanding of the neurobiology of fear and avoidance. Method: The authors review recent literature on the phenomenology, neurobiology, and treatment of panic disorder and impressive developments in documenting the neuroanatomy of conditioned fear in animals. Results: There appears to be a remarkable similarity between the physiological and behavioral consequences of response to a conditioned fear stimulus and a panic attack. In animals, these responses are mediated by a ``fear network'' in the brain that is centered in the amygdala and involves its interaction with the hippocampus and medial prefrontal cortex. Projections from the amygdala to hypothalamic and brainstem sites explain many of the observed signs of conditioned fear responses. It is speculated that a similar network is involved in panic disorder. A convergence of evidence suggests that both heritable factors and stressful life events, particularly in early childhood, are responsible for the onset of panic disorder. Conclusions: Medications, particularly those that influence the serotonin system, are hypothesized to desensitize the fear network from the level of the amygdala through its projects to the hypothalamus and the brainstem. Effective psychosocial treatments may also reduce contextual fear and cognitive misattributions at the level of the prefrontal cortex and hippocampus. Neuroimaging studies should help clarify whether these hypotheses are correct.
    BibTeX:
    @article{Gorman2000,
      author = {Gorman, JM and Kent, JM and Sullivan, GM and Coplan, JD},
      title = {Neuroanatomical hypothesis of panic disorder, revised},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {2000},
      volume = {157},
      number = {4},
      pages = {493-505}
    }
    
    Gottesman, I. & Gould, T. The endophenotype concept in psychiatry: Etymology and strategic intentions {2003} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {160}({4}), pp. {636-645} 
    article  
    Abstract: Endophenotypes, measurable components unseen by the unaided eye along the pathway between disease and distal genotype, have emerged as an important concept in the study of complex neuropsychiatric diseases. An endophenotype may be neurophysiological, biochemical, endocrinological, neuroanatomical, cognitive, or neuropsychological (including configured self-report data) in nature. Endophenotypes represent simpler clues to genetic underpinnings than the disease syndrome itself, promoting the view that psychiatric diagnoses can be decomposed or deconstructed, which can result in more straightforward-and successful-genetic analysis. However, to be most useful, endophenotypes for psychiatric disorders must meet certain criteria, including association with a candidate gene or gene region, heritability that is inferred from relative risk for the disorder in relatives, and disease association parameters. in addition to furthering genetic analysis, endophenotypes can clarify classification and diagnosis and foster the development of animal models. The authors discuss the etymology and strategy behind the use of endophenotypes in neuropsychiatric research and, more generally, in research on other diseases with complex genetics.
    BibTeX:
    @article{Gottesman2003,
      author = {Gottesman, II and Gould, TD},
      title = {The endophenotype concept in psychiatry: Etymology and strategic intentions},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {2003},
      volume = {160},
      number = {4},
      pages = {636-645}
    }
    
    Gottfried, J., O'Doherty, J. & Dolan, R. Encoding predictive reward value in human amygdala and orbitofrontal cortex {2003} SCIENCE
    Vol. {301}({5636}), pp. {1104-1107} 
    article  
    Abstract: Adaptive behavior is optimized in organisms that maintain flexible representations of the value of sensory-predictive cues. To identify central representations of predictive reward value in humans, we used reinforcer devaluation while measuring neural activity with functional magnetic resonance imaging. We presented two arbitrary visual stimuli, both before and after olfactory devaluation, in a paradigm of appetitive conditioning. In amygdala and orbitofrontal cortex, responses evoked by a predictive target stimulus were decreased after devaluation, whereas responses to the nondevalued stimulus were maintained. Thus, differential activity in amygdala and orbitofrontal cortex encodes the current value of reward representations accessible to predictive cues.
    BibTeX:
    @article{Gottfried2003,
      author = {Gottfried, JA and O'Doherty, J and Dolan, RJ},
      title = {Encoding predictive reward value in human amygdala and orbitofrontal cortex},
      journal = {SCIENCE},
      year = {2003},
      volume = {301},
      number = {5636},
      pages = {1104-1107}
    }
    
    Gould, E., Reeves, A., Graziano, M. & Gross, C. Neurogenesis in the neocortex of adult primates {1999} SCIENCE
    Vol. {286}({5439}), pp. {548-552} 
    article  
    Abstract: In primates, prefrontal, inferior temporal, and posterior parietal cortex are important for cognitive function. It is shown that in adult macaques, new neurons are added to these three neocortical association areas, but not to a primary sensory area (striate cortex). The new neurons appeared to originate in the subventricular zone and to migrate through the white matter to the neocortex, where they extended axons, These new neurons, which are continually added in adulthood, may play a role in the functions of association neocortex.
    BibTeX:
    @article{Gould1999,
      author = {Gould, E and Reeves, AJ and Graziano, MSA and Gross, CG},
      title = {Neurogenesis in the neocortex of adult primates},
      journal = {SCIENCE},
      year = {1999},
      volume = {286},
      number = {5439},
      pages = {548-552}
    }
    
    GRADY, C., MCINTOSH, A., HORWITZ, B., MAISOG, J., UNGERLEIDER, L., MENTIS, M., PIETRINI, P., SCHAPIRO, M. & HAXBY, J. AGE-RELATED REDUCTIONS IN HUMAN RECOGNITION MEMORY DUE TO IMPAIRED ENCODING {1995} SCIENCE
    Vol. {269}({5221}), pp. {218-221} 
    article  
    Abstract: The participation of the medial temporal cortex and other cerebral structures in the memory impairment that accompanies aging was examined by means of positron emission tomography. Cerebral blood flow (rCBF) was measured during encoding and recognition of faces. Young people showed increased rCBF in the right hippocampus and the left prefrontal and temporal cortices during encoding and in the right prefrontal and parietal cortex during recognition. Old people showed no significant activation in areas activated during encoding in young people but did show right prefrontal activation during recognition. Age-related impairments of memory may be due to a failure to encode the stimuli adequately, which is reflected in the lack of cortical and hippocampal activation during encoding.
    BibTeX:
    @article{GRADY1995,
      author = {GRADY, CL and MCINTOSH, AR and HORWITZ, B and MAISOG, JM and UNGERLEIDER, LG and MENTIS, MJ and PIETRINI, P and SCHAPIRO, MB and HAXBY, JV},
      title = {AGE-RELATED REDUCTIONS IN HUMAN RECOGNITION MEMORY DUE TO IMPAIRED ENCODING},
      journal = {SCIENCE},
      year = {1995},
      volume = {269},
      number = {5221},
      pages = {218-221}
    }
    
    GRAFTON, S., HAZELTINE, E. & IVRY, R. FUNCTIONAL MAPPING OF SEQUENCE LEARNING IN NORMAL HUMANS {1995} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {7}({4}), pp. {497-510} 
    article  
    Abstract: The brain localization of motor sequence learning was studied in normal subjects with positron emission tomography. Subjects performed a serial reaction time (SRT) task by responding to a series of stimuli that occurred at four different spatial positions. The stimulus locations were either determined randomly or according to a 6-element sequence that cycled continuously The SRT task was performed under two conditions. With attentional interference from a secondary counting task there was no development of awareness of the sequence. Learning-related increases of cerebral blood flow were located in contralateral motor effector areas including motor cortex, supplementary motor area, and putamen, consistent with the hypothesis that nondeclarative motor learning occurs in cerebral areas that control limb movements. Additional cortical sites included the rostral prefrontal cortex and parietal cortex. The SRT learning task was then repeated with a new sequence and no attentional interference. In this condition, 7 of 12 subjects developed awareness of the sequence. Learning-related blood flow increases were present in right dorsolateral prefrontal cortex, right premotor cortex, right ventral putamen, and biparieto-occipital cortex. The right dorsolateral prefrontal and parietal areas have been previously implicated in spatial working memory and right prefrontal cortex is also implicated in retrieval tasks of verbal episodic memory. Awareness of the sequence at the end of learning was associated With greater activity in bilateral parietal, superior temporal, and right premotor cortex. Motor learning can take place in different cerebral areas, contingent on the attentional demands of the task.
    BibTeX:
    @article{GRAFTON1995,
      author = {GRAFTON, ST and HAZELTINE, E and IVRY, R},
      title = {FUNCTIONAL MAPPING OF SEQUENCE LEARNING IN NORMAL HUMANS},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {1995},
      volume = {7},
      number = {4},
      pages = {497-510}
    }
    
    Grant, S., London, E., Newlin, D., Villemagne, V., Liu, X., Contoreggi, C., Phillips, R., Kimes, A. & Margolin, A. Activation of memory circuits during cue-elicited cocaine craving {1996} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {93}({21}), pp. {12040-12045} 
    article  
    Abstract: Evidence accumulated over more than 45 years has indicated that environmental stimuli can induce craving for drugs of abuse in individuals who have addictive disorders. However, the brain mechanisms that subserve such craving have not been elucidated. Here a positron emission tomographic study shows increased glucose metabolism in cortical and limbic regions implicated in several forms of memory when human volunteers who abuse cocaine are exposed to drug-related stimuli. Correlations of metabolic increases in the dorsolateral prefrontal cortex, medial temporal lobe (amygdala), and cerebellum with self-reports of craving suggest that a distributed neural network, which integrates emotional and cognitive aspects of memory, links environmental cues with cocaine craving.
    BibTeX:
    @article{Grant1996,
      author = {Grant, S and London, ED and Newlin, DB and Villemagne, VL and Liu, X and Contoreggi, C and Phillips, RL and Kimes, AS and Margolin, A},
      title = {Activation of memory circuits during cue-elicited cocaine craving},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1996},
      volume = {93},
      number = {21},
      pages = {12040-12045}
    }
    
    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}
    }
    
    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}}
    }
    
    Grezes, J. & Decety, J. Functional anatomy of execution, mental simulation, observation, and verb generation of actions: A meta-analysis {2001} HUMAN BRAIN MAPPING
    Vol. {12}({1}), pp. {1-19} 
    article  
    Abstract: There is a large body of psychological and neuroimaging experiments that have interpreted their findings in favor of a functional equivalence between action generation, action simulation, action verbalization, and perception of action. On the basis of these data, the concept of shared motor representations has been proposed. Indeed several authors have argued that our capacity to understand other people's behavior and to attribute intention or beliefs to others is rooted in a neural, most likely distributed, execution/observation mechanism. Recent neuroimaging studies have explored the neural network engaged during motor execution, simulation, verbalization, and observation. The focus of this metaanalysis is to evaluate in specific detail to what extent the activated foci elicited by these studies overlap. (C) 2001 Wiley-Liss, Inc.
    BibTeX:
    @article{Grezes2001,
      author = {Grezes, J and Decety, J},
      title = {Functional anatomy of execution, mental simulation, observation, and verb generation of actions: A meta-analysis},
      journal = {HUMAN BRAIN MAPPING},
      year = {2001},
      volume = {12},
      number = {1},
      pages = {1-19}
    }
    
    GROENEWEGEN, H., BERENDSE, H., WOLTERS, J. & LOHMAN, A. THE ANATOMICAL RELATIONSHIP OF THE PREFRONTAL CORTEX WITH THE STRIATOPALLIDAL SYSTEM, THE THALAMUS AND THE AMYGDALA - EVIDENCE FOR A PARALLEL ORGANIZATION {1990} PROGRESS IN BRAIN RESEARCH
    Vol. {85}, pp. {95-118} 
    article  
    Abstract: Recent findings in primates indicate that the connections of the frontal lobe, the basal ganglia, and the thalamus are organized in a number of parallel, functionally segregated circuits. In the present account, we have focused on the organization of the connections between the prefrontal cortex, the basal ganglia and the mediodorsal thalamic nucleus in the rat. It is concluded that in this species, in analogy with the situation in primates, a number of parallel basal ganglia-thalamocortical circuits exist. Furthermore, data are presented indicating that the projections from particular parts of the amygdala and from individual nuclei of he midline and intralaminar thalamic complex to the prefrontal cortex and the striatum are in register with the arrangements in the parallel circuits. These findings emphasize that the functions of the different subregions of the prefrontal cortex cannot be considered separately but must be viewed as components of the integrative functions of the circuits in which they are involved.
    BibTeX:
    @article{GROENEWEGEN1990,
      author = {GROENEWEGEN, HJ and BERENDSE, HW and WOLTERS, JG and LOHMAN, AHM},
      title = {THE ANATOMICAL RELATIONSHIP OF THE PREFRONTAL CORTEX WITH THE STRIATOPALLIDAL SYSTEM, THE THALAMUS AND THE AMYGDALA - EVIDENCE FOR A PARALLEL ORGANIZATION},
      journal = {PROGRESS IN BRAIN RESEARCH},
      year = {1990},
      volume = {85},
      pages = {95-118}
    }
    
    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}
    }
    
    HAGGER, C., BUCKLEY, P., KENNY, J., FRIEDMAN, L., UBOGY, D. & MELTZER, H. IMPROVEMENT IN COGNITIVE FUNCTIONS AND PSYCHIATRIC-SYMPTOMS IN TREATMENT-REFRACTORY SCHIZOPHRENIC-PATIENTS RECEIVING CLOZAPINE {1993} BIOLOGICAL PSYCHIATRY
    Vol. {34}({10}), pp. {702-712} 
    article  
    Abstract: Cognitive functions and psychopathology were assessed in 36 treatment-refractory schizophrenic patients before initiation of clozapine, and at 6 weeks and 6 months, thereafter. Before treatment, cognitive impairment was found in each measure of memory, attention, and executive function as compared with 26 normal controls. After both 6 weeks and 6 months of treatment, significant improvement occurred in the Controlled Oral Word Association Test, a measure of retrieval from reference memory. Improvement was also noted at 6 months in the Category Instance Generation Test, another measure of retrieval from reference memory, and in some, but not all, tests of executive function, attention, and recall memory. Clozapine treatment also resulted in significant improvement in Brief Psychiatric Rating Scale (BPRS) Total and Positive symptom scores at both 6-week and 6-month assessment points. There was some evidence for a relationship between improvement in psychopathology and cognitive function. The improvement in cognitive function during clozapine treatment could have consequences for capacity to work and social function.
    BibTeX:
    @article{HAGGER1993,
      author = {HAGGER, C and BUCKLEY, P and KENNY, JT and FRIEDMAN, L and UBOGY, D and MELTZER, HY},
      title = {IMPROVEMENT IN COGNITIVE FUNCTIONS AND PSYCHIATRIC-SYMPTOMS IN TREATMENT-REFRACTORY SCHIZOPHRENIC-PATIENTS RECEIVING CLOZAPINE},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {1993},
      volume = {34},
      number = {10},
      pages = {702-712}
    }
    
    Hakak, Y., Walker, J., Li, C., Wong, W., Davis, K., Buxbaum, J., Haroutunian, V. & Fienberg, A. Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia {2001} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {98}({8}), pp. {4746-4751} 
    article  
    Abstract: Neuropathological and brain imaging studies suggest that schizophrenia may result from neurodevelopmental defects. Cytoarchitectural studies indicate cellular abnormalities suggestive of a disruption in neuronal connectivity in schizophrenia, particularly in the dorsolateral prefrontal cortex. Yet, the molecular mechanisms underlying these findings remain unclear. To identify molecular substrates associated with schizophrenia, DNA microarray analysis was used to assay gene expression levels in postmortem dorsolateral prefrontal cortex of schizophrenic and control patients. Genes determined to have altered expression levels in schizophrenics relative to controls are involved in a number of biological processes, including synaptic plasticity, neuronal development, neurotransmission, and signal transduction. Most notable was the differential expression of myelination-related genes suggesting a disruption in oligodendrocyte function in schizophrenia.
    BibTeX:
    @article{Hakak2001,
      author = {Hakak, Y and Walker, JR and Li, C and Wong, WH and Davis, KL and Buxbaum, JD and Haroutunian, V and Fienberg, AA},
      title = {Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {2001},
      volume = {98},
      number = {8},
      pages = {4746-4751}
    }
    
    Halgren, E., Marinkovic, K. & Chauvel, P. Generators of the late cognitive potentials in auditory and visual oddball tasks {1998} ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
    Vol. {106}({2}), pp. {156-164} 
    article  
    Abstract: Recordings directly within the brain can establish local evoked potential generation without the ambiguities always associated with extracranial electromagnetic measures. Depth recordings have found that sensory stimuli activate primary cortex and then material-specific encoders. Sensory-specific areas remain active for long periods, but by about 200 ms are joined by activation in widespread brain systems. One system is related to the orientation of attention. It is centered in paralimbic and attentional frontoparietocingular cortex, and associated with the P3a. A second system associated with P3b envelopes cognitive contextual integration. It engages the ventral temporofrontal event-encoding cortices (inferotemporal, perirhinal, and ventrolateral prefrontal), association cortices (superior temporal sulcal and posterior parietal), and the hippocampus. Thus, even in simple tasks, activation is widespread but concentrated in particular multilobar systems. With this information, the late cognitive potentials can be used to monitor the probable location, timing and intensity of brain activation during cognitive tasks. (C) 1998 Elsevier Science Ireland Ltd.
    BibTeX:
    @article{Halgren1998,
      author = {Halgren, E and Marinkovic, K and Chauvel, P},
      title = {Generators of the late cognitive potentials in auditory and visual oddball tasks},
      journal = {ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY},
      year = {1998},
      volume = {106},
      number = {2},
      pages = {156-164}
    }
    
    Hariri, A., Bookheimer, S. & Mazziotta, J. Modulating emotional responses: effects of a neocortical network on the limbic system {2000} NEUROREPORT
    Vol. {11}({1}), pp. {43-48} 
    article  
    Abstract: Humans share with animals a primitive neural system for processing emotions such as fear and anger. Unlike other animals, humans have the unique ability to control and modulate instinctive emotional reactions through intellectual processes such as reasoning, rationalizing, and labeling our experiences. This study used functional MRI to identify the neural networks underlying this ability. Subjects either matched the affect of one of two faces to that of a simultaneously presented target face (a perceptual task) or identified the affect of a target face by choosing one of two simultaneously presented linguistic labels (an intellectual task). Matching angry or frightened expressions was associated with increased regional cerebral blood flow (rCBF) in the left and right amygdala, the brain's primary fear centers. Labeling these same expressions was associated with a diminished rCBF response in the amygdalae. This decrease correlated with a simultaneous increase in rCBF in the right prefrontal cortex, a neocortical region implicated in regulating emotional responses. These results provide evidence for a network in which higher regions attenuate emotional responses at the most fundamental levels in the brain and suggest a neural basis for modulating emotional experience through interpretation and labeling. NeuroReport 11:43-48 (C) 2000 Lippincott Williams & Williams.
    BibTeX:
    @article{Hariri2000,
      author = {Hariri, AR and Bookheimer, SY and Mazziotta, JC},
      title = {Modulating emotional responses: effects of a neocortical network on the limbic system},
      journal = {NEUROREPORT},
      year = {2000},
      volume = {11},
      number = {1},
      pages = {43-48}
    }
    
    Hariri, A., Drabant, E., Munoz, K., Kolachana, L., Mattay, V., Egan, M. & Weinberger, D. A susceptibility gene for affective disorders and the response of the human amygdala {2005} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {62}({2}), pp. {146-152} 
    article  
    Abstract: Background: A common regulatory variant (5-HTTLPR) in the human serotonin transporter gene (SLC6A4), resulting in altered transcription and transporter availability, has been associated with vulnerability for affective disorders, including anxiety and depression. A recent functional magnetic resonance imaging study suggested that this association may be mediated by 5-HTTLPR effects on the response bias of the human amygdala-a brain region critical for emotional and social behavior-to environmental threat. Objectives and Design: To examine the effects of 5-HTTLPR genotype on the reactivity of the human amygdala to salient environmental cues with functional magnetic resonance imaging in a large (N = 92) cohort of volunteers carefully screened for past and present medical or psychiatric illness, and to explore the effects of 5-HTTLPR genotype as well as amygdala reactivity on harm avoidance, a putative personality measure related to trait anxiety. Results: We now confirm the finding of 5-HTTLPR short allele-driven amygdala hyperreactivity in a large independent cohort of healthy subjects with no history of psychiatric illness or treatment. Furthermore, we demonstrate that these genotype effects on amygdala function are consistent with a dominant short allele effect and are equally prominent in men and women. However, neither 5-HTTLPR genotype, amygdala reactivity, nor genotype-driven Variability in this reactivity was reflected in harm avoidance scores. Conclusions: Our results reveal a potent modulatory effect of the 5-HTTLPR on amygdala reactivity to environmental threat. Since this genetically driven effect exists in healthy subjects, it does not, in and of itself, predict dimensions of mood or temperament. As such, the 5-HTTLPR may represent a classic susceptibility factor for affective disorders by biasing the functional reactivity of the human amygdala in the context of stressful life experiences and/or deficient cortical regulatory input.
    BibTeX:
    @article{Hariri2005,
      author = {Hariri, AR and Drabant, EM and Munoz, KE and Kolachana, LS and Mattay, VS and Egan, MF and Weinberger, DR},
      title = {A susceptibility gene for affective disorders and the response of the human amygdala},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {2005},
      volume = {62},
      number = {2},
      pages = {146-152}
    }
    
    Harrison, P. The neuropathology of schizophrenia - A critical review of the data and their interpretation {1999} BRAIN
    Vol. {122}({Part 4}), pp. {593-624} 
    article  
    Abstract: Despite a hundred years' research, the neuropathology of schizophrenia remains obscure. However, neither can the null hypothesis be sustained-that it is a `functional' psychosis, a disorder with no structural basis. A number of abnormalities have been identified and confirmed by meta-analysis, including ventricular enlargement and decreased cerebral (cortical and hippocampal) volume. These are characteristic of schizophrenia as a whole, rather than being restricted to a subtype, and are present in first-episode, unmedicated patients. There is considerable evidence for preferential involvement of the temporal lobe and moderate evidence for an alteration in normal cerebral asymmetries. There are several candidates for the histological and molecular correlates of the macroscopic features. The probable proximal explanation for decreased cortical volume is reduced neuropil and neuronal size, rather than a loss of neurons. These morphometric changes are in turn suggestive of alterations in synaptic, dendritic and axonal organization, a view supported by immunocytochemical and ultrastructural findings. Pathology in subcortical structures is not well established, apart from dorsal thalamic nuclei, which are smaller and contain fewer neurons. Other cytoarchitectural features of schizophrenia which are often discussed, notably entorhinal cortex heterotopias and hippocampal neuronal disarray, remain to be confirmed. The phenotype of the affected neuronal and synaptic populations is uncertain. A case can be made for impairment of hippocampal and corticocortical excitatory pathways, but in general the relationship between neurochemical findings (which centre upon dopamine, 5-hydroxytryptamine, glutamate and GABA systems) and the neuropathology of schizophrenia is unclear. Gliosis is not an intrinsic feature; its absence supports, but does not prove, the prevailing hypothesis that schizophrenia is a disorder of prenatal neurodevelopment. The cognitive impairment which frequently accompanies schizophrenia is not due to Alzheimer's disease or any other recognized neurodegenerative disorder. Its basis is unknown. Functional imaging data indicate that the pathophysiology of schizophrenia reflects aberrant activity in, and integration of, the components of distributed circuits involving the prefrontal cortex, hippocampus and certain subcortical structures. It is hypothesized that the neuropathological features represent the anatomical substrate of these functional abnormalities in neural connectivity. Investigation of this proposal is a goal of current neuropathological studies, which must also seek (i) to establish which of the recent histological findings are robust and cardinal, and (ii) to define the relationship of the pathological phenotype with the clinical syndrome, its neurochemistry and its pathogenesis.
    BibTeX:
    @article{Harrison1999,
      author = {Harrison, PJ},
      title = {The neuropathology of schizophrenia - A critical review of the data and their interpretation},
      journal = {BRAIN},
      year = {1999},
      volume = {122},
      number = {Part 4},
      pages = {593-624}
    }
    
    Harrison, P. & Weinberger, D. Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence {2005} MOLECULAR PSYCHIATRY
    Vol. {10}({1}), pp. {40-68} 
    article DOI  
    Abstract: This review critically summarizes the neuropathology and genetics of schizophrenia, the relationship between them, and speculates on their functional convergence. The morphological correlates of schizophrenia are subtle, and range from a slight reduction in brain size to localized alterations in the morphology and molecular composition of specific neuronal, synaptic, and glial populations in the hippocampus, dorsolateral prefrontal cortex, and dorsal thalamus. These findings have fostered the view of schizophrenia as a disorder of connectivity and of the synapse. Although attractive, such concepts are vague, and differentiating primary events from epiphenomena has been difficult. A way forward is provided by the recent identification of several putative susceptibility genes ( including neuregulin, dysbindin, COMT, DISC1, RGS4, GRM3, and G72). We discuss the evidence for these and other genes, along with what is known of their expression profiles and biological roles in brain and how these may be altered in schizophrenia. The evidence for several of the genes is now strong. However, for none, with the likely exception of COMT, has a causative allele or the mechanism by which it predisposes to schizophrenia been identified. Nevertheless, we speculate that the genes may all converge functionally upon schizophrenia risk via an influence upon synaptic plasticity and the development and stabilization of cortical microcircuitry. NMDA receptor-mediated glutamate transmission may be especially implicated, though there are also direct and indirect links to dopamine and GABA signalling. Hence, there is a correspondence between the putative roles of the genes at the molecular and synaptic levels and the existing understanding of the disorder at the neural systems level. Characterization of a core molecular pathway and a `genetic cytoarchitecture' would be a profound advance in understanding schizophrenia, and may have equally significant therapeutic implications.
    BibTeX:
    @article{Harrison2005,
      author = {Harrison, PJ and Weinberger, DR},
      title = {Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence},
      journal = {MOLECULAR PSYCHIATRY},
      year = {2005},
      volume = {10},
      number = {1},
      pages = {40-68},
      doi = {{10.1038/sj.mp.4001558}}
    }
    
    HAXBY, J., HORWITZ, B., UNGERLEIDER, L., MAISOG, J., PIETRINI, P. & GRADY, C. THE FUNCTIONAL-ORGANIZATION OF HUMAN EXTRASTRIATE CORTEX - A PET-RCBF STUDY OF SELECTIVE ATTENTION TO FACES AND LOCATIONS {1994} JOURNAL OF NEUROSCIENCE
    Vol. {14}({11, Part 1}), pp. {6336-6353} 
    article  
    Abstract: The functional dissociation of human extrastriate cortical processing streams for the perception of face identity and location was investigated in healthy men by measuring visual task-related changes in regional cerebral blood flow (rCBF) with positron emission tomography (PET) and H-2 O-15. Separate scans were obtained while subjects performed face matching, location matching, or sensorimotor control tasks. The matching tasks used identical stimuli for some scans and stimuli of equivalent visual complexity for others. Face matching was associated with selective rCBF increases in the fusiform gyrus in occipital and occipitotemporal cortex bilaterally and in a right prefrontal area in the inferior frontal gyrus. Location matching was associated with selective rCBF increases in dorsal occipital, superior parietal, and intraparietal sulcus cortex bilaterally and in dorsal right premotor cortex. Decreases in rCBF, relative to the sensorimotor control task, were observed for both matching tasks in auditory, auditory association, somatosensory, and midcingulate cortex. These results suggest that, within a sensory modality, selective attention is associated with increased activity in those cortical areas that process the attended information but is not associated with decreased activity in areas that process unattended visual information. Selective attention to one sensory modality, on the other hand, is associated with decreased activity in cortical areas dedicated to processing input from other sensory modalities. Direct comparison of our results with those from other PET-rCBF studies of extrastriate cortex demonstrates agreement in the localization of cortical areas mediating face and location perception and dissociations between these areas and those mediating the perception of color and motion.
    BibTeX:
    @article{HAXBY1994,
      author = {HAXBY, JV and HORWITZ, B and UNGERLEIDER, LG and MAISOG, JM and PIETRINI, P and GRADY, CL},
      title = {THE FUNCTIONAL-ORGANIZATION OF HUMAN EXTRASTRIATE CORTEX - A PET-RCBF STUDY OF SELECTIVE ATTENTION TO FACES AND LOCATIONS},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1994},
      volume = {14},
      number = {11, Part 1},
      pages = {6336-6353}
    }
    
    Haxby, J., Ungerleider, L., Horwitz, B., Maisog, J., Rapoport, S. & Grady, C. Face encoding and recognition in the human brain {1996} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {93}({2}), pp. {922-927} 
    article  
    Abstract: A dissociation between human neural systems that participate in the encoding and later recognition of new memories for faces was demonstrated by measuring memory task-related changes in regional cerebral blood flow with positron emission tomography. There was almost no overlap between the brain structures associated with these memory functions. A region in the right hippocampus and adjacent cortex was activated during memory encoding but not during recognition, The most striking finding in neocortex was the lateralization of prefrontal participation. Encoding activated left prefrontal cortex, whereas recognition activated right prefrontal cortex. These results indicate that the hippocampus and adjacent cortex participate in memory function primarily at the time of new memory encoding. Moreover, face recognition is not mediated simply by recapitulation of operations performed at the time of encoding but, rather, involves anatomically dissociable operations.
    BibTeX:
    @article{Haxby1996,
      author = {Haxby, JV and Ungerleider, LG and Horwitz, B and Maisog, JM and Rapoport, SI and Grady, CL},
      title = {Face encoding and recognition in the human brain},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1996},
      volume = {93},
      number = {2},
      pages = {922-927}
    }
    
    Heckers, S., Rauch, S., Goff, D., Savage, C., Schacter, D., Fischman, A. & Alpert, N. Impaired recruitment of the hippocampus during conscious recollection in schizophrenia {1998} NATURE NEUROSCIENCE
    Vol. {1}({4}), pp. {318-323} 
    article  
    Abstract: Poor attention and impaired memory are enduring and core features of schizophrenia. These impairments have been attributed either to global cortical dysfunction or to perturbations of specific components associated with the dorsolateral prefrontal cortex (DLPFC), hippocampus and cerebellum. Here, we used positron emission tomography (PET) to dissociate activations in DLPFC and hippocampus during verbal episodic memory retrieval. We found reduced hippocampal activation during conscious recollection of studied words, but robust activation of the DLPFC during the effort to retrieve poorly encoded material in schizophrenic patients. This finding provides the first evidence of hippocampal dysfunction during episodic memory retrieval in schizophrenia.
    BibTeX:
    @article{Heckers1998,
      author = {Heckers, S and Rauch, SL and Goff, D and Savage, CR and Schacter, DL and Fischman, AJ and Alpert, NM},
      title = {Impaired recruitment of the hippocampus during conscious recollection in schizophrenia},
      journal = {NATURE NEUROSCIENCE},
      year = {1998},
      volume = {1},
      number = {4},
      pages = {318-323}
    }
    
    Heinrichs, R. & Zakzanis, K. Neurocognitive deficit in schizophrenia: A quantitative review of the evidence {1998} NEUROPSYCHOLOGY
    Vol. {12}({3}), pp. {426-445} 
    article  
    Abstract: The neurocognitive Literature on test performance in schizophrenia is reviewed quantitatively. The authors report 22 mean effect sizes from 204 studies to index schizophrenia versus control differences in global and selective verbal memory, nonverbal memory, bilateral and unilateral motor performance, visual and auditory attention, general intelligence, spatial ability, executive function, language, and interhemispheric tactile-transfer test performance. Moderate to large raw effect sizes (d >.60) were obtained for all 22 neurocognitive test variables, and none of the associated confidence intervals included zero. The results indicate that schizophrenia is characterized by a broadly based cognitive impairment, with varying degrees of deficit in all ability domains measured by standard clinical tests.
    BibTeX:
    @article{Heinrichs1998,
      author = {Heinrichs, RW and Zakzanis, KK},
      title = {Neurocognitive deficit in schizophrenia: A quantitative review of the evidence},
      journal = {NEUROPSYCHOLOGY},
      year = {1998},
      volume = {12},
      number = {3},
      pages = {426-445},
      note = {104th Annual Conference of the American-Psychological-Association, TORONTO, CANADA, AUG 09-13, 1996}
    }
    
    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}
    }
    
    Herman, J., Figueiredo, H., Mueller, N., Ulrich-Lai, Y., Ostrander, M., Choi, D. & Cullinan, W. Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness {2003} FRONTIERS IN NEUROENDOCRINOLOGY
    Vol. {24}({3}), pp. {151-180} 
    article DOI  
    Abstract: Appropriate regulatory control of the hypothatamo-pituitary-adrenocortical stress axis is essential to health and survival. The following review documents the principle extrinsic and intrinsic mechanisms responsible for regulating stress-responsive CRH neurons of the hypothalamic paraventricular nucleus, which summate excitatory and inhibitory inputs into a net secretory signal at the pituitary gland. Regions that directly innervate these neurons are primed to relay sensory information, including visceral afferents, nociceptors and circumventricular organs, thereby promoting `reactive' corticosteroid responses to emergent homeostatic challenges. Indirect inputs from the limbic-associated structures are capable of activating these same cells in the absence of frank physiological challenges; such `anticipatory' signals regulate glucocorticoid release under conditions in which physical challenges may be predicted, either by innate programs or conditioned stimuli. Importantly, `anticipatory' circuits are integrated with neural pathways subserving `reactive' responses at multiple levels. The resultant hierarchical organization of stress-responsive neurocircuitries is capable of comparing information from multiple limbic sources with internally generated and peripherally sensed information, thereby tuning the relative activity of the adrenal cortex. Imbalances among these limbic pathways and homeostatic sensors are likely to underlie hypothalamo-pituitary adrenocortical dysfunction associated with numerous disease processes. (C) 2003 Elsevier Inc. All rights reserved.
    BibTeX:
    @article{Herman2003,
      author = {Herman, JP and Figueiredo, H and Mueller, NK and Ulrich-Lai, Y and Ostrander, MM and Choi, DC and Cullinan, WE},
      title = {Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness},
      journal = {FRONTIERS IN NEUROENDOCRINOLOGY},
      year = {2003},
      volume = {24},
      number = {3},
      pages = {151-180},
      doi = {{10.1016/j.yfrne.2003.07.001}}
    }
    
    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}}
    }
    
    Horvitz, J. Mesolimbocortical and nigrostriatal dopamine responses to salient non-reward events {2000} NEUROSCIENCE
    Vol. {96}({4}), pp. {651-656} 
    article  
    Abstract: While it has previously been assumed that mesolimbic dopamine neurons carry a reward signal, recent data from single-unit, microdialysis and voltammetry studies suggest that these neurons respond to a large category of salient and arousing events, including appetitive, aversive, high intensity, and novel stimuli. Elevations in dopamine release within mesolimbic, mesocortical and nigrostriatal target sites coincide with arousal, and the increase in dopamine activity within target sites modulates a number of behavioral functions. However, because dopamine neurons respond to a category of salient events that extend beyond that of reward stimuli, dopamine levels are not likely to code for the reward Value of encountered events. The paper (i) examines evidence showing that dopamine neurons respond to salient and arousing change in environmental conditions, regardless of the motivational valence of that change, and (ii) asks how this might shape our thinking about the role of dopamine systems in goal-directed behavior. (C) 2000 IBRO. Published by Elsevier Science Ltd.
    BibTeX:
    @article{Horvitz2000,
      author = {Horvitz, JC},
      title = {Mesolimbocortical and nigrostriatal dopamine responses to salient non-reward events},
      journal = {NEUROSCIENCE},
      year = {2000},
      volume = {96},
      number = {4},
      pages = {651-656}
    }
    
    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}
    }
    
    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}
    }
    
    Huttenlocher, P. & Dabholkar, A. Regional differences in synaptogenesis in human cerebral cortex {1997} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {387}({2}), pp. {167-178} 
    article  
    Abstract: The formation of synaptic contacts in human cerebral cortex was compared in two cortical regions: auditory cortex (Heschl's gyrus) and prefrontal cortex (middle frontal gyrus). Synapse formation in both cortical regions begins in the fetus, before conceptual age 27 weeks. Synaptic density increases more rapidly in auditory cortex, where the maximum is reached near postnatal age 3 months. Maximum synaptic density in middle frontal gyrus is not reached until after age 15 months. Synaptogenesis occurs concurrently with dendritic and axonal growth and with myelination of the subcortical white matter. A phase of net synapse elimination occurs late in childhood, earlier in auditory cortex, where it has ended by age 12 years, than in prefrontal cortex, where it extends to midadolescence. Synaptogenesis and synapse elimination in humans appear to be heterochronous in different cortical regions and, in that respect, appears to differ from the rhesus monkey, where they are concurrent. In other respects, including overproduction of synaptic contacts in infancy, persistence of high levels of synaptic density to late childhood or adolescence, the absolute values of maximum and adult synaptic density, and layer specific differences, findings in the human resemble those in rhesus monkeys. (C) 1997 Wiley-Liss, Inc.
    BibTeX:
    @article{Huttenlocher1997,
      author = {Huttenlocher, PR and Dabholkar, AS},
      title = {Regional differences in synaptogenesis in human cerebral cortex},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {1997},
      volume = {387},
      number = {2},
      pages = {167-178}
    }
    
    Hyman, S.E., Malenka, R.C. & Nestler, E.J. Neural mechanisms of addiction: The role of reward-related learning and memory {2006} ANNUAL REVIEW OF NEUROSCIENCE
    Vol. {29}, pp. {565-598} 
    article DOI  
    Abstract: Addiction is a state of compulsive drug use; despite treatment and other attempts to control drug taking, addiction tends to persist. Clinical and laboratory observations have converged on the hypothesis that addiction represents the pathological usurpation of neural processes that normally serve reward-related learning. The major substrates of persistent compulsive drug use are hypothesized to be molecular and cellular mechanisms that underlie long-term associative memories in several forebrain circuits (involving the ventral and dorsal striatum and prefrontal cortex) that receive input from midbrain dopamine neurons. Here we review progress in identifying candidate mechanisms of addiction.
    BibTeX:
    @article{Hyman2006,
      author = {Hyman, Steven E. and Malenka, Robert C. and Nestler, Eric J.},
      title = {Neural mechanisms of addiction: The role of reward-related learning and memory},
      journal = {ANNUAL REVIEW OF NEUROSCIENCE},
      year = {2006},
      volume = {29},
      pages = {565-598},
      doi = {{10.1146/annurev.neuro.29.051605.113009}}
    }
    
    Ikemoto, S. & Panksepp, J. The role of nucleus accumbens dopamine in motivated behavior: a unifying interpretation with special reference to reward-seeking {1999} BRAIN RESEARCH REVIEWS
    Vol. {31}({1}), pp. {6-41} 
    article  
    Abstract: Studies addressing behavioral functions of dopamine (DA) in the nucleus accumbens septi (NAS) are reviewed. A role of NAS DA in reward has long been suggested. However, some investigators have questioned the role of NAS DA in rewarding effects because of its role in aversive contexts. As findings supporting the role of NAS DA in mediating aversively motivated behaviors accumulate, it is necessary to accommodate such data for understanding the role of NAS DA in behavior. The aim of the present paper is to provide a unifying interpretation that can account for the functions of NAS DA in a variety of behavioral contexts: (1) its role in appetitive behavioral arousal, (2) its role as a facilitator as well as an inducer of reward processes, and (3) its presently undefined role in aversive contexts. The present analysis suggests that NAS DA plays an important role in sensorimotor integrations that facilitate flexible approach responses. Flexible approach responses an contrasted with fixed instrumental approach responses (habits), which may involve the nigro-striatal DA system more than the meso-accumbens DA system. Functional properties of NAS DA transmission are considered in two stages: unconditioned behavioral invigoration effects and incentive learning effects. (1) When organisms are presented with salient stimuli (e.g., novel stimuli and incentive stimuli), NAS DA is released and invigorates flexible approach responses (invigoration effects). (2) When proximal exteroceptive receptors are stimulated by unconditioned stimuli, NAS DA is released and enables stimulus representations to acquire incentive properties within specific environmental context. It is important to make a distinction that NAS DA is a critical component for the conditional formation of incentive representations but not the retrieval of incentive stimuli or behavioral expressions based on over-learned incentive responses (i.e., habits). Nor is NAS DA essential for the cognitive perception of environmental stimuli. Therefore, even without normal NAS DA transmission, the habit response system still allows animals to perform instrumental responses given that the tasks take place in fixed environment. Such a role of NAS DA as an incentive-property constructor is not limited to appetitive contexts but also aversive contexts. This dual action of NAS DA in invigoration and incentive learning may explain the rewarding effects of NAS DA as well as other effects of NAS DA in a variety of contexts including avoidance and unconditioned/conditioned increases in open-field locomotor activity. Particularly, the present hypothesis offers the following interpretation for the finding that both conditioned and unconditioned aversive stimuli stimulate DA release in the NAS: NAS DA invigorates approach responses toward `safety'. Moreover. NAS DA modulates incentive properties of the environment so that organisms emit approach responses toward `safety' (i.e., avoidance responses) when animals later encounter similar environmental contexts. There may be no obligatory relationship between NAS DA release and positive subjective effects, even though these systems probably interact with other brain systems which can mediate such effects. The present conceptual framework may be valuable in understanding the dynamic interplay of NAS DA neurochemistry and behavior, both normal and pathophysiological. (C) 1999 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{Ikemoto1999,
      author = {Ikemoto, S and Panksepp, J},
      title = {The role of nucleus accumbens dopamine in motivated behavior: a unifying interpretation with special reference to reward-seeking},
      journal = {BRAIN RESEARCH REVIEWS},
      year = {1999},
      volume = {31},
      number = {1},
      pages = {6-41}
    }
    
    Impagnatiello, F., Guidotti, A., Pesold, C., Dwivedi, Y., Caruncho, H., Pisu, M., Uzunov, D., Smalheiser, N., Davis, J., Pandey, G., Pappas, G., Tueting, P., Sharma, R. & Costa, E. A decrease of reelin expression as a putative vulnerability factor in schizophrenia {1998} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {95}({26}), pp. {15718-15723} 
    article  
    Abstract: Postmortem prefrontal cortices (PFC) (Brodmann's areas 10 and 46), temporal cortices (Brodmann's area 22), hippocampi, caudate nuclei, and cerebella of schizophrenia patients and their matched nonpsychiatric subjects were compared for reelin (RELN) mRNA and reelin (RELN) protein content. In all of the brain areas studied, RELN and its mRNA were significantly reduced ( approximate to 50 in patients with schizophrenia; this decrease was similar in patients affected by undifferentiated or paranoid schizophrenia. To exclude possible artifacts caused by postmortem mRNA degradation, we measured the mRNAs in the same PFC extracts from gamma-aminobutyric acid (GABA)(A) receptors alpha(1) and alpha(5) and nicotinic acetylcholine receptor alpha(7) subunits. Whereas the expression of the alpha(7) nicotinic acetylcholine receptor subunit was normal, that of the alpha(1) and alpha(5) receptor subunits of GABA(A) was increased when schizophrenia was present. RELN mRNA was preferentially expressed in GABAergic interneurons of PFC, temporal cortex, hippocampus, and glutamatergic granule cells of cerebellum. A protein putatively functioning as an intracellular target for the signal-transduction cascade triggered by RELN protein released into the extracellular matrix is termed mouse disabled-1 (DAB1) and is expressed at comparable levels in the neuroplasm of the PFC and hippocampal pyramidal neurons, cerebellar Purkinje neurons of schizophrenia patients, and nonpsychiatric subjects; these three types of neurons do not express RELN protein. In the same samples of temporal cortex, we found a decrease in RELN protein of approximate to 50% but no changes in DAB1 protein expression. We also observed a large (up to 70 decrease of GAD67 but only a small decrease of GAD65 protein content. These findings are interpreted within a neurodevelopmental/vulnerability ``two-hit'' model for the etiology of schizophrenia.
    BibTeX:
    @article{Impagnatiello1998,
      author = {Impagnatiello, F and Guidotti, AR and Pesold, C and Dwivedi, Y and Caruncho, H and Pisu, MG and Uzunov, DP and Smalheiser, NR and Davis, JM and Pandey, GN and Pappas, GD and Tueting, P and Sharma, RP and Costa, E},
      title = {A decrease of reelin expression as a putative vulnerability factor in schizophrenia},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1998},
      volume = {95},
      number = {26},
      pages = {15718-15723}
    }
    
    Itti, L. & Koch, C. Computational modelling of visual attention {2001} NATURE REVIEWS NEUROSCIENCE
    Vol. {2}({3}), pp. {194-203} 
    article  
    Abstract: Five important trends have emerged from recent work on computational models of focal visual attention that emphasize the bottom-up, image-based control of attentional deployment. First, the perceptual saliency of stimuli critically depends on the surrounding context. Second, a unique `saliency map' that topographically encodes for stimulus conspicuity over the visual scene has proved to be an efficient and plausible bottom-up control strategy Third, inhibition of return, the process by which the currently attended location is prevented from being attended again, is a crucial element of attentional deployment. Fourth, attention and eye movements tightly interplay, posing computational challenges with respect to the coordinate system used to control attention. And last, scene understanding and object recognition strongly constrain the selection of attended locations. Insights from these five key areas provide a framework for a computational and neurobiological understanding of visual attention.
    BibTeX:
    @article{Itti2001,
      author = {Itti, L and Koch, C},
      title = {Computational modelling of visual attention},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2001},
      volume = {2},
      number = {3},
      pages = {194-203}
    }
    
    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}
    }
    
    JAVITT, D. & ZUKIN, S. RECENT ADVANCES IN THE PHENCYCLIDINE MODEL OF SCHIZOPHRENIA {1991} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {148}({10}), pp. {1301-1308} 
    article  
    Abstract: Objective: Phencyclidine (PCP, ``angel dust'') induces a psychotomimetic state that closely resembles schizophrenia. As opposed to amphetamine-induced psychosis, PCP-induced psychosis incorporates both positive (e.g., hallucinations, paranoia) and negative (e.g., emotional withdrawal, motor retardation) schizophrenic symptoms. PCP-induced psychosis also uniquely incorporates the formal thought disorder and neuropsychological deficits associated with schizophrenia. The purpose of the present paper is to review recent advances in the study of the molecular mechanisms of PCP action and to describe their implications for the understanding of schizophrenic pathophysiology. Method: Twenty-five papers were identified that described the clinical dose and serum and CSF levels at which PCP induces its psychotomimetic effects. The dose range of PCP-induced effects were compared to the dose range at which PCP interacts with specific molecular targets and affects neurotransmission. Results: It was found that PCP-induced psychotomimetic effects are associated with submicromolar serum concentrations of PCP. At these concentrations PCP interacts selectively with a specific binding site (PCP receptor) that is associated with the N-methyl-D-aspartate (NMDA)-type excitatory amino acid receptor. Occupation of its receptor by PCP induces noncompetitive inhibition of NMDA receptor-mediated neurotransmission. Other NMDA antagonists such as the dissociative anesthetic ketamine induce PCP-like neurobehavioral effects in proportion to their potency in binding to the PCP receptor and inducing NMDA receptor inhibition. Conclusions: These findings suggest that endogenous dysfunction of NMDA receptor-mediated neurotransmission might contribute to the pathogenesis of schizoprenia. The relative implications of the PCP and amphetamine models of schizophrenia are discussed in relationship to the diagnosis and etiology of schizophrenia.
    BibTeX:
    @article{JAVITT1991,
      author = {JAVITT, DC and ZUKIN, SR},
      title = {RECENT ADVANCES IN THE PHENCYCLIDINE MODEL OF SCHIZOPHRENIA},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {1991},
      volume = {148},
      number = {10},
      pages = {1301-1308}
    }
    
    JAY, T. & WITTER, M. DISTRIBUTION OF HIPPOCAMPAL CA1 AND SUBICULAR EFFERENTS IN THE PREFRONTAL CORTEX OF THE RAT STUDIED BY MEANS OF ANTEROGRADE TRANSPORT OF PHASEOLUS-VULGARIS-LEUKOAGGLUTININ {1991} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {313}({4}), pp. {574-586} 
    article  
    Abstract: Projections of the hippocampal formation to the prefrontal cortex were visualized in the rat by means of the anterograde tracer Phaseolus vulgaris-leucoagglutinin. These projections distribute only to the prelimbic and the medial orbital cortices and arise exclusively from restricted portions of field CA1 of the Ammon's horn and the subiculum. The most dorsal portion of CA1 does not contribute fibers to this projection. In the subiculum, its origin is restricted to the proximal half, i.e., the portion that directly borders field CA1. Fibers from field CA1 and the subiculum have comparable distribution patterns in the prelimbic and medial orbital cortices. The density and distribution in the prefrontal cortex of the projections from the proximal portion of the subiculum depends on the location of the injections along the dorsoventral axis of the hippocampal formation: the intermediate portion of the subiculum projects more densely and diffusely than its dorsal and ventral portions. In the prelimbic cortex, labeled fibers are present in all layers, showing marked morphological differences in deep versus superficial layers. In layers V and VI, most of the fibers are vertically oriented, while in layers II and III they are short and oriented towards the pial surface. Although no clear differences in terminal distribution were observed along the rostrocaudal extent of the prelimbic cortex, its dorsal and ventral portions show different innervation patterns. In the ventral portion of the prelimbic cortex, varicose fibers and terminal arborizations were present in all cortical layers, deep (V and VI) as well as superficial (II and III). In its dorsal part, the innervation was less dense and mostly present in the deep layers (V and VI). The fiber and terminal distribution in the medial orbital cortex was diffuse in all layers with a slight preference for layers deep to layer II.
    BibTeX:
    @article{JAY1991,
      author = {JAY, TM and WITTER, MP},
      title = {DISTRIBUTION OF HIPPOCAMPAL CA1 AND SUBICULAR EFFERENTS IN THE PREFRONTAL CORTEX OF THE RAT STUDIED BY MEANS OF ANTEROGRADE TRANSPORT OF PHASEOLUS-VULGARIS-LEUKOAGGLUTININ},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {1991},
      volume = {313},
      number = {4},
      pages = {574-586}
    }
    
    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}
    }
    
    Jentsch, J. & Roth, R. The neuropsychopharmacology of phencyclidine: From NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia {1999} NEUROPSYCHOPHARMACOLOGY
    Vol. {20}({3}), pp. {201-225} 
    article  
    Abstract: Administration of noncompetitive NMDA/glutamate receptor antagonists, such as phencyclidine (PCP) and ketamine, to humans induces a broad range of schizophrenic-like symptomatology,findings that have contributed to a hypoglutamatergic hypothesis of schizophrenia, Moreover, a history of eexperimental investigations of the effects of these drugs in animals suggests that NMDA receptor antagonists may model some behavioral symptoms of schizophrenia in nonhuman subjects. In this review, the usefulness of PCP administration as a potential animal model of schizophrenia is considered. To support the contention that NMDA receptor antagonist administration represents a viable model of schizophrenia, the behavioral and neurobiological effects of these drugs are discussed, especially with regard to differing profiles following single-dose and long-term exposure. The neurochemical effects of NMDA receptor antagonist administration are argued to support a neurobiological hypothesis of schizophrenia, which includes pathophysiology within several neurotransmitter systems, manifested in behavioral pathology. Future directions for the application of NMDA receptor antagonist models of schizophrenia to preclinical and pathophysiological research are offered. [Neuropsychopharmacology 20:201-225, 1999] (C) 1999 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.
    BibTeX:
    @article{Jentsch1999,
      author = {Jentsch, JD and Roth, RH},
      title = {The neuropsychopharmacology of phencyclidine: From NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia},
      journal = {NEUROPSYCHOPHARMACOLOGY},
      year = {1999},
      volume = {20},
      number = {3},
      pages = {201-225}
    }
    
    Jentsch, J. & Taylor, J. Impulsivity resulting from frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli {1999} PSYCHOPHARMACOLOGY
    Vol. {146}({4}), pp. {373-390} 
    article  
    Abstract: Drug abuse and dependence define behavioral states involving increased allocation of behavior towards drug seeking and taking at the expense of more appropriate behavioral patterns. As such. addiction can be viewed as increased control of behavior by the desired drug (due to its unconditioned, rewarding properties). It is also clear that drug-associated (conditioned) stimuli acquire heightened abilities to control behaviors. These phenomena have been linked with dopamine function within the ventral striatum and amygdala and have been described specifically in terms of motivational and incentive learning processes. New data are emerging that suggest that regions of the frontal cortex involved in inhibitory response control are directly affected by long-term exposure to drugs of abuse. The result of chronic drug use may be frontal cortical cognitive dysfunction, resulting in an inability to inhibit inappropriate unconditioned or conditioned responses elicited by drugs, by related stimuli or by internal drive states. Drug-seeking behavior may thus be due to two related phenomena: (1) augmented incentive motivational qualities of the drug and associated stimuli (due to limbic/amygdalar dysfunction) and (2) impaired inhibitory control (due to frontal cortical dysfunction). In this review, we consider the neuro-anatomical and neurochemical substrates subserving inhibitory control and motivational processes in the rodent and primate brain and their putative impact on drug seeking. The evidence for cognitive impulsivity in drug abuse associated with dysfunction of the frontostriatal system will be discussed, and an integrative hypothesis for compulsive reward-seeking in drug abuse will be presented.
    BibTeX:
    @article{Jentsch1999a,
      author = {Jentsch, JD and Taylor, JR},
      title = {Impulsivity resulting from frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli},
      journal = {PSYCHOPHARMACOLOGY},
      year = {1999},
      volume = {146},
      number = {4},
      pages = {373-390}
    }
    
    JOHNSON, S. & NORTH, R. OPIOIDS EXCITE DOPAMINE NEURONS BY HYPERPOLARIZATION OF LOCAL INTERNEURONS {1992} JOURNAL OF NEUROSCIENCE
    Vol. {12}({2}), pp. {483-488} 
    article  
    Abstract: Increased activity of dopamine-containing neurons in the ventral tegmental area is necessary for the reinforcing effects of opioids and other abused drugs. Intracellular recordings from these cells in slices of rat brain in vitro showed that opioids do not affect the principal (dopamine-containing) neurons but hyperpolarize secondary (GABA-containing) interneurons. Experiments with agonists and antagonists selective for opioid receptor subtypes indicated that the hyperpolarization of secondary cells involved the mu-receptor. Most principal cells showed spontaneous bicuculline-sensitive synaptic potentials when the extracellular potassium concentration was increased from 2.5 to 6.5 or 10.5 mM; these were prevented by TTX and assumed to result from action potentials arising in slightly depolarized local interneurons. The frequency of these synaptic potentials, but not their amplitudes, was reduced by opioids selective for mu-receptors. It is concluded that hyperpolarization of the interneurons by opioids reduces the spontaneous GABA-mediated synaptic input to the dopamine cells. In vivo, this would lead to excitation of the dopamine cells by disinhibition, which would be expected to contribute to the positive reinforcement seen with mu-receptor agonists such as morphine and heroin.
    BibTeX:
    @article{JOHNSON1992,
      author = {JOHNSON, SW and NORTH, RA},
      title = {OPIOIDS EXCITE DOPAMINE NEURONS BY HYPERPOLARIZATION OF LOCAL INTERNEURONS},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1992},
      volume = {12},
      number = {2},
      pages = {483-488}
    }
    
    JOHNSON, S. & NORTH, R. 2 TYPES OF NEURON IN THE RAT VENTRAL TEGMENTAL AREA AND THEIR SYNAPTIC INPUTS {1992} JOURNAL OF PHYSIOLOGY-LONDON
    Vol. {450}, pp. {455-468} 
    article  
    Abstract: 1. Intracellular recordings were made from 241 ventral tegmental neurones in slices of rat midbrain. Seventy-seven per cent of neurones were hyperpolarized by dopamine (principal cells); 16% were hyperpolarized by opioid peptides (secondary cells). 2. Most principal cells fired spontaneously (1-3 Hz) with a threshold of -53 mV; most secondary cells did not fire spontaneously. Action potentials of principal cells were longer (0.9 ms) than those of secondary cells (0.5 ms). 3. Focal electrical stimulation within the ventral tegmental area evoked a biphasic synaptic potential, depolarization followed by hyperpolarization, with a duration of about 200 ms. Experiments with receptor antagonists showed that the depolarizing component resulted from activation of both N-methyl-D-aspartate (NMDA) and non-NMDA receptors and the hyperpolarizing component resulted from activation of GABA(A) receptors. 4. A later hyperpolarizing synaptic potential developed after a latency of 50 ms, reached its peak in 250 ms and had a duration of about 1 s. It reversed polarity at -108 mV (external potassium concentration was 2.5 mM), was blocked by phaclofen (30-mu-M-1 mM) or 2-hydroxysaclofen (100-300-mu-M). In some cells, a phaclofen-resistant component remained that was increased by cocaine and blocked by sulpiride (1-mu-M). 5. It is concluded that the ventral tegmental area contains two types of neurone having properties similar to those in the substantia nigra. The cells receive synaptic inputs mediated by excitatory amino acids acting at NMDA and non-NMDA receptors, GABA acting at GABA(A) and GABA(B) receptors, and dopamine acting at D2 receptors.
    BibTeX:
    @article{JOHNSON1992a,
      author = {JOHNSON, SW and NORTH, RA},
      title = {2 TYPES OF NEURON IN THE RAT VENTRAL TEGMENTAL AREA AND THEIR SYNAPTIC INPUTS},
      journal = {JOURNAL OF PHYSIOLOGY-LONDON},
      year = {1992},
      volume = {450},
      pages = {455-468}
    }
    
    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}
    }
    
    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}
    }
    
    JONIDES, J., SMITH, E., KOEPPE, R., AWH, E., MINOSHIMA, S. & MINTUN, M. SPATIAL WORKING-MEMORY IN HUMANS AS REVEALED BY PET {1993} NATURE
    Vol. {363}({6430}), pp. {623-625} 
    article  
    Abstract: THE concept of working memory is central to theories of human cognition because working memory is essential to such human skills as language comprehension and deductive reasoning1-4. Working memory is thought to be composed of two parts, a set of buffers that temporarily store information in either a phonological or visuospatial form, and a central executive responsible for various computations such as mental arithmetic5,6. Although most data on working memory come from behavioural studies of normal and brain-injured humans7, there is evidence about its physiological basis from invasive studies of monkeys8-10. Here we report positron emission tomography (PET) studies of regional cerebral blood flow in normal humans that reveal activation in right-hemisphere prefrontal, occipital, parietal and premotor cortices accompanying spatial working memory processes. These results begin to uncover the circuitry of a working memory system in humans.
    BibTeX:
    @article{JONIDES1993,
      author = {JONIDES, J and SMITH, EE and KOEPPE, RA and AWH, E and MINOSHIMA, S and MINTUN, MA},
      title = {SPATIAL WORKING-MEMORY IN HUMANS AS REVEALED BY PET},
      journal = {NATURE},
      year = {1993},
      volume = {363},
      number = {6430},
      pages = {623-625}
    }
    
    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}
    }
    
    Just, M., Cherkassky, V., Keller, T. & Minshew, N. Cortical activation and synchronization during sentence comprehension in high-functioning autism: evidence of underconnectivity {2004} BRAIN
    Vol. {127}({Part 8}), pp. {1811-1821} 
    article DOI  
    Abstract: The brain activation of a group of high-functioning autistic participants was measured using functional MRI during sentence comprehension and the results compared with those of a Verbal IQ-matched control group. The groups differed in the distribution of activation in two of the key language areas. The autism group produced reliably more activation than the control group in Wernicke's (left laterosuperior temporal) area and reliably less activation than the control group in Broca's (left inferior frontal gyrus) area. Furthermore, the functional connectivity, i.e. the degree of synchronization or correlation of the time series of the activation, between the various participating cortical areas was consistently lower for the autistic than the control participants. These findings suggest that the neural basis of disordered language in autism entails a lower degree of information integration and synchronization across the large-scale cortical network for language processing. The article presents a theoretical account of the findings, related to neurobiological foundations of underconnectivity in autism.
    BibTeX:
    @article{Just2004,
      author = {Just, MA and Cherkassky, VL and Keller, TA and Minshew, NJ},
      title = {Cortical activation and synchronization during sentence comprehension in high-functioning autism: evidence of underconnectivity},
      journal = {BRAIN},
      year = {2004},
      volume = {127},
      number = {Part 8},
      pages = {1811-1821},
      doi = {{10.1093/brain/awh199}}
    }
    
    KALIVAS, P. NEUROTRANSMITTER REGULATION OF DOPAMINE NEURONS IN THE VENTRAL TEGMENTAL AREA {1993} BRAIN RESEARCH REVIEWS
    Vol. {18}({1}), pp. {75-113} 
    article  
    Abstract: Over the last 10 years there has been important progress towards understanding how neurotransmitters regulate dopaminergic output. Reasonable estimates can be made of the synaptic arrangement of afferents to dopamine and non-dopamine cells in the ventral tegmental area (VTA). These models are derived from correlative findings using a variety of techniques. In addition to improved lesioning and pathway-tracing techniques, the capacity to measure mRNA in situ allows the localization of transmitters and receptors to neurons and/or axon terminals in the VTA. The application of intracellular electrophysiology to VTA tissue slices has permitted great strides towards understanding the influence of transmitters on dopamine cell function, as well as towards elucidating relative synaptic organization. Finally, the advent of in vivo dialysis has verified the effects of transmitters on dopamine and gamma-aminobutyric acid transmission in the VTA. Although reasonable estimates can be made of a single transmitter's actions under largely pharmacological conditions, our knowledge of how transmitters work in concert in the VTA to regulate the functional state of dopamine cells is only just emerging. The fact that individual transmitters can have seemingly opposite effects on dopaminergic function demonstrates that the actions of neurotransmitters in the VTA are, to some extent, state-dependent. Thus, different transmitters perform similar functions or the same transmitter may perform opposing functions when environmental circumstances are altered. Understanding the dynamic range of a transmitter's action and how this couples in concert with other transmitters to modulate dopamine neurons in the VTA is essential to defining the role of dopamine cells in the etiology and maintenance of neuropsychiatric disorders. Further, it will permit a more rational exploration of drugs possessing utility in treating disorders involving dopamine transmission.
    BibTeX:
    @article{KALIVAS1993,
      author = {KALIVAS, PW},
      title = {NEUROTRANSMITTER REGULATION OF DOPAMINE NEURONS IN THE VENTRAL TEGMENTAL AREA},
      journal = {BRAIN RESEARCH REVIEWS},
      year = {1993},
      volume = {18},
      number = {1},
      pages = {75-113}
    }
    
    KALIVAS, P. & DUFFY, P. TIME COURSE OF EXTRACELLULAR DOPAMINE AND BEHAVIORAL SENSITIZATION TO COCAINE .1. DOPAMINE AXON TERMINALS {1993} JOURNAL OF NEUROSCIENCE
    Vol. {13}({1}), pp. {266-275} 
    article  
    Abstract: Repeated administration of cocaine to rodents produces a progressive augmentation in motor activity known as behavioral sensitization. By using microdialysis in the ventral striatum, some studies have found that the development of behavioral sensitization is associated with a similar augmentation in dopamine release, while others have not. It was postulated that differences in doses and withdrawal periods may account for the discrepancies between studies. Rats were behaviorally sensitized to daily peripheral injections using two cocaine treatment regimens (15 mg/kg, i.p. x 5 d or 30 mg/kg, i.p. x 5 d). Using in vivo microdialysis in the ventral striatum, the effect of acute cocaine (1 5 mg/kg, i.p.) on extracellular dopamine content and motor behavior was examined at various times after discontinuing daily treatments. Twenty-four hours after discontinuing the low dose of daily cocaine, the increase in motor activity and extracellular dopamine elicited by an acute cocaine challenge was significantly elevated. In contrast, following the higher daily treatment regimen there was a significant augmentation in motor activity, but the increase in extracellular dopamine produced by cocaine was significantly reduced. When rats were challenged 10-14 d after discontinuing either dosage regimen of daily cocaine, the increase in both motor activity and extracellular dopamine was augmented. In general, the increase in extracellular dopamine by an acute cocaine challenge increased over time when rats were challenged between 1 and 22 d after discontinuing daily cocaine. Basal concentrations of extracellular dopamine were determined by measuring the in vivo flux of dopamine across the dialysis membrane, and there was no significant difference at 24 hr or 2 weeks following the last daily injection of saline or cocaine. It is concluded that behavioral sensitization to cocaine is generally associated with an augmentation in extracellular dopamine in the ventral striatum, but that high doses of daily cocaine produce apparent tolerance to the augmentation in extracellular dopamine during the early withdrawal period.
    BibTeX:
    @article{KALIVAS1993a,
      author = {KALIVAS, PW and DUFFY, P},
      title = {TIME COURSE OF EXTRACELLULAR DOPAMINE AND BEHAVIORAL SENSITIZATION TO COCAINE .1. DOPAMINE AXON TERMINALS},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1993},
      volume = {13},
      number = {1},
      pages = {266-275}
    }
    
    KALIVAS, P., SORG, B. & HOOKS, M. THE PHARMACOLOGY AND NEURAL CIRCUITRY OF SENSITIZATION TO PSYCHOSTIMULANTS {1993} BEHAVIOURAL PHARMACOLOGY
    Vol. {4}({4}), pp. {315-334} 
    article  
    Abstract: Behavioral sensitization to amphetamine-like psychostimulants is manifest as a progressive increase in drug-induced anxiety and paranoia which can culminate in psychopathologies, such as paranoid psychosis and panic attacks. Sensitization may also mediate the facilitation of drug relapse in addicts by increasing the reinforcing value of acute drug administration. The primary animal model for psychostimulant-induced psychopathologies involves repeated, non-contingent administration of drug to rodents, which can produce a progressive and enduring augmentation in motor activity and increased susceptibility to drug self-administration. Because of the mature literature implicating mesoaccumbens dopamine transmission in the acute motor and reinforcing effects of amphetamine-like stimulants, investigation into the neural basis of behavioral sensitization has focused on this projection. Over the last decade, with a few exceptions, the neurochemical and molecular literature that has emerged from this effort is replete with inconsistencies. In contrast, the presence of behavioral sensitization is a highly replicable event. It is proposed that behavioral sensitization arises from an alteration in the neural circuitry that subserves the translation of motivationally relevant stimuli into adaptive motor responses. The mesoaccumbens dopamine projection is embedded in this circuit and an enduring change in dopamine transmission may alter the functional state of the circuit to produce behavioral sensitization. However, combinations of alterations in other connections within the circuit can also support behavioral sensitization. The specific changes in the circuit that promote behavioral sensitization are under the control of experimental parameters, such as the drug employed, dosage regimen, withdrawal period and the presence of conditioning cues. Thus, the profile of neurochemical alterations observed after exposure to repeated psychostimulants may vary depending upon the experimental protocol and strain of animals, even though all laboratories report the presence of behavioral sensitization.
    BibTeX:
    @article{KALIVAS1993b,
      author = {KALIVAS, PW and SORG, BA and HOOKS, MS},
      title = {THE PHARMACOLOGY AND NEURAL CIRCUITRY OF SENSITIZATION TO PSYCHOSTIMULANTS},
      journal = {BEHAVIOURAL PHARMACOLOGY},
      year = {1993},
      volume = {4},
      number = {4},
      pages = {315-334}
    }
    
    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. The role of prefrontal cortex in working-memory capacity, executive attention, and general fluid intelligence: An individual-differences perspective {2002} PSYCHONOMIC BULLETIN & REVIEW
    Vol. {9}({4}), pp. {637-671} 
    article  
    Abstract: We provide an ``executive-attention'' framework for organizing the cognitive neuroscience research on the constructs of working-memory capacity (WMC), general fluid intelligence, and prefrontal cortex (PFC) function. Rather than provide a novel theory of PFC function, we synthesize a wealth of single-cell, brain-imaging, and neuropsychological research through the lens of our theory of normal individual differences in WMC and attention control (Engle, Kane, Tuholski, 1999; Engle, Tuholski, Laughlin, & Conway, 1999). Our critical review confirms the prevalent view that dorsolateral PFC circuitry is critical to executive-attention functions. Moreover, although the dorsolateral PFC is but one critical structure in a network of anterior and posterior ``attention control'' areas, it does have a unique executive-attention role in actively maintaining access to stimulus representations and goals in interference-rich contexts. Our review suggests the utility of an executive-attention framework for guiding future research on both PFC function and cognitive control.
    BibTeX:
    @article{Kane2002,
      author = {Kane, MJ and Engle, RW},
      title = {The role of prefrontal cortex in working-memory capacity, executive attention, and general fluid intelligence: An individual-differences perspective},
      journal = {PSYCHONOMIC BULLETIN & REVIEW},
      year = {2002},
      volume = {9},
      number = {4},
      pages = {637-671}
    }
    
    KAPUR, S., CRAIK, F., TULVING, E., WILSON, A., HOULE, S. & BROWN, G. NEUROANATOMICAL CORRELATES OF ENCODING IN EPISODIC MEMORY - LEVELS OF PROCESSING EFFECT {1994} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {91}({6}), pp. {2008-2011} 
    article  
    Abstract: Cognitive studies of memory processes demonstrate that memory for stimuli is a function of how they are encoded; stimuli processed semantically are better remembered than those processed in a perceptual or shallow fashion. This study investigates the neural correlates of this cognitive phenomenon. Twelve subjects performed two different cognitive tasks on a series of visually presented nouns. In one task, subjects detected the presence or absence of the letter a; in the other, subjects categorized each noun as living or nonliving. Positron emission tomography (PET) scans using O-15-labeled water were obtained during both tasks. Subjects showed substantially better recognition memory for nouns seen in the living/nonliving task, compared to nouns seen in the a-checking task. Comparison of the PET images between the two cognitive tasks revealed a significant activation in the left inferior prefrontal cortex (Brodmann's areas 45, 46, 47, and 10) in the semantic task as compared to the perceptual task. We propose that memory processes are subserved by a wide neurocognitive network and that encoding processes involve preferential activation of the structures in the left inferior prefrontal cortex.
    BibTeX:
    @article{KAPUR1994,
      author = {KAPUR, S and CRAIK, FIM and TULVING, E and WILSON, AA and HOULE, S and BROWN, GM},
      title = {NEUROANATOMICAL CORRELATES OF ENCODING IN EPISODIC MEMORY - LEVELS OF PROCESSING EFFECT},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1994},
      volume = {91},
      number = {6},
      pages = {2008-2011}
    }
    
    Kapur, S. & Remington, G. Serotonin-dopamine interaction and its relevance to schizophrenia {1996} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {153}({4}), pp. {466-476} 
    article  
    Abstract: Objective: The therapeutic success of clozapine and risperidone has focused attention on the interaction between the serotonin and dopamine systems as an avenue for superior therapeutics in schizophrenia. The authors review the neurobiological basis for this interaction and its clinical relevance. Method: The authors synthesized information from move than 100 published articles obtained through electronic and bibliography-directed searches. Findings: The serotonin system inhibits dopaminergic function at the level of the origin of the dopamine system in the midbrain as well as at the terminal dopaminergic fields in the forebrain. Serotonergic antagonists release the dopamine system from this inhibition. This disinhibition of the dopamine system in the striatum may alleviate neuroleptic-induced extrapyramidal symp toms, and a similar disinhibition in the prefrontal cortex may ameliorate negative symptoms. However, the benefits of combined serotonergic-dopaminergic blockade may be observed in only a narrow dose range and may be lost with noses that produce suprathreshold dopaminergic blockade. Conclusions: Serotonergic modulation of dopaminergic function provides a viable mechanism for enhancing therapeutics in schizophrenia, but much remains unclear. Future research will have to establish the existence of this interaction in humans in vivo, specify the conditions under which it leads to optimal therapeutic benefits, and explore the possibility of using specific serotonergic treatments as flexible adjuncts to typical neuroleptics, rather than the present trend toward using single drugs with combined actions.
    BibTeX:
    @article{Kapur1996,
      author = {Kapur, S and Remington, G},
      title = {Serotonin-dopamine interaction and its relevance to schizophrenia},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {1996},
      volume = {153},
      number = {4},
      pages = {466-476}
    }
    
    Kastner, S. & Ungerleider, L. Mechanisms of visual attention in the human cortex {2000} ANNUAL REVIEW OF NEUROSCIENCE
    Vol. {23}, pp. {315-341} 
    article  
    Abstract: A typical scene contains many different objects that, because of the limited processing capacity of the visual system, compete for neural representation. The competition among multiple objects in visual cortex can be biased by both bottom-up sensory-driven mechanisms and top-down influences, such as selective attention. Functional brain imaging studies reveal that, both in the absence and in the presence of visual stimulation, biasing signals due to selective attention can modulate neural activity in visual cortex in several ways. Although the competition among stimuli for representation is ultimately resolved within visual cortex, the source of top-down biasing signals derives from a network of areas in frontal and parietal cortex.
    BibTeX:
    @article{Kastner2000,
      author = {Kastner, S and Ungerleider, LG},
      title = {Mechanisms of visual attention in the human cortex},
      journal = {ANNUAL REVIEW OF NEUROSCIENCE},
      year = {2000},
      volume = {23},
      pages = {315-341}
    }
    
    Kawaguchi, Y. & Kubota, Y. GABAergic cell subtypes and their synaptic connections in rat frontal cortex {1997} CEREBRAL CORTEX
    Vol. {7}({6}), pp. {476-486} 
    article  
    Abstract: Physiological, morphological and immunohistochemical characteristics of non pyramidal cells in frontal cortex of young rats were studied in vitro by whole-cell recording and biocytin injection. Several groups of GABAergic non-pyramidal cells were identified: (i) parvalbumin fast-spiking (FS) cells with low input resistances and spikes of short duration, including extended plexus (basket) cells and chandelier cells. These cells showed abrupt episodes of non-adapting repetitive discharges; (ii) late-spiking (LS) cells exhibiting slowly developing ramp depolarizations, including neurogliaform cells; (iii) the remaining groups contained both burst-spiking (BS) or regular-spiking (RS) non pyramidal (NP) cells. BSNP cells exhibited bursting activity (two or more spikes on slow depolarizing humps) from hyperpolarized potentials. Both these physiological types corresponded to a range of morphologies: (i) somatostatin-containing Martinotti cells with ascending axonal arbors to layer I (some were also positive for calbindin D-28k); (ii) VIP-containing double bouquet cells with descending axonal arbors as well as arcade cells (these included small cells immunoreactive for CCK or calretinin). Each subtype of cells made GABAergic synapses onto relatively specific portions of cortical cells, but similar domains were innervated by multiple classes of GABA cells.
    BibTeX:
    @article{Kawaguchi1997,
      author = {Kawaguchi, Y and Kubota, Y},
      title = {GABAergic cell subtypes and their synaptic connections in rat frontal cortex},
      journal = {CEREBRAL CORTEX},
      year = {1997},
      volume = {7},
      number = {6},
      pages = {476-486}
    }
    
    Keefe, R., Silva, S., Perkins, D. & Lieberman, J. The effects of atypical antipsychotic drugs on neurocognitive impairment in schizophrenia: A review and meta-analysis {1999} SCHIZOPHRENIA BULLETIN
    Vol. {25}({2}), pp. {201-222} 
    article  
    Abstract: Cognitive deficits are a fundamental feature of the psychopathology of schizophrenia. Yet the effect of treatment on this dimension of the illness has been unclear. Atypical antipsychotic medications have been reported to reduce the neurocognitive impairment associated with schizophrenia. However, studies of the pattern and degree of cognitive improvement with these compounds have been methodologically limited and have produced variable results, and few findings have been replicated. To clarify our understanding of the effects of atypical antipsychotic drugs on neurocognitive deficits in patients with schizophrenia, we have (1) reported on newly established standards for research design in studies of treatment effects on cognitive function in schizophrenia, (2) reviewed the literature on this topic and determined the extent to which 15 studies on the effect of atypical antipsychotics met these standards, (3) performed a meta-analysis of the 15 studies, which suggested general cognitive enhancement with atypical antipsychotics, and (4) described the pharmacological profile of these agents and considered the pharmacological basis for their effects on neurocognition. Finally, we suggest directions for the development of new therapeutic strategies.
    BibTeX:
    @article{Keefe1999,
      author = {Keefe, RSE and Silva, SG and Perkins, DO and Lieberman, JA},
      title = {The effects of atypical antipsychotic drugs on neurocognitive impairment in schizophrenia: A review and meta-analysis},
      journal = {SCHIZOPHRENIA BULLETIN},
      year = {1999},
      volume = {25},
      number = {2},
      pages = {201-222}
    }
    
    Kelley, A. & Berridge, K. The neuroscience of natural rewards: Relevance to addictive drugs {2002} JOURNAL OF NEUROSCIENCE
    Vol. {22}({9}), pp. {3306-3311} 
    article  
    BibTeX:
    @article{Kelley2002a,
      author = {Kelley, AE and Berridge, KC},
      title = {The neuroscience of natural rewards: Relevance to addictive drugs},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2002},
      volume = {22},
      number = {9},
      pages = {3306-3311}
    }
    
    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}
    }
    
    Kelley, W., Miezin, F., McDermott, K., Buckner, R., Raichle, M., Cohen, N., Ollinger, J., Akbudak, E., Conturo, T., Snyder, A. & Petersen, S. Hemispheric specialization in human dorsal frontal cortex and medial temporal lobe for verbal and nonverbal memory encoding {1998} NEURON
    Vol. {20}({5}), pp. {927-936} 
    article  
    Abstract: The involvement of dorsal frontal and medial temporal regions during the encoding of words, namable line-drawn objects, and unfamiliar faces was examined using functional magnetic resonance imaging (fMRI). Robust dorsal frontal activations were observed in each instance, but lateralization was strongly dependent on the materials being encoded. Encoding of words produced left-lateralized dorsal frontal activation, whereas encoding of unfamiliar faces produced homologous right-lateralized activation. Encoding of namable objects, which are amenable to both verbal and nonverbal encoding, yielded bilateral dorsal frontal activation. A similar pattern of results was observed in the medial temporal lobe. These results indicate that regions in both hemispheres underlie human longterm memory encoding, and these regions can be engaged differentially according to the nature of the material being encoded.
    BibTeX:
    @article{Kelley1998,
      author = {Kelley, WM and Miezin, FM and McDermott, KB and Buckner, RL and Raichle, ME and Cohen, NJ and Ollinger, JM and Akbudak, E and Conturo, TE and Snyder, AZ and Petersen, SE},
      title = {Hemispheric specialization in human dorsal frontal cortex and medial temporal lobe for verbal and nonverbal memory encoding},
      journal = {NEURON},
      year = {1998},
      volume = {20},
      number = {5},
      pages = {927-936}
    }
    
    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}
    }
    
    Kim, J. & Shadlen, M. Neural correlates of a decision in the dorsolateral prefrontal cortex of the macaque {1999} NATURE NEUROSCIENCE
    Vol. {2}({2}), pp. {176-185} 
    article  
    Abstract: To make a visual discrimination, the brain must extract relevant information from the retina, represent appropriate variables in the visual cortex and read out this representation to decide which of two or more alternatives is more likely. We recorded from neurons in the dorsolateral prefrontal cortex (areas 8 and 46) of the rhesus monkey while it performed a motion discrimination task. The monkey indicated its judgment of direction by making appropriate eye movements. As the monkey viewed the motion stimulus, the neural response predicted the monkey's subsequent gaze shift, hence its judgment of direction. The response comprised a mixture of high-level oculomotor signals and weaker visual sensory signals that reflected the strength and direction of motion. This combination of sensory integration and motor planning could reflect the conversion of visual motion information into a categorical decision about direction and thus give insight into the neural computations behind a simple cognitive act.
    BibTeX:
    @article{Kim1999,
      author = {Kim, JN and Shadlen, MN},
      title = {Neural correlates of a decision in the dorsolateral prefrontal cortex of the macaque},
      journal = {NATURE NEUROSCIENCE},
      year = {1999},
      volume = {2},
      number = {2},
      pages = {176-185}
    }
    
    Klein, E., Kreinin, I., Christyakov, A., Koren, D., Mecz, L., Marmur, S., Ben-Shachar, D. & Feinsod, M. Therapeutic efficacy of right prefrontal slow repetitive transcranial magnetic stimulation in major depression - A double-blind controlled study {1999} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {56}({4}), pp. {315-320} 
    article  
    Abstract: Background: Transcranial magnetic stimulation (TMS), a noninvasive technique for stimulation of the brain, has recently been suggested to be effective for the treatment of major depression. We conducted a double-blind, placebo-controlled study to assess the efficacy of slow repetitive TMS (rTMS) in patients with major depression. Methods: Seventy patients with major depression (53 women, 17 men; mean age, 58.7 years; SD, 17.2 years) were randomly assigned to receive rTMS or sham rTMS in a double-blind design. Treatment was administered in 10 daily sessions during a 2-week period. Severity of depression was blindly assessed before, during, and after completion of the treatment protocol. Results: All patients completed the first week of treatment and 67 completed the entire protocol. Patients who received rTMS had a significantly greater improvement in depression scores compared with those who received sham treatment. At the end of 2 weeks, 17 of 35 patients in the rTMS group, but only 8 of 32 in the sham-treated group, had an improvement of greater than 50% in their depression ratings. Conclusions: This controlled study provides evidence for the short-term efficacy of slow rTMS in patients with recurrent major depression. Additional studies will be necessary to assess the efficacy of rTMS as compared with electroconvulsive therapy as well as the long-term outcome of this treatment in major depression and possibly other psychiatric disorders.
    BibTeX:
    @article{Klein1999,
      author = {Klein, E and Kreinin, I and Christyakov, A and Koren, D and Mecz, L and Marmur, S and Ben-Shachar, D and Feinsod, M},
      title = {Therapeutic efficacy of right prefrontal slow repetitive transcranial magnetic stimulation in major depression - A double-blind controlled study},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1999},
      volume = {56},
      number = {4},
      pages = {315-320}
    }
    
    de Kloet, E., Joels, M. & Holsboer, F. Stress and the brain: From adaptation to disease {2005} NATURE REVIEWS NEUROSCIENCE
    Vol. {6}({6}), pp. {463-475} 
    article DOI  
    Abstract: In response to stress, the brain activates several neuropeptide-secreting systems. This eventually leads to the release of adrenal corticosteroid hormones, which subsequently feed back on the brain and bind to two types of nuclear receptor that act as transcriptional regulators. By targeting many genes, corticosteroids function in a binary fashion, and serve as a master switch in the control of neuronal and network responses that underlie behavioural adaptation. In genetically predisposed individuals, an imbalance in this binary control mechanism can introduce a bias towards stress-related brain disease after adverse experiences. New candidate susceptibility genes that serve as markers for the prediction of vulnerable phenotypes are now being identified.
    BibTeX:
    @article{Kloet2005,
      author = {de Kloet, ER and Joels, M and Holsboer, F},
      title = {Stress and the brain: From adaptation to disease},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2005},
      volume = {6},
      number = {6},
      pages = {463-475},
      doi = {{10.1038/nrn1683}}
    }
    
    Knight, R. Contribution of human hippocampal region to novelty detection {1996} NATURE
    Vol. {383}({6597}), pp. {256-259} 
    article  
    Abstract: THE ability to respond to unexpected stimuli (the `orienting response') is a fundamental characteristic of mammalian behaviour(1), but the brain mechanisms by which novelty is detected remain poorly defined. Electrophysiological recordings of scalp and intracranial event-related potentials (ERPs) have shown that novel stimuli activate a distributed network involving prefrontal and posterior association cortex(2-6). In addition, ERP(7,8) and single-neuron(9,10) recordings, as well as neuroimaging(11) and modelling(12) studies, have suggested that temporal cortical regions, including the hippocampus, are also involved. To examine further the role of the medial temporal lobe in novelty processing, I measured physiological responses to novel auditory and tactile stimuli in patients with damage to the posterior hippocampal region. In normal control subjects, unexpected novel stimuli produce a characteristic ERP signal, accompanied by an autonomic skin response. Both responses are reduced in hippocampal lesion patients, whereas the response to expected control stimuli is unaffected. Thus the hippocampal region, in addition to its known role in memory formation, is an essential component of the distributed limbic-cortical network that detects and responds to novel stimuli.
    BibTeX:
    @article{Knight1996,
      author = {Knight, RT},
      title = {Contribution of human hippocampal region to novelty detection},
      journal = {NATURE},
      year = {1996},
      volume = {383},
      number = {6597},
      pages = {256-259}
    }
    
    Koch, M. The neurobiology of startle {1999} PROGRESS IN NEUROBIOLOGY
    Vol. {59}({2}), pp. {107-128} 
    article  
    Abstract: Startle is a fast response to sudden, intense stimuli and probably protects the organism from injury by a predator or by a blow. The acoustic startle response (ASR) of mammals is mediated by a relatively simple neuronal circuit located in the lower brainstem. Neurons of the caudal pontine reticular nucleus (PnC) are key elements of this primary ASR pathway. The ASR in humans and animals has a non-zero baseline, that is, the response magnitude can be increased or decreased by a variety of pathological conditions and experimental manipulations. Therefore, the ASR has been used as a behavioral tool to assess the neuronal basis of behavioral plasticity and to model neuropathological dysfunctions of sensorimotor information processing. Cross-species examples for the increase of the ASR magnitude are sensitization, fear-potentiation and drug-induced enhancement. Examples for the reduction of the ASR magnitude are habituation, prepulse inhibition, drug-induced inhibition and the attenuation by positive affect. This review describes the neuronal basis underlying the mediation of the ASR, as well as the neuronal and neurochemical substrates of different phenomena of enhancement and attenuation of the ASR. It also attempts to elucidate the biological background of these forms of behavioral plasticity. Special emphasis is put on the potential relevance of ASR modulations for the understanding of human psychiatric and neurological diseases. (C) 1999 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{Koch1999,
      author = {Koch, M},
      title = {The neurobiology of startle},
      journal = {PROGRESS IN NEUROBIOLOGY},
      year = {1999},
      volume = {59},
      number = {2},
      pages = {107-128}
    }
    
    Koechlin, E., Basso, G., Pietrini, P., Panzer, S. & Grafman, J. The role of the anterior prefrontal cortex in human cognition {1999} NATURE
    Vol. {399}({6732}), pp. {148-151} 
    article  
    Abstract: Complex problem-solving and planning involve the most anterior part of the frontal lobes including the fronto-polar prefrontal cortex (FPPC)(1-6), which is especially well developed in humans compared with other primates(7,8). The specific role of this region in human cognition, however, is poorly understood. Here we show using functional magnetic resonance imaging, that bilateral regions in the FPPC alone are selectively activated when subjects have to keep in mind a main goal while performing concurrent (sub)goals. Neither keeping in mind a goal over time (working memory) nor successively allocating attentional resources between alternative goals (dual-task performance) could by themselves activate these regions. Our results indicate that the FPPC selectively mediates the human ability to hold in mind goals while exploring and processing secondary goals, a process generally required in planning and reasoning.
    BibTeX:
    @article{Koechlin1999,
      author = {Koechlin, E and Basso, G and Pietrini, P and Panzer, S and Grafman, J},
      title = {The role of the anterior prefrontal cortex in human cognition},
      journal = {NATURE},
      year = {1999},
      volume = {399},
      number = {6732},
      pages = {148-151}
    }
    
    Konishi, S., Nakajima, K., Uchida, I., Kikyo, H., Kameyama, M. & Miyashita, Y. Common inhibitory mechanism in human inferior prefrontal cortex revealed by event-related functional MRI {1999} BRAIN
    Vol. {122}({Part 5}), pp. {981-991} 
    article  
    Abstract: Inhibition of an ongoing reaction tendency for adaptation to changing environments is a major function of the human prefrontal cortex. This function has been investigated frequently using the go/no-go task and set-shifting tasks such as the Wisconsin Card Sorting Test (WCST), Studies in humans and monkeys suggest the involvement of the dorsolateral prefrontal cortex in the two task paradigms. However, it remains unknown where in the dorsolateral prefrontal cortex this function is localized, whether a common inhibitory mechanism is used in these task paradigms and how this inhibitory function acts on two different targets, i,e, the go response in the go/no-go task and the cognitive set in the WCST. In the go/no-go task of this study, subjects were instructed to either respond (go trial) or not respond (no-go trial), depending on the cue stimulus presented. The signals of functional MRT (fMRI) related to the inhibitory function should be transient by nature. Thus, we used the temporal resolution of fMRI (event-related fMRI) by which transient signals in go and no-go trials can be analysed separately and compared with each other, We found a focus that showed transient no-go dominant activity in the posterior part of the inferior frontal sulcus in the right hemisphere, This was true irrespective of whether the subjects used their right or left hands. These results suggest that the transient activation in the right inferior prefrontal area is related to the neural mechanism underlying the response inhibition function, Furthermore, this area was found to be overlapped spatially with the area that was activated transiently during cognitive set shifting in the WCST The transient signals in the go/no-go task peaked 5s after the transient expression of the inhibitory function, and the transient signals in the WCST peaked 7s after the transient expression, reflecting different durations of neuronal activity in the two inhibitory task paradigms, These results imply that the right inferior prefrontal area is commonly involved in the inhibition of different targets, i,e, the go response during performance of the go/no-go task and the cognitive set during performance of the WCST.
    BibTeX:
    @article{Konishi1999,
      author = {Konishi, S and Nakajima, K and Uchida, I and Kikyo, H and Kameyama, M and Miyashita, Y},
      title = {Common inhibitory mechanism in human inferior prefrontal cortex revealed by event-related functional MRI},
      journal = {BRAIN},
      year = {1999},
      volume = {122},
      number = {Part 5},
      pages = {981-991}
    }
    
    Koob, G. & Le Moal, M. Drug addiction, dysregulation of reward, and allostasis {2001} NEUROPSYCHOPHARMACOLOGY
    Vol. {24}({2}), pp. {97-129} 
    article  
    Abstract: This paper reviews recent developments in the neurocircuitry and neurobiology of addiction from a perspective of allostasis. A model is proposed for brain changes that occur during the development of addiction that explain the persistent vulnerability to relapse long after drug-taking has ceased. Addiction is presented as a cycle of spiralling dysregulation of brain reward systems that progressively increases, resulting in the compulsive use and loss of control over drug-taking. The development of addiction recruits different sources of reinforcement, different neuroadaptive mechanisms, and different neurochemical changes to dysregulate the brain reward system. Counteradaptive processes such as opponent-process that are part of normal homeostatic limitation of reward function fail to return within the normal homeostatic range and are hypothesized to form an allostatic state. Allostasis from the addiction perspective is defined as the process of maintaining apparent reward function stability by changes in brain reward mechanisms. The allostatic state represents a chronic deviation of reward set point and is fueled not only by dysregulation of reward circuits per se, but also by the activation of brain and hormonal stress responses. The manifestation of this allostatic state as compulsive drug-taking and loss of control over drug-taking is hypothesized to be expressed through activation of brain circuits involved in compulsive behavior such as the cortico-striatal-thalamic loop. The view that addiction is the pathology that results from an allostatic mechanism using the circuits established for natural rewards provides a realistic approach to identifying the neurobiological factors that produce vulnerability to addiction and relapse. [Neuropsychopharmacology 24:97-129, 2002] (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.
    BibTeX:
    @article{Koob2001,
      author = {Koob, GF and Le Moal, M},
      title = {Drug addiction, dysregulation of reward, and allostasis},
      journal = {NEUROPSYCHOPHARMACOLOGY},
      year = {2001},
      volume = {24},
      number = {2},
      pages = {97-129}
    }
    
    Kramer, A., Hahn, S., Cohen, N., Banich, M., McAuley, E., Harrison, C., Chason, J., Vakil, E., Bardell, L., Boileau, R. & Colcombe, A. Ageing, fitness and neurocognitive function {1999} NATURE
    Vol. {400}({6743}), pp. {418-419} 
    article  
    BibTeX:
    @article{Kramer1999,
      author = {Kramer, AF and Hahn, S and Cohen, NJ and Banich, MT and McAuley, E and Harrison, CR and Chason, J and Vakil, E and Bardell, L and Boileau, RA and Colcombe, A},
      title = {Ageing, fitness and neurocognitive function},
      journal = {NATURE},
      year = {1999},
      volume = {400},
      number = {6743},
      pages = {418-419}
    }
    
    Kringelbach, M. & Rolls, E. The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology {2004} PROGRESS IN NEUROBIOLOGY
    Vol. {72}({5}), pp. {341-372} 
    article DOI  
    Abstract: The human orbitofrontal cortex is an important brain region for the processing of rewards and punishments, which is a prerequisite for the complex and flexible emotional and social behaviour which contributes to the evolutionary success of humans. Yet much remains to be discovered about the functions of this key brain region, and new evidence from functional neuroimaging and clinical neuropsychology is affording new insights into the different functions of the human orbitofrontal cortex. We review the neuroanatomical and neuropsychological literature on the human orbitofrontal cortex, and propose two distinct trends of neural activity based on a meta-analysis of neuroimaging studies. One is a mediolateral distinction, whereby medial orbitofrontal cortex activity is related to monitoring the reward value of many different reinforcers, whereas lateral orbitofrontal cortex activity is related to the evaluation of punishers which may lead to a change in ongoing behaviour. The second is a posterior-anterior distinction with more complex or abstract reinforcers (such as monetary gain and loss) represented more anteriorly in the orbitofrontal cortex than simpler reinforcers such as taste or pain. Finally, we propose new neuroimaging methods for obtaining further evidence on the localisation of function in the human orbitofrontal cortex. (C) 2004 Elsevier Ltd. All rights reserved.
    BibTeX:
    @article{Kringelbach2004,
      author = {Kringelbach, ML and Rolls, ET},
      title = {The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology},
      journal = {PROGRESS IN NEUROBIOLOGY},
      year = {2004},
      volume = {72},
      number = {5},
      pages = {341-372},
      doi = {{10.1016/j.pneurobio.2004.03.006}}
    }
    
    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{Lane1997b,
      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., Ahern, G., Schwartz, G. & Davidson, R. Neuroanatomical correlates of happiness, sadness, and disgust {1997} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {154}({7}), pp. {926-933} 
    article  
    Abstract: Objective: Happiness, sadness, and disgust are three emotions that differ in their valence (positive or negative) and associated action tendencies (approach or withdrawal). This study was designed to investigate the neuroanatomical correlates of these discrete emotions. Method: Twelve healthy female subjects were studied. Positron emission tomography and [O-15]H2O were used to measure regional blain activity. There were 12 conditions per subject: happiness, sadness, and disgust and three control conditions, each induced by film and recall. Emotion and control tasks were alternated throughout. Condition order was pseudorandomized and counterbalanced across subjects. Analyses focused on brain activity pastel ns for each emotion when combining film and recall data. Results: Happiness, sadness, and disgust were each associated with increases in activity in the thalamus and menial prefrontal cortex (Brodmann's area 9). These three emotions were also associated with activation of anterior and posterior temporal structures, primarily when induced by film. Recalled sadness was associated with increased activation in the anterior insula. Happiness was distinguished from sadness by greater activity in the vicinity of ventral mesial frontal cortex. Conclusions: While this study should be considered preliminary, it identifies regions of the brain that participate in happiness, sadness, and disgust, regions that distinguish between positive and negative emotions, and regions that depend on both the elicitor and valence of emotion or their interaction.
    BibTeX:
    @article{Lane1997a,
      author = {Lane, RD and Reiman, EM and Ahern, GL and Schwartz, GE and Davidson, RJ},
      title = {Neuroanatomical correlates of happiness, sadness, and disgust},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {1997},
      volume = {154},
      number = {7},
      pages = {926-933},
      note = {54th Annual Meeting of the American-Psychosomatic-Society, WILLIAMSBURG, VA, MAR 07-09, 1996}
    }
    
    Lane, R., Reiman, E., Bradley, M., Lang, P., Ahern, G., Davidson, R. & Schwartz, G. Neuroanatomical correlates of pleasant and unpleasant emotion {1997} NEUROPSYCHOLOGIA
    Vol. {35}({11}), pp. {1437-1444} 
    article  
    Abstract: Substantial evidence suggests that a key distinction in the classification of human emotion is that between an appetitive motivational system associated with positive or pleasant emotion and an aversive motivational system associated with negative or unpleasant emotion. To explore the neural substrates of these two systems, 12 healthy women viewed sets of pictures previously demonstrated to elicit pleasant, unpleasant and neutral emotion, while positron emission tomographic (PET) measurements of regional cerebral blood flow were obtained. Pleasant and unpleasant emotions were each distinguished from neutral emotion conditions by significantly increased cerebral blood flow in the vicinity of the medial prefrontal cortex (Brodmann's area 9), thalamus, hypothalamus and midbrain (P < 0.005). Unpleasant was distinguished from neutral or pleasant emotion by activation of the bilateral occipito temporal cortex and cerebellum, and left parahippocampal gyrus, hippocampus and amygdala (P < 0.005). Pleasant was also distinguished from neutral but not unpleasant emotion by activation of the head of the left caudate nucleus (P < 0.005). These findings are consistent with those from other recent PET studies of human emotion and demonstrate that there are both common and unique components of the neural networks mediating pleasant and unpleasant emotion in healthy women. (C) 1997 Elsevier Science Ltd.
    BibTeX:
    @article{Lane1997,
      author = {Lane, RD and Reiman, EM and Bradley, MM and Lang, PJ and Ahern, GL and Davidson, RJ and Schwartz, GE},
      title = {Neuroanatomical correlates of pleasant and unpleasant emotion},
      journal = {NEUROPSYCHOLOGIA},
      year = {1997},
      volume = {35},
      number = {11},
      pages = {1437-1444}
    }
    
    Laruelle, M., AbiDargham, A., vanDyck, C., Gil, R., DSouza, C., Erdos, J., McCance, E., Rosenblatt, W., Fingado, C., Zoghbi, S., Baldwin, R., Seibyl, J., Krystal, J., Charney, D. & Innis, R. Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects {1996} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {93}({17}), pp. {9235-9240} 
    article  
    Abstract: The dopamine hypothesis of schizophrenia proposes that hyperactivity of dopaminergic transmission is associated with this illness, but direct observation of abnormalities of dopamine function in schizophrenia has remained elusive, We used a newly developed single photon emission computerized tomography method to measure amphetamine-induced dopamine release in the striatum of fifteen patients with schizophrenia and fifteen healthy controls, Amphetamine-induced dopamine release was estimated by the amphetamine-induced reduction in dopamine D-2 receptor availability, measured as the binding potential of the specific D-2 receptor radiotracer [I-123] (S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]b enzamide ([I-123]IBZM), The amphetamine-induced decrease in [I-123]IBZM binding potential was significantly greater in the schizophrenic group (-19.5 +/- 4.1 compared with the control group (-7.6 +/- 2.1, In the schizophrenic group, elevated amphetamine effect on [I-123]IBZM binding potential was associated with emergence or worsening of positive psychotic symptoms, This result suggests that psychotic symptoms elicited in this experimental setting in schizophrenic patients are associated with exaggerated stimulation of dopaminergic transmission. Such an observation would be compatible with an abnormal responsiveness of dopaminergic neurons in schizophrenia.
    BibTeX:
    @article{Laruelle1996,
      author = {Laruelle, M and AbiDargham, A and vanDyck, CH and Gil, R and DSouza, CD and Erdos, J and McCance, E and Rosenblatt, W and Fingado, C and Zoghbi, SS and Baldwin, RM and Seibyl, JP and Krystal, JH and Charney, DS and Innis, RB},
      title = {Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1996},
      volume = {93},
      number = {17},
      pages = {9235-9240}
    }
    
    Lawrie, S. & Abukmeil, S. Brain abnormality in schizophrenia - A systematic and quantitative review of volumetric magnetic resonance imaging studies {1998} BRITISH JOURNAL OF PSYCHIATRY
    Vol. {172}, pp. {110-120} 
    article  
    Abstract: Background Numerous in vivo brain imaging studies suggest that cerebral structure is abnormal in schizophrenia, but implicate different regions to varying extents. Method We identified published MRI studies in schizophrenia with searches of the computerised literature and key journals. Reports giving the volumes of cortical structures in people with schizophrenia and controls were included. The percentage differences in volumes were calculated and the median taken as a summary measure for each brain region. Results Forty relevant studies were identified. The median percentage volume differences revealed overall reductions in the whole brain (3, temporal robe (6% left, 9.5% right), and the amygdala/hippocampal complex (6.5 5.5; and increases in the lateral ventricles (44 36, that were greatest in the body and occipital horns. Segmentation studies suggest that grey matter is reduced but that white matter volumes may actually be increased. In men, substantial reductions were also evident in the amygdala and hippocampus, as well as the largest reductions of all in the parahippocampus (14 9. Few studies gave figures for women alone. Conclusions Several brain structures in schizophrenia are affected to a greater extent than expected from overall reductions in brain volume. Further studies are required in affected women, and to try to identify clinical and aetiological associations of these findings.
    BibTeX:
    @article{Lawrie1998,
      author = {Lawrie, SM and Abukmeil, SS},
      title = {Brain abnormality in schizophrenia - A systematic and quantitative review of volumetric magnetic resonance imaging studies},
      journal = {BRITISH JOURNAL OF PSYCHIATRY},
      year = {1998},
      volume = {172},
      pages = {110-120}
    }
    
    LeDoux, J. Fear and the brain: Where have we been, and where are we going? {1998} BIOLOGICAL PSYCHIATRY
    Vol. {44}({12}), pp. {1229-1238} 
    article  
    Abstract: In recent years, there has been all explosion of interest ill the neural basis of emotion. Much of this enthusiasm has been triggered by studies of the amygdala and its contribution to fear. This work has shown that the amygdala detects and organizes responses to natural dangers (like predators) and learns about novel threats and the stimuli that predict their occurrence. The latter process has been studied extensively using a procedure called classical fear conditioning. This article surveys the progress that has been made in understanding the neural basis of fear and its implications for anxiety disorders, as well as the gaps in our knowledge. Biol Psychiatry 1998;44:1229-1238 (C) 1998 Society of Biological Psychiatry.
    BibTeX:
    @article{LeDoux1998,
      author = {LeDoux, J},
      title = {Fear and the brain: Where have we been, and where are we going?},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {1998},
      volume = {44},
      number = {12},
      pages = {1229-1238},
      note = {Research Symposium on Brain Neurocircuitry of Anxiety and Fear - Implications for Clinical Research and Practice, BOSTON, MASSACHUSETTS, MAR 26, 1998}
    }
    
    LEMOAL, M. & SIMON, H. MESOCORTICOLIMBIC DOPAMINERGIC NETWORK - FUNCTIONAL AND REGULATORY ROLES {1991} PHYSIOLOGICAL REVIEWS
    Vol. {71}({1}), pp. {155-234} 
    article  
    BibTeX:
    @article{LEMOAL1991,
      author = {LEMOAL, M and SIMON, H},
      title = {MESOCORTICOLIMBIC DOPAMINERGIC NETWORK - FUNCTIONAL AND REGULATORY ROLES},
      journal = {PHYSIOLOGICAL REVIEWS},
      year = {1991},
      volume = {71},
      number = {1},
      pages = {155-234}
    }
    
    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}}
    }
    
    Lewis, D. & Levitt, P. Schizophrenia as a disorder of neurodevelopment {2002} ANNUAL REVIEW OF NEUROSCIENCE
    Vol. {25}, pp. {409-432} 
    article DOI  
    Abstract: A combination of genetic susceptibility and environmental perturbations appear to be necessary for the expression of schizophrenia. In addition, the pathogenesis of the disease is hypothesized to be neurodevelopmental in nature based on reports of an excess of adverse events during the pre- and perinatal periods, the presence of cognitive and behavioral signs during childhood and adolescence, and the lack of evidence of a neurodegenerative process in most individuals with schizophrenia. Recent studies of neurodevelopmental mechanisms strongly suggest that no single gene or factor is responsible for driving a highly complex biological process. Together, these findings suggest that combinatorial genetic and environmental factors, which disturb a normal developmental course early in life, result in molecular and histogenic responses that cumulatively lead to different developmental trajectories and the clinical phenotype recognized as schizophrenia.
    BibTeX:
    @article{Lewis2002,
      author = {Lewis, DA and Levitt, P},
      title = {Schizophrenia as a disorder of neurodevelopment},
      journal = {ANNUAL REVIEW OF NEUROSCIENCE},
      year = {2002},
      volume = {25},
      pages = {409-432},
      doi = {{10.1146/annurev.neuro.25.112701.142754}}
    }
    
    Lieberman, J., Tollefson, G., Charles, C., Zipursky, R., Sharma, T., Kahn, R., Keefe, R., Green, A., Gur, R., McEvoy, J., Perkins, D., Hamer, R., Gu, H., Tohen, M. & HGDH Study Grp Antipsychotic drug effects on brain morphology in first-episode psychosis {2005} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {62}({4}), pp. {361-370} 
    article  
    Abstract: Background: Pathomorphologic brain changes occurring as early as first-episode schizophrenia have been extensively described. Longitudinal studies have demonstrated that these changes may be progressive and associated with clinical outcome. This raises the possibility that antipsychotics might alter such pathomorphologic progression in early-stage schizophrenia. Objective: To test a priori hypotheses that olanzapine-treated patients have less change over time in whole brain gray matter volumes and lateral ventricle volumes than haloperidol-treated patients and that gray matter and lateral ventricle volume changes are associated with changes in psychopathology and neurocognition. Design: Longitudinal, randomized, controlled, multisite, double-blind study. Patients treated and followed up for up to 104 weeks. Neurocognitive and magnetic resonance imaging (MRI) assessments performed at weeks 0 (baseline), 12, 24, 52, and 104. Mixed-models analyses with time-dependent covariates evaluated treatment effects on MRI end points and explored relationships between MRI, psychopathologic, and neurocognitive outcomes. Setting: Fourteen academic medical centers (United States, 11; Canada, 1; Netherlands, 1; England, 1). Participants: Patients with first-episode psychosis (DSM-IV) and healthy volunteers. Interventions: Random allocation to a conventional antipsychotic, haloperidol (2-20 mg/d), or an atypical antipsychotic, olanzapine (5-20 mg/d). Main Outcome Measures: Brain volume changes assessed by MRI. Results: Of 263 randomized patients, 161 had baseline and at least 1 postbaseline MRI evaluation. Haloperidol-treated patients exhibited significant decreases in gray matter volume, whereas olanzapine-treated patients did not. A matched sample of healthy volunteers (n = 58) examined contemporaneously showed no change in gray matter volume. Conclusions: Patients with first-episode psychosis exhibited a significant between-treatment difference in MRI volume changes. Haloperidol was associated with significant reductions in gray matter volume, whereas olanzapine was not. Post hoc analyses suggested that treatment effects on brain volume and psychopathology of schizophrenia may be associated. The differential treatment effects on brain morphology could be due to haloperidol-associated toxicity or greater therapeutic effects of olanzapine.
    BibTeX:
    @article{Lieberman2005,
      author = {Lieberman, JA and Tollefson, GD and Charles, C and Zipursky, R and Sharma, TN and Kahn, RS and Keefe, RSE and Green, AI and Gur, RE and McEvoy, J and Perkins, D and Hamer, RM and Gu, HB and Tohen, M and HGDH Study Grp},
      title = {Antipsychotic drug effects on brain morphology in first-episode psychosis},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {2005},
      volume = {62},
      number = {4},
      pages = {361-370},
      note = {42nd Meeting of the American-College-of-Neuropsychopharmacology, San Juan, PR, DEC 07-11, 2003}
    }
    
    Lim, K., Hedehus, M., Moseley, M., de Crespigny, A., Sullivan, E. & Pfefferbaum, A. Compromised white matter tract integrity in schizophrenia inferred from diffusion tensor imaging {1999} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {56}({4}), pp. {367-374} 
    article  
    Abstract: Background: Current investigations suggest that brain white matter may be qualitatively altered in schizophrenia even in the face of normal white matter volume. Diffusion tensor imaging provides a new approach for quantifying the directional coherence and possibly connectivity of white matter fibers in vivo. Methods: Ten men who were veterans of the US Armed Forces and met the DSM-IV criteria for schizophrenia and 10 healthy, age-matched control men were scanned using magnetic resonance diffusion tensor imaging and magnetic resonance structural imaging. Results: Relative to controls, the patients with schizophrenia exhibited lower anisotropy in white matter, despite absence of a white matter volume deficit. In contrast to the white matter pattern, gray matter anisotropy did not distinguish the groups, even though the patients with schizophrenia had a significant gray matter volume deficit. The abnormal white matter anisotropy in patients with schizophrenia was present in both hemispheres and was widespread, extending from the frontal to occipital brain regions. Conclusions: Despite the small sample size, diffusion tensor imaging was powerful enough to yield significant group differences, indicating widespread alteration in brain white matter integrity but not necessarily white matter volume in schizophrenia.
    BibTeX:
    @article{Lim1999,
      author = {Lim, KO and Hedehus, M and Moseley, M and de Crespigny, A and Sullivan, EV and Pfefferbaum, A},
      title = {Compromised white matter tract integrity in schizophrenia inferred from diffusion tensor imaging},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1999},
      volume = {56},
      number = {4},
      pages = {367-374}
    }
    
    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. LONG-TERM SYNAPTIC DEPRESSION IN THE MAMMALIAN BRAIN {1994} NEURON
    Vol. {12}({3}), pp. {457-472} 
    article  
    Abstract: A generally accepted hypothesis in neurobiology has been that at the cellular level, memories are stored, at least in part, as long-term alterations in the strength of synaptic transmission. In recent years, considerable attention has been paid to persistent, use-dependent mechanisms that increase synaptic strength, which are collectively referred to as long-term potentiation (LTP). This review shall examine the opposite phenomenon, use-dependent decreases in synaptic strength, or long-term depression (LTD). LTD is a broad term that is used to describe synaptic depression according to several different learning rules and in a wide variety of brain structures.
    BibTeX:
    @article{LINDEN1994,
      author = {LINDEN, DJ},
      title = {LONG-TERM SYNAPTIC DEPRESSION IN THE MAMMALIAN BRAIN},
      journal = {NEURON},
      year = {1994},
      volume = {12},
      number = {3},
      pages = {457-472}
    }
    
    LIPSKA, B., JASKIW, G. & WEINBERGER, D. POSTPUBERTAL EMERGENCE OF HYPERRESPONSIVENESS TO STRESS AND TO AMPHETAMINE AFTER NEONATAL EXCITOTOXIC HIPPOCAMPAL DAMAGE - A POTENTIAL ANIMAL-MODEL OF SCHIZOPHRENIA {1993} NEUROPSYCHOPHARMACOLOGY
    Vol. {9}({1}), pp. {67-75} 
    article  
    Abstract: The constellation of major phenomena associated with schizophrenia (e.g., postpubertal onset, congenital hippocampal area damage, cortical functional deficits, limbic dopamine (DA) dysregulation, and vulnerability to stress) have been difficult to explain with a unitary animal model. Although it has been shown that rats develop increased mesolimbic DA transmission and reduced cortical DA turnover following adult excitotoxic lesions of the ventral hippocampus (VH), the implication of early developmental VH lesions are not known. To determine the developmental sequelae of such changes, we produced ibotenic acid lesions of the ventral hippocampal formation in rats on the 7th day after birth (PD7). Motor activity in a novel environment, after saline injection and after d-amphetamine administration were similar in control and lesioned rats at PD35. However, in early adulthood, at PD56, animals with the hippocampal lesion were hyperactive in each of these conditions. The emergence of the hyperactivity at PD56 could be prevented by pretreatment with haloperidol. Moreover, rats lesioned as neonates, in contrast to a similar lesion induced in adult animals, were also hyperresponsive to stress evaluated with a swim test. This latter effect is analogous to that seen after adult lesions of the medial prefrontal cortex, rather than after adult lesions of VH, suggesting that the neonatal VH lesion may affect functional development of the medial prefrontal cortex. These results demonstrate that in rats with neonatally induced excitotoxic VH lesions, behavioral indices consistent with increased mesolimbic DA responsivity to stressful and to pharmacologic stimuli emerge only in early adulthood. Homologous mechanisms may underlie certain aspects of the pathophysiology of schizophrenia.
    BibTeX:
    @article{LIPSKA1993,
      author = {LIPSKA, BK and JASKIW, GE and WEINBERGER, DR},
      title = {POSTPUBERTAL EMERGENCE OF HYPERRESPONSIVENESS TO STRESS AND TO AMPHETAMINE AFTER NEONATAL EXCITOTOXIC HIPPOCAMPAL DAMAGE - A POTENTIAL ANIMAL-MODEL OF SCHIZOPHRENIA},
      journal = {NEUROPSYCHOPHARMACOLOGY},
      year = {1993},
      volume = {9},
      number = {1},
      pages = {67-75}
    }
    
    Louie, K. & Wilson, M. Temporally structured replay of awake hippocampal ensemble activity during rapid eye movement sleep {2001} NEURON
    Vol. {29}({1}), pp. {145-156} 
    article  
    Abstract: Human dreaming occurs during rapid eye movement (REM) sleep. To investigate the structure of neural activity during REM sleep, we simultaneously recorded the activity of multiple neurons in the rat hippocampus during both sleep and awake behavior. We show that temporally sequenced ensemble firing rate patterns reflecting tens of seconds to minutes of behavioral experience are reproduced during REM episodes at an equivalent timescale. Furthermore, within such REM episodes behavior-dependent modulation of the subcortically driven theta rhythm is also reproduced. These results demonstrate that long temporal sequences of patterned multineuronal activity suggestive of episodic memory traces are reactivated during REM sleep. Such reactivation may be important for memory processing and provides a basis for the electrophysiological examination of the content of dream states.
    BibTeX:
    @article{Louie2001,
      author = {Louie, K and Wilson, MA},
      title = {Temporally structured replay of awake hippocampal ensemble activity during rapid eye movement sleep},
      journal = {NEURON},
      year = {2001},
      volume = {29},
      number = {1},
      pages = {145-156}
    }
    
    Luck, S. & Vogel, E. The capacity of visual working memory for features and conjunctions {1997} NATURE
    Vol. {390}({6657}), pp. {279-281} 
    article  
    Abstract: Short-term memory storage can be divided into separate subsystems for verbal information and visual information(1), and recent studies have begun to delineate the neural substrates of these working-memory systems(2-6). Although the verbal storage system has been well characterized, the storage capacity of visual working memory has not yet been established for simple, suprathreshold features or for conjunctions of features. Here we demonstrate that it is possible to retain information about only four colours or orientations in visual working memory at one time. However, it is also possible to retain both the colour and the orientation of four objects, indicating that visual working memory stores integrated objects rather than individual features. Indeed, objects defined by a conjunction of four features can be retained in working memory just as well as single-feature objects, allowing sixteen individual features to be retained when distributed across four objects. Thus, the capacity of visual working memory must be understood in terms of integrated objects rather than individual features, which places significant constraints on cognitive and neurobiological models of the temporary storage of visual information(7).
    BibTeX:
    @article{Luck1997,
      author = {Luck, SJ and Vogel, EK},
      title = {The capacity of visual working memory for features and conjunctions},
      journal = {NATURE},
      year = {1997},
      volume = {390},
      number = {6657},
      pages = {279-281}
    }
    
    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}
    }
    
    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}
    }
    
    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}
    }
    
    Marcus, J., Aschkenasi, C., Lee, C., Chemelli, R., Saper, C., Yanagisawa, M. & Elmquist, J. Differential expression of orexin receptors 1 and 2 in the rat brain {2001} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {435}({1}), pp. {6-25} 
    article  
    Abstract: Orexins (hypocretins) are neuropeptides synthesized in the central nervous system exclusively by neurons of the lateral hypothalamus. Orexin-containing neurons have widespread projections and have been implicated in complex physiological functions including feeding behavior, sleep states, neuroendocrine function, and autonomic control. Two orexin receptors (OX,R and OX,R) have been identified, with distinct expression patterns throughout the brain, but a systematic examination of orexin receptor expression in the brain has not appeared. We used in situ hybridization histochemistry to examine the patterns of expression of mRNA for both orexin receptors throughout the brain. OX,R mRNA was observed in many brain regions including the prefrontal and infralimbic cortex, hippocampus, paraventricular thalamic nucleus, ventromedial hypothalamic nucleus, dorsal raphe nucleus, and locus coeruleus. OX,R mRNA was prominent in a complementary distribution including the cerebral cortex, septal nuclei, hippocampus, medial thalamic groups, raphe nuclei, and many hypothalamic nuclei including the tuberomammillary nucleus, dorsomedial nucleus, paraventricular nucleus, and ventral premammillary nucleus. The differential distribution of orexin receptors is consistent with the proposed multifaceted roles of orexin in regulating homeostasis and may explain the unique role of the OX,R receptor in regulating sleep state stability. (C) 2001 Wiley-Liss, Inc.
    BibTeX:
    @article{Marcus2001,
      author = {Marcus, JN and Aschkenasi, CJ and Lee, CE and Chemelli, RM and Saper, CB and Yanagisawa, M and Elmquist, JK},
      title = {Differential expression of orexin receptors 1 and 2 in the rat brain},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {2001},
      volume = {435},
      number = {1},
      pages = {6-25}
    }
    
    Maren, S. Neurobiology of Pavlovian fear conditioning {2001} ANNUAL REVIEW OF NEUROSCIENCE
    Vol. {24}, pp. {897-931} 
    article  
    Abstract: Learning the relationships between aversive events and the environmental stimuli that predict such events is essential to the survival of organisms throughout the animal kingdom. Pavlovian fear conditioning is an exemplar of this form of learning that is exhibited by both rats and humans. Recent years have seen an incredible surge in interest in the neurobiology of fear conditioning. Neural circuits underlying fear conditioning have been mapped, synaptic plasticity in these circuits has been identified, and biochemical and genetic manipulations are beginning to unravel the molecular machinery responsible for the storage of fear memories. These advances represent an important step in understanding the neural substrates of a rapidly acquired and adaptive form of associative learning and memory in mammals.
    BibTeX:
    @article{Maren2001,
      author = {Maren, S},
      title = {Neurobiology of Pavlovian fear conditioning},
      journal = {ANNUAL REVIEW OF NEUROSCIENCE},
      year = {2001},
      volume = {24},
      pages = {897-931}
    }
    
    Maren, S. & Quirk, G. Neuronal signalling of fear memory {2004} NATURE REVIEWS NEUROSCIENCE
    Vol. {5}({11}), pp. {844-852} 
    article DOI  
    Abstract: The learning and remembering of fearful events depends on the integrity of the amygdala, but how are fear memories represented in the activity of amygdala neurons? Here, we review recent electrophysiological studies indicating that neurons in the lateral amygdala encode aversive memories during the acquisition and extinction of Pavlovian fear conditioning. Studies that combine unit recording with brain lesions and pharmacological inactivation provide evidence that the lateral amygdala is a crucial locus of fear memory. Extinction of fear memory reduces associative plasticity in the lateral amygdala and involves the hippocampus and prefrontal cortex. Understanding the signalling of aversive memory by amygdala neurons opens new avenues for research into the neural systems that support fear behaviour.
    BibTeX:
    @article{Maren2004,
      author = {Maren, S and Quirk, GJ},
      title = {Neuronal signalling of fear memory},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2004},
      volume = {5},
      number = {11},
      pages = {844-852},
      doi = {{10.1038/nrn1535}}
    }
    
    Marsicano, G., Wotjak, C., Azad, S., Bisogno, T., Rammes, G., Cascio, M., Hermann, H., Tang, J., Hofmann, C., Zieglgansberger, W., Di Marzo, V. & Lutz, B. The endogenous cannabinoid system controls extinction of aversive memories {2002} NATURE
    Vol. {418}({6897}), pp. {530-534} 
    article DOI  
    Abstract: Acquisition and storage of aversive memories is one of the basic principles of central nervous systems throughout the animal kingdom(1). In the absence of reinforcement, the resulting behavioural response will gradually diminish to be finally extinct. Despite the importance of extinction(2), its cellular mechanisms are largely unknown. The cannabinoid receptor 1 (CB1)(3) and endocannabinoids(4) are present in memory-related brain areas(5,6) and modulate memory(7,8). Here we show that the endogenous cannabinoid system has a central function in extinction of aversive memories. CB1-deficient mice showed strongly impaired short-term and long-term extinction in auditory fear-conditioning tests, with unaffected memory acquisition and consolidation. Treatment of wild-type mice with the CB1 antagonist SR141716A mimicked the phenotype of CB1-deficient mice, revealing that CB1 is required at the moment of memory extinction. Consistently, tone presentation during extinction trials resulted in elevated levels of endocannabinoids in the basolateral amygdala complex,a region known to control extinction of aversive memories(9). In the basolateral amygdala, endocannabinoids and CB1 were crucially involved in long-term depression of GABA (gamma-aminobutyric acid)-mediated inhibitory currents. We propose that endocannabinoids facilitate extinction of aversive memories through their selective inhibitory effects on local inhibitory networks in the amygdala.
    BibTeX:
    @article{Marsicano2002,
      author = {Marsicano, G and Wotjak, CT and Azad, SC and Bisogno, T and Rammes, G and Cascio, MG and Hermann, H and Tang, JR and Hofmann, C and Zieglgansberger, W and Di Marzo, V and Lutz, B},
      title = {The endogenous cannabinoid system controls extinction of aversive memories},
      journal = {NATURE},
      year = {2002},
      volume = {418},
      number = {6897},
      pages = {530-534},
      doi = {{10.1038/nature00839}}
    }
    
    Martin, A. & Chao, L. Semantic memory and the brain: structure and processes {2001} CURRENT OPINION IN NEUROBIOLOGY
    Vol. {11}({2}), pp. {194-201} 
    article  
    Abstract: Recent functional brain imaging studies suggest that object concepts may be represented, in part, by distributed networks of discrete cortical regions that parallel the organization of sensory and motor systems. In addition, different regions of the left lateral prefrontal cortex, and perhaps anterior temporal cortex, may have distinct roles in retrieving, maintaining and selecting semantic information.
    BibTeX:
    @article{Martin2001,
      author = {Martin, A and Chao, LL},
      title = {Semantic memory and the brain: structure and processes},
      journal = {CURRENT OPINION IN NEUROBIOLOGY},
      year = {2001},
      volume = {11},
      number = {2},
      pages = {194-201}
    }
    
    Mattay, V., Goldberg, T., Fera, F., Hariri, A., Tessitore, A., Egan, M., Kolachana, B., Callicott, J. & Weinberger, D. Catechol O-methyltransferase val(158)-met genotype and individual variation in the brain response to amphetamine {2003} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {100}({10}), pp. {6186-6191} 
    article  
    Abstract: Monamines subserve many critical roles in the brain, and monoaminergic drugs such as amphetamine have a long history in the treatment of neuropsychiatric disorders and also as a substance of abuse. The clinical effects of amphetamine are quite variable, from positive effects on mood and cognition in some individuals, to negative responses in others, perhaps related to individual variations in monaminergic function and monoamine system genes. We explored the effect of a functional polymorphism (val(158)-Met) in the catechol O-methyltransferase gene, which has been shown to modulate prefrontal dopamine animals and prefrontal cortical function in humans, on the modulatory actions of amphetamine on the prefrontal cortex. Amphetamine enhanced the efficiency of prefrontal cortex function assayed with functional MRI during a working memory task in subjects with the high enzyme activity val/val genotype, who presumably have relatively less prefrontal synaptic dopamine, at all levels of task difficulty. In contrast, in subjects with the low activity met/met genotype who tend to have superior baseline prefrontal function, the drug had no effect on cortical efficiency at low-to-moderate working memory load and caused deterioration at high working memory load. These data illustrate an application of functional neuroimaging in pharmacogenomics and extend basic evidence of an inverted-''U'' functional-response curve to increasing dopamine signaling in the prefrontal cortex. Further, individuals with the met/met catechol O-methyltransferase genotype appear to beat increased risk for an adverse response to amphetamine.
    BibTeX:
    @article{Mattay2003,
      author = {Mattay, VS and Goldberg, TE and Fera, F and Hariri, AR and Tessitore, A and Egan, MF and Kolachana, B and Callicott, JH and Weinberger, DR},
      title = {Catechol O-methyltransferase val(158)-met genotype and individual variation in the brain response to amphetamine},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {2003},
      volume = {100},
      number = {10},
      pages = {6186-6191}
    }
    
    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., 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}}
    }
    
    MAZOYER, B., TZOURIO, N., FRAK, V., SYROTA, A., MURAYAMA, N., LEVRIER, O., SALAMON, G., DEHAENE, S., COHEN, L. & MEHLER, J. THE CORTICAL REPRESENTATION OF SPEECH {1993} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {5}({4}), pp. {467-479} 
    article  
    Abstract: In this study, we compare regional cerebral blood flow (rCBF) while French monolingual subjects listen to continuous speech in an unknown language, to lists of French words, or to meaningful and distorted stories in French. Our results show that, in addition to regions devoted to single-word comprehension, processing of meaningful stories activates the left middle temporal gyrus, the left and right temporal poles, and a superior prefrontal area in the left frontal lobe. Among these regions, only the temporal poles remain activated whenever sentences with acceptable syntax and prosody are presented.
    BibTeX:
    @article{MAZOYER1993,
      author = {MAZOYER, BM and TZOURIO, N and FRAK, V and SYROTA, A and MURAYAMA, N and LEVRIER, O and SALAMON, G and DEHAENE, S and COHEN, L and MEHLER, J},
      title = {THE CORTICAL REPRESENTATION OF SPEECH},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {1993},
      volume = {5},
      number = {4},
      pages = {467-479}
    }
    
    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}
    }
    
    McBride, W., Murphy, J. & Ikemoto, S. Localization of brain reinforcement mechanisms: intracranial self-administration and intracranial place-conditioning studies {1999} BEHAVIOURAL BRAIN RESEARCH
    Vol. {101}({2}), pp. {129-152} 
    article  
    Abstract: Intracranial self-administration (ICSA) and intracranial place conditioning (ICPC) methodologies have been mainly used to study drug reward mechanisms, but they have also been applied toward examining brain reward mechanisms. ICSA studies in rodents have established that the ventral tegmental area (VTA) is a site supporting morphine and ethanol reinforcement. ICPC studies confirmed that injection of morphine into the VTA produces conditioned place preference (CPP). Further confirmation that activation of opioid receptors within the VTA is reinforcing comes from the findings that the endogenous opioid peptide met-enkephalin injected into the VTA produces CPP, and that the mu- and delta-opioid agonists, DAMGO and DPDPE, are self-infused into the VTA. Activation of the VTA dopamine (DA) system may produce reinforcing effects in general because (a) neurotensin is self-administered into the VTA, and injection of neurotensin into the VTA produces CPP and enhances DA release in the nucleus accumbens (NAC), and (b) GABA(A) antagonists are self-administered into the anterior VTA and injections of GABA(A) antagonists into the anterior VTA enhance DA release in the NAG. The NAC also appears to have a major role in brain reward mechanisms, whereas most data from ICSA and ICPC studies do not support an involvement of the caudate-putamen in reinforcement processes. Rodents will self-infuse a variety of drugs of abuse (e.g, amphetamine, morphine, phencyclidine and cocaine) into the NAG, and this occurs primarily in the shell region. ICPC studies also indicate that injection of amphetamine into the shell portion of the NAC produces CPP. Activation of the DA system within the shell subregion of the NAC appears to play a key role in brain reward mechanisms. Rats will ICSA the DA uptake blocker, nomifensine, into the NAC shell; co-infusion with a D-2 antagonist can block this behavior. In addition, rats will self-administer a mixture of a D-1 plus a D-2 agonist into the shell, but not the core, region of the NAG. The ICSA of this mixture can be blocked with the co-infusion of either a D-1 or a D-2 antagonist. However, the interactions of other transmitter systems within the NAC may also play key roles because NMDA antagonists and the muscarinic agonist carbachol are self-infused into the NAG. The medial prefrontal (MPF) cortex supports the ICSA of cocaine and phencyclidine. The DA system also seems to play a role in this behavior since cocaine self-infusion into the MPF cortex can be blocked by co-infusing a D-2 antagonist, or with 6-OHDA lesions of the MPF cortex. Limited studies have been conducted on other CNS regions to elucidate their role in brain and drug reward mechanisms using ICSA or ICPC procedures. Among these regions, ICPC findings suggest that cocaine and amphetamine are rewarding in the rostral ventral pallidum (VP); ICSA and ICPC studies indicate that morphine is rewarding in the dorsal hippocampus, central gray and lateral hypothalamus. Finally, substance P mediated systems within the caudal VP (nucleus basalis magnocellularis) and serotonin systems of the dorsal and median raphe nuclei may also be important anatomical components involved in brain reward mechanisms. Overall, the ICSA and ICPC studies indicate that there are a number of receptors, neuronal pathways, and discrete CNS sites involved in brain reward mechanisms. (C) 1999 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{McBride1999,
      author = {McBride, WJ and Murphy, JM and Ikemoto, S},
      title = {Localization of brain reinforcement mechanisms: intracranial self-administration and intracranial place-conditioning studies},
      journal = {BEHAVIOURAL BRAIN RESEARCH},
      year = {1999},
      volume = {101},
      number = {2},
      pages = {129-152}
    }
    
    MCCARTHY, G., BLAMIRE, A., PUCE, A., NOBRE, A., BLOCH, G., HYDER, F., GOLDMANRAKIC, P. & SHULMAN, R. FUNCTIONAL MAGNETIC-RESONANCE-IMAGING OF HUMAN PREFRONTAL CORTEX ACTIVATION DURING A SPATIAL WORKING-MEMORY TASK {1994} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {91}({18}), pp. {8690-8694} 
    article  
    Abstract: High-speed magnetic resonance (MR) imaging was used to detect activation in the human prefrontal cortex induced by a spatial working memory task modeled on those used to elucidate neuronal circuits in nonhuman primates. Subjects were required to judge whether the location occupied by the current stimulus had been occupied previously over a sequence of 14 or 15 stimuli presented in various locations. Control tasks were similar in all essential respects, except that the subject's task was to detect when one of the stimuli presented was colored red (color detection) or when a dot briefly appeared within the stimulus (dot detection). In all tasks, two to three target events occurred randomly. The MR signal increased in an area of the middle frontal gyrus corresponding to Brodmann's area 46 in all eight subjects performing the spatial working memory task. Right hemisphere activation was greater and more consistent than left. The MR signal change occurred within 6-9 sec of task onset and declined within a similar period after task completion. An increase in MR signal was also noted in the control tasks, but the magnitude of change was less than that recorded in the working memory task. These differences were replicated when testing was repeated in five of the original subjects. The localization of spatial working memory function in humans to a circumscribed area of the middle frontal gyrus supports the compartmentalization of working memory functions in the human prefrontal cortex and the localization of spatial memory processes to comparable areas in humans and nonhuman primates.
    BibTeX:
    @article{MCCARTHY1994,
      author = {MCCARTHY, G and BLAMIRE, AM and PUCE, A and NOBRE, AC and BLOCH, G and HYDER, F and GOLDMANRAKIC, P and SHULMAN, RG},
      title = {FUNCTIONAL MAGNETIC-RESONANCE-IMAGING OF HUMAN PREFRONTAL CORTEX ACTIVATION DURING A SPATIAL WORKING-MEMORY TASK},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1994},
      volume = {91},
      number = {18},
      pages = {8690-8694}
    }
    
    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}
    }
    
    McClure, S., Laibson, D., Loewenstein, G. & Cohen, J. Separate neural systems value immediate and delayed monetary rewards {2004} SCIENCE
    Vol. {306}({5695}), pp. {503-507} 
    article  
    Abstract: When humans are offered the choice between rewards available at different points in time, the relative values of the options are discounted according to their expected delays until delivery. Using functional magnetic resonance imaging, we examined the neural correlates of time discounting while subjects made a series of choices between monetary reward options that varied by delay to delivery. We demonstrate that two separate systems are involved in such decisions. Parts of the limbic system associated with the midbrain dopamine system, including paralimbic cortex, are preferentially activated by decisions involving immediately available rewards. In contrast, regions of the lateral prefrontal. cortex and posterior parietal cortex are engaged uniformly by intertemporal choices irrespective of delay. Furthermore, the relative engagement of the two systems is directly associated with subjects' choices, with greater relative fronto-parietal activity when subjects choose longer term options.
    BibTeX:
    @article{McClure2004,
      author = {McClure, SM and Laibson, DI and Loewenstein, G and Cohen, JD},
      title = {Separate neural systems value immediate and delayed monetary rewards},
      journal = {SCIENCE},
      year = {2004},
      volume = {306},
      number = {5695},
      pages = {503-507}
    }
    
    McDonald, A. Cortical pathways to the mammalian amygdala {1998} PROGRESS IN NEUROBIOLOGY
    Vol. {55}({3}), pp. {257-332} 
    article  
    Abstract: The amygdaloid nuclear complex is critical for producing appropriate emotional and behavioral responses to biologically relevant sensory stimuli. It constitutes an essential link between sensory and limbic areas of the cerebral cortex and subcortical brain regions, such as the hypothalamus, brainstem, and striatum, that are responsible for eliciting emotional and motivational responses. This review summarizes the anatomy and physiology of the cortical pathways to the amygdala in the rat, cat and monkey. Although the basic anatomy of these systems in the cat and monkey was largely delineated in studies conducted during the 1970s and 1980s, detailed information regarding the cortico-amygdalar pathways in the rat was only obtained in the past several years. The purpose of this review is to describe the results of recent studies in the rat and to compare the organization of cortico-amygdalar projections in this species with that seen in the cat and monkey. In all three species visual, auditory, and somatosensory information is transmitted to the amygdala by a series of modality-specific cortico-cortical pathways (''cascades'') that originate in the primary sensory cortices and flow toward higher order association areas. The cortical areas in the more distal portions of these cascades have stronger and more extensive projections to the amygdala than the more proximal areas. In all three species olfactory and gustatory/visceral information has access to the amygdala at an earlier stage of cortical processing than vis auditory and somatosensory information. There are also important polysensory cortical inputs to the mammalian amygdala from the prefrontal and hippocampal regions. Whereas the overall organization of cortical pathways is basically similar in all mammalian species, there is anatomical evidence which suggests that there are important differences in the extent of convergence of cortical projections in the primate versus the nonprimate amygdala. (C) 1998 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{McDonald1998,
      author = {McDonald, AJ},
      title = {Cortical pathways to the mammalian amygdala},
      journal = {PROGRESS IN NEUROBIOLOGY},
      year = {1998},
      volume = {55},
      number = {3},
      pages = {257-332}
    }
    
    McEwen, B.S. Physiology and neurobiology of stress and adaptation: Central role of the brain {2007} PHYSIOLOGICAL REVIEWS
    Vol. {87}({3}), pp. {873-904} 
    article DOI  
    Abstract: McEwen BS. Physiology and Neurobiology of Stress and Adaptation: Central Role of the Brain. Physiol Rev 87:873-904, 2007; doi:10.1152/physrev.00041.2006.-The brain is the key organ of the response to stress because it determines what is threatening and, therefore, potentially stressful, as well as the physiological and behavioral responses which can be either adaptive or damaging. Stress involves two-way communication between the brain and the cardiovascular, immune, and other systems via neural and endocrine mechanisms. Beyond the ``flight-or-fight'' response to acute stress, there are events in daily life that produce a type of chronic stress and lead over time to wear and tear on the body (''allostatic load''). Yet, hormones associated with stress protect the body in the short-run and promote adaptation (''allostasis''). The brain is a target of stress, and the hippocampus was the first brain region, besides the hypothalamus, to be recognized as a target of glucocorticoids. Stress and stress hormones produce both adaptive and maladaptive effects on this brain region throughout the life course. Early life events influence life-long patterns of emotionality and stress responsiveness and alter the rate of brain and body aging. The hippocampus, amygdala, and prefrontal cortex undergo stress-induced structural remodeling, which alters behavioral and physiological responses. As an adjunct to pharmaceutical therapy, social and behavioral interventions such as regular physical activity and social support reduce the chronic stress burden and benefit brain and body health and resilience.
    BibTeX:
    @article{McEwen2007,
      author = {McEwen, Bruce S.},
      title = {Physiology and neurobiology of stress and adaptation: Central role of the brain},
      journal = {PHYSIOLOGICAL REVIEWS},
      year = {2007},
      volume = {87},
      number = {3},
      pages = {873-904},
      doi = {{10.1152/physrev.00041.2006}}
    }
    
    McFarland, K. & Kalivas, P. The circuitry mediating cocaine-induced reinstatement of drug-seeking behavior {2001} JOURNAL OF NEUROSCIENCE
    Vol. {21}({21}), pp. {8655-8663} 
    article  
    Abstract: The role of limbic-striato-pallidal circuitry in cocaine-induced reinstatement was evaluated. The transient inhibition of brain nuclei associated with motor systems [including the ventral tegmental area (VTA), dorsal prefrontal cortex (dPFC), core of the nucleus accumbens (NAcore), and ventral pallidum (VP)] prevented cocaine-induced reinstatement. However, only the VP proved to be necessary for food reinstatement, suggesting that the identified circuit is specific to drug-related reinstatement. Supporting the possibility that the VTA-dPFC-NAcore-VP is a series circuit mediating reinstatement, simultaneous unilateral microinjection of GABA agonists into the dPFC in one hemisphere and into the VP in the contralateral hemisphere abolished cocaine reinstatement. Although dopamine projections from the VTA innervate all three forebrain nuclei, the blockade of dopamine receptors only in the dPFC antagonized cocaine-induced reinstatement. Furthermore, DA administration into the dPFC was sufficient to elicit a reinstatement in drug-related responding. These data demonstrate that dopamine release in the dPFC initiates a dPFC-NAcore-VP series circuit that mediates cocaine-induced drug-seeking behavior.
    BibTeX:
    @article{McFarland2001,
      author = {McFarland, K and Kalivas, PW},
      title = {The circuitry mediating cocaine-induced reinstatement of drug-seeking behavior},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2001},
      volume = {21},
      number = {21},
      pages = {8655-8663}
    }
    
    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}
    }
    
    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}
    }
    
    MELTZER, H. THE MECHANISM OF ACTION OF NOVEL ANTIPSYCHOTIC-DRUGS {1991} SCHIZOPHRENIA BULLETIN
    Vol. {17}({2}), pp. {263-287} 
    article  
    Abstract: It is no longer tenable to attribute all the antipsychotic action of antipsychotic drugs to dopamine (DA) D2 receptor blockade and subsequent development of depolarization inactivation of the mesolimbic or mesocortical DA neurons. The chief evidence for this position is that clozapine (CLOZ) does not differ from typical antipsychotic drugs in these regards but is more effective than typical neuroleptic drugs. The mechanism of action of atypical antipsychotic drugs related to CLOZ may involve reduction of dopaminergic activity in the mesolimbic system by a variety of mechanisms, including D1 and D2 receptor blockade. Relatively higher affinity for the serotonin (5HT)2 receptor than for the D2 receptor may also be important to the action of CLOZ-like compounds. Enhanced DA release in the mesocortical system may be relevant to the effectiveness of these agents in treating negative symptoms. Several other classes of new agents alter the dopaminergic system by means of alternative mechanisms. Partial DA agonists may modulate DA neurotransmission more adequately than pure antagonists by producing a mix of direct agonist and antagonistic effects. DA autoreceptor agonists and 5HT3 antagonists appear to act by diminishing the release of DA from some, but not all, DA neurons. Substituted benzamides are ``pure'' D2 antagonists with some in vivo selectivity for limbic D2 over striatal D2 receptors. Highly selective D1 antagonists have been proposed to produce equivalent antipsychotic activity and fewer extrapyramidal symptoms than D2 antagonists. Antagonists of the recently identified D3 receptors are being sought. Excessive stimulation of the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor, leading to neurotoxicity or diminished activation of this receptor, is the target of novel approaches to treating schizophrenia. Phencyclidine (PCP) antagonists that would activate the NMDA receptor and sigma receptor antagonists are of interest as antipsychotic agents. Therapeutic strategies for treating schizophrenia, schizophrenia-related disorders, and other psychoses will likely be genuinely diverse in the next decade.
    BibTeX:
    @article{MELTZER1991,
      author = {MELTZER, HY},
      title = {THE MECHANISM OF ACTION OF NOVEL ANTIPSYCHOTIC-DRUGS},
      journal = {SCHIZOPHRENIA BULLETIN},
      year = {1991},
      volume = {17},
      number = {2},
      pages = {263-287}
    }
    
    Meltzer, H. & McGurk, S. The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia {1999} SCHIZOPHRENIA BULLETIN
    Vol. {25}({2}), pp. {233-255} 
    article  
    Abstract: Cognitive function is markedly impaired in most patients with schizophrenia. Antecedents of this impairment are evident in childhood. The cognitive disability is nearly fully developed at the first episode of psychosis in most patients, The contribution of cognitive impairment to outcome in schizophrenia, especially work function, has been established. Preliminary results indicate that cognitive function, along with disorganization symptoms, discriminate schizophrenia patients who are able to work full-time from those who are not. Typical neuroleptic drugs lack the ability to improve the various domains of cognitive function impaired in schizophrenia. Atypical antipsychotic drugs pharmacologically related to clozapine-quetiapine, olanzapine, risperidone, sertindole, and ziprasidone-share the ability to produce fewer extrapyramidal symptoms than typical neuroleptic drugs and more potent antagonism of serotonin(2a) relative to dopamine(2) receptors. However, they have a number of different clinical effects. We have identified all the studies of clozapine, olanzapine, and risperidone that provide data on their effects on cognition in schizophrenia. Data for each drug are reviewed separately in order to identify differences among them in their effects on cognition. Twelve studies that report cognitive effects of clozapine are reviewed. These studies provide (1) strong evidence that clozapine improves attention and verbal fluency and (2) moderate evidence that clozapine improves some types of executive function. However, results of the effects of clozapine on working memory and secondary verbal and spatial memory were inconclusive. Risperidone has relatively consistent positive effects on working memory, executive functioning, and attention, whereas improvement in verbal learning and memory was inconsistent. Preliminary evidence presented here suggests that olanzapine improves verbal learning and memory, verbal fluency, and executive function, but not attention, working memory, or visual learning and memory. Thus, atypical antipsychotic drugs as a group appear to be superior to typical neuroleptics with regard to cognitive function. However, available data suggest that these drugs produce significant differences in specific cognitive functions. These differences may be valuable adjunctive guides for their use in clinical practice if cognitive improvements reach clinical significance. The effects of the atypical antipsychotic drugs on cholinergic and 5-HT2a-mediated neurotransmission as the possible basis for their ability to improve cognition are discussed. It is suggested that the development of drugs for schizophrenia should focus on improving the key cognitive deficits in schizophrenia: executive function, verbal fluency, working memory, verbal and visual learning and memory, and attention.
    BibTeX:
    @article{Meltzer1999,
      author = {Meltzer, HY and McGurk, SR},
      title = {The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia},
      journal = {SCHIZOPHRENIA BULLETIN},
      year = {1999},
      volume = {25},
      number = {2},
      pages = {233-255}
    }
    
    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}
    }
    
    Mesulam, M. From sensation to cognition {1998} BRAIN
    Vol. {121}({Part 6}), pp. {1013-1052} 
    article  
    Abstract: Sensory information undergoes extensive associative elaboration and attentional modulation as it becomes incorporated into the texture of cognition. This process occurs along a core synaptic hierarchy which includes the primary sensory, upstream unimodal, downstream unimodal, heteromodal, paralimbic and limbic zones of the cerebral cortex. Connections from one zone to another are reciprocal and allow higher synaptic levels to exert a feedback (top-down) influence upon earlier levels of processing. Each cortical area provides a nexus for the convergence of afferents and divergence of efferents. The resultant synaptic organization supports parallel as well as serial processing, and allows each sensory event to initiate multiple cognitive and behavioural outcomes. Upstream sectors of unimodal association areas encode basic features of sensation such as colour, motion, form and pitch. More complex contents of sensory experience such as objects, faces, word-forms, spatial locations and sound sequences become encoded within downstream sectors of unimodal areas by groups of coarsely tuned neurons. The highest synaptic levels of sensory-fugal processing are occupied by heteromodal, paralimbic and limbic cortices, collectively known as transmodal areas. The unique role of these areas is to bind multiple unimodal and other transmodal areas into distributed but integrated multimodal representations. Transmodal areas in the midtemporal cortex, Wernicke's area, the hippocampalentorhinal complex and the posterior parietal cortex provide critical gateways for transforming perception into recognition, word-forms into meaning, scenes and events into experiences, and spatial locations into targets for exploration. All cognitive processes arise from analogous associative transformations of similar sets of sensory inputs. The differences in the resultant cognitive operation are determined by the anatomical and physiological properties of the transmodal node that acts as the critical gateway for the dominant transformation. Interconnected sets of transmodal nodes provide anatomical and computational epicentres for large-scale neurocognitive networks. In keeping with the principles of selectively distributed processing, each epicentre of a large-scale network displays a relative specialization for a specific behavioural component of its principal neurospychological domain. The destruction of transmodal epicentres causes global impairments such as multimodal anemia, neglect and amnesia, whereas their selective disconnection from relevant unimodal areas elicits modality-specific impairments such as prosopagnosia, pure word blindness and category-specific anemias. The human brain contains at least five anatomically distinct networks. The network for spatial awareness is based on transmodal epicentres in the posterior parietal cortex and the frontal eye fields; the language network on epicentres in Wernicke's and Broca's areas; the explicit memory/emotion network on epicentres in the hippocampal-entorhinal complex and the amygdala; the face-object recognition network on epicentres in the midtemporal and temporopolar cortices; and the working memory-executive function network on epicentres in the lateral prefrontal cortex and perhaps the posterior parietal cortex. Individual sensory modalities give rise to streams of processing directed to transmodal nodes belonging to each of these networks. The fidelity of sensory channels is actively protected through approximately four synaptic levels of sensory-fugal processing. The modality-specific cortices at these four synaptic levels encode the most veridical representations of experience. Attentional, motivational and emotional modulations, including those related to working memory, novelty-seeking and mental imagery, become increasingly more pronounced within downstream components of unimodal areas, where they help to create a highly edited subjective version of the world. The prefrontal cortex plays a critical role in these attentional and emotional modulations and allows neural responses to reflect the significance rather than the surface properties of sensory events. Additional modulatory influences are exerted by the cholinergic and monoaminergic pathways of the ascending reticular activating system. Working memory, one of the most prominent manifestations of prefrontal cortex activity, prolongs the neural impact of environmental and mental events in a way that enriches the texture of consciousness. The synaptic architecture of large-scale networks and the manifestations of working memory, novelty-seeking behaviours and mental imagery collectively help to loosen the rigid stimulus-response bonds that dominate the behaviour of lower animal species. This phylogenetic trend has helped to shape the unique properties of human consciousness and to induce the emergence of second-order (symbolic) representations related to language. Through the advent of language and the resultant ability to communicate abstract concepts, the critical pacemaker for human cognitive development has shifted from the extremely slow process of structural brain evolution to the much more rapid one of distributed computations where each individual intelligence can become incorporated into an interactive lattice that promotes the transgenerational transfer and accumulation of knowledge.
    BibTeX:
    @article{Mesulam1998,
      author = {Mesulam, MM},
      title = {From sensation to cognition},
      journal = {BRAIN},
      year = {1998},
      volume = {121},
      number = {Part 6},
      pages = {1013-1052}
    }
    
    Middleton, F. & Strick, P. Basal ganglia and cerebellar loops: motor and cognitive circuits {2000} BRAIN RESEARCH REVIEWS
    Vol. {31}({2-3}), pp. {236-250} 
    article  
    Abstract: The traditional view that the basal ganglia and cerebellum are simply involved in the control of movement has been challenged in recent years. One of the pivotal reasons for this reappraisal has been new information about basal ganglia and cerebellar connections with the cerebral cortex. In essence, recent anatomical studies have revealed that these connections are organized into discrete circuits or `loops'. Rather than serving as a means for widespread cortical areas to gain access to the motor system, these loops reciprocally interconnect a large and diverse set of cerebral cortical areas with the basal ganglia and cerebellum The properties of neurons within the basal ganglia or cerebellar components of these circuits resembles the properties of neurons within the cortical areas subserved by these loops. For example, neuronal activity within basal ganglia and cerebellar loops with meter areas of the cerebral cortex is highly correlated with parameters of movement, while neuronal activity within basal ganglia and cerebellar loops with areas of the prefrontal cortex is more related to aspects of cognitive function. Thus, individual loops appear to be involved in distinct behavioral Functions. Studies of basal ganglia and cerebellar pathology support this conclusion. Damage to the basal ganglia or cerebellar component?, of circuits with motor areas of cortex leads to motor symptoms, whereas damage of the subcortical components of circuits with non-motor areas of cortex causes higher-order deficits. In this report, we review some of the new anatomical, physiological and behavioral findings that have contributed to a reappraisal of function concerning the basal ganglia and cerebellar loops with the cerebral cortex. (C) 2000 Published by Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{Middleton2000,
      author = {Middleton, FA and Strick, PL},
      title = {Basal ganglia and cerebellar loops: motor and cognitive circuits},
      journal = {BRAIN RESEARCH REVIEWS},
      year = {2000},
      volume = {31},
      number = {2-3},
      pages = {236-250},
      note = {Nobel Symposium 111: Schizophrenia - Pathophysiological Mechanisms, STOCKHOLM, SWEDEN, OCT 01-03, 1998}
    }
    
    MIDDLETON, F. & STRICK, P. ANATOMICAL EVIDENCE FOR CEREBELLAR AND BASAL GANGLIA INVOLVEMENT IN HIGHER COGNITIVE FUNCTION {1994} SCIENCE
    Vol. {266}({5184}), pp. {458-461} 
    article  
    Abstract: The possibility that neurons in the basal ganglia and cerebellum innervate areas of cerebral cortex that are involved in cognitive function has been a contriversial subject. Here, retrograde transneuronal transport of herpes simplex virus type 1 (HSV1) was used to identify subcortical neurons that project via the thalamus to area 46 of the primate prefrontal cortex. This cortical area is known to be involved in spatial working memory. Many neurons in restricted regions of the dentate nucleus of the cerebral and in the internal segment of the globus pallidus were labeled by transneuronal transport of visus from area 46. The location of these neurons was different from those labeled after HSV1 transport from motor areas of the cerebral cortex. These observations define an anatomical substrate for the involvement of basal ganglia and cerrebellar output in higher cognitive function.
    BibTeX:
    @article{MIDDLETON1994,
      author = {MIDDLETON, FA and STRICK, PL},
      title = {ANATOMICAL EVIDENCE FOR CEREBELLAR AND BASAL GANGLIA INVOLVEMENT IN HIGHER COGNITIVE FUNCTION},
      journal = {SCIENCE},
      year = {1994},
      volume = {266},
      number = {5184},
      pages = {458-461}
    }
    
    Milad, M. & Quirk, G. Neurons in medial prefrontal cortex signal memory for fear extinction {2002} NATURE
    Vol. {420}({6911}), pp. {70-74} 
    article DOI  
    Abstract: Conditioned fear responses to a tone previously paired with a shock diminish if the tone is repeatedly presented without the shock, a process known as extinction. Since Pavlov(1) it has been hypothesized that extinction does not erase conditioning, but forms a new memory. Destruction of the ventral medial prefrontal cortex, which consists of infralimbic and prelimbic cortices, blocks recall of fear extinction(2,3), indicating that medial prefrontal cortex might store long-term extinction memory. Here we show that infralimbic neurons recorded during fear conditioning and extinction fire to the tone only when rats are recalling extinction on the following day. Rats that froze the least showed the greatest increase in infralimbic tone responses. We also show that conditioned tones paired with brief electrical stimulation of infralimbic cortex elicit low freezing in rats that had not been extinguished. Thus, stimulation resembling extinction-induced infralimbic tone responses is able to simulate extinction memory. We suggest that consolidation of extinction learning potentiates infralimbic activity, which inhibits fear during subsequent encounters with fear stimuli.
    BibTeX:
    @article{Milad2002,
      author = {Milad, MR and Quirk, GJ},
      title = {Neurons in medial prefrontal cortex signal memory for fear extinction},
      journal = {NATURE},
      year = {2002},
      volume = {420},
      number = {6911},
      pages = {70-74},
      doi = {{10.1038/nature01138}}
    }
    
    Miller, E. The prefrontal cortex and cognitive control {2000} NATURE REVIEWS NEUROSCIENCE
    Vol. {1}({1}), pp. {59-65} 
    article  
    Abstract: One of the enduring mysteries of brain function concerns the process of cognitive control. How does complex and seemingly wilful behaviour emerge from interactions between millions of neurons? This has long been suspected to depend on the prefrontal cortex - the neocortex at the anterior end of the brain - but now we are beginning to uncover its neural basis. Nearly ail intended behaviour is learned and so depends on a cognitive system that can acquire and implement the `rules of the game' needed to achieve a given goal in a given situation. Studies indicate that the prefrontal cortex is central in this process. It provides an infrastructure for synthesizing a diverse range of information that lays the foundation for the complex forms of behaviour observed in primates.
    BibTeX:
    @article{Miller2000,
      author = {Miller, EK},
      title = {The prefrontal cortex and cognitive control},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2000},
      volume = {1},
      number = {1},
      pages = {59-65}
    }
    
    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}
    }
    
    Miller, E., Erickson, C. & Desimone, R. Neural mechanisms of visual working memory in prefrontal cortex of the macaque {1996} JOURNAL OF NEUROSCIENCE
    Vol. {16}({16}), pp. {5154-5167} 
    article  
    Abstract: Prefrontal (PF) cells were studied in monkeys performing a delayed matching to sample task, which requires working memory. The stimuli were complex visual patterns and to solve the task, the monkeys had to discriminate among the stimuli, maintain a memory of the sample stimulus during the delay periods, and evaluate whether a test stimulus matched the sample presented earlier in the trial. PF cells have properties consistent with a role in all three of these operations. Approximately 25% of the cells responded selectively to different visual stimuli. Half of the cells showed heightened activity during the delay after the sample and, for many of these cells, the magnitude of delay activity was selective for different samples. Finally, more than half of the cells responded differently to the test stimuli depending on whether they matched the sample. Because inferior temporal (IT) cortex also is important for working memory, we compared PF cells with IT cells studied in the same task, Compared with IT cortex, PF responses were less often stimulus-selective but conveyed more information about whether a given test stimulus was a match to the sample. Furthermore, sample-selective delay activity in PF cortex was maintained throughout the trial even when other test stimuli intervened during the delay, whereas delay activity in IT cortex was disrupted by intervening stimuli. The results suggest that PF cortex plays a primary role in working memory tasks and may be a source of feedback inputs to IT cortex, biasing activity in favor of behaviorally relevant stimuli.
    BibTeX:
    @article{Miller1996,
      author = {Miller, EK and Erickson, CA and Desimone, R},
      title = {Neural mechanisms of visual working memory in prefrontal cortex of the macaque},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1996},
      volume = {16},
      number = {16},
      pages = {5154-5167}
    }
    
    MILLER, E., LI, L. & DESIMONE, R. ACTIVITY OF NEURONS IN ANTERIOR INFERIOR TEMPORAL CORTEX DURING A SHORT-TERM-MEMORY TASK {1993} JOURNAL OF NEUROSCIENCE
    Vol. {13}({4}), pp. {1460-1478} 
    article  
    Abstract: Inferior temporal (IT) cortex of primates is known to play an important role in visual memory. Previous studies of IT neurons during performance of working memory tasks have found modulation of responses when a current stimulus matched an item in memory; however, this effect was lost if other stimuli intervened in the retention interval. To examine how IT cortex retains memories while new stimuli are activating the cells, we recorded from IT neurons while monkeys performed a delayed matching-to-sample task, with multiple intervening items between the sample and matching test stimulus. About half of the cells responded differently to a test stimulus if it matched the sample, and this difference was maintained following intervening stimuli. For most of the affected cells, the responses to matching stimuli were suppressed; however, for a few cells the opposite effect was seen. Temporal contiguity alone could not explain the results, as there was no modulation of responses when a stimulus on one trial was repeated on the next trial. Thus, an active reset mechanism appears to restrict the memory comparison to just the stimuli presented within a trial. The suppressive effects appear to be generated within or before IT cortex since the suppression of response to matching stimuli began almost immediately with the onset of the visual response. The memory of the sample stimulus affected not only the responses to matching stimuli but also those to nonmatching stimuli. There was suggestive evidence that the more similar a nonmatching stimulus to the sample, the more the response was suppressed. About a quarter of the cells showed stimulus-selective activity in the delay interval following the sample. However, this activity appeared to be eliminated by intervening stimuli. Thus, it is unlikely that delay-interval activity in IT contributed to the performance of this particular version of delayed matching to sample. To determine how much information about the match-nonmatch status of the stimulus was conveyed by individual neurons, we analyzed the responses with discriminant analysis. The responses of an individual IT neuron could be used to classify a stimulus as matching or nonmatching on about 60% of the trials. To achieve the same performance as the animal would require averaging the responses of a minimum of 25 IT neurons. There was rio evidence that mnemonic information was carried by temporal variations in the spike trains. By contrast, there was a modest amount of temporal variation in sensory responses to different visual stimuli. This variation appeared to be due to different stimuli having different effects on the early and late (transient and sustained) portions of the response. We propose that two populations of IT cells contribute to memory. One functions as adaptive mnemonic filters and the other provides a sensory referent. The difference in response between the two populations is a measure of the difference between the current stimulus and stored memory traces. A temporal `'figure-ground'' mechanism such as this could contribute to performance of a variety of mnemonic tasks, including working memory tasks.
    BibTeX:
    @article{MILLER1993,
      author = {MILLER, EK and LI, L and DESIMONE, R},
      title = {ACTIVITY OF NEURONS IN ANTERIOR INFERIOR TEMPORAL CORTEX DURING A SHORT-TERM-MEMORY TASK},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1993},
      volume = {13},
      number = {4},
      pages = {1460-1478}
    }
    
    Minichiello, L., Korte, M., Wolfer, D., Kuhn, R., Unsicker, K., Cestari, V., Rossi-Arnaud, C., Lipp, H., Bonhoeffer, T. & Klein, R. Essential role for TrkB receptors in hippocampus-mediated learning {1999} NEURON
    Vol. {24}({2}), pp. {401-414} 
    article  
    Abstract: Brain-derived neurotrophic factor (BDNF) and its receptor TrkB regulate both short-term synaptic functions and long-term potentiation (LTP) of brain synapses, raising the possibility that BDNF/TrkB may be involved in cognitive functions. We have generated conditionally gene targeted mice in which the knockout of the trkB gene is restricted to the forebrain and occurs only during postnatal development. Adult mutant mice show increasingly impaired learning behavior or inappropriate coping responses when facing complex and/or stressful learning paradigms but succeed in simple passive avoidance learning. Homozygous mutants show impaired LTP at CA1 hippocampal synapses. Interestingly, heterozygotes show a partial but substantial reduction of LTP but appear behaviorally normal. Thus, CA1 LTP may need to be reduced below a certain threshold before behavioral defects become apparent.
    BibTeX:
    @article{Minichiello1999,
      author = {Minichiello, L and Korte, M and Wolfer, D and Kuhn, R and Unsicker, K and Cestari, V and Rossi-Arnaud, C and Lipp, HP and Bonhoeffer, T and Klein, R},
      title = {Essential role for TrkB receptors in hippocampus-mediated learning},
      journal = {NEURON},
      year = {1999},
      volume = {24},
      number = {2},
      pages = {401-414}
    }
    
    Mirnics, K., Middleton, F., Marquez, A., Lewis, D. & Levitt, P. Molecular characterization of schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex {2000} NEURON
    Vol. {28}({1}), pp. {53-67} 
    article  
    Abstract: Microarray expression profiling of prefrontal cortex from matched pairs of schizophrenic and control subjects and hierarchical data analysis revealed that transcripts encoding proteins involved in the regulation of presynaptic function (PSYN) were decreased in all subjects with schizophrenia. Genes of the PSYN group showed a different combination of decreased expression across subjects. Over 250 other gene groups did not show altered expression. Selected PSYN microarray observations were verified by in situ hybridization. Two of the most consistently changed transcripts in the PSYN functional gene group, N-ethylmaleimide sensitive factor and synapsin II, were decreased in ten of ten and nine of ten subjects with schizophrenia, respectively. The combined data suggest that subjects with schizophrenia share a common abnormality in presynaptic function. We set forth a predictive, testable model.
    BibTeX:
    @article{Mirnics2000,
      author = {Mirnics, K and Middleton, FA and Marquez, A and Lewis, DA and Levitt, P},
      title = {Molecular characterization of schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex},
      journal = {NEURON},
      year = {2000},
      volume = {28},
      number = {1},
      pages = {53-67}
    }
    
    MOGHADDAM, B. STRESS PREFERENTIALLY INCREASES EXTRANEURONAL LEVELS OF EXCITATORY AMINO-ACIDS IN THE PREFRONTAL CORTEX - COMPARISON TO HIPPOCAMPUS AND BASAL GANGLIA {1993} JOURNAL OF NEUROCHEMISTRY
    Vol. {60}({5}), pp. {1650-1657} 
    article  
    Abstract: The technique of intracerebral microdialysis was used to assess the effect of stress on the extracellular concentrations of excitatory amino acids, glutamate and aspartate, in the rat medial prefrontal cortex, hippocampus, striatum, and nucleus accumbens. A 20-min restraint procedure led to an increase in extracellular glutamate in all regions tested. The increase in glutamate levels was significantly higher in the prefrontal cortex than that observed in other regions. With the exception of the striatum, extracellular levels of aspartate were increased in all regions. Furthermore, the increase in aspartate levels was significantly higher in prefrontal cortex compared to hippocampus and nucleus accumbens. Local perfusion of tetrodotoxin during the restraint procedure significantly decreased the stress-induced increase in extracellular excitatory amino acids. In order to ensure that the above results were not an artifact of restraint not associated with stress (e.g., decreased mobility), we also examined the effect of swimming stress on the extracellular levels of excitatory amino acids in selected regions, i.e., striatum and medial prefrontal cortex. Both regions displayed a significant increase in extracellular levels of aspartate and glutamate following 20 min of swimming in room temperature water. This study provides direct evidence that stress increases the neuronal release of excitatory amino acids in a regionally selective manner. The implications of the present findings for stress-induced catecholamine release and/or hippocampal degeneration are discussed.
    BibTeX:
    @article{MOGHADDAM1993,
      author = {MOGHADDAM, B},
      title = {STRESS PREFERENTIALLY INCREASES EXTRANEURONAL LEVELS OF EXCITATORY AMINO-ACIDS IN THE PREFRONTAL CORTEX - COMPARISON TO HIPPOCAMPUS AND BASAL GANGLIA},
      journal = {JOURNAL OF NEUROCHEMISTRY},
      year = {1993},
      volume = {60},
      number = {5},
      pages = {1650-1657}
    }
    
    Moghaddam, B., Adams, B., Verma, A. & Daly, D. Activation of glutamatergic neurotransmission by ketamine: A novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex {1997} JOURNAL OF NEUROSCIENCE
    Vol. {17}({8}), pp. {2921-2927} 
    article  
    Abstract: Subanesthetic doses of ketamine, a noncompetitive NMDA receptor antagonist, impair prefrontal cortex (PFC) function in the rat and produce symptoms in humans similar to those observed in schizophrenia and dissociative states, including impaired performance of frontal robe-sensitive tests. Several lines of evidence suggest that ketamine may impair PFC function in part by interacting with dopamine neurotransmission in this region. This study sought to determine the mechanism by which ketamine may disrupt dopaminergic neurotransmission in, and cognitive functions associated with, the PFC. A thorough dose-response study using microdialysis in conscious rats indicated that low doses of ketamine (10, 20, and 30 mg/kg) increase glutamate outflow in the PFC, suggesting that at these doses ketamine may increase glutamatergic neurotransmission in the PFC at non-NMDA glutamate receptors. An anesthetic dose of ketamine (200 mg/kg) decreased, and an intermediate dose of 50 mg/kg did not affect, glutamate levels. Ketamine, at 30 mg/kg, also increased the release of dopamine in the PFC. This increase was blocked by intra-PFC application of the AMPA/kainate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione CNQX. Furthermore, ketamine-induced activation of dopamine release and impairment of spatial delayed alternation in the rodent, a PFC-sensitive cognitive task, was ameliorated by systemic pretreatment with AMPA/kainate receptor antagonist LY293558. These findings suggest that ketamine may disrupt dopaminergic neurotransmission in the PFC as well as cognitive functions associated with this region, in part, by increasing the release of glutamate, thereby stimulating postsynaptic non-NMDA glutamate receptors.
    BibTeX:
    @article{Moghaddam1997,
      author = {Moghaddam, B and Adams, B and Verma, A and Daly, D},
      title = {Activation of glutamatergic neurotransmission by ketamine: A novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1997},
      volume = {17},
      number = {8},
      pages = {2921-2927}
    }
    
    MOGHADDAM, B. & BUNNEY, B. ACUTE EFFECTS OF TYPICAL AND ATYPICAL ANTIPSYCHOTIC-DRUGS ON THE RELEASE OF DOPAMINE FROM PREFRONTAL CORTEX, NUCLEUS-ACCUMBENS, AND STRIATUM OF THE RAT - AN INVIVO MICRODIALYSIS STUDY {1990} JOURNAL OF NEUROCHEMISTRY
    Vol. {54}({5}), pp. {1755-1760} 
    article  
    BibTeX:
    @article{MOGHADDAM1990,
      author = {MOGHADDAM, B and BUNNEY, BS},
      title = {ACUTE EFFECTS OF TYPICAL AND ATYPICAL ANTIPSYCHOTIC-DRUGS ON THE RELEASE OF DOPAMINE FROM PREFRONTAL CORTEX, NUCLEUS-ACCUMBENS, AND STRIATUM OF THE RAT - AN INVIVO MICRODIALYSIS STUDY},
      journal = {JOURNAL OF NEUROCHEMISTRY},
      year = {1990},
      volume = {54},
      number = {5},
      pages = {1755-1760}
    }
    
    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}
    }
    
    Monsell, S. Task switching {2003} TRENDS IN COGNITIVE SCIENCES
    Vol. {7}({3}), pp. {134-140} 
    article DOI  
    Abstract: Everyday life requires frequent shifts between cognitive tasks. Research reviewed in this article probes the control processes that reconfigure mental resources for a change of task by requiring subjects to switch frequently among a small set of simple tasks. Subjects' responses are substantially slower and, usually, more error-prone immediately after a task switch. This `switch cost' is reduced, but not eliminated, by an opportunity for preparation. It seems to result from both transient and long-term carry-over of `task-set' activation and inhibition as well as time consumed by task-set reconfiguration processes. Neuroimaging studies of task switching have revealed extra activation in numerous brain regions when subjects prepare to change tasks and when they perform a changed task, but we cannot yet separate `controlling' from `controlled' regions.
    BibTeX:
    @article{Monsell2003,
      author = {Monsell, S},
      title = {Task switching},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      year = {2003},
      volume = {7},
      number = {3},
      pages = {134-140},
      doi = {{10.1016/S1364(03)00028-7}}
    }
    
    MORGAN, M. & LEDOUX, J. DIFFERENTIAL CONTRIBUTION OF DORSAL AND VENTRAL MEDIAL PREFRONTAL CORTEX TO THE ACQUISITION AND EXTINCTION OF CONDITIONED FEAR IN RATS {1995} BEHAVIORAL NEUROSCIENCE
    Vol. {109}({4}), pp. {681-688} 
    article  
    Abstract: The emotional reactivity of rats with lesions of the dorsal portion of medial prefrontal cortex (mPFC) was examined using a classical fear conditioning paradigm. Conditioned fear behavior (freezing responses) was measured during both the acquisition and extinction phases of the task. Lesions enhanced fear reactivity to both the conditioned stimlulus (CS) and contextual stimuli during both phases, suggesting that dorsal mPFC lesions produce a general increase in fear reactivity in response to fear conditioning. M. A. Morgan, L. M. Romanski, and J. E. LeDoux (1993) found that lesions just ventral to the present lesions had no effect during acquisition of the same task and prolonged the fear response to the CS (but not the context) during extinction. Thus, both dorsal and ventral regions of mPFC are involved in the fear system, but each modulates different aspects of fear responsivity.
    BibTeX:
    @article{MORGAN1995,
      author = {MORGAN, MA and LEDOUX, JE},
      title = {DIFFERENTIAL CONTRIBUTION OF DORSAL AND VENTRAL MEDIAL PREFRONTAL CORTEX TO THE ACQUISITION AND EXTINCTION OF CONDITIONED FEAR IN RATS},
      journal = {BEHAVIORAL NEUROSCIENCE},
      year = {1995},
      volume = {109},
      number = {4},
      pages = {681-688}
    }
    
    MORGAN, M., ROMANSKI, L. & LEDOUX, J. EXTINCTION OF EMOTIONAL LEARNING - CONTRIBUTION OF MEDIAL PREFRONTAL CORTEX {1993} NEUROSCIENCE LETTERS
    Vol. {163}({1}), pp. {109-113} 
    article  
    Abstract: Stimuli associated with painful or otherwise unpleasant events acquire aversive emotional properties in animals and humans. Subsequent presentation of the stimulus alone (in the absence of the unpleasant event) leads to the eventual extinction of the aversive reaction. Although the neural basis of emotional learning has been studied extensively, considerably less is known about the neural basis of emotional extinction. In the present study, we show that the medial prefrontal cortex plays an important role in the regulation of fear extinction in rats, a finding that may help elucidate the mechanisms and, possibly, the treatment of disorders of uncontrolled fear, such as anxiety, phobic, panic and posttraumatic stress disorders in humans.
    BibTeX:
    @article{MORGAN1993,
      author = {MORGAN, MA and ROMANSKI, LM and LEDOUX, JE},
      title = {EXTINCTION OF EMOTIONAL LEARNING - CONTRIBUTION OF MEDIAL PREFRONTAL CORTEX},
      journal = {NEUROSCIENCE LETTERS},
      year = {1993},
      volume = {163},
      number = {1},
      pages = {109-113}
    }
    
    Mummery, C., Patterson, K., Price, C., Ashburner, J., Frackowiak, R. & Hodges, J. A voxel-based morphometry study of semantic dementia: Relationship between temporal lobe atrophy and semantic memory {2000} ANNALS OF NEUROLOGY
    Vol. {47}({1}), pp. {36-45} 
    article  
    Abstract: The cortical anatomy of G patients with semantic dementia (the temporal lobe variant of frontotemporal dementia) was contrasted with that of a group of age-matched normal subjects by using voxel-based morphometry, a technique that identifies changes in gray matter volume on a voxel-by-voxel basis. Among the circumscribed regions of neuronal loss, the left temporal pole (Brodmann area 38) was the most significantly and consistently affected region. Cortical atrophy in the left hemisphere also involved the inferolateral temporal lobe (Brodmann area 20/21) and fusiform gyrus. In addition, the right temporal pole (Brodmann area 38), the ventromedial frontal cortex (Brodmann area 11/32) bilaterally, and the amygdaloid complex were affected, but no significant atrophy was measured in the hippocampus, entorhinal, or caudal perirhinal cortex. The degree of semantic memory impairment across the G cases correlated significantly with the extent of atrophy of the left anterior temporal lobe but not with atrophy in the adjacent ventromedial frontal cortex. These results confirm that the anterior temporal lobe is critically involved in semantic processing, and dissociate its function from that of the adjacent frontal region.
    BibTeX:
    @article{Mummery2000,
      author = {Mummery, CJ and Patterson, K and Price, CJ and Ashburner, J and Frackowiak, RSJ and Hodges, JR},
      title = {A voxel-based morphometry study of semantic dementia: Relationship between temporal lobe atrophy and semantic memory},
      journal = {ANNALS OF NEUROLOGY},
      year = {2000},
      volume = {47},
      number = {1},
      pages = {36-45}
    }
    
    Murphy, B., Arnsten, A., GoldmanRakic, P. & Roth, R. Increased dopamine turnover in the prefrontal cortex impairs spatial working memory performance in rats and monkeys {1996} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {93}({3}), pp. {1325-1329} 
    article  
    Abstract: The selective activation of the prefrontal cortical dopamine system by mild stress can be mimicked by anxiogenic beta-carbolines such as FG7142. To investigate the functional relevance of elevated levels of dopamine turnover in the prefrontal cortex, the current study examined the effects of FG7142 on the performance of spatial working memory tasks in the rat and monkey. FG7142 selectively increased prefrontal cortical dopamine turnover in rats and significantly impaired performance on spatial working memory tasks in both rats and monkeys. Spatial discrimination, a task with similar motor and motivational demands (rats), or delayed response performance following zero-second delays (monkeys) was unaffected by FG7142, Further, biochemical analysis in rats revealed a significant positive correlation between dopamine turnover In the prefrontal cortex and cognitive impairment on the delayed alternation Bask, The cognitive deficits in both rats and monkeys were prevented by pretreatment with the benzodiazepine receptor antagonist, RO15-1788, which blocked the increase in dopamine turnover and by the dopamine receptor antagonists, haloperidol, clozapine, and SCH23390, These findings indicate that excessive dopamine activity in the prefrontal cortex is detrimental to cognitive functions mediated by the prefrontal cortex.
    BibTeX:
    @article{Murphy1996,
      author = {Murphy, BL and Arnsten, AFT and GoldmanRakic, PS and Roth, RH},
      title = {Increased dopamine turnover in the prefrontal cortex impairs spatial working memory performance in rats and monkeys},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1996},
      volume = {93},
      number = {3},
      pages = {1325-1329}
    }
    
    Myers, K. & Davis, M. Behavioral and neural analysis of extinction {2002} NEURON
    Vol. {36}({4}), pp. {567-584} 
    article  
    Abstract: The neural mechanisms by which fear is inhibited are poorly understood at the present time. Behaviorally, a conditioned fear response may be reduced in intensity through a number of means. Among the simplest of these is extinction, a form of learning characterized by a decrease in the amplitude and frequency of a conditioned response when the conditioned stimulus that elicits it is repeatedly nonreinforced. Because clinical interventions for patients suffering from fear dysregulation seek to inhibit abnormal, presumably learned fear responses, an understanding of fear extinction is likely to inform and increase the efficacy of these forms of treatment. This review considers the behavioral, cellular, and molecular literatures on extinction and presents the most recent advances in our understanding while identifying issues that require considerable further research.
    BibTeX:
    @article{Myers2002,
      author = {Myers, KM and Davis, M},
      title = {Behavioral and neural analysis of extinction},
      journal = {NEURON},
      year = {2002},
      volume = {36},
      number = {4},
      pages = {567-584}
    }
    
    Nieoullon, A. Dopamine and the regulation of cognition and attention {2002} PROGRESS IN NEUROBIOLOGY
    Vol. {67}({1}), pp. {53-83} 
    article  
    Abstract: Dopamine (DA) acts as a key neurotransmitter in the brain. Numerous studies have shown its regulatory role for motor and limbic functions. However, in the early stages of Parkinson's disease (PD), alterations of executive functions also suggest a role for DA in regulating cognitive functions. Some other diseases, which can also involve DA dysfunction, such as schizophrenia or attention deficit hyperactivity disorder (ADHD) in children, as shown from the ameliorative action of dopaminergic antagonists and agonists, respectively, also show alteration of cognitive functions. Experimental studies showed that selective lesions of the dopaminergic neurons in rats or primates can actually provide cognitive deficits, especially when the mesocorticolimbic component of the dopaminergic systems is altered. Data from the experiments also showed significant alteration in attentional processes, thus raising the question of direct involvement of DA in regulating attention. Since the dopaminergic influence is mainly exerted over the frontal lobe and basal ganglia, it has been suggested that cognitive deficits express alteration in these subcortical brain structures closely linked to cortical areas, more than simple deficit in dopaminergic transmission. This point is still a matter of debate but, undoubtedly, DA acts as a powerful regulator of different aspects of cognitive brain functions. In this respect, normalizing DA transmission will contribute to improve the cognitive deficits not only related to neurologic or psychiatric diseases, but also in normal aging. Ontogenic and phylogenetic analysis of dopaminergic systems can provide evidences for a role of DA in the development of cognitive general capacities. DA can have a trophic action during maturation, which may influence the later cortical specification, particularly of pre-frontal cortical areas. Moreover, the characteristic extension of the dopaminergic cortical innervation in the rostro-caudal direction during the last stages of evolution in mammals can also be related to the appearance of progressively more developed cognitive capacities. Such an extension of cortical DA innervation could be related to increased processing of cortical information through basal ganglia, either during the course of evolution or development. DA has thus to be considered as a key neuroregulator which contributes to behavioral adaptation and to anticipatory processes necessary for preparing voluntary action consequent upon intention. All together, it can be suggested that a correlation exists between DA innervation and expression of cognitive capacities. Altering the dopaminergic transmission could, therefore, contribute to cognitive impairment. (C) 2002 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{Nieoullon2002,
      author = {Nieoullon, A},
      title = {Dopamine and the regulation of cognition and attention},
      journal = {PROGRESS IN NEUROBIOLOGY},
      year = {2002},
      volume = {67},
      number = {1},
      pages = {53-83}
    }
    
    Nyberg, L., Cabeza, R. & Tulving, E. PET studies of encoding and retrieval: The HERA model {1996} PSYCHONOMIC BULLETIN & REVIEW
    Vol. {3}({2}), pp. {135-148} 
    article  
    Abstract: We review positron emission tomography (PET) studies whose results converge on the hemispheric encoding/retrieval asymmetry (HERA) model of the involvement of prefrontal cortical regions in the processes of human memory. The model holds that the left prefrontal cortex is differentially more involved in retrieval of information from semantic memory, and in simultaneously encoding novel aspects of the retrieved information into episodic memory, than is the right prefrontal cortex. The right prefrontal cortex, on the other hand, is differentially more involved in episodic memory retrieval than is the left prefrontal cortex. This general pattern holds for different kinds of information (e.g., verbal materials, pictures, faces) and a variety of conditions of encoding and retrieval.
    BibTeX:
    @article{Nyberg1996,
      author = {Nyberg, L and Cabeza, R and Tulving, E},
      title = {PET studies of encoding and retrieval: The HERA model},
      journal = {PSYCHONOMIC BULLETIN & REVIEW},
      year = {1996},
      volume = {3},
      number = {2},
      pages = {135-148}
    }
    
    O'Doherty, J., Dayan, P., Schultz, J., Deichmann, R., Friston, K. & Dolan, R. Dissociable roles of ventral and dorsal striatum in instrumental conditioning {2004} SCIENCE
    Vol. {304}({5669}), pp. {452-454} 
    article  
    Abstract: Instrumental conditioning studies how animals and humans choose actions appropriate to the affective structure of an environment. According to recent reinforcement learning models, two distinct components are involved: a ``critic,'' which learns to predict future reward, and an `` actor,'' which maintains information about the rewarding outcomes of actions to enable better ones to be chosen more frequently. We scanned human participants with functional magnetic resonance imaging while they engaged in instrumental conditioning. Our results suggest partly dissociable contributions of the ventral and dorsal striatum, with the former corresponding to the critic and the latter corresponding to the actor.
    BibTeX:
    @article{O'Doherty2004,
      author = {O'Doherty, J and Dayan, P and Schultz, J and Deichmann, R and Friston, K and Dolan, RJ},
      title = {Dissociable roles of ventral and dorsal striatum in instrumental conditioning},
      journal = {SCIENCE},
      year = {2004},
      volume = {304},
      number = {5669},
      pages = {452-454}
    }
    
    O'Doherty, J., Deichmann, R., Critchley, H. & Dolan, R. Neural responses during anticipation of a primary taste reward {2002} NEURON
    Vol. {33}({5}), pp. {815-826} 
    article  
    Abstract: The aim of this study was to determine the brain regions involved in anticipation of a primary taste reward and to compare these regions to those responding to the receipt of a taste reward. Using fMRI, we scanned human subjects who were presented with visual cues that signaled subsequent reinforcement with a pleasant sweet taste (1 M glucose), a moderately unpleasant salt taste (0.2 M saline), or a neutral taste. Expectation of a pleasant taste produced activation in dopaminergic midbrain, posterior dorsal amygdala, striatum, and orbitofrontal cortex (OFC). Apart from OFC, these regions were not activated by reward receipt. The findings indicate that when rewards are predictable, brain regions recruited during expectation are, in part, dissociable from areas responding to reward receipt.
    BibTeX:
    @article{O'Doherty2002,
      author = {O'Doherty, JP and Deichmann, R and Critchley, HD and Dolan, RJ},
      title = {Neural responses during anticipation of a primary taste reward},
      journal = {NEURON},
      year = {2002},
      volume = {33},
      number = {5},
      pages = {815-826}
    }
    
    O'Doherty, J., Kringelbach, M., Rolls, E., Hornak, J. & Andrews, C. Abstract reward and punishment representations in the human orbitofrontal cortex {2001} NATURE NEUROSCIENCE
    Vol. {4}({1}), pp. {95-102} 
    article  
    Abstract: The orbitofrontal cortex (OFC) is implicated in emotion and emotion-related learning. Using event-related functional magnetic resonance imaging (fMRI), we measured brain activation in human subjects doing an emotion-related visual reversal-learning task in which choice of the correct stimulus led to a probabilistically determined `monetary' reward and choice of the incorrect stimulus led to a monetary loss. Distinct areas of the OFC were activated by monetary rewards and punishments. Moreover, in these areas, we found a correlation between the magnitude of the brain activation and the magnitude of the rewards and punishments received. These findings indicate that one emotional involvement of the human orbitofrontal cortex is its representation of the magnitudes of abstract rewards and punishments, such as receiving or losing money.
    BibTeX:
    @article{O'Doherty2001,
      author = {O'Doherty, J and Kringelbach, ML and Rolls, ET and Hornak, J and Andrews, C},
      title = {Abstract reward and punishment representations in the human orbitofrontal cortex},
      journal = {NATURE NEUROSCIENCE},
      year = {2001},
      volume = {4},
      number = {1},
      pages = {95-102}
    }
    
    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., 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}}
    }
    
    ODONNELL, P. & GRACE, A. SYNAPTIC-INTERACTIONS AMONG EXCITATORY AFFERENTS TO NUCLEUS-ACCUMBENS NEURONS - HIPPOCAMPAL GATING OF PREFRONTAL CORTICAL INPUT {1995} JOURNAL OF NEUROSCIENCE
    Vol. {15}({5, Part 1}), pp. {3622-3639} 
    article  
    Abstract: The interactions among excitatory inputs arising from the prefrontal cortex, amygdala, and hippocampus, and innervating nucleus accumbens neurons were studied using in vivo intracellular recording techniques. Neurons recorded in the accumbens displayed one of three activity states: (1) silent, (2) spontaneously firing at low, constant rates, or (3) a bistable membrane potential, characterized by alternating periods of activity and silence occurring in concert with spontaneous transitions between two steady-state membrane potentials (average, -77.3 +/- 7.1 mV base, -63.0 +/- 7.4 mV plateau). These neurons also exhibited a high degree of convergence of responses elicited by stimulation of each of the three excitatory inputs tested. Activation of hippocampal afferents, but not cortical, amygdaloid, or thalamic afferents, induced bistable cells to switch to the depolarized (active) state. In contrast, no bistable cells were encountered in the nucleus accumbens following an acute transection of the fornix. Furthermore, microinjection of lidocaine in the vicinity of the hippocampal afferents at the level of the fornix caused a reversible elimination of the plateau phase in bistable cells. These data suggest that hippocampal input is necessary for accumbens neurons to enter a depolarized, active state, Furthermore, activation of prefrontal cortical inputs fail to evoke spike firing in accumbens neurons unless they are in this active state. Consequently, the hippocampus appears to be capable of gating prefrontal corticoaccumbens throughput.
    BibTeX:
    @article{ODONNELL1995,
      author = {ODONNELL, P and GRACE, AA},
      title = {SYNAPTIC-INTERACTIONS AMONG EXCITATORY AFFERENTS TO NUCLEUS-ACCUMBENS NEURONS - HIPPOCAMPAL GATING OF PREFRONTAL CORTICAL INPUT},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1995},
      volume = {15},
      number = {5, Part 1},
      pages = {3622-3639}
    }
    
    Okubo, Y., Suhara, T., Suzuki, K., Kobayashi, K., Inoue, O., Terasaki, O., Someya, Y., Sassa, T., Sudo, Y., Matsushima, E., Iyo, M., Tateno, Y. & Toru, M. Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET {1997} NATURE
    Vol. {385}({6617}), pp. {634-636} 
    article  
    Abstract: Schizophrenia is believed to involve altered activation of dopamine receptors, and support for this hypothesis comes from the antipsychotic effect of antagonists of the dopamine D2 receptor (D2R)(1). D2R is expressed most highly in the striatum, but most of the recent positron emission tomography (PET) studies have failed to show any change in D2R densities in the striatum of schizophrenics(2-5), raising the possibility that other receptors may also be involved. In particular, the dopamine D1 receptor (D1R), which is highly expressed in the prefrontal cortex(6), has been implicated in the control of working memory(7,8), and working memory dysfunction is a prominent feature of schizophrenia(9). We have therefore used PET to examine the distribution of D1R and D2R in brains of drug-naive or drug-free schizophrenic patients. Although no differences were observed in the striatum relative to control subjects, binding of radioligand to D1R was reduced in the prefrontal cortex of schizophrenics. This reduction was related to the severity of the negative symptoms (for instance, emotional withdrawal) and to poor performance in the Wisconsin Card Sorting Test(10). We propose that dysfunction of D1R signalling in the prefrontal cortex may contribute to the negative symptoms and cognitive deficits seen in schizophrenia.
    BibTeX:
    @article{Okubo1997,
      author = {Okubo, Y and Suhara, T and Suzuki, K and Kobayashi, K and Inoue, O and Terasaki, O and Someya, Y and Sassa, T and Sudo, Y and Matsushima, E and Iyo, M and Tateno, Y and Toru, M},
      title = {Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET},
      journal = {NATURE},
      year = {1997},
      volume = {385},
      number = {6617},
      pages = {634-636}
    }
    
    Ongur, D., Drevets, W. & Price, J. Glial reduction in the subgenual prefrontal cortex in mood disorders {1998} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {95}({22}), pp. {13290-13295} 
    article  
    Abstract: Mood disorders are among the most common neuropsychiatric illnesses, yet little is known about their neurobiology. Recent neuroimaging studies have found that the volume of the subgenual part of Brodmann's area 24 (sg24) is reduced in familial forms of major depressive disorder (MDD) and bipolar disorder (BD), In this histological study, we used unbiased stereological techniques to examine the cellular composition of area sg24 in two different sets of brains. There was no change in the number or size of neurons in area sg24 in mood disorders. In contrast, the numbers of glia were reduced markedly in both MDD and ED. The reduction in glial number was most prominent in subgroups of subjects with familial MDD (24 P = 0.01) or ED (41 P = 0.01). The glial reduction in subjects without a clear family history was lower in magnitude and not statistically significant. Consistent with neuroimaging findings, cortical volume was reduced in area sg24 in subjects with familial mood disorders. Schizophrenic brains studied as psychiatric controls had normal neuronal and glial numbers and cortical volume. Glial and neuronal numbers also were counted in area 3b of the somatosensory cortex in the same group of brains and were normal in all psychiatric groups. Glia affect several processes, including regulation of extracellular potassium, glucose storage and metabolism, and glutamate uptake, all of which are crucial for normal neuronal activity. We thus have identified a biological marker associated with familial mood disorders that may provide important clues regarding the pathogenesis of these common psychiatric conditions.
    BibTeX:
    @article{Ongur1998,
      author = {Ongur, D and Drevets, WC and Price, JL},
      title = {Glial reduction in the subgenual prefrontal cortex in mood disorders},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1998},
      volume = {95},
      number = {22},
      pages = {13290-13295}
    }
    
    Ongur, D. & Price, J. The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans {2000} CEREBRAL CORTEX
    Vol. {10}({3}), pp. {206-219} 
    article  
    Abstract: This paper reviews architectonic subdivisions and connections of the orbital and medial prefrontal cortex (OMPFC) in rats, monkeys and humans. Cortico-cortical connections provide the basis for recognition of `medial' and `orbital' networks within the OMPFC. These networks also have distinct connections with structures in other parts of the brain. The orbital network receives sensory inputs from several modalities, including olfaction, taste, visceral afferents, somatic sensation and vision, which appear to be especially related to food or eating. In contrast, the medial network provides the major cortical output to visceromotor structures in the hypothalamus and brainstem. The two networks have distinct connections with areas of the striatum and mediodorsal thalamus. In particular, projections to the nucleus accumbens and the adjacent ventromedial caudate and putamen arise predominantly from the medial network. Both networks also have extensive connections with limbic structures. Based on these and other observations, the OMPFC appears to function as a sensory-visceromotor link, especially for eating. This linkage appears to he critical for the guidance of reward-related behavior and for setting of mood. Imaging and histological observations on human brains indicate that clinical depressive disorders are associated with specific functional and cellular changes in the OMPFC, including activity and volume changes, and specific changes in the number of glial cells.
    BibTeX:
    @article{Ongur2000,
      author = {Ongur, D and Price, JL},
      title = {The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans},
      journal = {CEREBRAL CORTEX},
      year = {2000},
      volume = {10},
      number = {3},
      pages = {206-219}
    }
    
    Owen, A., Doyon, J., Petrides, M. & Evans, A. Planning and spatial working memory: A positron emission tomography study in humans {1996} EUROPEAN JOURNAL OF NEUROSCIENCE
    Vol. {8}({2}), pp. {353-364} 
    article  
    Abstract: Previous work with both neurosurgical and neurodegenerative patient groups has suggested that high level planning is mediated by neural circuitry which includes both the prefrontal cortex and the striatum. In this study, the functional anatomy of cognitive planning was investigated further, using positron emission tomography (PET). Regional cerebral blood flow (rCBF) was measured in 12 normal volunteers while performing easy and difficult versions of (i) a modified Tower of London planning task; (ii) a mnemonic Variant of this task that required short-term retention and reproduction of problem solutions; and (iii) a control condition that involved identical visual stimuli and motor responses. Significant increases in rCBF were observed in the left hemisphere, in both the mid-dorsolateral frontal cortex and in the head of the caudate nucleus, when the difficult planning task was compared with the control condition. Moreover, subtraction of a simple planning condition from the more difficult one revealed focal increases in rCBF in the caudate nucleus and the thalamus only. During both mnemonic variants of the planning task, changes were also observed in the mid-dorsolateral frontal cortex and in more ventral frontopolar regions, bilaterally. When compared directly, the planning and memory conditions differed in terms of these ventral activation foci, but not in the pattern of activation observed in the mid-dorsolateral frontal cortex. These findings further implicate frontostriatal circuitry in high-level planning and provide evidence for functionally distinct contributions from ventral and dorsolateral frontal regions to spatial working memory.
    BibTeX:
    @article{Owen1996,
      author = {Owen, AM and Doyon, J and Petrides, M and Evans, AC},
      title = {Planning and spatial working memory: A positron emission tomography study in humans},
      journal = {EUROPEAN JOURNAL OF NEUROSCIENCE},
      year = {1996},
      volume = {8},
      number = {2},
      pages = {353-364}
    }
    
    OWEN, A., SAHAKIAN, B., SEMPLE, J., POLKEY, C. & ROBBINS, T. VISUOSPATIAL SHORT-TERM RECOGNITION MEMORY AND LEARNING AFTER TEMPORAL-LOBE EXCISIONS, FRONTAL-LOBE EXCISIONS OR AMYGDALO-HIPPOCAMPECTOMY IN MAN {1995} NEUROPSYCHOLOGIA
    Vol. {33}({1}), pp. {1-24} 
    article  
    Abstract: Three groups of neurosurgical patients with temporal lobe excisions, frontal lobe excisions or unilateral amygdalo-hippocampectomy were assessed on a computerized battery of tasks designed to investigate visuo-spatial short-term recognition memory and learning. A double dissociation is reported between deficits of pattern recognition memory and spatial recognition memory which were observed in the two posterior groups and frontal lobe patients, respectively. In addition, both the temporal lobe and amygdalo-hippocampectomy patients were also impaired on a delayed matching-to-sample paradigm whilst frontal lobe patients performed at an equivalent level to controls. Finally, whilst the impaired performance of the three groups was indistinguishable on a test of paired-associate learning, quite different patterns of deficit were observed on a test of spatial working memory. These results are discussed with reference to recent suggestions that visual recognition memory is mediated by a neural system which includes, as major components, the inferotemporal cortex, the medial temporal lobe structures and particular sectors of the frontal lobe, and are compared to previous findings from patients with idiopathic Parkinson's disease and dementia of the Alzheimer type.
    BibTeX:
    @article{OWEN1995,
      author = {OWEN, AM and SAHAKIAN, BJ and SEMPLE, J and POLKEY, CE and ROBBINS, TW},
      title = {VISUOSPATIAL SHORT-TERM RECOGNITION MEMORY AND LEARNING AFTER TEMPORAL-LOBE EXCISIONS, FRONTAL-LOBE EXCISIONS OR AMYGDALO-HIPPOCAMPECTOMY IN MAN},
      journal = {NEUROPSYCHOLOGIA},
      year = {1995},
      volume = {33},
      number = {1},
      pages = {1-24}
    }
    
    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}
    }
    
    PARK, S. & HOLZMAN, P. SCHIZOPHRENICS SHOW SPATIAL WORKING MEMORY DEFICITS {1992} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {49}({12}), pp. {975-982} 
    article  
    Abstract: The present study demonstrates that schizophrenics are impaired on spatial delayed-response tasks, analogous to those that have been used to assess the working memory function of the dorsolateral prefrontal cortex in rhesus monkeys. Schizophrenic patients and two control groups, normal subjects and bipolar psychiatric patients, were tested on the oculomotor version of the memory task, a haptic version of the same task, and two control tasks: a sensory task that did not require working memory and a digit span test. The schizophrenic patients showed marked deficits relative to the two control groups in both the oculomotor and haptic delayed-response tasks. They were not, however, impaired on the digit span test, which taps verbal working memory as well as voluntary attention, and on the sensory control task, in which their responses were guided by external cues rather than by spatial working memory. These findings provide direct evidence that schizophrenics suffer a loss in representational processing and that this deficit is modality independent. These data on spatial working memory add to the growing evidence for involvement of the dorsolateral prefrontal cortex in schizophrenic disease.
    BibTeX:
    @article{PARK1992,
      author = {PARK, S and HOLZMAN, PS},
      title = {SCHIZOPHRENICS SHOW SPATIAL WORKING MEMORY DEFICITS},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1992},
      volume = {49},
      number = {12},
      pages = {975-982}
    }
    
    PascualLeone, A., Rubio, B., Pallardo, F. & Catala, M. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression {1996} LANCET
    Vol. {348}({9022}), pp. {233-237} 
    article  
    Abstract: Background Lesion and neuroimaging studies suggest that left prefrontal lobe dysfunction is pathophysiologically linked to depression. Rapid-rate transcranial magnetic stimulation (rTMS) to prefrontal lateralised effect on mood In normal several preliminary studies suggest a beneficial effect of rTMS on depression. However, adequately controlled studies have not been conducted. Methods We have studied the effects of focal rTMS on the depressive symptoms in 17 patients with medication-resistant depression of psychotic subtype. The study was designed as a multiple cross-over, randomised placebo-controlled trial. Sham rTMS and stimulation of different cortical areas were used as controls. Findings Left dorsolateral prefrontal cortex rTMS resulted in a significant decrease in scores on the Hamilton depression rating scale HDRS (from 25.2 to 13.8) and the self-rated Beck questionnaire BQ (from 47.9 to 25.7). 11 of the 17 patients showed pronounced improvement that lasted for about 2 weeks after 5 days of daily rTMS sessions. No patient experienced any significant undesirable side-effects. Interpretation Our findings emphasise the role of the left dorsolateral prefrontal cortex in depression, and suggest that rTMS of the left dorsolateral prefrontal cortex might become a safe, non-convulsive alternative to electroconvulsive treatment in depression.
    BibTeX:
    @article{PascualLeone1996,
      author = {PascualLeone, A and Rubio, B and Pallardo, F and Catala, MD},
      title = {Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression},
      journal = {LANCET},
      year = {1996},
      volume = {348},
      number = {9022},
      pages = {233-237}
    }
    
    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., 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}
    }
    
    Petrides, M. & Pandya, D. Dorsolateral prefrontal cortex: comparative cytoarchitectonic analysis in the human and the macaque brain and corticocortical connection patterns {1999} EUROPEAN JOURNAL OF NEUROSCIENCE
    Vol. {11}({3}), pp. {1011-1036} 
    article  
    Abstract: The cytoarchitecture of the human and the macaque monkey dorsolateral prefrontal cortex has been examined in a strictly comparative manner in order to resolve major discrepancies between the available segmentations of this cortical region in the human and the monkey brain. In addition, the connections of the dorsolateral prefrontal cortical areas were re-examined in the monkey. The present analysis showed that only a restricted portion of what had previously been labelled as area 46 in the monkey has the same characteristics as area 46 of the human brain; the remaining part of this monkey region has the characteristics of a portion of the middle frontal gyrus in the human brain that had previously been included as part of area 9. We have labelled this cortical area as 9/46 in both species. These two areas (i.e. 46 and 9/46), which constitute the lower half of the mid-dorsolateral frontal cortex, have a well-developed granular layer IV, and can easily be distinguished from area 9, on the upper part of the mid-dorsolateral region, which does not have a well-developed granular layer IV. Area 9 has the same basic pattern of connections as areas 46 and 9/46, but, unlike the latter areas, it does not receive input from the lateral parietal cortex. Caudal to area 9, on the dorsomedial portion of the frontal cortex, there is a distinct strip of cortex (area 8B) which, unlike area 9, receives significant input from the prestriate cortex and the medial parietal cortex. The present results provide a basis for a closer integration of findings from functional neuroimaging studies in human subjects with experimental work in the monkey.
    BibTeX:
    @article{Petrides1999,
      author = {Petrides, M and Pandya, DN},
      title = {Dorsolateral prefrontal cortex: comparative cytoarchitectonic analysis in the human and the macaque brain and corticocortical connection patterns},
      journal = {EUROPEAN JOURNAL OF NEUROSCIENCE},
      year = {1999},
      volume = {11},
      number = {3},
      pages = {1011-1036}
    }
    
    PETTEGREW, J., KESHAVAN, M., PANCHALINGAM, K., STRYCHOR, S., KAPLAN, D., TRETTA, M. & ALLEN, M. ALTERATIONS IN BRAIN HIGH-ENERGY PHOSPHATE AND MEMBRANE PHOSPHOLIPID-METABOLISM IN 1ST-EPISODE, DRUG-NAIVE SCHIZOPHRENICS - A PILOT-STUDY OF THE DORSAL PREFRONTAL CORTEX BY INVIVO PHOSPHORUS 31 NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY {1991} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {48}({6}), pp. {563-568} 
    article  
    Abstract: In this pilot study, membrane phospholipid and high-energy phosphate metabolism were studied in the dorsal prefrontal cortex of 11 drug-naive, first-episode schizophrenic patients and compared with those of 10 healthy control volunteers comparable in age, education, and parental education. The schizophrenic patients had significantly reduced levels of phosphomonoesters and inorganic orthophosphate and significantly increased levels of phosphodiesters and adenosine triphosphate compared with the controls. The levels of phosphocreatine and adenosine diphosphate did not differ in the two subject groups. The adenosine triphosphate and inorganic orthophosphate findings suggest functional hypoactivity of the dorsal prefrontal cortex. The phosphomonoester and phosphodiester findings are compatible with either premature aging or an exaggeration of normal programmed regressive events occurring in the neural systems sampled.
    BibTeX:
    @article{PETTEGREW1991,
      author = {PETTEGREW, JW and KESHAVAN, MS and PANCHALINGAM, K and STRYCHOR, S and KAPLAN, DB and TRETTA, MG and ALLEN, M},
      title = {ALTERATIONS IN BRAIN HIGH-ENERGY PHOSPHATE AND MEMBRANE PHOSPHOLIPID-METABOLISM IN 1ST-EPISODE, DRUG-NAIVE SCHIZOPHRENICS - A PILOT-STUDY OF THE DORSAL PREFRONTAL CORTEX BY INVIVO PHOSPHORUS 31 NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1991},
      volume = {48},
      number = {6},
      pages = {563-568}
    }
    
    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. & LeDoux, J. Contributions of the amygdala to emotion processing: From animal models to human behavior {2005} NEURON
    Vol. {48}({2}), pp. {175-187} 
    article DOI  
    Abstract: Research on the neural systems underlying emotion in animal models over the past two decades has implicated the amygdala in fear and other emotional processes. This work stimulated interest in pursuing the brain mechanisms of emotion in humans. Here, we review research on the role of the amygdala in emotional processes in both animal models and humans. The review is not exhaustive, but it highlights five major research topics that illustrate parallel roles for the amygdala in humans and other animals, including implicit emotional learning and memory, emotional modulation of memory, emotional influences on attention and perception, emotion and social behavior, and emotion inhibition and regulation.
    BibTeX:
    @article{Phelps2005,
      author = {Phelps, EA and LeDoux, JE},
      title = {Contributions of the amygdala to emotion processing: From animal models to human behavior},
      journal = {NEURON},
      year = {2005},
      volume = {48},
      number = {2},
      pages = {175-187},
      doi = {{10.1016/j.neuron.2005.09.025}}
    }
    
    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}}
    }
    
    Piazza, P. & LeMoal, M. Pathophysiological basis of vulnerability to drug abuse: Role of an interaction between stress, glucocorticoids, and dopaminergic neurons {1996} ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
    Vol. {36}, pp. {359-378} 
    article  
    Abstract: Research on drug abuse has recently focused on understanding the vulnerability to develop addiction that is present in certain individuals. These investigations suggest that addiction results from an interaction between drugs and specific individual substrates. Differences in the propensity to develop drug intake can be demonstrated in animals with equal access to drugs under stable laboratory conditions and can be predicted by drug-independent behaviors. Stress, corticosterone, and mesencephalic dopaminergic neurons seem to be organized in a pathophysiological chain determining such a vulnerability. An increased corticosterone secretion, or a higher sensitivity to the effects of this hormone, either naturally present in certain individuals or induced by stress in others, increases the vulnerability to develop drug intake, via an enhancement of the activity of mesencephalic dopaminergic neurons. These findings suggest that addiction therapies should counteract the biological peculiarity that leads some individuals to respond in a pathophysiological way to drugs.
    BibTeX:
    @article{Piazza1996,
      author = {Piazza, PV and LeMoal, M},
      title = {Pathophysiological basis of vulnerability to drug abuse: Role of an interaction between stress, glucocorticoids, and dopaminergic neurons},
      journal = {ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY},
      year = {1996},
      volume = {36},
      pages = {359-378}
    }
    
    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}
    }
    
    Pierce, R. & Kalivas, P. A circuitry model of the expression of behavioral sensitization to amphetamine-like psychostimulants {1997} BRAIN RESEARCH REVIEWS
    Vol. {25}({2}), pp. {192-216} 
    article  
    Abstract: Repeated exposure to psychostimulants such as cocaine and amphetamine produces behavioral sensitization, which is characterized by an augmented locomotor response to a subsequent psychostimulant challenge injection. Experimentation focused on the neural underpinnings of behavioral sensitization has progressed from a singular focus on dopamine transmission in the nucleus accumbens and striatum to the study of cellular and molecular mechanisms that occur throughout the neural circuitry in which the mesocorticolimbic dopamine projections are embedded. This research effort has yielded a conglomerate of data that has resisted simple interpretations, primarily because no single neuronal effect is likely to be responsible for the expression of behavioral sensitization. The present review examines the literature and critically evaluates the extent to which the neural consequences of repeated psychostimulant administration are associated with the expression of behavioral sensitization. The neural alterations found to contribute to the long-term expression of behavioral sensitization are centered in a collection of interconnected limbic nuclei, which are termed the `motive' circuit. This neural circuit is used as a template to organize the relevant biochemical and molecular findings into a model of the expression of behavioral sensitization. (C) 1997 Elsevier Science B.V.
    BibTeX:
    @article{Pierce1997,
      author = {Pierce, RC and Kalivas, PW},
      title = {A circuitry model of the expression of behavioral sensitization to amphetamine-like psychostimulants},
      journal = {BRAIN RESEARCH REVIEWS},
      year = {1997},
      volume = {25},
      number = {2},
      pages = {192-216}
    }
    
    PIERROTDESEILLIGNY, C., RIVAUD, S., GAYMARD, B. & AGID, Y. CORTICAL CONTROL OF REFLEXIVE VISUALLY-GUIDED SACCADES {1991} BRAIN
    Vol. {114}({Part 3}), pp. {1473-1485} 
    article  
    Abstract: Reflexive visually-guide saccade triggering may be facilitated or inhibited by the cerebral cortex. To study this control, saccades made towards suddenly appearing visual targets (saccade task) or away from them (antisaccade task) were recorded electro-oculographically in 45 patients with limited unilateral cerebral infraction. Lesions affected (1) the superior part of the angular gyrus (area 39 of Brodmann) in the posterior parietal cortex (PPC), (2) the dorsolateral prefrontal cortex (PFC) (area 46 of Brodmann), (3) the frontal eye field (FEF), or (4) the supplementary motor area (SMA). As these 4 types of lesions were located either in the right or the left cerebral hemisphere, patients were divided into 8 groups. Saccade latency, in the saccade task, and the percentage of errors (misdirected saccades made towards the visual target), in the antisaccade task, were compared in each group of patients with the values of 20 control subjects. In the saccade task, saccade latency was significantly increased bilaterally in the right PPC group. In the left PPC group, the increase in latency was less marked, and significant only for saccades made contralaterally to the lesion. In the different frontal groups, latency was unchanged or only slightly increased. These results confirm that the main area facilitating the triggering of reflexive visually-guided saccades is located in the PPC, in or near the superior part of the angular gyrus. The difference between right and left parietal lesions could be due to the predominance of the right hemisphere in the control of these saccades. In the antisaccade task, the percentage of errors was significantly increased bilaterally in both PFC groups compared with the control group and also to the FEF and SMA group. These results suggest that the PFC is the main area in the cerebral hemisphere inhibiting reflexive visually-guided saccades.
    BibTeX:
    @article{PIERROTDESEILLIGNY1991,
      author = {PIERROTDESEILLIGNY, C and RIVAUD, S and GAYMARD, B and AGID, Y},
      title = {CORTICAL CONTROL OF REFLEXIVE VISUALLY-GUIDED SACCADES},
      journal = {BRAIN},
      year = {1991},
      volume = {114},
      number = {Part 3},
      pages = {1473-1485}
    }
    
    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}
    }
    
    Poldrack, R., Wagner, A., Prull, M., Desmond, J., Glover, G. & Gabrieli, J. Functional specialization for semantic and phonological processing in the left inferior prefrontal cortex {1999} NEUROIMAGE
    Vol. {10}({1}), pp. {15-35} 
    article  
    Abstract: Neuroimaging and neuropsychological studies have implicated left inferior prefrontal cortex (LIPC) in both semantic and phonological processing. In this study, functional magnetic resonance imaging was used to examine whether separate LIPC regions participate in each of these types of processing. Performance of a semantic decision task resulted in extensive LIPC activation compared to a perceptual control task. Phonological processing of words and pseudowords in a syllable-counting task resulted in activation of the dorsal aspect of the left inferior frontal gyrus near the inferior frontal sulcus (BA44/45) compared to a perceptual control task, with greater activation for nonwords compared to words. In a direct comparison of semantic and phonological tasks, semantic processing preferentially activated the ventral aspect of the left inferior frontal gyrus (BA 47/45). A review of the literature demonstrated a similar distinction between left prefrontal regions involved in semantic processing and phonological/lexical processing. The results suggest that a distinct region in the left inferior frontal cortex is involved in semantic processing, whereas other regions may subserve phonological processes engaged during both semantic and phonological tasks. (C) 1999 Academic Press.
    BibTeX:
    @article{Poldrack1999,
      author = {Poldrack, RA and Wagner, AD and Prull, MW and Desmond, JE and Glover, GH and Gabrieli, JDE},
      title = {Functional specialization for semantic and phonological processing in the left inferior prefrontal cortex},
      journal = {NEUROIMAGE},
      year = {1999},
      volume = {10},
      number = {1},
      pages = {15-35}
    }
    
    Price, C. The anatomy of language: contributions from functional neuroimaging {2000} JOURNAL OF ANATOMY
    Vol. {197}({Part 3}), pp. {335-359} 
    article  
    Abstract: This article illustrates how functional neuroimaging can be used to test the validity of neurological and cognitive models of language. Three models of language are described: the 19th Century neurological model which describes both the anatomy and cognitive components of auditory and visual word processing, and 2 20th Century cognitive models that are not constrained by anatomy but emphasise 2 different routes to reading that are not present in the neurological model. A series of functional imaging studies are then presented which show that, as predicted by the 19th Century neurologists, auditory and visual word repetition engage the let posterior superior temporal and posterior inferior frontal cortices. More specifically, the roles Wernicke and Broca assigned to these regions lie respectively in the posterior superior temporal sulcus and the anterior insula. In addition, a region in the left posterior inferior temporal cortex is activated for word retrieval, thereby providing a second route to reading, as predicted by the 20th Century cognitive models. This region and its function may have been missed by the 19th Century neurologists because selective damage is rare. The angular gyrus, previously linked to the visual word form system, is shown to be part of a distributed semantic system that can be accessed by objects and faces as well as speech. Other components of the semantic system include several regions in the inferior and middle temporal lobes. From these functional imaging results, a new anatomically constrained model of word processing is proposed which reconciles the anatomical ambitions of the 19th Century neurologists and the cognitive finesse of the 20th Century cognitive models. The review focuses on single word processing and does not attempt to discuss how words are combined to generate sentences or how several languages are learned and interchanged. Progress in unravelling these and other related issues will depend on the integration of behavioural, computational and neurophysiological approaches, including neuroimaging.
    BibTeX:
    @article{Price2000,
      author = {Price, CJ},
      title = {The anatomy of language: contributions from functional neuroimaging},
      journal = {JOURNAL OF ANATOMY},
      year = {2000},
      volume = {197},
      number = {Part 3},
      pages = {335-359}
    }
    
    Quirk, G., Russo, G., Barron, J. & Lebron, K. The role of ventromedial prefrontal cortex in the recovery of extinguished fear {2000} JOURNAL OF NEUROSCIENCE
    Vol. {20}({16}), pp. {6225-6231} 
    article  
    Abstract: Conditioned fear responses to a tone paired with footshock extinguish when the tone is presented repeatedly in the absence of shock. Rather than erase the tone-shock association, extinction is thought to involve new learning accompanied by inhibition of conditioned responding. Despite much interest in extinction from a clinical perspective, little is known about the neural circuits that are involved. Although the prefrontal cortex has a well established role in the inhibition of inappropriate behaviors, previous reports have disagreed as to the role of the ventromedial prefrontal cortex (vmPFC) in extinction. We have reexamined the effects of electrolytic vmPFC lesions made before training on the acquisition, extinction, and recovery of conditioned fear responses in a 2 d experiment. On Day 1 vmPFC lesions had no effect on acquisition or extinction of conditioned freezing and suppression of bar pressing. On Day 2 sham rats recovered only 27% of their acquired freezing, whereas vmPFC-lesioned rats recovered 86 which was indistinguishable from a control group that never received extinction. The high recovery in lesioned rats could not be attributed to decreased motivation or altered sensitivity to footshock. vmPFC lesions that spared the caudal infralimbic (IL) nucleus had no effect. Thus, the vmPFC (particularly the IL nucleus) is not necessary for expression of extinction, but it is necessary for the recall of extinction learning after a long delay. These data suggest a role of the vmPFC in consolidation of extinction learning or the recall of contexts in which extinction took place.
    BibTeX:
    @article{Quirk2000,
      author = {Quirk, GJ and Russo, GK and Barron, JL and Lebron, K},
      title = {The role of ventromedial prefrontal cortex in the recovery of extinguished fear},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2000},
      volume = {20},
      number = {16},
      pages = {6225-6231}
    }
    
    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}
    }
    
    Raine, A., Lencz, T., Bihrle, S., LaCasse, L. & Colletti, P. Reduced prefrontal gray matter volume and reduced autonomic activity in antisocial personality disorder {2000} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {57}({2}), pp. {119-127} 
    article  
    Abstract: Background: Major damage to gray and white matter in the prefrontal cortex and autonomic deficits have been found to result in pseudopsychopathic personality in patients with neurological disorders, but it is not known whether people with antisocial personality disorder (APD) in the community who do not have discernable brain trauma also have subtle prefrontal deficits. Methods: Prefrontal gray and white matter volumes were assessed using structural magnetic resonance imaging in 21 community volunteers with APD (APD group) and in 2 control groups, comprising 34 healthy subjects (control group), 26 subjects with substance dependence (substance-dependent group), and 21 psychiatric controls. Autonomic activity (skin conductance and heart rate) was also assessed during a social stresser in which participants gave a videotaped speech on their faults. Results: The APD group showed an 11.0% reduction in prefrontal gray matter volume in the absence of ostensible brain lesions and reduced autonomic activity during the stresser. These deficits predicted group membership independent of psychosocial risk factors. Conclusions: To our knowledge, these findings provide the first evidence for a structural brain deficit in APD. This prefrontal structural deficit may underlie the low arousal, poor fear conditioning, lack of conscience, and decision-making deficits that have been found to char acterize antisocial, psychopathic behavior.
    BibTeX:
    @article{Raine2000,
      author = {Raine, A and Lencz, T and Bihrle, S and LaCasse, L and Colletti, P},
      title = {Reduced prefrontal gray matter volume and reduced autonomic activity in antisocial personality disorder},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {2000},
      volume = {57},
      number = {2},
      pages = {119-127}
    }
    
    Rajkowska, G. Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells {2000} BIOLOGICAL PSYCHIATRY
    Vol. {48}({8}), pp. {766-777} 
    article  
    Abstract: The influence of stress and glucocorticoids on neuronal pathology has been demonstrated in animal and clinical studies. It has been proposed that stress-induced changes in the hippocampus may be central to the development of depression in genetically vulnerable individuals. New evidence implicates the prefrontal cortex (PFC) in addition to the hippocampus as a site of neuropathology in depression. The PFC: may be involved in stress-mediated neurotoxicity because stress alters PFC functions and glucocorticoid receptors, the PFC is directly interconnected with the hippocampus, and metabolic alterations are present in the PFC in depressed patients. Postmortem studies in major depression and bipolar disorder provide the first evidence for specific neuronal and glial histopathology in mood disorders. Three patterns of morphometric cellular changes are noted: cell loss (subgenual PFC), cell atrophy (dorsolateral PFC and orbitofrontal cortex), and increased numbers of cells (hypothalamus, dorsal raphe nucleus). The relevance of cellular changes in mood disorders to stress and prolonged PFC development and a role of neurotrophic/neuroprotective factors are suggested, and a link between cellular changes and the action of therapeutic drugs is discussed. The precise anatomic localization of dysfunctional neurons and glia in mood disorders may reveal cortical targets for novel antidepressants and mood stabilizers. Biol Psychiatry 2000;48:766-777 (C) 2000 Society of Biological Psychiatry.
    BibTeX:
    @article{Rajkowska2000,
      author = {Rajkowska, G},
      title = {Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {2000},
      volume = {48},
      number = {8},
      pages = {766-777},
      note = {Conference on Depression in the 21st Century: New Insight into Drug Development and Neurobiology, DANA POINT, CALIFORNIA, FEB 02-22, 2000}
    }
    
    Rajkowska, G., Miguel-Hidalgo, J., Wei, J., Dilley, G., Pittman, S., Meltzer, H., Overholser, J., Roth, B. & Stockmeier, C. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression {1999} BIOLOGICAL PSYCHIATRY
    Vol. {45}({9}), pp. {1085-1098} 
    article  
    Abstract: Background: This report provides histopathological evidence to support prior neuroimaging findings of decreased volume and altered metabolism in the frontal cortex in major depressive disorder Methods: Computer-assisted three-dimensional cell counting was used to reveal abnormal cytoarchitecture in left rostral and caudal orbitofrontal and dorsolateral prefrontal cortical regions in subjects with major depression as compared to psychiatrically normal controls. Results: Depressed subjects had decreases in cortical thickness, neuronal sizes, and neuronal and glial densities in the upper (Il-N) cortical layers of the rostral orbitofrontal region. In the caudal orbitofrontal cortex in depressed subjects, there were prominent reductions in glial densities in the lower (V-VI) cortical layers that were accompanied by small but significant decreases in neuronal sizes. In the dorsolateral prefrontal cortex of depressed subjects marked reductions in the density and size of neurons and glial cells were found in both supra- and infragranular layers, Conclusions: These results reveal that major depression can be distinguished by specific histopathology of both neurons and glial cells in the prefrontal cortex. Our data will contribute to the interpretation of neuroimaging findings and identification of dysfunctional neuronal circuits in major depression. (C) 1999 Society of Biological Psychiatry.
    BibTeX:
    @article{Rajkowska1999,
      author = {Rajkowska, G and Miguel-Hidalgo, JJ and Wei, JR and Dilley, G and Pittman, SD and Meltzer, HY and Overholser, JC and Roth, BL and Stockmeier, CA},
      title = {Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {1999},
      volume = {45},
      number = {9},
      pages = {1085-1098}
    }
    
    Rao, S., Mayer, A. & Harrington, D. The evolution of brain activation during temporal processing {2001} NATURE NEUROSCIENCE
    Vol. {4}({3}), pp. {317-323} 
    article  
    Abstract: Timing is crucial to many aspects of human performance. To better understand its neural underpinnings, we used event-related fMRI to examine the time course of activation associated with different components of a time perception task. We distinguished systems associated with encoding time intervals from those related to comparing intervals and implementing a response. Activation in the basal ganglia occurred early, and was uniquely associated with encoding time intervals, whereas cerebellar activation unfolded late, suggesting an involvement in processes other than explicit timing. Early cortical activation associated with encoding of time intervals was observed in the right inferior parietal cortex and bilateral premotor cortex, implicating these systems in attention and temporary maintenance of intervals. Late activation in the right dorsolateral prefrontal cortex emerged during comparison of time intervals. Our results illustrate a dynamic network of cortical-subcortical activation associated with different components of temporal information processing.
    BibTeX:
    @article{Rao2001,
      author = {Rao, SM and Mayer, AR and Harrington, DL},
      title = {The evolution of brain activation during temporal processing},
      journal = {NATURE NEUROSCIENCE},
      year = {2001},
      volume = {4},
      number = {3},
      pages = {317-323}
    }
    
    Rao, S., Rainer, G. & Miller, E. Integration of what and where in the primate prefrontal cortex {1997} SCIENCE
    Vol. {276}({5313}), pp. {821-824} 
    article  
    Abstract: The visual system separates processing of an object's form and color (''what'') from its spatial location (''where''). In order to direct action to objects, the identity and location of those objects must somehow be integrated. To examine whether this process occurs within the prefrontal (PF) cortex, the activity of 195 PF neurons was recorded during a task that engaged both what and where working memory. Some neurons showed either object-tuned (what) or location-tuned (where) delay activity. However, over half (52 percent, or 64/123) of the PF neurons with delay activity showed both what and where tuning. These neurons may contribute to the linking of object information with the spatial information needed to guide behavior.
    BibTeX:
    @article{Rao1997,
      author = {Rao, SC and Rainer, G and Miller, EK},
      title = {Integration of what and where in the primate prefrontal cortex},
      journal = {SCIENCE},
      year = {1997},
      volume = {276},
      number = {5313},
      pages = {821-824}
    }
    
    Rauschecker, J. & Tian, B. Mechanisms and streams for processing of ``what'' and ``where'' in auditory cortex {2000} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {97}({22}), pp. {11800-11806} 
    article  
    Abstract: The functional specialization and hierarchical organization of multiple: areas in rhesus monkey auditory cortex were examined with various types of complex sounds. Neurons in the lateral belt areas of the superior temporal gyrus were tuned to the best center frequency and bandwidth of band-passed noise bursts. They were also selective for the rate and direction of linear frequency modulated sweeps. Many neurons showed a preference for a limited number of species-specific vocalizations (''monkey calls''). These response selectivities can be explained by nonlinear spectral and temporal integration mechanisms. In a separate series of experiments, monkey calls were presented at different spatial locations, and the tuning of lateral belt neurons to monkey calls and spatial location was determined. Of the three belt areas the anterolateral area shows the highest degree of specificity for monkey calls, whereas neurons in the caudolateral area display the greatest spatial selectivity. We conclude that the cortical auditory system of primates is divided into at least two processing streams, a spatial stream that originates in the caudal part of the superior temporal gyrus and projects to the parietal cortex, and a pattern or object stream originating in the more anterior portions of the lateral belt. A similar division of labor can be seen in human auditory cortex by using functional neuroimaging.
    BibTeX:
    @article{Rauschecker2000,
      author = {Rauschecker, JP and Tian, B},
      title = {Mechanisms and streams for processing of ``what'' and ``where'' in auditory cortex},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {2000},
      volume = {97},
      number = {22},
      pages = {11800-11806},
      note = {National Academy of Sciences Colloquium on Auditory Neuroscience - Development, Transduction, and Integration, IRVINE, CALIFORNIA, MAY 19-21, 2000}
    }
    
    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}
    }
    
    Reiman, E., Lane, R., Ahern, G., Schwartz, G., Davidson, R., Friston, K., Yun, L. & Chen, K. Neuroanatomical correlates of externally and internally generated human emotion {1997} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {154}({7}), pp. {918-925} 
    article  
    Abstract: Objective: Positron emission tomography was used to investigate the neural substrates of normal human emotion and their dependence on the type of emotional stimulus. Method: Twelve healthy female subjects underwent 12 measurements of regional brain activity following the intravenous bolus administration of [O-15]H2O as they alternated between emotion-generating and control film and recall tasks. Automated image analysis techniques were used to characterize and compare the increases in regional brain activity associated with the emotional response to complex visual (film) and cognitive (recall) stimuli. Results: Film- and recall-generated emotion were each associated with significantly increased activity in the vicinity of the medial prefrontal cortex and thalamus, suggesting that these regions participate in aspects of emotion that no not depend on the nature of the emotional stimulus. Film-generated emotion was associated with significantly greater increases in activity bilaterally in the occipitotemporoparietal cortex, lateral cerebellum, hypothalamus, and a region that includes the anterior temporal cortex, amygdala, and hippocampal formation, suggesting that these regions participate in the emotional response to certain exteroceptive sensory stimuli. Recall-generated sadness was associated with significantly greater increases in activity in the vicinity of the anterior insular cortex, suggesting that this region participates iir the emotional response to potentially distressing cognitive or interoceptive sensory stimuli. Conclusions: While this study should be considered preliminary it identified brain regions that participate in externally and internally generated human emotion.
    BibTeX:
    @article{Reiman1997,
      author = {Reiman, EM and Lane, RD and Ahern, GL and Schwartz, GE and Davidson, RJ and Friston, KJ and Yun, LS and Chen, KW},
      title = {Neuroanatomical correlates of externally and internally generated human emotion},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {1997},
      volume = {154},
      number = {7},
      pages = {918-925},
      note = {52nd Annual Meeting of the American-Psychosomatic-Society, BOSTON, MA, APR 13-16, 1994}
    }
    
    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}
    }
    
    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}
    }
    
    ROBERTSON, G. & FIBIGER, H. NEUROLEPTICS INCREASE C-FOS EXPRESSION IN THE FOREBRAIN - CONTRASTING EFFECTS OF HALOPERIDOL AND CLOZAPINE {1992} NEUROSCIENCE
    Vol. {46}({2}), pp. {315-328} 
    article  
    Abstract: The mechanisms by which the atypical neuroleptic clozapine produces its therapeutic effects in the treatment of schizophrenia without causing the extrapyramidal side effects that are characteristic of most antipsychotic drugs remain unclear. Recently, a single injection of the typical antipsychotic haloperidol has been shown to increase c-fos expression in the striatum [Dragunow et al. (1990) Neuroscience 37, 287-294]. C-fos is a proto-oncogene that encodes a 55,000 mol. wt phosphoprotein, Fos, which is thought to assist in the regulation of ``target genes'' containing an AP-1 binding site. Because a wide variety of physiological and pharmacological stimuli increase c-fos expression, it has been proposed that Fos immunohistochemistry might be useful in mapping functional pathways in the central nervous system. The present experiments examined some potential neuroanatomical differences in the actions of clozapine and haloperidol by comparing their effects on c-fos expression in the medial prefrontal cortex, nucleus accumbens, striatum and lateral septum. The effects of the selective dopamine receptor antagonists SCH 23390 (D1) and raclopride (D2) were also examined. Haloperidol (0.5, 1 mg/kg) and raclopride (1, 2 mg/kg) produced large increases in the number of Fos-containing neurons in the striatum and nucleus accumbens. SCH 23390 (0.5, 1 mg/kg) reduced the number of Fos-positive neurons in the nucleus accumbens and striatum, and had no effect in the other regions. Neither haloperidol nor raclopride increased the number of Fos-positive neurons in the medial prefronal cortex. Haloperidol, but not raclopride, produced a modest increase in c-fos expression in the lateral septal nucleus. Clozapine (10, 20 mg/kg) was without effect in the striatum; however, it significantly increased the number of Fos-positive neurons in the nucleus accumbens, medial prefrontal cortex and lateral septal nucleus. Destruction of mesotelencephalic dopaminergic neurons with 6-hydroxydopamine abolished the increase in Fos expression in the nucleus accumbens and striatum produced by haloperidol and raclopride, and also blocked the clozapine-induced increase in the nucleus accumbens. However, the inductive effects of clozapine and haloperidol on c-fos expression in the lateral septal nucleus and of clozapine in the medial prefrontal cortex were not affected by the 6-hydroxydopamine lesions. These results suggest that clozapine's unique therapeutic profile may be related to its failure to induce Fos in the striatum as well as its idiosyncratic actions in the lateral septum and medial prefrontal cortex. The effects of clozapine in these latter regions do not appear to be mediated by dopaminergic mechanisms.
    BibTeX:
    @article{ROBERTSON1992,
      author = {ROBERTSON, GS and FIBIGER, HC},
      title = {NEUROLEPTICS INCREASE C-FOS EXPRESSION IN THE FOREBRAIN - CONTRASTING EFFECTS OF HALOPERIDOL AND CLOZAPINE},
      journal = {NEUROSCIENCE},
      year = {1992},
      volume = {46},
      number = {2},
      pages = {315-328}
    }
    
    Robinson, T. & Berridge, K. Addiction {2003} ANNUAL REVIEW OF PSYCHOLOGY
    Vol. {54}, pp. {25-53} 
    article DOI  
    Abstract: The development of addiction involves a transition from casual to compulsive patterns of drug use. This transition to addiction is accompanied by many drug-induced changes in the brain and associated changes in psychological functions. In this article we present a critical analysis of the major theoretical explanations of how drug-induced alterations in psychological function might cause a transition to addiction. These include: (a) the traditional hedonic view that drug pleasure and subsequent unpleasant withdrawal symptoms are the chief causes of addiction; (b) the view that addiction is due to aberrant learning, especially the development of strong stimulus-response habits; (c) our incentive-sensitization view, which suggests that sensitization of a neural system that attributes incentive salience causes compulsive motivation or ``wanting'' to take addictive drugs; and (d) the idea that dysfunction of frontal cortical systems, which normally regulate decision making and inhibitory control over behavior, leads to impaired judgment and impulsivity in addicts.
    BibTeX:
    @article{Robinson2003,
      author = {Robinson, TE and Berridge, KC},
      title = {Addiction},
      journal = {ANNUAL REVIEW OF PSYCHOLOGY},
      year = {2003},
      volume = {54},
      pages = {25-53},
      doi = {{10.1146/annurev.psych.54.101601.145237}}
    }
    
    Robinson, T. & Kolb, B. Alterations in the morphology of dendrites and dendritic spines in the nucleus accumbens and prefrontal cortex following repeated treatment with amphetamine or cocaine {1999} EUROPEAN JOURNAL OF NEUROSCIENCE
    Vol. {11}({5}), pp. {1598-1604} 
    article  
    Abstract: Repeated treatment with psychostimulant drugs produces changes in brain and behaviour that far outlast their initial neuropharmacological actions. The nature of persistent drug-induced neurobehavioural adaptations is of interest because they are thought to contribute to the development of dependence and addiction, and other forms of psychopathology, e.g. amphetamine psychosis. There are many reports that psychostimulants produce biochemical adaptations in brain monoamine systems, especially dopamine systems. The purpose of the present study was to determine if they might also alter the morphology of neurons in brain regions that receive monoaminergic innervation. Rats were given repeated injections of either amphetamine or cocaine, or, to control for general motor activity allowed access to running wheel. They were then left undisturbed for 24-25 days before their brains were processed for Golgi-Cox staining. Treatment with either amphetamine or cocaine (but not wheel running experience) increased the number of dendritic branches and the density of dendritic spines on medium spiny neurons in the shell of the nucleus accumbens, and on apical dendrites of layer V pyramidal cells in the prefrontal cortex, cocaine also increased dendritic branching and spine density on the basilar dendrites of pyramidal cells. In addition, both drugs doubled the incidence of branched spines on medium spiny neurons. It is suggested that some of the persistent neurobehavioural consequences of repeated exposure to psychostimulant drugs may be due to their ability to reorganize patterns of synaptic connectivity in the nucleus accumbens and prefrontal cortex.
    BibTeX:
    @article{Robinson1999,
      author = {Robinson, TE and Kolb, B},
      title = {Alterations in the morphology of dendrites and dendritic spines in the nucleus accumbens and prefrontal cortex following repeated treatment with amphetamine or cocaine},
      journal = {EUROPEAN JOURNAL OF NEUROSCIENCE},
      year = {1999},
      volume = {11},
      number = {5},
      pages = {1598-1604}
    }
    
    Robinson, T. & Kolb, B. Persistent structural modifications in nucleus accumbens and prefrontal cortex neurons produced by previous experience with amphetamine {1997} JOURNAL OF NEUROSCIENCE
    Vol. {17}({21}), pp. {8491-8497} 
    article  
    Abstract: Experience-dependent changes in behavior are thought to involve structural modifications in the nervous system, especially alterations in patterns of synaptic connectivity. Repeated experience with drugs of abuse can result in very long-lasting changes in behavior, including a persistent hypersensitivity (sensitization) to their psychomotor activating and rewarding effects. It was hypothesized, therefore, that repeated treatment with the psychomotor stimulant drug amphetamine, which produces robust sensitization, would produce structural adaptations in brain regions that mediate its psychomotor activating and rewarding effects. Consistent with this hypothesis, it was found that amphetamine treatment altered the morphology of neurons in the nucleus accumbens and prefrontal cortex. Exposure to amphetamine produced a long-lasting (>1 month) increase in the length of dendrites, in the density of dendritic spines, and in the number of branched spines on the major output cells of the nucleus accumbens, the medium spiny neurons, as indicated by analysis of Golgi-stained material. Amphetamine treatment produced similar effects on the apical (but not basilar) dendrites of layer III pyramidal neurons in the prefrontal cortex. The ability of amphetamine to alter patterns of synaptic connectivity in these structures may contribute to some of the long-term behavioral consequences of repeated amphetamine use, including amphetamine psychosis and addiction.
    BibTeX:
    @article{Robinson1997,
      author = {Robinson, TE and Kolb, B},
      title = {Persistent structural modifications in nucleus accumbens and prefrontal cortex neurons produced by previous experience with amphetamine},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1997},
      volume = {17},
      number = {21},
      pages = {8491-8497}
    }
    
    Rogers, R., Everitt, B., Baldacchino, A., Blackshaw, A., Swainson, R., Wynne, K., Baker, N., Hunter, J., Carthy, T., Booker, E., London, M., Deakin, J., Sahakian, B. & Robbins, T. Dissociable deficits in the decision-making cognition of chronic amphetamine abusers, opiate abusers, patients with focal damage to prefrontal cortex, and tryptophan-depleted normal volunteers: Evidence for monoaminergic mechanisms {1999} NEUROPSYCHOPHARMACOLOGY
    Vol. {20}({4}), pp. {322-339} 
    article  
    Abstract: We used a novel computerized decision-making task to compare the decision-making behavior of chronic amphetamine abusers, chronic opiate abusers, and patients with focal lesions of orbital prefrontal cortex (PFC) or dorsolateral/medial PFC. We also assessed the effects of reducing central 5-hydroxytryptamine (5-HT) activity using a tryptophan-depleting amino acid drink in normal volunteers. Chronic amphetamine abusers showed sub-optimal decisions (correlated with years of abuse), and deliberated or significantly longer before making their choices. The opiate abusers exhibited only the second of these behavioral changes. Importantly, both sub-optimal choices and increased deliberation times were evident in the patients with damage to orbitofrontal PFC but not other sectors of PFC. Qualitatively, the performance of the subjects with lowered plasma tryptophan was similar to that associated with amphetamine abuse, consistent with recent reports of depleted 5-HT in the orbital regions of PFC of methamphetamine abusers. Overall, these data suggest that chronic amphetamine abusers show similar decision-making deficits to those seen after focal damage to orbitofrontal PFC. These deficits may reflect altered neuromodulation of the orbitofrontal PFC and interconnected limbic-striatal systems by both the ascending 5-HT and mesocortical dopamine (DA) projections. [Neuropsychopharmacology 20:322-339, 1999]. (C) 1999 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.
    BibTeX:
    @article{Rogers1999,
      author = {Rogers, RD and Everitt, BJ and Baldacchino, A and Blackshaw, AJ and Swainson, R and Wynne, K and Baker, NB and Hunter, J and Carthy, T and Booker, E and London, M and Deakin, JFW and Sahakian, BJ and Robbins, TW},
      title = {Dissociable deficits in the decision-making cognition of chronic amphetamine abusers, opiate abusers, patients with focal damage to prefrontal cortex, and tryptophan-depleted normal volunteers: Evidence for monoaminergic mechanisms},
      journal = {NEUROPSYCHOPHARMACOLOGY},
      year = {1999},
      volume = {20},
      number = {4},
      pages = {322-339}
    }
    
    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{Rogers1999a,
      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}
    }
    
    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}
    }
    
    Rolls, E. The orbitofrontal cortex {1996} PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
    Vol. {351}({1346}), pp. {1433-1443} 
    article  
    Abstract: The 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 odours is represented. The orbitofrontal cortex also receives information about the sight of objects from the temporal lobe cortical visual areas, and is involved in learning and in reversing stimulus-reinforcement associations. The stimulus might be a visual or olfactory stimulus, and the primary (unlearned) reinforcer a taste or touch. Damage to the orbitofrontal cortex impairs the learning and reversal of stimulus-reinforcement associations, and thus the correction of behavioural responses when these are no longer appropriate because previous reinforcement contingencies change. The information which reaches the orbitofrontal cortex for these functions includes information about faces, and damage to the orbitofrontal cortex can impair face expression identification. This evidence thus shows that the orbitofrontal cortex is involved in decoding some primary reinforcers such as taste; in learning and reversing associations of visual and other stimuli to these primary reinforcers; and plays an executive function in controlling and correcting reward-related and punishment-related behaviour, and thus in emotion.
    BibTeX:
    @article{Rolls1996,
      author = {Rolls, ET},
      title = {The orbitofrontal cortex},
      journal = {PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES},
      year = {1996},
      volume = {351},
      number = {1346},
      pages = {1433-1443}
    }
    
    Romanski, L., Tian, B., Fritz, J., Mishkin, M., Goldman-Rakic, P. & Rauschecker, J. Dual streams of auditory afferents target multiple domains in the primate prefrontal cortex {1999} NATURE NEUROSCIENCE
    Vol. {2}({12}), pp. {1131-1136} 
    article  
    Abstract: `What' and `where' visual streams define ventrolateral object and dorsolateral spatial processing domains in the prefrontal cortex of nonhuman primates. We looked for similar streams for auditory-prefrontal connections in rhesus macaques by combining microelectrode recording with anatomical tract-tracing. Injection of multiple tracers into physiologically mapped regions AL, ML and CL of the auditory belt cortex revealed that anterior belt cortex was reciprocally connected with the frontal pole (area 10), rostral principal sulcus (area 46) and ventral prefrontal regions (areas 12 and 45), whereas the caudal belt was mainly connected with the caudal principal sulcus (area 46) and frontal eye fields (area 8a). Thus separate auditory streams originate in caudal and rostral auditory cortex and target spatial and non-spatial domains of the frontal lobe, respectively.
    BibTeX:
    @article{Romanski1999,
      author = {Romanski, LM and Tian, B and Fritz, J and Mishkin, M and Goldman-Rakic, PS and Rauschecker, JP},
      title = {Dual streams of auditory afferents target multiple domains in the primate prefrontal cortex},
      journal = {NATURE NEUROSCIENCE},
      year = {1999},
      volume = {2},
      number = {12},
      pages = {1131-1136}
    }
    
    Rowe, J., Toni, I., Josephs, O., Frackowiak, R. & Passingham, R. The prefrontal cortex: Response selection or maintenance within working memory? {2000} SCIENCE
    Vol. {288}({5471}), pp. {1656-1660} 
    article  
    Abstract: It is controversial whether the dorsolateral prefrontal cortex is involved in the maintenance of items in working memory or in the selection of responses. We used event-related functional magnetic resonance imaging to study the performance of a spatial working memory task by humans, We distinguished the maintenance of spatial items from the selection of an item from memory to guide a response. Selection, but not maintenance, was associated with activation of prefrontal area 46 of the dorsal lateral prefrontal cortex, In contrast, maintenance was associated with activation of prefrontal area 8 and the intraparietal cortex The results support a role for the dorsal prefrontal cortex in the selection of representations. ntis accounts for the fact that this area is activated both when subjects select between items on working memory tasks and when they freely select between movements on tasks of willed action.
    BibTeX:
    @article{Rowe2000,
      author = {Rowe, JB and Toni, I and Josephs, O and Frackowiak, RSJ and Passingham, RE},
      title = {The prefrontal cortex: Response selection or maintenance within working memory?},
      journal = {SCIENCE},
      year = {2000},
      volume = {288},
      number = {5471},
      pages = {1656-1660}
    }
    
    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}}
    }
    
    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}}
    }
    
    SAITO, K., ELCE, J., HAMOS, J. & NIXON, R. WIDESPREAD ACTIVATION OF CALCIUM-ACTIVATED NEUTRAL PROTEINASE (CALPAIN) IN THE BRAIN IN ALZHEIMER-DISEASE - A POTENTIAL MOLECULAR-BASIS FOR NEURONAL DEGENERATION {1993} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {90}({7}), pp. {2628-2632} 
    article  
    Abstract: Calcium-activated neutral proteinases (CANPs or calpains) are believed to be key enzymes in intracellular signaling cascades and potential mediators of calcium-induced neuronal degeneration. To investigate their involvement in Alzheimer disease, we identified three isoforms of muCANP (calpain I) in human postmortem brain corresponding to an 80-kDa precursor and two autolytically activated isoforms (78 and 76 kDa). As an index of changes in the in vivo activity of muCANP in Alzheimer disease, the ratio of the 76-kDa activated isoform of muCANP to its 80-kDa precursor was measured by immunoassay in selected brain regions from 22 individuals with Alzheimer disease and 18 normal controls. This muCANP activation ratio was elevated 3-fold in the prefrontal cortex from patients with Alzheimer disease but not from patients with Huntington disease. The activation ratio was also significantly elevated, but to a lesser degree, in brain regions where Alzheimer pathology is milder and has not led to overt neuronal degeneration. These findings indicate that muCANP activation is not simply a consequence of cellular degeneration but may be associated with dysfunction in many neurons before gross structural changes occur. The known influences of CANPs on cytoskeleton and membrane dynamics imply that persistent CANP activation may contribute to neurofibrillary pathology and abnormal amyloid precursor protein processing prior to causing synapse loss or cell death in the most vulnerable neuronal populations. Pharmacological modulation of the CANP system may merit consideration as a potential therapeutic strategy in Alzheimer disease.
    BibTeX:
    @article{SAITO1993,
      author = {SAITO, KI and ELCE, JS and HAMOS, JE and NIXON, RA},
      title = {WIDESPREAD ACTIVATION OF CALCIUM-ACTIVATED NEUTRAL PROTEINASE (CALPAIN) IN THE BRAIN IN ALZHEIMER-DISEASE - A POTENTIAL MOLECULAR-BASIS FOR NEURONAL DEGENERATION},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1993},
      volume = {90},
      number = {7},
      pages = {2628-2632}
    }
    
    Sanfey, A., Rilling, J., Aronson, J., Nystrom, L. & Cohen, J. The neural basis of economic decision-making in the ultimatum game {2003} SCIENCE
    Vol. {300}({5626}), pp. {1755-1758} 
    article  
    Abstract: The nascent field of neuroeconomics seeks to ground economic decision-making in the biological substrate of the brain. We used functional magnetic resonance imaging of Ultimatum Game players to investigate neural substrates of cognitive and emotional processes involved in economic decision-making. In this game, two players split a sum of money; one player proposes a division and the other can accept or reject this. We scanned players as they responded to fair and unfair proposals. Unfair offers elicited activity in brain areas related to both emotion ( anterior insula) and cognition ( dorsolateral prefrontal cortex). Further, significantly heightened activity in anterior insula for rejected unfair offers suggests an important role for emotions in decision-making.
    BibTeX:
    @article{Sanfey2003,
      author = {Sanfey, AG and Rilling, JK and Aronson, JA and Nystrom, LE and Cohen, JD},
      title = {The neural basis of economic decision-making in the ultimatum game},
      journal = {SCIENCE},
      year = {2003},
      volume = {300},
      number = {5626},
      pages = {1755-1758}
    }
    
    Sapolsky, R. Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders {2000} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {57}({10}), pp. {925-935} 
    article  
    Abstract: An extensive literature stretching back decades has shown that prolonged stress or prolonged exposure to glucocorticoids, the adrenal steroids secreted during stress, can have adverse effects on the rodent hippocampus. More recent findings suggest a similar phenomenon in the human hippocampus associated with many neuropsychiatric disorders. This review examines the evidence for hippocampal atrophy in (1) Cushing syndrome, which is characterized by a pathologic oversecretion of glucocorticoids; (2) episodes of repeated and severe major depression, which is often associated with hypersecretion of glucocorticoids; and (3) posttraumatic stress disorder. Key questions that will be examined include whether the hippocampal atrophy arises from the neuropsychiatric disorder, or precedes and predisposes toward it; whether glucocorticoids really are plausible candidates for contributing to the atrophy; and what cellular mechanisms underlie the overall decreases in hippocampal volume. Explicit memory deficits have been demonstrated in Cushing syndrome, depression, and posttraumatic stress disorder; an extensive literature suggests that hippocampal atrophy of the magnitude found in these disorders can give rise to such cognitive deficits.
    BibTeX:
    @article{Sapolsky2000,
      author = {Sapolsky, RM},
      title = {Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {2000},
      volume = {57},
      number = {10},
      pages = {925-935}
    }
    
    Sara, S. Retrieval and reconsolidation: Toward a neurobiology of remembering {2000} LEARNING & MEMORY
    Vol. {7}({2}), pp. {73-84} 
    article  
    Abstract: A permanently existing ``idea'' which makes its appearance before the footlights of consciousness at periodical intervals is as mythological an entity as the Jack of Spades.
    BibTeX:
    @article{Sara2000,
      author = {Sara, SJ},
      title = {Retrieval and reconsolidation: Toward a neurobiology of remembering},
      journal = {LEARNING & MEMORY},
      year = {2000},
      volume = {7},
      number = {2},
      pages = {73-84}
    }
    
    SAWAGUCHI, T. & GOLDMANRAKIC, P. THE ROLE OF D1-DOPAMINE RECEPTOR IN WORKING-MEMORY - LOCAL INJECTIONS OF DOPAMINE ANTAGONISTS INTO THE PREFRONTAL CORTEX OF RHESUS-MONKEYS PERFORMING AN OCULOMOTOR DELAYED-RESPONSE TASK {1994} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {71}({2}), pp. {515-528} 
    article  
    Abstract: 1. To examine the role of dopamine receptors in the prefrontal cortex (PFC) on working memory, we injected dopamine antagonists (SCH23390, SCH39166, haloperidol, sulpiride, and raclopride) locally into the dorsolateral PFC in two monkeys trained to perform an oculomotor delayed-response (ODR) task. In the ODR task, monkeys fixate a central spot on a cathode ray tube (CRT) monitor while a visual cue is briefly (300 ms) presented in one of several peripheral locations in the visual field. After a delay of 1.5-6 s, the fixation spot is turned off, instructing the monkey to move its eyes to the target location that had been indicated by the visuospatial cue before the delay. Each monkey also performed a control task in which the cue remained on during the delay period. In this task the monkey's response was sensory rather than memory guided. 2. Local intracerebral injection of the selective dopamine antagonists SCH23390 (10-80 mu g) and SCH39 166 (1-5 mu g) and/or the nonselective dopamine antagonist haloperidol (10-100 mu g) induced deficits in ODR task performance at a total of 22 sites in the dorsolateral PFC. The deficit was characterized by a decrease in the accuracy of the memory-guided saccade as well as an increase in the latency of the response. The deficit usually appeared within 1-3 min after the injection, reached a peak at 20-40 min, and recovered at 60-90 min. 3. Performance change was restricted to a few specific target locations, which varied with the injection site and were most often contralateral to the injection site. 4. The degree of impairment in the ODR task occasioned by the injection of the dopamine antagonists was sensitive to the duration of delay; longer delays were associated with larger decreases in the accuracy and delayed onset of the memory-guided saccade. 5. The deficit was dose dependent; higher doses induced larger errors and increases in the onset of the memory-guided saccade. 6. Dopamine antagonists did not affect performance on the control task, which required the same eye movements but was sensory guided. Thus, in the same experimental session in which ODR performance was impaired, the accuracy and the latency of the sensory-guided saccades were normal for every target location. 7. Local injections of ketanserin [100 mu g, a selective antagonist of 5-hydroxytryptamine-2 (5HT-2) receptors] or SCH23388 (100 mu g, an inactive analogue of SCH23390) into or very near sites that were associated with positive results from SCH23390 injections failed to induce any clear changes in performance on either the ODR or control task. Therefore the effect of SCH23390 does not appear to be a consequence of its nonspecific effects or its possible effects on 5HT-2 receptors. 8. The local injection of sulpiride (50-100 mu g, a selective D2 antagonist) or raclopride (100 mu g, a D2/D3 antagonist) was without clear effect on either the ODR or control task, suggesting that neither D2 nor D3 receptors are critical for ODR performance, at least under present conditions. Nor did the injection of saline have any significant effects on either the ODR or control task. 9. These results provide evidence that D1-dopamine receptors in the dorsolateral PFC of monkeys participate in the maintenance of internalized visuospatial representations and/or in the control of eye movements governed by these internal cues.
    BibTeX:
    @article{SAWAGUCHI1994,
      author = {SAWAGUCHI, T and GOLDMANRAKIC, PS},
      title = {THE ROLE OF D1-DOPAMINE RECEPTOR IN WORKING-MEMORY - LOCAL INJECTIONS OF DOPAMINE ANTAGONISTS INTO THE PREFRONTAL CORTEX OF RHESUS-MONKEYS PERFORMING AN OCULOMOTOR DELAYED-RESPONSE TASK},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1994},
      volume = {71},
      number = {2},
      pages = {515-528}
    }
    
    SAWAGUCHI, T. & GOLDMANRAKIC, P. D1 DOPAMINE-RECEPTORS IN PREFRONTAL CORTEX - INVOLVEMENT IN WORKING MEMORY {1991} SCIENCE
    Vol. {251}({4996}), pp. {947-950} 
    article  
    Abstract: The prefrontal cortex is involved in the cognitive process of working memory. Local injections of SCH23390 and SCH39166, selective antagonists of the D1 dopamine receptor, into the prefrontal cortex of rhesus monkeys induced errors and increased latency in performance on an oculomotor task that required memory-guided saccades. The deficit was dose-dependent and sensitive to the duration of the delay period. These D1 antagonists had no effect on performance in a control task requiring visually guided saccades, indicating that sensory and motor functions were unaltered. Thus, D1 dopamine receptors play a selective role in the mnemonic, predictive functions of the primate prefrontal cortex.
    BibTeX:
    @article{SAWAGUCHI1991,
      author = {SAWAGUCHI, T and GOLDMANRAKIC, PS},
      title = {D1 DOPAMINE-RECEPTORS IN PREFRONTAL CORTEX - INVOLVEMENT IN WORKING MEMORY},
      journal = {SCIENCE},
      year = {1991},
      volume = {251},
      number = {4996},
      pages = {947-950}
    }
    
    Schacter, D. & Buckner, R. Priming and the brain {1998} NEURON
    Vol. {20}({2}), pp. {185-195} 
    article  
    BibTeX:
    @article{Schacter1998,
      author = {Schacter, DL and Buckner, RL},
      title = {Priming and the brain},
      journal = {NEURON},
      year = {1998},
      volume = {20},
      number = {2},
      pages = {185-195}
    }
    
    Schmahmann, J. & Sherman, J. The cerebellar cognitive affective syndrome {1998} BRAIN
    Vol. {121}({Part 4}), pp. {561-579} 
    article  
    Abstract: Anatomical, physiological and functional neuroimaging studies suggest that the cerebellum participates in the organization of higher order function, but there are very few descriptions of clinically relevant cases that address this possibility. We performed neurological examinations, bedside mental state rests, neuropsychological studies and anatomical neuroimaging on 20 patients with diseases confined to the cerebellum, and evaluated the nature and severity of the changes in neurological and mental function. Behavioural changes were clinically prominent in patients with lesions involving the posterior lobe of the cerebellum and the vermis, and in some cases they were the most noticeable aspects of the presentation. These changes were characterized by: impairment of executive functions such as planning, set shifting, verbal fluency, abstract reasoning and working memory; difficulties with spatial cognition including visual-spatial organization and memory; personality change with blunting of affect or disinhibited and inappropriate behaviour; and language deficits including agrammatism and dysprosodia. Lesions of the anterior lobe of the cerebellum produced only minor changes in executive and visual-spatial functions. We have called this newly defined clinical entity the `cerebellar cognitive affective syndrome'. The constellation of deficits is suggestive of disruption of the cerebellar modulation of neural circuits that link prefrontal, posterior parietal. superior temporal and limbic cortices with the cerebellum.
    BibTeX:
    @article{Schmahmann1998,
      author = {Schmahmann, JD and Sherman, JC},
      title = {The cerebellar cognitive affective syndrome},
      journal = {BRAIN},
      year = {1998},
      volume = {121},
      number = {Part 4},
      pages = {561-579},
      note = {27th Annual Meeting of the Society-of-Neuroscience, NEW ORLEANS, LOUISIANA, OCT 25-30, 1997}
    }
    
    Schoenbaum, G., Chiba, A. & Gallagher, M. Orbitofrontal cortex and basolateral amygdala encode expected outcomes during learning {1998} NATURE NEUROSCIENCE
    Vol. {1}({2}), pp. {155-159} 
    article  
    Abstract: Reciprocal connections between the orbitofrontal cortex and the basolateral nucleus of the amygdala may provide a critical circuit for the learning that underlies goal-directed behavior. We examined neural activity in rat orbitofrontal cortex and basolateral amygdala during instrumental learning in an olfactory discrimination task. Neurons in both regions fired selectively during the anticipation of rewarding or aversive outcomes. This selective activity emerged early in training, before the rats had learned reliably to avoid the aversive outcome. The results support the concept that the basolateral amygdala and orbitofrontal cortex cooperate to encode information that may be used to guide goal-directed behavior.
    BibTeX:
    @article{Schoenbaum1998,
      author = {Schoenbaum, G and Chiba, AA and Gallagher, M},
      title = {Orbitofrontal cortex and basolateral amygdala encode expected outcomes during learning},
      journal = {NATURE NEUROSCIENCE},
      year = {1998},
      volume = {1},
      number = {2},
      pages = {155-159}
    }
    
    Schultz, W. Getting formal with dopamine and reward {2002} NEURON
    Vol. {36}({2}), pp. {241-263} 
    article  
    Abstract: Recent neurophysiological studies reveal that neurons in certain brain structures carry specific signals about past and future rewards. Dopamine neurons display a short-latency, phasic reward signal indicating the difference between actual and predicted rewards. The signal is useful for enhancing neuronal processing and learning behavioral reactions. It is distinctly different from dopamine's tonic enabling of numerous behavioral processes. Neurons in the striatum, frontal cortex, and amygdala also process reward information but provide more differentiated information for identifying and anticipating rewards and organizing goal-directed behavior. The different reward signals have complementary functions, and the optimal use of rewards in voluntary behavior would benefit from interactions between the signals. Addictive psychostimulant drugs may exert their action by amplifying the dopamine reward signal.
    BibTeX:
    @article{Schultz2002,
      author = {Schultz, W},
      title = {Getting formal with dopamine and reward},
      journal = {NEURON},
      year = {2002},
      volume = {36},
      number = {2},
      pages = {241-263}
    }
    
    Schultz, W. Multiple reward signals in the brain {2000} NATURE REVIEWS NEUROSCIENCE
    Vol. {1}({3}), pp. {199-207} 
    article  
    Abstract: The fundamental biological importance of rewards has created an increasing interest in the neuronal processing of reward information. The suggestion that the mechanisms underlying drug addiction might involve natural reward systems has also stimulated interest. This article focuses on recent neurophysiological studies in primates that have revealed that neurons in a limited number of brain structures carry specific signals about past and future rewards. This research provides the first step towards an understanding of how rewards influence behaviour before they are received and how the brain might use reward information to control learning and goal-directed behaviour.
    BibTeX:
    @article{Schultz2000,
      author = {Schultz, W},
      title = {Multiple reward signals in the brain},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2000},
      volume = {1},
      number = {3},
      pages = {199-207}
    }
    
    SCHULTZ, W., APICELLA, P. & LJUNGBERG, T. RESPONSES OF MONKEY DOPAMINE NEURONS TO REWARD AND CONDITIONED-STIMULI DURING SUCCESSIVE STEPS OF LEARNING A DELAYED-RESPONSE TASK {1993} JOURNAL OF NEUROSCIENCE
    Vol. {13}({3}), pp. {900-913} 
    article  
    Abstract: The present investigation had two aims: (1) to study responses of dopamine neurons to stimuli with attentional and motivational significance during several steps of learning a behavioral task, and (2) to study the activity of dopamine neurons during the performance of cognitive tasks known to be impaired after lesions of these neurons. Monkeys that had previously learned a simple reaction time task were trained to perform a spatial delayed response task via two intermediate tasks. During the learning of each new task, a total of 25% of 76 dopamine neurons showed phasic responses to the delivery of primary liquid reward, whereas only 9% of 163 neurons responded to this event once task performance was established. This produced an average population response during but not after learning of each task. Reward responses during learning were significantly more numerous and pronounced in area A10, as compared to areas A8 and A9. Dopamine neurons also showed phasic responses to the two conditioned stimuli. These were the instruction cue, which was the first stimulus in each trial and indicated the target of the upcoming arm movement (58% of 76 neurons during and 44% of 163 neurons after learning), and the trigger stimulus, which was a conditioned incentive stimulus predicting reward and eliciting a saccadic eye movement and an arm reaching movement (38% of neurons during and 40% after learning). None of the dopamine neurons showed sustained activity in the delay between the instruction and trigger stimuli that would resemble the activity of neurons in dopamine terminal areas, such as the striatum and frontal cortex. Thus, dopamine neurons respond phasically to alerting external stimuli with behavioral significance whose detection is crucial for learning and performing delayed response tasks. The lack of sustained activity suggests that dopamine neurons do not encode representational processes, such as working memory, expectation of external stimuli or reward, or preparation of movement. Rather, dopamine neurons are involved with transient changes of impulse activity in basic attentional and motivational processes underlying learning and cognitive behavior.
    BibTeX:
    @article{SCHULTZ1993,
      author = {SCHULTZ, W and APICELLA, P and LJUNGBERG, T},
      title = {RESPONSES OF MONKEY DOPAMINE NEURONS TO REWARD AND CONDITIONED-STIMULI DURING SUCCESSIVE STEPS OF LEARNING A DELAYED-RESPONSE TASK},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1993},
      volume = {13},
      number = {3},
      pages = {900-913}
    }
    
    SCHULTZ, W., APICELLA, P., SCARNATI, E. & LJUNGBERG, T. NEURONAL-ACTIVITY IN MONKEY VENTRAL STRIATUM RELATED TO THE EXPECTATION OF REWARD {1992} JOURNAL OF NEUROSCIENCE
    Vol. {12}({12}), pp. {4595-4610} 
    article  
    Abstract: Projections from cortical and subcortical limbic structures to the basal ganglia are predominantly directed to the ventral striatum. The present study investigated how the expectation of external events with behavioral significance is reflected in the activity of ventral striatal neurons. A total of 420 neurons were studied in macaque monkeys performing in a delayed go-no-go task. Lights of different colors instructed the animal to do an arm-reaching movement or refrain from moving, respectively, when a trigger light was illuminated a few seconds later. Task performance was reinforced by liquid reward in both situations. A total of 60 ventral striatal neurons showed sustained increases of activity before the occurrence of individual task events. In 43 of these neurons, activations specifically preceded the delivery of reward, independent of the movement or no-movement reaction. In a series of additional tests, these activations were time locked to the subsequent reward, disappeared within a few trials when reward was omitted, and were temporally unrelated to mouth movements. Changes in the appetitive value of the reward liquid modified the magnitude of activations, suggesting a possible relationship to the hedonic properties of the expected event. Activations also occurred when reward was delivered in a predictable manner outside of any behavioral task. These data suggest that neurons in the ventral striatum are activated during states of expectation of individual environmental events that are predictable to the subject through its past experience. The prevalence of activations related to the expectation of reward suggests that ventral striatal neurons have access to central representations of reward and thereby participate in the processing of information underlying the motivational control of goal-directed behavior.
    BibTeX:
    @article{SCHULTZ1992,
      author = {SCHULTZ, W and APICELLA, P and SCARNATI, E and LJUNGBERG, T},
      title = {NEURONAL-ACTIVITY IN MONKEY VENTRAL STRIATUM RELATED TO THE EXPECTATION OF REWARD},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1992},
      volume = {12},
      number = {12},
      pages = {4595-4610}
    }
    
    Schultz, W., Dayan, P. & Montague, P. A neural substrate of prediction and reward {1997} SCIENCE
    Vol. {275}({5306}), pp. {1593-1599} 
    article  
    Abstract: The capacity to predict future events permits a creature to detect, model, and manipulate the causal structure of its interactions with its environment. Behavioral experiments suggest that learning is driven by changes in the expectations about future salient events such as rewards and punishments. Physiological work has recently complemented these studies by identifying dopaminergic neurons in the primate whose fluctuating output apparently signals changes or errors in the predictions of future salient and rewarding events. Taken together, these findings can be understood through quantitative theories of adaptive optimizing control.
    BibTeX:
    @article{Schultz1997,
      author = {Schultz, W and Dayan, P and Montague, PR},
      title = {A neural substrate of prediction and reward},
      journal = {SCIENCE},
      year = {1997},
      volume = {275},
      number = {5306},
      pages = {1593-1599}
    }
    
    Schultz, W. & Dickinson, A. Neuronal coding of prediction errors {2000} ANNUAL REVIEW OF NEUROSCIENCE
    Vol. {23}, pp. {473-500} 
    article  
    Abstract: Associative learning enables animals ro anticipate the occurrence or important outcomes. Learning occurs when the actual outcome differs from the predicted outcome, resulting in a prediction error. Neurons in several brain structures appear to code prediction errors in relation to rewards, punishments, external stimuli, and behavioral reactions. In one form, dopamine neurons, norepinephrine neurons, and nucleus basalis neurons broadcast prediction errors as global reinforcement or teaching signals to large postsynaptic structures. In other cases, error signals are coded by selected neurons in the cerebellum, superior colliculus, frontal eye fields, parietal cortex, striatum, and visual system, where they influence specific subgroups of neurons. Prediction errors can be used in postsynaptic structures for the immediate selection of behavior or for synaptic changes underlying behavioral learning. The coding of prediction errors may represent a basic mode of brain function that may also contribute to the processing of sensory information and the short-term control of behavior.
    BibTeX:
    @article{Schultz2000a,
      author = {Schultz, W and Dickinson, A},
      title = {Neuronal coding of prediction errors},
      journal = {ANNUAL REVIEW OF NEUROSCIENCE},
      year = {2000},
      volume = {23},
      pages = {473-500}
    }
    
    Schultz, W., Tremblay, L. & Hollerman, J. Reward processing in primate orbitofrontal cortex and basal ganglia {2000} CEREBRAL CORTEX
    Vol. {10}({3}), pp. {272-283} 
    article  
    Abstract: This article reviews and interprets neuronal activities related to the expectation and delivery of reward in the primate orbitofrontal cortex, in comparison with slowly discharging neurons in the striatum (caudate, putamen and ventral striatum, including nucleus accumbens) and midbrain dopamine neurons. Orbitofrontal neurons showed three principal forms of reward-related activity during the performance of delayed response tasks, namely responses to reward-predicting instructions, activations during the expectation period immediately preceding reward and responses following reward. These activations discriminated between different rewards, often on the basis of the animals' preferences. Neurons in the striatum were also activated in relation to the expectation and detection of reward but in addition showed activities related to the preparation, initiation and execution of movements which reflected the expected reward. Dopamine neurons responded to rewards and reward-predicting stimuli, and coded an error in the prediction of reward. Thus, the investigated cortical and basal ganglia structures showed multiple, heterogeneous, partly simultaneous activations which were related to specific aspects of rewards. These activations may represent the neuronal substrates of rewards during learning and established behavioral performance. The processing of reward expectations suggests an access to central representations of rewards which may be used for the neuronal control of goal-directed behavior.
    BibTeX:
    @article{Schultz2000b,
      author = {Schultz, W and Tremblay, L and Hollerman, JR},
      title = {Reward processing in primate orbitofrontal cortex and basal ganglia},
      journal = {CEREBRAL CORTEX},
      year = {2000},
      volume = {10},
      number = {3},
      pages = {272-283}
    }
    
    Schwartz, J., Stoessel, P., Baxter, L., Martin, K. & Phelps, M. Systematic changes in cerebral glucose metabolic rate after successful behavior modification treatment of obsessive-compulsive disorder {1996} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {53}({2}), pp. {109-113} 
    article  
    Abstract: Background: We sought to determine in a new patient sample whether symptomatic improvement in obsessive-compulsive disorder treated with behavior modification is accompanied by significant changes in glucose metabolic rates in the caudate nucleus, measured with positron emission tomography, as seen in a previous study. Second, by combining samples from this and the previous study, we also examined whether there were pathologic correlational relationships among brain activity in the orbital cortex, caudate nucleus, and thalamus that obtained before behavioral treatment of obsessive-compulsive disorder, but that decreased significantly with symptom improvement. Methods: Nine patients with obsessive-compulsive disorder were studied with positron emission tomography before and after 10 weeks of structured exposure and response prevention behavioral and cognitive treatment. Results were analyzed both alone and combined with those from nine similar subjects from the previous study. Results: Behavior therapy responders had significant (P<.05) bilateral decreases in caudate glucose metabolic rates that were greater than those seen in poor responders to treatment. Before treatment, there were significant correlations of brain activity between the orbital gyri and the head of the caudate nucleus and the orbital gyri and the thalamus on the right. These correlations decreased significantly after effective treatment. Conclusions: These results replicate and extend previous findings of changes in caudate nucleus function with behavior therapy for obsessive-compulsive disorder. A prefrontal cortico-striato-thalamic brain system is implicated in mediation of symptoms of obsessive-compulsive disorder.
    BibTeX:
    @article{Schwartz1996,
      author = {Schwartz, JM and Stoessel, PW and Baxter, LR and Martin, KM and Phelps, ME},
      title = {Systematic changes in cerebral glucose metabolic rate after successful behavior modification treatment of obsessive-compulsive disorder},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1996},
      volume = {53},
      number = {2},
      pages = {109-113}
    }
    
    Seamans, J. & Yang, C. The principal features and mechanisms of dopamine modulation in the prefrontal cortex {2004} PROGRESS IN NEUROBIOLOGY
    Vol. {74}({1}), pp. {1-57} 
    article DOI  
    Abstract: Mesocotical dopamine (DA) inputs to the prefrontal cortex (PFC) play a crtical role in normal cognitive process and neuropsychiatic pathologies. This DA input regulates aspects of working memory function, planning and attention, and its dysfunctions may underlie positive and negative symtoms and cognitive deficits associated with schizophrenia. Despite intense research, there is still a lack of clear understanding of the basic principles of actions of DA in the PFC. In recent years, there has been considerable efforts by many groups to understand the cellular mechanisms of DA modulation of PFC neurons. However, the results of these efforts often lead to contradictions and controversies. One principal feature of DA that is agreed by most researchers is that DA is a neuromodulator and is clearly not an excitatory or inhibitory neurotransmitter. The present article aims to identify certain principles of DA mechanisms by drawing on published, as well as unpublished data from PFC and other CNS sites to shed light on aspects of DA neuromodulation and address some of the existing controversies. Eighteen key features about DA modulation have been identified. These points directly impact on the end result of DA neuromodulation, and in some cases explain why DA does not yield identical effects under all experimental conditions. It will become apparent that DA's actions in PFC are subtle and depend on a variety of factors that can no longer be ignored. Some of these key factors include distinct bell-shaped dose-response profiles of postsynaptic DA effects, different postsynaptic responses that are contingent on the duration of DA receptor stimulation, prolonged duration effects, bidirectional effects following activation of D1 and D2 classes of receptors and membrane potential state and history dependence of subsequent DA actions. It is hoped that these factors will be borne in mind in future research and as a result a more consistent picture of DA neuromodulation in the PFC will emerge. Based on these factors, a theory is proposed for DA's action in PFC. This theory suggests that DA acts to expand or contract the breadth of information held in working memory buffers in PFC networks. (C) 2004 Elsevier Ltd. All rights reserved.
    BibTeX:
    @article{Seamans2004,
      author = {Seamans, JK and Yang, CR},
      title = {The principal features and mechanisms of dopamine modulation in the prefrontal cortex},
      journal = {PROGRESS IN NEUROBIOLOGY},
      year = {2004},
      volume = {74},
      number = {1},
      pages = {1-57},
      doi = {{10.1016/j.pneurobio.2004.05.006}}
    }
    
    Selemon, L. & Goldman-Rakic, P. The reduced neuropil hypothesis: A circuit based model of schizophrenia {1999} BIOLOGICAL PSYCHIATRY
    Vol. {45}({1}), pp. {17-25} 
    article  
    Abstract: In recent years, quantitative studies of the neuropathology of schizophrenia have reignited interest in the cerebral cortex and focused attention on the cellular and subcellular constituents that may be altered in this disease. Findings have ranged from compromised circuitry in prefrontal areas to outright neuronal loss in temporal and cingulate cortices. Herein, we propose that a reduction in interneuronal neuropil in the prefrontal cortex is a prominent feature of cortical pathology in schizophrenia and review the growing evidence for this view from reports of altered neuronal density and immunohistochemical markers in various cortical regions. The emerging picture of neuropathology in schizophrenia is one of subtle changes in cellular architecture and brain circuity that nonetheless have a devastating impact on cortical function. Biol Psychiatry 1999;45:17-25 (C) 1999 Society of Biological Psychiatry.
    BibTeX:
    @article{Selemon1999,
      author = {Selemon, LD and Goldman-Rakic, PS},
      title = {The reduced neuropil hypothesis: A circuit based model of schizophrenia},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {1999},
      volume = {45},
      number = {1},
      pages = {17-25}
    }
    
    SELEMON, L., RAJKOWSKA, G. & GOLDMANRAKIC, P. ABNORMALLY HIGH NEURONAL DENSITY IN THE SCHIZOPHRENIC CORTEX - A MORPHOMETRIC ANALYSIS OF PREFRONTAL AREA-9 AND OCCIPITAL AREA-17 {1995} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {52}({10}), pp. {805-818} 
    article  
    Abstract: Background: In the past two decades, gross morphologic changes have been uncovered in the schizophrenic brain, eg, increased ventricular width and decreased cortical volume; however, relatively little is known about the area-specific and laminar density of cells in the schizophrenic cortex, particularly in prefrontal areas. Method: A direct, three-dimensional counting method was used to determine cell density in 16 brains from patients with schizophrenia, 19 from normal subjects, six from patients with schizoaffective disorder, and nine from patients with advanced-stage Huntington's disease. Results: Increased neuronal density was found in prefrontal area 9 (17 and occipital area 17 (10 in the schizophrenic brains. In area 9, neuronal density was increased in layers III to VI; cell packing of pyramidal and nonpyramidal neurons was elevated. Cortical thickness in the schizophrenic brains was slightly but not significantly reduced in both areas, with a disproportionate reduction in layer V in area 9. In contrast, brains with Huntington's disease exhibited markedly higher glial density (50 and drastically reduced cortical thickness (28. Conclusion: Abnormally high density in the cerebral cortices of schizophrenics suggests that neuronal atrophy is the anatomic substrate for deficient information processing in schizophrenia.
    BibTeX:
    @article{SELEMON1995,
      author = {SELEMON, LD and RAJKOWSKA, G and GOLDMANRAKIC, PS},
      title = {ABNORMALLY HIGH NEURONAL DENSITY IN THE SCHIZOPHRENIC CORTEX - A MORPHOMETRIC ANALYSIS OF PREFRONTAL AREA-9 AND OCCIPITAL AREA-17},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1995},
      volume = {52},
      number = {10},
      pages = {805-818},
      note = {23rd Annual Meeting of the Society-for-Neuroscience, WASHINGTON, DC, NOV 07, 1993}
    }
    
    SESACK, S., DEUTCH, A., ROTH, R. & BUNNEY, B. TOPOGRAPHICAL ORGANIZATION OF THE EFFERENT PROJECTIONS OF THE MEDIAL PREFRONTAL CORTEX IN THE RAT - AN ANTEROGRADE TRACT-TRACING STUDY WITH PHASEOLUS-VULGARIS LEUCOAGGLUTININ {1989} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {290}({2}), pp. {213-242} 
    article  
    BibTeX:
    @article{SESACK1989,
      author = {SESACK, SR and DEUTCH, AY and ROTH, RH and BUNNEY, BS},
      title = {TOPOGRAPHICAL ORGANIZATION OF THE EFFERENT PROJECTIONS OF THE MEDIAL PREFRONTAL CORTEX IN THE RAT - AN ANTEROGRADE TRACT-TRACING STUDY WITH PHASEOLUS-VULGARIS LEUCOAGGLUTININ},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {1989},
      volume = {290},
      number = {2},
      pages = {213-242}
    }
    
    SESACK, S. & PICKEL, V. PREFRONTAL CORTICAL EFFERENTS IN THE RAT SYNAPSE ON UNLABELED NEURONAL TARGETS OF CATECHOLAMINE TERMINALS IN THE NUCLEUS-ACCUMBENS-SEPTI AND ON DOPAMINE NEURONS IN THE VENTRAL TEGMENTAL AREA {1992} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {320}({2}), pp. {145-160} 
    article  
    Abstract: Physiological and pharmacological studies indicate that descending projections from the prefrontal cortex modulate dopaminergic transmission in the nucleus accumbens septi and ventral tegmental area. We investigated the ultrastructural bases for these interactions in rat by examining the synaptic associations between prefrontal cortical terminals labeled with anterograde markers (lesion-induced degeneration or transport of Phaseolus vulgaris leucoag-glutinin; PHA-L) and neuronal processes containing immunoreactivity for the catecholamine synthesizing enzyme, tryosine hydroxylase. Prefrontal cortical terminals in the nucleus accumbens and ventral tegmental area contained clear, round vesicles and formed primarily asymmetric synapses on spines or small dendrites. In the ventral tegmental area, these terminals also formed asymmetric synapses on large dendrites and a few symmetric axodendritic synapses. In the nucleus accumbens septi, degenerating prefrontal cortical terminals synapsed on spiny dendrites which received convergent input from terminals containing peroxidase immunoreactivity for tyrosine hydroxylase, or from unlabeled terminals. In single sections, some tyrosine hydroxylase-labeled terminals formed thin and punctate symmetric synapses with dendritic shafts, or the heads and necks of spines. Close appositions, but not axo-axonic synapses, were frequently observed between degenerating prefrontal cortical afferents and tyrosine hydroxylase-labeled or unlabeled terminals. In the ventral tegmental area, prefrontal cortical terminals labeled with immunoperoxidase for PHA-L were in synaptic contact with dendrites containing immunogold reaction product for tyrosine hydroxylase, or with unlabeled dendrites. These results suggest that: (1) catecholaminergic (mainly dopaminergic) and prefrontal cortical terminals in the nucleus accumbens septi dually synapse on common spiny neurons; and (2) dopaminergic neurons in the ventral tegmental area receive monosynaptic input from prefrontal cortical afferents. This study provides the first ultrastructural basis for multiple sites of cellular interaction between prefrontal cortical efferents and mesolimbic dopaminergic neurons.
    BibTeX:
    @article{SESACK1992,
      author = {SESACK, SR and PICKEL, VM},
      title = {PREFRONTAL CORTICAL EFFERENTS IN THE RAT SYNAPSE ON UNLABELED NEURONAL TARGETS OF CATECHOLAMINE TERMINALS IN THE NUCLEUS-ACCUMBENS-SEPTI AND ON DOPAMINE NEURONS IN THE VENTRAL TEGMENTAL AREA},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {1992},
      volume = {320},
      number = {2},
      pages = {145-160}
    }
    
    Shadlen, M. & Newsome, W. Neural basis of a perceptual decision in the parietal cortex (area LIP) of the rhesus monkey {2001} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {86}({4}), pp. {1916-1936} 
    article  
    Abstract: We recorded the activity of single neurons in the posterior parietal cortex (area LIP) of two rhesus monkeys while they discriminated the direction of motion in random-dot visual stimuli. The visual task was similar to a motion discrimination task that has been used in previous investigations of motion-sensitive regions of the extrastriate cortex. The monkeys were trained to decide whether the direction of motion was toward one of two choice targets that appeared on either side of the random-dot stimulus. At the end of the trial, the monkeys reported their direction judgment by making an eye movement to the appropriate target. We studied neurons in LIP that exhibited spatially selective persistent activity during delayed saccadic eye movement tasks. These neurons are thought to carry high-level signals appropriate for identifying salient visual targets and for guiding saccadic eye movements. We arranged the motion discrimination task so that one of the choice targets was in the LIP neuron's response field (RF) while the other target was positioned well away from the RE During motion viewing, neurons in LIP altered their firing rate in a manner that predicted the saccadic eye movement that the monkey would make at the end of the trial. The activity thus predicted the monkey's judgment of motion direction. This predictive activity began early in the motion-viewing period and became increasingly reliable as the monkey viewed the random-dot motion. The neural activity predicted the monkey's direction judgment on both easy and difficult trials (strong and weak motion), whether or not the judgment was correct. In addition, the timing and magnitude of the response was affected by the strength of the motion signal in the stimulus. When the direction of motion was toward the RF, stronger motion led to larger neural responses earlier in the motion-viewing period. When motion was away from the RF, stronger motion led to greater suppression of ongoing activity. Thus the activity of single neurons in area LIP reflects both the direction of an impending gaze shift and the quality of the sensory information that instructs such a response. The time course of the neural response suggests that LIP accumulates sensory signals relevant to the selection of a target for an eye movement.
    BibTeX:
    @article{Shadlen2001,
      author = {Shadlen, MN and Newsome, WT},
      title = {Neural basis of a perceptual decision in the parietal cortex (area LIP) of the rhesus monkey},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {2001},
      volume = {86},
      number = {4},
      pages = {1916-1936}
    }
    
    Shadmehr, R. & Holcomb, H. Neural correlates of motor memory consolidation {1997} SCIENCE
    Vol. {277}({5327}), pp. {821-825} 
    article  
    Abstract: Computational studies suggest that acquisition of a motor skill involves learning an internal model of the dynamics of the task, which enables the brain to predict and compensate for mechanical behavior. During the hours that follow completion of practice, representation of the internal model gradually changes, becoming less fragile with respect to behavioral interference. Here, functional imaging of the brain demonstrates that within 6 hours after completion of practice, while performance remains unchanged, the brain engages new regions to perform the task; there is a shift from prefrontal regions of the cortex to the premotor, posterior parietal, and cerebellar cortex structures. This shift is specific to recall of an established motor skill and suggests that with the passage of time, there is a change in the neural representation of the internal model and that this change may underlie its increased functional stability.
    BibTeX:
    @article{Shadmehr1997,
      author = {Shadmehr, R and Holcomb, HH},
      title = {Neural correlates of motor memory consolidation},
      journal = {SCIENCE},
      year = {1997},
      volume = {277},
      number = {5327},
      pages = {821-825}
    }
    
    SHALLICE, T., FLETCHER, P., FRITH, C., GRASBY, P., FRACKOWIAK, R. & DOLAN, R. BRAIN-REGIONS ASSOCIATED WITH ACQUISITION AND RETRIEVAL OF VERBAL EPISODIC MEMORY {1994} NATURE
    Vol. {368}({6472}), pp. {633-635} 
    article  
    Abstract: IT is widely held that conscious recall of past experiences involves a specific system-episodic memory1. Patients with amnesia have gross impairments of episodic memory while other kinds of memory remain intact2,3, suggesting that a separable brain system underlies episodic memory. We have used positron emission tomography (PET) to identify components of this system in normal volunteers. A dual-task interference paradigm4 was used to isolate brain areas associated with acquisition, and a cueing paradigm5 to isolate the areas concerned with retrieval from verbal episodic memory. Acquisition was associated with activity in the left prefrontal cortex and the retrosplenial area, whereas retrieval was associated with activity in right prefrontal cortex and the precuneus. Our results provide clear evidence that episodic memory involves a network of specific prefrontal and posterior structures6,7 which can be fractionated into different component processes.
    BibTeX:
    @article{SHALLICE1994,
      author = {SHALLICE, T and FLETCHER, P and FRITH, CD and GRASBY, P and FRACKOWIAK, RSJ and DOLAN, RJ},
      title = {BRAIN-REGIONS ASSOCIATED WITH ACQUISITION AND RETRIEVAL OF VERBAL EPISODIC MEMORY},
      journal = {NATURE},
      year = {1994},
      volume = {368},
      number = {6472},
      pages = {633-635}
    }
    
    Silverman, D., Munakata, J., Ennes, H., Mandelkern, M., Hoh, C. & Mayer, E. Regional cerebral activity in normal and pathological perception of visceral pain {1997} GASTROENTEROLOGY
    Vol. {112}({1}), pp. {64-72} 
    article  
    Abstract: Background & Aims: To characterize the cerebral processing of noxious visceral events, changes in regional cerebral blood flow associated with perception of intestinal pain were examined, Methods: The effects of rectal pressure stimuli on regional cerebral blood flow were assessed with O-15-water positron emission tomography (PET) in 12 subjects, half with irritable bowel syndrome (IBS), PET scans were obtained at baseline and during both actual and simulated delivery of anticipated stimuli, Changes in regional cerebral blood flow were interpreted using statistical parametric mapping and region of interest methods of analysis, Results: in healthy subjects, perception of pain during actual or simulated delivery of painful stimuli was significantly associated (P < 0.01) with activity of the anterior cingulate cortex (ACC; Brodmann's areas 24 and 32), whereas no ACC response to perception of nonpainful stimuli was observed, In patients with IBS, the ACC failed to respond to the same stimuli, whereas significant activation (P < 0.01) of the left prefrontal cortex (maximal in Brodmann's area 10) was seen, Conclusions: The perception of acute rectal pain is associated with activation of the ACC in healthy subjects, and patients with IBS show an aberrant brain activation pattern both during noxious rectal distention and during the anticipation of rectal pain.
    BibTeX:
    @article{Silverman1997,
      author = {Silverman, DHS and Munakata, JA and Ennes, H and Mandelkern, MA and Hoh, CK and Mayer, EA},
      title = {Regional cerebral activity in normal and pathological perception of visceral pain},
      journal = {GASTROENTEROLOGY},
      year = {1997},
      volume = {112},
      number = {1},
      pages = {64-72}
    }
    
    Sinha, R. How does stress increase risk of drug abuse and relapse? {2001} PSYCHOPHARMACOLOGY
    Vol. {158}({4}), pp. {343-359} 
    article DOI  
    Abstract: Rationale: The notion that stress leads to drug abuse in vulnerable individuals and relapse in addicts is not new. Most major theories of addiction postulate that stress plays an important role in increasing drug use and relapse. Several animal studies and some human laboratory studies have shown that stress exposure enhances drug self-administration. Although clinical observations suggest that exposure to stress increases drug use, and are associated with craving and relapse in addicts, human research in this area is largely correlational and at times contradictory. Objective: Given the growing preclinical evidence that supports the key role of stress in substance abuse, careful examination of this research area in humans is warranted. This paper examines empirical evidence on how stress may increase the vulnerability to drug abuse, and explores whether chronic drug abuse alters the stress response and coping in addicts, thereby increasing the likelihood of drug seeking and relapse. Unanswered questions on the association between stress and substance abuse in humans are identified. Conclusion: Preclinical research has shown that stress, in addition to drug itself, plays a key role in perpetuating drug abuse and relapse. However, the mechanisms underlying this association in humans remain unclear. A greater understanding of how stress may perpetuate drug abuse will likely have a significant impact on both prevention and treatment development in the field of addiction.
    BibTeX:
    @article{Sinha2001,
      author = {Sinha, R},
      title = {How does stress increase risk of drug abuse and relapse?},
      journal = {PSYCHOPHARMACOLOGY},
      year = {2001},
      volume = {158},
      number = {4},
      pages = {343-359},
      doi = {{10.1007/s002130100917}}
    }
    
    Small, D., Zatorre, R., Dagher, A., Evans, A. & Jones-Gotman, M. Changes in brain activity related to eating chocolate - From pleasure to aversion {2001} BRAIN
    Vol. {124}({Part 9}), pp. {1720-1733} 
    article  
    Abstract: We performed successive (H2O)-O-15-PET scans on volunteers as they ate chocolate to beyond satiety. Thus, the sensory stimulus and act (eating) were held constant while the reward value of the chocolate and motivation of the subject to eat were manipulated by feeding. Non-specific effects of satiety (such as feelings of fullness and autonomic changes) were also present and probably contributed to the modulation of brain activity. After eating each piece of chocolate, subjects gave ratings of how pleasant/ unpleasant the chocolate was and of how much they did or did not want another piece of chocolate. Regional cerebral blood flow was then regressed against subjects' ratings. Different groups of structures were recruited selectively depending on whether subjects were eating chocolate when they were highly motivated to eat and rated the chocolate as very pleasant [subcallosal region, caudomedial orbitofrontal cortex (OFC), insula/operculum, striatum and midbrain] or whether they ate chocolate despite being satiated (parahippocampal gyrus, caudolateral OFC and prefrontal regions). As predicted, modulation was observed in cortical chemosensory areas, including the insula and caudomedial and caudolateral OFC, suggesting that the reward value of food is represented here. Of particular interest, the medial and lateral caudal OFC showed opposite patterns of activity. This pattern of activity indicates that there may be a functional segregation of the neural representation of reward and punishment within this region. The only brain region that was active during both positive and negative compared with neutral conditions was the posterior cingulate cortex. Therefore, these results support the hypothesis that there are two separate motivational systems: one orchestrating approach and another avoidance behaviours.
    BibTeX:
    @article{Small2001,
      author = {Small, DM and Zatorre, RJ and Dagher, A and Evans, AC and Jones-Gotman, M},
      title = {Changes in brain activity related to eating chocolate - From pleasure to aversion},
      journal = {BRAIN},
      year = {2001},
      volume = {124},
      number = {Part 9},
      pages = {1720-1733}
    }
    
    Smith, E. & Jonides, J. Neuroscience - Storage and executive processes in the frontal lobes {1999} SCIENCE
    Vol. {283}({5408}), pp. {1657-1661} 
    article  
    Abstract: The human frontal cortex helps mediate working memory, a system that is used for temporary storage and manipulation of information and that is involved in many higher cognitive functions. Working memory includes two components: short-term storage (on the order of seconds) and executive processes that operate on the contents of storage. Recently, these two components have been investigated in functional neuroimaging studies. Studies of storage indicate that different frontal regions are activated for different kinds of information: storage for verbal materials activates Broca's area and Left-hemisphere supplementary and premotor areas; storage of spatial information activates the right-hemisphere premotor cortex; and storage of object information activates other areas of the prefrontal cortex. Two of the fundamental executive processes are selective attention and task management. Both processes activate the anterior cingulate and dorsolateral prefrontal cortex.
    BibTeX:
    @article{Smith1999,
      author = {Smith, EE and Jonides, J},
      title = {Neuroscience - Storage and executive processes in the frontal lobes},
      journal = {SCIENCE},
      year = {1999},
      volume = {283},
      number = {5408},
      pages = {1657-1661}
    }
    
    Smith, E. & Jonides, J. Neuroimaging analyses of human working memory {1998} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {95}({20}), pp. {12061-12068} 
    article  
    Abstract: We review a program of research that uses neuroimaging techniques to determine the functional and neural architecture of human working memory. A first set of studies indicates that verbal working memory includes a storage component, which is implemented neurally by areas in the left-hemisphere posterior parietal cortex, and a subvocal rehearsal component, which is implemented by left-hemisphere speech areas, including Broca's area as well as the premotor and supplementary motor areas. We provide a number of neuroimaging dissociations between the storage and rehearsal areas. A second set of studies focuses on spatial working memory and indicates that it is mediated by a network of predominantly right-hemisphere regions that include areas in posterior parietal, occipital, and frontal cortex. We provide some suggestive evidence that these areas, too, divide into storage and rehearsal regions, with right-hemisphere posterior parietal and premotor regions subserving spatial rehearsal. In a final set of studies, we turn to ``executive processes,'' metaprocesses that regulate the processing of working-memory contents. We focus on the executive process of inhibition as it is used in verbal working memory. We provide evidence that such inhibition is mediated by the left-hemisphere prefrontal region and that it can be dissociated from verbal storage and rehearsal processes.
    BibTeX:
    @article{Smith1998,
      author = {Smith, EE and Jonides, J},
      title = {Neuroimaging analyses of human working memory},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1998},
      volume = {95},
      number = {20},
      pages = {12061-12068}
    }
    
    Smith, E. & Jonides, J. Working memory: A view from neuroimaging {1997} COGNITIVE PSYCHOLOGY
    Vol. {33}({1}), pp. {5-42} 
    article  
    Abstract: We have used neuroimaging techniques, mainly positron emission tomography (PET), to study cognitively driven issues about working memory. Two kinds of experiments are described. In the first kind, we employ standard subtraction logic to uncover the basic components of working memory. These studies indicate that: (a) there are different working-memory systems for spatial, object, and verbal information (with the spatial system localized more in the right hemisphere, and the verbal system more in the left hemisphere); (b) within at least the spatial and verbal systems, separable components seem to be responsible for the passive storage of information and the active maintenance of information (with the storage component being localized more in the back of the brain, and the maintenance component in the front); and (c) there may be separate components responsible for processing the contents of working memory (Localized in prefrontal cortex). In our second kind of experiment we have focused on verbal working memory and incrementally varied one task parameter-memory load-in an effort to obtain a more fine-grained analysis of the system's operations. The results indicate that all relevant components of the system show some increase in activity with increasing memory load (e.g., the frontal regions responsible for verbal rehearsal show incremental increases in activation with increasing memory load). In contrast, brain regions that are not part of the working-memory system show no effect of memory load. Furthermore, the time courses of activation may differ for regions that are sensitive to load versus those that are not Taken together, our results provide support for certain cognitive models of working memory (e.g., Baddeley, 1992) and also suggest some distinctions that these models have not emphasized. And more fundamentally, the results provide a neural base for cognitive models of working memory. (C) 1997 Academic Press.
    BibTeX:
    @article{Smith1997,
      author = {Smith, EE and Jonides, J},
      title = {Working memory: A view from neuroimaging},
      journal = {COGNITIVE PSYCHOLOGY},
      year = {1997},
      volume = {33},
      number = {1},
      pages = {5-42}
    }
    
    SMITH, E., JONIDES, J., KOEPPE, R., AWH, E., SCHUMACHER, E. & MINOSHIMA, S. SPATIAL VERSUS OBJECT WORKING-MEMORY - PET INVESTIGATIONS {1995} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {7}({3}), pp. {337-356} 
    article  
    Abstract: We used positron emission tomography (PET) to answer the following question: Is working memory a unitary storage system, or does it instead include different storage buffers for different kinds of information? In Experiment 1,PET measures were taken while subjects engaged in either a spatial-memory task (retain the position of three dots for 3 sec) or an object-memory task (retain the identity of two objects for 3 sec). The results manifested a striking double dissociation, as the spatial task activated only right-hemisphere regions, whereas the object task activated primarily left-hemisphere regions. The spatial (right-hemisphere) regions included occipital, parietal, and prefrontal areas, while the object (left-hemisphere) regions included inferotemporal and parietal areas. Experiment 2 was similar to Experiment 1 except that the stimuli and trial events were identical for the spatial and object tasks; whether spatial or object memory was required was manipulated by instructions. The PET results once more showed a double dissociation, as the spatial task activated primarily right-hemisphere regions (again including occipital, parietal and prefrontal areas), whereas the object task activated only left-hemisphere regions (again including inferotemporal and parietal areas). Experiment 3 was a strictly behavioral study, which produced another double dissociation. It used the same tasks as Experiment 2, and showed that a variation in spatial similarity affected performance in the spatial but not the object task, whereas a variation in shape similarity affected performance in the object but not the spatial task. Taken together, the results of the three experiments clearly imply that different working-memory buffers are used for storing spatial and object information.
    BibTeX:
    @article{SMITH1995,
      author = {SMITH, EE and JONIDES, J and KOEPPE, RA and AWH, E and SCHUMACHER, EH and MINOSHIMA, S},
      title = {SPATIAL VERSUS OBJECT WORKING-MEMORY - PET INVESTIGATIONS},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {1995},
      volume = {7},
      number = {3},
      pages = {337-356}
    }
    
    Soares, J. & Mann, J. The anatomy of mood disorders - Review of structural neuroimaging studies {1997} BIOLOGICAL PSYCHIATRY
    Vol. {41}({1}), pp. {86-106} 
    article  
    Abstract: The structural neuroimaging findings in mood disorders were reviewed, to evaluate evidence for a neuroanatomic model of pathophysiology, involving the prefrontal cortex, the basal ganglia, the amygdala-hippocampus complex, thalamus, and connections among these structures. Global atrophy is not consistently found. The best replicated finding is an increased rate of white matter and periventricular hyperintensities. A smaller frontal lobe, cerebellum, caudate, and putamen appear present in unipolar depression, A larger third ventricle, anal smaller cerebellum and perhaps temporal lobe appear present in bipolar disorder. These localized structural changes involve regions that may be critical in the pathogenesis of mood disorders. Generalized and localized anatomic alterations may be related to age or vascular disease. The clinical and biological correlates of these changes need to be investigated to allow development of a more complete model of pathophysiology of mood disorders. (C) 1997 J.C. Soares and J.J. Mann.
    BibTeX:
    @article{Soares1997,
      author = {Soares, JC and Mann, JJ},
      title = {The anatomy of mood disorders - Review of structural neuroimaging studies},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {1997},
      volume = {41},
      number = {1},
      pages = {86-106}
    }
    
    Solanto, M. Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration {1998} BEHAVIOURAL BRAIN RESEARCH
    Vol. {94}({1}), pp. {127-152} 
    article  
    Abstract: The psychostimulants, D-amphetamine (D-AMP) and methylphenidate (MPH), are widely used to treat attention-deficit hyperactivity disorder (ADHD) in both children and adults. The purpose of this paper is to integrate results of basic and clinical research with stimulants in order to enhance understanding of the neuropharmacological mechanisms of therapeutic action of these drugs. Neurochemical, neurophysiological and neuroimaging studies in animals reveal that the facilitative effects of stimulants on locomotor activity, reinforcement processes, and rate-dependency are mediated by dopaminergic effects at the nucleus accumbens, whereas effects on delayed responding and working memory are mediated by noradrenergic afferents from the locus coeruleus (LC) to prefrontal cortex (PFC). Enhancing effects of the stimulants on attention and stimulus control of behavior are mediated by both dopaminergic and noradrenergic systems. In humans, stimulants appear to exert rate-dependent effects on activity levels, and primarily enhance the motor output, rather than stimulus evaluation stages of information-processing. Similarity of response of individuals with and without ADHD suggests that the stimulants do not target a specific neurobiological deficit in ADHD, but rather exert compensatory effects. Integration of evidence from pre-clinical and clinical research suggests that these effects may involve stimulation of pre-synaptic inhibitory autoreceptors, resulting in reduced activity in dopaminergic and noradrenergic pathways. The implications of these and other hypotheses for further pre-clinical and clinical research are discussed. (C) 1998 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{Solanto1998,
      author = {Solanto, MV},
      title = {Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration},
      journal = {BEHAVIOURAL BRAIN RESEARCH},
      year = {1998},
      volume = {94},
      number = {1},
      pages = {127-152}
    }
    
    Spear, L. The adolescent brain and age-related behavioral manifestations {2000} NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
    Vol. {24}({4}), pp. {417-463} 
    article  
    Abstract: To successfully negotiate the developmental transition between youth and adulthood, adolescents must maneuver this often stressful period while acquiring skills necessary for independence. Certain behavioral features, including age-related increases in social behavior and risk-taking/novelty-seeking, are common among adolescents of diverse mammalian species and may aid in this process. Reduced positive incentive values from stimuli may lead adolescents to pursue new appetitive reinforcers through drug use and other risk-taking behaviors, with their relative insensitivity to drugs supporting comparatively greater per occasion use. Pubertal increases in gonadal hormones are a hallmark of adolescence, although there is little evidence for a simple association of these hormones with behavioral change during adolescence. Prominent developmental transformations are seen in prefrontal cortex and limbic brain regions of adolescents across a variety of species, alterations that include an apparent shift in the balance between mesocortical and mesolimbic dopamine systems. Developmental changes in these stressor-sensitive regions, which are critical for attributing incentive salience to drugs and other stimuli, likely contribute to the unique characteristics of adolescence. (C) 2000 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{Spear2000,
      author = {Spear, LP},
      title = {The adolescent brain and age-related behavioral manifestations},
      journal = {NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS},
      year = {2000},
      volume = {24},
      number = {4},
      pages = {417-463}
    }
    
    SQUIRE, L., OJEMANN, J., MIEZIN, F., PETERSEN, S., VIDEEN, T. & RAICHLE, M. ACTIVATION OF THE HIPPOCAMPUS IN NORMAL HUMANS - A FUNCTIONAL ANATOMICAL STUDY OF MEMORY {1992} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {89}({5}), pp. {1837-1841} 
    article  
    Abstract: We studied regional cerebral blood flow using the (H2O)-O-15 method while normal subjects performed four similar tasks involving three-letter word beginnings (stems). Prior to each task, subjects studied a list of words. Local blood now was then monitored during a 40-sec period while subjects (i) silently viewed word stems, (ii) completed stems to form the first words to come to mind, but the stems were not the beginnings of any study words (baseline), (iii) completed stems and half of them could form study words (priming), or (iv) tried to recall study words, and half of the stems could form these words (memory). There were three major findings. (i) The memory task engaged the right hippocampal region when the memory task was compared to either the baseline or the priming condition. The right hemispheric locus suggests that performance is driven by the visual characteristics of the words rather than by semantic or phonetic analysis. (ii) In the priming-minus-baseline comparison, there was reduction in blood flow in the right posterior cortex. (iii) Right prefrontal cortex was activated in the memory-minus-baseline condition. The results provide evidence for selective activation of the human hippocampal region in association with memory function. The results also lead to a suggestion about the neural basis of repetition priming: following presentation of a stimulus, less neural activity is required to process the same stimulus.
    BibTeX:
    @article{SQUIRE1992,
      author = {SQUIRE, LR and OJEMANN, JG and MIEZIN, FM and PETERSEN, SE and VIDEEN, TO and RAICHLE, ME},
      title = {ACTIVATION OF THE HIPPOCAMPUS IN NORMAL HUMANS - A FUNCTIONAL ANATOMICAL STUDY OF MEMORY},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1992},
      volume = {89},
      number = {5},
      pages = {1837-1841}
    }
    
    STEPHAN, K., FINK, G., PASSINGHAM, R., SILBERSWEIG, D., CEBALLOSBAUMANN, A., FRITH, C. & FRACKOWIAK, R. FUNCTIONAL-ANATOMY OF THE MENTAL REPRESENTATION OF UPPER EXTREMITY MOVEMENTS IN HEALTHY-SUBJECTS {1995} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {73}({1}), pp. {373-386} 
    article  
    Abstract: 1. Differences in the distribution of relative regional cerebral blood How during motor imagery and execution of a joy-stick movement were investigated in six healthy volunteers with the use of positron emission tomography (PET). Both tasks were compared with a common baseline condition, motor preparation, and with each other. Data were analyzed for individual subjects and for the group, and areas of significant flow differences were related to anatomy by magnetic resonance imaging (MRI). 2. Imagining movements activated a number of frontal and parietal regions: medial and lateral premotor areas, anterior cingulate areas, ventral opercular premotor areas, and parts of superior and inferior parietal areas were all activated bilaterally when compared with preparation to move. 3. Execution of movements compared with imagining movements led to additional activations of the left primary sensorimotor cortex and adjacent areas: dorsal parts of the medial and lateral premotor cortex; adjacent cingulate areas; and rostral parts of the left superior parietal cortex. 4. Functionally distinct rostral and caudal parts of the posterior supplementary motor area (operationally defined as the SMA behind the coronal plane at the level of the anterior commissure) were identified. In the group, the rostral part of posterior SMA was activated by imagining movements, and a more caudoventral part was additionally activated during their execution. A similar dissociation was observed in the cingulate areas. Individual subjects showed that the precise site of these activations varied with the individual anatomy; however, a constant pattern of preferential activation within separate but adjacent gyri of the left hemisphere was preserved. 5. Functionally distinct regions were also observed in the parietal lobe: the caudal part of the superior parietal cortex [medial Brodmann area (BA) 7] was activated by imagining movements compared with preparing to execute them, whereas the more rostral parts of the superior parietal lobe (BA 5), mainly on the left, were additionally activated by execution of the movements. 6. Within the operculum, three functionally distinct areas were observed: rostrally, prefrontal areas (BA 44 and 45) were more active during imagined than executed movements; a ventral premotor area (BA 6) was activated during both imagined and executed movements; and more caudally in the parietal lobe. an area was found that was mainly activated by execution, presumably SII. 7. These data suggest that imagined movements can be viewed as a special form of `'motor behavior'' that, when compared with preparing to move, activate areas associated heretofore with selection of actions and multisensory integration. The neural substrate of imagining a movement differs from that involved in its execution most notably by the absence of activation of the primary sensorimotor cortex in the central sulcus and immediately adjacent premotor, cingulate, and parietal structures.
    BibTeX:
    @article{STEPHAN1995,
      author = {STEPHAN, KM and FINK, GR and PASSINGHAM, RE and SILBERSWEIG, D and CEBALLOSBAUMANN, AO and FRITH, CD and FRACKOWIAK, RSJ},
      title = {FUNCTIONAL-ANATOMY OF THE MENTAL REPRESENTATION OF UPPER EXTREMITY MOVEMENTS IN HEALTHY-SUBJECTS},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1995},
      volume = {73},
      number = {1},
      pages = {373-386}
    }
    
    Stone, V., Baron-Cohen, S. & Knight, R. Frontal lobe contributions to theory of mind {1998} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {10}({5}), pp. {640-656} 
    article  
    Abstract: ``Theory of mind,'' the ability to make inferences about others' mental states, seems to be a modular cognitive capacity that underlies humans' ability to engage in complex social interaction. It develops in several distinct stages, which can be measured with social reasoning tests of increasing difficulty. Individuals with Asperger's syndrome, a mild form of autism, perform well on simpler theory of mind tests but show deficits on more developmentally advanced theory of mind tests. We tested patients with bilateral damage to orbito-frontal cortex (n = 5) and unilateral damage in left dorsolateral prefrontal cortex (n = 5) on a series of theory of mind tasks varying in difficulty. Bilateral orbito-frontal lesion patients performed similarly to individuals with Asperger's syndrome, performing well on simpler tests and showing deficits on tasks requiring more subtle social reasoning, such as the ability to recognize a faux pas. In contrast, no specific theory of mind deficits were evident in the unilateral dorsolateral frontal lesion patients. The dorsola