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    Abi-Dargham, A., Mawlawi, O., Lombardo, I., Gil, R., Martinez, D., Huang, Y., Hwang, D., Keilp, J., Kochan, L., Van Heertum, R., Gorman, J. & Laruelle, M. Prefrontal dopamine D-1 receptors and working memory in schizophrenia {2002} JOURNAL OF NEUROSCIENCE
    Vol. {22}({9}), pp. {3708-3719} 
    article  
    Abstract: Studies in nonhuman primates documented that appropriate stimulation of dopamine (DA) D-1 receptors in the dorsolateral prefrontal cortex (DLPFC) is critical for working memory processing. The defective ability of patients with schizophrenia at working memory tasks is a core feature of this illness. It has been postulated that this impairment relates to a deficiency in mesocortical DA function. In this study, D-1 receptor availability was measured with positron emission tomography and the selective D-1 receptor antagonist [C-11] NNC 112 in 16 patients with schizophrenia (seven drug-naive and nine drug-free patients) and 16 matched healthy controls. [C-11] NNC 112 binding potential (BP) was significantly elevated in the DLPFC of patients with schizophrenia (1.63+/-0.39 ml/gm) compared with control subjects (1.27+/-0.44 ml/gm; p=0.02). In patients with schizophrenia, increased DLPFC [C-11] NNC 112 BP was a strong predictor of poor performance at the n-back task, a test of working memory. These findings confirm that alteration of DLPFC D-1 receptor transmission is involved in working memory deficits presented by patients with schizophrenia. Increased D-1 receptor availability observed in patients with schizophrenia might represent a compensatory (but ineffective) upregulation secondary to sustained deficiency in mesocortical DA function.
    BibTeX:
    @article{Abi-Dargham2002,
      author = {Abi-Dargham, A and Mawlawi, O and Lombardo, I and Gil, R and Martinez, D and Huang, YY and Hwang, DR and Keilp, J and Kochan, L and Van Heertum, R and Gorman, JM and Laruelle, M},
      title = {Prefrontal dopamine D-1 receptors and working memory in schizophrenia},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2002},
      volume = {22},
      number = {9},
      pages = {3708-3719}
    }
    
    Adams, B. & Moghaddam, B. Corticolimbic dopamine neurotransmission is temporally dissociated from the cognitive and locomotor effects of phencyclidine {1998} JOURNAL OF NEUROSCIENCE
    Vol. {18}({14}), pp. {5545-5554} 
    article  
    Abstract: The behavioral syndrome produced by phencyclidine (PCP) and its analog ketamine represents a pharmacological model for some aspects of schizophrenia. Despite the multifaceted properties of these drugs, the main mechanism for their psychotomimetic and cognitive-impairing effects has been thought heretofore to involve the corticolimbic dopamine system. The present study examined the temporal relationship between alterations in corticolimbic dopamine and glutamate neurotransmission and two dopamine-dependent behavioral effects of PCP in the rodent that have relevance to the clinical phenomenology, namely, impairment of working memory, which is used to model the frontal lobe deficits associated with schizophrenia, and hyperlocomotion, which is used as a predictor of the propensity of a drug to elicit or exacerbate psychosis. PCP increased dopamine and glutamate efflux in the prefrontal cortex and nucleus accumbens, as measured by microdialysis. The increase in dopamine in both regions remained elevated well above baseline 2.5 hr after the injection, at which time the experiment was terminated. However, locomotor activity returned to baseline in <2 hr after injection. Furthermore, impaired performance in a discrete trial delayed alternation task, a rodent working memory task, was only evident up to 60 min after PCP injection; animals tested 80 min after injection, when cortical dopamine release was elevated at 300% of baseline, did not exhibit impaired performance. These findings indicate that activation of dopamine neurotransmission is not sufficient to sustain PCP-induced locomotion and impairment of working memory. Thus, effects of PCP, including a glutamatergic hyperstimulation, may be necessary to account for the psychotomimetic and cognitive-impairing effects of this drug.
    BibTeX:
    @article{Adams1998,
      author = {Adams, B and Moghaddam, B},
      title = {Corticolimbic dopamine neurotransmission is temporally dissociated from the cognitive and locomotor effects of phencyclidine},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1998},
      volume = {18},
      number = {14},
      pages = {5545-5554}
    }
    
    AGGLETON, J., HUNT, P. & RAWLINS, J. THE EFFECTS OF HIPPOCAMPAL-LESIONS UPON SPATIAL AND NONSPATIAL TESTS OF WORKING MEMORY {1986} BEHAVIOURAL BRAIN RESEARCH
    Vol. {19}({2}), pp. {133-146} 
    article  
    BibTeX:
    @article{AGGLETON1986,
      author = {AGGLETON, JP and HUNT, PR and RAWLINS, JNP},
      title = {THE EFFECTS OF HIPPOCAMPAL-LESIONS UPON SPATIAL AND NONSPATIAL TESTS OF WORKING MEMORY},
      journal = {BEHAVIOURAL BRAIN RESEARCH},
      year = {1986},
      volume = {19},
      number = {2},
      pages = {133-146}
    }
    
    Ahles, T., Saykin, A., Furstenberg, C., Cole, B., Mott, L., Skalla, K., Whedon, M., Bivens, S., Mitchell, T., Greenberg, E. & Silberfarb, P. Neuropsychologic impact of standard-dose systemic chemotherapy in long-term survivors of breast cancer and lymphoma {2002} JOURNAL OF CLINICAL ONCOLOGY
    Vol. {20}({2}), pp. {485-493} 
    article  
    Abstract: Purpose : The primary purpose of this study was to compare the neuropsychologic functioning of long-term survivors of breast cancer and lymphoma who had: been treated with standard-dose systemic chemotherapy or local therapy only. Patients and Methods: Long-term survivors (5 years! postdiagnosis, not presently receiving cancer treatment, and disease-free) of breast cancer or lymphoma who had been treated with systemic chemotherapy, (breast cancer: n = 35, age, 59.1 +/- 10.7 years; lymphoma: n = 36, age, 55.9 +/- 12.1 years) or local therapy, only (breast cancer: n = 35, age, 60.6 +/- 10.5 years; lymphoma: n = 22, age, 48.7 +/- 11.7 years) completed a battery of neuropsychologic and psychologic tests (Center for Epidemiological Study-Depression, Spielberger State-Trait Anxiety Inventory, and Fatigue Symptom Inventory). Results: Multivariate analysis of variance, controlling for age and education, revealed that survivors who had been treated with systemic chemotherapy scored significantly lower an the battery of neuropsychologic tests compared with those treated with local therapy only (P < .04), particularly in the domains of verbal memory (P < .01) and psychomotor functioning (P < .03). Survivors treated with systemic chemotherapy were also more likely to score in the lower quartile on the Neuropsychological Performance Index (39% v 14 P < .01) and to self-report greater problems with working memory on the Squire Memory Self-Rating Questionnaire (P < .02). Conclusion: Data from this study support the hypothesis that systemic chemotherapy can have a negative impact on cognitive functioning as measured by standardized neuropsychologic tests and self-report of memory changes. However, analysis of the Neuropsychological Performance Index suggests that only a subgroup Of Survivors may experience long-term cognitive deficits associated with systemic chemotherapy. (C) 2002 by American Society of Clinical Oncology.
    BibTeX:
    @article{Ahles2002,
      author = {Ahles, TA and Saykin, AJ and Furstenberg, CT and Cole, B and Mott, LA and Skalla, K and Whedon, MB and Bivens, S and Mitchell, T and Greenberg, ER and Silberfarb, PM},
      title = {Neuropsychologic impact of standard-dose systemic chemotherapy in long-term survivors of breast cancer and lymphoma},
      journal = {JOURNAL OF CLINICAL ONCOLOGY},
      year = {2002},
      volume = {20},
      number = {2},
      pages = {485-493}
    }
    
    Aleman, A., Hijman, R., de Haan, E. & Kahn, R. Memory impairment in schizophrenia: A meta-analysis {1999} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {156}({9}), pp. {1358-1366} 
    article  
    Abstract: Objective: Memory impairment is well documented in schizophrenia. Less is known, however, about the exact magnitude, pattern, and extent of the impairment. The effect of potential moderator variables, such as medication status and duration of illness, is also unclear. In this article, the authors presented meta-analyses of the published literature on recall and recognition memory performance between patients with schizophrenia and normal comparison subjects. Method: Meta-analyses were conducted on 70 studies that reported measures of long-term memory (free recall, cued recall, and recognition of verbal and nonverbal material) and short-term memory (digit span). Tests of categorical models were used in analyses of potential moderators (clinical variables and study characteristics). Results: The findings revealed a significant and stable association between schizophrenia and memory impairment. The composite effect size for recall performance was large. Recognition showed less, but still significant, impairment. The magnitude of memory impairment was not affected by age, medication, duration of illness, patient status, severity of psychopathology, or positive symptoms. Negative symptoms showed a small but significant relation with memory impairment. Conclusions: This meta-analysis documented significant memory impairment in schizophrenia. The impairment was stable, wide ranging, and not substantially affected by potential moderating factors such as severity of psychopathology and duration of illness.
    BibTeX:
    @article{Aleman1999,
      author = {Aleman, A and Hijman, R and de Haan, EHF and Kahn, RS},
      title = {Memory impairment in schizophrenia: A meta-analysis},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {1999},
      volume = {156},
      number = {9},
      pages = {1358-1366}
    }
    
    Anderson, J., Bothell, D., Byrne, M., Douglass, S., Lebiere, C. & Qin, Y. An integrated theory of the mind {2004} PSYCHOLOGICAL REVIEW
    Vol. {111}({4}), pp. {1036-1060} 
    article DOI  
    Abstract: Adaptive control of thought-rational (ACT-R; J. R. Anderson & C. Lebiere, 1998) has evolved into a theory that consists of multiple modules but also explains how these modules are integrated to produce coherent cognition. The perceptual-motor modules, the goal module, and the declarative memory module are presented as examples of specialized systems in ACT-R. These modules are associated with distinct cortical regions. These modules place chunks in buffers where they can be detected by a production system that responds to patterns of information in the buffers. At any point in time, a single production rule is selected to respond to the current pattern. Subsymbolic processes serve to guide the selection of rules to fire as well as the internal operations of: some modules. Much of learning involves tuning of these subsymbolic processes. A number of simple and complex empirical examples are described to illustrate how these modules function singly and in concert.
    BibTeX:
    @article{Anderson2004,
      author = {Anderson, JR and Bothell, D and Byrne, MD and Douglass, S and Lebiere, C and Qin, YL},
      title = {An integrated theory of the mind},
      journal = {PSYCHOLOGICAL REVIEW},
      year = {2004},
      volume = {111},
      number = {4},
      pages = {1036-1060},
      doi = {{10.1037/0033-295x.111.4.1036}}
    }
    
    Andreasen, N. Linking mind and brain in the study of mental illnesses: A project for a scientific psychopathology {1997} SCIENCE
    Vol. {275}({5306}), pp. {1586-1593} 
    article  
    Abstract: Brain research on mental illnesses has made substantial advances in recent years, supported by conceptual and technological developments in cognitive neuroscience. Brain-based cognitive models of illnesses such as schizophrenia and depression have been tested with a variety of techniques, including the lesion method, tract tracing, neuroimaging, animal modeling, single-cell recording, electrophysiology, neuropsychology, and experimental cognitive psychology. A relatively sophisticated picture is emerging that conceptualizes mental illnesses as disorders of mind arising in the brain. Convergent data using multiple neuroscience techniques indicate that the neural mechanisms of mental illnesses can be understood as dysfunctions in specific neural circuits and that their functions and dysfunctions can be influenced or altered by a variety of cognitive and pharmacological factors.
    BibTeX:
    @article{Andreasen1997,
      author = {Andreasen, NC},
      title = {Linking mind and brain in the study of mental illnesses: A project for a scientific psychopathology},
      journal = {SCIENCE},
      year = {1997},
      volume = {275},
      number = {5306},
      pages = {1586-1593}
    }
    
    ANDREASEN, N., OLEARY, D., ARNDT, S., CIZADLO, T., HURTIG, R., REZAI, K., WATKINS, G., PONTO, L. & HICHWA, R. SHORT-TERM AND LONG-TERM VERBAL MEMORY - A POSITRON EMISSION TOMOGRAPHY STUDY {1995} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {92}({11}), pp. {5111-5115} 
    article  
    Abstract: Short-term and long-term retention of err perimentally presented words were compared in a sample of 33 healthy normal volunteers by the [O-15]H2O method with positron emission tomography (PET). The design included three conditions. For the long-term condition, subjects thoroughly studied 18 words 1 week before the PET study. For the short-term condition, subjects were shown another set of 18 words 60 sec before imaging, with instructions to remember them. For the baseline condition, subtracted from the two memory conditions, subjects read a third set of words that they had not previously seen in the experiment. Similar regions were activated in both short-term and long-term conditions: large right frontal areas, biparietal areas, and the left cerebellum. In addition, the short-term condition also activated a relatively large region in the left prefrontal region. These complex distributed circuits appear to represent the neural substrates for aspects of memory such as encoding, retrieval, and storage. They indicate that circuitry involved in episodic memory has much larger cortical and cerebellar components than has been emphasized in earlier lesion studies.
    BibTeX:
    @article{ANDREASEN1995a,
      author = {ANDREASEN, NC and OLEARY, DS and ARNDT, S and CIZADLO, T and HURTIG, R and REZAI, K and WATKINS, GL and PONTO, LLB and HICHWA, RD},
      title = {SHORT-TERM AND LONG-TERM VERBAL MEMORY - A POSITRON EMISSION TOMOGRAPHY STUDY},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1995},
      volume = {92},
      number = {11},
      pages = {5111-5115}
    }
    
    Andreasen, N., OLeary, D., Cizadlo, T., Arndt, S., Rezai, K., Ponto, L., Watkins, G. & Hichwa, R. Schizophrenia and cognitive dysmetria: A positron-emission tomography study of dysfunctional prefrontal-thalamic-cerebellar circuitry {1996} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {93}({18}), pp. {9985-9990} 
    article  
    Abstract: Patients suffering from schizophrenia display subtle cognitive abnormalities that may reflect a difficulty in rapidly coordinating the steps that occur in a variety of mental activities. Working interactively with the prefrontal cortex, the cerebellum may play a role in coordinating both motor and cognitive performance. This positron-emission tomography study suggests the presence of a prefrontal-thalamic-cerebellar network that is activated when normal subjects recall complex narrative material, but is dysfunctional in schizophrenic patients when they perform the same task. These results support a role for the cerebellum in cognitive functions and suggest that patients with schizophrenia may suffer from a `'cognitive dysmetria'' due to dysfunctional prefrontal-thalamic-cerebellar circuitry.
    BibTeX:
    @article{Andreasen1996,
      author = {Andreasen, NC and OLeary, DS and Cizadlo, T and Arndt, S and Rezai, K and Ponto, LLB and Watkins, GL and Hichwa, RD},
      title = {Schizophrenia and cognitive dysmetria: A positron-emission tomography study of dysfunctional prefrontal-thalamic-cerebellar circuitry},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1996},
      volume = {93},
      number = {18},
      pages = {9985-9990}
    }
    
    ANDREASEN, N., OLEARY, D., CIZADLO, T., ARNDT, S., REZAI, K., WATKINS, L., PONTO, L. & HICHWA, R. REMEMBERING THE PAST - 2 FACETS OF EPISODIC MEMORY EXPLORED WITH POSITRON EMISSION TOMOGRAPHY {1995} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {152}({11}), pp. {1576-1585} 
    article  
    Abstract: Objective: This study used positron emission tomography to examine two kinds of personal memory that are used in psychiatric evaluation: focused episodic memory (recall of past experience, employed in `'taking a history'') and random episodic memory (uncensored thinking about experience, examined during analytic therapy using free association). For comparison, a third memory task was used to tap impersonal memory that represents general information about the world (''semantic memory''). Method: Thirteen subjects were studied using the [O-15]H2O method to obtain quantitative measurements of cerebral blood flow. The three conditions were subtracted and their relative relationships examined. Results: The random episodic condition produced activations in widely distributed association cortex (right and left frontal, parietal, angular/supramarginal, and posterior inferior temporal regions). Focused episodic memory engaged a network that included the medial inferior frontal region, precuneus/retrosplenial cingulate, anterior cingulate, thalamus, and cerebellum. The use of medial frontal regions and the precuneus/retrosplenial cingulate was common to both focused and random episodic memory. The major difference between semantic and episodic memory was activation of Broca's area and the left frontal operculum by semantic memory. Conclusions: These results indicate that free-ranging mental activity (random episodic memory) produces large activations in association cortex and may reflect both active retrieval of past experiences and planning of future experiences. Focused episodic memory shares some components of this circuit (inferior frontal and precuneus), which may reflect the time-linked components of both aspects of episodic memory, and which permit human beings to experience personal identity, consciousness, and self-awareness.
    BibTeX:
    @article{ANDREASEN1995,
      author = {ANDREASEN, NC and OLEARY, DS and CIZADLO, T and ARNDT, S and REZAI, K and WATKINS, L and PONTO, LLB and HICHWA, RD},
      title = {REMEMBERING THE PAST - 2 FACETS OF EPISODIC MEMORY EXPLORED WITH POSITRON EMISSION TOMOGRAPHY},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {1995},
      volume = {152},
      number = {11},
      pages = {1576-1585}
    }
    
    Arnsten, A. Catecholamine modulation of prefrontal cortical cognitive function {1998} TRENDS IN COGNITIVE SCIENCES
    Vol. {2}({11}), pp. {436-447} 
    article  
    Abstract: The prefrontal cortex (PFC) utilizes working memory to guide behavior and to release the organism from dependence on environmental cues and is commonly disrupted in neuropsychiatric disorders, normal aging, or exposure to uncontrollable stress. This review posits that the PFC is very sensitive to changes in the neuromodulatory inputs it receives from norepinephrine (NE) and dopamine (DA) systems and that this sensitivity can lead to marked changes in the working-memory functions of the PFC. While NE and DA have important beneficial influences on processing in this area, very high levels of catecholamine release, for example, during exposure to uncontrollable stress, the cognitive functions of the PFC. This fresh understanding of the neurochemical influences PFC function has lead to new treatments for cognitive disorders such as such as Hyperactivity Disorder (ADHD), and may help to elucidate the of PFC dysfunction in other mental disorders.
    BibTeX:
    @article{Arnsten1998,
      author = {Arnsten, AFT},
      title = {Catecholamine modulation of prefrontal cortical cognitive function},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      year = {1998},
      volume = {2},
      number = {11},
      pages = {436-447}
    }
    
    Arnsten, A. Catecholamine regulation of the prefrontal cortex {1997} JOURNAL OF PSYCHOPHARMACOLOGY
    Vol. {11}({2}), pp. {151-162} 
    article  
    Abstract: The catecholamines dopamine (DA) and norepinephrine provide an essential modulatory influence on the working memory and attentional functions of the prefrontal cortex (PFC). The following critique reviews evidence that (1) either insufficient or excessive DA D-1 receptor stimulation is detrimental to PFC function, while DA stimulation of the D-2 family of receptors may contribute to detrimental actions in PFC and (2) that norepinephrine has an important beneficial influence on PFC function through its actions at post-synaptic, alpha(2A) adrenergic receptors, but impairs PFC function through actions at alpha(1) receptors. Critical levels of catecholamine stimulation may be needed to optimize PFC cognitive function; high levels of catecholamine release during stress may serve to take the PFC `off-line' to allow faster, more habitual responses mediated by the posterior and/or subcortical structures to regulate behavior. These studies have relevance to our understanding and treatment of disorders with prominent symptoms of PFC dysfunction.
    BibTeX:
    @article{Arnsten1997,
      author = {Arnsten, AFT},
      title = {Catecholamine regulation of the prefrontal cortex},
      journal = {JOURNAL OF PSYCHOPHARMACOLOGY},
      year = {1997},
      volume = {11},
      number = {2},
      pages = {151-162}
    }
    
    ARNSTEN, A., CAI, J., MURPHY, B. & GOLDMANRAKIC, P. DOPAMINE D-1 RECEPTOR MECHANISMS IN THE COGNITIVE PERFORMANCE OF YOUNG-ADULT AND AGED MONKEYS {1994} PSYCHOPHARMACOLOGY
    Vol. {116}({2}), pp. {143-151} 
    article  
    Abstract: Dopamine (DA) D-1 receptor compounds were examined in monkeys for effects on the working memory functions of the prefrontal cortex and on the fine motor abilities of the primary motor cortex. The D-1 antagonist, SCH23390, the partial D-1 agonist, SKF38393, and the full D-1 agonist, dihydrexidine, were characterized in young control monkeys, and in aged monkeys with naturally occurring catecholamine depletion. In addition, SKF38393 was tested in young monkeys experimentally depleted of catecholamines with chronic reserpine treatment. Injections of SCH23390 significantly impaired the memory performance of young control monkeys, but did not impair aged monkeys with presumed catecholamine depletion. Conversely, the partial agonist, SKF38393, improved the depleted monkeys (aged or reserpine-treated) but did not improve young control animals. The full agonist, dihydrexidine, did improve memory performance in young control monkeys, as well as in a subset of aged monkeys. Consistent with D, receptor mechanisms, agonist-induced improvements were blocked by SCH23390. Drug effects on memory performance occurred independently of effects on fine motor performance. These results underscore the importance of DA D-1 mechanisms in cognitive function, and provide functional evidence of DA system degeneration in aged monkeys. Finally, high doses of D-1 agonists impaired memory performance in aged monkeys, suggesting that excessive D-1 stimulation may be deleterious to cognitive function.
    BibTeX:
    @article{ARNSTEN1994,
      author = {ARNSTEN, AFT and CAI, JX and MURPHY, BL and GOLDMANRAKIC, PS},
      title = {DOPAMINE D-1 RECEPTOR MECHANISMS IN THE COGNITIVE PERFORMANCE OF YOUNG-ADULT AND AGED MONKEYS},
      journal = {PSYCHOPHARMACOLOGY},
      year = {1994},
      volume = {116},
      number = {2},
      pages = {143-151}
    }
    
    Arnsten, A. & Goldman-Rakic, P. Noise stress impairs prefrontal cortical cognitive function in monkeys - Evidence for a hyperdopaminergic mechanism {1998} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {55}({4}), pp. {362-368} 
    article  
    Abstract: Background: Stress can exacerbate a number of psychiatric disorders, many of which are associated with prefrontal cortical (PFC) cognitive deficits. Biochemical studies demonstrate that mild stress preferentially increases dopamine turnover in the PFC. Our study examined the effects of acute, mild stress exposure on higher cognitive function in monkeys and the role of dopaminergic mechanisms in the stress response. Methods: The effects of loud (105-dB) noise stress were examined on a spatial working memory task (delayed response) dependent on the PFC, and on a reference memory task with similar motor and motivational demands (visual pattern discrimination) dependent on the inferior temporal cortex. The role of dopamine mechanisms was tested by challenging the stress response with agents that decrease dopamine receptor stimulation. Results: Exposure to noise stress significantly impaired delayed-response performance. Stress did not impair performance on ``0-second'' delay control trials and did not alter visual pattern discrimination performance, which is consistent with impaired PFC cognitive function rather than nonspecific changes in performance. Stress-induced deficits in delayed-response performance were ameliorated by pretreatment with drugs that block dopamine receptors (haloperidol, SCH 23390) or reduce stress-induced PFC dopamine turnover in rodents (clonidine, naloxone hydrochloride). Conclusions: These results indicate that stress impairs PFC cognitive function through a hyperdopaminergic mechanism. Stress may take the PFC ``off-line'' to allow more habitual responses mediated by posterior cortical and subcortical structures to regulate behavior. This mechanism may have survival value, but may often be maladaptive in human society, contributing to the vulnerability of the PFC in many neuropsychiatric disorders.
    BibTeX:
    @article{Arnsten1998a,
      author = {Arnsten, AFT and Goldman-Rakic, PS},
      title = {Noise stress impairs prefrontal cortical cognitive function in monkeys - Evidence for a hyperdopaminergic mechanism},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1998},
      volume = {55},
      number = {4},
      pages = {362-368}
    }
    
    Arnsten, A. & Li, B. Neurobiology of executive functions: Catecholamine influences on prefrontal cortical functions {2005} BIOLOGICAL PSYCHIATRY
    Vol. {57}({11}), pp. {1377-1384} 
    article DOI  
    Abstract: The prefrontal cortex guides behaviours, thoughts, and feelings using representational knowledge, i.e., working memory. These fundamental cognitive abilities subserve the so-called executive functions, the ability to inhibit inappropriate behaviours and thoughts, regulate our attention. monitor our actions and plan and organize for the future. Neuropsychological and imaging studies indicate that these prefrontal cortex functions are weaker in patients with attention-deficit/hyperactivity disorder and contribute substantially to attention-deficit hyperactivity disorder symptomology. Research in animals indicates that The prefrontal cortex is very sensitive to its neurochemical environment and that small changes in catecholamine modulation of prefrontal cortex cells can have profound effects on the ability of the prefrontal cortex to guide behaviour. Optimal levels norepinephrine acting at postsynaptic &alpha;-2A-adrenoceptors and dopamine acting at D1 receptors are essential to prefrontal cortex function. Blockade of norepinephrine &alpha;-2-adrenoceptors in prefrontal cortax markedly impairs prefrontal cortex function and mimics most of the symtoms of attention-deficit/hyperactivity disorder, including impulsivity and locomotor hyperactivity. Conversely, stimulation of &alpha;-2-adrenoceptors in prefrontal cortex strengthens prefrontal cortex regulation of behavior and reduces distractibility. Most effective treatments for attention-deficit/hyperactivity disorder facilitate catecholamine transmission and likely have their therapeutic actions by optimizing catecholamine actions in prefrontal cortex.
    BibTeX:
    @article{Arnsten2005,
      author = {Arnsten, AFT and Li, BM},
      title = {Neurobiology of executive functions: Catecholamine influences on prefrontal cortical functions},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {2005},
      volume = {57},
      number = {11},
      pages = {1377-1384},
      note = {Conference on Advancing the Neuroscience of Attention-Deficit/Hyperactivity Disorder (ADHD), Boston, MA, FEB 28, 2004},
      doi = {{10.1016/j.bps.2004.08.019}}
    }
    
    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}}
    }
    
    Arvanitakis, Z., Wilson, R., Bienias, J., Evans, D. & Bennett, D. Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function {2004} ARCHIVES OF NEUROLOGY
    Vol. {61}({5}), pp. {661-666} 
    article  
    Abstract: Background: Few prospective studies have assessed diabetes mellitus as a risk factor for incident Alzheimer disease (AD) and decline in cognitive function. Objective: To evaluate the association of diabetes mellitus with risk of AD and change in different cognitive systems. Design: Longitudinal cohort study. Participants: For up to 9 years, 824 older (those >55 years) Catholic nuns, priests, and brothers underwent detailed annual clinical evaluations. Main Outcome Measures: Clinically diagnosed AD and change in global and specific measures of cognitive function. Results: Diabetes mellitus was present in 127 (15.4 of the participants. During a mean of 5.5 years of observation, 151 persons developed AD. In a proportional hazards model adjusted for age, sex, and educational level, those with diabetes mellitus had a 65% increase in the risk of developing AD compared with those without diabetes mellitus (hazard ratio, 1.65; 95% confidence interval, 1.10-2.47). In random effects models, diabetes mellitus was associated with lower levels of global cognition, episodic memory, semantic memory, working memory, and visuospatial ability at baseline. Diabetes mellitus was associated with a 44% greater rate of decline in perceptual speed (P=.02), but not in other cognitive systems. Conclusions: Diabetes mellitus may be associated with an increased risk of developing AD and may affect cognitive systems differentially.
    BibTeX:
    @article{Arvanitakis2004,
      author = {Arvanitakis, Z and Wilson, RS and Bienias, JL and Evans, DA and Bennett, DA},
      title = {Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function},
      journal = {ARCHIVES OF NEUROLOGY},
      year = {2004},
      volume = {61},
      number = {5},
      pages = {661-666}
    }
    
    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}
    }
    
    Awh, E. & Jonides, J. Overlapping mechanisms of attention and spatial working memory {2001} TRENDS IN COGNITIVE SCIENCES
    Vol. {5}({3}), pp. {119-126} 
    article  
    Abstract: Spatial selective attention and spatial working memory have largely been studied in isolation. Studies of spatial attention have provided clear evidence that observers can bias visual processing towards specific locations, enabling faster and better processing of information at those locations than at unattended locations. We present evidence supporting the view that this process of visual selection is a key component of rehearsal in spatial working memory. Thus, although working memory has sometimes been depicted as a storage system that emerges `downstream' of early sensory processing, current evidence suggests that spatial rehearsal recruits top-down processes that modulate the earliest stages of visual analysis.
    BibTeX:
    @article{Awh2001,
      author = {Awh, E and Jonides, J},
      title = {Overlapping mechanisms of attention and spatial working memory},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      year = {2001},
      volume = {5},
      number = {3},
      pages = {119-126}
    }
    
    Awh, E., Jonides, J., Smith, E., Schumacher, E., Koeppe, R. & Katz, S. Dissociation of storage and rehearsal in verbal working memory: Evidence from positron emission tomography {1996} PSYCHOLOGICAL SCIENCE
    Vol. {7}({1}), pp. {25-31} 
    article  
    Abstract: Current cognitive models of verbal working memory include two components: a phonological store and a rehearsal mechanism that refreshes the contents of this store. We present research using positron emission tomography (PET) to provide further evidence for this functional division. In Experiment 1, subjects performed a valiant of Sternberg's (1966) item recognition task. Experiment 2 used a continuous memory task with control conditions designed to separate the brain regions underlying storage and rehearsal. The results show that independent brain regions mediate storage and rehearsal. In Experiment 3, a dual-task procedure supported the assumption that these memory tasks elicited a rehearsal strategy.
    BibTeX:
    @article{Awh1996,
      author = {Awh, E and Jonides, J and Smith, EE and Schumacher, EH and Koeppe, RA and Katz, S},
      title = {Dissociation of storage and rehearsal in verbal working memory: Evidence from positron emission tomography},
      journal = {PSYCHOLOGICAL SCIENCE},
      year = {1996},
      volume = {7},
      number = {1},
      pages = {25-31}
    }
    
    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}}
    }
    
    Baddeley, A. The episodic buffer: a new component of working memory? {2000} TRENDS IN COGNITIVE SCIENCES
    Vol. {4}({11}), pp. {417-423} 
    article  
    Abstract: In 1974, Baddeley and Hitch proposed a three-component model of working memory. Over the years, this has been successful in giving an integrated account not only of data from normal adults, but also neuropsychological, developmental and neuroimaging data. There are, however, a number of phenomena that are not readily captured by the original model. These are outlined here and a fourth component to the model, the episodic buffer, is proposed. It comprises a limited capacity system that provides temporary storage of information held in a multimodal code, which is capable of binding information from the subsidiary systems, and from long-term memory, into a unitary episodic representation. Conscious awareness is assumed to be the principal mode of retrieval from the buffer. the revised model differs from the old principally in focussing attention on the processes of integrating information, rather than on the isolation of the subsystems. In doing so, it provides a better basis for tackling the more complex aspects of executive control in working memory.
    BibTeX:
    @article{Baddeley2000,
      author = {Baddeley, A},
      title = {The episodic buffer: a new component of working memory?},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      year = {2000},
      volume = {4},
      number = {11},
      pages = {417-423}
    }
    
    Baddeley, A. Exploring the central executive {1996} QUARTERLY JOURNAL OF EXPERIMENTAL PSYCHOLOGY SECTION A-HUMAN EXPERIMENTAL PSYCHOLOGY
    Vol. {49}({1}), pp. {5-28} 
    article  
    Abstract: The central executive component of working memory is a poorly specified and very powerful system that could be criticized as little more than a homunculus. A research strategy is outlined that attempts to specify and analyse its component functions and is illustrated with four lines of research. The first concerns the study of the capacity to coordinate performance on two separate tasks. A second involves the capacity to switch retrieval strategies as reflected in random generation. The capacity to attend selectively to one stimulus and inhibit the disrupting effect of others comprises the third line of research, and the fourth involves the capacity to hold and manipulate information in long-term memory, as reflected in measures of working memory span. It is suggested that this multifaceted approach is a fruitful one that leaves open the question of whether it will ultimately prove more appropriate to regard the executive as a unified system with multiple functions, or simply as an agglomeration of independent though interacting control processes. In the meantime, it seems useful to continue to use the concept of a central executive as a reminder of the crucially important control functions of working memory.
    BibTeX:
    @article{Baddeley1996,
      author = {Baddeley, A},
      title = {Exploring the central executive},
      journal = {QUARTERLY JOURNAL OF EXPERIMENTAL PSYCHOLOGY SECTION A-HUMAN EXPERIMENTAL PSYCHOLOGY},
      year = {1996},
      volume = {49},
      number = {1},
      pages = {5-28},
      note = {International Conference on Working Memory, CAMBRIDGE, ENGLAND, 1994}
    }
    
    Baddeley, A. The fractionation of working memory {1996} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {93}({24}), pp. {13468-13472} 
    article  
    Abstract: In performing many complex tasks, it is necessary to hold information In temporary storage to complete the task, The system used for this rs referred to as working memory. Evidence for the need to postulate separable memory systems is summarized, and one particular model of working memory is described, together with its fractionation into three principal subsystems. The model has proved durable and useful and, with the development of electrophysiological and positive emission tomography scanning measures, Is proving to map readily onto recent neuroanatomical developments.
    BibTeX:
    @article{Baddeley1996a,
      author = {Baddeley, A},
      title = {The 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 = {13468-13472},
      note = {Colloquium on Memory - Recording Experience in Cells and Circuits, IRVINE, CA, FEB 17-20, 1996}
    }
    
    BADDELEY, A. WORKING MEMORY {1992} SCIENCE
    Vol. {255}({5044}), pp. {556-559} 
    article  
    Abstract: The term working memory refers to a brain system that provides temporary storage and manipulation of the information necessary for such complex cognitive tasks as language comprehension, learning, and reasoning. This definition has evolved from the concept of a unitary short-term memory system. Working memory has been found to require the simultaneous storage and processing of information. It can be divided into the following three subcomponents: (i) the central executive, which is assumed to be an attentional-controlling system, is important in skills such as chess playing and is particularly susceptible to the effects of Alzheimer's disease; and two slave systems, namely (ii) the visuospatial sketch pad, which manipulates visual images and (iii) the phonological loop, which stores and rehearses speech-based information and is necessary for the acquisition of both native and second-language vocabulary.
    BibTeX:
    @article{BADDELEY1992,
      author = {BADDELEY, A},
      title = {WORKING MEMORY},
      journal = {SCIENCE},
      year = {1992},
      volume = {255},
      number = {5044},
      pages = {556-559}
    }
    
    BADDELEY, A. IS WORKING MEMORY WORKING - THE 15TH BARTLETT LECTURE {1992} QUARTERLY JOURNAL OF EXPERIMENTAL PSYCHOLOGY SECTION A-HUMAN EXPERIMENTAL PSYCHOLOGY
    Vol. {44}({1}), pp. {1-31} 
    article  
    BibTeX:
    @article{BADDELEY1992a,
      author = {BADDELEY, A},
      title = {IS WORKING MEMORY WORKING - THE 15TH BARTLETT LECTURE},
      journal = {QUARTERLY JOURNAL OF EXPERIMENTAL PSYCHOLOGY SECTION A-HUMAN EXPERIMENTAL PSYCHOLOGY},
      year = {1992},
      volume = {44},
      number = {1},
      pages = {1-31}
    }
    
    BADDELEY, A., BRESSI, S., DELLASALA, S., LOGIE, R. & SPINNLER, H. THE DECLINE OF WORKING MEMORY IN ALZHEIMERS-DISEASE - A LONGITUDINAL-STUDY {1991} BRAIN
    Vol. {114}({Part 6}), pp. {2521-2542} 
    article  
    Abstract: A previous study (Baddeley et al., 1986) explored the hypothesis that patients suffering from dementia of the Alzheimer type (AD) are particularly impaired in the functioning of the central executive component of working memory. It showed that, when patients are required to perform 2 concurrent tasks simultaneously, the AD patients are particularly impaired. even when level of performance on the individual tasks is equated with that of age-matched controls. Although the results were clear, interpretation was still complicated by 2 issues: first, the question of comparability of performance on the separate tests between AD and control patients; secondly, the question of whether our results could be interpreted simply in terms of a limited general processing capacity being more taxed by more difficult dual tasks than by the individual tasks performed alone. The present study followed up the AD and control patients after 6 and 12 mths. We were able to allow for the problem of comparability of performance by using patients as their own control. Under these conditions. there is a very clear tendency for dual task performance to deteriorate while single task performance is maintained. A second experiment varied difficulty within a single task in which patients and controls were required to categorize words as belonging to 1, 2 or 4 semantic categories. There was a clear effect of number of categories on performance and a systematic decline in performance over time. There was, however, no interaction between task difficulty as measured by number of alternatives and rate of deterioration, suggesting that the progressive deterioration in performance shown by AD patients is a function of whether single or dual task performance is required, and is not dependent on simple level of task difficulty. Implications for the analysis of the central executive component of working memory are discussed.
    BibTeX:
    @article{BADDELEY1991,
      author = {BADDELEY, AD and BRESSI, S and DELLASALA, S and LOGIE, R and SPINNLER, H},
      title = {THE DECLINE OF WORKING MEMORY IN ALZHEIMERS-DISEASE - A LONGITUDINAL-STUDY},
      journal = {BRAIN},
      year = {1991},
      volume = {114},
      number = {Part 6},
      pages = {2521-2542}
    }
    
    Baddeley, A., Gathercole, S. & Papagno, C. The phonological loop as a language learning device {1998} PSYCHOLOGICAL REVIEW
    Vol. {105}({1}), pp. {158-173} 
    article  
    Abstract: A relatively simple model of the phonological loop (A. D. Baddeley, 1986), a component of working memory, has proved capable of accommodating a great deal of experimental evidence from normal adult participants, children, and neuropsychological patients. Until recently, however, the role of this subsystem in everyday cognitive activities was unclear. In this article the authors review studies of word learning by normal adults and children, neuropsychological patients, and special developmental populations, which provide evidence that the phonological loop plays a crucial role in learning the novel phonological forms of new words. The authors propose that the primary purpose for which the phonological loop evolved is to store unfamiliar sound patterns while more permanent memory records are being constructed. Its use in retaining sequences of familiar words is, it is argued, secondary.
    BibTeX:
    @article{Baddeley1998,
      author = {Baddeley, A and Gathercole, S and Papagno, C},
      title = {The phonological loop as a language learning device},
      journal = {PSYCHOLOGICAL REVIEW},
      year = {1998},
      volume = {105},
      number = {1},
      pages = {158-173}
    }
    
    BADDELEY, A., LOGIE, R., BRESSI, S., DELLASALA, S. & SPINNLER, H. DEMENTIA AND WORKING MEMORY {1986} QUARTERLY JOURNAL OF EXPERIMENTAL PSYCHOLOGY SECTION A-HUMAN EXPERIMENTAL PSYCHOLOGY
    Vol. {38}({4}), pp. {603-618} 
    article  
    BibTeX:
    @article{BADDELEY1986,
      author = {BADDELEY, A and LOGIE, R and BRESSI, S and DELLASALA, S and SPINNLER, H},
      title = {DEMENTIA AND WORKING MEMORY},
      journal = {QUARTERLY JOURNAL OF EXPERIMENTAL PSYCHOLOGY SECTION A-HUMAN EXPERIMENTAL PSYCHOLOGY},
      year = {1986},
      volume = {38},
      number = {4},
      pages = {603-618}
    }
    
    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}
    }
    
    Ballard, D., Hayhoe, M., Pook, P. & Rao, R. Deictic codes for the embodiment of cognition {1997} BEHAVIORAL AND BRAIN SCIENCES
    Vol. {20}({4}), pp. {723+} 
    article  
    Abstract: To describe phenomena that occur at different time scales, computational models of the brain must incorporate different levels of abstraction. At time scales of approximately 1/3 of a second, orienting movements of the body play a crucial role in cognition and form a useful computational level - more abstract than that used to capture natural phenomena but less abstract than what is traditionally used to study high-level cognitive processes such as reasoning. At this ``embodiment level,'' the constraints of the physical system determine the nature of cognitive operations. The key synergy is that at time scales of about 1/3 of a second, the natural sequentiality of body movements can be matched to the natural computational economies of sequential decision systems through a system of implicit reference called deictic in which pointing movements are used to bind objects in the world to cognitive programs. This target article focuses on how deictic bindings make it possible to perform natural tasks. Deictic computation provides a mechanism for representing the essential features that link external sensory data with internal cognitive programs and motor actions. One of the central features of cognition, working memory, can be related to moment-by-moment dispositions of body features such as eye movements and hand movements.
    BibTeX:
    @article{Ballard1997,
      author = {Ballard, DH and Hayhoe, MM and Pook, PK and Rao, RPN},
      title = {Deictic codes for the embodiment of cognition},
      journal = {BEHAVIORAL AND BRAIN SCIENCES},
      year = {1997},
      volume = {20},
      number = {4},
      pages = {723+}
    }
    
    Baltes, P., Staudinger, U. & Lindenberger, U. Lifespan psychology: Theory and application to intellectual functioning {1999} ANNUAL REVIEW OF PSYCHOLOGY
    Vol. {50}, pp. {471-507} 
    article  
    Abstract: The focus of this review is on theory and research of lifespan (lifespan developmental) psychology. The theoretical analysis integrates evolutionary and ontogenetic perspectives on cultural and human development across several levels of analysis. Specific predictions are advanced dealing with the general architecture of lifespan ontogeny, including its directionality and age-differential allocation of developmental resources into the three major goals of developmental adaptation: growth, maintenance, and regulation of loss. Consistent with this general lifespan architecture, a meta-theory of development is outlined that is based on the orchestrated and adaptive interplay between three processes of behavioral regulation: selection, optimization, and compensation. Finally, these propositions and predictions about the general nature of lifespan development are examined and supported by empirical evidence on the development of cognition and intelligence across the life span.
    BibTeX:
    @article{Baltes1999,
      author = {Baltes, PB and Staudinger, UM and Lindenberger, U},
      title = {Lifespan psychology: Theory and application to intellectual functioning},
      journal = {ANNUAL REVIEW OF PSYCHOLOGY},
      year = {1999},
      volume = {50},
      pages = {471-507}
    }
    
    Barbas, H. Connections underlying the synthesis of cognition, memory, and emotion in primate prefrontal cortices {2000} BRAIN RESEARCH BULLETIN
    Vol. {52}({5}), pp. {319-330} 
    article  
    Abstract: Distinct domains of the prefrontal cortex in primates have a set of connections suggesting that they have different roles in cognition, memory, and emotion. Caudal lateral prefrontal areas (areas 8 and 46) receive projections from cortices representing early stages in visual or auditory processing, and from intraparietal and posterior cingulate areas associated with oculomotor guidance and attentional processes. Cortical input to areas 46 and 8 is complemented by projections from the thalamic multiform and parvicellular sectors of the mediodorsal nucleus associated with oculomotor functions and working memory. In contrast, caudal orbitofrontal areas receive diverse input from cortices representing late stages of processing within every unimodal sensory cortical system. In addition, orbitofrontal and caudal medial(limbic) prefrontal cortices receive robust projections from the amygdala, associated with emotional memory, and from medial temporal and thalamic structures associated with long-term memory. Prefrontal cortices are linked with motor control structures related to their specific roles in central executive functions. Caudal lateral prefrontal areas project to brainstem oculomotor structures, and are connected with premotor cortices effecting head, limb and body movements. In contrast, medial prefrontal and orbitofrontal limbic cortices project to hypothalamic visceromotor centers for the expression of emotions. Lateral, orbitofrontal, and medial prefrontal cortices are robustly interconnected, suggesting that they participate in concert in central executive functions. Prefrontal limbic cortices issue widespread projections through their deep layers and terminate in the upper layers of lateral (eulaminate) cortices, suggesting a predominant role in feedback communication. In contrast, when lateral prefrontal cortices communicate with limbic areas they issue projections from their upper layers and their axons terminate in the deep layers, suggesting a role in feedforward communication. Through their widespread connections, prefrontal limbic cortices may exercise a tonic influence on lateral prefrontal cortices, inextricably linking areas associated with cognitive and emotional processes. The integration of cognitive, mnemonic and emotional processes is likely to be disrupted in psychiatric and neurodegenerative diseases which preferentially affect limbic cortices and consequently disconnect major feedback pathways to the neuraxis, (C) 2000 Elsevier Science Inc.
    BibTeX:
    @article{Barbas2000,
      author = {Barbas, H},
      title = {Connections underlying the synthesis of cognition, memory, and emotion in primate prefrontal cortices},
      journal = {BRAIN RESEARCH BULLETIN},
      year = {2000},
      volume = {52},
      number = {5},
      pages = {319-330},
      note = {Meeting on Human Cerebral Cortex - From Gene to Structure and Function, AMSTERDAM, NETHERLANDS, APR 25, 1998}
    }
    
    Barch, D., Braver, T., Nystrom, L., Forman, S., Noll, D. & Cohen, J. Dissociating working memory from task difficulty in human prefrontal cortex {1997} NEUROPSYCHOLOGIA
    Vol. {35}({10}), pp. {1373-1380} 
    article  
    Abstract: A functional magnetic resonance imaging (fMRI) study was conducted to determine whether prefrontal cortex (PFC) increases activity in working memory (WM) tasks as a specific result of the demands placed on WM, or to other processes affected by the greater difficulty of such tasks. Increased activity in dorsolateral PFC (DLPFC) was observed during task conditions that placed demands on active maintenance (long retention interval) relative to control conditions matched for difficulty. Furthermore, the activity was sustained over the entire retention interval and did not increase when task difficulty was manipulated independently of WM requirements. This contrasted with the transient increases in activity observed in the anterior cingulate, and other regions of frontal cortex, in response to increased task difficulty but not WM demands. Thus, this study established a double-dissociation between regions responsive to WM versus task difficulty, indicating a specific involvement of DLPFC and related structures in WM function. (C) 1997 Elsevier Science Ltd.
    BibTeX:
    @article{Barch1997,
      author = {Barch, DM and Braver, TS and Nystrom, LE and Forman, SD and Noll, DC and Cohen, JD},
      title = {Dissociating working memory from task difficulty in human prefrontal cortex},
      journal = {NEUROPSYCHOLOGIA},
      year = {1997},
      volume = {35},
      number = {10},
      pages = {1373-1380}
    }
    
    Barch, D., Carter, C., Braver, T., Sabb, F., MacDonald, A., Noll, D. & Cohen, J. Selective deficits in prefrontal cortex function in medication-naive patients with schizophrenia {2001} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {58}({3}), pp. {280-288} 
    article  
    Abstract: Background: Previously we proposed that dorsolateral prefrontal cortex (PFC) supports a specific working memory (WM) subcomponent: the ability to represent and maintain context information necessary to guide appropriate task behavior. By context, we mean prior task-relevant information represented in such a form that it supports selection of the appropriate behavioral response. Furthermore, we hypothesized that WM deficits in schizophrenia reflect impaired context processing due to a disturbance in dorsolateral PFC. We use functional magnetic resonance imaging to examine PFC activation in medication-naive, first-episode patients with schizophrenia during a WM, task-isolating context processing. Methods: Fourteen first-episode, medication-naive patients with schizophrenia and 12 controls similar in age, sex, and parental education underwent functional magnetic resonance imaging during performance of an A-X version of the Continuous Performance Test. Results: Patients with schizophrenia demonstrated deficits in dorsolateral PFC activation in task conditions requiring context processing but showed intact activation of posterior and inferior PFC. In addition, patients demonstrated intact activation of the primary motor and somatosensory cortex in response to stimulus processing demands. Conclusions: These results demonstrate selectivity in dorsolateral PFC dysfunction among medication-naive first-episode patients with schizophrenia, suggesting that a specific deficit in PFC function is present at illness onset, prior to the administration of medication or the most confounding effects of illness duration. Furthermore, these results are consistent with the hypothesis that WM deficits in patients with schizophrenia reflect an impairment in context processing due to a disturbance in dorsolateral PFC function.
    BibTeX:
    @article{Barch2001,
      author = {Barch, DM and Carter, CS and Braver, TS and Sabb, FW and MacDonald, A and Noll, DC and Cohen, JD},
      title = {Selective deficits in prefrontal cortex function in medication-naive patients with schizophrenia},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {2001},
      volume = {58},
      number = {3},
      pages = {280-288},
      note = {29th Annual Meeting of the Society-for-Neuroscience, MIAMI BEACH, FL, OCT 23-28, 1999}
    }
    
    Bargh, J. & Ferguson, M. Beyond behaviorism: On the automaticity of higher mental processes {2000} PSYCHOLOGICAL BULLETIN
    Vol. {126}({6, Sp. Iss. SI}), pp. {925-945} 
    article DOI  
    Abstract: The first 100 years of experimental psychology were dominated by 2 major schools of thought: behaviorism and cognitive science. Here the authors consider the common philosophical commitment to determinism by both schools, and how the radical behaviorists' thesis of the determined nature of higher mental processes is being pursued today in social cognition research on automaticity, in harmony with ``dual process'' models in contemporary cognitive science, which equate determined processes with those that are automatic and which require no intervening conscious choice or guidance, as opposed to ``controlled'' processes which do, the social cognition research on the automaticity of higher mental processes provides compelling evidence for the determinism of those processes. This research has revealed that social interaction, evaluation and judgment, and the operation of internal goal structures can all proceed without the intervention of conscious acts of will and guidance of the process.
    BibTeX:
    @article{Bargh2000,
      author = {Bargh, JA and Ferguson, MJ},
      title = {Beyond behaviorism: On the automaticity of higher mental processes},
      journal = {PSYCHOLOGICAL BULLETIN},
      year = {2000},
      volume = {126},
      number = {6, Sp. Iss. SI},
      pages = {925-945},
      doi = {{10.1037//0033-2909.126.6.925}}
    }
    
    Barkley, R. Behavioral inhibition, sustained attention, and executive functions: Constructing a unifying theory of ADHD {1997} PSYCHOLOGICAL BULLETIN
    Vol. {121}({1}), pp. {65-94} 
    article  
    Abstract: Attention deficit hyperactivity disorder (ADHD) comprises a deficit in behavioral inhibition. A theoretical model is constructed that links inhibition to 4 executive neuropsychological functions that appear to depend on it for their effective execution: (a) working memory, (b) self-regulation of affect-motivation-arousal, (c) internalization of speech, and (d) reconstitution (behavioral analysis and synthesis). Extended to ADHD, the model predicts that ADHD should be associated with secondary impairments in these 4 executive abilities and the motor control they afford. The author reviews evidence for each of these domains of functioning and finds it to be strongest for deficits in behavioral inhibition, working memory, regulation of motivation, and motor control in those with ADHD. Although the model is promising as a potential theory of self-control and ADHD, far more research is required to evaluate its merits and the many predictions it makes about ADHD.
    BibTeX:
    @article{Barkley1997,
      author = {Barkley, RA},
      title = {Behavioral inhibition, sustained attention, and executive functions: Constructing a unifying theory of ADHD},
      journal = {PSYCHOLOGICAL BULLETIN},
      year = {1997},
      volume = {121},
      number = {1},
      pages = {65-94}
    }
    
    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}
    }
    
    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., 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. & 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}
    }
    
    Bennett, D., Wilson, R., Schneider, J., Evans, D., Beckett, L., Aggarwal, N., Barnes, L., Fox, J. & Bach, J. Natural history of mild cognitive impairment in older persons {2002} NEUROLOGY
    Vol. {59}({2}), pp. {198-205} 
    article  
    Abstract: Background: Cognitive abilities of older persons range from normal, to mild cognitive impairment, to dementia. Few large longitudinal studies have compared the natural history of mild cognitive impairment with similar persons without cognitive impairment. Methods: Participants were older Catholic clergy without dementia, 211 with mild cognitive impairment and 587 without cognitive impairment, who underwent annual clinical evaluation for AD and an assessment of different cognitive abilities. Cognitive performance tests were summarized to yield a composite measure of global cognitive function and separate summary measures of episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability. The authors compared the risk of death, risk of incident AD, and rates of change in global cognition and different cognitive domains among persons with mild cognitive impairment to those without cognitive impairment. All models controlled for age, sex, and education. Results: On average, persons with mild cognitive impairment had significantly lower scores at baseline in all cognitive domains. Over an average of 4.5 years of follow-up, 30% of persons with mild cognitive impairment died, a rate 1.7 times higher than those without cognitive impairment (95% CI, 1.2 to 2.5). In addition, 64 (34 persons with mild cognitive impairment developed AD, a rate 3.1 times higher than those without cognitive impairment (95% CI, 2.1 to 4.5). Finally, persons with mild cognitive impairment declined significantly faster on measures of episodic memory, semantic memory, and perceptual speed, but not on measures of working memory or visuospatial ability, as compared with persons without cognitive impairment. Conclusions: Mild cognitive impairment is associated with an increased risk of death and incident AD, and a greater rate of decline in selected cognitive abilities.
    BibTeX:
    @article{Bennett2002,
      author = {Bennett, DA and Wilson, RS and Schneider, JA and Evans, DA and Beckett, LA and Aggarwal, NT and Barnes, LL and Fox, JH and Bach, J},
      title = {Natural history of mild cognitive impairment in older persons},
      journal = {NEUROLOGY},
      year = {2002},
      volume = {59},
      number = {2},
      pages = {198-205}
    }
    
    Bergson, C., Mrzljak, L., Smiley, J., Pappy, M., Levenson, R. & GoldmanRakic, P. Regional, cellular, and subcellular variations in the distribution of D-1 and D-2 dopamine receptors in primate brain {1995} JOURNAL OF NEUROSCIENCE
    Vol. {15}({12}), pp. {7821-7836} 
    article  
    Abstract: The pathways governing signal transduction in the mesocortical and nigrostriatal dopamine systems of the brain are of central importance in a variety of drug actions and neurological diseases. We have analyzed the regional, cellular, and subcellular distribution of the closely related D-1 and D-5 subtypes of dopamine receptors in the cerebral cortex and selected subcortical structures of rhesus monkey using subtype specific antibodies. The distribution of D-1 and D-5 receptors was highly differentiated in subcortical structures. In the neostriatum, both D-1 and to a lesser extent D-5 antibodies labeled medium spiny neurons, while only D-5 antibodies labeled the large aspiny neurons typical of cholinergic interneurons. In the caudate nucleus, D-1 labeling was concentrated in the spines and shafts of projection neurons, whereas D-5 antibodies predominantly labeled the shafts, and less commonly, the spines of these cells. The D-1 receptor was abundantly expressed in the neuropil of the substantia nigra pars reticulata while the D-5 antibodies labeled only a few scattered cell bodies in this structure. Conversely, D-5 antibodies labeled cholinergic neurons in the basal forebrain more intensely than D-1 antibodies. Within the cerebral cortex and hippocampus, D-1 and D-5 antibody labeling was prominent in pyramidal cells. Double-label experiments revealed that the two receptors were frequently coexpressed in neurons of both structures. Ultrastructurally, D-1 receptors were especially prominent in dendritic spines whereas dendritic shafts were more prominently labeled by the D-5 receptor. The anatomical segregation of the D-1 and D-5 receptors at the subcellular level in cerebral cortex and at the cellular level in subcortical areas suggest that these closely related receptors may be preferentially associated with different circuit elements and may play distinct regulatory roles in synaptic transmission.
    BibTeX:
    @article{Bergson1995,
      author = {Bergson, C and Mrzljak, L and Smiley, JF and Pappy, M and Levenson, R and GoldmanRakic, PS},
      title = {Regional, cellular, and subcellular variations in the distribution of D-1 and D-2 dopamine receptors in primate brain},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1995},
      volume = {15},
      number = {12},
      pages = {7821-7836}
    }
    
    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}
    }
    
    Bilder, R., Volavka, J., Lachman, H. & Grace, A. The catechol-O-methyltransferase polymorphism: Relations to the tonic-phasic dopamine hypothesis and neuropsychiatric phenotypes {2004} NEUROPSYCHOPHARMACOLOGY
    Vol. {29}({11}), pp. {1943-1961} 
    article DOI  
    Abstract: Diverse phenotypic associations with the catechol-O-methyltransferase (COMT) Val(158)Met polymorphism have been reported. We suggest that some of the complex effects of this polymorphism be understood from the perspective of the tonic-phasic dopamine (DA) hypothesis. We hypothesize that the COMT Met allele (associated with low enzyme activity) results in increased levels of tonic DA and reciprocal reductions in phasic DA in subcortical regions and increased D I transmission cortically. This pattern of effects is hypothesized to yield increased stability but decreased flexibility of neural network activation states that underlie important aspects of working memory and executive functions; these effects may be beneficial or detrimental depending on the phenotype, a range of endogenous factors, and environmental exigencies. The literature on phenotypic associations of the COMT Val(158)Met polymorphism is reviewed, highlighting areas where this hypothesis may have explanatory value, and pointing to possible directions for refinement of relevant phenotypes and experimental evaluation of this hypothesis.
    BibTeX:
    @article{Bilder2004,
      author = {Bilder, RM and Volavka, J and Lachman, HM and Grace, AA},
      title = {The catechol-O-methyltransferase polymorphism: Relations to the tonic-phasic dopamine hypothesis and neuropsychiatric phenotypes},
      journal = {NEUROPSYCHOPHARMACOLOGY},
      year = {2004},
      volume = {29},
      number = {11},
      pages = {1943-1961},
      doi = {{10.1038/sj.npp.1300542}}
    }
    
    BOTTINI, G., CORCORAN, R., STERZI, R., PAULESU, E., SCHENONE, P., SCARPA, P., FRACKOWIAK, R. & FRITH, C. THE ROLE OF THE RIGHT-HEMISPHERE IN THE INTERPRETATION OF FIGURATIVE ASPECTS OF LANGUAGE - A POSITRON EMISSION TOMOGRAPHY ACTIVATION STUDY {1994} BRAIN
    Vol. {117}({Part 6}), pp. {1241-1253} 
    article  
    Abstract: We investigated cerebral activity in six normal volunteers using PET to explore the hypothesis that the right hemisphere has a specific role in the interpretation of figurative aspects of language such as metaphors. WE also mapped the anatomical structures involved in sentence comprehension. During regional cerebral blood flow measurement subjects were asked to perform three different linguistic tasks: (i) metaphorical comprehension; (ii) literal comprehension of sentences; and (iii) a lexical-decision task. We found that comprehension of sentences compared with the lexical-decision task induced extensive activation in several regions of The left hemisphere, including the prefrontal and basal frontal cortex, the middle and inferior temporal gyri and temporal pole, the parietal cortex and the precuneus. Comprehension of metaphors was associated with similar activations in the left hemisphere, but in addition, a number of sites were activated in the right hemisphere: the prefrontal cortex, the middle temporal gyrus, the precuneus and the posterior cingulate. We conclude that the interpretation of language involves widespread distributed systems bilaterally with the right hemisphere having a special role in the appreciation of metaphors.
    BibTeX:
    @article{BOTTINI1994,
      author = {BOTTINI, G and CORCORAN, R and STERZI, R and PAULESU, E and SCHENONE, P and SCARPA, P and FRACKOWIAK, RSJ and FRITH, CD},
      title = {THE ROLE OF THE RIGHT-HEMISPHERE IN THE INTERPRETATION OF FIGURATIVE ASPECTS OF LANGUAGE - A POSITRON EMISSION TOMOGRAPHY ACTIVATION STUDY},
      journal = {BRAIN},
      year = {1994},
      volume = {117},
      number = {Part 6},
      pages = {1241-1253}
    }
    
    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}}
    }
    
    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}
    }
    
    Braver, T., Reynolds, J. & Donaldson, D. Neural mechanisms of transient and sustained cognitive control during task switching {2003} NEURON
    Vol. {39}({4}), pp. {713-726} 
    article  
    Abstract: A hybrid blocked and event-related functional magnetic resonance imaging (fMRI) study decomposed brain activity during task switching into sustained and transient components. Contrasting task-switching blocks against single-task blocks revealed sustained activation in right anterior prefrontal cortex (PFC). Contrasting task-switch trials against task-repeat and single-task trials revealed activation in left lateral PFC and left superior parietal cortex. In both sets of regions, activation dynamics were strongly modulated by trial-by-trial fluctuations in response speed. In addition, right anterior PFC; activity selectively covaried with the magnitude of mixing cost (i.e., task-repeat versus single-task trial performance), and left superior parietal activity selectively covaried with the magnitude of the switching cost (i.e., task-switch versus task-repeat trial performance). These results indicate a functional double dissociation in brain regions supporting different components of cognitive control during task switching and suggest that both sustained and transient control processes mediate the behavioral performance costs of task switching.
    BibTeX:
    @article{Braver2003,
      author = {Braver, TS and Reynolds, JR and Donaldson, DI},
      title = {Neural mechanisms of transient and sustained cognitive control during task switching},
      journal = {NEURON},
      year = {2003},
      volume = {39},
      number = {4},
      pages = {713-726}
    }
    
    Brunel, N. & Wang, X. Effects of neuromodulation in a cortical network model of object working memory dominated by recurrent inhibition {2001} JOURNAL OF COMPUTATIONAL NEUROSCIENCE
    Vol. {11}({1}), pp. {63-85} 
    article  
    Abstract: Experimental evidence suggests that the maintenance of an item in working memory is achieved through persistent activity in selective neural assemblies of the cortex. To understand the. mechanisms underlying this phenomenon, it is essential to investigate how persistent activity is affected by external inputs or neuromodulation. We have addressed these questions using a recurrent network model of object working memory. Recurrence is dominated by inhibition, although persistent activity is generated through recurrent excitation in small subsets of excitatory neurons. Our main findings are as follows. (1) Because of the strong feedback inhibition, persistent activity shows an inverted U shape as a function of increased external drive to the network. (2) A transient external excitation can switch off a network from a selective persistent state to its spontaneous state. (3) The maintenance of the sample stimulus in working memory is not affected by intervening stimuli (distractors) during the delay period, provided the stimulation intensity is not large. On the other hand, if stimulation intensity is large enough, distractors disrupt sample-related persistent activity, and the network is able to maintain a memory only of the last shown stimulus. (4) A concerted modulation of GABAA and NMDA conductances leads to a decrease of spontaneous activity but an increase of persistent activity; the enhanced signal-to-noise ratio is shown to increase the resistance of the network to distractors. (5) Two mechanisms are identified that produce an inverted U shaped dependence of persistent activity on modulation. The present study therefore points to several mechanisms that enhance the signal-to-noise ratio in working memory states. These mechanisms could be implemented in the prefrontal cortex by dopaminergic projections from the midbrain.
    BibTeX:
    @article{Brunel2001,
      author = {Brunel, N and Wang, XJ},
      title = {Effects of neuromodulation in a cortical network model of object working memory dominated by recurrent inhibition},
      journal = {JOURNAL OF COMPUTATIONAL NEUROSCIENCE},
      year = {2001},
      volume = {11},
      number = {1},
      pages = {63-85}
    }
    
    Buccino, G., Vogt, S., Ritzl, A., Fink, G., Zilles, K., Freund, H. & Rizzolatti, G. Neural circuits underlying imitation learning of hand actions: An event-related fMRI study {2004} NEURON
    Vol. {42}({2}), pp. {323-334} 
    article  
    Abstract: The neural bases of imitation learning are virtually unknown. In the present study, we addressed this issue using an event-related fMRI paradigm. Musically naive participants were scanned during four events: (1) observation of guitar chords played by a guitarist, (2) a pause following model observation, (3) execution of the observed chords, and (4) rest. The results showed that the basic circuit underlying imitation learning consists of the inferior parietal lobule and the posterior part of the inferior frontal gyrus plus the adjacent premotor cortex (mirror neuron circuit). This circuit, known to be involved in action understanding, starts to be active during the observation of the guitar chords. During pause, the middle frontal gyrus (area 46) plus structures involved in motor preparation (dorsal premotor cortex, superior parietal lobule, rostral mesial areas) also become active. Given the functional properties of area 46, a model of imitation learning is proposed based on interactions between this area and the mirror neuron system.
    BibTeX:
    @article{Buccino2004,
      author = {Buccino, G and Vogt, S and Ritzl, A and Fink, GR and Zilles, K and Freund, HJ and Rizzolatti, G},
      title = {Neural circuits underlying imitation learning of hand actions: An event-related fMRI study},
      journal = {NEURON},
      year = {2004},
      volume = {42},
      number = {2},
      pages = {323-334}
    }
    
    Buckner, R. Memory and executive function in aging and AD: Multiple factors that cause decline and reserve factors that compensate {2004} NEURON
    Vol. {44}({1}), pp. {195-208} 
    article  
    Abstract: Memory decline in aging results from multiple factors that influence both executive function and the medial temporal lobe memory system. In advanced aging, frontal-striatal systems are preferentially vulnerable to white matter change, atrophy, and certain forms of neurotransmitter depletion. Frontal-striatal change may underlie mild memory difficulties in aging that are most apparent on tasks demanding high levels of attention and controlled processing. Through separate mechanisms, Alzheimer's disease preferentially affects the medial temporal lobe and cortical networks, including posterior cingulate and retrosplenial cortex early in its progression, often before clinical symptoms are recognized. Disruption of the medial temporal lobe memory system leads directly to memory impairment. Recent findings further suggest that age-associated change is not received passively. Reliance on reserve is emerging as an important factor that determines who ages gracefully and who declines rapidly. Functional imaging studies, in particular, suggest increased recruitment of brain areas in older adults that may reflect a form of compensation.
    BibTeX:
    @article{Buckner2004,
      author = {Buckner, RL},
      title = {Memory and executive function in aging and AD: Multiple factors that cause decline and reserve factors that compensate},
      journal = {NEURON},
      year = {2004},
      volume = {44},
      number = {1},
      pages = {195-208}
    }
    
    Buckner, R. & Koutstaal, W. Functional neuroimaging studies of encoding, priming, and explicit memory retrieval {1998} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {95}({3}), pp. {891-898} 
    article  
    Abstract: Human functional neuroimaging techniques provide a powerful means of linking neural level descriptions of brain function and cognition, The exploration of the functional anatomy underlying human memory comprises a prime example, Three highly reliable findings linking memory-related cognitive processes to brain activity are discussed, First, priming is accompanied by reductions in the amount of neural activation relative to naive or unprimed task performance, These reductions can be shown to be both anatomically and functionally specific and are found for both perceptual and conceptual task components, Second, verbal encoding, allowing subsequent conscious retrieval, is associated with activation of higher order brain regions including areas within the left inferior and dorsal prefrontal cortex, These areas also are activated by working memory and effortful word generation tasks, suggesting that these tasks, often discussed as separable, might rely on interdependent processes, Finally, explicit (intentional) retrieval shares much of the same functional anatomy as the encoding and word generation tasks but is associated with the recruitment of additional brain areas, including the anterior prefrontal cortex (right > left), These findings illustrate how neuroimaging techniques can be used to study memory processes and can both complement and extend data derived through other means, More recently developed methods, such as event-related functional MRI, will continue this progress and may provide additional new directions for research.
    BibTeX:
    @article{Buckner1998,
      author = {Buckner, RL and Koutstaal, W},
      title = {Functional neuroimaging studies of encoding, priming, and explicit memory retrieval},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1998},
      volume = {95},
      number = {3},
      pages = {891-898},
      note = {Colloquium on Neuroimaging of Human Brain Function, IRVINE, CALIFORNIA, MAY 29-31, 1997}
    }
    
    Buhusi, C. & Meck, W. What makes us tick? Functional and neural mechanisms of interval timing {2005} NATURE REVIEWS NEUROSCIENCE
    Vol. {6}({10}), pp. {755-765} 
    article DOI  
    Abstract: Time is a fundamental dimension of life. It is crucial for decisions about quantity, speed of movement and rate of return, as well as for motor control in walking, speech, playing or appreciating music, and participating in sports. Traditionally, the way in which time is perceived, represented and estimated has been explained using a pacemaker accumulator model that is not only straightforward, but also surprisingly powerful in explaining behavioural and biological data. However, recent advances have challenged this traditional view. It is now proposed that the brain represents time in a distributed manner and tells the time by detecting the coincidental activation of different neural populations.
    BibTeX:
    @article{Buhusi2005,
      author = {Buhusi, CV and Meck, WH},
      title = {What makes us tick? Functional and neural mechanisms of interval timing},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2005},
      volume = {6},
      number = {10},
      pages = {755-765},
      doi = {{10.1038/nrn1764}}
    }
    
    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}
    }
    
    Bunge, S., Hazeltine, E., Scanlon, M., Rosen, A. & Gabrieli, J. Dissociable contributions of prefrontal and parietal cortices to response selection {2002} NEUROIMAGE
    Vol. {17}({3}), pp. {1562-1571} 
    article DOI  
    Abstract: The ability to select between possible responses to a given situation is central to human cognition. The goal of this study was to distinguish between brain areas representing candidate responses and areas selecting between competing response alternatives. Event-related fMRI data were acquired while 10 healthy adults performed a task used to examine response competition: the Eriksen flanker task. Left parietal cortex was activated by either of two manipulations that increased the need to maintain a representation of possible responses. In contrast, lateral prefrontal. and rostral anterior cingulate cortices were specifically engaged by the need to select among competing response alternatives. These findings support the idea that parietal cortex is involved in activating possible responses on the basis of learned stimulus-response associations, and that prefrontal. cortex is recruited when there is a need to select between competing responses. (C) 2002 Elsevier Science (USA).
    BibTeX:
    @article{Bunge2002a,
      author = {Bunge, SA and Hazeltine, E and Scanlon, MD and Rosen, AC and Gabrieli, JDE},
      title = {Dissociable contributions of prefrontal and parietal cortices to response selection},
      journal = {NEUROIMAGE},
      year = {2002},
      volume = {17},
      number = {3},
      pages = {1562-1571},
      doi = {{10.1006/nimg.2002.1252}}
    }
    
    Bunge, S., Ochsner, K., Desmond, J., Glover, G. & Gabrieli, J. Prefrontal regions involved in keeping information in and out of mind {2001} BRAIN
    Vol. {124}({Part 10}), pp. {2074-2086} 
    article  
    Abstract: Goal-directed behaviour depends on keeping relevant information in mind (working memory) and irrelevant information out of mind (behavioural inhibition or interference resolution). Prefrontal cortex is essential for working memory and for interference resolution, but it is unknown whether these two mental abilities are mediated by common or distinct prefrontal regions. To address this question, functional MRI was used to identify brain regions activated by separate manipulations of working memory load and interference within a single task (the Sternberg item recognition paradigm). Both load and interference manipulations were associated with performance decrements. Subjects were unaware of the interference manipulation. There was a high degree of overlap between the regions activated by load and interference, which included bilateral ventrolateral and dorsolateral prefrontal cortex, anterior insula, anterior cingulate and parietal cortex. Critically, no region was activated exclusively by interference. Several regions within this common network exhibited a brain-behaviour correlation across subjects for the load or interference manipulation. Activation within the right middle frontal gyrus and left inferior frontal gyrus was correlated with the ability to resolve interference efficiently, but not the ability to manage an increased working memory load efficiently. Conversely, activation of the anterior cingulate was correlated with load susceptibility, but was not correlated with interference susceptibility. These findings suggest that, within the circuitry engaged by this task, some regions are more critically involved in the resolution of interference whereas others are more involved in the resolution of an increase in load. The anterior cingulate was engaged to a greater extent by the load than interference manipulation, suggesting that this region, which is thought to be involved in detecting the need for greater allocation of attentional resources, may be particularly implicated during awareness of the need for cognitive control. In the present study, interference resolution did not involve recruitment of additional inhibitory circuitry, but was instead mediated by a subset of the neural system supporting working memory.
    BibTeX:
    @article{Bunge2001,
      author = {Bunge, SA and Ochsner, KN and Desmond, JE and Glover, GH and Gabrieli, JDE},
      title = {Prefrontal regions involved in keeping information in and out of mind},
      journal = {BRAIN},
      year = {2001},
      volume = {124},
      number = {Part 10},
      pages = {2074-2086}
    }
    
    Burgess, N. & Hitch, G. Memory for serial order: A network model of the phonological loop and its timing {1999} PSYCHOLOGICAL REVIEW
    Vol. {106}({3}), pp. {551-581} 
    article  
    Abstract: A connectionist model of human short-term memory is presented that extends the ``phonological loop'' (A. D. Baddeley, 1986) to encompass serial order and learning. Psychological and neuropsychological data motivate separate layers of lexical, timing, and input and output phonemic information. Connection weights between layers show Hebbian learning and decay over short and long time scales. At recall, the timing signal is rerun, phonemic information feeds back from output to input, and lexical nodes compete to be selected. The selected node then receives decaying inhibition. The model provides an explanatory mechanism for the phonological loop and for the effects of serial position, presentation modality, lexicality, grouping, and Hebb repetition. It makes new psychological and neuropsychological predictions and is a starting point for understanding the role of the phonological loop in vocabulary acquisition and for interpreting data from functional neuroimaging.
    BibTeX:
    @article{Burgess1999,
      author = {Burgess, N and Hitch, GJ},
      title = {Memory for serial order: A network model of the phonological loop and its timing},
      journal = {PSYCHOLOGICAL REVIEW},
      year = {1999},
      volume = {106},
      number = {3},
      pages = {551-581}
    }
    
    BURGESS, N. & HITCH, G. TOWARD A NETWORK MODEL OF THE ARTICULATORY LOOP {1992} JOURNAL OF MEMORY AND LANGUAGE
    Vol. {31}({4}), pp. {429-460} 
    article  
    BibTeX:
    @article{BURGESS1992,
      author = {BURGESS, N and HITCH, GJ},
      title = {TOWARD A NETWORK MODEL OF THE ARTICULATORY LOOP},
      journal = {JOURNAL OF MEMORY AND LANGUAGE},
      year = {1992},
      volume = {31},
      number = {4},
      pages = {429-460}
    }
    
    Burgess, N., Maguire, E., Spiers, H. & O'Keefe, J. A temporoparietal and prefrontal network for retrieving the spatial context of lifelike events {2001} NEUROIMAGE
    Vol. {14}({2}), pp. {439-453} 
    article DOI  
    Abstract: Virtual reality (VR) and event-related functional magnetic resonance imaging were used to study memory for the spatial context of controlled but lifelike events. Subjects received a set of objects from two different people in two different places within a VR environment. Memory for the objects, and for where and from whom they were received was tested by putting the subject back into a place in the company of a person and giving a paired forced choice of objects. In four conditions objects had to be chosen according to different criteria: which was received in that place, which was received from that person, which object was recognized, and which object was widest. Event-related functional magnetic resonance imaging was performed during testing to identify areas involved in retrieval of the spatial context of an event. A network of areas was identified consisting of a temporoparietal pathway running between the precuneus and parahippocampi via retrosplenial cortex and the parieto-occipital sulcus, left hippocampus, bilateral posterior parietal, dorsolateral, ventrolateral and anterior prefrontal cortices, and the anterior cingulate. Of these areas the parahippocampal, right posterior parietal, and posteriodorsal medial parietal areas were specifically involved in retrieval of spatial context compared to retrieval of nonspatial context. The posterior activations are consistent with a model of long-term storage of allocentric representations Mi medial temporal regions with translation to body-centered and head-centered representations computed in right posterior parietal cortex and buffered in the temporoparietal pathway so as to provide an imageable representation in the precuneus. Prefrontal activations are consistent with strategic retrieval processes, including those required to overcome the interference between the highly similar events. (C) 2001 Academic Press.
    BibTeX:
    @article{Burgess2001,
      author = {Burgess, N and Maguire, EA and Spiers, HJ and O'Keefe, J},
      title = {A temporoparietal and prefrontal network for retrieving the spatial context of lifelike events},
      journal = {NEUROIMAGE},
      year = {2001},
      volume = {14},
      number = {2},
      pages = {439-453},
      doi = {{10.1006/nimg.2001.0806}}
    }
    
    Burgess, P., Alderman, N., Evans, J., Emslie, H. & Wilson, B. The ecological validity of tests of executive function {1998} JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
    Vol. {4}({6}), pp. {547-558} 
    article  
    Abstract: Ninety-two mixed etiology neurological patients and 216 control participants were assessed on a range of neuropsychological tests, including 10 neuropsychological measures of executive function derived from 6 different tests. People who knew the patients well (relatives or carers) completed a questionnaire about the patient's dysexecutive problems in everyday life, and this paper reports the extent to which the tests predicted the patients' everyday life problems. All of the tests were significantly predictive of at least some of the behavioral and cognitive deficits reported by patients' carers. However, factor analysis of the patients' dysexecutive symptoms suggested a fractionation of the dysexecutive syndrome, with neuropsychological tests loading differentially on 3 underlying cognitive factors (Inhibition, Intentionality, and Executive Memory), supporting the conclusions that different tests measure different cognitive processes, and that then may be limits to the fractionation of the executive system.
    BibTeX:
    @article{Burgess1998,
      author = {Burgess, PW and Alderman, N and Evans, J and Emslie, H and Wilson, BA},
      title = {The ecological validity of tests of executive function},
      journal = {JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY},
      year = {1998},
      volume = {4},
      number = {6},
      pages = {547-558}
    }
    
    Bush, G., Frazier, J., Rauch, S., Seidman, L., Whalen, P., Jenike, M., Rosen, B. & Biederman, J. Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI and the counting stroop {1999} BIOLOGICAL PSYCHIATRY
    Vol. {45}({12}), pp. {1542-1552} 
    article  
    Abstract: Background: The anterior cingulate cognitive division (ACcd) plays a central role in attentional processing by: 1) modulating stimulus selection (i.e,, focusing attention) and/or 2) mediating response selection. We hypothesized that ACcd dysfunction might therefore contribute to producing core features of attention-defcit/hyperactivity disorder (ADHD), namely inattention and impulsivity. ADHD subjects have indeed shown performance deficits on the Color Stroop, an attentional/cognitive interference task known to recuit. the ACcd. Recently, the Counting Stroop, a Stroop-variant specialized for functional magnetic resonance imaging (fMRI), produced ACcd activation in healthy adults. In the present fMRI study, the Counting Stroop was used to examine the functional integrity of the ACcd in ADHD. Methods: Sixteen unmedicated adults from two groups (8 with ADHD and 8 matched control subjects) performed the Counting Stroop during fMRI Results: While both groups showed an interference effect, the ADHD group, in contrast to control subjects, failed to activate the ACcd during the Counting Stroop. Direct comparisons showed ACcd activity was significantly higher in the control group. ADHD subjects did activate a frontostriatal-insular network indicating ACcd hypoactivity was not caused by globally poor nehrronal responsiveness, Conclusions: The data support a hypothesized dysfunction of the ACcd in ADHD.
    BibTeX:
    @article{Bush1999,
      author = {Bush, G and Frazier, JA and Rauch, SL and Seidman, LJ and Whalen, PJ and Jenike, MA and Rosen, BR and Biederman, J},
      title = {Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI and the counting stroop},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {1999},
      volume = {45},
      number = {12},
      pages = {1542-1552}
    }
    
    Bushara, K., Weeks, R., Ishii, K., Catalan, M., Tian, B., Rauschecker, J. & Hallett, M. Modality-specific frontal and parietal areas for auditory and visual spatial localization in humans {1999} NATURE NEUROSCIENCE
    Vol. {2}({8}), pp. {759-766} 
    article  
    Abstract: Although the importance of the posterior parietal and prefrontal regions in spatial localization of visual stimuli is well established, their role in auditory space perception is less clear. Using positron emission tomography (PET) during auditory and visual spatial localization in the same subjects, modality-specific areas were identified in the superior parietal lobule, middle temporal and lateral prefrontal cortices. These findings suggest that, similar to the visual system, the hierarchical organization of the auditory system extends beyond the temporal lobe to include areas in the posterior parietal and prefrontal regions specialized in auditory spatial processing. Our results may explain the dissociation of visual and auditory spatial localization deficits following lesions involving these regions.
    BibTeX:
    @article{Bushara1999,
      author = {Bushara, KO and Weeks, RA and Ishii, K and Catalan, MJ and Tian, B and Rauschecker, JP and Hallett, M},
      title = {Modality-specific frontal and parietal areas for auditory and visual spatial localization in humans},
      journal = {NATURE NEUROSCIENCE},
      year = {1999},
      volume = {2},
      number = {8},
      pages = {759-766}
    }
    
    Cabeza, R. Hemispheric asymmetry reduction in older adults: The HAROLD model {2002} PSYCHOLOGY AND AGING
    Vol. {17}({1}), pp. {85-100} 
    article DOI  
    Abstract: A model of the effects of aging on brain activity during cognitive performance is introduced. The model is called HAROLD (hemispheric asymmetry reduction in older adults), and it states that, under similar circumstances, prefrontal activity during cognitive performances tends to be less lateralized in older adults than in younger adults. The model is supported by functional neuroimaging and other evidence in the domains of episodic memory, semantic memory, working memory, perception, and inhibitory control. Age-related hemispheric asymmetry reductions may have a compensatory function or they may reflect a dedifferentiation process. They may have a cognitive or neural origin, and they may reflect regional or network mechanisms. The HAROLD model is a cognitive neuroscience model that integrates ideas and findings from psychology and neuroscience of aging.
    BibTeX:
    @article{Cabeza2002,
      author = {Cabeza, R},
      title = {Hemispheric asymmetry reduction in older adults: The HAROLD model},
      journal = {PSYCHOLOGY AND AGING},
      year = {2002},
      volume = {17},
      number = {1},
      pages = {85-100},
      doi = {{10.1037//0882-7974.17.1.85}}
    }
    
    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{Cabeza2002a,
      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. & 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{Cabeza1997,
      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}
    }
    
    Cahill, L. Why sex matters for neuroscience {2006} NATURE REVIEWS NEUROSCIENCE
    Vol. {7}({6}), pp. {477-484} 
    article DOI  
    Abstract: A rapidly burgeoning literature documents copious sex influences on brain anatomy, chemistry and function. This article highlights some of the more intriguing recent discoveries and their implications. Consideration of the effects of sex can help to explain seemingly contradictory findings. Research into sex influences is mandatory to fully understand a host of brain disorders with sex differences in their incidence and/or nature. The striking quantity and diversity of sex-related influences on brain function indicate that the still widespread assumption that sex influences are negligible cannot be justified, and probably retards progress in our field.
    BibTeX:
    @article{Cahill2006,
      author = {Cahill, L},
      title = {Why sex matters for neuroscience},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2006},
      volume = {7},
      number = {6},
      pages = {477-484},
      doi = {{10.1038/nrn1909}}
    }
    
    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}
    }
    
    Callicott, J., Mattay, V., Verchinski, B., Marenco, S., Egan, M. & Weinberger, D. Complexity of prefrontal cortical dysfunction in schizophrenia: More than up or down {2003} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {160}({12}), pp. {2209-2215} 
    article  
    Abstract: Objective: Numerous neuroimaging studies have examined the function of the dorsolateral prefrontal cortex in schizophrenia; although abnormalities usually are identified, it is unclear why some studies find too little activation and others too much. The authors' goal was to explore this phenomenon. Method: They used the N-back working memory task and functional magnetic resonance imaging at 3 T to examine a group of 14 patients with schizophrenia and a matched comparison group of 14 healthy subjects. Results: Patients' performance was significantly worse on the two-back working memory task than that of healthy subjects. However, there were areas within the dorsolateral prefrontal cortex of the patients that were more active and areas that were less active than those of the healthy subjects. When the groups were subdivided on the basis of performance on the working memory task into healthy subjects and patients with high or low performance, locales of greater prefrontal activation and locales of less activation were found in the high-performing patients but only locales of underactivation were found in the low-performing patients. Conclusions: These findings suggest that patients with schizophrenia whose performance on the N-back working memory task is similar to that of healthy comparison subjects use greater prefrontal resources but achieve lower accuracy (i.e., inefficiency) and that other patients with schizophrenia fail to sustain the prefrontal network that processes the information, achieving even lower accuracy as a result. These findings add to other evidence that abnormalities of prefrontal cortical function in schizophrenia are not reducible to simply too much or too little activity but, rather, reflect a compromised neural strategy for handling information mediated by the dorsolateral prefrontal cortex.
    BibTeX:
    @article{Callicott2003,
      author = {Callicott, JH and Mattay, VS and Verchinski, BA and Marenco, S and Egan, MF and Weinberger, DR},
      title = {Complexity of prefrontal cortical dysfunction in schizophrenia: More than up or down},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {2003},
      volume = {160},
      number = {12},
      pages = {2209-2215}
    }
    
    Cannon, T., Huttunen, M., Lonnqvist, J., Tuulio-Henriksson, A., Pirkola, T., Glahn, D., Finkelstein, J., Hietanen, M., Kaprio, J. & Koskenvuo, M. The inheritance of neuropsychological dysfunction in twins discordant for schizophrenia {2000} AMERICAN JOURNAL OF HUMAN GENETICS
    Vol. {67}({2}), pp. {369-382} 
    article  
    Abstract: While genetic influences in schizophrenia are substantial, the disorder's molecular genetic basis remains elusive. Progress has been hindered by lack of means to detect nonpenetrant carriers of the predisposing genes and by uncertainties concerning the extent of locus heterogeneity. One approach to solving this complexity is to examine the inheritance of pathophysiological processes mediating between genotype and disease phenotype. Here we evaluate whether deficits in neurocognitive functioning covary with degree of genetic relationship with a proband in the unaffected MZ and DZ co-twins of patients with schizophrenia. Twin pairs discordant for schizophrenia were recruited from a total population cohort and were compared with a demographically balanced sample of control twin pairs, on a comprehensive neuropsychological test battery. The following four neuropsychological functions contributed uniquely to the discrimination of degree of genetic loading for schizophrenia and, when combined, were more highly correlated within MZ pairs than within DZ pairs, in both discordant and control twins: spatial working memory (i.e., remembering a sequence of spatial locations over a brief delay), divided attention (i.e., simultaneous performance of a counting and visual-search task), intrusions during recall of a word list (i.e., ``remembering'' nonlist items), and choice reaction time to visual targets. Together with evidence from human and animal studies of mediation of these functions by partially distinct brain systems, our findings suggest that there are multiple independently inherited dimensions of neural deficit in schizophrenia and encourage a search for genes contributing to quantitative variation in discrete aspects of disease liability. On tests of verbal and visual episodic memory, but not on the liability-related measures, patients were more impaired than their own MZ co-twins, suggesting a preferential impact of nongenetic influences on long-term memory systems.
    BibTeX:
    @article{Cannon2000,
      author = {Cannon, TD and Huttunen, MO and Lonnqvist, J and Tuulio-Henriksson, A and Pirkola, T and Glahn, D and Finkelstein, J and Hietanen, M and Kaprio, J and Koskenvuo, M},
      title = {The inheritance of neuropsychological dysfunction in twins discordant for schizophrenia},
      journal = {AMERICAN JOURNAL OF HUMAN GENETICS},
      year = {2000},
      volume = {67},
      number = {2},
      pages = {369-382}
    }
    
    Canolty, R.T., Edwards, E., Dalal, S.S., Soltani, M., Nagarajan, S.S., Kirsch, H.E., Berger, M.S., Barbaro, N.M. & Knight, R.T. High gamma power is phase-locked to theta oscillations in human neocortex {2006} SCIENCE
    Vol. {313}({5793}), pp. {1626-1628} 
    article DOI  
    Abstract: We observed robust coupling between the high- and low-frequency bands of ongoing electrical activity in the human brain. In particular, the phase of the low-frequency theta ( 4 to 8 hertz) rhythm modulates power in the high gamma ( 80 to 150 hertz) band of the electrocorticogram, with stronger modulation occurring at higher theta amplitudes. Furthermore, different behavioral tasks evoke distinct patterns of theta/high gamma coupling across the cortex. The results indicate that transient coupling between low- and high-frequency brain rhythms coordinates activity in distributed cortical areas, providing a mechanism for effective communication during cognitive processing in humans.
    BibTeX:
    @article{Canolty2006,
      author = {Canolty, R. T. and Edwards, E. and Dalal, S. S. and Soltani, M. and Nagarajan, S. S. and Kirsch, H. E. and Berger, M. S. and Barbaro, N. M. and Knight, R. T.},
      title = {High gamma power is phase-locked to theta oscillations in human neocortex},
      journal = {SCIENCE},
      year = {2006},
      volume = {313},
      number = {5793},
      pages = {1626-1628},
      doi = {{10.1126/science.1128115}}
    }
    
    Caplan, D. & Waters, G. Verbal working memory and sentence comprehension {1999} BEHAVIORAL AND BRAIN SCIENCES
    Vol. {22}({1}), pp. {77+} 
    article  
    Abstract: This target article discusses the verbal working memory system used in sentence comprehension. We review the concept of working memory as a short-duration system in which small amounts of information are simultaneously stored and manipulated in the service of accomplishing a task. We summarize the argument that syntactic processing in sentence comprehension requires such a storage and computational system. We then ask whether the working memory system used in syntactic processing is the same as that used in verbally mediated tasks that involve conscious controlled processing. Evidence is brought to bear from various sources: the relationship between individual differences in working memory and individual differences in die efficiency. of syntactic processing; the effect of concurrent verbal memory load on syntactic processing; and syntactic processing in patients with poor short-term memory patients with poor working memory, and patients with aphasia. Experimental results from these normal subjects and patients with various brain lesions converge on the conclusion that there is a specialization in the verbal working memory system for assigning the syntactic structure of a sentence and using that structure in determining sentence meaning that is separate from the working memory system underlying the use of sentence meaning to accomplish other functions. We present a theory of die divisions of the verbal working memory system and suggestions regarding its neural basis.
    BibTeX:
    @article{Caplan1999,
      author = {Caplan, D and Waters, GS},
      title = {Verbal working memory and sentence comprehension},
      journal = {BEHAVIORAL AND BRAIN SCIENCES},
      year = {1999},
      volume = {22},
      number = {1},
      pages = {77+}
    }
    
    Carter, C., Perlstein, W., Ganguli, R., Brar, J., Mintun, M. & Cohen, J. Functional hypofrontality and working memory dysfunction in schizophrenia {1998} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {155}({9}), pp. {1285-1287} 
    article  
    Abstract: Objective: Hypofrontality is a common but not invariable finding in schizophrenia. Inconsistencies in the literature may reflect, in part, the fact that abnormal physiological responses in the prefrontal cortex are best identified under conditions that place well-specified functional demands on this region. Method: The authors studied eight patients with schizophrenia and eight matched comparison subjects using [O-15]H2O positron emission tomography and the ``N-back'' task, which activates the prefrontal cortex as a function of working memory load in normal subjects. Results: Under low-working-memory-load conditions, the accuracy of both groups in the N-back task was equal, but when the memory load increased, the patients' performance deteriorated more than did that of the comparison subjects. The regional cerebral blood flow response to increased working memory load was significantly reduced in the patients' right dorsolateral prefrontal cortex. Conclusions: These results confirm the importance of using tasks that tap specific cognitive functions, linked to specific neural systems, in studies of brain-behavior relationships in schizophrenia. Hypofrontality is reliably demonstrated in schizophrenia during tasks that engage working memory functions of the prefrontal cortex.
    BibTeX:
    @article{Carter1998,
      author = {Carter, CS and Perlstein, W and Ganguli, R and Brar, J and Mintun, M and Cohen, JD},
      title = {Functional hypofrontality and working memory dysfunction in schizophrenia},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {1998},
      volume = {155},
      number = {9},
      pages = {1285-1287}
    }
    
    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{Casey1997,
      author = {Casey, BJ and Trainor, RJ and Orendi, JL and Schubert, AB and Nystrom, LE and Giedd, JN and Castellanos, FX and Haxby, JV and Noll, DC and Cohen, JD and Forman, SD and Dahl, RE and Rapoport, JL},
      title = {A developmental functional MRI study of prefrontal activation during performance of a Go-No-Go task},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {1997},
      volume = {9},
      number = {6},
      pages = {835-847}
    }
    
    Castellanos, F. & Tannock, R. Neuroscience of attention-deficit/hyperactivity disorder: The search for endophenotypes {2002} NATURE REVIEWS NEUROSCIENCE
    Vol. {3}({8}), pp. {617-628} 
    article DOI  
    Abstract: Research on attention-deficit/hyperactivity disorder (ADHD), a highly prevalent and controversial condition, has, for the most part, been descriptive and atheoretical. The imperative to discover the genetic and environmental risk factors for ADHD is motivating the search for quantifiable intermediate constructs, termed endophenotypes. In this selective review, we conclude that such endophenotypes should be solidly grounded in the neurosciences. We propose that three such endophenotypes - a specific abnormality in reward-related circuitry that leads to shortened delay gradients, deficits in temporal processing that result in high intrasubject intertrial variability, and deficits in working memory - are most amenable to integrative collaborative approaches that aim to uncover the causes of ADHD.
    BibTeX:
    @article{Castellanos2002,
      author = {Castellanos, FX and Tannock, R},
      title = {Neuroscience of attention-deficit/hyperactivity disorder: The search for endophenotypes},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2002},
      volume = {3},
      number = {8},
      pages = {617-628},
      doi = {{10.1038/nrn896}}
    }
    
    Castner, S., Williams, G. & Goldman-Rakic, P. Reversal of antipsychotic-induced working memory deficits by short-term doper D1 receptor stimulation {2000} SCIENCE
    Vol. {287}({5460}), pp. {2020-2022} 
    article  
    Abstract: Chronic blockade of dopamine D2 receptors, a common mechanism of action for antipsychotic drugs, down-regulates D1 receptors in the prefrontal cortex and, as shown here, produces severe impairments in working memory. These deficits were reversed in monkeys by short-term coadministration of a D1 agonist, ABT 431, and this improvement was sustained for more than a year after cessation of D1 treatment. These findings indicate that pharmacological modulation of the D1 signaling pathway can produce long-lasting changes in functional circuits underlying working memory. Resetting this pathway by brief exposure to the agonist may provide a valuable strategy for therapeutic intervention in schizophrenia and other dopamine dysfunctional states.
    BibTeX:
    @article{Castner2000,
      author = {Castner, SA and Williams, GV and Goldman-Rakic, PS},
      title = {Reversal of antipsychotic-induced working memory deficits by short-term doper D1 receptor stimulation},
      journal = {SCIENCE},
      year = {2000},
      volume = {287},
      number = {5460},
      pages = {2020-2022}
    }
    
    Catalan, M., Honda, M., Weeks, R., Cohen, L. & Hallett, M. The functional neuroanatomy of simple and complex sequential finger movements: a PET study {1998} BRAIN
    Vol. {121}({Part 2}), pp. {253-264} 
    article  
    Abstract: The brain regions activated by simple repetitive and sequential finger movements of different length were localized by measuring regional cerebral blood flow (rCBF) with PET The experimental design consisted of finger movements cued by auditory pacing at 0.5 HZ. In all conditions of different sequence length the contralateral primary sensorimotor and premotor cortex, supplementary motor area and ipsilateral cerebellar cortex were activated. These areas showed a large increase in activation from rest to simple repetitive movement, and a further increase with the shortest sequence, suggesting art executive role in running sequences. The ipsilateral premotor area (Brodmann area 6), bilateral posterior parietal areas (Brodmann area 7) and precuneus showed art increase in rCBF related only to the length of the sequences, without any change from rest to simple repetitive movement. These areas are more selectively related to sequence performance. This finding is consistent with the hypothesis that these areas function in the storage of motor sequences in spatial working memory. Our results suggest that sequential finger movements recruit discrete sets of brain areas with different functions.
    BibTeX:
    @article{Catalan1998,
      author = {Catalan, MJ and Honda, M and Weeks, RA and Cohen, LG and Hallett, M},
      title = {The functional neuroanatomy of simple and complex sequential finger movements: a PET study},
      journal = {BRAIN},
      year = {1998},
      volume = {121},
      number = {Part 2},
      pages = {253-264}
    }
    
    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}
    }
    
    Chapman, P., White, G., Jones, M., Cooper-Blacketer, D., Marshall, V., Irizarry, M., Younkin, L., Good, M., Bliss, T., Hyman, B., Younkin, S. & Hsiao, K. Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice {1999} NATURE NEUROSCIENCE
    Vol. {2}({3}), pp. {271-276} 
    article  
    Abstract: We investigated synaptic communication and plasticity in hippocampal slices from mice overexpressing mutated 695-amino-acid human amyloid precursor protein (APP(695)SWE), which show behavioral and histopathological abnormalities simulating Alzheimer's disease. Although aged APP transgenic mice exhibit normal fast synaptic transmission and short term plasticity, they are severely impaired in in-vitro and in-vivo long-term potentiation (LTP) in both the CA1 and dentate gyrus regions of the hippocampus. The LTP deficit was correlated with impaired performance in a spatial working memory task in aged transgenics. These deficits are accompanied by minimal or no loss of presynaptic or postsynaptic elementary structural elements in the hippocampus, suggesting that impairments in functional synaptic plasticity may underlie some of the cognitive deficits in these mice and, possibly, in Alzheimer's patients.
    BibTeX:
    @article{Chapman1999,
      author = {Chapman, PF and White, GL and Jones, MW and Cooper-Blacketer, D and Marshall, VJ and Irizarry, M and Younkin, L and Good, MA and Bliss, TVP and Hyman, BT and Younkin, SG and Hsiao, KK},
      title = {Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice},
      journal = {NATURE NEUROSCIENCE},
      year = {1999},
      volume = {2},
      number = {3},
      pages = {271-276}
    }
    
    Chelazzi, L., Duncan, J., Miller, E. & Desimone, R. Responses of neurons in inferior temporal cortex during memory-guided visual search {1998} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {80}({6}), pp. {2918-2940} 
    article  
    Abstract: A typical scene will contain many different objects, few of which are relevant to behavior at any given moment. Thus attentional mechanisms are needed to select relevant objects for visual processing and control over behavior. We examined this role of attention in the inferior temporal cortex of macaque monkeys, using a visual search paradigm. While the monkey maintained fixation, a cue stimulus was presented at the center of gaze, followed by a blank delay period. After the delay, an array of two to five choice stimuli was presented extrafoveally, and the monkey was rewarded for detecting a target stimulus matching the cue. The behavioral response was a saccadic eye movement to the target in one version of the task and a lever release in another. The array was composed of one ``good'' stimulus (effective in driving the cell when presented alone) and one or more ``poor'' stimuli (ineffective in driving the cell when presented alone). Most cells showed higher delay activity after a good stimulus used as the cue than after a poor stimulus. The baseline activity of cells was also higher preceding a good cue, if the animal expected it to occur. This activity may depend on a top-down bias in favor of cells coding the relevant stimulus. When the choice array was presented, most cells showed suppressive interactions between the stimuli as well as strong attention effects. When the choice array was presented in the contralateral visual field, most cells initially responded the same, regardless of which stimulus was the target. However, within 150-200 ms of array onset, responses were determined by the target stimulus. If the target was the good stimulus, the response to the array became equal to the response to the good stimulus presented alone. If the target was a poor stimulus, the response approached the response to that stimulus presented alone. Thus the influence of the nontarget stimulus was eliminated. These effects occurred well in advance of the behavioral response. When the array was positioned with stimuli on opposite sides of the vertical meridian, the contralateral stimulus appeared to dominate the response, and this dominant effect could not be overcome by attention. Overall, the results support a ``biased competition'' model of attention, according to which 1) objects in the visual field compete for representation in the cortex, and 2) this competition is biased in favor of the behaviorally relevant object by virtue of `'top-down'' feedback from structures involved in working memory.
    BibTeX:
    @article{Chelazzi1998,
      author = {Chelazzi, L and Duncan, J and Miller, EK and Desimone, R},
      title = {Responses of neurons in inferior temporal cortex during memory-guided visual search},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1998},
      volume = {80},
      number = {6},
      pages = {2918-2940}
    }
    
    CHEN, L., LIN, L., GREEN, E., BARNES, C. & MCNAUGHTON, B. HEAD-DIRECTION CELLS IN THE RAT POSTERIOR CORTEX .1. ANATOMICAL DISTRIBUTION AND BEHAVIORAL MODULATION {1994} EXPERIMENTAL BRAIN RESEARCH
    Vol. {101}({1}), pp. {8-23} 
    article  
    Abstract: We examined the behavioral modulation of head-directional information processing in neurons of the rat posterior cortices, including the medial prestriate (area Oc2M) and retrosplenial cortex (areas RSA and RSG). Single neurons were recorded in freely moving rats which were trained to perform a spatial working memory task on a radial-arm maze in a cue-controlled room. A dual-light-emitting diode (dual-LED) recording headstage, mounted on the animals' heads, was used to track head position and orientation. Planar modes of motion, such as turns, straight motion, and nonlocomotive slates, were categorized using an objective scheme based upon the differential contributions of movement parameters, including linear and angular velocity of the head. Of 662 neurons recorded from the posterior cortices, 41 head-direction (HD) cells were identified based on the criterion of maintained directional bias in the absence of visual cues or in the dark. HD cells constituted 7 of 257 (2.7 cells recorded in Oc2M, 26 of 311 (8.4 cells in RSA, and 8 of 94 (8.5 cells in RSG. Spatial tuning of HD cell firing was modulated by the animal's behaviors in some neurons. The behavioral modulation occurred either at the preferred direction or at all directions. Moreover, the behavioral selectivity was more robust for turns than straight motions, suggesting that the angular movements may significantly contribute to the head-directional processing. These behaviorally selective HD cells were observed most frequently in Oc2M (4/7, 57, as only 5 of 26 (19 of RSA cells and none of the RSG cells showed behavioral modulation. These data, taken together with the anatomical evidence for a cascade of projections from Oc2M to RSA and thence to RSG, suggest that there may be a simple association between movement and head-directionality that serves to transform the egocentric movement representation in the neocortex into an allocentric directional representation in the periallocortex.
    BibTeX:
    @article{CHEN1994,
      author = {CHEN, LL and LIN, LH and GREEN, EJ and BARNES, CA and MCNAUGHTON, BL},
      title = {HEAD-DIRECTION CELLS IN THE RAT POSTERIOR CORTEX .1. ANATOMICAL DISTRIBUTION AND BEHAVIORAL MODULATION},
      journal = {EXPERIMENTAL BRAIN RESEARCH},
      year = {1994},
      volume = {101},
      number = {1},
      pages = {8-23}
    }
    
    Christoff, K. & Gabrieli, J. The frontopolar cortex and human cognition: Evidence for a rostrocaudal hierarchical organization within the human prefrontal cortex {2000} PSYCHOBIOLOGY
    Vol. {28}({2}), pp. {168-186} 
    article  
    Abstract: Numerous brain lesion and functional neuroimaging studies have suggested that the dorsolateral and frontopolar prefrontal regions are involved in complex cognitive processes subserving thought and memory. However, previously proposed functional subdivisions of prefrontal function have concentrated predominantly on posterior prefrontal cortex, including the dorsolateral, ventral, and medial regions. Far less consideration has been given to characterizing the psychological processes mediated by the frontopolar cortex. Here we review published neuroimaging studies of reasoning and episodic memory, two domains in which the frontopolar cortex has been frequently activated. The results suggest that dorsolateral prefrontal cortex is involved when externally generated information is being evaluated, whereas the frontopolar cortex becomes recruited when internally generated information needs to be evaluated. A hierarchical model of prefrontal function is proposed in which dorsolateral and frontopolar regions are serially recruited as a reasoning or memory task requires evaluation of internally generated information.
    BibTeX:
    @article{Christoff2000,
      author = {Christoff, K and Gabrieli, JDE},
      title = {The frontopolar cortex and human cognition: Evidence for a rostrocaudal hierarchical organization within the human prefrontal cortex},
      journal = {PSYCHOBIOLOGY},
      year = {2000},
      volume = {28},
      number = {2},
      pages = {168-186}
    }
    
    Clark, L., Iversen, S. & Goodwin, G. Sustained attention deficit in bipolar disorder {2002} BRITISH JOURNAL OF PSYCHIATRY
    Vol. {180}, pp. {313-319} 
    article  
    Abstract: Background Recovery in bipolar disorder is central to its definition but is rarely complete. Previous work has suggested that neuropsychological impairment persists during the euthymic state but has been confounded partly by mild affective symptoms in remitted patients. Aims To characterise neuropsychological functioning in the euthymic phase of bipolar disorder with an emphasis on tasks of executive functioning. Method Thirty euthymic patients with bipolar disorder were compared with thirty healthy controls on neuropsychological tasks differentially sensitive to damage within prefrontal cortex. Results Bipolar 1 patients were impaired on tasks of attentional set shifting, verbal memory and sustained attention. Only sustained attention deficit survived controlling for mild affective symptoms. This deficit was related to progression of illness, but was none the less present in a subgroup of patients near illness onset. Conclusions Sustained attention deficit may represent a neuropsychological vulnerability marker for bipolar disorder, providing a focus for further understanding of the phenotype and analysis of the neuronal networks involved. Declaration of interest None.
    BibTeX:
    @article{Clark2002,
      author = {Clark, L and Iversen, SD and Goodwin, GM},
      title = {Sustained attention deficit in bipolar disorder},
      journal = {BRITISH JOURNAL OF PSYCHIATRY},
      year = {2002},
      volume = {180},
      pages = {313-319},
      note = {29th Annual Meeting of the Society-for-Neuroscience, MIAMI BEACH, FLORIDA, OCT 23-28, 1999}
    }
    
    Clark, R., Zola, S. & Squire, L. Impaired recognition memory in rats after damage to the hippocampus {2000} JOURNAL OF NEUROSCIENCE
    Vol. {20}({23}), pp. {8853-8860} 
    article  
    Abstract: Rats with radio-frequency or ibotenic acid lesions of the hippocampus and rats with radio-frequency lesions of the fornix were tested on the visual paired comparison task (VPC), a test of recognition memory. Memory was assessed at five different delay intervals ranging from 10 sec to 24 hr. All operated groups performed normally at the shorter delays (10 sec and 1 min). Across longer delays, the two groups with hippocampal damage were impaired. Rats with fornix lesions performed well on the VPC task but were impaired on a spatial task (spontaneous alternation). The results show that the hippocampus is essential for normal recognition memory. Moreover, fornix lesions need not mimic the effects of direct damage to hippocampal tissue. The findings are discussed in the context of the contribution of the hippocampus to recognition memory.
    BibTeX:
    @article{Clark2000,
      author = {Clark, RE and Zola, SM and Squire, LR},
      title = {Impaired recognition memory in rats after damage to the hippocampus},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2000},
      volume = {20},
      number = {23},
      pages = {8853-8860}
    }
    
    Coghill, R., Sang, C., Maisog, J. & Iadarola, M. Pain intensity processing within the human brain: A bilateral, distributed mechanism {1999} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {82}({4}), pp. {1934-1943} 
    article  
    Abstract: Functional imaging studies of human subjects have identified a diverse assortment of brain areas that are engaged in the processing of pain. Although many of these brain areas are highly interconnected and are engaged in multiple processing roles, each area has been typically considered in isolation. Accordingly, little attention has been given to the global functional organization of brain mechanisms mediating pain processing. In the present investigation, we have combined positron emission tomography with psychophysical assessment of graded painful stimuli to better characterize the multiregional organization of supraspinal pain processing mechanisms and to identify a brain mechanism subserving the processing of pain intensity. Multiple regression analysis revealed statistically reliable relationships between perceived pain intensity and activation of a functionally diverse group of brain regions, including those important in sensation, motor control, affect, and attention. Pain intensity-related activation occurred bilaterally in the cerebellum, putamen, thalamus, insula, anterior cingulate cortex, and secondary somatosensory cortex, contralaterally in the primary somatosensory cortex and supplementary motor area, and ipsilaterally in the ventral premotor area. These results confirm the existence of a highly distributed, bilateral supraspinal mechanism engaged in the processing of pain intensity. The conservation of pain intensity information across multiple, functionally distinct brain areas contrasts sharply with traditional views that sensory-discriminative processing of pain is confined within the somatosensory cortex and can account for the preservation of conscious awareness of pain intensity after extensive cerebral cortical lesions.
    BibTeX:
    @article{Coghill1999,
      author = {Coghill, RC and Sang, CN and Maisog, JH and Iadarola, MJ},
      title = {Pain intensity processing within the human brain: A bilateral, distributed mechanism},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1999},
      volume = {82},
      number = {4},
      pages = {1934-1943}
    }
    
    Cohen, J., Barch, D., Carter, C. & Servan-Schreiber, D. Context-processing deficits in schizophrenia: Converging evidence from three theoretically motivated cognitive tasks {1999} JOURNAL OF ABNORMAL PSYCHOLOGY
    Vol. {108}({1}), pp. {120-133} 
    article  
    Abstract: To test the hypothesis that the ability to actively represent and maintain context information is a central function of working memory and that a disturbance in this function contributes to cognitive deficits in schizophrenia, the authors modified 3 tasks-the AX version of the Continuous Performance Test, Stroop, and a lexical disambiguation task-and administered them to patients with schizophrenia as well as to depressed and healthy controls. The results suggest an accentuation of deficits in patients with schizophrenia in context-sensitive conditions and cross-task correlations of performance in these conditions. However, the results do not definitively eliminate the possibility of a generalized deficit. The significance of these findings is discussed with regard to the specificity of deficits in schizophrenia and the hypothesis concerning the neural and cognitive mechanisms that underlie these deficits.
    BibTeX:
    @article{Cohen1999,
      author = {Cohen, JD and Barch, DM and Carter, C and Servan-Schreiber, D},
      title = {Context-processing deficits in schizophrenia: Converging evidence from three theoretically motivated cognitive tasks},
      journal = {JOURNAL OF ABNORMAL PSYCHOLOGY},
      year = {1999},
      volume = {108},
      number = {1},
      pages = {120-133}
    }
    
    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}
    }
    
    COLBOURNE, F. & CORBETT, D. DELAYED POSTISCHEMIC HYPOTHERMIA - A 6 MONTH SURVIVAL STUDY USING BEHAVIORAL AND HISTOLOGICAL ASSESSMENTS OF NEUROPROTECTION {1995} JOURNAL OF NEUROSCIENCE
    Vol. {15}({11}), pp. {7250-7260} 
    article  
    Abstract: In the gerbil, brief global forebrain ischemia induces profound habituation and working memory impairments that stem from delayed hippocampal CA1 death, Short duration postischemic hypothermia has been shown to reduce CA1 loss, but such reports are controversial, as it is thought that protection may be transient. The purpose of this study was to investigate whether prolonged postischemic hypothermia provided long-term CA1 and functional neuroprotection. Previously, 90% of anterior CA1 neurons were rescued (30 d survival) when 24 hr of hypothermia (32 degrees C) was induced 1 hr following a 5 min occlusion that otherwise produced more than 95% loss (Colbourne and Corbett, 1994). We now find about 70% CA1 savings with this same hypothermic treatment in gerbils that survived for 6 months postischemia. While this is a significant reduction from 30 day survival (medial CA1 only), it nonetheless shows, for the first time, persistent, if not permanent neuroprotection, especially in middle and lateral CA1, In addition, in nontreated animals, ischemia impaired learning in an open field and T-maze for up to 6 months. Postischemic hypothermia significantly reduced these deficits, Hypothermia (32 degrees), when initiated 4 hr after ischemia, rescued approximate to 12% of CA1 neurons at 6 months with a slight behavioral benefit. Milder hypothermia (34 degrees C, 1-25 hr postischemia, 30 d survival) also reduced habituation impairments and saved approximate to 60% of CA1 neurons. Similar trends were found at more caudal CA1 levels. These results clearly show that postischemic hypothermia provides effective and long-lasting neuroprotection, which depends upon the delay to initiation, duration, and degree of cooling and survival time. The protracted functional and histological benefit observed justifies further basic and clinical investigation.
    BibTeX:
    @article{COLBOURNE1995,
      author = {COLBOURNE, F and CORBETT, D},
      title = {DELAYED POSTISCHEMIC HYPOTHERMIA - A 6 MONTH SURVIVAL STUDY USING BEHAVIORAL AND HISTOLOGICAL ASSESSMENTS OF NEUROPROTECTION},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1995},
      volume = {15},
      number = {11},
      pages = {7250-7260}
    }
    
    Collette, F. & Van der Linden, M. Brain imaging of the central executive component of working memory {2002} NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
    Vol. {26}({2}), pp. {105-125} 
    article  
    Abstract: This review presents neuroimaging studies which have explored the cerebral substrates of the central executive component of the working memory model proposed by Baddeley and Hitch [working memory (1986); Recent advances in learning and motivation (1974)]. These studies have demonstrated that different executive functions (manipulating and updating of information, dual-task coordination, inhibition and shifting processes) not only recruit various frontal areas, but also depend upon posterior (mainly parietal) regions. Such results are in agreement with the hypothesis that executive functions rely on a distributed cerebral network not restricted to anterior cerebral areas. Moreover, the intervention of similar prefrontal regions in a large number of executive tasks suggests that the central executive functioning must be understood in terms of different interactions between a network of regions rather than in terms of a specific association between one region and one higher-level cognitive process. (C) 2002 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{Collette2002,
      author = {Collette, F and Van der Linden, M},
      title = {Brain imaging of the central executive component of working memory},
      journal = {NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS},
      year = {2002},
      volume = {26},
      number = {2},
      pages = {105-125}
    }
    
    Compte, A., Brunel, N., Goldman-Rakic, P. & Wang, X. Synaptic mechanisms and network dynamics underlying spatial working memory in a cortical network model {2000} CEREBRAL CORTEX
    Vol. {10}({9}), pp. {910-923} 
    article  
    Abstract: Single-neuron recordings from behaving primates have established a link between working memory processes and information-specific neuronal persistent activity in the prefrontal cortex. Using a network model endowed with a columnar architecture and based on the physiological properties of cortical neurons and synapses, we have examined the synaptic mechanisms of selective persistent activity underlying spatial working memory in the prefrontal cortex. Our model reproduces the phenomenology of the oculomotor delayed-response experiment of Funahashi et al. (S. Funahashi, C.J. Bruce and P.S. Goldman-Rakic, Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex. J Neurophysiol 61:331-349, 1989). To observe stable spontaneous and persistent activity, we find that recurrent synaptic excitation should be primarily mediated by NMDA receptors, and that overall recurrent synaptic interactions should be dominated by inhibition. Isodirectional tuning of adjacent pyramidal cells and interneurons can be accounted for by a structured pyramid-to-interneuron connectivity. Robust memory storage against random drift of the tuned persistent activity and against distracters (intervening stimuli during the delay period) may be enhanced by neuromodulation of recurrent synapses. Experimentally testable predictions concerning the neural basis of working memory are discussed.
    BibTeX:
    @article{Compte2000,
      author = {Compte, A and Brunel, N and Goldman-Rakic, PS and Wang, XJ},
      title = {Synaptic mechanisms and network dynamics underlying spatial working memory in a cortical network model},
      journal = {CEREBRAL CORTEX},
      year = {2000},
      volume = {10},
      number = {9},
      pages = {910-923}
    }
    
    CONWAY, A. & ENGLE, R. WORKING-MEMORY AND RETRIEVAL - A RESOURCE-DEPENDENT INHIBITION MODEL {1994} JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL
    Vol. {123}({4}), pp. {354-373} 
    article  
    Abstract: Four experiments examined individual differences in working memory (WM) capacity and how those differences affect performance on retrieval from both primary and secondary memory. The results showed that WM differences appear only in retrieval from primary memory and then only under conditions that lead to interference or response competition within the task. This suggests that WM capacity is important to retrieval that is based on controlled effortful search but not search that is based on automatic activation. A view is presented suggesting that individual differences in attentional resources lead to differences in the ability to inhibit or suppress irrelevant information. The paradigm also allowed more general comparisons between the processes involved in retrieval from primary and secondary memory. As expected, it was found that retrieval from primary memory was a function of set size. However, for sets larger than 2 items, retrieval from secondary memory was independent of set size.
    BibTeX:
    @article{CONWAY1994,
      author = {CONWAY, ARA and ENGLE, RW},
      title = {WORKING-MEMORY AND RETRIEVAL - A RESOURCE-DEPENDENT INHIBITION MODEL},
      journal = {JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL},
      year = {1994},
      volume = {123},
      number = {4},
      pages = {354-373}
    }
    
    Conway, M. & Pleydell-Pearce, C. The construction of autobiographical memories in the self-memory system {2000} PSYCHOLOGICAL REVIEW
    Vol. {107}({2}), pp. {261-288} 
    article DOI  
    Abstract: The authors describe a model of autobiographical memory in which memories are transitory mental constructions within a self-memory system (SMS). The SMS contains an autobiographical knowledge base and current goals of the working self. Within the SMS, control processes modulate access to the knowledge base by successively shaping cues used to activate autobiographical memory knowledge structures and, in this way, form specific memories. The relation of the knowledge base to active goals is reciprocal, and the knowledge base ``grounds'' the goals of the working self. It is shown how this model can be used to draw together a wide range of diverse data from cognitive, social, developmental, personality, clinical, and neuropsychological autobiographical memory research.
    BibTeX:
    @article{Conway2000,
      author = {Conway, MA and Pleydell-Pearce, CW},
      title = {The construction of autobiographical memories in the self-memory system},
      journal = {PSYCHOLOGICAL REVIEW},
      year = {2000},
      volume = {107},
      number = {2},
      pages = {261-288},
      doi = {{10.1037//0033-295X.107.2.261}}
    }
    
    Cools, R., Barker, R., Sahakian, B. & Robbins, T. Enhanced or impaired cognitive function in Parkinson's disease as a function of dopaminergic medication and task demands {2001} CEREBRAL CORTEX
    Vol. {11}({12}), pp. {1136-1143} 
    article  
    Abstract: We investigated how dopamine (DA) systems contribute to cognitive performance in the domain of learning and attentional flexibility by examining effects of withdrawing DA-ergic medication in patients with Parkinson's disease (PD). Medication remediated impairments in switching between two tasks, thought to depend on circuitry connecting the dorsolateral prefrontal cortex and the posterior parietal cortex to the dorsal caudate nucleus, which is profoundly DA-depleted in PD. By contrast, the same medication impaired probabilistic reversal learning that implicates orbitofrontal cortex-ventral striatal circuitry, which is relatively spared of DA loss in PD. Hence, DA-ergic medication improves or impairs cognitive performance depending on the nature of the task and the basal level of DA function in underlying cortico-striatal circuitry.
    BibTeX:
    @article{Cools2001,
      author = {Cools, R and Barker, RA and Sahakian, BJ and Robbins, TW},
      title = {Enhanced or impaired cognitive function in Parkinson's disease as a function of dopaminergic medication and task demands},
      journal = {CEREBRAL CORTEX},
      year = {2001},
      volume = {11},
      number = {12},
      pages = {1136-1143}
    }
    
    Cools, R., Clark, L., Owen, A. & Robbins, T. Defining the neural mechanisms of probabilistic reversal learning using event-related functional magnetic resonance imaging {2002} JOURNAL OF NEUROSCIENCE
    Vol. {22}({11}), pp. {4563-4567} 
    article  
    Abstract: Event-related functional magnetic resonance imaging was used to measure blood oxygenation level-dependent responses in 13 young healthy human volunteers during performance of a probabilistic reversal-learning task. The task allowed the separate investigation of the relearning of stimulus-reward associations and the reception of negative feedback. Significant signal change in the right ventrolateral prefrontal cortex was demonstrated on trials when subjects stopped responding to the previously relevant stimulus and shifted responding to the newly relevant stimulus. Significant signal change in the region of the ventral striatum was also observed on such reversal errors, from a region of interest analysis. The ventrolateral prefrontal cortex and ventral striatum were not significantly activated by the other, preceding reversal errors, or when subjects received negative feedback for correct responses. Moreover, the response on the final reversal error, before shifting, was not modulated by the number of preceding reversal errors, indicating that error-related activity does not simply accumulate in this network. The signal change in this ventral frontostriatal circuit is therefore associated with reversal learning and is uncontaminated by negative feedback. Overall, these data concur with findings in rodents and nonhuman primates of reversal-learning deficits after damage to ventral frontostriatal circuitry, and also support recent clinical findings using this task.
    BibTeX:
    @article{Cools2002,
      author = {Cools, R and Clark, L and Owen, AM and Robbins, TW},
      title = {Defining the neural mechanisms of probabilistic reversal learning using event-related functional magnetic resonance imaging},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2002},
      volume = {22},
      number = {11},
      pages = {4563-4567}
    }
    
    COOPER, J., SAGAR, H., JORDAN, N., HARVEY, N. & SULLIVAN, E. COGNITIVE IMPAIRMENT IN EARLY, UNTREATED PARKINSONS-DISEASE AND ITS RELATIONSHIP TO MOTOR DISABILITY {1991} BRAIN
    Vol. {114}({Part 5}), pp. {2095-2122} 
    article  
    Abstract: Current knowledge of cognitive dysfunction in Parkinson's disease (PD) has largely been obtained from studies of chronically treated patients in whom effects of disease chronicity, treatment, depression and dementia are confounding factors. Studies of untreated patients have examined few cognitive domains and relationships between cognition, depression and motor disability have been incompletely explored. Accordingly, we studied 60 consecutive patients with newly diagnosed, untreated, idiopathic PD and 37 matched, healthy control subjects; no subject had clinical dementia or depression. All subjects received tests of specific processes of memory and cognition, including working memory, verbal and non-verbal short- and long-term memory, language, visuospatial capacity, set-formation and shifting and sequencing. Patients also received quantitative global clinical measures of severity of dementia, depression and motor disability. The PD group as a whole showed deficits in immediate recall of verbal material, language production and semantic fluency, set-formation, cognitive sequencing and working memory and visumotor construction. However, this group was unimpaired in immediate memory span, long-term forgetting, naming, comprehension and visual perception. Language deficits and more severe frontal lobe impairments were confined to those PD patients scoring abnormally on a Mini Mental State examination. Motor disability correlated strongly with severity of depression but weakly with cognitive impairment. Cognitive sequencing, set-formation and set-shifting deficits tended to associate with depression, but otherwise there was no association between cognition and depression. The results indicate dissociation of cognition and motor control in early PD which suggests that cognitive dysfunction is largely independent of frontostriatal dopamine deficiency underlying motor disability. Some, but not all, of the frontal lobe deficits of chronic disease are detectable in early, untreated PD. The pathogenesis of the cognitive deficits shown here appears to involve extrastriatal dopamine systems or non-dopaminergic pathology. Longitudinal study is necessary to determine whether increasing disease duration exacerbates the early cognitive deficits and affects new cognitive domains, in addition to producing increasing motor disability.
    BibTeX:
    @article{COOPER1991,
      author = {COOPER, JA and SAGAR, HJ and JORDAN, N and HARVEY, NS and SULLIVAN, EV},
      title = {COGNITIVE IMPAIRMENT IN EARLY, UNTREATED PARKINSONS-DISEASE AND ITS RELATIONSHIP TO MOTOR DISABILITY},
      journal = {BRAIN},
      year = {1991},
      volume = {114},
      number = {Part 5},
      pages = {2095-2122}
    }
    
    Corbetta, M., Kincade, J., Ollinger, J., McAvoy, M. & Shulman, G. Voluntary orienting is dissociated from target detection in human posterior parietal cortex {2000} NATURE NEUROSCIENCE
    Vol. {3}({3}), pp. {292-297} 
    article  
    Abstract: Human ability to attend to visual stimuli based on their spatial locations requires the parietal cortex. One hypothesis maintains that parietal cortex controls the voluntary orienting of attention toward a location of interest. Another hypothesis emphasizes its role in reorienting attention toward visual targets appearing at unattended locations. Here, using event-related functional magnetic resonance (ER-fMRI), we show that distinct parietal regions mediated these different attentional processes. Cortical activation occurred primarily in the intraparietal sulcus when a location was attended before visual-target presentation, but in the right temporoparietal junction when the target was detected, particularly at an unattended location.
    BibTeX:
    @article{Corbetta2000,
      author = {Corbetta, M and Kincade, JM and Ollinger, JM and McAvoy, MP and Shulman, GL},
      title = {Voluntary orienting is dissociated from target detection in human posterior parietal cortex},
      journal = {NATURE NEUROSCIENCE},
      year = {2000},
      volume = {3},
      number = {3},
      pages = {292-297}
    }
    
    Corbetta, M., Kincade, J. & Shulman, G. Neural systems for visual orienting and their relationships to spatial working memory {2002} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {14}({3}), pp. {508-523} 
    article  
    Abstract: We investigated neural correlates of human visual orienting using event-related functional magnetic resonance imaging (fMRI). When subjects voluntarily directed attention to a peripheral location, we recorded robust and sustained signals uniquely from the intraparietal sulcus (IPs) and superior frontal cortex (near the frontal eye field, FEF). In the ventral IPs and FEF only, the blood oxygen level dependent signal was modulated by the direction of attention. The IN and FEF also maintained the most sustained level of activation during a 7-sec delay, when subjects maintained attention at the peripheral cued location (working memory). Therefore, the IPs and FEF form a dorsal network that controls the endogenous allocation and maintenance of visuospatial attention, A separate right hemisphere network was activated by the detection of targets at Unattended locations, Activation was largely independent of the target's location (visual field). This network included among other regions the right temporo-parietal junction and the inferior frontal gyrus. We propose that this cortica l network is important for reorienting to sensory events.
    BibTeX:
    @article{Corbetta2002,
      author = {Corbetta, M and Kincade, JM and Shulman, GL},
      title = {Neural systems for visual orienting and their relationships to spatial working memory},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {2002},
      volume = {14},
      number = {3},
      pages = {508-523}
    }
    
    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}
    }
    
    Coull, J., Frith, C., Frackowiak, R. & Grasby, P. A fronto-parietal network for rapid visual information processing: A PET study of sustained attention and working memory {1996} NEUROPSYCHOLOGIA
    Vol. {34}({11}), pp. {1085-1095} 
    article  
    Abstract: The rapid visual information processing (RVIP) task, a lest of sustained attention which also requires working memory for its successful execution, has been used in a number of human psychopharmacological studies. Single digits are presented in quick succession (100 or 200 digits/min) on a computer screen, and target sequences of numbers must be detected with a button press. Although previous neuroimaging studies have implicated the frontal and parietal cortices in performance of simple sustained attention tasks, the neuroanatomical substrates of RVIP performance are not yet known. This information would prove invaluable in the interpretation of drug effects on this task, possibly delineating a neuron;al network for neurotransmitter action. Therefore, this study investigated the functional anatomy of the RVIP task using positron emission tomography (PET) derived measures of regional cerebral blood flow (rCBF) in eight healthy volunteers. Subjects were required to perform variants of the RVIP task which manipulated both the level of working memory load and the speed of stimulus presentation. Compared with a rest condition (eyes closed), the RVIP task increased rCBF bilaterally in the inferior frontal gyri, parietal cortex and fusiform gyrus, and also in the right frontal superior gyrus rostrally. In comparison with a simple sustained attention control condition, the aforementioned right frontal activations were no longer apparent. We suggest that these data are consistent with the existence of a right fronto-parietal network for sustained, and possibly selective: attention, and a left fronto-parietal network for the phonological loop component of working memory. Copyright (C) 1996 Elsevier Science Ltd.
    BibTeX:
    @article{Coull1996,
      author = {Coull, JT and Frith, CD and Frackowiak, RSJ and Grasby, PM},
      title = {A fronto-parietal network for rapid visual information processing: A PET study of sustained attention and working memory},
      journal = {NEUROPSYCHOLOGIA},
      year = {1996},
      volume = {34},
      number = {11},
      pages = {1085-1095}
    }
    
    Coulson, S., King, J. & Kutas, M. Expect the unexpected: Event-related brain response to morphosyntactic violations {1998} LANGUAGE AND COGNITIVE PROCESSES
    Vol. {13}({1}), pp. {21-58} 
    article  
    Abstract: Arguments about the existence of language-specific neural systems and particularly arguments about the independence of syntactic and semantic processing have recently focused on differences between the event-related potentials (ERPs) elicited by violations of syntactic structure (e.g. the P600) and those elicited by violations of semantic expectancy (e.g. the N400). However, the scalp distribution of the P600 component elicited by syntactic violations appears to resemble that elicited by rare categorical events (''odd-balls'') in non-linguistic contexts, frequently termed the P3b. The relationship between the P600 and the P3b was explored by manipulating the grammaticality of sentences read for comprehension, as well as two factors known to influence P3b amplitude: odd-ball probability and event saliency. Oddball probability was manipulated by varying the frequency of morphosyntactic violations within blocks of sentences, and event saliency was manipulated by using two types of morphosyntactic violations, one of which was more striking than the other. The results indicate that the amplitude of the P600, like the P3b, was sensitive to both the probability and saliency manipulations, and that the scalp distributions for the effect of probability and grammaticality are essentially similar. An unexpected, but not wholly surprising, finding was the elicitation of an anterior negativity between 300 and 500 msec post-word onset, which may index working memory operations involved in sentence processing.
    BibTeX:
    @article{Coulson1998,
      author = {Coulson, S and King, JW and Kutas, M},
      title = {Expect the unexpected: Event-related brain response to morphosyntactic violations},
      journal = {LANGUAGE AND COGNITIVE PROCESSES},
      year = {1998},
      volume = {13},
      number = {1},
      pages = {21-58}
    }
    
    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}
    }
    
    Cowan, N. The magical number 4 in short-term memory: A reconsideration of mental storage capacity {2001} BEHAVIORAL AND BRAIN SCIENCES
    Vol. {24}({1}), pp. {87+} 
    article  
    Abstract: Miller (1956) summarized evidence that people can remember about seven chunks in short-term memory (STM) tasks. However, that number was meant more as a rough estimate and a rhetorical device than as a real capacity limit. Others have since suggested that there is a more precise capacity limit, but that it is only three to five chunks. The present target article brings together a wide variety of data on capacity limits suggesting that the smaller capacity limit is real. Capacity limits will be useful in analyses of information processing only if the boundary conditions for observing them can be carefully described. Four basic conditions in which chunks can be identified and capacity limits can accordingly be observed are: (1) when information overload limits chunks to individual stimulus items, (2) when other steps are taken specifically to block the recoding of stimulus items into larger chunks, (3) in performance discontinuities caused by the capacity limit, and (4) in various indirect effects of the capacity limit. Under these conditions, rehearsal and long-term memory cannot be used to combine stimulus items into chunks of an unknown size; nor can storage mechanisms that are not capacity-limited, such as sensory memory, allow the capacity-limited storage mechanism to be refilled during recall. A single, central capacity limit averaging about four chunks is implicated along with other, noncapacity-limited sources. The pure STM capacity limit expressed in chunks is distinguished from compound STM limits obtained when the number of separately held chunks is unclear. Reasons why pure capacity estimates fall within a narrow range are discussed and a capacity limit for the focus of attention is proposed.
    BibTeX:
    @article{Cowan2001,
      author = {Cowan, N},
      title = {The magical number 4 in short-term memory: A reconsideration of mental storage capacity},
      journal = {BEHAVIORAL AND BRAIN SCIENCES},
      year = {2001},
      volume = {24},
      number = {1},
      pages = {87+}
    }
    
    Crick, F. & Koch, C. Consciousness and neuroscience {1998} CEREBRAL CORTEX
    Vol. {8}({2}), pp. {97-107} 
    article  
    Abstract: The main purposes of this review are to set out for neuroscientists one possible approach to the problem of consciousness and to describe the relevant ongoing experimental work. We have not attempted an exhaustive review of other approaches.
    BibTeX:
    @article{Crick1998,
      author = {Crick, F and Koch, C},
      title = {Consciousness and neuroscience},
      journal = {CEREBRAL CORTEX},
      year = {1998},
      volume = {8},
      number = {2},
      pages = {97-107}
    }
    
    Critchley, H., Mathias, C. & Dolan, R. Neural activity in the human brain relating to uncertainty and arousal during anticipation {2001} NEURON
    Vol. {29}({2}), pp. {537-545} 
    article  
    Abstract: We used functional magnetic resonance neuroimaging to measure brain activity during delay between reward-related decisions and their outcomes, and the modulation of this delay activity by uncertainty and arousal. Feedback, indicating financial gain or loss, was given following a fixed delay. Anticipatory arousal was indexed by galvanic skin conductance. Delay-period activity was associated with bilateral activation in orbital and medial prefrontal, temporal, and right parietal cortices. During delay, activity in anterior cingulate and orbitofrontal cortices was modulated by outcome uncertainty, whereas anterior cingulate, dorsolateral prefrontal, and parietal cortices activity was modulated by degree of anticipatory arousal. A distinct region of anterior cingulate was commonly activated by both uncertainty and arousal. Our findings highlight distinct contributions of cognitive uncertainty and autonomic arousal to anticipatory neural activity in prefrontal cortex.
    BibTeX:
    @article{Critchley2001,
      author = {Critchley, HD and Mathias, CJ and Dolan, RJ},
      title = {Neural activity in the human brain relating to uncertainty and arousal during anticipation},
      journal = {NEURON},
      year = {2001},
      volume = {29},
      number = {2},
      pages = {537-545}
    }
    
    Culham, J., Brandt, S., Cavanagh, P., Kanwisher, N., Dale, A. & Tootell, R. Cortical fMRI activation produced by attentive tracking of moving targets {1998} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {80}({5}), pp. {2657-2670} 
    article  
    Abstract: Attention can be used to keep track of moving items, particularly when there are multiple targets of interest that cannot all be followed with eye movements. Functional magnetic resonance imaging (fMRI) was used to investigate cortical regions involved in attentive tracking. Cortical flattening techniques facilitated within-subject comparisons of activation produced by attentive tracking, visual motion, discrete attention shifts, and eye movements. In the main task, subjects viewed a display of nine green `'bouncing balls'' and used attention to mentally track a subset of them while fixating. At the start of each attentive-tracking condition, several target balls (e.g., 3/9) turned red for 2 s and then reverted to green. Subjects then used attention to keep track of the previously indicated targets, which were otherwise indistinguishable from the nontargets. Attentive-tracking conditions alternated with passive viewing of the same display when no targets had been indicated. Subjects were pretested with an eye-movement monitor to ensure they could perform the task accurately while fixating. For seven subjects, functional activation was superimposed on each individual's cortically unfolded surface. Comparisons between attentive tracking and passive viewing revealed bilateral activation in parietal cortex (intraparietal sulcus, postcentral sulcus, superior parietal lobule, and precuneus), frontal cortex (frontal eye fields and precentral sulcus), and the MT complex (including motion-selective areas MT and MST). Attentional enhancement was absent in early visual areas and weak in the MT complex. However, in parietal and frontal areas, the signal change produced by the moving stimuli was more than doubled when items were tracked attentively. Comparisons between attentive tracking and attention shifting revealed essentially identical activation patterns that differed only in the magnitude of activation. This suggests that parietal cortex is involved not only in discrete shifts of attention between objects at different spatial locations but also in continuous ``attentional pursuit'' of moving objects. Attentive-tracking activation patterns were also similar, though not identical, to those produced by eye movements. Taken together, these results suggest that attentive tracking is mediated by a network of areas that includes parietal and frontal regions responsible for attention shifts and eye movements and the MT complex, thought to be responsible for motion perception. These results are consistent with theoretical models of attentive tracking as an attentional process that assigns spatial tags to targets and registers changes in their position, generating a high-level percept of apparent motion.
    BibTeX:
    @article{Culham1998,
      author = {Culham, JC and Brandt, SA and Cavanagh, P and Kanwisher, NG and Dale, AM and Tootell, RBH},
      title = {Cortical fMRI activation produced by attentive tracking of moving targets},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {1998},
      volume = {80},
      number = {5},
      pages = {2657-2670}
    }
    
    Culham, J. & Kanwisher, N. Neuroimaging of cognitive functions in human parietal cortex {2001} CURRENT OPINION IN NEUROBIOLOGY
    Vol. {11}({2}), pp. {157-163} 
    article  
    Abstract: Functional neuroimaging has proven highly valuable in mapping human sensory regions, particularly visual areas in occipital cortex. Recent evidence suggests that human parietal cortex may also consist of numerous specialized subregions similar to those reported in neurophysiological studies of non-human primates. However, parietal activation generalizes across a wide variety of cognitive tasks and the extension of human brain mapping into higher-order `association cortex' may prove to be a challenge.
    BibTeX:
    @article{Culham2001,
      author = {Culham, JC and Kanwisher, NG},
      title = {Neuroimaging of cognitive functions in human parietal cortex},
      journal = {CURRENT OPINION IN NEUROBIOLOGY},
      year = {2001},
      volume = {11},
      number = {2},
      pages = {157-163}
    }
    
    Curtis, C. & D'Esposito, M. Persistent activity in the prefrontal cortex during working memory {2003} TRENDS IN COGNITIVE SCIENCES
    Vol. {7}({9}), pp. {415-423} 
    article DOI  
    Abstract: The dorsolateral prefrontal cortex (DLPFC) plays a crucial role in working memory. Notably, persistent activity in the DLPFC is often observed during the retention interval of delayed response tasks. The code carried by the persistent activity remains unclear, however. We critically evaluate how well recent findings from functional magnetic resonance imaging studies are compatible with current models of the role of the DLFPC in working memory. These new findings suggest that the DLPFC aids in the maintenance of information by directing attention to internal representations of sensory stimuli and motor plans that are stored in more posterior regions.
    BibTeX:
    @article{Curtis2003,
      author = {Curtis, CE and D'Esposito, M},
      title = {Persistent activity in the prefrontal cortex during working memory},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      year = {2003},
      volume = {7},
      number = {9},
      pages = {415-423},
      doi = {{10.1016/S1364-6613(03)00197-9}}
    }
    
    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}
    }
    
    D'Esposito, M., Postle, B. & Rypma, B. Prefrontal cortical contributions to working memory: evidence from event-related fMRI studies {2000} EXPERIMENTAL BRAIN RESEARCH
    Vol. {133}({1}), pp. {3-11} 
    article  
    Abstract: Working memory refers to the short-term retention of information that is no longer accessible in the environment, and the manipulation of this information, for subsequent use in guiding behavior. In this review, we will present data from a series of event-related functional magnetic-resonance-imaging (fMRI) studies of delayed-response tasks that were designed to investigate the role of different regions of the prefrontal cortex (PFC) during different working-memory component processes. From these data, we conclude that: (1) lateral PFC is anatomically organized according to the types of cognitive operations that one performs when attempting to temporarily maintain and manipulate information; and (2) consistent with the picture that has emerged from the monkey electrophysiological literature, human lateral PFC is involved in several encoding- and response-related processes as well as mnemonic and nonmnemonic processes that are engaged during the temporary maintenance of information. Thus, lateral PFC activity cannot be ascribed to the function of a single, unitary cognitive operation.
    BibTeX:
    @article{D'Esposito2000,
      author = {D'Esposito, M and Postle, BR and Rypma, B},
      title = {Prefrontal cortical contributions to working memory: evidence from event-related fMRI studies},
      journal = {EXPERIMENTAL BRAIN RESEARCH},
      year = {2000},
      volume = {133},
      number = {1},
      pages = {3-11},
      note = {Workshop on Executive Control and the Frontal Lobe, DELMENHORST, GERMANY, DEC 01-03, 1998}
    }
    
    Dalley, J., Cardinal, R. & Robbins, T. Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates {2004} NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
    Vol. {28}({7}), pp. {771-784} 
    article DOI  
    Abstract: The prefrontal cortex has been implicated in a variety of cognitive and executive processes, including working memory, decision-making, inhibitory response control, attentional set-shifting and the temporal integration of voluntary behaviour. This article reviews current progress in our understanding of the rodent prefrontal cortex, especially evidence for functional divergence of the anatomically distinct sub-regions of the rat prefrontal cortex. Recent findings suggest clear distinctions between the dorsal (precentral and anterior cingulate) and ventral (prelimbic, infralimbic and medial orbital) sub-divisions of the medial prefrontal cortex, and between the orbitofrontal cortex (ventral orbital, ventrolateral orbital, dorsal and ventral agranular cortices) and the adjacent medial wall of the prefrontal cortex. The dorso-medial prefrontal cortex is implicated in memory for motor responses, including response selection, and the temporal processing of information. Ventral regions of the medial prefrontal cortex are implicated in interrelated `supervisory' attentional functions, including attention to stimulus features and task contingencies (or action-outcome rules), attentional set-shifting, and behavioural flexibility. The orbitofrontal cortex is implicated in lower-order discriminations, including reversal of stimulus-reward associations (reversal learning), and choice involving delayed reinforcement. It is anticipated that a greater understanding of the prefrontal cortex will come from using tasks that load specific cognitive and executive processes, in parallel with discovering new ways of manipulating the different sub-regions and neuromodulatory systems of the prefrontal cortex. (C) 2004 Elsevier Ltd. All rights reserved.
    BibTeX:
    @article{Dalley2004,
      author = {Dalley, JW and Cardinal, RN and Robbins, TW},
      title = {Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates},
      journal = {NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS},
      year = {2004},
      volume = {28},
      number = {7},
      pages = {771-784},
      doi = {{10.1016/j.neubiorev.2004.09.006}}
    }
    
    DANEMAN, M. & CARPENTER, P. INDIVIDUAL-DIFFERENCES IN WORKING MEMORY AND READING {1980} JOURNAL OF VERBAL LEARNING AND VERBAL BEHAVIOR
    Vol. {19}({4}), pp. {450-466} 
    article  
    BibTeX:
    @article{DANEMAN1980,
      author = {DANEMAN, M and CARPENTER, PA},
      title = {INDIVIDUAL-DIFFERENCES IN WORKING MEMORY AND READING},
      journal = {JOURNAL OF VERBAL LEARNING AND VERBAL BEHAVIOR},
      year = {1980},
      volume = {19},
      number = {4},
      pages = {450-466}
    }
    
    Daneman, M. & Merikle, P. Working memory and language comprehension: A meta-analysis {1996} PSYCHONOMIC BULLETIN & REVIEW
    Vol. {3}({4}), pp. {422-433} 
    article  
    Abstract: This paper presents a meta-analysis of the data from 6,179 participants in 77 studies that investigated the association between working-memory capacity and language comprehension ability. A primary goal of the meta-analysis was to compare the predictive power of the measures of working memory developed by Daneman and Carpenter (1980) with the predictive power of other measures of working memory. The results of the meta-analysis support Daneman and Carpenter's (1980) claim that measures that tap the combined processing and storage capacity of working memory (e.g., reading span, listening span) are better predictors of comprehension than are measures that tap only the storage capacity (e.g., word span, digit span). The meta-analysis also showed that math process plus storage measures of working memory are good predictors of comprehension. Thus, the superior predictive pou er of the process plus storage measures is not Limited to measures that involve the manipulation of words and sentences.
    BibTeX:
    @article{Daneman1996,
      author = {Daneman, M and Merikle, PM},
      title = {Working memory and language comprehension: A meta-analysis},
      journal = {PSYCHONOMIC BULLETIN & REVIEW},
      year = {1996},
      volume = {3},
      number = {4},
      pages = {422-433}
    }
    
    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}
    }
    
    DECKER, M. & MCGAUGH, J. THE ROLE OF INTERACTIONS BETWEEN THE CHOLINERGIC SYSTEM AND OTHER NEUROMODULATORY SYSTEMS IN LEARNING AND MEMORY {1991} SYNAPSE
    Vol. {7}({2}), pp. {151-168} 
    article  
    Abstract: Extensive evidence indicates that disruption of cholinergic function is characteristic of aging and Alzheimer's disease (AD), and experimental manipulation of the cholinergic system in laboratory animals suggests age-related cholinergic dysfunction may play an important role in cognitive deterioration associated with aging and AD. Recent research, however, suggests that cholinergic dysfunction does not provide a complete account of age-related cognitive deficits and that age-related changes in cholinergic function typically occur within the context of changes in several other neuromodulatory systems. Evidence reviewed in this paper suggests that interactions between the cholinergic system and several of these neurotransmitters and neuromodulators-including norepinephrine, dopamine, serotonin, GABA, opioid peptides, galanin, substance P, and angiotensin II-may be important in learning and memory. Thus, it is important to consider not only the independent contributions of age-related changes in neuromodulatory systems to cognitive decline, but also the contribution of interactions between these systems to the learning and memory deficits associated with aging and AD.
    BibTeX:
    @article{DECKER1991,
      author = {DECKER, MW and MCGAUGH, JL},
      title = {THE ROLE OF INTERACTIONS BETWEEN THE CHOLINERGIC SYSTEM AND OTHER NEUROMODULATORY SYSTEMS IN LEARNING AND MEMORY},
      journal = {SYNAPSE},
      year = {1991},
      volume = {7},
      number = {2},
      pages = {151-168}
    }
    
    Dehaene, S., Kerszberg, M. & Changeux, J. A neuronal model of a global workspace in effortful cognitive tasks {1998} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {95}({24}), pp. {14529-14534} 
    article  
    Abstract: A minimal hypothesis is proposed concerning the brain processes underlying effortful tasks. It distinguishes two main computational spaces: a unique global workspace composed of distributed and heavily interconnected neurons with long-range axons, and a set of specialized and modular perceptual, motor, memory, evaluative, and attentional processors, Workspace neurons are mobilized in effortful tasks for which the specialized processors do not suffice. They selectively mobilize or suppress, through descending connections, the contribution of specific processor neurons. In the course of task performance, workspace neurons become spontaneously coactivated, forming discrete though variable spatio-temporal patterns subject to modulation by vigilance signals and to selection by reward signals. A computer simulation of the Stroop task shows workspace activation to increase during acquisition of a novel task, effortful execution, and after errors. We outline predictions for spatio-temporal activation patterns during brain imaging, particularly about the contribution of dorsolateral prefrontal cortex and anterior cingulate to the workspace.
    BibTeX:
    @article{Dehaene1998,
      author = {Dehaene, S and Kerszberg, M and Changeux, JP},
      title = {A neuronal model of a global workspace in effortful cognitive tasks},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1998},
      volume = {95},
      number = {24},
      pages = {14529-14534}
    }
    
    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}
    }
    
    Desimone, R. Visual attention mediated by biased competition in extrastriate visual cortex {1998} PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
    Vol. {353}({1373}), pp. {1245-1255} 
    article  
    Abstract: According to conventional neurobiological accounts of visual attention, attention serves to enhance extrastriate neuronal responses to a stimulus at one spatial location in the visual field. However, recent results from recordings in extrastriate cortex of monkeys suggest that any enhancing effect of attention is best understood in the context of competitive interactions among neurons representing all of the stimuli present in the visual field. These interactions can be biased in favour of behaviourally relevant stimuli as a result of many different processes, both spatial and non-spatial, and both bottom-up and top-down. The resolution of this competition results in the suppression of the neuronal representations of behaviourally irrelevant stimuli in extrastriate cortex. A main source of top-down influence may derive from neuronal systems underlying working memory.
    BibTeX:
    @article{Desimone1998,
      author = {Desimone, R},
      title = {Visual attention mediated by biased competition in extrastriate visual cortex},
      journal = {PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES},
      year = {1998},
      volume = {353},
      number = {1373},
      pages = {1245-1255}
    }
    
    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}
    }
    
    Desmond, J., Gabrieli, J., Wagner, A., Ginier, B. & Glover, G. Lobular patterns of cerebellar activation in verbal working-memory and finger-tapping tasks as revealed by functional MRI {1997} JOURNAL OF NEUROSCIENCE
    Vol. {17}({24}), pp. {9675-9685} 
    article  
    Abstract: The lobular distributions of functional activation of the cerebellum during verbal working-memory and finger movement tasks were investigated using functional magnetic resonance imaging (fMRI). Relative to a rest control, finger tapping of the right hand produced ipsilateral-increased activation in HIV/HV [Roman numeral designations based on Larsell's (Larsell and Jansen, 1972) nomenclature] and HVI and weaker activation in HVIII that was stronger on the ipsilateral side. For a working-memory task, subjects were asked to remember six (high load) or one (low load) visually presented letters across a brief delay. To assess the motoric aspects of rehearsal in the absence of working memory, we asked the subjects to repeatedly read subvocally six or one letters at a rate that approximated the internally generated rehearsal of working memory (motoric rehearsal task). For both tasks, bilateral regions of the superior cerebellar hemispheres (left superior HVIIA and right HVI) and portions of posterior vermis (VI and superior VIIA) exhibited increased activation during high relative to low load conditions. In contrast, the right inferior cerebellar hemisphere (HVIIB) exhibited this load effect only during the working-memory task. We hypothesize that HVI and superior HVIIA activation represents input from the articulatory control system of working memory from the frontal lobes and that HVIIB activation is derived from the phonological store in temporal and parietal regions. From these inputs, the cerebellum could compute the discrepancy between actual and intended phonological rehearsal and use this information to update a feedforward command to the frontal lobes, thereby facilitating the phonological loop.
    BibTeX:
    @article{Desmond1997,
      author = {Desmond, JE and Gabrieli, JDE and Wagner, AD and Ginier, BL and Glover, GH},
      title = {Lobular patterns of cerebellar activation in verbal working-memory and finger-tapping tasks as revealed by functional MRI},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1997},
      volume = {17},
      number = {24},
      pages = {9675-9685}
    }
    
    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}
    }
    
    Dias, R., Robbins, T. & Roberts, A. Dissociable forms of inhibitory control within prefrontal cortex with an analog of the Wisconsin Card Sort Test: Restriction to novel situations and independence from `'on-line'' processing {1997} JOURNAL OF NEUROSCIENCE
    Vol. {17}({23}), pp. {9285-9297} 
    article  
    Abstract: Attentional set-shifting and discrimination reversal are sensitive to prefrontal damage in the marmoset in a manner qualitatively similar to that seen in man and Old World monkeys, respectively (Dias et al., 1996b), Preliminary findings have demonstrated that although lateral but not orbital prefrontal cortex is the critical locus in shifting an attentional set between perceptual dimensions, orbital but not lateral prefrontal cortex is the critical locus in reversing a stimulus-reward association within a particular perceptual dimension (Dias et al., 1996a). The present study presents this analysis in full and extends the results in three main ways by demonstrating that (1) mechanisms of inhibitory control and `'on-line'' processing are independent within the prefrontal cortex, (2) impairments in inhibitory control induced by prefrontal damage are restricted to novel situations, and (3) those prefrontal areas involved in the suppression of previously established response sets are not involved in the acquisition of such response sets. These findings suggest that inhibitory control is a general process that operates across functionally distinct regions within the prefrontal cortex. Although damage to lateral prefrontal cortex causes a loss of inhibitory control in attentional selection, damage to orbitofrontal cortex causes a loss of inhibitory control in affective processing. These findings provide an explanation for the apparent discrepancy between human and nonhuman primate studies in which disinhibition as measured on the Wisconsin Card Sort Test is associated with dorsolateral prefrontal damage, whereas disinhibition as measured on discrimination reversal is associated with orbitofrontal damage.
    BibTeX:
    @article{Dias1997,
      author = {Dias, R and Robbins, TW and Roberts, AC},
      title = {Dissociable forms of inhibitory control within prefrontal cortex with an analog of the Wisconsin Card Sort Test: Restriction to novel situations and independence from `'on-line'' processing},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1997},
      volume = {17},
      number = {23},
      pages = {9285-9297}
    }
    
    Dove, A., Pollmann, S., Schubert, T., Wiggins, C. & von Cramon, D. Prefrontal cortex activation in task switching: an event-related fMRI study {2000} COGNITIVE BRAIN RESEARCH
    Vol. {9}({1}), pp. {103-109} 
    article  
    Abstract: When a switch between two tasks has to be carried out, performance is slower than in trials where the same task is performed repeatedly. This finding has been attributed to rime-consuming control processes required for task switching. Previous results of other paradigms investigating cognitive control processes suggested that prefrontal cortex is involved in executive control. We used event-related fMRI to investigate prefrontal cortex involvement in task switching. Regions in the lateral prefrontal and premotor cortex bilaterally, the anterior insula bilaterally, the left intraparietal sulcus, the SMA/pre-SMA region and the cuneus/precuneus were activated by the task repetition condition and showed additional activation in the task switch condition. This confirmed the hypothesis that lateral prefrontal cortex is involved in task switching. However, the results also showed that this region is neither the only region involved in task switching nor a region specifically involved in task switching. (C) 2000 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{Dove2000,
      author = {Dove, A and Pollmann, S and Schubert, T and Wiggins, CJ and von Cramon, DY},
      title = {Prefrontal cortex activation in task switching: an event-related fMRI study},
      journal = {COGNITIVE BRAIN RESEARCH},
      year = {2000},
      volume = {9},
      number = {1},
      pages = {103-109}
    }
    
    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}
    }
    
    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}
    }
    
    Duncan, J. An adaptive coding model of neural function in prefrontal cortex {2001} NATURE REVIEWS NEUROSCIENCE
    Vol. {2}({11}), pp. {820-829} 
    article  
    Abstract: The prefrontal cortex has a vital role in effective, organized behaviour, Both functional neuroimaging in humans and electrophysiology in awake monkeys indicate that a fundamental principle of prefrontal function might be adaptive neural coding - in large regions of the prefrontal cortex, neurons adapt their properties to carry specifically information that is relevant to current concerns, producing a dense, distributed representation of related inputs, actions, rewards and other information. A model based on such adaptive coding integrates the role of the prefrontal cortex in working memory attention and control. Adaptive coding points to new perspectives on several basic questions, including mapping of cognitive to neurophysiological functions, the influences of task content and difficulty; and the nature of frontal lobe specializations.
    BibTeX:
    @article{Duncan2001,
      author = {Duncan, J},
      title = {An adaptive coding model of neural function in prefrontal cortex},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2001},
      volume = {2},
      number = {11},
      pages = {820-829}
    }
    
    Duncan, J., Emslie, H., Williams, P., Johnson, R. & Freer, C. Intelligence and the frontal lobe: The organization of goal-directed behavior {1996} COGNITIVE PSYCHOLOGY
    Vol. {30}({3}), pp. {257-303} 
    article  
    Abstract: Basic to the study of individual differences is the concept of `'general intelligence'' or Spearman's g. In this article we suggest that g is largely a reflection of the control functions of the frontal lobe. A series of experiments investigates a phenomenon we call goal neglect: disregard of a task requirement even though it has been understood and remembered. Subjectively it is as though the neglected requirement `'slips the subject's mind.'' Previously described in frontal patients, we show that goal neglect can also be seen in some members of the normal population. In line with conventional distinctions between controlled and automatic processing, eliciting conditions for goal neglect include novelty, weak error feedback, and multiple concurrent task requirements. Under these conditions neglect is linked closely to g and extremely common after frontal lesions. Following many other models, we suggest that behavior in any task is structured by a set of action constraints or requirements, derived in part from verbal instructions and specified at multiple levels of abstraction. A frontal process of constraint or requirement activation is fundamental to Spearman's g. (C) 1996 Academic Press, Inc.
    BibTeX:
    @article{Duncan1996,
      author = {Duncan, J and Emslie, H and Williams, P and Johnson, R and Freer, C},
      title = {Intelligence and the frontal lobe: The organization of goal-directed behavior},
      journal = {COGNITIVE PSYCHOLOGY},
      year = {1996},
      volume = {30},
      number = {3},
      pages = {257-303}
    }
    
    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}
    }
    
    Durmer, J. & Dinges, D. Neurocognitive consequences of sleep deprivation {2005} SEMINARS IN NEUROLOGY
    Vol. {25}({1}), pp. {117-129} 
    article  
    Abstract: Deficits in daytime performance due to sleep loss are experienced universally and associated with a significant social, financial, and human cost. Microsleeps, sleep attacks, and lapses in cognition increase with sleep loss as a function of state instability. Sleep deprivation studies repeatedly show a variable (negative) impact on mood, cognitive performance, and motor function due to an increasing sleep propensity and destabilization of the wake state. Specific neurocognitive domains including executive attention, working memory, and divergent higher cognitive functions are particularly vulnerable to sleep loss. In humans, functional metabolic and neurophysiological studies demonstrate that neural systems involved in executive function (i.e., prefrontal cortex) are more susceptible to sleep deprivation in some individuals than others. Recent chronic partial sleep deprivation experiments, which more closely replicate sleep loss in society, demonstrate that profound neurocognitive deficits accumulate over time in the face of subjective adaptation to the sensation of sleepiness. Sleep deprivation associated with disease-related sleep fragmentation (i.e., sleep apnea and restless legs syndrome) also results in neurocognitive performance decrements similar to those seen in sleep restriction studies. Performance deficits associated with sleep disorders are often viewed as a simple function of disease severity; however, recent experiments suggest that individual vulnerability to sleep loss may play a more critical role than previously thought.
    BibTeX:
    @article{Durmer2005,
      author = {Durmer, JS and Dinges, DF},
      title = {Neurocognitive consequences of sleep deprivation},
      journal = {SEMINARS IN NEUROLOGY},
      year = {2005},
      volume = {25},
      number = {1},
      pages = {117-129}
    }
    
    Durstewitz, D., Seamans, J. & Sejnowski, T. Dopamine-mediated stabilization of delay-period activity in a network model of prefrontal cortex {2000} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {83}({3}), pp. {1733-1750} 
    article  
    Abstract: The prefrontal cortex (PFC) is critically involved in working memory, which underlies memory-guided, goal-directed behavior. During working-memory tasks, PFC neurons exhibit sustained. elevated activity, which may reflect the active holding of goal-related. information or the preparation of forthcoming actions. Dopamine via the D1 receptor strongly modulates both this sustained (delay-period) activity and behavioral performance in working-memory tasks. However, the function of dopamine during delay-period activity and the underlying neural mechanisms are only poorly understood. Recently we proposed that dopamine might stabilize active neural representations in PFC circuits during tasks involving working memory and render them robust against interfering stimuli and noise. To further test this idea and to examine the dopamine-modulated ionic currents that could give rise to increased stability of neural representations, we developed a network model of the PFC consisting of multicompartment neurons equipped with Hodgkin-Huxley-like channel kinetics that could reproduce in vitro whole cell and in vivo recordings from PFC neurons. Dopaminergic effects on intrinsic ionic and synaptic conductances were implemented in the model based on in vitro data. Simulated dopamine strongly enhanced high, delay-type activity but not low, spontaneous activity in the model network. Furthermore the strength of an afferent stimulation needed to disrupt delay-type activity increased with the magnitude of the dopamine-induced shifts in network parameters, making the currently active representation much more stable. Stability could be increased by dopamine-induced enhancements of the persistent Na+ and N-methyl-D-aspartate (NMDA) conductances. Stability also was enhanced by a reduction in AMPA conductances. The increase in GABA, conductances that occurs after stimulation of dopaminergic D1 receptors was necessary in this context to prevent uncontrolled, spontaneous switches into high-activity states (i.e., spontaneous activation of task-irrelevant representations). In conclusion, the dopamine-induced changes in the biophysical properties of intrinsic ionic and synaptic conductances conjointly acted to highly increase stability of activated representations in PFC networks and at the same time retain control over network behavior and thus preserve its ability to adequately respond to task-related stimuli. Predictions of the model can be tested in vivo by locally applying specific D1 receptor, NMDA, or GABA, antagonists while recording from PFC neurons in delayed reaction-type tasks with interfering stimuli.
    BibTeX:
    @article{Durstewitz2000,
      author = {Durstewitz, D and Seamans, JK and Sejnowski, TJ},
      title = {Dopamine-mediated stabilization of delay-period activity in a network model of prefrontal cortex},
      journal = {JOURNAL OF NEUROPHYSIOLOGY},
      year = {2000},
      volume = {83},
      number = {3},
      pages = {1733-1750}
    }
    
    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}
    }
    
    Egan, M., Kojima, M., Callicott, J., Goldberg, T., Kolachana, B., Bertolino, A., Zaitsev, E., Gold, B., Goldman, D., Dean, M., Lu, B. & Weinberger, D. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function {2003} CELL
    Vol. {112}({2}), pp. {257-269} 
    article  
    Abstract: Brain-derived neurotrophic factor (BDNF) modulates hippocampal plasticity and hippocampal-dependent memory in cell models and in animals. We examined the effects of a valine (val) to methionine (met) substitution in the 5' pro-region of the human BDNF protein. In human subjects, the met allele was associated with poorer episodic memory, abnormal hippocampal activation assayed with fMRI, and lower hippocampal n-acetyl aspartate (NAA), assayed with MRI spectroscopy. Neurons transfected with met-BDNF-GFP showed lower depolarization-induced secretion, while constitutive secretion was unchanged. Furthermore, met-BDNF-GFP failed to localize to secretory granules or synapses. These results demonstrate a role for BDNF
    BibTeX:
    @article{Egan2003,
      author = {Egan, MF and Kojima, M and Callicott, JH and Goldberg, TE and Kolachana, BS and Bertolino, A and Zaitsev, E and Gold, B and Goldman, D and Dean, M and Lu, B and Weinberger, DR},
      title = {The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function},
      journal = {CELL},
      year = {2003},
      volume = {112},
      number = {2},
      pages = {257-269}
    }
    
    Egorov, A., Hamam, B., Fransen, E., Hasselmo, M. & Alonso, A. Graded persistent activity in entorhinal cortex neurons {2002} NATURE
    Vol. {420}({6912}), pp. {173-178} 
    article  
    Abstract: Working memory represents the ability of the brain to hold externally or internally driven information for relatively short periods of time(1,2). Persistent neuronal activity is the elementary process underlying working memory but its cellular basis remains unknown. The most widely accepted hypothesis is that persistent activity is based on synaptic reverberations in recurrent circuits. The entorhinal cortex in the parahippocampal region is crucially involved in the acquisition, consolidation and retrieval of long-term memory traces for which working memory operations are essential(2). Here we show that individual neurons from layer V of the entorhinal cortex-which link the hippocampus to extensive cortical regions(3)-respond to consecutive stimuli with graded changes in firing frequency that remain stable after each stimulus presentation. In addition, the sustained levels of firing frequency can be either increased or decreased in an input-specific manner. This firing behaviour displays robustness to distractors; it is linked to cholinergic muscarinic receptor activation, and relies on activity-dependent changes of a Ca2+-sensitive cationic current. Such an intrinsic neuronal ability to generate graded persistent activity constitutes an elementary mechanism for working memory.
    BibTeX:
    @article{Egorov2002,
      author = {Egorov, AV and Hamam, BN and Fransen, E and Hasselmo, ME and Alonso, AA},
      title = {Graded persistent activity in entorhinal cortex neurons},
      journal = {NATURE},
      year = {2002},
      volume = {420},
      number = {6912},
      pages = {173-178}
    }
    
    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}
    }
    
    Elliott, R., Sahakian, B., McKay, A., Herrod, J., Robbins, T. & Paykel, E. Neuropsychological impairments in unipolar depression: The influence of perceived failure on subsequent performance {1996} PSYCHOLOGICAL MEDICINE
    Vol. {26}({5}), pp. {975-989} 
    article  
    Abstract: The CANTAB battery of neuropsychological tests was used to compare the performance of 28 patients with unipolar depression with that of 22 age and IQ matched controls. The patients were impaired on almost all tests studied with deficits in pattern and spatial recognition memory, matching to sample, spatial span, spatial working memory and planning. Most of the patients showed at least some impairment and deficits were seen across cognitive domains. An important finding was the detrimental effect of failure on subsequent performance; having solved one problem incorrectly, patients were far more likely than controls to fail the subsequent problem. Superimposed on the general deficits, there were also specific deficits in executive tasks characteristic of frontostriatal dysfunction and deficits in mnemonic tasks characteristic of temporal lobe dysfunction. This combination of a specific form of motivational deficit, resulting in oversensitivity to negative feedback, and superimposed specific neuropsychological deficits were correlated with severity of depression. The most significant correlations were seen between mnemonic deficits and clinical rating scores. Comparisons of the deficits seen in the depressed patients in this study with other patient groups assessed with the CANTAB neuropsychological battery, showed that one of the hypotheses of the neuropsychological deficits in depression, that of `frontosubcortical' or `frontostriatal' dysfunction, was not supported. These findings are discussed in relation to the likely neural substrates of depression.
    BibTeX:
    @article{Elliott1996,
      author = {Elliott, R and Sahakian, BJ and McKay, AP and Herrod, JJ and Robbins, TW and Paykel, ES},
      title = {Neuropsychological impairments in unipolar depression: The influence of perceived failure on subsequent performance},
      journal = {PSYCHOLOGICAL MEDICINE},
      year = {1996},
      volume = {26},
      number = {5},
      pages = {975-989}
    }
    
    ELMAN, J. LEARNING AND DEVELOPMENT IN NEURAL NETWORKS - THE IMPORTANCE OF STARTING SMALL {1993} COGNITION
    Vol. {48}({1}), pp. {71-99} 
    article  
    Abstract: It is a striking fact that in humans the greatest learning occurs precisely at that point in time - childhood - when the most dramatic maturational changes also occur. This report describes possible synergistic interactions between maturational change and the ability to learn a complex domain (language), as investigated in connectionist networks. The networks are trained to process complex sentences involving relative clauses, number agreement, and several types of verb argument structure. Training fails in the case of networks which are fully formed and `adultlike' in their capacity. Training succeeds only when networks begin with limited working memory and gradually `mature' to the adult state. This result suggests that rather than being a limitation, developmental restrictions on resources may constitute a necessary prerequisite for mastering certain complex domains. Specifically, successful learning may depend on starting small.
    BibTeX:
    @article{ELMAN1993,
      author = {ELMAN, JL},
      title = {LEARNING AND DEVELOPMENT IN NEURAL NETWORKS - THE IMPORTANCE OF STARTING SMALL},
      journal = {COGNITION},
      year = {1993},
      volume = {48},
      number = {1},
      pages = {71-99}
    }
    
    Elvevag, B. & Goldberg, T. Cognitive impairment in schizophrenia is the core of the disorder {2000} CRITICAL REVIEWS IN NEUROBIOLOGY
    Vol. {14}({1}), pp. {1-21} 
    article  
    Abstract: Patients with schizophrenia exhibit an exceedingly wide range of symptoms from a variety of domains. The cardinal features are abnormal ideas (such as delusions); abnormal perceptions (such as hallucinations); formal thought disorder (as evidenced by disorganized speech); motor, volitional, and behavioral disorders; and emotional disorders (such as affective flattening or inappropriateness). In addition to these diverse, and sometimes bizarre symptoms, it has become increasingly apparent that the disorder is, to variable degrees, accompanied by a broad spectrum of cognitive impairments. This review addresses the question of whether the cognitive deficits seen in schizophrenic patients are the core features of the disorder. In other words, we explore whether schizophrenia is best characterized by symptoms or cognitive deficits (we suggest the latter) and moreover, whether there is a specific cognitive deficit profile that may assist in diagnosis. First, we discuss what the cognitive deficits are. Then we address in turn the reality, frequency, predictive validity, specificity, course and susceptibility to neuroleptic effects of these cognitive impairments. In brief, we argue that various cognitive deficits are enduring features of the schizophrenia illness, that they are not state-related and are not specific to subtypes of the illness, and, more specifically, that working memory and attention are characteristically impaired in patients with schizophrenia, irrespective of their level of intelligence. Last, we conclude that problems in these cognitive domains are at the very core of the dysfunction in this disease.
    BibTeX:
    @article{Elvevag2000,
      author = {Elvevag, B and Goldberg, TE},
      title = {Cognitive impairment in schizophrenia is the core of the disorder},
      journal = {CRITICAL REVIEWS IN NEUROBIOLOGY},
      year = {2000},
      volume = {14},
      number = {1},
      pages = {1-21}
    }
    
    ENDSLEY, M. TOWARD A THEORY OF SITUATION AWARENESS IN DYNAMIC-SYSTEMS {1995} HUMAN FACTORS
    Vol. {37}({1}), pp. {32-64} 
    article  
    Abstract: This paper presents a theoretical model of situation awareness based on its role in dynamic human decision making in a variety of domains. Situation awareness is presented as a predominant concern in system operation, based on a descriptive view of decision making. The relationship between situation awareness and numerous individual and environmental factors is explored. Among these factors, attention and working memory are presented as critical factors limiting operators from acquiring and interpreting information from the environment to form situation awareness, and mental models and goal-directed behavior are hypothesized as important mechanisms for overcoming these limits. The impact of design features, workload, stress, system complexity, and automation on operator situation awareness is addressed, and a taxonomy of errors in situation awareness is introduced, based on the model presented. The model is used to generate design implications for enhancing operator situation awareness and future directions for situation awareness research.
    BibTeX:
    @article{ENDSLEY1995,
      author = {ENDSLEY, MR},
      title = {TOWARD A THEORY OF SITUATION AWARENESS IN DYNAMIC-SYSTEMS},
      journal = {HUMAN FACTORS},
      year = {1995},
      volume = {37},
      number = {1},
      pages = {32-64}
    }
    
    Engel, A. & Singer, W. Temporal binding and the neural correlates of sensory awareness {2001} TRENDS IN COGNITIVE SCIENCES
    Vol. {5}({1}), pp. {16-25} 
    article  
    Abstract: Theories of binding have recently come into the focus of the consciousness debate. In this review, we discuss the potential relevance of temporal binding mechanisms for sensory awareness. Specifically, we suggest that neural synchrony with a precision in the millisecond range may be crucial for conscious processing, and may be involved in arousal, perceptual integration, attentional selection and working memory. Recent evidence from both animal and human studies demonstrates that specific changes in neuronal synchrony occur during all of these processes and that they are distinguished by the emergence of fast oscillations with frequencies in the gamma-range.
    BibTeX:
    @article{Engel2001,
      author = {Engel, AK and Singer, W},
      title = {Temporal binding and the neural correlates of sensory awareness},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      year = {2001},
      volume = {5},
      number = {1},
      pages = {16-25}
    }
    
    Engle, R. Working memory capacity as executive attention {2002} CURRENT DIRECTIONS IN PSYCHOLOGICAL SCIENCE
    Vol. {11}({1}), pp. {19-23} 
    article  
    Abstract: Performance on measures of working memory (WM) capacity predicts performance on a wide range of real-world cognitive tasks. I review the idea ,that WM capacity (a) is separable from short-term memory, (b) is an important component of general fluid intelligence, and (c) represents a domain-free limitation in ability to control attention. Studies show that individual differences in WM capacity are reflected in performance on antisaccade, Stroop, and dichotic-listening WM capacity, or executive attention, is most important under conditions in which interference leads to retrieval of response tendencies that conflict with the current task.
    BibTeX:
    @article{Engle2002,
      author = {Engle, RW},
      title = {Working memory capacity as executive attention},
      journal = {CURRENT DIRECTIONS IN PSYCHOLOGICAL SCIENCE},
      year = {2002},
      volume = {11},
      number = {1},
      pages = {19-23}
    }
    
    ENGLE, R., CANTOR, J. & CARULLO, J. INDIVIDUAL-DIFFERENCES IN WORKING MEMORY AND COMPREHENSION - A TEST OF 4 HYPOTHESES {1992} JOURNAL OF EXPERIMENTAL PSYCHOLOGY-LEARNING MEMORY AND COGNITION
    Vol. {18}({5}), pp. {972-992} 
    article  
    Abstract: A relationship has consistently been found between measures of working memory and reading comprehension. Four hypotheses for this relationship were tested in 3 experiments. In the first 2 experiments, a moving window procedure was used to present the operation-word and reading span tasks. High- and low-span subjects did not differentially trade off time on the elements of the tasks and the to-be-remembered word. Furthermore, the correlation between span and comprehension was undiminished when the viewing times were partialed out. Experiment 3 compared a traditional experimenter-paced simple word-span and a subject-paced span in their relationship with comprehension. The experimenter-paced word-span correlated with comprehension but the subject-paced span did not. The results of all 3 experiments support a general capacity explanation for the relationship between working memory and comprehension.
    BibTeX:
    @article{ENGLE1992,
      author = {ENGLE, RW and CANTOR, J and CARULLO, JJ},
      title = {INDIVIDUAL-DIFFERENCES IN WORKING MEMORY AND COMPREHENSION - A TEST OF 4 HYPOTHESES},
      journal = {JOURNAL OF EXPERIMENTAL PSYCHOLOGY-LEARNING MEMORY AND COGNITION},
      year = {1992},
      volume = {18},
      number = {5},
      pages = {972-992}
    }
    
    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}
    }
    
    Ennaceur, A., Neave, N. & Aggleton, J. Spontaneous object recognition and object location memory in rats: The effects of lesions in the cingulate cortices, the medial prefrontal cortex, the cingulum bundle and the fornix {1997} EXPERIMENTAL BRAIN RESEARCH
    Vol. {113}({3}), pp. {509-519} 
    article  
    Abstract: The first experiment assessed the effects of neurotoxic lesions in either the anterior cingulate cortex (ACc) or the retrosplenial cortex (RSc) on a test of object recognition. Neither lesion affected performance on this task, which takes advantage of the rat's normal preference to spend more time investigating novel rather than familiar stimuli. In response to this negative result, a second experiment assessed the effects of much more extensive cingulate lesions (Cg) on both object recognition and object location memory. The latter task also used a preference measure, but in this case it concerned preference for a novel location. For comparison purposes this second study included groups of rats with lesions in closely allied regions: the fornix (Fx), the cingulum bundle (CB) and the medial prefrontal cortex (Pfc). Comparisons with sham-operated control rats showed that none of the four groups (Cg, Fx, CB, Pfc) was impaired on the object recognition task, adding further weight to the view that these structures are not necessary for assessing stimulus familiarity. The Fx and Cg groups were, however, impaired on the object location task, suggesting that these regions are necessary for remembering other attributes of a stimulus (spatial location).
    BibTeX:
    @article{Ennaceur1997,
      author = {Ennaceur, A and Neave, N and Aggleton, JP},
      title = {Spontaneous object recognition and object location memory in rats: The effects of lesions in the cingulate cortices, the medial prefrontal cortex, the cingulum bundle and the fornix},
      journal = {EXPERIMENTAL BRAIN RESEARCH},
      year = {1997},
      volume = {113},
      number = {3},
      pages = {509-519}
    }
    
    ERICSSON, K. & CHARNESS, N. EXPERT PERFORMANCE - ITS STRUCTURE AND ACQUISITION {1994} AMERICAN PSYCHOLOGIST
    Vol. {49}({8}), pp. {725-747} 
    article  
    Abstract: Counter to the common belief that expert performance reflects innate abilities and capacities, recent research in different domains of expertise has shown that expert performance is predominantly mediated by acquired complex skills and physiological adaptations. For elite performers, supervised practice starts at very young ages and is maintained at high daily levels for more than a decade. The effects of extended deliberate practice are more far-reaching than is commonly believed. Performers can acquire skills that circumvent basic limits on working memory capacity and sequential processing. Deliberate practice can also lead to anatomical changes resulting from adaptations to intense physical activity. The study of expert performance has important implications for our understanding of the structure and limits of human adaptation and optimal learning.
    BibTeX:
    @article{ERICSSON1994,
      author = {ERICSSON, KA and CHARNESS, N},
      title = {EXPERT PERFORMANCE - ITS STRUCTURE AND ACQUISITION},
      journal = {AMERICAN PSYCHOLOGIST},
      year = {1994},
      volume = {49},
      number = {8},
      pages = {725-747}
    }
    
    ERICSSON, K. & KINTSCH, W. LONG-TERM WORKING-MEMORY {1995} PSYCHOLOGICAL REVIEW
    Vol. {102}({2}), pp. {211-245} 
    article  
    Abstract: To account for the large demands on working memory during text comprehension and expert performance, the traditional models of working memory involving temporary storage must be extended to include working memory based on storage in long-term memory. In the proposed theoretical framework cognitive processes are viewed as a sequence of stable states representing end products of processing. In skilled activities, acquired memory skills allow these end products to be stored in longterm memory and kept directly accessible by means of retrieval cues in short-term memory, as proposed by skilled memory theory. These theoretical claims are supported by a review of evidence on memory in text comprehension and expert performance in such domains as mental calculation, medical diagnosis, and chess.
    BibTeX:
    @article{ERICSSON1995,
      author = {ERICSSON, KA and KINTSCH, W},
      title = {LONG-TERM WORKING-MEMORY},
      journal = {PSYCHOLOGICAL REVIEW},
      year = {1995},
      volume = {102},
      number = {2},
      pages = {211-245}
    }
    
    Ericsson, K. & Lehmann, A. Expert and exceptional performance: Evidence of maximal adaptation to task constraints {1996} ANNUAL REVIEW OF PSYCHOLOGY
    Vol. {47}, pp. {273-305} 
    article  
    Abstract: Expert and exceptional performance are shown to be mediated by cognitive and perceptual-motor skills and by domain-specific physiological and anatomical adaptations. The highest levels of human performance in different domains can only be attained after around ten years of extended, daily amounts of deliberate practice activities. Laboratory analyses of expert performance in many domains such as chess, medicine, auditing, computer programming, bridge, physics, sports, typing, juggling, dance, and music reveal maximal adaptations of experts to domain-specific constraints. For example, acquired anticipatory skills circumvent general limits on reaction time, and distinctive memory skills allow a domain-specific expansion of working memory capacity to support planning, reasoning, and evaluation. Many of the mechanisms of superior expert performance serve the dual purpose of mediating experts' current performance and of allowing continued improvement of this performance in response to informative feedback during practice activities.
    BibTeX:
    @article{Ericsson1996,
      author = {Ericsson, KA and Lehmann, AC},
      title = {Expert and exceptional performance: Evidence of maximal adaptation to task constraints},
      journal = {ANNUAL REVIEW OF PSYCHOLOGY},
      year = {1996},
      volume = {47},
      pages = {273-305}
    }
    
    Everitt, B. & Robbins, T. Central cholinergic systems and cognition {1997} ANNUAL REVIEW OF PSYCHOLOGY
    Vol. {48}, pp. {649-684} 
    article  
    Abstract: The organization and possible functions of basal forebrain and pontine cholinergic systems are reviewed. Whereas the basal forebrain cholinergic neuronal projections likely subserve a common electrophysiological function, e.g. to boost signal-to-noise ratios in cortical target areas, this function has different effects on psychological processes dependent upon the neural network operations within these various cortical domains. Evidence is presented that (a) the nucleus basalis-neocortical cholinergic system contributes greatly to visual attentional function, but not to mnemonic processes per se; (b) the septohippocampal projection is involved in the modulation of short-term spatial (working) memory processes, perhaps by prolonging the neural representation of external stimuli within the hippocampus; and (c) the diagonal band-cingulate cortex cholinergic projection impacts on the ability to utilize response rules through conditional discrimination. We also suggest that nucleus basalis-amygdala cholinergic projections have a role in the retention of affective conditioning while brainstem cholinergic projections to the thalamus and midbrain dopamine neurons affect basic arousal processes (e.g. sleep-wake cycle) and behavioral activation, respectively. The possibilities and limitations of therapeutic interventions with procholinergic drugs in patients with Alzheimer's disease and other neurodegenerative disorders in which basal forebrain cholinergic neurons degenerate are also discussed.
    BibTeX:
    @article{Everitt1997,
      author = {Everitt, BJ and Robbins, TW},
      title = {Central cholinergic systems and cognition},
      journal = {ANNUAL REVIEW OF PSYCHOLOGY},
      year = {1997},
      volume = {48},
      pages = {649-684}
    }
    
    EYSENCK, M. & CALVO, M. ANXIETY AND PERFORMANCE - THE PROCESSING EFFICIENCY THEORY {1992} COGNITION & EMOTION
    Vol. {6}({6}), pp. {409-434} 
    article  
    Abstract: Anxiety often impairs performance of ``difficult'' tasks (especially under test conditions), but there are numerous exceptions. Theories of anxiety and performance need to address at least two major issues: (1) the complexity and apparent inconsistency of the findings; and (2) the conceptual definition of task difficulty. Some theorists (e.g. Humphreys & Revelle, 1984; Sarason, 1988) argue that anxiety causes worry, and worry always impairs performance on tasks with high attentional or short-term memory demands. According to the processing efficiency theory, worry has two main effects: (1) a reduction in the storage and processing capacity of the working memory system available for a concurrent task; and (2) an increment in on-task effort and activities designed to improve performance. There is a crucial distinction within the theory between performance effectiveness (= quality of performance) and processing efficiency (= performance effectiveness divided by effort). Anxiety characteristically impairs efficiency more than effectiveness.
    BibTeX:
    @article{EYSENCK1992,
      author = {EYSENCK, MW and CALVO, MG},
      title = {ANXIETY AND PERFORMANCE - THE PROCESSING EFFICIENCY THEORY},
      journal = {COGNITION & EMOTION},
      year = {1992},
      volume = {6},
      number = {6},
      pages = {409-434}
    }
    
    Faraone, S. & Biederman, J. Neurobiology of attention-deficit hyperactivity disorder {1998} BIOLOGICAL PSYCHIATRY
    Vol. {44}({10}), pp. {951-958} 
    article  
    Abstract: Attention-deficit hyperactivity disorder (ADHD) is an early-onset clinically heterogeneous disorder of inattention, hyperactivity, and impulsivity. Family, twin, adoption, segregation analysis, and molecular genetic studies show that is has a substantial genetic component. Although their results are still tentative, molecular genetic studies suggest that three genes may increase the susceptibility to ADHD: the D4 dopamine receptor gene, the dopamine transporter gene, and the D2 dopamine receptor gene. Studies of environmental adversity have implicated pregnancy and delivery complications, marital distress, family dysfunction, and low social class. The pattern of neuropsychological deficits found in ADHD children implicate executive functions and working memory; this pattern is similar to what has been found among adults with frontal lobe damage, which suggests that the frontal cortex or regions projecting to the frontal cortex are dysfunctional in at least some ADHD children. Moreover neuroimaging studies implicate frontosubcortical pathways in ADHD. Notably, these pathways are rich in catecholamines, which have been implicated in ADHD by the mechanism of action of stimulants-the class of drugs that effectively treats many ADHD children. Yet human studies of the catecholamine hypothesis of ADHD have produced conflicting results, perhaps due to the insensitivity of peripheral measures. (C) 1998 Society of Biological Psychiatry.
    BibTeX:
    @article{Faraone1998,
      author = {Faraone, SV and Biederman, J},
      title = {Neurobiology of attention-deficit hyperactivity disorder},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {1998},
      volume = {44},
      number = {10},
      pages = {951-958}
    }
    
    Ferrier, I., Stanton, B., Kelly, T. & Scott, J. Neuropsychological function in euthymic patients with bipolar disorder {1999} BRITISH JOURNAL OF PSYCHIATRY
    Vol. {175}, pp. {246-251} 
    article  
    Abstract: Background The assumption that patients with bipolar disorder make a full inter-episode recovery has been challenged by limited evidence that suggests that neuropsychological dysfunction in bipolar disorder may persist beyond episodes of illness. Aims To test the hypothesis that patients with euthymic bipolar disorder show neuropsychological impairment. Method A battery of neuropsychological tests (assessed attention, working memory, learning and executive function) was administered to three matched groups of subjects: good-outcome patients with bipolar disorder (n=21); poor-outcome patients with bipolar disorder (n=20); controls (n=20). All patients were clinically euthymic, although some had low levels of depressive symptoms. Results Patients performed worse than controls on a number of neuropsychological tests. When age, premorbid IQ and depressive symptoms were controlled for, the results indicated impairment of executive function. Conclusions These findings provide good evidence for the existence of neuropsychological impairment in patients with euthymic bipolar disorder, although the possible effect of medication should not be overlooked. This may be of clinical relevance and raises questions about the course and outcome of the illness. Declaration of interest None.
    BibTeX:
    @article{Ferrier1999,
      author = {Ferrier, IN and Stanton, BR and Kelly, TP and Scott, J},
      title = {Neuropsychological function in euthymic patients with bipolar disorder},
      journal = {BRITISH JOURNAL OF PSYCHIATRY},
      year = {1999},
      volume = {175},
      pages = {246-251}
    }
    
    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}
    }
    
    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}
    }
    
    de Fockert, J., Rees, G., Frith, C. & Lavie, N. The role of working memory in visual selective attention {2001} SCIENCE
    Vol. {291}({5509}), pp. {1803-1806} 
    article  
    Abstract: The hypothesis that working memory is crucial for reducing distraction by maintaining the prioritization of relevant information was tested in neuroimaging and psychological experiments with humans. Participants performed a selective attention task that required them to ignore distracter faces while holding in working memory a sequence of digits that were in the same order (Low memory Load) or a different order thigh memory Load) on every trial. Higher memory Load, associated with increased prefrontal activity, resulted in greater interference effects on behavioral performance from the distracter faces, plus increased face-related activity in the visual cortex. These findings confirm a major role for working memory in the control of visual selective attention.
    BibTeX:
    @article{Fockert2001,
      author = {de Fockert, JW and Rees, G and Frith, CD and Lavie, N},
      title = {The role of working memory in visual selective attention},
      journal = {SCIENCE},
      year = {2001},
      volume = {291},
      number = {5509},
      pages = {1803-1806}
    }
    
    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}}
    }
    
    Friederici, A., Ruschemeyer, S., Hahne, A. & Fiebach, C. The role of left inferior frontal and superior temporal cortex in sentence comprehension: Localizing syntactic and semantic processes {2003} CEREBRAL CORTEX
    Vol. {13}({2}), pp. {170-177} 
    article  
    Abstract: An event-related functional magnetic resonance imaging (fMRI) paradigm was used to specify those brain areas supporting the processing of sentence-level semantic and syntactic information. Hemodynamic responses were recorded while participants listened to correct, semantically incorrect and syntactically incorrect sentences. Both anomalous conditions recruited larger portions of the superior temporal region than correct sentences. Processing of semantic violations relied primarily on the mid-portion of the superior temporal region bilaterally and the insular cortex bilaterally, whereas processing of syntactic violations specifically involved the anterior portion of the left superior temporal gyrus, the left posterior frontal operculum adjacent to Broca's area and the putamen in the left basal ganglia. A comparison of the two anomalous conditions revealed higher levels of activation for the syntactic over the semantic condition in the left basal ganglia and for the semantic over the syntactic condition in the mid-portion of the superior temporal gyrus, bilaterally. These data indicate that both semantic and syntactic processes are supported by a temporo-frontal network with distinct areas specialized for semantic and syntactic processes.
    BibTeX:
    @article{Friederici2003,
      author = {Friederici, AD and Ruschemeyer, SA and Hahne, A and Fiebach, CJ},
      title = {The role of left inferior frontal and superior temporal cortex in sentence comprehension: Localizing syntactic and semantic processes},
      journal = {CEREBRAL CORTEX},
      year = {2003},
      volume = {13},
      number = {2},
      pages = {170-177}
    }
    
    FRIEDMAN, H. & GOLDMANRAKIC, P. COACTIVATION OF PREFRONTAL CORTEX AND INFERIOR PARIETAL CORTEX IN WORKING-MEMORY TASKS REVEALED BY 2DG FUNCTIONAL MAPPING IN THE RHESUS-MONKEY {1994} JOURNAL OF NEUROSCIENCE
    Vol. {14}({5, Part 1}), pp. {2775-2788} 
    article  
    Abstract: Functional studies of the dorsolateral prefrontal cortex and the inferior parietal lobe of the rhesus monkey have implicated the former in spatial mnemonic function and the latter in visuospatial processing. We used the C-14-2-deoxyglucose (2DG) method to assess the contribution of these cortical regions to the cognitive performance of monkeys on working memory tasks. In these experiments, one group of monkeys (WORK) was trained to perform tasks (delayed spatial alternation, spatial delayed response, or delayed object alternation) that specifically engaged working memory processing. Local cerebral glucose utilization (LCGU) rates in the WORK group was compared with LCGU rates for a second group of monkeys (CONT) tested on one of two tasks (visual pattern discrimination or sensory-motor) that relied upon associative memory. The results showed that in comparison to the CONT group, working memory performance significantly enhanced LCGU by 19% in the principal sulcus region of prefrontal cortex and by 11-20% in regions of the inferior parietal cortex corresponding to areas 7A, 7B, 71P, and 7M. By contrast, LCGU in the auditory cortex was similar for both groups. In all areas examined, metabolic activation peaked in lower layer III where the majority of associational and callosal neurons lie. Correlation analyses of LCGU and behavioral task parameters indicated that LCGU in the parietal subdivisions was significantly related either to the accuracy of performance or to the number of trials completed on the 2DG test. In contrast, LCGU in the principal sulcus was positively correlated with task difficulty. These findings suggest that the enhancement of LCGU in the principal sulcus was primarily influenced by the mnemonic components of the tasks whereas LCGU in the inferior parietal cortex was influenced by their sensory-motor demands. These are the first results showing concurrent metabolic activation of the prefrontal and parietal cortex in monkeys performing working memory tasks and they support the suggestion that these cortical regions represent two important nodes in a neural network mediating spatial working memory in the monkey (Goldman-Rakic, 1988). Further, the present report reinforces the power of the 2DG method for functional mapping as these areal and laminar results could not be readily appreciated at this resolution in any other methodological context.
    BibTeX:
    @article{FRIEDMAN1994,
      author = {FRIEDMAN, HR and GOLDMANRAKIC, PS},
      title = {COACTIVATION OF PREFRONTAL CORTEX AND INFERIOR PARIETAL CORTEX IN WORKING-MEMORY TASKS REVEALED BY 2DG FUNCTIONAL MAPPING IN THE RHESUS-MONKEY},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1994},
      volume = {14},
      number = {5, Part 1},
      pages = {2775-2788}
    }
    
    Friedman, N. & Miyake, A. The relations among inhibition and interference control functions: A latent-variable analysis {2004} JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL
    Vol. {133}({1}), pp. {101-135} 
    article DOI  
    Abstract: This study used data from 220 adults to examine the relations among 3 inhibition-related functions. Confirmatory factor analysis suggested that Prepotent Response Inhibition and Resistance to Distractor Interference were-closely related, but both were unrelated to Resistance to Proactive Interference. Structural equation modeling, which combined Prepotent Response Inhibition and Resistance to Distractor Interference into a single latent variable, indicated that 1 aspect of random number generation performance, task-switching ability, and everyday cognitive failures Were related to Response-Distractor Inhibition, whereas reading span recall and unwanted intrusive thoughts were related to Resistance to Proactive Interference. These results suggest that the term inhibition has been overextended and that researchers need to be more specific when discussing and measuring inhibition-related functions.
    BibTeX:
    @article{Friedman2004,
      author = {Friedman, NP and Miyake, A},
      title = {The relations among inhibition and interference control functions: A latent-variable analysis},
      journal = {JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL},
      year = {2004},
      volume = {133},
      number = {1},
      pages = {101-135},
      doi = {{10.1037/0096-3445.133.1.101}}
    }
    
    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., 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. Executive frontal functions {2000} EXPERIMENTAL BRAIN RESEARCH
    Vol. {133}({1}), pp. {66-70} 
    article  
    Abstract: This chapter presents a conceptual model of the representational and executive functions of the cortex of the frontal lobe derived from empirical evidence obtained principally in the monkey. According to this model, the neuronal networks of the frontal lobe that represent motor or executive memories are probably the same networks that cooperate with other cerebral structures in the temporal organization of behavior. The prefrontal cortex. at the top of the perception-action cycle, plays a critical role in the mediation of contingencies of action across time, an essential aspect of the temporal organization of behavior. That role of cross-temporal mediation is based on the interplay of two short-term cognitive functions: one retrospective, of short-term memory or sensory working memory, and the other prospective, of attentive set (or motor working memory). Both appear represented in the neuronal populations of dorsolateral prefrontal cortex. At least one of the mechanisms for the retention of working memory of either kind seems to be the reentry of excitability through recurrent cortical circuits. With those two complementary and temporally symmetrical cognitive functions of active memory for the sensory past and for the motor future, the prefrontal cortex secures the temporal closure at the top of the perception-action cycle.
    BibTeX:
    @article{Fuster2000,
      author = {Fuster, JM},
      title = {Executive frontal functions},
      journal = {EXPERIMENTAL BRAIN RESEARCH},
      year = {2000},
      volume = {133},
      number = {1},
      pages = {66-70},
      note = {Workshop on Executive Control and the Frontal Lobe, DELMENHORST, GERMANY, DEC 01-03, 1998}
    }
    
    Fuster, J. Network memory {1997} TRENDS IN NEUROSCIENCES
    Vol. {20}({10}), pp. {451-459} 
    article  
    Abstract: Our thinking on the cortical organization of primate memory is undergoing a copernican change, from a neuropsychology that localizes different memories in different areas to one that views memory as a distributed property of cortical systems. We are shifting our focus from `systems of memory' to the memory of systems,The same cortical systems that serve us to perceive and move in the world serve us to remember it. Our memories are networks of interconnected cortical neurons, formed by association, that contain our experiences in their connectional structure. Perceptual and motor memory networks are hierarchically organized in post-rolandic and pre-rolandic neocortex, respectively. Recall, recognition and working memory consist largely in their reactivation, also by association.
    BibTeX:
    @article{Fuster1997,
      author = {Fuster, JM},
      title = {Network memory},
      journal = {TRENDS IN NEUROSCIENCES},
      year = {1997},
      volume = {20},
      number = {10},
      pages = {451-459}
    }
    
    Gabrieli, J., Desmond, J., Demb, J., Wagner, A., Stone, M., Vaidya, C. & Glover, G. Functional magnetic resonance imaging of semantic memory processes in the frontal lobes {1996} PSYCHOLOGICAL SCIENCE
    Vol. {7}({5}), pp. {278-283} 
    article  
    Abstract: Frontal-lobe activation during semantic memory performance was examined using functional magnetic resonance imaging (fMRI), a noninvasive technique for localizing neural activity associated with cognitive function. Left inferior prefrontal cortex was more activated for semantic than for perceptual encoding of words, and for initial than for repeated semantic encoding of words. Decreased activation for semantic encoding of repeated words reflects repetition priming, that is, implicit retrieval of memory gained in the initial semantic encoding of a word. The left inferior prefrontal region may subserve semantic working memory processes that participate in semantic encoding and that have decreased demands when such encoding can be facilitated hy recent semantic experience. These results demonstrate that fMRI can visualize changes in an individual's brain function associated with the encoding and retrieval of new memories.
    BibTeX:
    @article{Gabrieli1996,
      author = {Gabrieli, JDE and Desmond, JE and Demb, JB and Wagner, AD and Stone, MV and Vaidya, CJ and Glover, GH},
      title = {Functional magnetic resonance imaging of semantic memory processes in the frontal lobes},
      journal = {PSYCHOLOGICAL SCIENCE},
      year = {1996},
      volume = {7},
      number = {5},
      pages = {278-283}
    }
    
    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}
    }
    
    Garavan, H., Pankiewicz, J., Bloom, A., Cho, J., Sperry, L., Ross, T., Salmeron, B., Risinger, R., Kelley, D. & Stein, E. Cue-induced cocaine craving: Neuroanatomical specificity for drug users and drug stimuli {2000} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {157}({11}), pp. {1789-1798} 
    article  
    Abstract: Objective: Cocaine-related cues have been hypothesized to perpetuate drug abuse by inducing a craving response that prompts drug-seeking behavior. However, the mechanisms, underlying neuroanatomy, and specificity of this neuroanatomy are not yet fully understood. Method: To address these issues, experienced cocaine users (N=17) and comparison subjects (N=14) underwent functional magnetic resonance imaging while viewing three separate films that portrayed 1) individuals smoking crack cocaine, 2) outdoor nature scenes, and 3) explicit sexual content. Candidate craving sites were identified as those that showed significant activation in the cocaine users when viewing the cocaine film. These sites were then required to show significantly greater activation when contrasted with comparison subjects viewing the cocaine film (population specificity) and cocaine users viewing the nature film (content specificity). Results: Brain regions that satisfied these criteria were largely left lateralized and included the frontal lobe (medial and middle frontal gyri, bilateral inferior frontal gyrus), parietal lobe (bilateral inferior parietal lobule), insula, and limbic lobe (anterior and posterior cingulate gyrus). Of the 13 regions identified as putative craving sites,just three(anterior cingulate, right inferior parietal lobule, and the caudate/lateral dorsal nucleus) showed significantly greater activation during the cocaine film than during the sex film in the cocaine users, which suggests that cocaine cues activated similar neuroanatomical substrates as naturally evocative stimuli in the cocaine users. Finally, contrary to the effects of the cocaine film, cocaine users showed a smaller response than the comparison subjects to the sex film. Conclusions: These data suggest that cocaine craving is not associated with a dedicated and unique neuroanatomical circuitry; instead, unique to the cocaine user is the ability of learned, drug-related cues to produce brain activation comparable to that seen with nondrug evocative stimuli in healthy comparison subjects.
    BibTeX:
    @article{Garavan2000,
      author = {Garavan, H and Pankiewicz, J and Bloom, A and Cho, JK and Sperry, L and Ross, TJ and Salmeron, BJ and Risinger, R and Kelley, D and Stein, EA},
      title = {Cue-induced cocaine craving: Neuroanatomical specificity for drug users and drug stimuli},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {2000},
      volume = {157},
      number = {11},
      pages = {1789-1798}
    }
    
    Garavan, H., Ross, T., Murphy, K., Roche, R. & Stein, E. Dissociable executive functions in the dynamic control of behavior: Inhibition, error detection, and correction {2002} NEUROIMAGE
    Vol. {17}({4}), pp. {1820-1829} 
    article DOI  
    Abstract: The present study employed event-related fMRI and EEG to investigate the biological basis of the cognitive control of behavior. Using a GO/NOGO task optimized to produce response inhibitions, frequent commission errors, and the opportunity for subsequent behavioral correction, we identified distinct cortical areas associated with each of these specific executive processes. Two cortical systems, one involving right prefrontal and parietal areas and the second regions of the cingulate, underlay inhibitory control. The involvement of these two systems was predicated upon the difficulty or urgency of the inhibition and each was employed to different extents by high- and low-absent-minded subjects. Errors were associated with medial activation incorporating the anterior cingulate and pre-SMA while behavioral alteration subsequent to errors was associated with both the anterior cingulate and the left prefrontal cortex. Furthermore, the EEG data demonstrated that successful response inhibition depended upon the timely activation of cortical areas as predicted by race models of response selection. The results highlight how higher cognitive functions responsible for behavioral control can result from the dynamic interplay of distinct cortical systems. (C) 2002 Elsevier Science (USA).
    BibTeX:
    @article{Garavan2002,
      author = {Garavan, H and Ross, TJ and Murphy, K and Roche, RAP and Stein, EA},
      title = {Dissociable executive functions in the dynamic control of behavior: Inhibition, error detection, and correction},
      journal = {NEUROIMAGE},
      year = {2002},
      volume = {17},
      number = {4},
      pages = {1820-1829},
      doi = {{10.1006/nimg.2002.1326}}
    }
    
    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}
    }
    
    Gauthier, S., Reisberg, B., Zaudig, M., Petersen, R., Ritchie, K., Broich, K., Belleville, S., Brodaty, H., Bennett, D., Chertkow, H., Cummings, J., de Leon, M., Feldman, H., Ganguli, M., Hampel, H., Scheltens, P., Tierney, M., Whitehouse, P., Winblad, B. & Int Psychogeriatric Assoc Expert C Mild cognitive impairment {2006} LANCET
    Vol. {367}({9518}), pp. {1262-1270} 
    article  
    Abstract: Mild cognitive impairment is a syndrome defined as cognitive decline greater than expected for an individual's age and education level but that does not interfere notably with activities of daily life. Prevalence in population-based epidemiological studies ranges from 3% to 19% in adults older than 65 years. Some people with mild cognitive impairment seem to remain stable or return to normal over time, but more than half progress to dementia within 5 years. Mild cognitive impairment can thus be regarded as a risk state for dementia, and its identification could lead to secondary prevention by controlling risk factors such as systolic hypertension. The amnestic subtype of mild cognitive impairment has a high risk of progression to Alzheimer's disease, and it could constitute a prodromal stage of this disorder. Other definitions and subtypes of mild cognitive impairment need to be studied as potential prodromes of Alzheimer's disease and other types of dementia.
    BibTeX:
    @article{Gauthier2006,
      author = {Gauthier, S and Reisberg, B and Zaudig, M and Petersen, RC and Ritchie, K and Broich, K and Belleville, S and Brodaty, H and Bennett, D and Chertkow, H and Cummings, JL and de Leon, M and Feldman, H and Ganguli, M and Hampel, H and Scheltens, P and Tierney, MC and Whitehouse, P and Winblad, B and Int Psychogeriatric Assoc Expert C},
      title = {Mild cognitive impairment},
      journal = {LANCET},
      year = {2006},
      volume = {367},
      number = {9518},
      pages = {1262-1270}
    }
    
    GEARY, D. MATHEMATICAL DISABILITIES - COGNITIVE, NEUROPSYCHOLOGICAL, AND GENETIC COMPONENTS {1993} PSYCHOLOGICAL BULLETIN
    Vol. {114}({2}), pp. {345-362} 
    article  
    Abstract: Cognitive, neuropsychological, and genetic correlates of mathematical achievement and mathematical disability (MD) are reviewed in an attempt to identify the core deficits underlying MD. Three types of distinct cognitive, neuropsychological, or cognitive and neuropsychological deficits associated with MD are identified. The first deficit is manifested by difficulties in the representation or retrieval of arithmetic facts from semantic memory. The second type of deficit is manifested by problems in the execution of arithmetical procedures. The third type involves problems in the visuospatial representation of numerical information. Potential cognitive, neuropsychological, and genetic factors contributing to these deficits, and the relationship between MD and reading disabilities, are discussed. Finally, suggestions for the subtyping of mathematical disorders are offered.
    BibTeX:
    @article{GEARY1993,
      author = {GEARY, DC},
      title = {MATHEMATICAL DISABILITIES - COGNITIVE, NEUROPSYCHOLOGICAL, AND GENETIC COMPONENTS},
      journal = {PSYCHOLOGICAL BULLETIN},
      year = {1993},
      volume = {114},
      number = {2},
      pages = {345-362}
    }
    
    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}
    }
    
    Gibson, E. Linguistic complexity: locality of syntactic dependencies {1998} COGNITION
    Vol. {68}({1}), pp. {1-76} 
    article  
    Abstract: This paper proposes a new theory of the relationship between the sentence processing mechanism and the available computational resources. This theory - the Syntactic Prediction Locality Theory (SPLT) - has two components: an integration cost component and a component for the memory cost associated with keeping track of obligatory syntactic requirements. Memory cost is hypothesized to be quantified in terms of the number of syntactic categories that are necessary to complete the current input string as a grammatical sentence. Furthermore, in accordance with results from the working memory literature both memory cost and integration cost are hypothesized to be heavily influenced by locality (1) the longer a predicted category must be kept in memory before the prediction is satisfied, the greater is the cost for maintaining that prediction; and (2) the greater the distance between an incoming word and the most local head or dependent to which it attaches, the greater the integration cost. The SPLT is shown to explain a wide range of processing complexity phenomena not previously accounted for under a single theory, including (1) the lower complexity of subject-extracted relative clauses compared to object-extracted relative clauses, (2) numerous processing overload effects across languages, including the unacceptability of multiply center-embedded structures, (3) the lower complexity of cross-serial dependencies relative to center-embedded dependencies, (4) heaviness effects, such that sentences are easier to understand when larger phrases are placed later and (5) numerous ambiguity effects, such as those which have been argued to be evidence for the Active Filler Hypothesis. (C) 1998 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{Gibson1998,
      author = {Gibson, E},
      title = {Linguistic complexity: locality of syntactic dependencies},
      journal = {COGNITION},
      year = {1998},
      volume = {68},
      number = {1},
      pages = {1-76}
    }
    
    Gitelman, D., Nobre, A., Parrish, T., LaBar, K., Kim, Y., Meyer, J. & Mesulam, M. A large-scale distributed network for covert spatial attention - Further anatomical delineation based on stringent behavioural and cognitive controls {1999} BRAIN
    Vol. {122}({Part 6}), pp. {1093-1106} 
    article  
    Abstract: Functional MRI was used to examine cerebral activations in 12 subjects while they performed a spatial attention task. This study applied more stringent behavioural and cognitive controls than previously used for similar experiments: (i) subjects were included only if they showed evidence of attentional shifts while performing the task in the magnet; (ii) the experimental task and baseline condition were designed to eliminate the contributions of motor output, visual fixation, inhibition of eye movements, working memory and the conditional (no-go) component of responding, Activations were seen in all three hypothesized cortical epicentres forming a network for spatial attention: the lateral premotor cortex (frontal eye fields), the posterior parietal cortex and the cingulate cortex, Subcortical activations were seen in the basal ganglia and the thalamus, Although the task required attention to be equally shifted to the left and to the right, eight of 10 subjects showed a greater area of activation in the right parietal cortex, consistent with the specialization of the right hemisphere for spatial attention, Other areas of significant activation included the posterior temporo-occipital cortex and the anterior insula, The temporo-occipital activation was within a region broadly defined as MT+ (where MT is the middle temporal area) which contains the human equivalent of area MT in the macaque monkey, This temporo-occipital area appears to constitute a major component of the functional network activated by this spatial attention task, Its activation may reflect the `inferred' shift of the attentional focus across the visual scene.
    BibTeX:
    @article{Gitelman1999,
      author = {Gitelman, DR and Nobre, AC and Parrish, TB and LaBar, KS and Kim, YH and Meyer, JR and Mesulam, MM},
      title = {A large-scale distributed network for covert spatial attention - Further anatomical delineation based on stringent behavioural and cognitive controls},
      journal = {BRAIN},
      year = {1999},
      volume = {122},
      number = {Part 6},
      pages = {1093-1106}
    }
    
    GIVENS, B. & OLTON, D. CHOLINERGIC AND GABAERGIC MODULATION OF MEDIAL SEPTAL AREA - EFFECT ON WORKING MEMORY {1990} BEHAVIORAL NEUROSCIENCE
    Vol. {104}({6}), pp. {849-855} 
    article  
    BibTeX:
    @article{GIVENS1990,
      author = {GIVENS, BS and OLTON, DS},
      title = {CHOLINERGIC AND GABAERGIC MODULATION OF MEDIAL SEPTAL AREA - EFFECT ON WORKING MEMORY},
      journal = {BEHAVIORAL NEUROSCIENCE},
      year = {1990},
      volume = {104},
      number = {6},
      pages = {849-855}
    }
    
    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}
    }
    
    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, J., RANDOLPH, C., CARPENTER, C., GOLDBERG, T. & WEINBERGER, D. FORMS OF MEMORY FAILURE IN SCHIZOPHRENIA {1992} JOURNAL OF ABNORMAL PSYCHOLOGY
    Vol. {101}({3}), pp. {487-494} 
    article  
    Abstract: Effortful and automatic memory task performances were examined in 36 schizophrenic patients and 18 normal control Ss. Tasks included free recall, recognition, and frequency estimation. Patients demonstrated impairment in recall, in recognition, in semantic encoding, and in frequency estimation. Deficits were observed across tasks despite differences in attentional demands. The results suggest a basic compromise of memory function, which is consistent with recent neuro-imaging evidence of structural or physiological abnormalities in frontal and temporal lobe structures in schizophrenia.
    BibTeX:
    @article{GOLD1992,
      author = {GOLD, JM and RANDOLPH, C and CARPENTER, CJ and GOLDBERG, TE and WEINBERGER, DR},
      title = {FORMS OF MEMORY FAILURE IN SCHIZOPHRENIA},
      journal = {JOURNAL OF ABNORMAL PSYCHOLOGY},
      year = {1992},
      volume = {101},
      number = {3},
      pages = {487-494}
    }
    
    Gold, J. & Shadlen, M. Neural computations that underlie decisions about sensory stimuli {2001} TRENDS IN COGNITIVE SCIENCES
    Vol. {5}({1}), pp. {10-16} 
    article  
    Abstract: Decision-making behavior has been studied extensively, but the neurophysiological mechanisms responsible for this remarkable cognitive ability are just beginning to be understood. Here we propose neural computations that can account for the formation of categorical decisions about sensory stimuli by accumulating information over time into a single quantity: the logarithm of the likelihood ratio favoring one alternative over another. We also review electrophysio-logical studies that have identified brain structures that may be involved in computing this sort of decision variable. The ideas presented constitute a framework for understanding how and where perceptual decisions are formed in the brain.
    BibTeX:
    @article{Gold2001,
      author = {Gold, JI and Shadlen, MN},
      title = {Neural computations that underlie decisions about sensory stimuli},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      year = {2001},
      volume = {5},
      number = {1},
      pages = {10-16}
    }
    
    Goldberg, T., Egan, M., Gscheidle, T., Coppola, R., Weickert, T., Kolachana, B., Goldman, D. & Weinberger, D. Executive subprocesses in working memory - Relationship to catechol-O-methyltransferase Val158Met genotype and schizophrenia {2003} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {60}({9}), pp. {889-896} 
    article  
    Abstract: Background: Cognitive dysfunction in the working memory domain seems to be under genetic control and is a candidate intermediate phenotype in schizophrenia. Genes that affect working memory processing may contribute to risk for schizophrenia. Methods: Working memory and attentional processing were assessed in a large and unselected sample of schizophrenic patients, their healthy siblings, and controls (N=250). We used the n-back task because it allows parametric analysis over increasing loads and delays and parsing of subcomponents of executive cognition and working memory, including temporal indexing and updating. Participants were genotyped for catechol-O-methyltransferase (COMT) at the Val158Met locus, which has been shown to affect executive cognition and frontal lobe function, likely because of genetically determined variation in prefrontal dopamine signaling. Results: A significant COMT genotype effect was found: Val/Val individuals had the lowest n-back performance, and Met/Met individuals had the highest performance. Effects were similar in the 1- and 2-back conditions and across all groups, whereas no effect on the Continuous Performance Test was seen, suggesting that genotype was not affecting working memory subprocesses related to attention, load, or delay. Siblings also performed significantly worse than controls on the 1- and 2-back conditions. Conclusions: A prefrontal cognitive mechanism common to the 1- and 2-back conditions, probably executive processes involved in information updating and temporal indexing, is sensitive to the COMT genotype. Considering that the 3 participant groups were affected more or less linearly by the COMT genotype, an additive genetic model in which the effect of allele load is similar in its effects on prefrontally based working memory irrespective of the genetic or environiriental background in which it is expressed is suggested. The findings also provide convergent evidence that an intermediate phenotype related to prefrontal cortical function represents a viable approach to understanding neuropsychiatric disorders with complex genetic etiologies and individual differences in cognition.
    BibTeX:
    @article{Goldberg2003,
      author = {Goldberg, TE and Egan, MF and Gscheidle, T and Coppola, R and Weickert, T and Kolachana, BS and Goldman, D and Weinberger, DR},
      title = {Executive subprocesses in working memory - Relationship to catechol-O-methyltransferase Val158Met genotype and schizophrenia},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {2003},
      volume = {60},
      number = {9},
      pages = {889-896}
    }
    
    Goldman-Rakic, P. The physiological approach: Functional architecture of working memory and disordered cognition in schizophrenia {1999} BIOLOGICAL PSYCHIATRY
    Vol. {46}({5}), pp. {650-661} 
    article  
    Abstract: The method of single-cell recording in awake behaving monkeys as they perform behavioral tasks is perhaps the most powerful approach to understanding the neural basis of behavior. In contrast to cellular analyses in vitro, e.g., in slice preparations, the in vivo approach allows direct correlation of cellular activity and specific processes as they are isolated by behavioral paradigms. As brain mechanisms are studied under natural conditions, inferences about the dynamic basis of information processing are direct. Limitations of this approach include the inability to unequivocally identify the cell under investigation, though location by cytoarchitectonic area and cortical depth is possible. Neurophysiological studies have not only given a dynamic view of neural processing ``on line'' but have allowed investigators to examine fundamental issues about normal brain function and dementia. Here I illustrate some of these issues and the power of single cell physiology to address them. Before doing so, it should be patently obvious that recording one cell at a time is a technical necessity and in no way should be taken to imply that any behavior is dependent on a single cell. Rather the neuron investigated is a representative of a cohort of cells acting in aggregate. Biol Psychiatry 1999;46:650-661 (C) 1999 Society of Biological Psychiatry.
    BibTeX:
    @article{Goldman-Rakic1999,
      author = {Goldman-Rakic, PS},
      title = {The physiological approach: Functional architecture of working memory and disordered cognition in schizophrenia},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {1999},
      volume = {46},
      number = {5},
      pages = {650-661},
      note = {Conference on Schizophrenia - From Molecule to Public Policy, SANTA FE, NEW MEXICO, OCT, 1998}
    }
    
    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. PREFRONTAL CORTICAL DYSFUNCTION IN SCHIZOPHRENIA - THE RELEVANCE OF WORKING MEMORY {1991} PSYCHOPATHOLOGY AND THE BRAIN, pp. {1-21}  inproceedings  
    BibTeX:
    @inproceedings{GOLDMANRAKIC1991,
      author = {GOLDMANRAKIC, PS},
      title = {PREFRONTAL CORTICAL DYSFUNCTION IN SCHIZOPHRENIA - THE RELEVANCE OF WORKING MEMORY},
      booktitle = {PSYCHOPATHOLOGY AND THE BRAIN},
      year = {1991},
      pages = {1-21},
      note = {79TH ANNUAL MEETING OF THE AMERICAN PSYCHOPATHOLOGICAL ASSOC, NEW YORK, NY, 1989}
    }
    
    GoldmanRakic, P. Architecture of the prefrontal cortex and the central executive {1995}
    Vol. {769}STRUCTURE AND FUNCTIONS OF THE HUMAN PREFRONTAL CORTEX, pp. {71-83} 
    inproceedings  
    BibTeX:
    @inproceedings{GoldmanRakic1995,
      author = {GoldmanRakic, PS},
      title = {Architecture of the prefrontal cortex and the central executive},
      booktitle = {STRUCTURE AND FUNCTIONS OF THE HUMAN PREFRONTAL CORTEX},
      year = {1995},
      volume = {769},
      pages = {71-83},
      note = {Workshop on Structure and Functions of the Human Prefrontal Cortex, NEW YORK, NY, MAR 02-04, 1995}
    }
    
    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. CELLULAR AND CIRCUIT BASIS OF WORKING MEMORY IN PREFRONTAL CORTEX OF NONHUMAN-PRIMATES {1990} PROGRESS IN BRAIN RESEARCH
    Vol. {85}, pp. {325-336} 
    article  
    BibTeX:
    @article{GOLDMANRAKIC1990,
      author = {GOLDMANRAKIC, PS},
      title = {CELLULAR AND CIRCUIT BASIS OF WORKING MEMORY IN PREFRONTAL CORTEX OF NONHUMAN-PRIMATES},
      journal = {PROGRESS IN BRAIN RESEARCH},
      year = {1990},
      volume = {85},
      pages = {325-336}
    }
    
    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}
    }
    
    Gorno-Tempini, M., Dronkers, N., Rankin, K., Ogar, J., Phengrasamy, L., Rosen, H., Johnson, J., Weiner, M. & Miller, B. Cognition and anatomy in three variants of primary progressive aphasia {2004} ANNALS OF NEUROLOGY
    Vol. {55}({3}), pp. {335-346} 
    article DOI  
    Abstract: We performed a comprehensive cognitive, neuroimaging, and genetic study of 31 patients with primary progressive aphasia (PPA), a decline in language functions that remains isolated for at least 2 years. Detailed speech and language evaluation was used to identify three different clinical variants: nonfluent progressive aphasia (NFPA; n = 11), semantic dementia (SD; n = 10), and a third variant termed logopenic progressive aphasia (LPA; n = 10). Voxel-based morphometry (VBM) on MRIs showed that, when all 31 PPA patients were analyzed together, the left perisylvian region and the anterior temporal lobes were atrophied. However, when each clinical variant was considered separately, distinctive patterns emerged: (1) NFPA, characterized by apraxia of speech and deficits in processing complex syntax, was associated with left inferior frontal and insular atrophy; (2) SD, characterized by fluent speech and semantic memory deficits, was associated with anterior temporal damage; and (3) LPA, characterized by slow speech and impaired syntactic comprehension and naming, showed atrophy in the left posterior temporal cortex and inferior parietal lobule. Apolipoprotein E epsilon4 haplotype frequency was 20% in NFPA, 0% in SD, and 67% in LPA. Cognitive, genetic, and anatomical features indicate that different PPA clinical variants may correspond to different underlying pathological processes.
    BibTeX:
    @article{Gorno-Tempini2004,
      author = {Gorno-Tempini, ML and Dronkers, NF and Rankin, KP and Ogar, JM and Phengrasamy, L and Rosen, HJ and Johnson, JK and Weiner, MW and Miller, BL},
      title = {Cognition and anatomy in three variants of primary progressive aphasia},
      journal = {ANNALS OF NEUROLOGY},
      year = {2004},
      volume = {55},
      number = {3},
      pages = {335-346},
      doi = {{10.1002/ana.10825}}
    }
    
    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}
    }
    
    GRADY, C., MAISOG, J., HORWITZ, B., UNGERLEIDER, L., MENTIS, M., SALERNO, J., PIETRINI, P., WAGNER, E. & HAXBY, J. AGE-RELATED-CHANGES IN CORTICAL BLOOD-FLOW ACTIVATION DURING VISUAL PROCESSING OF FACES AND LOCATION {1994} JOURNAL OF NEUROSCIENCE
    Vol. {14}({3, Part 2}), pp. {1450-1462} 
    article  
    Abstract: We examined age-related changes in object and spatial visual processing in two separate experiments. Regional cerebral blood flow (rCBF) was measured in young and old subjects with positron emission tomography and H-2 O-15 during tests of face matching, location matching, and a control task. The task demands in the two experiments were identical, but the stimuli in Experiment II were constructed to equalize stimulus complexity across all three tasks. The old subjects performed more slowly than the young subjects in both experiments, and showed significantly slower reaction times during location matching compared to face matching in Experiment II. Both young and old subjects showed occipitotemporal rCBF activation during face matching and occipitoparietal activation during location matching when these conditions were compared to the control task. However, in both experiments and in both tasks, young subjects showed greater activation of prestriate cortex (Brodmann's area 18), and old subjects had larger rCBF increases in occipitotemporal cortex (area 37). Areas in prefrontal cortex, as well as in inferior and medial parietal cortex, were more activated in the old subjects during location matching in both experiments. These results demonstrate that reliable age-related changes during visual processing can be found in rCBF patterns, suggesting more efficient use of occipital visual areas by younger subjects and more reliance by older subjects on one or more cortical networks, particularly for spatial vision, perhaps to compensate for reduced processing efficiency of occipital cortex. Both the differentially increased reaction times and the more widespread prefrontal activation in the old subjects during location matching suggest that spatial vision may be affected to a greater degree by aging than is object vision.
    BibTeX:
    @article{GRADY1994,
      author = {GRADY, CL and MAISOG, JM and HORWITZ, B and UNGERLEIDER, LG and MENTIS, MJ and SALERNO, JA and PIETRINI, P and WAGNER, E and HAXBY, JV},
      title = {AGE-RELATED-CHANGES IN CORTICAL BLOOD-FLOW ACTIVATION DURING VISUAL PROCESSING OF FACES AND LOCATION},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1994},
      volume = {14},
      number = {3, Part 2},
      pages = {1450-1462}
    }
    
    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}
    }
    
    GRAESSER, A., SINGER, M. & TRABASSO, T. CONSTRUCTING INFERENCES DURING NARRATIVE TEXT COMPREHENSION {1994} PSYCHOLOGICAL REVIEW
    Vol. {101}({3}), pp. {371-395} 
    article  
    Abstract: The authors describe a constructionist theory that accounts for the knowledge-based inferences that are constructed-when readers comprehend narrative text. Readers potentially generate a rich variety of inferences when they construct a referential situation model of what the text is about. The proposed constructionist theory specifies that some, but not all, of this information is constructed under most conditions of comprehension. The distinctive assumptions of the constructionist theory embrace a principle of search (or effort) after meaning. According to this principle, readers attempt to construct a meaning representation that addresses the reader's goals, that is coherent at both local and global levels, and that explains why actions, events, and states are mentioned in the text. This study reviews empirical evidence that addresses this theory and contrasts it with alternative theoretical frameworks.
    BibTeX:
    @article{GRAESSER1994,
      author = {GRAESSER, AC and SINGER, M and TRABASSO, T},
      title = {CONSTRUCTING INFERENCES DURING NARRATIVE TEXT COMPREHENSION},
      journal = {PSYCHOLOGICAL REVIEW},
      year = {1994},
      volume = {101},
      number = {3},
      pages = {371-395}
    }
    
    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}
    }
    
    Granon, S., Passetti, F., Thomas, K., Dalley, J., Everitt, B. & Robbins, T. Enhanced and impaired attentional performance after infusion of D1 dopaminergic receptor agents into rat prefrontal cortex {2000} JOURNAL OF NEUROSCIENCE
    Vol. {20}({3}), pp. {1208-1215} 
    article  
    Abstract: The role in spatial divided and sustained attention of D1 and D2-like dopamine (DA) receptors in the rat prelimbic medial prefrontal cortex (mPFC) was investigated in a five-choice serial reaction time task. Rats were trained to detect brief flashes of light (0.5-0.25 sec) presented randomly in a spatial array of five apertures. When performance stabilized, animals received bilateral microinfusions of either the D1 DA receptor antagonist SCH 23390, the D1 DA receptor agonist SKF 38393, or the D2 DA antagonist sulpiride into the mPFC. Rats were divided into two groups, with low (<75% correct) and high (>75 baseline levels of accuracy. Infusions of the D2 receptor antagonist sulpiride had no significant effect on any task variable. SCH 23390 (0.3 mu g) selectively impaired the accuracy of attentional performance in rats in the high baseline condition. By contrast, SKF 38393 (0.06 mu g) enhanced the accuracy of attentional performance in the low baseline condition, a lower dose (0.03 mu g) also increasing the speed of making correct responses. Finally, the beneficial effects of SKF-383893 on choice accuracy were antagonized by SCH 23390 (1.0 mu g). The results provide apparently the first demonstration of enhanced cognitive function after local administration of a D1 receptor agonist to the mPFC and suggest dissociable roles of D1 and D2 DA receptors of the mPFC in modulating attentional function.
    BibTeX:
    @article{Granon2000,
      author = {Granon, S and Passetti, F and Thomas, KL and Dalley, JW and Everitt, BJ and Robbins, TW},
      title = {Enhanced and impaired attentional performance after infusion of D1 dopaminergic receptor agents into rat prefrontal cortex},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2000},
      volume = {20},
      number = {3},
      pages = {1208-1215}
    }
    
    Gray, J., Chabris, C. & Braver, T. Neural mechanisms of general fluid intelligence {2003} NATURE NEUROSCIENCE
    Vol. {6}({3}), pp. {316-322} 
    article DOI  
    Abstract: We used an individual-differences approach to test whether general fluid intelligence (gF) is mediated by brain regions that support attentional (executive) control, including subregions of the prefrontal cortex. Forty-eight participants first completed a standard measure of gF (Raven's Advanced Progressive Matrices). They then performed verbal and nonverbal versions of a challenging working-memory task (three-back) while their brain activity was measured using functional magnetic resonance imaging (fMRI). Trials within the three-back task varied greatly in the demand for attentional control because of differences in trial-to-trial interference. On high-interference trials specifically, participants with higher gF were more accurate and had greater event-related neural activity in several brain regions. Multiple regression analyses indicated that lateral prefrontal and parietal regions may mediate the relation between ability (gF) and performance (accuracy despite interference), providing constraints on the neural mechanisms that support gF.
    BibTeX:
    @article{Gray2003,
      author = {Gray, JR and Chabris, CF and Braver, TS},
      title = {Neural mechanisms of general fluid intelligence},
      journal = {NATURE NEUROSCIENCE},
      year = {2003},
      volume = {6},
      number = {3},
      pages = {316-322},
      doi = {{10.1038/nn1014}}
    }
    
    Gray, R., Rajan, A., Radcliffe, K., Yakehiro, M. & Dani, J. Hippocampal synaptic transmission enhanced by low concentrations of nicotine {1996} NATURE
    Vol. {383}({6602}), pp. {713-716} 
    article  
    Abstract: NICOTINE obtained from tobacco can improve learning and memory on various tasks and has been linked to arousal, attention, rapid information processing, working memory, and longterm memories that can cause craving years after someone has stopped smoking(1,2). One likely target for these effects is the hippocampus, a centre for learning and memory that has rich cholinergic innervation and dense nicotinic acetylcholine receptor (nAChR) expression(3-6). During Alzheimer's dementia there are fewer nAChRs and the cholinergic inputs to the hippocampus degenerate(7). However, there is no evidence for fast synaptic transmission mediated by nAChRs in the hippocampus, and their role is not understood(8,9). Nicotine is known to act on presynaptic nAChRs within the habenula of chick to enhance glutamatergic transmission(10); here we report that a similar mechanism operates in the hippocampus. Measurements of intracellular Ca2+ in single mossy-fibre presynaptic terminals indicate that nAChRs containing the alpha 7 subunit can mediate a Ca2+ influx that is sufficient to induce vesicular neurotransmitter release. We propose that nicotine from tobacco influences cognition by enhancing synaptic transmission. Conversely, a decreased efficacy of transmission may account for the deficits associated with the loss of cholinergic innervation during Alzheimer's disease.
    BibTeX:
    @article{Gray1996,
      author = {Gray, R and Rajan, AS and Radcliffe, KA and Yakehiro, M and Dani, JA},
      title = {Hippocampal synaptic transmission enhanced by low concentrations of nicotine},
      journal = {NATURE},
      year = {1996},
      volume = {383},
      number = {6602},
      pages = {713-716}
    }
    
    Green, J.E., Choi, J.W., Boukai, A., Bunimovich, Y., Johnston-Halperin, E., DeIonno, E., Luo, Y., Sheriff, B.A., Xu, K., Shin, Y.S., Tseng, H.-R., Stoddart, J.F. & Heath, J.R. A 160-kilobit molecular electronic memory patterned at 10(11) bits per square centimetre {2007} NATURE
    Vol. {445}({7126}), pp. {414-417} 
    article DOI  
    Abstract: The primary metric for gauging progress in the various semiconductor integrated circuit technologies is the spacing, or pitch, between the most closely spaced wires within a dynamic random access memory (DRAM) circuit(1). Modern DRAM circuits have 140 nm pitch wires and a memory cell size of 0.0408 mu m(2). Improving integrated circuit technology will require that these dimensions decrease over time. However, at present a large fraction of the patterning and materials requirements that we expect to need for the construction of new integrated circuit technologies in 2013 have `no known solution'(1). Promising ingredients for advances in integrated circuit technology are nanowires(2), molecular electronics(3) and defect-tolerant architectures(4), as demonstrated by reports of single devices(5-7) and small circuits(8,9). Methods of extending these approaches to large-scale, high-density circuitry are largely undeveloped. Here we describe a 160,000-bit molecular electronic memory circuit, fabricated at a density of 10(11) bits cm(-2) ( pitch 33 nm; memory cell size 0.0011 mu m(2)), that is, roughly analogous to the dimensions of a DRAM circuit(1) projected to be available by 2020. A monolayer of bistable, [ 2] rotaxane molecules(10) served as the data storage elements. Although the circuit has large numbers of defects, those defects could be readily identified through electronic testing and isolated using software coding. The working bits were then configured to form a fully functional random access memory circuit for storing and retrieving information.
    BibTeX:
    @article{Green2007,
      author = {Green, Jonathan E. and Choi, Jang Wook and Boukai, Akram and Bunimovich, Yuri and Johnston-Halperin, Ezekiel and DeIonno, Erica and Luo, Yi and Sheriff, Bonnie A. and Xu, Ke and Shin, Young Shik and Tseng, Hsian-Rong and Stoddart, J. Fraser and Heath, James R.},
      title = {A 160-kilobit molecular electronic memory patterned at 10(11) bits per square centimetre},
      journal = {NATURE},
      year = {2007},
      volume = {445},
      number = {7126},
      pages = {414-417},
      doi = {{10.1038/nature05462}}
    }
    
    Green, M., Marshall, B., Wirshing, W., Ames, D., Marder, S., McGurk, S., Kern, R. & Mintz, J. Does risperidone improve verbal working memory in treatment-resistant schizophrenia? {1997} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {154}({6}), pp. {799-804} 
    article  
    Abstract: Objective: Treatment efficacy in schizophrenia is typically defined in terms of symptom reduction. However, new antipsychotic medications could potentially have an impact on aspects of disability, such as neurocognitive deficits. The authors evaluated the effects of risperidone on vel bal working memory, a memory component of theoretical interest because of its link to prefrontal activity and of practical interest because of its link to psychosocial rehabilitation. Method: Verbal working memory of 59 treatment-resistant schizophrenic patients was assessed as part of a randomized, double-blind comparison of treatment with risperidone and haloperidol. Verbal working memory was measured under both distracting and nondistracting conditions at baseline and after 4 weeks of both fixed- and flexible-dose pharmacotherapy. Results: Risperidone treatment had a greater beneficial effect on verbal working memory than haloperidol treatment across testing conditions (with and without distraction) and study phases (fixed and flexible nose). The treatment effect remained significant after the effects of benztropine cotreatment, change in psychotic symptoms, and change in negative symptoms were controlled. Neither benztropine status nor symptom changes were significantly related to memory Performance. Conclusions: Treatment with risperidone appears to exert a more favorable effect on verbal working memory than treatment with a conventional neuroleptic. The beneficial effect appears to be due, at least partially, to a direct effect of the drug, possibly through antagonism of the 5-HT2A receptor. Results from this study suggest that pharmacotherapeutic efficacy in schizophrenia treatment could be broadened to include impact on neurocognitive abilities.
    BibTeX:
    @article{Green1997,
      author = {Green, MF and Marshall, BD and Wirshing, WC and Ames, D and Marder, SR and McGurk, S and Kern, RS and Mintz, J},
      title = {Does risperidone improve verbal working memory in treatment-resistant schizophrenia?},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {1997},
      volume = {154},
      number = {6},
      pages = {799-804}
    }
    
    Greene, J., Sommerville, R., Nystrom, L., Darley, J. & Cohen, J. An fMRI investigation of emotional engagement in moral judgment {2001} SCIENCE
    Vol. {293}({5537}), pp. {2105-2108} 
    article  
    Abstract: The long-standing rationalist tradition in moral psychology emphasizes the rote of reason in moral judgment. A more recent trend places increased emphasis on emotion. Although both reason and emotion are likely to play important roles in moral judgment, relatively tittle is known about their neural correlates, the nature of their interaction, and the factors that modulate their respective behavioral influences in the context of moral judgment. In two functional magnetic resonance imaging (fMRI) studies using moral dilemmas as probes, we apply the methods of cognitive neuroscience to the study of moral judgment. We argue that moral dilemmas vary systematically in the extent to which they engage emotional processing and that these variations in emotional engagement influence moral judgment. These results may shed light on some puzzling patterns in moral judgment observed by contemporary philosophers.
    BibTeX:
    @article{Greene2001,
      author = {Greene, JD and Sommerville, RB and Nystrom, LE and Darley, JM and Cohen, JD},
      title = {An fMRI investigation of emotional engagement in moral judgment},
      journal = {SCIENCE},
      year = {2001},
      volume = {293},
      number = {5537},
      pages = {2105-2108}
    }
    
    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}
    }
    
    Gron, G., Wunderlich, A., Spitzer, M., Tomczak, R. & Riepe, M. Brain activation during human navigation: gender-different neural networks as substrate of performance {2000} NATURE NEUROSCIENCE
    Vol. {3}({4}), pp. {404-408} 
    article  
    Abstract: Visuospatial navigation in animals and human subjects is generally studied using maze exploration. We used functional MRI to observe brain activation in male and female subjects as they searched for the way out of a complex, three-dimensional, virtual-reality maze. Navigation activated the medial occipital gyri, lateral and medial parietal regions, posterior cingulate and parahippocampal gyri as well as the right hippocampus proper. Gender-specific group analysis revealed distinct activation of the left hippocampus in males, whereas females consistently recruited right parietal and right prefrontal cortex. Thus we demonstrate a neural substrate of well established human gender differences in spatial-cognition performance.
    BibTeX:
    @article{Gron2000,
      author = {Gron, G and Wunderlich, AP and Spitzer, M and Tomczak, R and Riepe, MW},
      title = {Brain activation during human navigation: gender-different neural networks as substrate of performance},
      journal = {NATURE NEUROSCIENCE},
      year = {2000},
      volume = {3},
      number = {4},
      pages = {404-408}
    }
    
    Halford, G., Wilson, W. & Phillips, S. Processing capacity defined by relational complexity: Implications for comparative, developmental, and cognitive psychology {1998} BEHAVIORAL AND BRAIN SCIENCES
    Vol. {21}({6}), pp. {803+} 
    article  
    Abstract: Working memory limits are best defined in terms of the complexity of the relations that can be processed in parallel. Complexity is defined as the number of related dimensions or sources of variation. A unary relation has one argument and one source of variation; its argument can be instantiated in only one way at a time. A binary relation has two arguments, two sources of variation, and two instantiations, and so on. Dimensionality is related to the number of chunks, because both attributes on dimensions and chunks are independent units of information of arbitrary size. Studies of working memory limits suggest that there is a soft limit corresponding to the parallel processing of one quaternary relation. More complex concepts are processed by ``segmentation'' or ``conceptual chunking.'' In segmentation, tasks are broken into components that do not exceed processing capacity and can be processed serially. In conceptual chunking, representations are ``collapsed'' to reduce their dimensionality and hence their processing load, but at the cost of making some relational information inaccessible. Neural net models of relational representations show that relations with more arguments have a higher computational cost that coincides with experimental findings on higher processing loads in humans. Relational complexity is related to processing load in reasoning and sentence comprehension and can distinguish between the capacities of higher species. The complexity of relations processed by children increases with ape. Implications for neural net models and theories of cognition and cognitive development are discussed.
    BibTeX:
    @article{Halford1998,
      author = {Halford, GS and Wilson, WH and Phillips, S},
      title = {Processing capacity defined by relational complexity: Implications for comparative, developmental, and cognitive psychology},
      journal = {BEHAVIORAL AND BRAIN SCIENCES},
      year = {1998},
      volume = {21},
      number = {6},
      pages = {803+}
    }
    
    Hargadon, A. & Sutton, R. Technology brokering and innovation in a product development firm {1997} ADMINISTRATIVE SCIENCE QUARTERLY
    Vol. {42}({4}), pp. {716-749} 
    article  
    Abstract: We blend network and organizational memory perspectives in a model of technology brokering that explains how an organization develops innovative products, The model is grounded in observations, interviews, informal conversations, and archived data gathered during an ethnography of IDEO, a product design firm, This firm exploits its network position, working for clients in at least 40 industries, to gain knowledge of existing technological solutions in various industries. It acts as a technology broker by introducing these solutions where they are not known and, in the process, creates new products that are original combinations of existing knowledge from disparate industries. Designers exploit their access to a broad range of technological solutions with organizational routines for acquiring and storing this knowledge in the organization's memory and, by making analogies between current design problems and the past solutions they have seen, retrieving that knowledge to generate new solutions to design problems in other industries. We discuss the implications of this research for understanding the individual and organizational processes and norms underlying technology and knowledge transfer more generally.
    BibTeX:
    @article{Hargadon1997,
      author = {Hargadon, A and Sutton, RI},
      title = {Technology brokering and innovation in a product development firm},
      journal = {ADMINISTRATIVE SCIENCE QUARTERLY},
      year = {1997},
      volume = {42},
      number = {4},
      pages = {716-749}
    }
    
    Harrington, D., Haaland, K. & Knight, R. Cortical networks underlying mechanisms of time perception {1998} JOURNAL OF NEUROSCIENCE
    Vol. {18}({3}), pp. {1085-1095} 
    article  
    Abstract: Precise timing of sensory information from multiple sensory streams is essential for many aspects of human perception and action. Animal and human research implicates the basal ganglia and cerebellar systems in timekeeping operations, but investigations into the role of the cerebral cortex have been limited. Individuals with focal left (LHD) or right hemisphere (RHD) lesions and control subjects performed two time perception tasks (duration perception, wherein the standard tone pair interval was 300 or 600 msec) and a frequency perception task, which controlled for deficits in time-independent processes shared by both tasks. When frequency perception deficits were controlled, only patients with RHD showed time perception deficits. Time perception competency was correlated with an independent test of switching nonspatial attention in the RHD but not the LHD patients, despite attention deficits in both groups. Lesion overlays of patients with RHD and impaired timing showed that 100% of the patients with anterior damage had lesions in premotor and prefrontal cortex (Brodmann areas 6, 8, 9, and 46), and 100% with posterior damage had lesions in the inferior parietal cortex. All LHD patients with normal timing had damage in these same regions, whereas few, if any, RHD patients with normal timing had similar lesion distributions. These results implicate a right hemisphere prefrontal-inferior parietal network in timing. Time-dependent attention and working memory functions may contribute to temporal perception deficits observed after damage to this network.
    BibTeX:
    @article{Harrington1998,
      author = {Harrington, DL and Haaland, KY and Knight, RT},
      title = {Cortical networks underlying mechanisms of time perception},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1998},
      volume = {18},
      number = {3},
      pages = {1085-1095}
    }
    
    HASHER, L., STOLZFUS, E., ZACKS, R. & RYPMA, B. AGE AND INHIBITION {1991} JOURNAL OF EXPERIMENTAL PSYCHOLOGY-LEARNING MEMORY AND COGNITION
    Vol. {17}({1}), pp. {163-169} 
    article  
    Abstract: Two experiments assess adult age differences in the extent of inhibition or negative priming generated in a selective-attention task. Younger adults consistently demonstrated negative priming effects; they were slower to name a letter on a current trial that had served as a distractor on the previous trial relative to one that had not occurred on the previous trial. Whether or not inhibition dissipated when the response to stimulus interval was lengthened from 500 ms in Experiment 1 to 1,200 ms in Experiment 2 depended upon whether young subjects were aware of the patterns across trial types. Older adults did not show inhibition at either interval. The age effects are interpreted within the Hasher-Zacks (1988) framework, which proposes inhibition as a central mechanism determining the contents of working memory and consequently influencing a wide array of cognitive functions.
    BibTeX:
    @article{HASHER1991,
      author = {HASHER, L and STOLZFUS, ER and ZACKS, RT and RYPMA, B},
      title = {AGE AND INHIBITION},
      journal = {JOURNAL OF EXPERIMENTAL PSYCHOLOGY-LEARNING MEMORY AND COGNITION},
      year = {1991},
      volume = {17},
      number = {1},
      pages = {163-169}
    }
    
    Hasher, L., Zacks, R. & May, C. Inhibitory control, circadian arousal, and age {1999}
    Vol. {17}ATTENTION AND PERFORMANCE XVII - COGNITIVE REGULATION OF PERFORMANCE: INTERACTION OF THEOR AND APPLICATION , pp. {653-675} 
    inproceedings  
    Abstract: The empirical work reported here is based on a model of cognitive control over the contents of working memory. Using a variety of tasks, we consider three major functions of inhibition: access, deletion, and restraint over strong thoughts and actions. The data suggest that inhibition affords control over the momentary contents of working memory. In particular, poor inhibitory control results in enriched or cluttered contents in working memory (that is, time-sharing between relevant and nonrelevant information), and in the inappropriate production of strong but incorrect responses. Reductions in inhibitory control can have consequences for a variety of cognitive processes including learning, retrieval, and comprehension. Such reductions can make a person highly distractible, forgetful, inappropriately absorbed in either thought or the external world and less able to satisfy personal goals. The data reviewed here suggest that reductions in inhibitory control are associated with aging and, for both younger and older adults, with performing tasks that require inhibitory control at an individual's nonoptimal time of day.
    BibTeX:
    @inproceedings{Hasher1999,
      author = {Hasher, L and Zacks, RT and May, CP},
      title = {Inhibitory control, circadian arousal, and age},
      booktitle = {ATTENTION AND PERFORMANCE XVII - COGNITIVE REGULATION OF PERFORMANCE: INTERACTION OF THEOR AND APPLICATION },
      year = {1999},
      volume = {17},
      pages = {653-675},
      note = {17th International Symposium on Attention and Performance, BEIT OREN, ISRAEL, JUL 07-12, 1996}
    }
    
    HASSELMO, M. & SCHNELL, E. LAMINAR SELECTIVITY OF THE CHOLINERGIC SUPPRESSION OF SYNAPTIC TRANSMISSION IN RAT HIPPOCAMPAL REGION CA1 - COMPUTATIONAL MODELING AND BRAIN SLICE PHYSIOLOGY {1994} JOURNAL OF NEUROSCIENCE
    Vol. {14}({6}), pp. {3898-3914} 
    article  
    Abstract: ACh may set the dynamics of cortical function to those appropriate for learning new information. In models of the putative associative memory function of piriform cortex, selective suppression of intrinsic but not afferent fiber synaptic transmission by ACh prevents recall of previous input from interfering with the learning of new input (Hasselmo, 1993). Selective cholinergic suppression may play a similar role in the hippocampal formation, where Schaffer collateral synapses in stratum radiatum (s. rad) may store associations between activity in region CA3 and the entorhinal cortex input to region CA1 terminating in stratum lacunosum-moleculare (s. l-m). A computational model of region CA1 predicts that for effective associative memory function of the Schaffer collaterals, cholinergic suppression of synaptic transmission should be stronger in s. rad than in s. l-m. In the hippocampal slice preparation, we tested the effect of the cholinergic agonist carbachol (0.01-500 mu M) On synaptic transmission in s. rad and s. l-m. Stimulating and recording electrodes were simultaneously placed in both layers, allowing analysis of the effect of carbachol on synaptic potentials in both layers during the same perfusion in each slice. Carbachol produced a significantly stronger suppression of stimulus-evoked EPSPs in s. rad than in s. l-m at all concentrations greater than 1 mu M. At 100 mu M, EPSP initial slopes were suppressed by 89.1 +/- 3.0% in s. rad, but only by 40.1 +/- 4.1 % in s. l-m. The muscarinic antagonist atropine (1 mu M) blocked cholinergic suppression in both layers. These data support the hypothesis that synaptic modification of the Schaffer collaterals may store associations between activity in region CA3 and the afferent input to region CA1 from the entorhinal cortex. In simulations, feedback regulation of cholinergic modulation based on activity in region CA1 sets the appropriate dynamics of learning for novel associations, and recall for familiar associations.
    BibTeX:
    @article{HASSELMO1994,
      author = {HASSELMO, ME and SCHNELL, E},
      title = {LAMINAR SELECTIVITY OF THE CHOLINERGIC SUPPRESSION OF SYNAPTIC TRANSMISSION IN RAT HIPPOCAMPAL REGION CA1 - COMPUTATIONAL MODELING AND BRAIN SLICE PHYSIOLOGY},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1994},
      volume = {14},
      number = {6},
      pages = {3898-3914}
    }
    
    Hedden, T. & Gabrieli, J. Insights into the ageing mind: A view from cognitive neuroscience {2004} NATURE REVIEWS NEUROSCIENCE
    Vol. {5}({2}), pp. {87-U12} 
    article DOI  
    Abstract: As we grow older, we may grow wiser, but we can also experience memory loss and cognitive slowing that can interfere with our daily routines. The cognitive neuroscience of human ageing, which relies largely on neuroimaging techniques, relates these cognitive changes to their neural substrates, including structural and functional changes in the prefrontal cortex, medial temporal lobe regions and white matter tracts. Much remains unknown about how normal ageing affects the neural basis of cognition, but recent research on individual differences in the trajectory of ageing effects is helping to distinguish normal from pathological origins of age-related cognitive changes.
    BibTeX:
    @article{Hedden2004,
      author = {Hedden, T and Gabrieli, JDE},
      title = {Insights into the ageing mind: A view from cognitive neuroscience},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2004},
      volume = {5},
      number = {2},
      pages = {87-U12},
      doi = {{10.1038/nrn1323}}
    }
    
    Henson, R. Short-term memory for serial order: The start-end model {1998} COGNITIVE PSYCHOLOGY
    Vol. {36}({2}), pp. {73-137} 
    article  
    Abstract: Three solutions to the problem of serial order can be identified: chaining, ordinal and positional theories. Error patterns in serial recall from short-term memory fail to support chaining theories, yet provide unequivocal evidence for positional theories. In a new model of short-term memory, the Start-End Model (SEM), the positions of items in a sequence are coded relative to the start and end of that sequence. Simulations confirm SEM's ability to capture the main phenomena in serial recall, such as the effects of primacy, recency, list length, grouping, modality, redundant suffices, proactive interference, retention interval, and phonological similarity. Moreover, SEM is the first model to capture the complete pattern of errors, including transpositions, repetitions, omissions, intrusions, confusions, and, in particular, positional errors between groups and between trials. Unlike other positional models however, SEM predicts that positional errors will maintain relative rather than absolute position, in agreement with recent experiments (Henson, 1977). (C) 1998 Academic Press.
    BibTeX:
    @article{Henson1998,
      author = {Henson, RNA},
      title = {Short-term memory for serial order: The start-end model},
      journal = {COGNITIVE PSYCHOLOGY},
      year = {1998},
      volume = {36},
      number = {2},
      pages = {73-137}
    }
    
    Hickok, G. & Poeppel, D. Opinion - The cortical organization of speech processing {2007} NATURE REVIEWS NEUROSCIENCE
    Vol. {8}({5}), pp. {393-402} 
    article DOI  
    Abstract: Despite decades of research, the functional neuroanatomy of speech processing has been difficult to characterize. A major impediment to progress may have been the failure to consider task effects when mapping speech-related processing systems. We outline a dual-stream model of speech processing that remedies this situation. In this model, a ventral stream processes speech signals for comprehension, and a dorsal stream maps acoustic speech signals to frontal lobe articulatory networks. The model assumes that the ventral stream is largely bilaterally organized - although there are important computational differences between the left- and right-hemisphere systems - and that the dorsal stream is strongly left-hemisphere dominant.
    BibTeX:
    @article{Hickok2007,
      author = {Hickok, Gregory and Poeppel, David},
      title = {Opinion - The cortical organization of speech processing},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2007},
      volume = {8},
      number = {5},
      pages = {393-402},
      doi = {{10.1038/nrn2113}}
    }
    
    Hickok, G. & Poeppel, D. Dorsal and ventral streams: a framework for understanding aspects of the functional anatomy of language {2004} COGNITION
    Vol. {92}({1-2}), pp. {67-99} 
    article DOI  
    Abstract: Despite intensive work on language-brain relations, and a fairly impressive accumulation of knowledge over the last several decades, there has been little progress in developing large-scale models of the functional anatomy of language that integrate neuropsychological, neuroimaging, and psycholinguistic data. Drawing on relatively recent developments in the cortical organization of vision, and on data from a variety of sources, we propose a new framework for understanding aspects of the functional anatomy of language which moves towards remedying this situation. The framework posits that early cortical stages of speech perception involve auditory fields in the superior temporal gyrus bilaterally (although asymmetrically). This cortical processing system then diverges into two broad processing streams, a ventral stream, which is involved in mapping sound onto meaning, and a dorsal stream, which is involved in mapping sound onto articulatory-based representations. The ventral stream projects ventro-laterally toward inferior posterior temporal cortex (posterior middle temporal gyrus) which serves as an interface between sound-based representations of speech in the superior temporal gyrus (again bilaterally) and widely distributed conceptual representations. The dorsal stream projects dorso-posteriorly involving a region in the posterior Sylvian fissure at the parietal-temporal boundary (area Spt), and ultimately projecting to frontal regions. This network provides a mechanism for the development and maintenance of ``parity'' between auditory and motor representations of speech. Although the proposed dorsal stream represents a very tight connection between processes involved in speech perception and speech production, it does not appear to be a critical component of the speech perception process under normal (ecologically natural) listening conditions, that is, when speech input is mapped onto a conceptual representation. We also propose some degree of bi-directionality in both the dorsal and ventral pathways. We discuss some recent empirical tests of this framework that utilize a range of methods. We also show how damage to different components of this framework can account for the major symptom clusters of the fluent aphasias, and discuss some recent evidence concerning how sentence-level processing might be integrated into the framework. (C) 2004 Elsevier B.V. All rights reserved.
    BibTeX:
    @article{Hickok2004,
      author = {Hickok, G and Poeppel, D},
      title = {Dorsal and ventral streams: a framework for understanding aspects of the functional anatomy of language},
      journal = {COGNITION},
      year = {2004},
      volume = {92},
      number = {1-2},
      pages = {67-99},
      doi = {{10.1016/j.cognition.2003.10.011}}
    }
    
    Hickok, G. & Poeppel, D. Towards a functional neuroanatomy of speech perception {2000} TRENDS IN COGNITIVE SCIENCES
    Vol. {4}({4}), pp. {131-138} 
    article  
    Abstract: The functional neuroanatomy of speech perception has been difficult to characterize. Part of the difficulty, we suggest, stems from the fact that the neural systems supporting `speech perception' vary as a function of the task. Specifically, the set of cognitive and neural systems involved in performing traditional laboratory speech perception tasks, such as syllable discrimination or identification, only partially overlap those involved in speech perception as it occurs during natural language comprehension. In this review, we argue that cortical fields in the posterior-superior temporal lobe, bilaterally, constitute the primary substrate for constructing sound-based representations of speech, and that these sound-based representations interface with different supramodal systems in a task-dependent manner. Tasks that require access to the mental lexicon (i.e. accessing meaning-based representations) rely on auditory-to-meaning interface systems in the cortex in the vicinity of the left temporal-parietal-occipital junction. Tasks that require explicit access to speech segments rely on auditory-motor interface systems in the left frontal and parietal lobes. this auditory-motor interface system also appears to be recruited in phonological working memory.
    BibTeX:
    @article{Hickok2000,
      author = {Hickok, G and Poeppel, D},
      title = {Towards a functional neuroanatomy of speech perception},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      year = {2000},
      volume = {4},
      number = {4},
      pages = {131-138}
    }
    
    Hikosaka, O., Takikawa, Y. & Kawagoe, R. Role of the basal ganglia in the control of purposive saccadic eye movements {2000} PHYSIOLOGICAL REVIEWS
    Vol. {80}({3}), pp. {953-978} 
    article  
    Abstract: In addition to their well-known role in skeletal movements, the basal ganglia control saccadic eye movements (saccades) by means of their connection to the superior colliculus (SC). The SC receives convergent inputs horn cerebral cortical areas and the basal ganglia. To make a saccade to an object purposefully, appropriate signals must be selected out of die cortical inputs, in which the basal ganglia play a crucial role. This is done by the sustained inhibitory input from the substantia nigra pars reticulata (SNr) to the SC. This inhibition can be removed by another inhibition from the caudate nucleus (CD) to the SNr, which results in a disinhibition of the SC. The basal ganglia have another mechanism, involving the external segment of the globus pallidus and the subthalamic nucleus, with which the SNr-SC inhibition can further be enhanced. The sensorimotor signals carried by the basal ganglia neurons are strongly modulated depending on the behavioral context, which reflects working memory, expectation, and attention. Expectation of reward is a critical determinant in that the saccade that has been rewarded is facilitated subsequently. The interaction between cortical and dopaminergic inputs to CD neurons may underlie the behavioral adaptation toward purposeful saccades.
    BibTeX:
    @article{Hikosaka2000,
      author = {Hikosaka, O and Takikawa, Y and Kawagoe, R},
      title = {Role of the basal ganglia in the control of purposive saccadic eye movements},
      journal = {PHYSIOLOGICAL REVIEWS},
      year = {2000},
      volume = {80},
      number = {3},
      pages = {953-978}
    }
    
    HITCH, G. ROLE OF SHORT-TERM WORKING MEMORY IN MENTAL ARITHMETIC {1978} COGNITIVE PSYCHOLOGY
    Vol. {10}({3}), pp. {302-323} 
    article  
    BibTeX:
    @article{HITCH1978,
      author = {HITCH, GJ},
      title = {ROLE OF SHORT-TERM WORKING MEMORY IN MENTAL ARITHMETIC},
      journal = {COGNITIVE PSYCHOLOGY},
      year = {1978},
      volume = {10},
      number = {3},
      pages = {302-323}
    }
    
    Hodges, H. Maze procedures: The radial-arm and water maze compared {1996} COGNITIVE BRAIN RESEARCH
    Vol. {3}({3-4}), pp. {167-181} 
    article  
    Abstract: Open mazes are primarily designed to measure place learning and memory, using environmental visuospatial cues. However, maze tasks differ along many dimensions, including (I) types of apparatus, which vary from arenas (water maze: WM) to highly structured routes (radial-arm maze: RAM); (2) availability of visuospatial, associative or sensory cues; (3) task requirements which range from spontaneous exploration to complex sequences of choices; and (4) motivation which may involve aversive escape, the opportunity to shelter or to discover novel objects or food at particular locations. Given this diversity, it is likely that mazes tap a variety of processes that contribute to, or affect spatial learning. Hence `spatial' abilities measured in one procedure may not resemble those engaged in another, posing problems for the interpretation of drug- or lesion-induced deficits. This review compares two types of maze that exemplify key differences in procedure: the RAM and the WM. (1) Visuospatial, associative and sensory factors contributing to place learning in the two mazes are discussed, together with the types of search strategy that they foster, their differing motivation and vulnerability to effects of non-spatial factors, such as stress and training regime. (2) The equivalence of memory processes (acquisition, working and reference memory) assessed in different mazes is considered, and the extent that these may generalise to non-spatial tasks. (3) Differences in application of the two mazes are evaluated. The WM is well-adapted to the study of selective visuospatial factors in place learning and working memory, but less suitable for repeated measures or for assessment of long-term memory deficits. The RAM detects steady-state reference and working-memory deficits, and is suitable for repeated measures, at the expense of precise analysis of the nature of the processes involved.
    BibTeX:
    @article{Hodges1996,
      author = {Hodges, H},
      title = {Maze procedures: The radial-arm and water maze compared},
      journal = {COGNITIVE BRAIN RESEARCH},
      year = {1996},
      volume = {3},
      number = {3-4},
      pages = {167-181}
    }
    
    Hopfinger, J., Buonocore, M. & Mangun, G. The neural mechanisms of top-down attentional control {2000} NATURE NEUROSCIENCE
    Vol. {3}({3}), pp. {284-291} 
    article  
    Abstract: Selective visual attention involves dynamic interplay between attentional control systems and sensory brain structures. We used event-related functional magnetic resonance imaging (fMRI) during a cued spatial-attention task to dissociate brain activity related to attentional control from that related to selective processing of target stimuli. Distinct networks were engaged by attention-directing cues versus subsequent targets. Superior frontal, inferior parietal and superior temporal cortex were selectively activated by cues, indicating that these structures are part of a network for voluntary attentional control. This control biased activity in multiple visual cortical areas, resulting in selective sensory processing of relevant visual targets.
    BibTeX:
    @article{Hopfinger2000,
      author = {Hopfinger, JB and Buonocore, MH and Mangun, GR},
      title = {The neural mechanisms of top-down attentional control},
      journal = {NATURE NEUROSCIENCE},
      year = {2000},
      volume = {3},
      number = {3},
      pages = {284-291}
    }
    
    HUGHES, C., RUSSELL, J. & ROBBINS, T. EVIDENCE FOR EXECUTIVE DYSFUNCTION IN AUTISM {1994} NEUROPSYCHOLOGIA
    Vol. {32}({4}), pp. {477-492} 
    article  
    Abstract: A group of young people with autism (ranging in ability from high functioning to moderately learning disabled), and ability-matched control groups of (i) non-autistic individuals with moderate learning disabilities, and (ii) normally developing children, were presented with two tests of executive function: the Intra-dimensional/Extra-dimensional set-shifting task and the Tower of London planning task. These tests were graded in difficulty and included internal control measures. On each task, the autistic group was differentially impaired with respect to both control groups. Moreover, this impairment was specific to the stages of each task which placed greatest demands upon executive control. This evidence for executive dysfunction in autism is discussed in the context of Norman and Shallice's (Centre for Human Information Processing Technical Report 99, 198O) `'Supervisory Attentional System'' model of frontal function.
    BibTeX:
    @article{HUGHES1994,
      author = {HUGHES, C and RUSSELL, J and ROBBINS, TW},
      title = {EVIDENCE FOR EXECUTIVE DYSFUNCTION IN AUTISM},
      journal = {NEUROPSYCHOLOGIA},
      year = {1994},
      volume = {32},
      number = {4},
      pages = {477-492}
    }
    
    Ishai, A., Ungerleider, L. & Haxby, J. Distributed neural systems for the generation of visual images {2000} NEURON
    Vol. {28}({3}), pp. {979-990} 
    article  
    Abstract: Visual perception of houses, faces, and chairs evoke differential responses in ventral temporal cortex. Using fMRI, we compared activations evoked by perception and imagery of these object categories. We found content-related activation during imagery in extrastriate cortex, but this activity was restricted to small subsets of the regions that showed category-related activation during perception. Within ventral temporal cortex, activation during imagery evoked stronger responses on the left whereas perception evoked stronger responses on the right. Additionally, visual imagery evoked activity in parietal and frontal cortex, but this activity was not content related. These results suggest that content-related activation during imagery in visual extrastriate cortex may be implemented by ``top-down'' mechanisms in parietal and frontal cortex that mediate the retrieval of face and object representations from long-term memory and their maintenance through visual imagery.
    BibTeX:
    @article{Ishai2000,
      author = {Ishai, A and Ungerleider, LG and Haxby, JV},
      title = {Distributed neural systems for the generation of visual images},
      journal = {NEURON},
      year = {2000},
      volume = {28},
      number = {3},
      pages = {979-990}
    }
    
    JARRARD, L. ON THE ROLE OF THE HIPPOCAMPUS IN LEARNING AND MEMORY IN THE RAT {1993} BEHAVIORAL AND NEURAL BIOLOGY
    Vol. {60}({1}), pp. {9-26} 
    article  
    BibTeX:
    @article{JARRARD1993,
      author = {JARRARD, LE},
      title = {ON THE ROLE OF THE HIPPOCAMPUS IN LEARNING AND MEMORY IN THE RAT},
      journal = {BEHAVIORAL AND NEURAL BIOLOGY},
      year = {1993},
      volume = {60},
      number = {1},
      pages = {9-26}
    }
    
    JEANNEROD, M. MENTAL-IMAGERY IN THE MOTOR CONTEXT {1995} NEUROPSYCHOLOGIA
    Vol. {33}({11}), pp. {1419-1432} 
    article  
    Abstract: The working hypothesis of the paper is that motor images are endowed with the same properties as those of the (corresponding) motor representations, and therefore have the same functional relationship to the imagined or represented movement and the same causal role in the generation of this movement. The fact that the timing of simulated movements follows the same constraints as that of actually executed movements is consistent with this hypothesis. Accordingly, many neural mechanisms are activated during motor imagery, as revealed by a sharp increase in tendinous reflexes in the limb imagined to move, and by vegetative changes which correlate with the level of mental effort. At the cortical level, a specific pattern of activation, that closely resembles that of action execution, is observed in areas devoted to motor control. This activation might be the substrate for the effects of mental training. A hierarchical model of the organization of action is proposed: this model implies a short-term memory storage of a `copy' of the various representational steps. These memories are erased when an action corresponding to the represented goal takes place. By contrast, if the action is incompletely or not executed, the whole system remains activated, and the content of the representation is rehearsed. This mechanism would be the substrate for conscious access to this content during motor imagery and mental training.
    BibTeX:
    @article{JEANNEROD1995,
      author = {JEANNEROD, M},
      title = {MENTAL-IMAGERY IN THE MOTOR CONTEXT},
      journal = {NEUROPSYCHOLOGIA},
      year = {1995},
      volume = {33},
      number = {11},
      pages = {1419-1432}
    }
    
    Jentsch, J., Redmond, D., Elsworth, J., Taylor, J., Youngren, K. & Roth, R. Enduring cognitive deficits and cortical dopamine dysfunction in monkeys after long-term administration of phencyclidine {1997} SCIENCE
    Vol. {277}({5328}), pp. {953-955} 
    article  
    Abstract: The effects of the psychotomimetic drug phencyclidine on the neurochemistry and function of the prefrontal cortex in vervet monkeys were investigated, Monkeys treated with phencyclidine twice a day for 14 days displayed performance deficits on a task that was sensitive to prefrontal cortex function; the deficits were ameliorated by the atypical antipsychotic drug clozapine, Repeated exposure to phencyclidine caused a reduction in both basal and evoked dopamine utilization in the dorsolateral prefrontal cortex, a brain region that has long been associated with cognitive function, Behavioral deficits and decreased dopamine utilization remained after phencyclidine treatment was stopped, an indication that these effects were not simply due to direct drug effects. The data suggest that repeated administration of phencyclidine in monkeys may be useful for studying psychiatric disorders associated with cognitive dysfunction and dopamine hypofunction in the prefrontal cortex, particularly schizophrenia.
    BibTeX:
    @article{Jentsch1997,
      author = {Jentsch, JD and Redmond, DE and Elsworth, JD and Taylor, JR and Youngren, KD and Roth, RH},
      title = {Enduring cognitive deficits and cortical dopamine dysfunction in monkeys after long-term administration of phencyclidine},
      journal = {SCIENCE},
      year = {1997},
      volume = {277},
      number = {5328},
      pages = {953-955}
    }
    
    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}
    }
    
    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., Schumacher, E., Smith, E., Lauber, E., Awh, E., Minoshima, S. & Koeppe, R. Verbal working memory load affects regional brain activation as measured by PET {1997} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {9}({4}), pp. {462-475} 
    article  
    Abstract: We report an experiment that assesses the effect of variations in memory load on brain activations that mediate verbal working memory. The paradigm that forms the basis of this experiment is the `'n-back'' task in which subjects must decide for each letter in a series whether it matches the one presented n items back in the series. This task is of interest because it recrdts processes involved in both the storage and manipulation of information in working memory. Variations in task difficulty were accomplished by varying the value of n. As n increased, subjects showed poorer behavioral performance as well as monotonically increasing magnitudes of brain activation in a large number of sites that together have been identified with verbal working-memory processes. By contrast, there was no reliable increase in activation in sites that are unrelated to working memory. These results validate the use of parametric manipulation of task variables in neuroimaging research, and they converge with the subtraction paradigm used most often in neuroimaging. In addition, the data support a model of working memory that includes both storage and executive processes that recruit a network of brain areas, all of which are involved in task performance.
    BibTeX:
    @article{Jonides1997,
      author = {Jonides, J and Schumacher, EH and Smith, EE and Lauber, EJ and Awh, E and Minoshima, S and Koeppe, RA},
      title = {Verbal working memory load affects regional brain activation as measured by PET},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {1997},
      volume = {9},
      number = {4},
      pages = {462-475}
    }
    
    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}
    }
    
    Jonides, J., Smith, E., Marshuetz, C., Koeppe, R. & Reuter-Lorenz, P. Inhibition in verbal working memory revealed by brain activation {1998} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {95}({14}), pp. {8410-8413} 
    article  
    Abstract: There are many occasions in which humans and other animals must inhibit the production of some behavior or inhibit the processing of some internal representation. Success in inhibitory processing under normal circumstances can be revealed by the fact that certain brain pathologies render inhibitory processing ineffective. These pathologies often have been associated with damage to frontal cortex, including lateral and inferior aspects. We provide behavioral evidence of a verbal working memory task that, by hypothesis, engaged inhibitory processing, and we show (by using positron emission tomography) that the inhibitory processing is associated with a lateral portion of the left prefrontal cortex. The task in which subjects engaged was item-recognition: Four target letters were presented for storage followed, after a brief interval, by a probe letter that could match a target letter or not. On some trials, when the probe did not match a target letter and therefore required a ``no'' response, the probe had matched a target letter of the previous trial, so on these trials a ``yes'' response was prepotent and had to be inhibited, by hypothesis. Compared with a condition in which no prepotent response was created, this condition yielded brain activation in left inferior frontal gyrus, in the region of Brodmann's area 45.
    BibTeX:
    @article{Jonides1998a,
      author = {Jonides, J and Smith, EE and Marshuetz, C and Koeppe, RA and Reuter-Lorenz, PA},
      title = {Inhibition in verbal working memory revealed by brain activation},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1998},
      volume = {95},
      number = {14},
      pages = {8410-8413}
    }
    
    JUNG, M. & MCNAUGHTON, B. SPATIAL SELECTIVITY OF UNIT-ACTIVITY IN THE HIPPOCAMPAL GRANULAR LAYER {1993} HIPPOCAMPUS
    Vol. {3}({2}), pp. {165-182} 
    article  
    Abstract: Single neuron activity was recorded in the granular layer of the fascia dentata in freely moving rats, while the animals performed a spatial `'working'' memory task on an eight-arm maze. Using recording methods that facilitate detection of units with low discharge rates, it was found that the majority (88 of cells in this layer have mean rates below 0.5 Hz, with a minimum of 0.01 Hz or less. The remaining recorded cells exhibited characteristics typical of the theta interneurons found throughout the hippocampus. Based on several criteria including relative proportion and the relation of their evoked discharges to the population spike elicited by perforant path stimulation, it was concluded that the low-rate cells correspond to granule cells. Granule cells exhibited clear spatially and directionally selective discharge that was at least as selective as that of a sample of CA3 pyramidal cells recorded under the same conditions. Granule cells had significantly smaller place fields than pyramidal cells, and tended to have more discontiguous subfields. There was no spatial correlation among simultaneously recorded adjacent granule cells. Granule cells also exhibited burst discharges reminiscent of complex spikes from pyramidal cells while the animals sat quietly; however, the spike duration of granule cells was significantly shorter than CA3 pyramidal cell spike durations. Under conditions of environmental stability, granule cell place fields were stable for at least several days. Following occasional maze rotations relative to the (somewhat impoverished) visual stimuli of the recording room, granule cell place fields were maintained relative to the distal spatial cues; however, frequent rotations of the maze sometimes resulted in a shift in the reference frame to the maze itself. These observations indicate that granule cells of the fascia dentata provide their CA3 targets with a high degree of spatial information, in the form of a sparsely coded, distributed representation.
    BibTeX:
    @article{JUNG1993,
      author = {JUNG, MW and MCNAUGHTON, BL},
      title = {SPATIAL SELECTIVITY OF UNIT-ACTIVITY IN THE HIPPOCAMPAL GRANULAR LAYER},
      journal = {HIPPOCAMPUS},
      year = {1993},
      volume = {3},
      number = {2},
      pages = {165-182}
    }
    
    JUST, M. & CARPENTER, P. A CAPACITY THEORY OF COMPREHENSION - INDIVIDUAL-DIFFERENCES IN WORKING MEMORY {1992} PSYCHOLOGICAL REVIEW
    Vol. {99}({1}), pp. {122-149} 
    article  
    Abstract: A theory of the way working memory capacity constrains comprehension is proposed. The theory proposes that both processing and storage are mediated by activation and that the total amount of activation available in working memory varies among individuals. Individual differences in working memory capacity for language can account for qualitative and quantitative differences among college-age adults in several aspects of language comprehension. One aspect is syntactic modularity: The larger capacity of some individuals permits interaction among syntactic and pragmatic information, so that their syntactic processes are not informationally encapsulated. Another aspect is syntactic ambiguity: The larger capacity of some individuals permits them to maintain multiple interpretations. The theory is instantiated as a production system model in which the amount of activation available to the model affects how it adapts to the transient computational and storage demands that occur in comprehension.
    BibTeX:
    @article{JUST1992,
      author = {JUST, MA and CARPENTER, PA},
      title = {A CAPACITY THEORY OF COMPREHENSION - INDIVIDUAL-DIFFERENCES IN WORKING MEMORY},
      journal = {PSYCHOLOGICAL REVIEW},
      year = {1992},
      volume = {99},
      number = {1},
      pages = {122-149}
    }
    
    Just, M., Carpenter, P., Keller, T., Eddy, W. & Thulborn, K. Brain activation modulated by sentence comprehension {1996} SCIENCE
    Vol. {274}({5284}), pp. {114-116} 
    article  
    Abstract: The comprehension of visually presented sentences produces brain activation that increases with the linguistic complexity of the sentence. The volume of neural tissue activated (number of voxels) during sentence comprehension was measured with echo-planar functional magnetic resonance imaging. The modulation of the volume of activation by sentence complexity was observed In a network of lour areas: the classical left-hemisphere language areas (the left laterosuperior temporal cortex, or Wernicke's area, and the left inferior frontal gyrus, or Broca's area) and their homologous right-hemisphere areas, although the right areas had much smaller volumes of activation than did the left areas. These findings generally indicate that the amount of neural activity that a given cognitive process engenders is dependent on the computational demand that the task imposes.
    BibTeX:
    @article{Just1996,
      author = {Just, MA and Carpenter, PA and Keller, TA and Eddy, WF and Thulborn, KR},
      title = {Brain activation modulated by sentence comprehension},
      journal = {SCIENCE},
      year = {1996},
      volume = {274},
      number = {5284},
      pages = {114-116}
    }
    
    KAIL, R. & SALTHOUSE, T. PROCESSING SPEED AS A MENTAL-CAPACITY {1994} ACTA PSYCHOLOGICA
    Vol. {86}({2-3}), pp. {199-225} 
    article  
    Abstract: Throughout the lifespan, there are pronounced age differences in speed of processing, differences that are consistently related to performance on measures of higher-order cognition. In this article, we examine domain-specific and global explanations of these age differences in processing speed; we conclude that although experience can play a role in age differences in speed, there is also evidence that a general mechanism limits speeded performance. We also review research that shows the influence of processing speed on the quality of performance on nonspeeded tasks such as reasoning and memory. We suggest that speed of processing should be viewed as a fundamental part of the architecture of the cognitive system as it develops across the entire lifespan.
    BibTeX:
    @article{KAIL1994,
      author = {KAIL, R and SALTHOUSE, TA},
      title = {PROCESSING SPEED AS A MENTAL-CAPACITY},
      journal = {ACTA PSYCHOLOGICA},
      year = {1994},
      volume = {86},
      number = {2-3},
      pages = {199-225}
    }
    
    Kalyuga, S., Ayres, P., Chandler, P. & Sweller, J. The expertise reversal effect {2003} EDUCATIONAL PSYCHOLOGIST
    Vol. {38}({1}), pp. {23-31} 
    article  
    Abstract: When new information is presented to learners, it must be processed in a severely limited working memory. Learning reduces working memory limitations by enabling the use of schemas, stored in long-term memory, to process information more efficiently. Several instructional techniques have been designed to facilitate schema construction and automation by reducing working memory load. Recently, however, strong evidence has emerged that the effectiveness of these techniques depends very much on levels of learner expertise. Instructional techniques that are highly effective with inexperienced learners can lose their effectiveness and even have negative consequences when used with more experienced learners. We call this phenomenon the expertise reversal effect. In this article, we review the empirical literature on the interaction between instructional techniques and levels. of learner experience that led to the identification of the expertise reversal effect.
    BibTeX:
    @article{Kalyuga2003,
      author = {Kalyuga, S and Ayres, P and Chandler, P and Sweller, J},
      title = {The expertise reversal effect},
      journal = {EDUCATIONAL PSYCHOLOGIST},
      year = {2003},
      volume = {38},
      number = {1},
      pages = {23-31},
      note = {9th European Conference for Research on Learning and Instruction, FRIBOURG, SWITZERLAND, AUG, 2001}
    }
    
    Kane, M., Bleckley, M., Conway, A. & Engle, R. A controlled-attention view of working-memory capacity {2001} JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL
    Vol. {130}({2}), pp. {169-183} 
    article  
    Abstract: In 2 experiments the authors examined whether individual differences in working-memory (WM) capacity are related to attentional control. Experiment 1 tested high- and low-WM-span (high-span and low-span) participants in a prosaccade task, in which a visual cue appeared in the same location as a subsequent to-be-identified target letter, and in an antisaccade task, in which a target appeared opposite the cued location. Span groups identified targets equally well in the prosaccade task, reflecting equivalence in automatic orienting. However, low-span participants were slower and less accurate than high-span participants in the antisaccade task, reflecting differences in attentional control. Experiment 2 measured eye movements across a long antisaccade session. Low-span participants made slower and more erroneous saccades than did high-span participants. In both experiments, low-span participants performed poorly when task switching from antisaccade to prosaccade blocks. The findings support a controlled-attention view of WM capacity.
    BibTeX:
    @article{Kane2001,
      author = {Kane, MJ and Bleckley, MK and Conway, ARA and Engle, RW},
      title = {A controlled-attention view of working-memory capacity},
      journal = {JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL},
      year = {2001},
      volume = {130},
      number = {2},
      pages = {169-183}
    }
    
    Kane, M. & Engle, R. Working-memory capacity and the control of attention: The contributions of goal neglect, response competition, and task set to Stroop interference {2003} JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL
    Vol. {132}({1}), pp. {47-70} 
    article DOI  
    Abstract: Individual differences in working-memory (WM) capacity predicted performance on the Stroop task in 5 experiments, indicating the importance of executive control and goal maintenance to selective attention. When the Stroop task encouraged goal neglect by including large numbers of congruent trials (RED Presented in red), low WM individuals committed more errors than did high WM individuals on the rare incongruent trials.(BLUE in red) that required maintaining access to the ``ignore-the-word'' goal for accurate responding. In contrast, in tasks with no or few congruent trials, or in high-congruency tasks that followed low-congruency tasks, WM predicted response-time interference. WM was related to latency, not accuracy, in contexts that reinforced the task goal and so minimized the difficulty of actively maintaining it. The data and a literature review suggest that Stroop interference is jointly determined by 2 mechanisms, goal maintenance and competition resolution, and that the dominance of each depends on WM capacity, as well as the task set induced by current and previous contexts.
    BibTeX:
    @article{Kane2003,
      author = {Kane, MJ and Engle, RW},
      title = {Working-memory capacity and the control of attention: The contributions of goal neglect, response competition, and task set to Stroop interference},
      journal = {JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL},
      year = {2003},
      volume = {132},
      number = {1},
      pages = {47-70},
      doi = {{10.1037/0096-3445.132.1.47}}
    }
    
    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}
    }
    
    Kane, M., Hambrick, D., Tuholski, S., Wilhelm, O., Payne, T. & Engle, R. The generality of working memory capacity: A latent-variable approach to verbal and visuospatial memory span and reasoning {2004} JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL
    Vol. {133}({2}), pp. {189-217} 
    article  
    Abstract: A latent-variable study examined whether verbal and visuospatial working memory (WM) capacity measures reflect a primarily domain-general construct by testing 236 participants in 3 span tests each of verbal WM, visuospatial WM, verbal short-term memory (STM), and visuospatial STM, as well as in tests of verbal and spatial reasoning and general fluid intelligence (Gf). Confirmatory factor analyses and structural equation models indicated that the WM tasks largely reflected a domain-general factor, whereas STM tasks, based on the same stimuli as the WM tasks, were much more domain specific. The WM construct was a strong predictor of Gf and a weaker predictor of domain-specific reasoning, and the reverse was true for the STM construct. The findings support a domain-general view of WM capacity, in which executive-attention processes drive the broad predictive utility of WM span measures, and domain-specific storage and rehearsal processes relate more strongly to domain-specific aspects of complex cognition.
    BibTeX:
    @article{Kane2004,
      author = {Kane, MJ and Hambrick, DZ and Tuholski, SW and Wilhelm, O and Payne, TW and Engle, RW},
      title = {The generality of working memory capacity: A latent-variable approach to verbal and visuospatial memory span and reasoning},
      journal = {JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL},
      year = {2004},
      volume = {133},
      number = {2},
      pages = {189-217}
    }
    
    Kanwisher, N. & Wojciulik, E. Visual attention: Insights from brain imaging {2000} NATURE REVIEWS NEUROSCIENCE
    Vol. {1}({2}), pp. {91-100} 
    article  
    Abstract: We are not passive recipients of the information that impinges on our retinae, but active participants in our own perceptual processes. Visual experience depends critically on attention. We select particular aspects of a visual scene for detailed analysis and control of subsequent behaviour, but ignore other aspects so completely that moments after they disappear from view we cannot report anything about them. Here we show that functional neuroimaging is revealing much more than where attention happens in the brain; it is beginning to answer some of the oldest and deepest questions about what visual attention is and how it works.
    BibTeX:
    @article{Kanwisher2000,
      author = {Kanwisher, N and Wojciulik, E},
      title = {Visual attention: Insights from brain imaging},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2000},
      volume = {1},
      number = {2},
      pages = {91-100}
    }
    
    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}
    }
    
    KESNER, R., BOLLAND, B. & DAKIS, M. MEMORY FOR SPATIAL LOCATIONS, MOTOR-RESPONSES, AND OBJECTS - TRIPLE DISSOCIATION AMONG THE HIPPOCAMPUS, CAUDATE-NUCLEUS, AND EXTRASTRIATE VISUAL-CORTEX {1993} EXPERIMENTAL BRAIN RESEARCH
    Vol. {93}({3}), pp. {462-470} 
    article  
    Abstract: Based on behavioral procedures aimed at measuring working or data-based memory for spatial location, response, and visual object information, it is shown that there is a triple dissociation among the hippocampus, caudate nucleus, and extrastriate visual cortex in mediating spatial location, response, and visual object information, respectively. The hippocampus appears to subserve only spatial location, the caudate nucleus only response, and the extrastriate visual cortex only visual object information. The results support the neurobiological foundation of the attribute memory model.
    BibTeX:
    @article{KESNER1993,
      author = {KESNER, RP and BOLLAND, BL and DAKIS, M},
      title = {MEMORY FOR SPATIAL LOCATIONS, MOTOR-RESPONSES, AND OBJECTS - TRIPLE DISSOCIATION AMONG THE HIPPOCAMPUS, CAUDATE-NUCLEUS, AND EXTRASTRIATE VISUAL-CORTEX},
      journal = {EXPERIMENTAL BRAIN RESEARCH},
      year = {1993},
      volume = {93},
      number = {3},
      pages = {462-470}
    }
    
    Kim, J. & Diamond, D. The stressed hippocampus, synaptic plasticity and lost memories {2002} NATURE REVIEWS NEUROSCIENCE
    Vol. {3}({6}), pp. {453-462} 
    article DOI  
    Abstract: Stress is a biologically significant factor that, by altering brain cell properties, can disturb cognitive processes such as learning and memory, and consequently limit the quality of human life. Extensive rodent and human research has shown that the hippocampus is not only crucially involved in memory formation, but is also highly sensitive to stress. So, the study of stress-induced cognitive and neurobiological sequelae in animal models might provide valuable insight into the mnemonic mechanisms that are vulnerable to stress. Here, we provide an overview of the neurobiology of stress-memory interactions, and present a neural-endocrine model to explain how stress modifies hippocampal functioning.
    BibTeX:
    @article{Kim2002,
      author = {Kim, JJ and Diamond, DM},
      title = {The stressed hippocampus, synaptic plasticity and lost memories},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2002},
      volume = {3},
      number = {6},
      pages = {453-462},
      doi = {{10.1038/nrn849}}
    }
    
    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}
    }
    
    KIMBERG, D. & FARAH, M. A UNIFIED ACCOUNT OF COGNITIVE IMPAIRMENTS FOLLOWING FRONTAL-LOBE DAMAGE - THE ROLE OF WORKING-MEMORY IN COMPLEX, ORGANIZED BEHAVIOR {1993} JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL
    Vol. {122}({4}), pp. {411-428} 
    article  
    Abstract: A computer model is presented that performs 4 tasks sometimes impaired by frontal damage: motor sequencing, the Stroop task, the Wisconsin Card Sorting Test, and a context memory task. In each task, patterns of performance typical of frontal-damaged patients are shown to result from the same type of damage to the model, specifically, weakening of associations among elements in working memory. The simulation shows how a single underlying type of damage could result in impairments on a variety of seemingly distinct tasks. Furthermore, the hypothesized damage affects the processing components that carry out the task rather than a distinct central executive.
    BibTeX:
    @article{KIMBERG1993,
      author = {KIMBERG, DY and FARAH, MJ},
      title = {A UNIFIED ACCOUNT OF COGNITIVE IMPAIRMENTS FOLLOWING FRONTAL-LOBE DAMAGE - THE ROLE OF WORKING-MEMORY IN COMPLEX, ORGANIZED BEHAVIOR},
      journal = {JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL},
      year = {1993},
      volume = {122},
      number = {4},
      pages = {411-428}
    }
    
    KING, J. & JUST, M. INDIVIDUAL-DIFFERENCES IN SYNTACTIC PROCESSING - THE ROLE OF WORKING MEMORY {1991} JOURNAL OF MEMORY AND LANGUAGE
    Vol. {30}({5}), pp. {580-602} 
    article  
    BibTeX:
    @article{KING1991,
      author = {KING, J and JUST, MA},
      title = {INDIVIDUAL-DIFFERENCES IN SYNTACTIC PROCESSING - THE ROLE OF WORKING MEMORY},
      journal = {JOURNAL OF MEMORY AND LANGUAGE},
      year = {1991},
      volume = {30},
      number = {5},
      pages = {580-602}
    }
    
    Kirchhoff, B., Wagner, A., Maril, A. & Stern, C. Prefrontal-temporal circuitry for episodic encoding and subsequent memory {2000} JOURNAL OF NEUROSCIENCE
    Vol. {20}({16}), pp. {6173-6180} 
    article  
    Abstract: Humans encounter and form memories for multiple types of experiences that differ in content, novelty, and memorability. Critical for understanding memory is determining (1) how the brain supports the encoding of events with differing content and (2) whether neural regions that are sensitive to novelty also influence whether stimuli will be subsequently remembered. This event-related functional magnetic resonance imaging (fMRI) study crossed content (picture/word), novelty (novel/repeated), and subsequent memory (remembered/forgotten) to examine prefrontal and temporal lobe contributions to encoding. Results revealed three patterns of encoding-related activation in anatomically connected inferior prefrontal and lateral temporal structures that appeared to vary depending on whether visuospatial/visuoobject, phonological/lexical, or semantic attributes were processed. Event content also modulated medial temporal lobe activity; word encoding predominately activated the left hemisphere, whereas picture encoding activated both hemispheres. Critically, in prefrontal and temporal regions that were modulated by novelty, the magnitude of encoding activation also predicted whether an event would be subsequently remembered. These results suggest that (1) regions that demonstrate a sensitivity to novelty may actively support encoding processes that impact subsequent explicit memory and (2) multiple content-dependent prefrontal-temporal circuits support event encoding. The similarities between prefrontal and lateral temporal encoding responses raise the possibility that prefrontal modulation of posterior cortical representations is central to encoding.
    BibTeX:
    @article{Kirchhoff2000,
      author = {Kirchhoff, BA and Wagner, AD and Maril, A and Stern, CE},
      title = {Prefrontal-temporal circuitry for episodic encoding and subsequent memory},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2000},
      volume = {20},
      number = {16},
      pages = {6173-6180}
    }
    
    Klimesch, W. EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis {1999} BRAIN RESEARCH REVIEWS
    Vol. {29}({2-3}), pp. {169-195} 
    article  
    Abstract: Evidence is presented that EEG oscillations in the alpha and theta band reflect cognitive and memory performance in particular. Good performance is related to two types of EEG phenomena (i) a tonic increase in alpha but a decrease in theta power, and (ii) a large phasic (event-related) decrease in alpha but increase in theta, depending on the type of memory demands. Because alpha frequency shows large interindividual differences which are related to age and memory performance, this double dissociation between alpha vs. theta and tonic vs. phasic changes can be observed only if fixed frequency bands are abandoned. It is suggested to adjust the frequency windows of alpha and theta for each subject by using individual alpha frequency as an anchor point. Based on this procedure, a consistent interpretation of a variety of findings is made possible. As an example, in a similar way as brain volume does, upper alpha power increases (but theta power decreases) from early childhood to adulthood, whereas the opposite holds true for the late part of the lifespan. Alpha power is lowered and theta power enhanced in subjects with a variety of different neurological disorders. Furthermore, after sustained wakefulness and during the transition from waking to sleeping when the ability to respond to external stimuli ceases, upper alpha power decreases, whereas theta increases. Event-related changes indicate that the extent of upper alpha desynchronization is positively correlated with (semantic) long-term memory performance, whereas theta synchronization is positively correlated with the ability to encode new information. The reviewed findings are interpreted on the basis of brain oscillations. It is suggested that the encoding of new information is reflected by theta oscillations in hippocampo-cortical feedback loops, whereas search and retrieval processes in (semantic) long-term memory are reflected by upper alpha oscillations in thalamo-cortical feedback loops. (C) 1999 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{Klimesch1999,
      author = {Klimesch, W},
      title = {EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis},
      journal = {BRAIN RESEARCH REVIEWS},
      year = {1999},
      volume = {29},
      number = {2-3},
      pages = {169-195}
    }
    
    Klingberg, T., Vaidya, C., Gabrieli, J., Moseley, M. & Hedehus, M. Myelination and organization of the frontal white matter in children: a diffusion tensor MRI study {1999} NEUROREPORT
    Vol. {10}({13}), pp. {2817-2821} 
    article  
    Abstract: MYELINATION is critical for the functional development of the brain, but the time course of myelination during childhood is not well known. Diffusion tensor MR imaging (DTI) provides a new method for estimating myelination in vivo. Myelin restricts diffusion of water transverse to the axons, causing diffusion to be anisotropic. By quantifying the anisotropy, the progressive myelination of axons can be studied. Central white matter of the frontal lobe was studied in seven children (mean age 10 years) and five adults (mean age 27 years). Anisotropy in the frontal white matter was significantly lower in children than in adults, suggesting less myelination in children. Measurement of the coherence of white matter revealed that the right frontal lobe had a than the left more regular organization of axons frontal lobe, in both children and adults. The results demonstrate that maturation of the frontal white matter continues into the second decade of life. The time course of prefrontal maturation makes it possible that myelination is a basis for the gradual development of prefrontal functions, such as increased working memory capacity. (C) 1999 Lippincott Williams & Wilkins.
    BibTeX:
    @article{Klingberg1999,
      author = {Klingberg, T and Vaidya, CJ and Gabrieli, JDE and Moseley, ME and Hedehus, M},
      title = {Myelination and organization of the frontal white matter in children: a diffusion tensor MRI study},
      journal = {NEUROREPORT},
      year = {1999},
      volume = {10},
      number = {13},
      pages = {2817-2821}
    }
    
    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}
    }
    
    Knutson, B., Fong, G., Bennett, S., Adams, C. & Homme, D. A region of mesial prefrontal cortex tracks monetarily rewarding outcomes: characterization with rapid event-related fMRI {2003} NEUROIMAGE
    Vol. {18}({2}), pp. {263-272} 
    article DOI  
    Abstract: The function of the mesial prefrontal cortex (MPFC: including Brodman areas 10/12/32) remains an enigma. Current theories suggest a role in representing internal information, including emotional introspection, autonomic control, and a ``default state'' of semantic processing. Recent evidence also suggests that parts of this region may also play a role in processing reward outcomes. In this study, we investigated the possibility that a region of the MPFC would be preferentially recruited by monetary reward outcomes using a parametric monetary incentive delay (MID) task. Twelve healthy volunteers participated in functional magnetic resonance scans while playing the MID task. Group analyses indicated that while the ventral striatum was recruited by anticipation of monetary reward, a region of the MPFC, instead responded to rewarding monetary outcomes. Specifically, volume-of-interest analyses indicated that when volunteers received 5.00 after anticipating a 5.00 win, MPFC activity increased, whereas when volunteers did not receive 5.00 after anticipating a 5.00 win, MPFC activity decreased, relative to outcomes with no incentive value. These findings suggest that in the context of processing monetary rewards, a region of the MPFC preferentially tracks rewarding outcomes. (C) 2003 Elsevier Science (USA). All rights reserved.
    BibTeX:
    @article{Knutson2003,
      author = {Knutson, B and Fong, GW and Bennett, SM and Adams, CM and Homme, D},
      title = {A region of mesial prefrontal cortex tracks monetarily rewarding outcomes: characterization with rapid event-related fMRI},
      journal = {NEUROIMAGE},
      year = {2003},
      volume = {18},
      number = {2},
      pages = {263-272},
      doi = {{10.1016/S1053-8119(02)00057-5}}
    }
    
    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}
    }
    
    Koechlin, E., Ody, C. & Kouneiher, F. The architecture of cognitive control in the human prefrontal cortex {2003} SCIENCE
    Vol. {302}({5648}), pp. {1181-1185} 
    article  
    Abstract: The prefrontal cortex (PFC) subserves cognitive control: the ability to coordinate thoughts or actions in relation with internal goals. Its functional architecture, however, remains poorly understood. Using brain imaging in humans, we showed that the lateral PFC is organized as a cascade of executive processes from premotor to anterior PFC regions that control behavior according to stimuli, the present perceptual context, and the temporal episode in which stimuli occur, respectively. The results support an unified modular model of cognitive control that describes the overall functional organization of the human lateral PFC and has basic methodological and theoretical implications.
    BibTeX:
    @article{Koechlin2003,
      author = {Koechlin, E and Ody, C and Kouneiher, F},
      title = {The architecture of cognitive control in the human prefrontal cortex},
      journal = {SCIENCE},
      year = {2003},
      volume = {302},
      number = {5648},
      pages = {1181-1185}
    }
    
    Kok, A. On the utility of P3 amplitude as a measure of processing capacity {2001} PSYCHOPHYSIOLOGY
    Vol. {38}({3}), pp. {557-577} 
    article  
    Abstract: The present review focuses on the utility of the amplitude of P3 of as a measure of processing capacity and mental workload. The paper starts with a brief outline of the conceptual framework underlying the relationship between P3 amplitude and task demands, and the cognitive task manipulations that determine demands on capacity. P3 amplitude results are then discussed on the basis of an extensive review of the relevant literature. It is concluded that although it has often been assumed that P3 amplitude depends on the capacity for processing task relevant stimuli, the utility of P3 amplitude as a sensitive and diagnostic measure of processing capacity remains limited. The major factor that prompts this conclusion is that the two principal task variables that have been used to manipulate capacity allocation, namely task difficulty and task emphasis, have opposite effects on the amplitude of P3. I suggest that this is because, in many tasks, an increase in difficulty transforms the structure or actual content of the flow of information in the processing systems, thereby interfering with the very processes that underlie P3 generation. Finally, in an attempt to theoretically integrate the results of the reviewed studies, it is proposed that P3 amplitude reflects activation of elements in a event-categorization network that is controlled by the joint operation of attention and working memory.
    BibTeX:
    @article{Kok2001,
      author = {Kok, A},
      title = {On the utility of P3 amplitude as a measure of processing capacity},
      journal = {PSYCHOPHYSIOLOGY},
      year = {2001},
      volume = {38},
      number = {3},
      pages = {557-577}
    }
    
    Komatitsch, D. & Vilotte, J. The spectral element method: An efficient tool to simulate the seismic response of 2D and 3D geological structures {1998} BULLETIN OF THE SEISMOLOGICAL SOCIETY OF AMERICA
    Vol. {88}({2}), pp. {368-392} 
    article  
    Abstract: We present the spectral element method to simulate elastic-wave propagation in realistic geological structures involving complicated free-surface topography and material interfaces for two- and three-dimensional geometries. The spectral element method introduced here is a high-order variational method for the spatial approximation of elastic-wave equations. The mass matrix is diagonal by construction in this method, which drastically reduces the computational cost and allows an efficient parallel implementation. Absorbing boundary conditions are introduced in variational form to simulate unbounded physical domains. The time discretization is based on an energy-momentum conserving scheme that can be put into a classical explicit-implicit predictor/multi-corrector format. Long-term energy conservation and stability properties are illustrated as well as the efficiency of the absorbing conditions. The associated Courant condition behaves as Delta t(C) < O (n(el)(-1/nd) N-2), with n(el) the number of elements, n(d) the spatial dimension, and N the polynomial order. In practice, a spatial sampling of approximately 5 points per wavelength is found to be very accurate when working with a polynomial degree of N = 8. The accuracy of the method is shown by comparing the spectral element solution to analytical solutions of the classical two-dimensional (2D) problems of Lamb and Garvin. The flexibility of the method is then illustrated by studying more realistic 2D models involving realistic geometries and complex free-boundary conditions. Very accurate modeling of Rayleigh-wave propagation, surface diffraction, and Rayleigh-to-body-wave mode conversion associated with the free-surface curvature are obtained at low computational cost. The method is shown to provide an efficient tool to study the diffraction of elastic waves by three-dimensional (3D) surface topographies and the associated local effects on strong ground motion. Complex amplification patterns, both in space and time, are shown to occur even for a gentle hill topography. Extension to a heterogeneous hill structure is considered. The efficient implementation on parallel distributed memory architectures will allow to perform real-time visualization and interactive physical investigations of 3D amplification phenomena for seismic risk assessment.
    BibTeX:
    @article{Komatitsch1998,
      author = {Komatitsch, D and Vilotte, JP},
      title = {The spectral element method: An efficient tool to simulate the seismic response of 2D and 3D geological structures},
      journal = {BULLETIN OF THE SEISMOLOGICAL SOCIETY OF AMERICA},
      year = {1998},
      volume = {88},
      number = {2},
      pages = {368-392}
    }
    
    Konishi, S., Nakajima, K., Uchida, I., Kameyama, M., Nakahara, K., Sekihara, K. & Miyashita, Y. Transient activation of inferior prefrontal cortex during cognitive set shifting {1998} NATURE NEUROSCIENCE
    Vol. {1}({1}), pp. {80-84} 
    article  
    Abstract: The Wisconsin Card Sorting Test, which probes the ability to shift attention from one category of stimulus attributes to another (shifting cognitive sets), is the most common paradigm used to detect human frontal lobe pathology. However, the exact relationship of this card test to prefrontal function and the precise anatomical localization of the cognitive shifts involved are controversial. By isolating shift-related signals using the temporal resolution of functional magnetic resonance imaging, we reproducibly found transient activation of the posterior part of the bilateral inferior frontal sulci, This activation was larger as the number of dimensions (relevant stimulus attributes that had to be recognized) were increased, These results suggest that the inferior frontal areas play an essential role in the flexible shifting of cognitive sets.
    BibTeX:
    @article{Konishi1998,
      author = {Konishi, S and Nakajima, K and Uchida, I and Kameyama, M and Nakahara, K and Sekihara, K and Miyashita, Y},
      title = {Transient activation of inferior prefrontal cortex during cognitive set shifting},
      journal = {NATURE NEUROSCIENCE},
      year = {1998},
      volume = {1},
      number = {1},
      pages = {80-84}
    }
    
    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}
    }
    
    Krakauer, J., Ghilardi, M. & Ghez, C. Independent learning of internal models for kinematic and dynamic control of reaching {1999} NATURE NEUROSCIENCE
    Vol. {2}({11}), pp. {1026-1031} 
    article  
    Abstract: Psychophysical studies of reaching movements suggest that hand kinematics are learned from errors in extent and direction in an extrinsic coordinate system, whereas dynamics are learned from proprioceptive errors in an intrinsic coordinate system. We examined consolidation and interference to determine if these two forms of learning were independent. Learning and consolidation of two novel transformations, a rotated spatial reference frame and altered intersegmental dynamics, did not interfere with each other and consolidated in parallel. Thus separate kinematic and dynamic models were constructed simultaneously based on errors computed in different coordinate frames, and possibly, in different sensory modalities, using separate working-memory systems. These results suggest that computational approaches to motor learning should include two separate performance errors rather than one.
    BibTeX:
    @article{Krakauer1999,
      author = {Krakauer, JW and Ghilardi, MF and Ghez, C},
      title = {Independent learning of internal models for kinematic and dynamic control of reaching},
      journal = {NATURE NEUROSCIENCE},
      year = {1999},
      volume = {2},
      number = {11},
      pages = {1026-1031}
    }
    
    Kril, J., Halliday, G., Svoboda, M. & Cartwright, H. The cerebral cortex is damaged in chronic alcoholics {1997} NEUROSCIENCE
    Vol. {79}({4}), pp. {983-998} 
    article  
    Abstract: There is some controversy in the literature concerning whether chronic alcohol consumption damages the cerebral cortex. White decreased neuronal density in specific cortical regions is well described in chronic alcoholics, a recent study by Badsberg Jensen and Pakkenberg(5) using unbiased stereological methods questions whether neurodegeneration occurs. In order to assess selective neurodegeneration in the cerebral cortex of chronic alcoholics, regional volumes and unbiased estimates of regional neuronal number (including neuronal identification with calcium-binding proteins) were calculated for 14 chronic alcoholics and 21 controls. Cases were carefully screened to exclude any interfering pathologies. Lifetime and maximum daily alcohol consumption was determined, and homogeneous groups were identified (four chronic alcoholics with Wernicke's encephalopathy and Korsakoff's psychosis, four chronic alcoholics with Wernicke's encephalopathy alone, six chronic alcoholics without Wernicke's encephalopathy or Korsakoff's psychosis, and 21 controls). Brain volume analysis revealed that discrete regions were significantly smaller in the chronic alcoholics compared to controls. As previously shown, white matter regions (particularly in the frontal lobe) were the most significantly reduced in volume. Alcoholics with Wernicke's encephalopathy (either alone or in combination with Korsakoff's psychosis) had significantly smaller white matter volumes than controls or alcoholics without these complications. Medial temporal lobe regions and the thalamus were also reduced in volume. Regression analyses revealed that the volume of both the white matter and thalamus negatively correlated with alcohol consumption. Consistent with the interpretation of previous neuronal density studies, selective neuronal loss was found in the superior frontal association cortex of chronic alcoholics, while no loss occurred from the motor cortex. The number of parvalbumin-, calbindin- and calretinin-immunoreactive neurons was found to be unaltered in chronic alcoholics, suggesting that the neurodegeneration is confined to the non-GABAergic pyramidal neurons. As neurodegeneration was observed in all alcoholic groups, damage to the frontal association cortex is not restricted to alcoholics with the amnesia of Korsakoff's psychosis. These results are consistent with the notion that chronic alcohol consumption is associated with selective neuronal vulnerability. The selective frontal neurodegeneration and the frontal focus of white matter atrophy are supported by neuropsychological, regional blood flow, and magnetic resonance imaging studies of frontal lobe dysfunction in chronic alcoholics and may correlate with abnormalities in working memory. (C) 1997 IBRO. Published by Elsevier Science Ltd.
    BibTeX:
    @article{Kril1997,
      author = {Kril, JJ and Halliday, GM and Svoboda, MD and Cartwright, H},
      title = {The cerebral cortex is damaged in chronic alcoholics},
      journal = {NEUROSCIENCE},
      year = {1997},
      volume = {79},
      number = {4},
      pages = {983-998}
    }
    
    Kuroki, T., Meltzer, H. & Ichikawa, J. Effects of antipsychotic drugs on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens {1999} JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
    Vol. {288}({2}), pp. {774-781} 
    article  
    Abstract: The present study was designed to compare the effects of typical and atypical antipsychotic drugs on extracellular dopamine (DA) levels in the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAC), using in vivo microdialysis with dual probe implantation in awake, freely moving rats. Amperozide (2 and 10 mg/kg), clozapine (5 and 20 mg/kg), and olanzapine (10 mg/kg), all of which are atypical antipsychotics, produced greater increases in extracellular DA levels in the mPFC than in the NAG. Olanzapine (1 mg/kg), risperidone (0.1 and 1 mg/kg), also an atypical antipsychotic, and S-(-)-sulpiride (25 mg/kg), a typical antipsychotic, produced comparable increases in extracellular DA levels in the mPFC and the NAG. S-(-)-sulpiride (10 mg/kg) and haloperidol (0.1 and 1 mg/kg), another typical antipsychotic, significantly increased extracellular DA levels in the NAC but not in the mPFC. The effects of the six antipsychotic drugs to increase extracellular DA levels in the mPFC relative to those in the NAC was positively correlated with the difference between their pKi values for serotonin (5-hydroxytryptamine, 5-HT2A) and DA-D-2 receptors and was inversely correlated to their pKi values for D-2 or D-3 receptors, but was not for 5-HT2A receptors alone. These results are consistent with the hypothesis that the ability of antipsychotic drugs to produce a greater increase in prefrontal compared with NAC extracellular DA levels may be related, in part, to weak D-2 and D-3 receptor affinity relative to 5-HT2A receptor antagonism.
    BibTeX:
    @article{Kuroki1999,
      author = {Kuroki, T and Meltzer, HY and Ichikawa, J},
      title = {Effects of antipsychotic drugs on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens},
      journal = {JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS},
      year = {1999},
      volume = {288},
      number = {2},
      pages = {774-781},
      note = {25th Annual Meeting of the Society-for-Neuroscience, SAN DIEGO, CALIFORNIA, NOV 11-16, 1995}
    }
    
    KYLLONEN, P. & CHRISTAL, R. REASONING ABILITY IS (LITTLE MORE THAN) WORKING-MEMORY CAPACITY {1990} INTELLIGENCE
    Vol. {14}({4}), pp. {389-433} 
    article  
    BibTeX:
    @article{KYLLONEN1990,
      author = {KYLLONEN, PC and CHRISTAL, RE},
      title = {REASONING ABILITY IS (LITTLE MORE THAN) WORKING-MEMORY CAPACITY},
      journal = {INTELLIGENCE},
      year = {1990},
      volume = {14},
      number = {4},
      pages = {389-433}
    }
    
    LaBar, K. & Cabeza, R. Cognitive neuroscience of emotional memory {2006} NATURE REVIEWS NEUROSCIENCE
    Vol. {7}({1}), pp. {54-64} 
    article DOI  
    Abstract: Emotional events often attain a privileged status in memory. Cognitive neuroscientists have begun to elucidate the psychological and neural mechanisms underlying emotional retention advantages in the human brain. The amygdala is a brain structure that directly mediates aspects of emotional learning and facilitates memory operations in other regions, including the hippocampus and prefrontal cortex. Emotion - memory interactions occur at various stages of information processing, from the initial encoding and consolidation of memory traces to their long-term retrieval. Recent advances are revealing new insights into the reactivation of latent emotional associations and the recollection of personal episodes from the remote past.
    BibTeX:
    @article{LaBar2006,
      author = {LaBar, KS and Cabeza, R},
      title = {Cognitive neuroscience of emotional memory},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2006},
      volume = {7},
      number = {1},
      pages = {54-64},
      doi = {{10.1038/nrn1825}}
    }
    
    LaBar, K., Gitelman, D., Parrish, T. & Mesulam, M. Neuroanatomic overlap of working memory and spatial attention networks: A functional MRI comparison within subjects {1999} NEUROIMAGE
    Vol. {10}({6}), pp. {695-704} 
    article  
    Abstract: Frontal and posterior parietal activations have been reported in numerous studies of working memory and visuospatial attention. To directly compare the brain regions engaged by these two cognitive functions, the same set of subjects consecutively participated in tasks of working memory and spatial attention while undergoing functional MRI (fMRI). The working memory task required the subject to maintain an on-line representation of foveally displayed letters against a background of distracters. The spatial attention task required the subject to shift visual attention covertly in response to a centrally presented directional cue. The spatial attention task had no working memory requirement, and the working memory task had no covert spatial attention requirement. subjects' ability to maintain central fixation was confirmed outside the MRI scanner using infrared oculography. According to cognitive conjunction analysis, the set of activations common to both tasks included the intraparietal sulcus, ventral precentral sulcus, supplementary motor area, frontal eye fields, thalamus, cerebellum, left temporal neocortex, and right insula. Double-subtraction analyses yielded additional activations attributable to verbal working memory in premotor cortex, left inferior prefrontal cortex, right inferior parietal lobule, precuneus, and right cerebellum. Additional activations attributable to covert spatial attention included the occipitotemporal junction and extrastriate cortex. The use of two different tasks in the same set of subjects allowed us to provide an unequivocal demonstration that the neural networks subserving spatial attention and working memory intersect at several frontoparietal sites. These findings support the view that major cognitive domains are represented by partially overlapping large-scale neural networks. The presence of this overlap also suggests that spatial attention and working memory share common cognitive features related to the dynamic shifting of attentional resources. (C) 1999 Academic Press.
    BibTeX:
    @article{LaBar1999,
      author = {LaBar, KS and Gitelman, DR and Parrish, TB and Mesulam, MM},
      title = {Neuroanatomic overlap of working memory and spatial attention networks: A functional MRI comparison within subjects},
      journal = {NEUROIMAGE},
      year = {1999},
      volume = {10},
      number = {6},
      pages = {695-704}
    }
    
    Lamme, V. Why visual attention and awareness are different {2003} TRENDS IN COGNITIVE SCIENCES
    Vol. {7}({1}), pp. {12-18} 
    article  
    Abstract: Now that the study of consciousness is warmly embraced by cognitive scientists, much confusion seems to arise between the concepts of visual attention and visual awareness. Often, visual awareness is equated to what is in the focus of attention. There are, however, two sets of arguments to separate attention from awareness: a psychological/theoretical one and a neurobiological one. By combining these arguments I present definitions of visual attention and awareness that clearly distinguish between the two, yet explain why attention and awareness are so intricately related. In fact, there seems more overlap between mechanisms of memory and awareness than between those of attention and awareness.
    BibTeX:
    @article{Lamme2003,
      author = {Lamme, VAF},
      title = {Why visual attention and awareness are different},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      year = {2003},
      volume = {7},
      number = {1},
      pages = {12-18}
    }
    
    LANGE, K., ROBBINS, T., MARSDEN, C., JAMES, M., OWEN, A. & PAUL, G. L-DOPA WITHDRAWAL IN PARKINSONS-DISEASE SELECTIVELY IMPAIRS COGNITIVE PERFORMANCE IN TESTS SENSITIVE TO FRONTAL-LOBE DYSFUNCTION {1992} PSYCHOPHARMACOLOGY
    Vol. {107}({2-3}), pp. {394-404} 
    article  
    Abstract: A group of ten patients with idiopathic Parkinson's disease (PD) was tested on a series of automated tests of learning, memory, planning and attention whilst either on or Off L-dopa medication. Controlled withdrawal Of L-dopa interfered with aspects of performance on three of the tests that had previously been shown to be sensitive to frontal lobe dysfunction; a spatial working memory task, the Tower of London planning test, and a visual discrimination paradigm that also included intra- and extra-dimensional shift tests of selective attention. More specifically, errors were increased in the spatial working memory test, and both the accuracy and latency of thinking were impaired. Thinking time was significantly slowed following L-dopa withdrawal, even though the possible contaminating effects on motor slowing were fully controlled by a yoked control procedure. Nine out of ten patients reached a further stage of the visual discrimination, set-shifting paradigm when on, rather than Off, L-dopa medication. Spatial span was also impaired off medication, but there were no effects of L-dopa withdrawal on tests of pattern and spatial recognition memory, simultaneous and delayed matching to sample or visuospatial conditional associative learning. Comparisons with a large control group confirmed previous findings that PD is associated with deficits on the majority of these tests. The results are discussed in terms of the fronto-striatal, dopamine dependent nature of some of the cognitive deficits found in PD, but the apparent dopamine-independent nature of deficits in other aspects of cognitive functioning, notably in tests of visual recognition memory and associative learning.
    BibTeX:
    @article{LANGE1992,
      author = {LANGE, KW and ROBBINS, TW and MARSDEN, CD and JAMES, M and OWEN, AM and PAUL, GM},
      title = {L-DOPA WITHDRAWAL IN PARKINSONS-DISEASE SELECTIVELY IMPAIRS COGNITIVE PERFORMANCE IN TESTS SENSITIVE TO FRONTAL-LOBE DYSFUNCTION},
      journal = {PSYCHOPHARMACOLOGY},
      year = {1992},
      volume = {107},
      number = {2-3},
      pages = {394-404}
    }
    
    Laufs, H., Krakow, K., Sterzer, P., Eger, E., Beyerle, A., Salek-Haddadi, A. & Kleinschmidt, A. Electroencephalographic signatures of attentional and cognitive default modes in spontaneous brain activity fluctuations at rest {2003} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {100}({19}), pp. {11053-11058} 
    article  
    Abstract: We assessed the relation between hemodynamic and electrical indices of brain function by performing simultaneous functional MRI (fMRI) and electroencephalography (EEG) in awake subjects at rest with eyes closed. Spontaneous power fluctuations of electrical rhythms were determined for multiple discrete frequency bands, and associated fMRI signal modulations were mapped on a voxel-by-voxel basis. There was little positive correlation of localized brain activity with alpha power (8-12 Hz), but strong and widespread negative correlation in lateral frontal and parietal cortices that are known to support attentional processes. Power in a 17-23 Hz range of beta activity was positively correlated with activity in retrosplenial, temporo-parietal, and clorsomedial prefrontal cortices. This set of areas has previously been characterized by high but coupled metabolism and blood flow at rest that decrease whenever subjects engage in explicit perception or action. The distributed patterns of fMRI activity that were correlated with power in different EEG bands overlapped strongly with those of functional connectivity, i.e., intrinsic covariations of regional activity at rest. This result indicates that, during resting wakefulness, and hence the absence of a task, these areas constitute separable and dynamic functional networks, and that activity in these networks is associated with distinct EEG signatures. Taken together with studies that have explicitly characterized the response properties of these distributed cortical systems, our findings may suggest that alpha oscillations signal a neural baseline with ``inattention'' whereas beta rhythms index spontaneous cognitive operations during conscious rest.
    BibTeX:
    @article{Laufs2003,
      author = {Laufs, H and Krakow, K and Sterzer, P and Eger, E and Beyerle, A and Salek-Haddadi, A and Kleinschmidt, A},
      title = {Electroencephalographic signatures of attentional and cognitive default modes in spontaneous brain activity fluctuations at rest},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {2003},
      volume = {100},
      number = {19},
      pages = {11053-11058}
    }
    
    Lavie, N. Distracted and confused?: Selective attention under load {2005} TRENDS IN COGNITIVE SCIENCES
    Vol. {9}({2}), pp. {75-82} 
    article DOI  
    Abstract: The ability to remain focused on goal-relevant stimuli in the presence of potentially interfering distractors is crucial for any coherent cognitive function. However, simply instructing people to ignore goal-irrelevant stimuli is not sufficient for preventing their processing. Recent research reveals that distractor processing depends critically on the level and type of load involved in the processing of goal-relevant information. Whereas high perceptual load can eliminate distractor processing, high load on `frontal' cognitive control processes increases distractor processing. These findings provide a resolution to the long-standing early and late selection debate within a load theory of attention that accommodates behavioural and neuroimaging data within a framework that integrates attention research with executive function.
    BibTeX:
    @article{Lavie2005,
      author = {Lavie, N},
      title = {Distracted and confused?: Selective attention under load},
      journal = {TRENDS IN COGNITIVE SCIENCES},
      year = {2005},
      volume = {9},
      number = {2},
      pages = {75-82},
      doi = {{10.1016/j.tics.2004.12.004}}
    }
    
    Lavie, N., Hirst, A., de Fockert, J. & Viding, E. Load theory of selective attention and cognitive control {2004} JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL
    Vol. {133}({3}), pp. {339-354} 
    article DOI  
    Abstract: A load theory of attention in which distractor rejection depends on the level and type of load involved in current processing was tested. A series of experiments demonstrates that whereas high perceptual load reduces distractor interference, working memory load or dual-task coordination load increases distractor interference. These findings suggest 2 selective attention mechanisms: a perceptual selection mechanism serving to reduce distractor perception in situations of high perceptual load that exhaust perceptual capacity in processing relevant stimuli and a cognitive control mechanism that reduces interference from perceived distractors as long as cognitive control functions are available to maintain current priorities (low cognitive load). This theory resolves the long-standing early versus late selection debate and clarifies the role of cognitive control in selective attention.
    BibTeX:
    @article{Lavie2004,
      author = {Lavie, N and Hirst, A and de Fockert, JW and Viding, E},
      title = {Load theory of selective attention and cognitive control},
      journal = {JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL},
      year = {2004},
      volume = {133},
      number = {3},
      pages = {339-354},
      doi = {{10.1037/0096-3445.133.3.339}}
    }
    
    LeBlanc, E., Janowsky, J., Chan, B. & Nelson, H. Hormone replacement therapy and cognition - Systematic review and meta-analysis {2001} JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
    Vol. {285}({11}), pp. {1489-1499} 
    article  
    Abstract: Context Some observational data suggest that hormone replacement therapy (HRT) may reduce the risk of cognitive decline and dementia but results have been conflicting. Objective To review and evaluate studies of HRT for preventing cognitive decline and dementia in healthy postmenopausal women. Data Sources Studies with English-language abstracts identified in MEDLINE (1966-August 2000), HealthSTAR (1975-August 2000, PsychINFO (1984-August 2000); Cochrane Library databases; and articles listed in reference lists of key articles, Study Selection Randomized controlled trials and cohort studies were reviewed for the effects of HRT on cognitive decline; cohort and case-control studies were reviewed for dementia risk. No randomized controlled trials regarding dementia risk were identified. Data Extraction Twenty-nine studies met inclusion criteria and were rated, Two reviewers rated study quality independently and 100% agreement was reached on Jadad scores and 80% agreement was reached on US Preventive Services Task Force quality scores. A final score was reached th rough consensus if reviewers disagreed. Data Synthesis Studies of cognition were not combined quantitatively because of heterogeneous study design. Women symptomatic from menopause had improvements in verbal memory, vigilance, reasoning, and motor speed, but no enhancement of other cognitive functions. Generally, no benefits were observed in asymptomatic women. A meta-analysis of observational studies suggested that HRT was associated with a decreased risk of dementia (summary odds ratio, 0.66; 95% confidence interval, 0.53-0.82). However, possible biases and lack of control for potential confounders limit interpretation of these studies. Studies did not contain enough information to assess adequately the effects of progestin use, various estrogen preparations or doses, or duration of therapy. Conclusions in women with menopausal symptoms, HRT may have specific cognitive effects, and future studies should target these effects, The meta-analysis found a decreased risk of dementia in HRT users but most studies had important methodological limitations.
    BibTeX:
    @article{LeBlanc2001,
      author = {LeBlanc, ES and Janowsky, J and Chan, BKS and Nelson, HD},
      title = {Hormone replacement therapy and cognition - Systematic review and meta-analysis},
      journal = {JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION},
      year = {2001},
      volume = {285},
      number = {11},
      pages = {1489-1499}
    }
    
    LeDoux, J. Emotion circuits in the brain {2000} ANNUAL REVIEW OF NEUROSCIENCE
    Vol. {23}, pp. {155-184} 
    article  
    Abstract: The field of neuroscience has, after a long period of looking the other way, again embraced emotion as an important research area. Much of the progress has come from studies of fear, and especially fear conditioning. This work has pinpointed the amygdala as an important component of the system involved in the acquisition, storage, and expression of fear memory and has elucidated in detail how stimuli enter, travel through, and exit the amygdala. Some progress has also been made in understanding the cellular and molecular mechanisms that underlie fear conditioning, and recent studies have also shown that the findings from experimental animals apply to the human brain. It is important to remember why this work on emotion succeeded where past efforts failed. It focused on a psychologically well-defined aspect of emotion, avoided vague and poorly defined concepts such as ``affect,'' ``hedonic tone,'' or ``emotional feelings,'' and used a simple and straightforward experimental approach. With so much research being done in this area today, it is important that the mistakes of the past not be made again. It is also time to expand from this foundation into broader aspects of mind and behavior.
    BibTeX:
    @article{LeDoux2000,
      author = {LeDoux, JE},
      title = {Emotion circuits in the brain},
      journal = {ANNUAL REVIEW OF NEUROSCIENCE},
      year = {2000},
      volume = {23},
      pages = {155-184}
    }
    
    Leon, M. & Shadlen, M. Effect of expected reward magnitude on the response of neurons in the dorsolateral prefrontal cortex of the macaque {1999} NEURON
    Vol. {24}({2}), pp. {415-425} 
    article  
    Abstract: The dorsolateral prefrontal cortex plays a critical role in guiding actions that ensue seconds after an instruction. We recorded from neurons in area 46 and the frontal eye field (FEF) while monkeys performed a memory-guided eye movement task. A visual cue signaled whether a small or large liquid reward would accompany a correct response. Many neurons in area 46 responded more when the monkey expected a larger reward. Reward-related enhancement was evident throughout the memory period and was most pronounced when the remembered target appeared in the neuron's response field. Enhancement was not present in the FEF. The mixture of neural signals representing spatial working memory and reward expectation appears to be a distinct feature of area 46.
    BibTeX:
    @article{Leon1999,
      author = {Leon, MI and Shadlen, MN},
      title = {Effect of expected reward magnitude on the response of neurons in the dorsolateral prefrontal cortex of the macaque},
      journal = {NEURON},
      year = {1999},
      volume = {24},
      number = {2},
      pages = {415-425}
    }
    
    Levin, E., McClernon, F. & Rezvani, A. Nicotinic effects on cognitive function: behavioral characterization, pharmacological specification, and anatomic localization {2006} PSYCHOPHARMACOLOGY
    Vol. {184}({3-4}), pp. {523-539} 
    article DOI  
    Abstract: Rationale: Nicotine has been shown in a variety of studies in humans and experimental animals to improve cognitive function. Nicotinic treatments are being developed as therapeutic treatments for cognitive dysfunction. Objectives: Critical for the development of nicotinic therapeutics is an understanding of the neurobehavioral bases for nicotinic involvement in cognitive function. Methods: Specific and diverse cognitive functions affected by nicotinic treatments are reviewed, including attention, learning, and memory. The neural substrates for these behavioral actions involve the identification of the critical pharmacologic receptor targets, in particular brain locations, and how those incipient targets integrate with broader neural systems involved with cognitive function. Results: Nicotine and nicotinic agonists can improve working memory function, learning, and attention. Both alpha 4 beta 2 and alpha 7 nicotinic receptors appear to be critical for memory function. The hippocampus and the amygdala in particular have been found to be important for memory, with decreased nicotinic activity in these areas impairing memory. Nicotine and nicotinic analogs have shown promise for inducing cognitive improvement. Positive therapeutic effects have been seen in initial studies with a variety of cognitive dysfunctions, including Alzheimer's disease, age-associated memory impairment, schizophrenia, and attention deficit hyperactivity disorder. Conclusions: Discovery of the behavioral, pharmacological, and anatomic specificity of nicotinic effects on learning, memory, and attention not only aids the understanding of nicotinic involvement in the basis of cognitive function, but also helps in the development of novel nicotinic treatments for cognitive dysfunction. Nicotinic treatments directed at specific receptor subtypes and nicotinic cotreatments with drugs affecting interacting transmitter systems may provide cognitive benefits most relevant to different syndromes of cognitive impairment such as Alzheimer's disease, schizophrenia, and attention deficit hyperactivity disorder. Further research is necessary in order to determine the efficacy and safety of nicotinic treatments of these cognitive disorders.
    BibTeX:
    @article{Levin2006,
      author = {Levin, ED and McClernon, FJ and Rezvani, AH},
      title = {Nicotinic effects on cognitive function: behavioral characterization, pharmacological specification, and anatomic localization},
      journal = {PSYCHOPHARMACOLOGY},
      year = {2006},
      volume = {184},
      number = {3-4},
      pages = {523-539},
      doi = {{10.1007/s00213-005-0164-7}}
    }
    
    Levin, E. & Simon, B. Nicotinic acetylcholine involvement in cognitive function in animals {1998} PSYCHOPHARMACOLOGY
    Vol. {138}({3-4}), pp. {217-230} 
    article  
    Abstract: Nicotinic cholinergic systems are involved with several important aspects of cognitive function including attention, learning and memory. Nicotinic cholinergic receptors are located in many regions of the brain, including areas important for cognitive function such as the hippocampus and frontal cortex. Nicotinic agonists have been found in rodent and non-human primate studies to improve performance on a variety of memory tasks. In a complementary fashion, nicotinic antagonists such as mecamylamine impair working memory function. In humans, similar effects have been seen. Nicotinic agonist treatment can improve attention, learning and memory and nicotinic antagonist treatment can cause deficits. To define the neural substrates of nicotinic involvement in cognitive function, three areas of investigation are underway. 1) Critical neuroanatomic loci for nicotinic effects are beginning to be determined. The hippocampus, frontal cortex and midbrain dopaminergic nuclei have been found to be important sites of action for nicotinic involvement in memory function. 2) Nicotinic receptor subtype involvement in cognitive function is being studied. There has been considerable recent work identifying nicotinic receptor subunit conformation including alpha and beta subunits. Nicotinic receptor subtypes appear to be associated with different functional systems; however, much remains to be done to determine the precise role each subtype plays in terms of cognitive function. 3) Nicotinic interactions with other transmitter systems are being assessed. Nicotine receptors interact In important ways with other systems to affect cognitive functioning, including muscarinic ACh, dopamine, norepinepherine, serotonin, glutamate, and other systems. Nicotinic function in clinical populations and potential for therapeutics has been investigated for Alzheimer's disease, Parkinson's disease, schizophrenia and attention deficit/hyperactivity disorder. Areas which need to receive greater attention are the exact anatomical location and the specific receptor subtypes critically involved in nicotine's effects. In addition, more work needs to be done to develop and determine the efficacy and safety of novel nicotinic ligands for use in the long-term treatment of human cognitive disorders.
    BibTeX:
    @article{Levin1998,
      author = {Levin, ED and Simon, BB},
      title = {Nicotinic acetylcholine involvement in cognitive function in animals},
      journal = {PSYCHOPHARMACOLOGY},
      year = {1998},
      volume = {138},
      number = {3-4},
      pages = {217-230}
    }
    
    Levy, R. & Goldman-Rakic, P. Segregation of working memory functions within the dorsolateral prefrontal cortex {2000} EXPERIMENTAL BRAIN RESEARCH
    Vol. {133}({1}), pp. {23-32} 
    article  
    Abstract: It is now widely accepted that the prefrontal cortex (PFC) plays a critical role in the neural network subserving working memory (WM). At least three related questions are still under debate: (1) is the PFC critical for all constituent processes of WM (i.e., short-term storage, manipulation, and utilization of mental represents tions) or only in one or a few of them? (2) Is there segregation of function among different cytoarchitectonic subdivisions of the PFC? (3) If this be the case, is this segregation based on the nature of the information being processed or on the type of cognitive operation performed? The present review article describes findings in the monkey supporting a modular ``domain-specific'' model of PFC functional organization with respect to WM operations. In this model, the dorsolateral prefrontal cortex (DLPFC) is composed of several subregions, based primarily on the nature of the information being processed in WM. Storage and processing functions are integrally related in each area. Future studies designed to map as yet uncharted areas of prefrontal cortex with refined anatomical and physiological approaches may provide a critical test of the model and evaluate the extent to which it applies generally or, instead, mainly to visual domains or only to dorsolateral convexity areas.
    BibTeX:
    @article{Levy2000,
      author = {Levy, R and Goldman-Rakic, PS},
      title = {Segregation of working memory functions within the dorsolateral prefrontal cortex},
      journal = {EXPERIMENTAL BRAIN RESEARCH},
      year = {2000},
      volume = {133},
      number = {1},
      pages = {23-32},
      note = {Workshop on Executive Control and the Frontal Lobe, DELMENHORST, GERMANY, DEC 01-03, 1998}
    }
    
    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}}
    }
    
    LIGHT, L. MEMORY AND AGING - 4 HYPOTHESES IN SEARCH OF DATA {1991} ANNUAL REVIEW OF PSYCHOLOGY
    Vol. {42}, pp. {333-376} 
    article  
    BibTeX:
    @article{LIGHT1991,
      author = {LIGHT, LL},
      title = {MEMORY AND AGING - 4 HYPOTHESES IN SEARCH OF DATA},
      journal = {ANNUAL REVIEW OF PSYCHOLOGY},
      year = {1991},
      volume = {42},
      pages = {333-376}
    }
    
    Logan, J., Sanders, A., Snyder, A., Morris, J. & Buckner, R. Under-recruitment and nonselective recruitment: Dissociable neural mechanisms associated with aging {2002} NEURON
    Vol. {33}({5}), pp. {827-840} 
    article  
    Abstract: Frontal contributions to cognitive decline in aging were explored using functional MRI. Frontal regions active in younger adults during self-initiated (intentional) memory encoding were under-recruited in older adults. Older adults showed less activity in anterior-ventral regions associated with controlled use of semantic information. Under-recruitment was reversed by requiring semantic elaboration suggesting it stemmed from difficulty in spontaneous recruitment of available frontal resources. In addition, older adults recruited multiple frontal regions in a nonselective manner for both verbal and nonverbal materials. Lack of selectivity was not reversed during semantically directed encoding even when under-recruitment was diminished. These findings suggest two separate forms of age-associated change in frontal cortex: under-recruitment and nonselective recruitment. The former is reversible and potentially amenable to cognitive training; the latter may reflect a less malleable change associated with cognitive decline in advanced aging.
    BibTeX:
    @article{Logan2002,
      author = {Logan, JM and Sanders, AL and Snyder, AZ and Morris, JC and Buckner, RL},
      title = {Under-recruitment and nonselective recruitment: Dissociable neural mechanisms associated with aging},
      journal = {NEURON},
      year = {2002},
      volume = {33},
      number = {5},
      pages = {827-840}
    }
    
    LOGIE, R., GILHOOLY, K. & WYNN, V. COUNTING ON WORKING-MEMORY IN ARITHMETIC PROBLEM-SOLVING {1994} MEMORY & COGNITION
    Vol. {22}({4}), pp. {395-410} 
    article  
    Abstract: Mental calculation is an important everyday skill involving access to well-learned procedures, problem solving, and working memory. Although there is an active literature on acquiring concepts and procedures for mental arithmetic, relatively little is known about the role of working memory in this task. This paper reports two experiments in which dual-task methodology is used to study the role of components of working memory in mental addition. In Experiment 1, mental addition of auditorily presented two-digit numbers was significantly disrupted by concurrent random letter generation and, to a lesser extent, by concurrent articulatory suppression, but was unimpaired by concurrent hand movement or by presentation of irrelevant pictures. Although the number of errors increased with two of the dual tasks, the incorrect responses tended to be quite close to the correct answer. In Experiment 2, the numbers for addition were presented visually. Here again, random generation produced the largest disruption of mental arithmetic performance, while a smaller amount of disruption was observed for articulatory suppression, hand movement, and unattended auditorily presented two-digit numbers. The overall levels of performance were better and the absolute size of the disruptive effects shown with visual presentation was very small compared with those found for auditory presentation. This pattern of results is consistent with a role for a central executive component of working memory in performing the calculations required for mental addition and in producing approximately correct answers. Visuospatial resources in working memory may also be involved in approximations. The data support the view that the subvocal rehearsal component of working memory provides a means of maintaining accuracy in mental arithmetic, and this matches a similar conclusion derived from previous work on counting. The general implications for the role of working memory in arithmetic problem solving will be discussed.
    BibTeX:
    @article{LOGIE1994,
      author = {LOGIE, RH and GILHOOLY, KJ and WYNN, V},
      title = {COUNTING ON WORKING-MEMORY IN ARITHMETIC PROBLEM-SOLVING},
      journal = {MEMORY & COGNITION},
      year = {1994},
      volume = {22},
      number = {4},
      pages = {395-410}
    }
    
    Luciana, M. & Nelson, C. The functional emergence of prefrontally-guided working memory systems in four- to eight-year-old children {1998} NEUROPSYCHOLOGIA
    Vol. {36}({3}), pp. {273-293} 
    article  
    Abstract: The neural processes that underlie the functional emergence of human cognitive functions, particularly those associated with the prefrontal cortex (PFC), are of growing interest to developmental psychologists and neuroscientists. Specifically, working memory functions have been correlated with PFC activity in nonhuman primates and adult humans but have not been extensively studied in children. We examined the developmental emergence of functions involved in working memory through the use of the Cambridge Neuropsychological Test Automated Battery (CANTAB), a computerized battery of nonverbal visually-presented neuropsychological tests designed to dissociate frontal from temporal lobe behavioral functions. Participants were normal children, aged 4-8 (n = 181) and a small group of young adults (n = 24) who completed measures of Spatial Memory Span, Spatial Working Memory, the Tower of London planning task, Visual Pattern and Spatial Recognition tasks, and a Set-Shifting task. Findings indicate a general age-related progression in ability levels on frontal lobe tasks, with 4-year-olds performing worse than 5- to 7-year-olds on all measures. Eight-year-olds are superior to younger children in their ability to solve complex problems but have not yet reached adult levels of performance on the most difficult items of the Tower of London and Spatial Working Memory tasks. We conclude that the development of working memory functions proceeds dimensionally, starting with refinement of basic perceptual and sensorimotor functions and culminating with the physiological maturation of widespread neural networks that integrate complex processing demands inherent to working memory tasks. (C) 1998 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{Luciana1998,
      author = {Luciana, M and Nelson, CA},
      title = {The functional emergence of prefrontally-guided working memory systems in four- to eight-year-old children},
      journal = {NEUROPSYCHOLOGIA},
      year = {1998},
      volume = {36},
      number = {3},
      pages = {273-293}
    }
    
    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}
    }
    
    Luine, V., Richards, S., Wu, V. & Beck, K. Estradiol enhances learning and memory in a spatial memory task and effects levels of monoaminergic neurotransmitters {1998} HORMONES AND BEHAVIOR
    Vol. {34}({2}), pp. {149-162} 
    article  
    Abstract: The effects of chronic estrogen treatment on radial arm maze performance and on levels of central monoaminergic and amino acid neurotransmitters were examined in ovariectomized (Ovx) rats. In an eight arms baited paradigm, choice accuracy was enhanced following 12 days but not 3 days of treatment. In addition, performance during acquisition of the eight arms baited maze task was better in estrogen-treated Ovx rats than in Ovx rats. Performance of treated rats was also enhanced in win-shift trials conducted 12 days postestrogen treatment. Working, reference, and working-reference memory was examined when four of the eight arms were baited, and only working memory was improved by estrogen and only after long-term treatment. Activity of Ovx rats on an open field, crossings and rearings, was increased at 5 but not at 35 days following estrogen treatment. In medial prefrontal cortex, levels of NE, DA, and 5-HT were decreased but glutamate and GABA levels were not affected following chronic estrogen treatment. Basal forebrain nuclei also showed changes in monoamines following estrogen. Hippocampal subfields showed no effects of estrogen treatment on monoaminergic or amino acid transmitters. Levels of GABA were increased in the vertical diagonal bands following chronic estrogen. Results show that estrogen enhances learning/memory on a task utilizing spatial memory. Effects in Ovx rats appear to require the chronic (several days) presence of estrogen. Changes in activity of both monoaminergic and amino acid transmitters in the frontal cortex and basal forebrain may contribute to enhancing effects of estrogen on learning/memory. (C) 1998 Academic Press.
    BibTeX:
    @article{Luine1998,
      author = {Luine, VN and Richards, ST and Wu, VY and Beck, KD},
      title = {Estradiol enhances learning and memory in a spatial memory task and effects levels of monoaminergic neurotransmitters},
      journal = {HORMONES AND BEHAVIOR},
      year = {1998},
      volume = {34},
      number = {2},
      pages = {149-162}
    }
    
    Luna, B., Thulborn, K., Munoz, D., Merriam, E., Garver, K., Minshew, N., Keshavan, M., Genovese, C., Eddy, W. & Sweeney, J. Maturation of widely distributed brain function subserves cognitive development {2001} NEUROIMAGE
    Vol. {13}({5}), pp. {786-793} 
    article DOI  
    Abstract: Cognitive and brain maturational changes continue throughout late childhood and adolescence. During this time, increasing cognitive control over behavior enhances the voluntary suppression of reflexive/impulsive response tendencies. Recently, with the advent of functional MRI, it has become possible to characterize changes in brain activity during cognitive development. In order to investigate the cognitive and brain maturation subserving the ability to voluntarily suppress context-inappropriate behavior, we tested 8-30 year olds in an oculomotor response-suppression task. Behavioral results indicated that adult-like ability to inhibit prepotent responses matured gradually through childhood and adolescence. Functional MRI results indicated that brain activation in frontal, parietal, striatal, and thalamic regions increased progressively from childhood to adulthood. Prefrontal cortex was more active in adolescents than in children or adults; adults demonstrated greater activation in the lateral cerebellum than younger subjects. These results suggest that efficient top-down modulation of reflexive acts may not be fully developed until adulthood and provide evidence that maturation of function across widely distributed brain regions lays the groundwork for enhanced voluntary control of behavior during cognitive development. (C) 2001 Academic: Press.
    BibTeX:
    @article{Luna2001,
      author = {Luna, B and Thulborn, KR and Munoz, DP and Merriam, EP and Garver, KE and Minshew, NJ and Keshavan, MS and Genovese, CR and Eddy, WF and Sweeney, JA},
      title = {Maturation of widely distributed brain function subserves cognitive development},
      journal = {NEUROIMAGE},
      year = {2001},
      volume = {13},
      number = {5},
      pages = {786-793},
      doi = {{10.1006/nimg.2000.0743}}
    }
    
    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}
    }
    
    MACDONALD, M., PEARLMUTTER, N. & SEIDENBERG, M. LEXICAL NATURE OF SYNTACTIC AMBIGUITY RESOLUTION {1994} PSYCHOLOGICAL REVIEW
    Vol. {101}({4}), pp. {676-703} 
    article  
    Abstract: Ambiguity resolution is a central problem in language comprehension. Lexical and syntactic ambiguities are standardly assumed to involve different types of knowledge representations and be resolved by different mechanisms. An alternative account is provided in which both types of ambiguity derive from aspects of lexical representation and are resolved by the same processing mechanisms. Reinterpreting syntactic ambiguity resolution as a form of lexical ambiguity resolution obviates the need for special parsing principles to account for syntactic interpretation preferences, reconciles a number of apparently conflicting results concerning the roles of lexical and contextual information in sentence processing, explains differences among ambiguities in terms of ease of resolution, and provides a more unified account of language comprehension than was previously available.
    BibTeX:
    @article{MACDONALD1994,
      author = {MACDONALD, MC and PEARLMUTTER, NJ and SEIDENBERG, MS},
      title = {LEXICAL NATURE OF SYNTACTIC AMBIGUITY RESOLUTION},
      journal = {PSYCHOLOGICAL REVIEW},
      year = {1994},
      volume = {101},
      number = {4},
      pages = {676-703}
    }
    
    Manes, F., Sahakian, B., Clark, L., Rogers, R., Antoun, N., Aitken, M. & Robbins, T. Decision-making processes following damage to the prefrontal cortex {2002} BRAIN
    Vol. {125}({Part 3}), pp. {624-639} 
    article  
    Abstract: Recent work has suggested an association between the orbitofrontal cortex in humans and practical decision making. The aim of this study was to investigate the profile of cognitive deficits, with particular emphasis on decision-making processes, following damage to different sectors of the human prefrontal cortex. Patients with discrete orbitofrontal (OBF) lesions, dorsolateral (DL) lesions, dorsomedial (DM) lesions and large frontal lesions (Large) were compared with matched controls on three different decision-making tasks: the Iowa Gambling Task and two recently developed tasks that attempt to fractionate some of the cognitive components of the Iowa task. A comprehensive battery including the assessment of recognition memory, working memory, planning ability and attentional set-shifting was also administered. Whilst combined frontal patients were impaired on several of the tasks employed, distinct profiles emerged for each patient group. In contrast to previous data, patients with focal OBF lesions performed at control levels on the three decision-making tasks (and the executive tasks), but showed some evidence of prolonged deliberation. DL patients showed pronounced impairment on working memory, planning, attentional shifting and the Iowa Gambling Task. DM patients were impaired at the Iowa Gambling Task and also at planning. The Large group displayed diffuse impairment, but were the only group to exhibit risky decision making. Methodological differences from previous studies of OBF patient groups are discussed, with particular attention to lesion laterality, lesion size and psychiatric presentation. Ventral and dorsal aspects of prefrontal cortex must interact in the maintenance of rational and,non-risky' decision making.
    BibTeX:
    @article{Manes2002,
      author = {Manes, F and Sahakian, B and Clark, L and Rogers, R and Antoun, N and Aitken, M and Robbins, T},
      title = {Decision-making processes following damage to the prefrontal cortex},
      journal = {BRAIN},
      year = {2002},
      volume = {125},
      number = {Part 3},
      pages = {624-639}
    }
    
    Manoach, D. Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings {2003} SCHIZOPHRENIA RESEARCH
    Vol. {60}({2-3}), pp. {285-298} 
    article DOI  
    Abstract: Working memory (WM) deficits are a persistent, disabling and relatively treatment-resistant feature of schizophrenia that may underlie many cognitive deficits and symptoms. They are associated with prefrontal cortex dysfunction. While most neuroimaging studies of WM demonstrate ``task-related hypofrontality'' in schizophrenic relative to healthy subjects, several recent studies have reported equal or increased prefrontal activity. These findings challenge central assumptions regarding cognitive deficits and prefrontal cortex dysfunction in schizophrenia. The goal of this review is to reconcile these seemingly discrepant findings. Methodological factors addressed include the use of intersubject averaging, WM task parameters and the reliability of the measures. Factors intrinsic to schizophrenia and their relevance to the selection of experimental methods and the interpretation of group data are also discussed. Both hypo- and hyperfrontality are hypothesized to be valid and informative reflections of prefrontal cortex dysfunction in schizophrenia. Due to the heterogeneity and variability of both performance and regional recruitment in schizophrenia, whether individual data is considered, the level and type of WM demands and the composition of the sample with regard to performance deficits all influence study outcome and contribute to discrepancies. Although the prefrontal cortex is consistently implicated in WM deficits, the basis of its dysfunction and its exact contribution remain unclear. Future work might focus on delineating the exact WM processes, domains and components that are deficient. In addition, variability in behavior and activation might best be regarded as intrinsic to schizophrenia and having a neural basis that requires explanation. In combination with other techniques, neuroirnaging can identify the neural circuitry responsible for WM deficits and elucidate the contribution of each anatomical component. (C) 2002 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{Manoach2003,
      author = {Manoach, DS},
      title = {Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings},
      journal = {SCHIZOPHRENIA RESEARCH},
      year = {2003},
      volume = {60},
      number = {2-3},
      pages = {285-298},
      doi = {{10.1016/S0920-9964(02)00294-3}}
    }
    
    Manoach, D., Gollub, R., Benson, E., Searl, M., Goff, D., Halpern, E., Saper, C. & Rauch, S. Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance {2000} BIOLOGICAL PSYCHIATRY
    Vol. {48}({2}), pp. {99-109} 
    article  
    Abstract: Background: Working memory (WM) deficits in schizophrenia have been associated with dorsolateral prefrontal cortex (DLPFC) dysfunction in neuroimaging studies. We previously found increased DLPFC activation in schizophrenic versus normal subjects during WM performance (Manoach et al 1999b), We now have investigated whether schizophrenic subjects recruit different brain regions, particularly the basal ganglia and thalamus, components of frontostriatal circuitry thought to mediate WM. Methods: We examined regional brain activition in nine normal and nine schizophrenic subjects during WM performance using functional magnetic resonance imaging. Subjects performed a modified version of the Sternberg Item Recognition Paradigm that included a monetary reward for correct responses. We compared high and low WM load conditions to each other and to a non-WM baseline condition. We examined activation in both individual subjects and averaged group data. Results: Relative to normal subjects, schizophrenic subjects exhibited deficient WM performance, at least an equal magnitude of right DLPFC activation, significantly greater left DLPFC activation and increased spatial heterogeneity of DLPFC activation. Furthermore, only the schizophrenic group activated the basal ganglia and thalamus, even when matched for task performance with the normal group. Conclusions: Aberrant WM performance and brain activation in schizophrenia may reflect dysfunction of frontostriatal circuitry that subserves WM, Future studies will elucidate the contribution of the anatomical components of this circuitry to WM deficits. Biol Psychiatry 2000;48: 99-109 (C) 2000 Society of Biological Psychiatry.
    BibTeX:
    @article{Manoach2000,
      author = {Manoach, DS and Gollub, RL and Benson, ES and Searl, MM and Goff, DC and Halpern, E and Saper, CB and Rauch, SL},
      title = {Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {2000},
      volume = {48},
      number = {2},
      pages = {99-109}
    }
    
    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}
    }
    
    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}
    }
    
    Mayr, U. & Keele, S. Changing internal constraints on action: The role of backward inhibition {2000} JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL
    Vol. {129}({1}), pp. {4-26} 
    article DOI  
    Abstract: Flexible control of action requires the ability to disengage from previous goals or task sets. The authors tested the hypothesis that disengagement during intentional shifts between task sets is accompanied by inhibition of the previous task set (''backward inhibition''). As an expression of backward inhibition the authors predicted increased response times when shifting to a task set that had to be abandoned recently and, thus, suffers residual inhibition. The critical backward inhibition effect on the level of abstractly defined perceptual task sets was obtained across 6 different experiments. In addition, it was shown that backward inhibition can be differentiated from negative priming (Experiment 2), that it is tied to top-down sequential control (Experiment 3), that it can account at least partially for ``residual shift costs'' in set-shifting experiments (Experiment 4), and that it occurs even in the context of preplanned sequences of task sets (Experiment 5).
    BibTeX:
    @article{Mayr2000,
      author = {Mayr, U and Keele, SW},
      title = {Changing internal constraints on action: The role of backward inhibition},
      journal = {JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL},
      year = {2000},
      volume = {129},
      number = {1},
      pages = {4-26},
      doi = {{10.1037//0096-3445.129.1.4}}
    }
    
    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}
    }
    
    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}
    }
    
    McCarthy, G., Puce, A., Constable, R., Krystal, J., Gore, J. & GoldmanRakic, P. Activation of human prefrontal cortex during spatial and nonspatial working memory tasks measured by functional MRI {1996} CEREBRAL CORTEX
    Vol. {6}({4}), pp. {600-611} 
    article  
    Abstract: Separate working memory domains for spatial location, and for objects, faces, and patterns, have been identified in the prefrontal cortex (PFC) of nonhuman primates. We have used functional magnetic resonance imaging to examine whether spatial and nonspatial visual working memory processes are similarly dissociable in human PFC. Subjects performed tasks which required them to remember either the location or shape of successive visual stimuli. We found that the mnemonic component of the working memory tasks affected the hemispheric pattern of PFC activation. The spatial (LOCATION) working memory task preferentially activated the middle frontal gyrus (MFG) in the right hemisphere, while the nonspatial (SHAPE) working memory task activated the MFG in both hemispheres. Furthermore, the area of activation in the left hemisphere extended into the inferior frontal gyrus for the nonspatial SHAPE task. A perceptual target (DOT) detection task also activated the MFG bilaterally, but at a level approximately half that of the working memory tasks. The activation in the MFG occurred within 3-6 s of task onset and declined following task offset. Time-course analysis revealed a different pattern for the cingulate gyrus, in which activation occurred upon task completion. Cingulate activation was greatest following the SHAPE task and was greater in the left hemisphere. The present results support the prominent role of the PFC and, specifically, the MFG in working memory, and indicate that the mnemonic content of the task affects the relative weighting of hemispheric activation.
    BibTeX:
    @article{McCarthy1996,
      author = {McCarthy, G and Puce, A and Constable, RT and Krystal, JH and Gore, JC and GoldmanRakic, P},
      title = {Activation of human prefrontal cortex during spatial and nonspatial working memory tasks measured by functional MRI},
      journal = {CEREBRAL CORTEX},
      year = {1996},
      volume = {6},
      number = {4},
      pages = {600-611}
    }
    
    MCDONALD, R. & WHITE, N. A TRIPLE DISSOCIATION OF MEMORY-SYSTEMS - HIPPOCAMPUS, AMYGDALA, AND DORSAL STRIATUM {1993} BEHAVIORAL NEUROSCIENCE
    Vol. {107}({1}), pp. {3-22} 
    article  
    Abstract: This study investigated the respective roles of the hippocampus, the amygdala, and the dorsal striatum in learning and memory. A standard set of experimental conditions for studying the effects of lesions to the three brain areas using an 8-arm radial maze was used: a win-shift version, a conditioned cue preference (CCP) version, and a win-stay version. Damage to the hippocampal system impaired acquisition of the win-shift task but not the CCP or win-stay tasks. Damage to the lateral amygdala impaired acquisition of the CCP task but not the win-shift or win-stay tasks. Damage to the dorsal striatum impaired acquisition of the win-stay task but not the win-shift or CCP tasks. These results are consistent with the hypothesis that the mammalian brain may be capable of acquiring different kinds of information with different, more-or-less independent neural systems. A neural system that includes the hippocampus may acquire information about the relationships among stimuli and events. A neural system that includes the amygdala may mediate the rapid acquisition of behaviors based on biologically significant events with affective properties. A neural system that includes the dorsal striatum may mediate the formation of reinforced stimulus-response associations.
    BibTeX:
    @article{MCDONALD1993,
      author = {MCDONALD, RJ and WHITE, NM},
      title = {A TRIPLE DISSOCIATION OF MEMORY-SYSTEMS - HIPPOCAMPUS, AMYGDALA, AND DORSAL STRIATUM},
      journal = {BEHAVIORAL NEUROSCIENCE},
      year = {1993},
      volume = {107},
      number = {1},
      pages = {3-22}
    }
    
    McEwen, B. Plasticity of the hippocampus: Adaptation to chronic stress and allostatic load {2001}
    Vol. {933}ROLE OF NEURAL PLASTICITY IN CHEMICAL INTOLERANCE, pp. {265-277} 
    inproceedings  
    Abstract: The hippocampus is an important structure for declarative, spatial, and contextual memory and is implicated in the perception of chronic pain. The hippocampal formation is vulnerable to damage from seizures, ischemia, and head trauma and is particularly sensitive to the effects of adrenal glucocorticoids secreted during the diurnal rhythm and chronic stress. Adrenal steroids typically have adaptive effects in the short run, but promote pathophysiology when there is either repeated stress or dysregulation of the HPA axis. The damaging actions of glucocorticoids under such conditions have been termed ``allostatic load'', referring to the cost to the body of adaptation to adverse conditions. Adrenal steroids display both protective and damaging effects in the hippocampus. They biphasically modulate excitability of hippocampal neurons, and high glucocorticoid levels and severe acute stress impair declarative memory in a reversible manner. The hippocampus also displays structural plasticity, involving ongoing neurogenesis of the dentate gyrus, synaptogenesis under control of estrogens in the CA1 region, and dendritic remodeling caused by repeated stress or elevated levels of exogenous glucocorticoids in the CA3 region. In all three forms of structural plasticity, excitatory amino acids participate along with circulating steroid hormones. Glucocorticoids and stressors suppress neurogenesis in the dentate gyrus. They also potentiate the damage produced by ischemia and seizures. Moreover, the aging rat hippocampus displays elevated and prolonged levels of excitatory amino acids released during acute stress. Our working hypothesis is that structural plasticity in response to repeated stress starts out as an adaptive and protective response, but ends up as damage if the imbalance in the regulation of the key mediators is not resolved. It is likely that morphological rearrangements in the hippocampus brought on by various types of allostatic load alter the manner in which the hippocampus participates in memory functions and it is conceivable that these may also have a role in chronic pain perception.
    BibTeX:
    @inproceedings{McEwen2001,
      author = {McEwen, BS},
      title = {Plasticity of the hippocampus: Adaptation to chronic stress and allostatic load},
      booktitle = {ROLE OF NEURAL PLASTICITY IN CHEMICAL INTOLERANCE},
      year = {2001},
      volume = {933},
      pages = {265-277},
      note = {Conference on the Role of Neural Plasticity in Chemical Intolerance, NEW YORK, NEW YORK, JUN 16-19, 2000}
    }
    
    McEwen, B. Effects of adverse experiences for brain structure and function {2000} BIOLOGICAL PSYCHIATRY
    Vol. {48}({8}), pp. {721-731} 
    article  
    Abstract: Studies of the hippocampus as a target of stress and stress hormones have revealed a considerable degree of structural plasticity in the adult brain. Repeated stress causes shortening and debranching of dendrites in the CA3 legion of the hippocampus and suppresses neurogenesis of dentate gyrus granule neurons. Both forms of structural remodeling of the hippocampus appear to be reversible and are mediated by glucocorticoid hormones working in concert with excitatory amino acids (EAA) and N-methyl-D-aspartate (NMDA) receptors, along with transmitters such as serotonin and the GABA-benzodiazepine system. Glucocorticoids, EAA, and NMDA receptors are also involved in neuronal damage and death that is caused in pyramidal neurons by seizures and by ischemia. A similar mechanism may be involved in hippocampal damage caused by severe and prolonged psychosocial stress. Studies using magnetic resonance imaging have shown that there is a selective atrophy of the human hippocampus in a number of psychiatric disorders, as well as during aging in some individuals, accompanied by deficits in declarative, spatial, and contextual memory performance. It is therefore important to appreciate how hippocampal dysfunction may play a role in the symptoms of the psychiatric illness and, from a therapeutic standpoint, to distinguish between a permanent loss of cells and a reversible remodeling to develop treatment strategies to prevent or reverse deficits. Remodeling of the hippocampus may be only the tip of the iceberg; other brain regions may also be affected Biol Psychiatry 2000;48: 721-731 (C) 2000 Society of Biological Psychiatry.
    BibTeX:
    @article{McEwen2000,
      author = {McEwen, BS},
      title = {Effects of adverse experiences for brain structure and function},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {2000},
      volume = {48},
      number = {8},
      pages = {721-731},
      note = {Conference on Depression in the 21st Century: New Insight into Drug Development and Neurobiology, DANA POINT, CALIFORNIA, FEB 02-22, 2000}
    }
    
    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}
    }
    
    McLachlan, J. Environmental signaling: What embryos and evolution teach us about endocrine disrupting chemicals {2001} ENDOCRINE REVIEWS
    Vol. {22}({3}), pp. {319-341} 
    article  
    Abstract: The term ``endocrine disrupting chemicals'' is commonly used to describe environmental agents that alter the endocrine system. Laboratories working in this emerging field-environmental endocrine research-have looked at chemicals that mimic or block endogenous vertebrate steroid hormones by interacting with the hormone's receptor. Environmental chemicals known to do this do so most often with receptors derived from the steroid/thyroid/retinoid gene family. They include ubiquitous and persistent organochlorines, as well as plasticizers, pharmaceuticals, and natural hormones. These chemicals function as estrogens, antiestrogens, and antiandrogens but have few, if any, structural similarities. Therefore, receptor-based or functional assays have the best chance of detecting putative biological activity of environmental chemicals. Three nuclear estrogen receptor forms-alpha, beta, and gamma -as well as multiple membrane forms and a possible mitochondrial form have been reported, suggesting a previously unknown diversity of signaling pathways available to estrogenic chemicals. Examples of environmental or ambient estrogenization occur in laboratory experiments, zoo animals, domestic animals, wildlife, and humans. Environmentally estrogenized phenotypes may differ depending upon the time of exposure-i.e., whether the exposure occurred at a developmental (organizational and irreversible) or post-developmental (activational and reversible) stage. The term ``estrogen'' must be defined in each case, since steroidal estrogens differ among themselves and from synthetic or plant-derived chemicals. An ``estrogen-like function'' seems to be an evolutionarily ancient signal that has been retained in a number of chemicals, some of which are vertebrate hormones. Signaling, required for symbiosis between plants and bacteria, may be viewed, therefore, as an early example of hormone cross-talk. Developmental feminization at the structural or functional level is an emerging theme in species exposed, during embryonic or fetal life, to estrogenic compounds. Human experience as well as studies in experimental animals with the potent estrogen diethylstilbestrol provide informative models. Advances in the molecular genetics of sex differentiation in vertebrates facilitate mechanistic understanding. Experiments addressing the concept of gene imprinting or induction of epigenetic memory by estrogen or other hormones suggest a link to persistent, heritable phenotypic changes seen after developmental estrogenization, independent of mutagenesis. Environmental endocrine science provides a new context in which to examine the informational content of ecosystem-wide communication networks. As common features come to light, this research may allow us to predict environmentally induced alterations in internal signaling systems of vertebrates and some invertebrates and eventually to explicate environmental contributions to human reproductive and developmental health.
    BibTeX:
    @article{McLachlan2001,
      author = {McLachlan, JA},
      title = {Environmental signaling: What embryos and evolution teach us about endocrine disrupting chemicals},
      journal = {ENDOCRINE REVIEWS},
      year = {2001},
      volume = {22},
      number = {3},
      pages = {319-341}
    }
    
    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}
    }
    
    Meneses, A. 5-HT system and cognition {1999} NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
    Vol. {23}({8}), pp. {1111-1125} 
    article  
    Abstract: The study of 5-hydroxytryptamine (5-HT) system has benefited from the identification, classification and cloning of multiple 5-HT receptors (S-HT1 to 5-HT7). Growing evidence suggests that 5-HT is important in learning and memory and all its receptors might be implicated in this. Actually, 5-HT pathways, 5-HT reuptake site/transporter complex and 5-HT receptors show regional distribution in brain areas implicated in learning and memory. Likewise, the stimulation or blockade of presynaptic 5-HT1A, 5-HT1B, 5-HT2A/2C and 5-HT3 receptors, postsynaptic 5-HT2B/2C and 5-HT4 receptors and 5-HT uptake/transporter sites modulate these processes. Available evidence strongly suggests that the 5-HT system may be important in normal function, the treatment and/or pathogenesis of cognitive disorders. Further investigation will help to specify the 5-HT system nature involvement in cognitive processes, pharmacotherapies, their mechanisms and action sites and to determine under which conditions they could operate. In this regard, it is probable that selective drugs with agonists, neutral antagonist, agonists or inverse agonist properties for 5-HT1A, 5-HT1B/1D, 5-HT2A/2B/2C, 5-HT4 and 5-HT7 receptors could constitute a new therapeutic opportunity for learning and memory alterations. (C) 1999 Elsevier Science Ltd. All rights reserved.
    BibTeX:
    @article{Meneses1999,
      author = {Meneses, A},
      title = {5-HT system and cognition},
      journal = {NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS},
      year = {1999},
      volume = {23},
      number = {8},
      pages = {1111-1125}
    }
    
    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}
    }
    
    Meyer-Lindenberg, A., Miletich, R., Kohn, P., Esposito, G., Carson, R., Quarantelli, M., Weinberger, D. & Berman, K. Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia {2002} NATURE NEUROSCIENCE
    Vol. {5}({3}), pp. {267-271} 
    article DOI  
    Abstract: Both dopaminergic neurotransmission and prefrontal cortex (PFC) function are known to be abnormal in schizophrenia. To test the hypothesis that these phenomena are related, we measured presynaptic dopaminergic function simultaneously with regional cerebral blood flow during the Wisconsin Card Sorting Test (WCST) and a control task in unmedicated schizophrenic subjects and matched controls. We show that the dopaminergic uptake constant K-i in the striatum was significantly higher for patients than for controls. Patients had significantly less WCST-related activation in PFC. The two parameters were strongly linked in patients, but not controls. The tight within-patient coupling of these values, with decreased PFC activation predicting exaggerated striatal 6-fluorodopa uptake, supports the hypothesis that prefrontal cortex dysfunction may lead to dopaminergic transmission abnormalities.
    BibTeX:
    @article{Meyer-Lindenberg2002,
      author = {Meyer-Lindenberg, A and Miletich, RS and Kohn, PD and Esposito, G and Carson, RE and Quarantelli, M and Weinberger, DR and Berman, KF},
      title = {Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia},
      journal = {NATURE NEUROSCIENCE},
      year = {2002},
      volume = {5},
      number = {3},
      pages = {267-271},
      doi = {{10.1038/nn804}}
    }
    
    Meyer-Lindenberg, A., Poline, J., Kohn, P., Holt, J., Egan, M., Weinberger, D. & Berman, K. Evidence for abnormal cortical functional connectivity during working memory in schizophrenia {2001} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {158}({11}), pp. {1809-1817} 
    article  
    Abstract: Objective: Disturbed neuronal interactions may be involved in schizophrenia because it is without clear regional pathology. Aberrant connectivity is further suggested by theoretical formulations and neurochemical and neuroanatomical data. The authors applied to schizophrenia a recently available functional neuroimaging analytic method that permits characterization of cooperative action on the systems level. Method: Thirteen medication-free patients and 13 matched healthy comparison subjects performed a working memory (n-back) task and sensorimotor baseline task during positron emission tomography. ``Functional connectivity'' patterns, reflecting distributed correlated activity that differed most between groups, were extracted by a canonical variates analysis. Results: More than half the variance was explained by a single pattern showing inferotemporal, (para-)hippocampal, and cerebellar loadings for patients versus dorsolateral prefrontal and anterior cingulate activity for comparison subjects. Expression of this pattern perfectly separated all patient scans from comparison scans, thus showing promise as a trait marker. This result was validated prospectively by successfully classifying unrelated scans from the same patients and data from a new cohort. An additional 19% of variance corresponded to the pattern activated by the working memory task. Expression of this pattern was more variable in patients during working memory but not the control condition, suggesting inability to sustain a task-adequate neural network, consistent with the disconnection hypothesis. Conclusions: Pronounced disruptions of distributed cooperative activity in schizophrenia were found. A pattern showing disturbed frontotemporal interactions showed promise as a trait marker and may be useful for future investigations.
    BibTeX:
    @article{Meyer-Lindenberg2001,
      author = {Meyer-Lindenberg, A and Poline, JB and Kohn, PD and Holt, JL and Egan, MF and Weinberger, DR and Berman, KF},
      title = {Evidence for abnormal cortical functional connectivity during working memory in schizophrenia},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {2001},
      volume = {158},
      number = {11},
      pages = {1809-1817}
    }
    
    Middleton, F., Mirnics, K., Pierri, J., Lewis, D. & Levitt, P. Gene expression profiling reveals alterations of specific metabolic pathways in schizophrenia {2002} JOURNAL OF NEUROSCIENCE
    Vol. {22}({7}), pp. {2718-2729} 
    article  
    Abstract: Dysfunction of the dorsal prefrontal cortex (PFC) in schizophrenia may be associated with alterations in the regulation of brain metabolism. To determine whether abnormal expression of genes encoding proteins involved in cellular metabolism contributes to this dysfunction, we used cDNA microarrays to perform gene expression profiling of all major metabolic pathways in postmortem samples of PFC area 9 from 10 subjects with schizophrenia and 10 matched control subjects. Genes comprising 71 metabolic pathways were assessed in each pair, and only five pathways showed consistent changes (decreases) in subjects with schizophrenia. Reductions in expression were identified for genes involved in the regulation of ornithine and polyamine metabolism, the mitochondrial malate shuttle system, the transcarboxylic acid cycle, aspartate and alanine metabolism, and ubiquitin metabolism. Interestingly, although most of the metabolic genes that were consistently decreased across subjects with schizophrenia were not similarly decreased in haloperidol-treated monkeys, the transcript encoding the cytosolic form of malate dehydrogenase displayed prominent drug-associated increases in expression compared with untreated animals. These molecular analyses implicate a highly specific pattern of metabolic alterations in the PFC of subjects with schizophrenia and raise the possibility that antipsychotic medications may exert a therapeutic effect, in part, by normalizing some of these changes.
    BibTeX:
    @article{Middleton2002,
      author = {Middleton, FA and Mirnics, K and Pierri, JN and Lewis, DA and Levitt, P},
      title = {Gene expression profiling reveals alterations of specific metabolic pathways in schizophrenia},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2002},
      volume = {22},
      number = {7},
      pages = {2718-2729}
    }
    
    Middleton, F. & Strick, P. Cerebellar projections to the prefrontal cortex of the primate {2001} JOURNAL OF NEUROSCIENCE
    Vol. {21}({2}), pp. {700-712} 
    article  
    Abstract: The cerebellum is known to project via the thalamus to multiple motor areas of the cerebral cortex. In this study, we examined the extent and anatomical organization of cerebellar input to multiple regions of prefrontal cortex. We first used conventional retrograde tracers to map the origin of thalamic projections to five prefrontal regions: medial area 9 (9m), lateral area 9 (9l), dorsal area 46 (46d), ventral area 46, and lateral area 12. Only areas 46d, 9m, and 9l received substantial input from thalamic regions included within the zone of termination of cerebellar efferents. This suggested that these cortical areas were the target of cerebellar output. We tested this possibility using retrograde transneuronal transport of the McIntyre-B strain of herpes simplex virus type 1 from areas of prefrontal cortex. Neurons labeled by retrograde transneuronal transport of virus were found in the dentate nucleus only after injections into areas 46d, 9m, and 9l. The precise location of labeled neurons in the dentate varied with the prefrontal area injected. In addition, the dentate neurons labeled after virus injections into prefrontal areas were located in regions spatially separate from those labeled after virus injections into motor areas of the cerebral cortex. Our observations indicate that the cerebellum influences several areas of prefrontal cortex via the thalamus. Furthermore, separate output channels exist in the dentate to influence motor and cognitive operations. These results provide an anatomical substrate for the cerebellum to be involved in cognitive functions such as planning, working memory, and rule-based learning.
    BibTeX:
    @article{Middleton2001,
      author = {Middleton, FA and Strick, PL},
      title = {Cerebellar projections to the prefrontal cortex of the primate},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2001},
      volume = {21},
      number = {2},
      pages = {700-712}
    }
    
    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. Basal ganglia output and cognition: Evidence from anatomical, behavioral, and clinical studies {2000} BRAIN AND COGNITION
    Vol. {42}({2}), pp. {183-200} 
    article  
    Abstract: The traditional view that the basal ganglia are simply involved in the control of movement has been challenged in recent years. Three lines of evidence indicate that the basal ganglia also are involved in nonmotor operations. First, the results of anatomical studies clearly indicate that the basal ganglia participate in multiple circuits or `loops' with cognitive areas of the cerebral cortex. Second, the activity of neurons within selected portions of the basal ganglia is more related to cognitive or sensory operations than to motor functions. Finally, in some instances basal ganglia lesions cause primarily cognitive or sensory disturbances without gross motor impairments. In this report, we briefly review some of these data and present a new anatomical framework for understanding the basal ganglia contributions to nonmotor function. (C) 2000 Academic Press.
    BibTeX:
    @article{Middleton2000a,
      author = {Middleton, FA and Strick, PL},
      title = {Basal ganglia output and cognition: Evidence from anatomical, behavioral, and clinical studies},
      journal = {BRAIN AND COGNITION},
      year = {2000},
      volume = {42},
      number = {2},
      pages = {183-200}
    }
    
    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}
    }
    
    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}
    }
    
    MILLER, E., LI, L. & DESIMONE, R. A NEURAL MECHANISM FOR WORKING AND RECOGNITION MEMORY IN INFERIOR TEMPORAL CORTEX {1991} SCIENCE
    Vol. {254}({5036}), pp. {1377-1379} 
    article  
    Abstract: Inferior temporal (IT) cortex is critical for visual memory, but it is not known how IT neurons retain memories while new information is streaming into the visual system. Single neurons were therefore recorded from IT cortex of two rhesus monkeys performing tasks that required them to hold items in memory while concurrently viewing other items. The neuronal response to an incoming visual stimulus was attenuated if it matched a stimulus actively held in working memory, even when several other stimuli intervened. The neuronal response to novel stimuli declined as the stimuli became familiar to the animal. IT neurons appear to function as adaptive mnemonic ``filters'' that preferentially pass information about new, unexpected, or not recently seen stimuli.
    BibTeX:
    @article{MILLER1991,
      author = {MILLER, EK and LI, L and DESIMONE, R},
      title = {A NEURAL MECHANISM FOR WORKING AND RECOGNITION MEMORY IN INFERIOR TEMPORAL CORTEX},
      journal = {SCIENCE},
      year = {1991},
      volume = {254},
      number = {5036},
      pages = {1377-1379}
    }
    
    Miyake, A., Friedman, N., Emerson, M., Witzki, A., Howerter, A. & Wager, T. The unity and diversity of executive functions and their contributions to complex ``frontal lobe'' tasks: A latent variable analysis {2000} COGNITIVE PSYCHOLOGY
    Vol. {41}({1}), pp. {49-100} 
    article DOI  
    Abstract: This individual differences study examined the separability of three often postulated executive functions-mental set shifting (''Shifting''), information updating and monitoring (''Updating''), and inhibition of prepotent responses (''Inhibition'')-and their roles in complex ``frontal lobe'' or ``executive'' tasks. One hundred thirty-seven college students performed a set of relatively simple experimental tasks that an considered to predominantly tap each target executive function as well as a set of frequently used executive tasks: the Wisconsin Card Sorting Test (WCST), Tower of Hanoi (TOH), random number generation (RNG), operation span, and dual tasking. Confirmatory factor analysis indicated that the three target executive functions are moderately correlated with one another, but are clearly separable. Moreover, structural equation modeling suggested that the three functions contribute differentially to performance on complex executive tasks. Specifically, WCST performance was related most strongly to Shifting, TOH to Inhibition, RNG to Inhibition and Updating, and operation span to Updating. Dual task performance was not related to any of the three target functions. These results suggest that it is important to recognize both the unity and diversity of executive functions and that latent variable analysis is a useful approach to studying the organization and roles Of executive functions. (C) 2000 Academic Press.
    BibTeX:
    @article{Miyake2000,
      author = {Miyake, A and Friedman, NP and Emerson, MJ and Witzki, AH and Howerter, A and Wager, TD},
      title = {The unity and diversity of executive functions and their contributions to complex ``frontal lobe'' tasks: A latent variable analysis},
      journal = {COGNITIVE PSYCHOLOGY},
      year = {2000},
      volume = {41},
      number = {1},
      pages = {49-100},
      note = {11th Annual Convention of the American-Psychological-Society, DENVER, COLORADO, JUN, 1999},
      doi = {{10.1006/cogp.1999.0734}}
    }
    
    Moghaddam, B. & Adams, B. Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats {1998} SCIENCE
    Vol. {281}({5381}), pp. {1349-1352} 
    article  
    Abstract: Glutamatergic abnormalities have been associated with several psychiatric disorders, including schizophrenia and addiction. Group II metabotropic glutamate receptors were targeted to normalize glutamatergic disruptions associated with an animal model of schizophrenia, the phencyclidine model. An agonist of this group of receptors, at a dose that was without effects on spontaneous activity and corticolimbic dopamine neurotransmission, attenuated the disruptive effects of phencyclidine on working memory, stereotypy, Locomotion, and cortical glutamate efflux. This behavioral reversal occurred in spite of sustained dopamine hyperactivity. Thus, targeting this group of receptors may present a nondopaminergic: therapeutic strategy for treatment of psychiatric disorders.
    BibTeX:
    @article{Moghaddam1998,
      author = {Moghaddam, B and Adams, BW},
      title = {Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats},
      journal = {SCIENCE},
      year = {1998},
      volume = {281},
      number = {5381},
      pages = {1349-1352}
    }
    
    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}
    }
    
    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}
    }
    
    Morgan, D., Diamond, D., Gottschall, P., Ugen, K., Dickey, C., Hardy, J., Duff, K., Jantzen, P., DiCarlo, G., Wilcock, D., Connor, K., Hatcher, J., Hope, C., Gordon, M. & Arendash, G. A beta peptide vaccination prevents memory loss in an animal model of Alzheimer's disease {2000} NATURE
    Vol. {408}({6815}), pp. {982-985} 
    article  
    Abstract: Vaccinations with amyloid-beta peptide (AB) can dramatically reduce amyloid deposition in a transgenic mouse model of Alzheimer's disease(1). To determine if the vaccinations had deleterious or beneficial functional consequences, we tested eight months of A beta vaccination in a different transgenic model for Alzheimer's disease in which mice develop learning deficits as amyloid accumulates(2,3). Here we show that vaccination with A beta protects transgenic mice from the learning and age-related memory deficits that normally occur in this mouse model for Alzheimer's disease. During testing for potential deleterious effects of the vaccine, all mice performed superbly on the radial-arm water-maze test of working memory. Later, at an age when untreated transgenic mice show memory deficits, the A beta -vaccinated transgenic mice showed cognitive performance superior to that of the control transgenic mice and, ultimately, performed as well as nontransgenic mice. The A beta -vaccinated mice also had a partial reduction in amyloid burden at the end of the study. This therapeutic approach may thus prevent and, possibly, treat Alzheimer's dementia.
    BibTeX:
    @article{Morgan2000,
      author = {Morgan, D and Diamond, DM and Gottschall, PE and Ugen, KE and Dickey, C and Hardy, J and Duff, K and Jantzen, P and DiCarlo, G and Wilcock, D and Connor, K and Hatcher, J and Hope, C and Gordon, M and Arendash, GW},
      title = {A beta peptide vaccination prevents memory loss in an animal model of Alzheimer's disease},
      journal = {NATURE},
      year = {2000},
      volume = {408},
      number = {6815},
      pages = {982-985}
    }
    
    Morgan, M. Ecstasy (MDMA): a review of its possible persistent psychological effects {2000} PSYCHOPHARMACOLOGY
    Vol. {152}({3}), pp. {230-248} 
    article  
    Abstract: Rationale: Recreational use of ``ecstasy'' (3.4-methylenedioxymethamphetamine; MDMA) has become increasingly widespread. Until recently, however, little was known about the possible persistent psychological effects of extensive use of this drug. Objective: The aim of the present review is to evaluate recent empirical evidence concerning the persistent psychological sequelae of recreational ecstasy use. Methods: The methodologies of open trial studies of recreational ecstasy users are evaluated and reports of the presence or absence of persistent psychological problems are related to the extent of past exposure to ecstasy. Results: There is growing evidence that chronic, heavy, recreational use of ecstasy is associated with sleep disorders, depressed mood, persistent elevation of anxiety, impulsiveness and hostility and selective impairment of episodic memory, working memory and attention. There is tentative evidence that these cognitive deficits persist for at least 6 months: after abstinence, whereas anxiety and hostility remit after a year of abstinence. The possibility that some of these psychological problems are caused by ecstasy-induced neurotoxicity is supported by preclinical evidence of MDMA-induced neurotoxicity and behavioural deficits, evidence of depleted serotonin in heavy ecstasy users, and by dose-response relationships between the extent of exposure to ecstasy and the severity of cognitive impairments. Conclusions An increasing number of young, heavy ecstasy users are at significant risk of persistent cognitive impairments and disturbances of affect and personality. Some of these problems may remit after abstinence, but residual neurotoxicity and decline of serotonergic, function with age may result in recurrent psychopathology and premature cognitive decline.
    BibTeX:
    @article{Morgan2000a,
      author = {Morgan, MJ},
      title = {Ecstasy (MDMA): a review of its possible persistent psychological effects},
      journal = {PSYCHOPHARMACOLOGY},
      year = {2000},
      volume = {152},
      number = {3},
      pages = {230-248}
    }
    
    MORRIS, R., DOWNES, J., SAHAKIAN, B., EVENDEN, J., HEALD, A. & ROBBINS, T. PLANNING AND SPATIAL WORKING MEMORY IN PARKINSONS-DISEASE {1988} JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
    Vol. {51}({6}), pp. {757-766} 
    article  
    BibTeX:
    @article{MORRIS1988,
      author = {MORRIS, RG and DOWNES, JJ and SAHAKIAN, BJ and EVENDEN, JL and HEALD, A and ROBBINS, TW},
      title = {PLANNING AND SPATIAL WORKING MEMORY IN PARKINSONS-DISEASE},
      journal = {JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY},
      year = {1988},
      volume = {51},
      number = {6},
      pages = {757-766}
    }
    
    MOSCOVITCH, M. MEMORY AND WORKING-WITH-MEMORY - A COMPONENT PROCESS MODEL BASED ON MODULES AND CENTRAL SYSTEMS {1992} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {4}({3}), pp. {257-267} 
    article  
    Abstract: A neuropsychological model of memory is proposed that incorporates Fodor's (1983) idea of modules and central systems. The model has four essential components: (1) a non-frontal neocortical component that consists of perceptual (and perhaps interpretative semantic) modules that mediate performance on item-specific, implicit tests of memory, (2) a modular medial temporal/hippocampal component that mediates encoding, storage, and retrieval on explicit, episodic tests of memory that are associative/cue dependent, (3) a central system, frontal-lobe component that mediates performance on explicit tests that are strategic and on procedural tests that are rule-bound, and (4) a basal ganglia component that mediates performance on sensorimotor, procedural tests of memory. The usefulness of the modular/central system construct is explored and evidence from studies of normal, amnesic, agnosic, and demented people is provided to support the model.
    BibTeX:
    @article{MOSCOVITCH1992,
      author = {MOSCOVITCH, M},
      title = {MEMORY AND WORKING-WITH-MEMORY - A COMPONENT PROCESS MODEL BASED ON MODULES AND CENTRAL SYSTEMS},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {1992},
      volume = {4},
      number = {3},
      pages = {257-267}
    }
    
    MUMBY, D. & PINEL, J. RHINAL CORTEX LESIONS AND OBJECT RECOGNITION IN RATS {1994} BEHAVIORAL NEUROSCIENCE
    Vol. {108}({1}), pp. {11-18} 
    article  
    Abstract: Rats with bilateral lesions of lateral entorhinal cortex and perirhinal cortex were tested on a nonrecurring-items delayed nonmatching-to-sample (DNMS) task resembling the one that is commonly used to study object recognition in monkeys. The rats were tested at retention delays of 4 s, 15 s, 60 s, 120 s, and 600 s before and after surgery. After surgery, they displayed a delay-dependent deficit: They performed normally at the 4-s delay but were impaired at delays of 15 s or longer. The addition of bilateral amygdala lesions did not increase their DNMS deficits. The present finding of a severe DNMS deficit following rhinal cortex damage is consistent with the authors' previous finding that bilateral lesions of the hippocampus and amygdala cause only mild DNMS deficits in rats unless there is also damage to rhinal cortex (D. G. Mumby, E. R. Wood, and J. P. J. Pinel, 1992). These findings add to accumulating evidence that the rhinal cortex, but not the amygdala, plays a critical role in object recognition.
    BibTeX:
    @article{MUMBY1994,
      author = {MUMBY, DG and PINEL, JPJ},
      title = {RHINAL CORTEX LESIONS AND OBJECT RECOGNITION IN RATS},
      journal = {BEHAVIORAL NEUROSCIENCE},
      year = {1994},
      volume = {108},
      number = {1},
      pages = {11-18}
    }
    
    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}
    }
    
    NELSON, C. THE ONTOGENY OF HUMAN-MEMORY - A COGNITIVE NEUROSCIENCE PERSPECTIVE {1995} DEVELOPMENTAL PSYCHOLOGY
    Vol. {31}({5}), pp. {723-738} 
    article  
    Abstract: The relation between early memory development and corresponding changes in brain development is explored in this article. It is proposed that a form of preexplicit memory (dependent on the hippocampus) develops in the first few months. Between 8 and 12 months, a more adultlike form of explicit memory emerges, which draws broadly on limbic and cortical structures. Two types of implicit memory also make their appearance in the first few months: procedural learning (dependent on striatal structures) and conditioning (which may rely on the olivary-cerebellar complex and possibly the hippocampus). Finally, working memory (dependent on the prefrontal cortex and associated neural circuitry) is also present early in life, although the ability to use working memory when motoric ability is also required (e.g., reaching for hidden objects) has a protracted developmental course relative to other forms of memory.
    BibTeX:
    @article{NELSON1995,
      author = {NELSON, CA},
      title = {THE ONTOGENY OF HUMAN-MEMORY - A COGNITIVE NEUROSCIENCE PERSPECTIVE},
      journal = {DEVELOPMENTAL PSYCHOLOGY},
      year = {1995},
      volume = {31},
      number = {5},
      pages = {723-738}
    }
    
    Newcomer, J., Farber, N., Jevtovic-Todorovic, V., Selke, G., Melson, A., Hershey, T., Craft, S. & Olney, J. Ketamine-induced NMDA receptor hypofunction as a model of memory impairment and psychosis {1999} NEUROPSYCHOPHARMACOLOGY
    Vol. {20}({2}), pp. {106-118} 
    article  
    Abstract: N-methyl-D-aspartate (NMDA) glutamate receptor antagonists are reported to induce schizophrenia-like symptoms in humans, including cognitive impairments. Shortcomings of most previous investigations include failure to maintain steady-state infusion conditions, test multiple doses and/or measure antagonist plasma concentrations. This double-blind, placebo-controlled, randomized within-subjects comparison of three fixed subanesthetic, steady-state doses of intravenous ketamine hz healthy males (n = 15) demonstrated dose-dependent increases in Brief Psychiatric Rating Scale positive (F[3,42] = 21.84; p < 0.0001) and negative symptoms (F[3, 42] = 2.89; p = 0.047), and Scale for the Assessment of Negative Symptoms (SANS) total scores (F[3,42] = 10.55; p < 0.0001). Ketamine also produced a robust dose-dependent decrease in verbal declarative memory performance (F[3, 41] = 5.11; p = 0.004), ann preliminary evidence for a similar dose-dependent decrease in nonverbal declarative memory, occurring at or below plasma concentrations producing other symptoms. Increasing NMDA receptor hypofunction is associated with early occurring memory impairment followed by other schizophrenia-like symptoms. [Neuropsychopharmacology 20:106-118, 1999] (C) 1998 American College of Neuropsychopharmacology Published by Elsevier Science lire.
    BibTeX:
    @article{Newcomer1999,
      author = {Newcomer, JW and Farber, NB and Jevtovic-Todorovic, V and Selke, G and Melson, AK and Hershey, T and Craft, S and Olney, JW},
      title = {Ketamine-induced NMDA receptor hypofunction as a model of memory impairment and psychosis},
      journal = {NEUROPSYCHOPHARMACOLOGY},
      year = {1999},
      volume = {20},
      number = {2},
      pages = {106-118}
    }
    
    Newhouse, P., Potter, A. & Levin, E. Nicotinic system involvement in Alzheimer's and Parkinson's diseases - Implications for therapeutics {1997} DRUGS & AGING
    Vol. {11}({3}), pp. {206-228} 
    article  
    Abstract: Advances in our understanding of the structure, function and distribution of nicotinic acetylcholine receptors in the CNS have provided the impetus for new studies examining the role(s) that these receptors and associated processes may play in CNS functions. Further motivation has come from the realisation that such receptors must be involved in the maintenance of cigarette smoking, and from clues provided by studies of degenerative neurological diseases such as Alzheimer's disease and Parkinson's disease, in which the loss of nicotinic receptors has been described. Ongoing investigations of the molecular substructure of central nicotinic receptors and their pharmacology have begun to open up new possibilities for novel CNS therapeutics with nicotinic agents. Exploiting these possibilities will require understanding of the role(s) that these receptor systems play in human cognitive, behavioural, motor and sensory functioning. Clues from careful studies of human cognition are beginning to emerge and will provide direction for studies of potentially therapeutic novel nicotinic agents. Despite the promising results of acute studies, few long term studies with nicotine or nicotinic drugs have been performed in dementing disorders. Thus, there is uncertainty as to whether long term nicotinic treatment will provide sustained cognitive benefit. It is even more uncertain whether such cognitive benefit will have a significant clinical impact on patients and their families. To maximise the potential benefit of long term treatment with nicotinic agonists (or other cholinergic drugs), we suggest that drug treatment should be combined with cognitive rehabilitation strategies. This will enable patients and/or their families to focus on the particular cognitive domains that may be improved.
    BibTeX:
    @article{Newhouse1997,
      author = {Newhouse, PA and Potter, A and Levin, ED},
      title = {Nicotinic system involvement in Alzheimer's and Parkinson's diseases - Implications for therapeutics},
      journal = {DRUGS & AGING},
      year = {1997},
      volume = {11},
      number = {3},
      pages = {206-228}
    }
    
    Nobre, A., Gitelman, D., Dias, E. & Mesulam, M. Covert visual spatial orienting and saccades: Overlapping neural systems {2000} NEUROIMAGE
    Vol. {11}({3}), pp. {210-216} 
    article  
    Abstract: We used functional magnetic resonance imaging (fMRI) to investigate the functional anatomical relationship between covert orienting of visual spatial attention and execution of saccadic eye movements. Brain areas engaged by shifting spatial attention covertly and by moving the eyes repetitively toward visual targets were compared and contrasted directly within the same subjects. The two tasks activated highly overlapping neural systems and showed that common parietal and frontal regions are more activated during the covert task than the overt oculomotor condition. The possible nature of the relationship between these two operations is discussed. (C) 2000 Academic Press.
    BibTeX:
    @article{Nobre2000,
      author = {Nobre, AC and Gitelman, DR and Dias, EC and Mesulam, MM},
      title = {Covert visual spatial orienting and saccades: Overlapping neural systems},
      journal = {NEUROIMAGE},
      year = {2000},
      volume = {11},
      number = {3},
      pages = {210-216}
    }
    
    Northoff, G., Heinzel, A., de Greck, M., Bennpohl, F., Dobrowolny, H. & Panksepp, J. Self-referential processing in our brain - A meta-analysis of imaging studies on the self {2006} NEUROIMAGE
    Vol. {31}({1}), pp. {440-457} 
    article DOI  
    Abstract: The question of the self has intrigued philosophers and psychologists for a long time. More recently, distinct concepts of self have also been suggested in neuroscience. However, the exact relationship between these concepts and neural processing across different brain regions remains unclear. This article reviews neuroimaging studies comparing neural correlates during processing of stimuli related to the self with those of non-self-referential stimuli. All studies revealed activation in the medial regions of our brains' cortex during self-related stimuli. The activation in these so-called cortical midline structures (CMS) occurred across all functional domains (e.g., verbal, spatial, emotional, and facial). Cluster and factor analyses indicate functional specialization into ventral, dorsal, and posterior CMS remaining independent of domains. Taken together, our results suggest that self-referential processing is mediated by cortical midline structures. Since the CNIS are densely and reciprocally connected to subcortical midline regions, we advocate an integrated cortical-subcortical midline system underlying human self. We conclude that self-referential processing in CNIS constitutes the core of our self and is critical for elaborating experiential feelings of self, uniting several distinct concepts evident in current neuroscience. (c) 2005 Elsevier Inc. All rights reserved.
    BibTeX:
    @article{Northoff2006,
      author = {Northoff, Georg and Heinzel, Alexander and de Greck, Moritz and Bennpohl, Felix and Dobrowolny, Henrik and Panksepp, Jaak},
      title = {Self-referential processing in our brain - A meta-analysis of imaging studies on the self},
      journal = {NEUROIMAGE},
      year = {2006},
      volume = {31},
      number = {1},
      pages = {440-457},
      doi = {{10.1016/j.neuroimage.2005.12.002}}
    }
    
    Nuechterlein, K., Barch, D., Gold, J., Goldberg, T., Green, M. & Heaton, R. Identification of separable cognitive factors in schizophrenia {2004} SCHIZOPHRENIA RESEARCH
    Vol. {72}({1}), pp. {29-39} 
    article DOI  
    Abstract: One of the primary goals in the NIMH initiative to encourage development of new interventions for cognitive deficits in schizophrenia, Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS), has been to develop a reliable and valid consensus cognitive battery for use in clinical trials. Absence of such a battery has hampered standardized evaluation of new treatments and, in the case of pharmacological agents, has been an obstacle to FDA approval of medications targeting cognitive deficits in schizophrenia. A fundamental step in developing such a battery was to identify the major separable cognitive impairments in schizophrenia. As part of this effort, we evaluated the empirical evidence for cognitive performance dimensions in schizophrenia, emphasizing factor analytic studies. We concluded that seven separable cognitive factors were replicable across studies and represent fundamental dimensions of cognitive deficit in schizophrenia: Speed of Processing, Attention/Vigilance, Working Memory, Verbal Learning and Memory, Visual Learning and Memory, Reasoning and Problem Solving, and Verbal Comprehension. An eighth domain, Social Cognition, was added due to recent increased interest in this area and other evidence of its relevance for clinical trials aiming to evaluate the impact of potential cognitive enhancers on cognitive performance and functional outcome. Verbal Comprehension was not considered appropriate for a cognitive battery intended to be sensitive to cognitive change, due to its resistance to change. The remaining seven domains were recommended for inclusion in the MATRICS-NIMH consensus cognitive battery and will serve as the basic structure for that battery. These separable cognitive dimensions also have broader relevance to future research aimed at understanding the nature and structure of core cognitive deficits in schizophrenia. (C) 2004 Elsevier B.V. All rights reserved.
    BibTeX:
    @article{Nuechterlein2004,
      author = {Nuechterlein, KH and Barch, DM and Gold, JM and Goldberg, TE and Green, MF and Heaton, RK},
      title = {Identification of separable cognitive factors in schizophrenia},
      journal = {SCHIZOPHRENIA RESEARCH},
      year = {2004},
      volume = {72},
      number = {1},
      pages = {29-39},
      doi = {{10.1016/j.schres.2004.09.007}}
    }
    
    NUECHTERLEIN, K., DAWSON, M., GITLIN, M., VENTURA, J., GOLDSTEIN, M., SNYDER, K., YEE, C. & MINTZ, J. DEVELOPMENTAL PROCESSES IN SCHIZOPHRENIC DISORDERS - LONGITUDINAL-STUDIES OF VULNERABILITY AND STRESS {1992} SCHIZOPHRENIA BULLETIN
    Vol. {18}({3}), pp. {387-425} 
    article  
    Abstract: The Developmental Processes in Schizophrenic Disorders project is a longitudinal study of schizophrenic patients who have recently had a first episode of psychosis. The project focuses on discriminating characteristics of schizophrenic patients that are ``stable vulnerability indicators,'' ``mediating vulnerability factors,'' and ``episode indicators'' by comparing normal subjects to schizophrenic patients assessed in clinically remitted and psychotic states. A parallel project goal is to identify predictors of relapse, social and work impairment, and illness course among potential psychobiological vulnerability factors and environmental potentiating factors. Hypothesized vulnerability factors and potential environmental stressors are examined first under standardized maintenance antipsychotic medication conditions for at least 1 year. Patients showing stable remission of psychosis after 1 year of maintenance antipsychotic medication are invited to enter drug crossover and withdrawal protocols to determine the need for continuous antipsychotic medication. Vulnerability and stress factors are again assessed. A summary of results to date is presented. Deficits in early components of processing visual arrays and in sustained discrimination of successive ambiguous perceptual inputs are relatively stable across psychotic and clinically remitted states in the schizophrenic patients. Performance on a vigilance task demanding active, working memory also remains abnormal during clinical remission but covaries significantly with psychotic state and is a candidate for a mediating vulnerability factor. Autonomic activation level does not appear to be an enduring vulnerability factor, but it predicts the extent of short-term symptomatic recovery and may mediate the impact of stressors. Under conditions of standardized, injectable antipsychotic medication, independent stressful life events and highly critical attitudes toward the patient in the social environment predict relapse risk. Prospective data suggest that signs and symptoms prodromal to psychotic relapse may be present in about 60 percent of patients.
    BibTeX:
    @article{NUECHTERLEIN1992,
      author = {NUECHTERLEIN, KH and DAWSON, ME and GITLIN, M and VENTURA, J and GOLDSTEIN, MJ and SNYDER, KS and YEE, CM and MINTZ, J},
      title = {DEVELOPMENTAL PROCESSES IN SCHIZOPHRENIC DISORDERS - LONGITUDINAL-STUDIES OF VULNERABILITY AND STRESS},
      journal = {SCHIZOPHRENIA BULLETIN},
      year = {1992},
      volume = {18},
      number = {3},
      pages = {387-425}
    }
    
    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'Sullivan, M., Jones, D., Summers, P., Morris, R., Williams, S. & Markus, H. Evidence for cortical ``disconnection'' as a mechanism of age-related cognitive decline {2001} NEUROLOGY
    Vol. {57}({4}), pp. {632-638} 
    article  
    Abstract: Background: Normal aging is accompanied by a decline of cognitive abilities, and executive skills may be affected selectively, but the underlying mechanisms remain obscure and preventive strategies are lacking. It has been suggested that cortical ``disconnection'' due to the loss of white matter fibers may play an important role. But, to date, there has been no direct demonstration of structural disconnection in humans in vivo. Methods: The authors used diffusion tensor MRI to look for evidence of ultrastructural changes in cerebral white matter in a group of 20 elderly volunteers with normal conventional MRI scans, and a group of 10 younger controls. The older group also underwent neuropsychological assessment. Results: Diffusional anisotropy, a marker of white matter tract integrity, was reduced in the white matter of older subjects and fell linearly with increasing age in the older group. Mean diffusivity was higher in the older group and increased with age. These changes were maximal in anterior white matter. In the older group, anterior mean diffusivity correlated with executive function assessed by the Trail Making Test. Conclusions: These findings provide direct evidence that white matter tract disruption occurs in normal aging and would be consistent with the cortical disconnection hypothesis of age-related cognitive decline. Maximal changes in anterior white matter provide a plausible structural basis for selective loss of executive functions. In addition to providing new information about the biological basis of cognitive abilities, diffusion tensor MRI may be a sensitive tool for assessing interventions aimed at preventing cognitive decline.
    BibTeX:
    @article{O'Sullivan2001,
      author = {O'Sullivan, M and Jones, DK and Summers, PE and Morris, RG and Williams, SCR and Markus, HS},
      title = {Evidence for cortical ``disconnection'' as a mechanism of age-related cognitive decline},
      journal = {NEUROLOGY},
      year = {2001},
      volume = {57},
      number = {4},
      pages = {632-638}
    }
    
    Ochsner, K., Bunge, S., Gross, J. & Gabrieli, J. Rethinking feelings: An fMRI study of the cognitive regulation of emotion {2002} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {14}({8}), pp. {1215-1229} 
    article  
    Abstract: The ability to cognitively regulate emotional responses to aversive events is important for mental and physical health. Little is known, however, about neural bases of the cognitive control of emotion. The present study employed functional magnetic resonance imaging to examine the neural systems used to reappraise highly negative scenes in unemotional terms. Reappraisal of highly negative scenes reduced subjective experience of negative affect. Neural correlates of reappraisal were increased activation of the lateral and medial prefrontal regions and decreased activation of the amygdala and medial orbito-frontal cortex. These findings support the hypothesis that prefrontal cortex is involved in constructing reappraisal strategies that can modulate activity in multiple emotion-processing systems.
    BibTeX:
    @article{Ochsner2002,
      author = {Ochsner, KN and Bunge, SA and Gross, JJ and Gabrieli, JDE},
      title = {Rethinking feelings: An fMRI study of the cognitive regulation of emotion},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {2002},
      volume = {14},
      number = {8},
      pages = {1215-1229}
    }
    
    Ochsner, K., Knierim, K., Ludlow, D., Hanelin, J., Ramachandran, T., Glover, G. & Mackey, S. Reflecting upon feelings: an fMRI study of neural systems supporting the attribution of emotion to self and other {2004} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {16}({10}), pp. {1746-1772} 
    article  
    Abstract: Understanding one's own and other individual's emotional states is essential for maintaining emotional equilibrium and strong social bonds. Although the neural substrates supporting reflection upon one's own feelings have been investigated, no studies have directly examined attributions about the internal emotional states of others to determine whether common or distinct neural systems support these abilities. The present study sought to directly compare brain regions involved in judging one's own, as compared to another individual's, emotional state. Thirteen participants viewed mixed valence blocks of photos drawn from the International Affective Picture System while whole-brain fMRI data were collected. Preblock cues instructed participants to evaluate either their emotional response to each photo, the emotional state of the central figure in each photo, or (in a baseline condition) whether the photo was taken indoors or outdoors. Contrasts indicated (1) that both self and other judgments activated the medial prefrontal cortex (MPFC), the superior temporal gyrus, and the posterior cingulate/precuneus, (2) that self judgments selectively activated subregions of the MPFC and the left temporal cortex, whereas (3) other judgments selectively activated the left lateral prefrontal cortex (including Broca's area) and the medial occipital cortex. These results suggest (1) that self and other evaluation of emotion rely on a network of common mechanisms centered on the MPFC, which has been hypothesized to support mental state attributions in general, and (2) that medial and lateral PFC regions selectively recruited by self or other judgments may be involved in attention to, and elaboration of, internally as opposed to externally generated information.
    BibTeX:
    @article{Ochsner2004a,
      author = {Ochsner, KN and Knierim, K and Ludlow, DH and Hanelin, J and Ramachandran, T and Glover, G and Mackey, SC},
      title = {Reflecting upon feelings: an fMRI study of neural systems supporting the attribution of emotion to self and other},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {2004},
      volume = {16},
      number = {10},
      pages = {1746-1772}
    }
    
    Ochsner, K., Ray, R., Cooper, J., Robertson, E., Chopra, S., Gabrieli, J. & Gross, J. For better or for worse: neural systems supporting the cognitive down- and up-regulation of negative emotion {2004} NEUROIMAGE
    Vol. {23}({2}), pp. {483-499} 
    article DOI  
    Abstract: Functional neuroimaging studies examining the neural bases of the cognitive control of emotion have found increased prefrontal and decreased amygdala activation for the reduction or down-regulation of negative emotion. It is unknown, however, (1) whether the same neural systems underlie the enhancement or tip-regulation of emotion, and (2) whether altering the nature of the regulatory strategy alters the neural systems mediating the regulation. To address these questions using functional magnetic resonance imaging (fMRI), participants up- and down-regulated negative emotion either by focusing internally on the self-relevance of aversive scenes or by focusing externally on alternative meanings for pictured actions and their situational contexts Results indicated (1a) that both up- and down-regulating negative emotion recruited prefrontal and anterior cingulate regions implicated in cognitive control, (1b) that amygdala activation was modulated up or down in accord with the regulatory goal, and (1c) that up-regulation uniquely recruited regions of left rostromedial PFC implicated in the retrieval of emotion knowledge, whereas down-regulation uniquely recruited regions of right lateral and orbital PFC implicated in behavioral inhibition. Results also indicated that (2) self-focused regulation recruited medial prefrontal regions implicated in internally focused processing, whereas situation-focused regulation recruited lateral prefrontal regions implicated in externally focused processing. These data suggest that both common and distinct neural systems support various forms of reappraisal and that which particular prefrontal systems modulate the amygdala in different ways depends on the regulatory goal and strategy employed. (C) 2004 Elsevier Inc. All rights reserved.
    BibTeX:
    @article{Ochsner2004,
      author = {Ochsner, KN and Ray, RD and Cooper, JC and Robertson, ER and Chopra, S and Gabrieli, JDE and Gross, JJ},
      title = {For better or for worse: neural systems supporting the cognitive down- and up-regulation of negative emotion},
      journal = {NEUROIMAGE},
      year = {2004},
      volume = {23},
      number = {2},
      pages = {483-499},
      doi = {{10.1016/j.neuroimage.2004.06.030}}
    }
    
    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}
    }
    
    OTTO, T. & EICHENBAUM, H. COMPLEMENTARY ROLES OF THE ORBITAL PREFRONTAL CORTEX AND THE PERIRHINAL ENTORHINAL CORTICES IN AN ODOR-GUIDED DELAYED-NONMATCHING-TO-SAMPLE TASK {1992} BEHAVIORAL NEUROSCIENCE
    Vol. {106}({5}), pp. {762-775} 
    article  
    Abstract: Continuing efforts toward designing odor-guided tasks for rats that are similar in memory demands to tasks used typically with primates have resulted in the development of a continuous delayed-nonmatching-to-sample (cDNM) task that is guided by olfactory stimuli. The results indicate that normal subjects acquire the cDNM task rapidly and that subsequent performance deteriorates with increases in memory delay or interitem interference. Moreover, different aspects of cDNM performance were shown to be differentially sensitive to selective lesions of the orbitofrontal and parahippocampal areas. Orbitofrontal cortex lesions disproportionately impaired cDNM acquisition; delay performance was impaired only under conditions of elevated levels of interitem interference. Combined perirhinal and entorhinal cortical lesions had no effect on cDNM acquisition but impaired cDNM performance at longer delays across all levels of interference. Fornix lesions did not impair either acquisition of cDNM or subsequent performance across long delays and increased interference. This pattern of impaired and spared capacities is similar to that observed in monkeys after lesions of analogous areas and is consistent with the notion that the prefrontal cortical system contributes preferentially to learning general task ``rules'' such as the nonmatching rule that is inherent in cDNM, whereas the perirhinal and entorhinal cortical areas are involved in the intermediate-term maintenance of memories for specific information.
    BibTeX:
    @article{OTTO1992,
      author = {OTTO, T and EICHENBAUM, H},
      title = {COMPLEMENTARY ROLES OF THE ORBITAL PREFRONTAL CORTEX AND THE PERIRHINAL ENTORHINAL CORTICES IN AN ODOR-GUIDED DELAYED-NONMATCHING-TO-SAMPLE TASK},
      journal = {BEHAVIORAL NEUROSCIENCE},
      year = {1992},
      volume = {106},
      number = {5},
      pages = {762-775}
    }
    
    Owen, A. The functional organization of working memory processes within human lateral frontal cortex: The contribution of functional neuroimaging {1997} EUROPEAN JOURNAL OF NEUROSCIENCE
    Vol. {9}({7}), pp. {1329-1339} 
    article  
    Abstract: Recent functional neuroimaging studies have provided a wealth of new information about the likely organization of working memory processes within the human lateral frontal cortex. This article seeks to evaluate the results of these studies in the context of two contrasting theoretical models of lateral frontal-lobe function, developed through lesion and electrophysiological recording work in non-human primates (Goldman-Rakic, 1994, 1995; Petrides, 1994, 1995). Both models focus on a broadly similar distinction between anatomically and cytoarchitectonically distinct dorsolateral and ventrolateral frontal cortical areas, but differ in the precise functions ascribed to those regions. Following a review of the relevant anatomical data, the origins of these two theoretical positions are considered in some detail and the main predictions arising from each are identified. Recent functional neuroimaging studies of working memory processes are then critically reviewed in order to assess the extent to which they support either, or both, sets of predictions. The results of this meta-analysis suggest that lateral regions of the frontal lobe are not functionally organized according to stimulus modality, as has been widely assumed, but that specific regions within the dorsolateral or ventrolateral frontal cortex make identical functional contributions to both spatial and non-spatial working memory.
    BibTeX:
    @article{Owen1997,
      author = {Owen, AM},
      title = {The functional organization of working memory processes within human lateral frontal cortex: The contribution of functional neuroimaging},
      journal = {EUROPEAN JOURNAL OF NEUROSCIENCE},
      year = {1997},
      volume = {9},
      number = {7},
      pages = {1329-1339}
    }
    
    OWEN, A., DOWNES, J., SAHAKIAN, B., POLKEY, C. & ROBBINS, T. PLANNING AND SPATIAL WORKING MEMORY FOLLOWING FRONTAL-LOBE LESIONS IN MAN {1990} NEUROPSYCHOLOGIA
    Vol. {28}({10}), pp. {1021-1034} 
    article  
    BibTeX:
    @article{OWEN1990,
      author = {OWEN, AM and DOWNES, JJ and SAHAKIAN, BJ and POLKEY, CE and ROBBINS, TW},
      title = {PLANNING AND SPATIAL WORKING MEMORY FOLLOWING FRONTAL-LOBE LESIONS IN MAN},
      journal = {NEUROPSYCHOLOGIA},
      year = {1990},
      volume = {28},
      number = {10},
      pages = {1021-1034}
    }
    
    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{Owen1996a,
      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., Evans, A. & Petrides, M. Evidence for a two-stage model of spatial working memory processing within the lateral frontal cortex: A positron emission tomography study {1996} CEREBRAL CORTEX
    Vol. {6}({1}), pp. {31-38} 
    article  
    Abstract: Previous work in nonhuman primates and in patients with frontal lobe damage has suggested that the frontal cortex plays a critical role in the performance of both spatial and nonspatial working memory tasks, The present study used positron emission tomography with magnetic resonance imaging to demonstrate the existence, within the human brain, of two functionally distinct subdivisions of the lateral frontal cortex, which may subserve different aspects of spatial working memory, Five spatial memory tasks were used, which varied in terms of the extent to which they required different executive processes. When the task required the organization and execution of a sequence of spatial moves retained in working memory, significant changes in blood flow were observed in ventrolateral frontal cortex (area 47) bilaterally. By contrast, when the task required active monitoring and manipulation of spatial information within working memory, additional activation foci were observed in mid-dorsolateral frontal cortex (areas 46 and 9), These findings support a two-stage model of spatial working memory processing within the lateral frontal cortex.
    BibTeX:
    @article{Owen1996,
      author = {Owen, AM and Evans, AC and Petrides, M},
      title = {Evidence for a two-stage model of spatial working memory processing within the lateral frontal cortex: A positron emission tomography study},
      journal = {CEREBRAL CORTEX},
      year = {1996},
      volume = {6},
      number = {1},
      pages = {31-38}
    }
    
    OWEN, A., JAMES, M., LEIGH, P., SUMMERS, B., MARSDEN, C., QUINN, N., LANGE, K. & ROBBINS, T. FRONTO-STRIATAL COGNITIVE DEFICITS AT DIFFERENT STAGES OF PARKINSONS-DISEASE {1992} BRAIN
    Vol. {115}({Part 6}), pp. {1727-1751} 
    article  
    Abstract: Groups of patients with idiopathic Parkinson's disease, either medicated or unmedicated, were compared with matched groups of normal controls on a computerized battery previously shown to be sensitive to frontal lobe dysfunction, including tests of planning, spatial working memory and attentional set-shifting. In a series of problems based on the `Tower of London' test, medicated patients with Parkinson's disease were shown to be impaired in the amount of time spent thinking about (planning) the solution to each problem. Additionally, an impairment in terms of the accuracy of the solution produced on this test was only evident in those patients with more severe clinical symptoms and was accompanied by deficits in an associated test of spatial short-term memory. Medicated patients with both mild and severe clinical symptoms were also impaired on a related test of spatial working memory. In contrast, a group of patients who were unmedicated and `early in the course' of the disease were unimpaired in all three of these tests. However, all three Parkinson's disease groups were impaired in the test of attentional set-shifting ability, although unimpaired in a test of pattern recognition which is insensitive to frontal lobe damage. These data are compared with those previously published from a group of young neurosurgical patients with localized excisions of the frontal lobes and are discussed in terms of the specific nature of the cognitive deficit at different stages of Parkinson's disease.
    BibTeX:
    @article{OWEN1992,
      author = {OWEN, AM and JAMES, M and LEIGH, PN and SUMMERS, BA and MARSDEN, CD and QUINN, NP and LANGE, KW and ROBBINS, TW},
      title = {FRONTO-STRIATAL COGNITIVE DEFICITS AT DIFFERENT STAGES OF PARKINSONS-DISEASE},
      journal = {BRAIN},
      year = {1992},
      volume = {115},
      number = {Part 6},
      pages = {1727-1751}
    }
    
    Owen, A., McMillan, K., Laird, A. & Bullmore, E. N-back working memory paradigm: A meta-analysis of normative functional neuroimaging {2005} HUMAN BRAIN MAPPING
    Vol. {25}({1}), pp. {46-59} 
    article DOI  
    Abstract: One of the most popular experimental paradigms for functional neuroimaging studies of working memory has been the n-back task, in which subjects are asked to monitor the identity or location of a series of verbal or nonverbal stimuli and to indicate when the currently presented stimulus is the same as the one presented n trials previously. We conducted a quantitative meta-analysis of 668 sets of activation coordinates in Talairach space reported in 24 primary studies of n-back task variants manipulating process (location vs. identity monitoring) and content (verbal or nonverbal) of working memory. We found the following cortical regions were activated robustly (voxelwise false discovery rate = 1: lateral premotor cortex; dorsal cingulate and medial premotor cortex; dorsolateral and ventrolateral prefrontal cortex; frontal poles; and medial and lateral posterior parietal cortex. Subsidiary meta-analyses based on appropriate subsets of the primary data demonstrated broadly similar activation patterns for identity monitoring of verbal stimuli and both location and identity monitoring of nonverbal stimuli. There was also some evidence for distinct frontoparietal activation patterns in response to different task variants. The functional specializations of each of the major cortical components in the generic large-scale frontoparietal system are discussed. We conclude that quantitative meta-analysis can be a powerful too] for combining results of multiple primary studies reported in Talairach space. Here, it provides evidence both for broadly consistent activation of frontal and parietal cortical regions by various versions of the n-back working memory paradigm, and for process- and content-specific frontoparietal activation by working memory. (c) 2005 Wiley-Liss, Inc.
    BibTeX:
    @article{Owen2005,
      author = {Owen, AM and McMillan, KM and Laird, AR and Bullmore, E},
      title = {N-back working memory paradigm: A meta-analysis of normative functional neuroimaging},
      journal = {HUMAN BRAIN MAPPING},
      year = {2005},
      volume = {25},
      number = {1},
      pages = {46-59},
      doi = {{10.1002/hbm.20131}}
    }
    
    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}
    }
    
    Owen, A., Stern, C., Look, R., Tracey, I., Rosen, B. & Petrides, M. Functional organization of spatial and nonspatial working memory processing within the human lateral frontal cortex {1998} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {95}({13}), pp. {7721-7726} 
    article  
    Abstract: The present study used functional magnetic resonance imaging to demonstrate that performance of visual spatial and visual nonspatial working memory tasks involve the same regions of the lateral prefrontal cortex when all factors unrelated to the type of stimulus material are appropriately controlled. These results provide evidence that spatial and nonspatial working memory may not be mediated, respectively, by mid-dorsolateral and mid-ventrolateral regions of the frontal lobe, as widely assumed, and support the alternative notion that specific regions of the lateral prefrontal cortex make identical executive functional contributions to both spatial and nonspatial working memory.
    BibTeX:
    @article{Owen1998,
      author = {Owen, AM and Stern, CE and Look, RB and Tracey, I and Rosen, BR and Petrides, M},
      title = {Functional organization of spatial and nonspatial working memory processing within the human lateral frontal cortex},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1998},
      volume = {95},
      number = {13},
      pages = {7721-7726}
    }
    
    Pantelis, C., Barnes, T., Nelson, H., Tanner, S., Weatherley, L., Owen, A. & Robbins, T. Frontal-striatal cognitive deficits in patients with chronic schizophrenia {1997} BRAIN
    Vol. {120}({Part 10}), pp. {1823-1843} 
    article  
    Abstract: Spatial working memory and planning abilities were assessed in 36 hospitalized patients with chronic schizophrenia, using the computerized Cambridge Neuropsychological Test Automated Battery (CANTAB), and compared with those of normal subjects and patients with neurological disorders (frontal lobe lesions; temporal lobe and amygdalo-hippocampal lesions; Parkinson's disease), matched for age, sex and National Adult Reading Test IQ. The patients in the group with temporal lobe lesions were unimpaired in their performance on these tasks. Patients with schizophrenia were impaired on visuo-spatial memory span compared with all the other groups, while severity of Parkinson's disease was correlated with the degree of impairment on this task. The patients with schizophrenia and those with frontal lobe lesions were impaired on a `spatial working memory' task, with increased `between-search errors'. Patients with Parkinson's disease performed this task poorly compared with the younger control subjects. Patients with schizophrenia were unable to develop a systematic strategy to complete this task, relying instead on a limited visuo-spatial memory span. Higher level planning ability was investigated using the CANTAB `Tower of London'. All groups were equally able to complete the task. However; the groups of patients with schizophrenia and frontal lobe lesions made fewer perfect solutions and required more moves for completion. Movement times were significantly slower in the schizophrenia group, suggesting impairment in the sensorimotor requirements of the task. The patients with schizophrenia were not impaired in their `initial thinking' (planning) latencies, but had significantly prolonged `subsequent thinking' (execution) latencies. This pattern resembled that of the group with frontal lobe lesions and contrasted with the prolonged `initial thinking' time seen in Parkinson's disease. The results of this study are indicative of an overall deficit of executive functioning in schizophrenia, even greater than that seen in patients with frontal lobe lesions. However the pattern of results in schizophrenia resembled that seen in patients with lesions of the frontal lobe or with basal ganglia dysfunction, providing support for the notion of a disturbance of frontostriatal circuits in schizophrenia. Our findings also indicate that there is a loss of the normal relationships between different domains of executive function in schizophrenia, with implications for impaired functional connectivity between different regions of the neocortex.
    BibTeX:
    @article{Pantelis1997,
      author = {Pantelis, C and Barnes, TRE and Nelson, HE and Tanner, S and Weatherley, L and Owen, AM and Robbins, TW},
      title = {Frontal-striatal cognitive deficits in patients with chronic schizophrenia},
      journal = {BRAIN},
      year = {1997},
      volume = {120},
      number = {Part 10},
      pages = {1823-1843}
    }
    
    Park, D., Lautenschlager, G., Hedden, T., Davidson, N., Smith, A. & Smith, P. Models of visuospatial and verbal memory across the adult life span {2002} PSYCHOLOGY AND AGING
    Vol. {17}({2}), pp. {299-320} 
    article DOI  
    Abstract: The authors investigated the distinctiveness and interrelationships among visuospatial and verbal memory processes in short-term. working. and long-term memories in 345 adults. Beginning in the 20s. a continuous. regular decline occurs for processing-intensive tasks (e.g.. speed of processing. working memory, and long-term memory), whereas verbal knowledge increases across the life span, There is little differentiation in the cognitive architecture of memory across the life span, Visuospatial and verbal working memory are distinct but highly interrelated systems with domain-specific short-term memory subsystems. In contrast to recent neuroimaging data, there is little evidence for dedifferentiation of function at the behavioral level in old compared with young adults. The authors conclude that efforts to connect behavioral and brain data yield a more complete understanding of the aging mind.
    BibTeX:
    @article{Park2002,
      author = {Park, DC and Lautenschlager, G and Hedden, T and Davidson, NS and Smith, AD and Smith, PK},
      title = {Models of visuospatial and verbal memory across the adult life span},
      journal = {PSYCHOLOGY AND AGING},
      year = {2002},
      volume = {17},
      number = {2},
      pages = {299-320},
      doi = {{10.1037//0882-7974.17.2.299}}
    }
    
    Park, D., Smith, A., Lautenschlager, G., Earles, J., Frieske, D., Zwahr, M. & Gaines, C. Mediators of long-term memory performance across the life span {1996} PSYCHOLOGY AND AGING
    Vol. {11}({4}), pp. {621-637} 
    article  
    Abstract: An individual-differences approach was used to examine the component processes that predict episodic long-term memory performance. A total of 301 participants ages 20-90 received a 7-hr cognitive battery across 3 days. Key constructs hypothesized to affect long-term memory function were assessed, including multiple measures of working memory and perceptual speed. Latent-construct, structural equation modeling was used to examine the relationship of these measures and age to different types of long-term memory tasks. Speed was a key construct for all 3 types of memory tasks, mediating substantial age-related variance; working memory was a fundamental construct for free and cued recall but not spatial memory. The data suggest that both speed and working memory are fundamental to explaining age-related changes in cognitive aging but that the relative contributions of these constructs vary as a function of the type df memory task.
    BibTeX:
    @article{Park1996,
      author = {Park, DC and Smith, AD and Lautenschlager, G and Earles, JL and Frieske, D and Zwahr, M and Gaines, CL},
      title = {Mediators of long-term memory performance across the life span},
      journal = {PSYCHOLOGY AND AGING},
      year = {1996},
      volume = {11},
      number = {4},
      pages = {621-637},
      note = {4th Biannual Cognitive Aging Conference, ATLANTA, GA, APR, 1994}
    }
    
    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}
    }
    
    PARK, S., HOLZMAN, P. & GOLDMANRAKIC, P. SPATIAL WORKING-MEMORY DEFICITS IN THE RELATIVES OF SCHIZOPHRENIC-PATIENTS {1995} ARCHIVES OF GENERAL PSYCHIATRY
    Vol. {52}({10}), pp. {821-828} 
    article  
    Abstract: Background: Studies in nonhuman primates provide evidence that intact spatial working memory depends on the integrity of specific areas in the prefrontal cortex. Patients with schizophrenia have been shown to be impaired on spatial working memory tasks. Relatives of schizophrenic patients show a range of cognitive deficits in the absence of clinical symptoms (eg, thought disorder, eye tracking dysfunctions). We predicted that a significant proportion of relatives of schizophrenic patients would show deficits in working memory as measured by a delayed response task. Methods: In experiment 1, we tested 18 schizophrenic patients, 15 first-degree relatives of schizophrenic patients, and 18 normal control subjects on an oculomotor delayed response task. In experiment 2, we assessed the performance of another group of 12 first-degree relatives of schizophrenic patients and 16 different normal control subjects on a visual-manual delayed response task. Results: Relatives of schizophrenic patients showed significant deficits in working memory on both the oculomotor and visual-manual delayed response tasks. Conclusions: Some relatives of schizophrenic patients are impaired on tasks that tap spatial working memory and that implicate the prefrontal system. The delayed response paradigm may be useful in elucidating the multidimensionality of the schizophrenic phenotype.
    BibTeX:
    @article{PARK1995,
      author = {PARK, S and HOLZMAN, PS and GOLDMANRAKIC, PS},
      title = {SPATIAL WORKING-MEMORY DEFICITS IN THE RELATIVES OF SCHIZOPHRENIC-PATIENTS},
      journal = {ARCHIVES OF GENERAL PSYCHIATRY},
      year = {1995},
      volume = {52},
      number = {10},
      pages = {821-828}
    }
    
    PASCUALLEONE, A., GRAFMAN, J., CLARK, K., STEWART, M., MASSAQUOI, S., LOU, J. & HALLETT, M. PROCEDURAL LEARNING IN PARKINSONS-DISEASE AND CEREBELLAR DEGENERATION {1993} ANNALS OF NEUROLOGY
    Vol. {34}({4}), pp. {594-602} 
    article  
    Abstract: We compared procedural learning, translation of procedural knowledge into declarative knowledge, and use of declarative knowledge in age-matched normal volunteers (n = 30), patients with Parkinson's disease (n = 20), and patients with cerebellar degeneration (n = 15) by using a serial reaction time task. Patients with Parkinson's disease achieved procedural knowledge and used declarative knowledge of the task to improve performance, but they required a larger number of repetitions of the task to translate procedural knowledge into declarative knowledge. Patients with cerebellar degeneration did not show performance improvement due to procedural learning, failed to achieve declarative knowledge, and showed limited use of declarative knowledge of the task to improve their performance. Both basal ganglia and cerebellum are involved in procedural learning, but their roles are different. The normal influence of the basal ganglia on the prefrontal cortex may be required for timely access of information to and from the working memory buffer, while the cerebellum may index and order events in the time domain and be therefore essential for any cognitive functions involving sequences.
    BibTeX:
    @article{PASCUALLEONE1993,
      author = {PASCUALLEONE, A and GRAFMAN, J and CLARK, K and STEWART, M and MASSAQUOI, S and LOU, JS and HALLETT, M},
      title = {PROCEDURAL LEARNING IN PARKINSONS-DISEASE AND CEREBELLAR DEGENERATION},
      journal = {ANNALS OF NEUROLOGY},
      year = {1993},
      volume = {34},
      number = {4},
      pages = {594-602}
    }
    
    PAULESU, E., FRITH, C. & FRACKOWIAK, R. THE NEURAL CORRELATES OF THE VERBAL COMPONENT OF WORKING MEMORY {1993} NATURE
    Vol. {362}({6418}), pp. {342-345} 
    article  
    Abstract: BY repeating words `in our head', verbal material (such as telephone numbers) can be kept in working memory1 almost indefinitely. This `articulatory loop' includes a subvocal rehearsal system2-6 and a phonological store3,6-10. Little is known about neural correlates of this model of verbal short-term memory. We therefore measured regional cerebral blood flow, an index of neuronal activity, in volunteers performing a task engaging both components of the articulatory loop (short-term memory for letters)5-10 and a task which engages only the subvocal rehearsal system (rhyming judgement for letters)4,11. Stimuli were presented visually and the subjects did not speak. We report here that comparisons of distribution of cerebral blood flow in these conditions localized the phonological store to the left supramarginal gyrus whereas the subvocal rehearsal system was associated with Broca's area. This is, to our knowledge, the first demonstration of the normal anatomy of the components of the `articulatory loop'.
    BibTeX:
    @article{PAULESU1993,
      author = {PAULESU, E and FRITH, CD and FRACKOWIAK, RSJ},
      title = {THE NEURAL CORRELATES OF THE VERBAL COMPONENT OF WORKING MEMORY},
      journal = {NATURE},
      year = {1993},
      volume = {362},
      number = {6418},
      pages = {342-345}
    }
    
    Paulesu, E., Frith, U., Snowling, M., Gallagher, A., Morton, J., Frackowiak, R. & Frith, C. Is developmental dyslexia a disconnection syndrome? Evidence from PET scanning {1996} BRAIN
    Vol. {119}({Part 1}), pp. {143-157} 
    article  
    Abstract: A rhyming and a short-term memory task with visually presented letters were used to study brain activity in five compensated adult developmental dyslexics. Their only cognitive difficulty was in phonological processing, manifest in a wide range of tasks including spoonerisms, phonemic fluency and digit naming speed. PET scans showed that for the dyslexics, a subset only of the brain regions normally involved in phonological processing was activated: Broca's area during the rhyming task, temporo-parietal cortex during the short-term memory task. In contrast to normal controls these areas were not activated in concert. Furthermore the left insula was never activated. We propose that the defective phonological system of these dyslexics is due to weak connectivity between anterior and posterior language areas. This could be due to a dysfunctional left insula which may normally act as an anatomical bridge between Broca's area, superior temporal and inferior parietal cortex. The independent activation of the posterior and anterior speech areas in dyslexics supports the notion that representations of unsegmented and segmented phonology are functionally and anatomically separate.
    BibTeX:
    @article{Paulesu1996,
      author = {Paulesu, E and Frith, U and Snowling, M and Gallagher, A and Morton, J and Frackowiak, RSJ and Frith, CD},
      title = {Is developmental dyslexia a disconnection syndrome? Evidence from PET scanning},
      journal = {BRAIN},
      year = {1996},
      volume = {119},
      number = {Part 1},
      pages = {143-157}
    }
    
    Pennington, B. & Ozonoff, S. Executive functions and developmental psychopathology {1996} JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
    Vol. {37}({1}), pp. {51-87} 
    article  
    Abstract: In this paper, we consider the domain of executive functions (EFs) and their possible role in developmental psychopathologies. We first consider general theoretical and measurement issues involved in studying EFs and then review studies of EFs in four developmental psychopathologies: attention deficit hyperactivity disorder (ADHD), conduct disorder (CD), autism, and Tourette syndrome (TS). Our review reveals that EF deficits are consistently found in both ADHD and autism but not in CD (without ADHD) or in TS. Moreover, both the severity and profile of EF deficits appears to differ across ADHD and autism. Molar EF deficits are more severe in the latter than the former. In the few studies of more specific EF tasks, there are impairments in motor inhibition in ADHD but not in autism, whereas there are impairments in verbal working memory in autism but not ADHD. We close with a discussion of implications for future research.
    BibTeX:
    @article{Pennington1996,
      author = {Pennington, BF and Ozonoff, S},
      title = {Executive functions and developmental psychopathology},
      journal = {JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY},
      year = {1996},
      volume = {37},
      number = {1},
      pages = {51-87}
    }
    
    Perlstein, W., Carter, C., Noll, D. & Cohen, J. Relation of prefrontal cortex dysfunction to working memory and symptoms in schizophrenia {2001} AMERICAN JOURNAL OF PSYCHIATRY
    Vol. {158}({7}), pp. {1105-1113} 
    article  
    Abstract: Objective: The dorsolateral prefrontal cortex has been implicated in both working memory and the pathophysiology of schizophrenia. A relationship among dorsolateral prefrontal cortex activity, working memory dysfunction, and symptoms in schizophrenia has not been firmly established, partly because of generalized cognitive impairments in patients and task complexity. Using tasks that parametrically manipulated working memory load, the authors tested three hypotheses: 1) patients with schizophrenia differ in prefrontal activity only when behavioral performance differentiates them from healthy comparison subjects, 2) dorsolateral prefrontal cortex dysfunction is associated with poorer task performance, and 3) dorsolateral prefrontal cortex dysfunction is associated with cognitive disorganization but not negative or positive symptoms. Method: Seventeen conventionally medicated patients with schizophrenia and 16 healthy comparison subjects underwent functional magnetic resonance imaging while performing multiple levels of the ``n-back'' sequential-letter working memory task. Results: Patients with schizophrenia showed a deficit in physiological activation of the right dorsolateral prefrontal cortex (Brodmann's area 46/9) in the context of normal task-dependent activity in other regions, but only under the condition that distinguished them from comparison subjects on task performance. Patients with greater dorsolateral prefrontal cortex dysfunction performed more poorly. Dorsolateral prefrontal cortex dysfunction was selectively associated with disorganization symptoms. Conclusions: These results are consistent with the hypotheses that working memory dysfunction in patients with schizophrenia is caused by a disturbance of the dorsolateral prefrontal cortex and that this disturbance is selectively associated with cognitive disorganization. Further, the pattern of behavioral performance suggests that dorsolateral prefrontal cortex dysfunction does not reflect a deficit in the maintenance of stimulus representations per se but points to deficits in more associative components of working memory.
    BibTeX:
    @article{Perlstein2001,
      author = {Perlstein, WM and Carter, CS and Noll, DC and Cohen, JD},
      title = {Relation of prefrontal cortex dysfunction to working memory and symptoms in schizophrenia},
      journal = {AMERICAN JOURNAL OF PSYCHIATRY},
      year = {2001},
      volume = {158},
      number = {7},
      pages = {1105-1113},
      note = {54th Annual Meeting of the Society-for-Biological-Psychiatry, WASHINGTON, D.C., MAY 13-16, 1999}
    }
    
    Perry, R. & Hodges, J. Attention and executive deficits in Alzheimer's disease - A critical review {1999} BRAIN
    Vol. {122}({Part 3}), pp. {383-404} 
    article  
    Abstract: In this review we summarize the progress that has been made in the research on attentional and executive deficits in Alzheimer's disease. Like memory, attention is now recognized as consisting of subtypes that differ in their function and anatomical basis, We base our review upon a classification of three subtypes of attention: selective, sustained and divided. This model derives from lesion studies, animal electrophysiological recordings and functional imaging. We examine how these subcomponents of attention can be reconciled with neuropsychological models of attentional control, particularly the Supervisory Attentional System and the Central Executive System of Shallice and Baddeley, respectively. We also discuss the relationship of attention to the concept of executive function. Current evidence suggests that after an initial amnesic stage in Alzheimer's disease, attention is the first non-memory domain to be affected, before deficits in language and visuospatial functions. This is consistent with the possibility that difficulties with activities of daily living, which occur in even mildly demented patients, may be related to attentional deficits. It appears that divided attention and aspects of selective attention, such as set-shifting and response selection, are particularly vulnerable while sustained attention is relatively preserved in the early stages. The phenomenon of cognitive slowing in Alzheimer's disease and normal ageing emphasizes the need to discriminate quantitative changes in attention dysfunction from qualitative changes which may be specifically related to the disease process. The neuropathological basis of these attentional deficits remains unsettled, with two competing hypotheses: spread of pathology from the medial temporal to basal forebrain structures versus corticocortical tract disconnection. Finally we discuss the difficulties of comparing evidence across studies and look at the implications for the design of future studies and future directions that may be fruitful in the research on attention in Alzheimer's disease.
    BibTeX:
    @article{Perry1999,
      author = {Perry, RJ and Hodges, JR},
      title = {Attention and executive deficits in Alzheimer's disease - A critical review},
      journal = {BRAIN},
      year = {1999},
      volume = {122},
      number = {Part 3},
      pages = {383-404}
    }
    
    Pesaran, B., Pezaris, J., Sahani, M., Mitra, P. & Andersen, R. Temporal structure in neuronal activity during working memory in macaque parietal cortex {2002} NATURE NEUROSCIENCE
    Vol. {5}({8}), pp. {805-811} 
    article DOI  
    Abstract: Many cortical structures have elevated firing rates during working memory, but it is not known how the activity is maintained. To investigate whether reverberating activity is important, we studied the temporal structure of local field potential (LFP) activity and spiking from area LIP in two awake macaques during a memory-saccade task. Using spectral analysis, we found spatially tuned elevated power in the gamma band (25-90 Hz) in LFP and spiking activity during the memory period. Spiking and LFP activity were also coherent in the gamma band but not at lower frequencies. Finally, we decoded LFP activity on a single-trial basis and found that LFP activity in parietal cortex discriminated between preferred and anti-preferred direction with approximately the same accuracy as the spike rate and predicted the time of a planned movement with better accuracy than the spike rate. This finding could accelerate the development of a cortical neural prosthesis.
    BibTeX:
    @article{Pesaran2002,
      author = {Pesaran, B and Pezaris, JS and Sahani, M and Mitra, PP and Andersen, RA},
      title = {Temporal structure in neuronal activity during working memory in macaque parietal cortex},
      journal = {NATURE NEUROSCIENCE},
      year = {2002},
      volume = {5},
      number = {8},
      pages = {805-811},
      doi = {{10.1038/nn890}}
    }
    
    Peterson, B., Skudlarski, P., Gatenby, J., Zhang, H., Anderson, A. & Gore, J. An fMRI study of Stroop word-color interference: Evidence for cingulate subregions subserving multiple distributed attentional systems {1999} BIOLOGICAL PSYCHIATRY
    Vol. {45}({10}), pp. {1237-1258} 
    article  
    Abstract: Background: The goal of this study was to model the functional connectivity of the neural systems that subserve attention and impulse control. Proper performance of the Stroop Word-Color Interference Task requires both attention and impulse control. Methods: Word-color interference was studied in 34 normal adult subjects using functional magnetic resonance imaging. Results: inter-regional correlation analyses suggested that the anterior cingulate is coupled functionally with multiple regions throughout the cerebrum. A factor analysis of the significant regional activations further emphasized this functional coupling. The cingulate or related mesial frontal cortices loaded on each of the seven factors identified in the factor analysis. Other regions that loaded significantly on on these factors have been described previously as belonging to anatomically connected circuits believed to subserve sensory tuning, receptive language, vigilance, working memory, response selection motor planning, and motor response functions. These seven factors appeared to be oriented topographically within the anterior cingulate, with sensory, working memory, and vigilance functions planning, and motor response positioned progressively more caudally. Conclusions: These findings support a parallel distributed processing model for word-color interference in which portions of the anterior cingulate cortex modify the strengths of multiple neural pathways used to read and name colors. Allocation of attentional resources is thought to modify pathway strengths by reducing cross-talk between information processing modules that subserve the competing demands of reading and color naming. The functional topography of these neural systems observed within the cingulate argues for the presence of multiple attentional subsystems, each contributing to improved task performance. The topography also suggests a role for the cingulate in coordinating and integrating the activity of these multiple attentional subsystems. Biol Psychiatry 1999;45:1237-1258 (C) 1999 Society of Biological Psychiatry.
    BibTeX:
    @article{Peterson1999,
      author = {Peterson, BS and Skudlarski, P and Gatenby, JC and Zhang, HP and Anderson, AW and Gore, JC},
      title = {An fMRI study of Stroop word-color interference: Evidence for cingulate subregions subserving multiple distributed attentional systems},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {1999},
      volume = {45},
      number = {10},
      pages = {1237-1258}
    }
    
    Petrides, M. Lateral prefrontal cortex: architectonic and functional organization {2005} PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
    Vol. {360}({1456}), pp. {781-795} 
    article DOI  
    Abstract: A comparison of the architecture of the human prefrontal cortex with that of the macaque monkey showed a very similar architectonic organization in these two primate species. There is no doubt that the prefrontal cortical areas of the human brain have undergone considerable development, but it is equally clear that the basic architectonic organization is the same in the two species. Thus, a comparative approach to the study of the functional organization of the primate prefrontal cortex is more likely to reveal the essential aspects of the various complex control processes that are the domain of frontal function. The lateral frontal cortex appears to be functionally organized along both a rostral-caudal axis and a dorsal-ventral axis. The most caudal frontal region, the motor region on the precentral gyrus, is involved in fine motor control and direct sensorimotor mappings, whereas the caudal lateral prefrontal region is involved in higher order control processes that regulate the selection among multiple competing responses and stimuli based on conditional operations. Further rostrally, the mid-lateral prefrontal region plays an even more abstract role in cognitive control. The mid-lateral prefrontal region is itself organized along a dorsal-ventral axis of organization, with the mid-dorsolateral prefrontal cortex being involved in the monitoring of information in working memory and the mid-ventrolateral prefrontal region being involved in active judgments on information held in posterior cortical association regions that are necessary for active retrieval and encoding of information.
    BibTeX:
    @article{Petrides2005,
      author = {Petrides, M},
      title = {Lateral prefrontal cortex: architectonic and functional organization},
      journal = {PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES},
      year = {2005},
      volume = {360},
      number = {1456},
      pages = {781-795},
      doi = {{10.1098/rstb.2005.1631}}
    }
    
    Petrides, M. Specialized systems for the processing of mnemonic information within the primate frontal cortex {1996} PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
    Vol. {351}({1346}), pp. {1455-1461} 
    article  
    Abstract: The lateral frontal cortex is involved in various aspects of executive processing within short- and long-term memory. It is argued that the different parts of the lateral frontal cortex make distinct contributions to memory that differ in terms of the level of executive processing that is carried out in interaction with posterior cortical systems. According to this hypothesis, the mid-dorsolateral frontal cortex (areas 46 and 9) is a specialized system for the monitoring and manipulation of information within working memory, whereas the mid-ventrolateral frontal cortex (areas 47/12 and 4-5) is involved in the active retrieval of information from the posterior cortical association areas. Data are presented which support this two-level hypothesis that posits two distinct levels of interaction of the lateral frontal cortex with posterior cortical association areas. Functional activation studies with normal human subjects have demonstrated specific activity within the mid-dorsolateral region of the frontal cortex during the performance of tasks requiring monitoring of self-generated and externally generated sequences of responses. In the monkey, lesions restricted to this region of the frontal cortex yield a severe impairment in performance of the above tasks, this impairment appearing against a background of normal performance on several basic mnemonic tasks. By contrast, a more severe impairment follows damage to the mid-ventrolateral frontal region and functional activation studies have demonstrated specific changes in activity in this region in relation to the active retrieval of information from memory.
    BibTeX:
    @article{Petrides1996,
      author = {Petrides, M},
      title = {Specialized systems for the processing of mnemonic information within the primate frontal cortex},
      journal = {PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES},
      year = {1996},
      volume = {351},
      number = {1346},
      pages = {1455-1461}
    }
    
    PETRIDES, M. IMPAIRMENTS ON NONSPATIAL SELF-ORDERED AND EXTERNALLY ORDERED WORKING-MEMORY TASKS AFTER LESIONS OF THE MID-DORSAL PART OF THE LATERAL FRONTAL-CORTEX IN THE MONKEY {1995} JOURNAL OF NEUROSCIENCE
    Vol. {15}({1, Part 1}), pp. {359-375} 
    article  
    Abstract: Monkeys with lesions of the mid-dorsal part of the lateral frontal cortex, which extends above the sulcus principalis as far as the midline (MDL lesions), were shown to exhibit severe and long-lasting impairments on certain nonspatial working memory tasks: the self-ordered and externally ordered tasks (experiments 1, 2, 3, 5, 6, and 8). These tasks, which were modeled on similar ones previously used with patients, measure the capacity to monitor, within working memory, self-generated choices and the occurrence of externally ordered stimuli. Monkeys with lesions of the adjacent posterior dorsolateral frontal cortex, which surrounds the arcuate sulcus (PA lesions), performed as well as the normal control animals on these tasks. Experiments 4 and 5 showed that the critical variable accounting for the impairment on the self-ordered and externally ordered working memory tasks by monkeys with MDL lesions is the size of the set of stimuli that must be monitored. Furthermore, the MDL lesions did not affect basic recognition memory (experiment 6), or primacy and recency mnemonic effects [i.e,, the capacity to discriminate between the initial (or final) items and other items in a list of stimuli (experiments 4 and 7), or the capacity to select from a set of stimuli on the basis of a learned fixed sequence (experiment 9)]. Thus, lesions of the mid-dorsal part of the lateral frontal cortex give rise to an impairment in working memory that depends on the size of the set of the stimuli that have to be monitored.
    BibTeX:
    @article{PETRIDES1995,
      author = {PETRIDES, M},
      title = {IMPAIRMENTS ON NONSPATIAL SELF-ORDERED AND EXTERNALLY ORDERED WORKING-MEMORY TASKS AFTER LESIONS OF THE MID-DORSAL PART OF THE LATERAL FRONTAL-CORTEX IN THE MONKEY},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1995},
      volume = {15},
      number = {1, Part 1},
      pages = {359-375}
    }
    
    PETRIDES, M., ALIVISATOS, B., EVANS, A. & MEYER, E. DISSOCIATION OF HUMAN MID-DORSOLATERAL FROM POSTERIOR DORSOLATERAL FRONTAL-CORTEX IN MEMORY PROCESSING {1993} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {90}({3}), pp. {873-877} 
    article  
    Abstract: Work with non-human primates had previously demonstrated that the mid-dorsolateral frontal cortex, which comprises cytoarchitectonic areas 46 and 9, plays a critical role in the performance of nonspatial self-ordered working memory tasks, whereas the immediately adjacent posterior dorsolateral frontal cortex (area 8) is critical for the learning and performance of visual conditional associative tasks. The present study used positron emission tomography with magnetic resonance imaging to demonstrate the existence, within the human brain, of these two functionally distinct subdivisions of the lateral frontal cortex. These findings provide direct evidence that, just as in the monkey brain, the human lateral frontal cortex is functionally heterogeneous and that comparable anatomical areas underlie similar functions in the two species.
    BibTeX:
    @article{PETRIDES1993a,
      author = {PETRIDES, M and ALIVISATOS, B and EVANS, AC and MEYER, E},
      title = {DISSOCIATION OF HUMAN MID-DORSOLATERAL FROM POSTERIOR DORSOLATERAL FRONTAL-CORTEX IN MEMORY PROCESSING},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1993},
      volume = {90},
      number = {3},
      pages = {873-877}
    }
    
    PETRIDES, M., ALIVISATOS, B., MEYER, E. & EVANS, A. FUNCTIONAL ACTIVATION OF THE HUMAN FRONTAL-CORTEX DURING THE PERFORMANCE OF VERBAL WORKING MEMORY TASKS {1993} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {90}({3}), pp. {878-882} 
    article  
    Abstract: Regional cerebral blood flow was measured with positron emission tomography during the performance of verbal working memory tasks. The same type of verbal response (i.e., reciting numbers) was required in the control and the two experimental tasks. In the control task, the subjects were required to count aloud. In the two experimental tasks, the subjects were required to maintain within working memory the numbers they generated (self-ordered task) or the numbers generated by the experimenter (externally ordered task). Examination of the difference in activation between these conditions revealed strong bilateral activation within the mid-dorsolateral frontal cortex during both experimental tasks. There was, however, no evidence of additional activation within the mid-dorsolateral frontal cortex when monitoring self-generated responses as compared with the monitoring of externally generated responses. These results provide evidence regarding the role of the mid-dorsolateral frontal cortex in mnemonic processing that are in agreement with recent findings from work with non-human primates.
    BibTeX:
    @article{PETRIDES1993,
      author = {PETRIDES, M and ALIVISATOS, B and MEYER, E and EVANS, AC},
      title = {FUNCTIONAL ACTIVATION OF THE HUMAN FRONTAL-CORTEX DURING THE PERFORMANCE OF VERBAL WORKING MEMORY TASKS},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1993},
      volume = {90},
      number = {3},
      pages = {878-882}
    }
    
    Petrides, M. & Pandya, D. Comparative cytoarchitectonic analysis of the human and the macaque ventrolateral prefrontal cortex and corticocortical connection patterns in the monkey {2002} EUROPEAN JOURNAL OF NEUROSCIENCE
    Vol. {16}({2}), pp. {291-310} 
    article DOI  
    Abstract: A comparison of the cytoarchitecture of the human and the macaque monkey ventrolateral prefrontal cortex demonstrated a region in the monkey that exhibits the architectonic characteristic of area 45 in the human brain. This region occupies the dorsal part of the ventrolateral prefrontal convexity just below area 9/46v. Rostroventral to area 45 in the human brain lies a large cortical region labelled as area 47 by Brodmann. The ventrolateral component of this region extending as far as the lateral orbital sulcus has architectonic characteristics similar to those of the ventrolateral prefrontal region labelled by Walker as area 12 in the macaque monkey. We designated this region in both the human and the monkey ventrolateral prefrontal cortex as area 47/12. Thus, area 47/12 designates the specific part of the zone previously labelled as area 47 in the human brain that has the same overall architectonic pattern as that of Walker's area 12 in the macaque monkey brain. The cortical connections of these two areas were examined in the monkey by injecting fluorescent retrograde tracers. Although both area 45 and area 47/12 as defined here had complex multimodal input, they could be differentiated in terms of some of their inputs. Retrograde tracers restricted to area 47/12 resulted in heavy labelling of neurons in the rostral inferotemporal visual association cortex and in temporal limbic areas (i.e. perirhinal and parahippocampal cortex). In contrast, injections of tracers into dorsally adjacent area 45 demonstrated strong labelling in the superior temporal gyrus (i.e. the auditory association cortex) and the multimodal cortex in the upper bank of the superior temporal sulcus.
    BibTeX:
    @article{Petrides2002,
      author = {Petrides, M and Pandya, DN},
      title = {Comparative cytoarchitectonic analysis of the human and the macaque ventrolateral prefrontal cortex and corticocortical connection patterns in the monkey},
      journal = {EUROPEAN JOURNAL OF NEUROSCIENCE},
      year = {2002},
      volume = {16},
      number = {2},
      pages = {291-310},
      doi = {{10.1046/j.1460-9568.2001.02090.x}}
    }
    
    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}
    }
    
    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{Phillips2003,
      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}}
    }
    
    PIERROTDESEILLIGNY, C., RIVAUD, S., GAYMARD, B., MURI, R. & VERMERSCH, A. CORTICAL CONTROL OF SACCADES {1995} ANNALS OF NEUROLOGY
    Vol. {37}({5}), pp. {557-567} 
    article  
    Abstract: A scheme for the cortical control of saccadic eye movements is proposed based partly on defects revealed by specific test paradigms in humans with discrete lesions. Three different cortical areas are capable of triggering saccades. The frontal eye field disengages fixation, and triggers intentional saccades to visible targets, to remembered target locations, or to the location where it is predicted that the target will reappear (i.e., saccades concerned with intentional exploration of the visual environment). The parietal eye field triggers saccades made reflexively on the sudden appearance of visual targets (i.e., saccades concerned with reflexive exploration of the visual environment). The supplementary eye field is important for triggering sequences of saccades and in controlling saccades made during head or body movement (i.e., saccades concerned with complex motor programming). Three other areas contribute to the preparation of certain types of saccades. The prefrontal cortex (area 46 of Brodmann) plays a crucial role for planning saccades to remembered target locations. The inferior parietal lobule is involved in the visuospatial integration used for calculating saccade amplitude. The hippocampus appears to control the temporal working memory required for memorization of the chronological order of sequences of saccades.
    BibTeX:
    @article{PIERROTDESEILLIGNY1995,
      author = {PIERROTDESEILLIGNY, C and RIVAUD, S and GAYMARD, B and MURI, R and VERMERSCH, AI},
      title = {CORTICAL CONTROL OF SACCADES},
      journal = {ANNALS OF NEUROLOGY},
      year = {1995},
      volume = {37},
      number = {5},
      pages = {557-567}
    }
    
    Pinel, P., Dehaene, S., Riviere, D. & LeBihan, D. Modulation of parietal activation by semantic distance in a number comparison task {2001} NEUROIMAGE
    Vol. {14}({5}), pp. {1013-1026} 
    article  
    Abstract: The time to compare two numbers shows additive effects of number notation and. of semantic distance, suggesting that the comparison task can be decomposed into distinct stages of identification and semantic processing. Using event-related fMRI and high-density ERPs, we isolated cerebral areas where activation was influenced by input notation (verbal or Arabic notation). The bilateral extrastriate cortices and a left precentral. region were more activated during verbal than during Arabic stimulation, while the right fusiform gyrus and a set of bilateral inferoparietal and frontal regions were more activated during Arabic than during verbal stimulation. We also identified areas that were influenced solely by the semantic content of the stimuli (numerical distance between numbers to be compared) independent of the input notation. Activation tightly con-elated with numerical distance was observed mainly in a group of parietal areas distributed bilaterally along the intraparietal sulci and in the precuneus, as well as in the left middle temporal gyrus and posterior cingulate. Our results! support the assumption of a central semantic representation of numerical quantity that relies on a common parietal network shared among notations, (C) 2001 Academic Press.
    BibTeX:
    @article{Pinel2001,
      author = {Pinel, P and Dehaene, S and Riviere, D and LeBihan, D},
      title = {Modulation of parietal activation by semantic distance in a number comparison task},
      journal = {NEUROIMAGE},
      year = {2001},
      volume = {14},
      number = {5},
      pages = {1013-1026}
    }
    
    Platel, H., Price, C., Baron, J., Wise, R., Lambert, J., Frackowiak, R., Lechevalier, B. & Eustache, F. The structural components of music perception - A functional anatomical study {1997} BRAIN
    Vol. {120}({Part 2}), pp. {229-243} 
    article  
    Abstract: This work explores the cerebral structures involved in the appreciation of music. We studied six young healthy subjects (right handed, French, without musical talent), using a high resolution PET device (CTI 953B) and O-15-labelled water In three tasks, we studied the effects of selective attention to pitch, timbre and rhythm; a final task studied semantic familiarity with tunes (considered as divided attention for pitch and rhythm). These four tasks were performed on the same material (a tape consisting of 30 randomly arranged sequences of notes). We selected a paradigm, without a reference task to compare the activations produced by attention to different parameters of the same stimulus. We expected that the activations recorded during each task would differ according to the differences in cognitive operations. We found activations preferentially in the left hemisphere for familiarity, pitch tasks and rhythm, and in the right hemisphere for the timbre task. The familiarity task activated the left inferior frontal gyrus, Brodmann area (BA) 47, and superior temporal gyrus (in its anterior part BA 22). These activations presumably represent lexico-semantic access to melodic representations. in the pitch task, activations were observed in the left cuneus/precuneus (BA 18/19). These results were unexpected and we interpret them as reflecting a visual mental imagery strategy employed to carry out this task. The rhythm task activated left inferior Broca's area (BA 44/6), with extention into the neighbouring insula, suggesting a role for this cerebral region in the processing of sequential sounds.
    BibTeX:
    @article{Platel1997,
      author = {Platel, H and Price, C and Baron, JC and Wise, R and Lambert, J and Frackowiak, RSJ and Lechevalier, B and Eustache, F},
      title = {The structural components of music perception - A functional anatomical study},
      journal = {BRAIN},
      year = {1997},
      volume = {120},
      number = {Part 2},
      pages = {229-243}
    }
    
    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}
    }
    
    Postle, B., Berger, J. & D'Esposito, M. Functional neuroanatomical double dissociation of mnemonic and executive control processes contributing to working memory performance {1999} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {96}({22}), pp. {12959-12964} 
    article  
    Abstract: We used event-related functional MRI to investigate the neural bases of two categories of mental processes believed to contribute to performance of an alphabetization working memory task: memory storage and memory manipulation. Our delayed-response tasks required memory for the identity and position-in-the-display of items in two- or five-letter memory sets (to identify load-sensitive regions) or memory for the identity and relative position-in-the-alphabet of items in five-letter memory sets (to identify manipulation-sensitive regions). Results revealed voxels in the left perisylvian cortex of five of five subjects showing load sensitivity (as contrasted with alphabetization-sensitive voxels in this region in only one subject) and voxels of dorsolateral prefrontal cortex in all subjects showing alphabetization sensitivity (as contrasted with load-sensitive voxels in this region in two subjects). This double dissociation was reliable at the group level. These data are consistent with the hypothesis that the nonmnemonic executive control processes that can contribute to working memory function are primarily prefrontal cortex-mediated whereas mnemonic processes necessary for working memory storage are primarily posteriorly mediated. More broadly, they support the view that working memory is a faculty that arises from the coordinated interaction of computationally and neuroanatomically dissociable processes.
    BibTeX:
    @article{Postle1999,
      author = {Postle, BR and Berger, JS and D'Esposito, M},
      title = {Functional neuroanatomical double dissociation of mnemonic and executive control processes contributing to working memory performance},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1999},
      volume = {96},
      number = {22},
      pages = {12959-12964}
    }
    
    POUCET, B. SPATIAL COGNITIVE MAPS IN ANIMALS - NEW HYPOTHESES ON THEIR STRUCTURE AND NEURAL MECHANISMS {1993} PSYCHOLOGICAL REVIEW
    Vol. {100}({2}), pp. {163-182} 
    article  
    Abstract: This article provides a hierarchical model of animal spatial cognitive maps. Such maps include both topological information, which affords loose, yet operational, representations of the connectivity of space and its overall arrangement, and metric information, which provides information about angles and distances. The model holds that maps can be initially described as a set of location-dependent reference frameworks providing directional information about other locations. The addition of an overall directional reference allows for the buildup of more complete (allocentric) representations. A survey of recent neurobiological data provides some hints about the brain structures involved in these processes and suggests that the hippocampal formation and the posterior parietal cortex would act differently by handling topological and metric information, respectively.
    BibTeX:
    @article{POUCET1993,
      author = {POUCET, B},
      title = {SPATIAL COGNITIVE MAPS IN ANIMALS - NEW HYPOTHESES ON THEIR STRUCTURE AND NEURAL MECHANISMS},
      journal = {PSYCHOLOGICAL REVIEW},
      year = {1993},
      volume = {100},
      number = {2},
      pages = {163-182}
    }
    
    Prabhakaran, V., Narayanan, K., Zhao, Z. & Gabrieli, J. Integration of diverse information in working memory within the frontal lobe {2000} NATURE NEUROSCIENCE
    Vol. {3}({1}), pp. {85-90} 
    article  
    Abstract: Ability to integrate diverse forms of information in current thought, or working memory, is essential for human reasoning and problem solving. We used functional imaging to identify brain regions preferentially involved in maintaining integrated versus unintegrated information in working memory. For equal amounts of verbal and spatial information, activation of prefrontal cortex was greater for maintaining integrated rather than unintegrated representations. Posterior brain regions showed the opposite pattern. These results demonstrate frontal-lobe specialization in maintaining working-memory representations that integrate verbal and spatial information. The role of prefrontal cortex in integrating multiple forms of information in working memory may underlie its unique contribution to high-level cognition that demands flexible mental representations.
    BibTeX:
    @article{Prabhakaran2000,
      author = {Prabhakaran, V and Narayanan, K and Zhao, Z and Gabrieli, JDE},
      title = {Integration of diverse information in working memory within the frontal lobe},
      journal = {NATURE NEUROSCIENCE},
      year = {2000},
      volume = {3},
      number = {1},
      pages = {85-90}
    }
    
    Ragozzino, M., Detrick, S. & Kesner, R. Involvement of the prelimbic-infralimbic areas of the rodent prefrontal cortex in behavioral flexibility for place and response learning {1999} JOURNAL OF NEUROSCIENCE
    Vol. {19}({11}), pp. {4585-4594} 
    article  
    Abstract: The present experiments investigated the role of the prelimbic-infralimbic areas in behavioral flexibility using a place-response learning paradigm. All rats received a bilateral cannula implant aimed at the prelimbic-infralimbic areas. To examine the role of the prelimbic-infralimbic areas in shifting strategies, rats were tested on a place and a response discrimination in a cross-maze. Some rats were tested on the place version first followed by the response version. The procedure for the other rats was reversed. Infusions of 2% tetracaine into the prelimbic-infralimbic areas did not impair acquisition of the place or response discriminations. Prelimbic-infralimbic inactivation did impair learning when rats were switched from one discrimination to the other (cross-modal shift). To investigate the role of the prelimbic-infralimbic areas in intramodal shifts (reversal learning), one group of rats was tested on a place reversal and another group tested on a response reversal. Prelimbic-infralimbic inactivation did not impair place or response intramodal shifts. Some rats that completed testing on a particular version in the cross-modal and intramodal experiments were tested on the same version in a new room for 3 d. The transfer tests revealed that rats use a spatial strategy on the place version and an egocentric response strategy on the response version. Overall, these results suggest that the prelimbic-infralimbic areas are important for behavioral flexibility involving crossmodal but not intramodal shifts.
    BibTeX:
    @article{Ragozzino1999,
      author = {Ragozzino, ME and Detrick, S and Kesner, RP},
      title = {Involvement of the prelimbic-infralimbic areas of the rodent prefrontal cortex in behavioral flexibility for place and response learning},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1999},
      volume = {19},
      number = {11},
      pages = {4585-4594}
    }
    
    Rainer, G., Asaad, W. & Miller, E. Selective representation of relevant information by neurons in the primate prefrontal cortex {1998} NATURE
    Vol. {393}({6685}), pp. {577-579} 
    article  
    Abstract: The severe limitation of the capacity of working memory, the ability to store temporarily and manipulate information(1), necessitates mechanisms that restrict access to it. Here we report tests to discover whether the activity of neurons in the prefrontal (PF) cortex, the putative neural correlate of working memory(2-8), might reflect these mechanisms and preferentially represent behaviourally relevant information. Monkeys performed a `delayed-matching-to-sample' task with an array of three objects. Only one of the objects in the array was relevant for task performance and the monkeys needed to find that object (the target) and remember its location. For many PF neurons, activity to physically identical arrays varied with the target location; the location of the non-target objects had little or no influence on activity. Information about the target location was present in activity as early as 140 ms after array onset. Also, information about which object was the target was reflected in the sustained activity of many PF neurons. These results suggest that the prefrontal cortex is involved in selecting and maintaining behaviourally relevant information.
    BibTeX:
    @article{Rainer1998,
      author = {Rainer, G and Asaad, WF and Miller, EK},
      title = {Selective representation of relevant information by neurons in the primate prefrontal cortex},
      journal = {NATURE},
      year = {1998},
      volume = {393},
      number = {6685},
      pages = {577-579}
    }
    
    Ramnani, N. & Owen, A. Anterior prefrontal cortex: Insights into function from anatomy and neuroimaging {2004} NATURE REVIEWS NEUROSCIENCE
    Vol. {5}({3}), pp. {184-194} 
    article DOI  
    Abstract: The anterior prefrontal cortex (aPFC), or Brodmann area 10, is one of the least well understood regions of the human brain. Work with non-human primates has provided almost no indications as to the function of this area. In recent years, investigators have attempted to integrate findings from functional neuroimaging studies in humans to generate models that might describe the contribution that this area makes to cognition. In all cases, however, such explanations are either too tied to a given task to be plausible or too general to be theoretically useful. Here, we use an account that is consistent with the connectional and cellular anatomy of the aPFC to explain the key features of existing models within a common theoretical framework. The results indicate a specific role for this region in integrating the outcomes of two or more separate cognitive operations in the pursuit of a higher behavioural goal.
    BibTeX:
    @article{Ramnani2004,
      author = {Ramnani, N and Owen, AM},
      title = {Anterior prefrontal cortex: Insights into function from anatomy and neuroimaging},
      journal = {NATURE REVIEWS NEUROSCIENCE},
      year = {2004},
      volume = {5},
      number = {3},
      pages = {184-194},
      doi = {{10.1038/nrn1343}}
    }
    
    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}
    }
    
    Raz, N., Gunning-Dixon, F., Head, D., Dupuis, J. & Acker, J. Neuroanatomical correlates of cognitive aging: Evidence from structural magnetic resonance imaging {1998} NEUROPSYCHOLOGY
    Vol. {12}({1}), pp. {95-114} 
    article  
    Abstract: To examine putative brain substrates of cognitive functions differentially affected by age the authors measured the volume of cortical regions and performance on tests of executive functions, working memory, explicit memory, and priming in healthy adults (18-77 years old). The results indicate that shrinkage of the prefrontal cortex mediates age-related increases in perseveration. The volume of visual processing areas predicted performance on nonverbal working memory tasks. Contrary to the hypotheses, in the examined age range, the volume of limbic structures was unrelated to any of the cognitive functions; verbal working memory, verbal explicit memory, and verbal priming were independent of cortical volumes. Nevertheless, among the participants aged above 60,reduction in the volume of limbic structures predicted declines in explicit memory. Chronological age adversely influenced all cognitive indices, although its effects on priming were only indirect, mediated by declines in verbal working memory.
    BibTeX:
    @article{Raz1998,
      author = {Raz, N and Gunning-Dixon, FM and Head, D and Dupuis, JH and Acker, JD},
      title = {Neuroanatomical correlates of cognitive aging: Evidence from structural magnetic resonance imaging},
      journal = {NEUROPSYCHOLOGY},
      year = {1998},
      volume = {12},
      number = {1},
      pages = {95-114},
      note = {6th Annual Meeting of the Cognitive Aging, ATLANTA, GEORGIA, NOV, 1996}
    }
    
    Rensink, R. Change detection {2002} ANNUAL REVIEW OF PSYCHOLOGY
    Vol. {53}, pp. {245-277} 
    article  
    Abstract: Five aspects of visual change detection are reviewed. The first concerns the concept of change itself, in particular the ways it differs from the related notions of motion and difference. The second involves the various methodological approaches that have been developed to study change detection; it is shown that under a variety of conditions observers are often unable to see large changes directly in their field of view. Next, it is argued that this ``change blindness'' indicates that focused attention is needed to detect change, and that this can help map out the nature of visual attention. The fourth aspect concerns how these results affect our understanding of visual perception-for example, the implication that a sparse, dynamic representation underlies much of our visual experience. Finally, a brief discussion is presented concerning the limits to our current understanding of change detection.
    BibTeX:
    @article{Rensink2002,
      author = {Rensink, RA},
      title = {Change detection},
      journal = {ANNUAL REVIEW OF PSYCHOLOGY},
      year = {2002},
      volume = {53},
      pages = {245-277}
    }
    
    Reuter-Lorenz, P., Jonides, J., Smith, E., Hartley, A., Miller, A., Marshuetz, C. & Koeppe, R. Age differences in the frontal lateralization of verbal and spatial working memory revealed by PET {2000} JOURNAL OF COGNITIVE NEUROSCIENCE
    Vol. {12}({1}), pp. {174-187} 
    article  
    Abstract: Age-related decline in working memory figures prominently in theories of cognitive aging. However, the effects of aging on the neural substrate of working memory are largely unknown. Positron emission tomography (PET) was used to investigate verbal and spatial short-term storage (3 sec) in older and younger adults. Previous investigations with younger subjects performing these same tasks have revealed asymmetries in the lateral organization of verbal and spatial working memory. Using volume of interest (VOI) analyses that specifically compared activation at sites identified with working memory to their homologous twin in the opposite hemisphere, we show pronounced age differences in this organization, particularly in the frontal lobes: In younger adults, activation is predominantly left lateralized for verbal working memory, and right lateralized for spatial working memory, whereas older adults show a global pattern of anterior bilateral activation for both types of memory. Analyses of frontal subregions indicate that several underlying patterns contribute to global bilaterality in older adults; most notably, bilateral activation in areas associated with rehearsal, and paradoxical laterality in dorsolateral prefrontal sites (DLPFC; greater left activation for spatial and greater right activation for verbal). We consider several mechanisms that could account for these age differences including the possibility that bilateral activation reflects recruitment to compensate for neural decline.
    BibTeX:
    @article{Reuter-Lorenz2000,
      author = {Reuter-Lorenz, PA and Jonides, J and Smith, EE and Hartley, A and Miller, A and Marshuetz, C and Koeppe, RA},
      title = {Age differences in the frontal lateralization of verbal and spatial working memory revealed by PET},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {2000},
      volume = {12},
      number = {1},
      pages = {174-187}
    }
    
    REYNA, V. & BRAINERD, C. FUZZY-TRACE THEORY - AN INTERIM SYNTHESIS {1995} LEARNING AND INDIVIDUAL DIFFERENCES
    Vol. {7}({1}), pp. {1-75} 
    article  
    Abstract: We review the current status of fuzzy-trace theory. The presentation is organized around five topics. First, theoretical ideas that immediately preceded the development of fuzzy-trace theory are sketched. Second, experimental findings that challenged those ideas (e.g., memory-reasoning independence, the intuitive nature of mature reasoning) are summarized. Third, the core assumptions that comprised the initial version of fuzzy-trace theory are described. Fourth, some modifications to those assumptions are explored that were necessitated by subsequent experimental findings. Fifth, four areas of experimentation are considered in which research under the aegis of fuzzy-trace theory is in progress: (a) suggestibility and false memories; (b) judgment and decision making; (c) the development of forgetting; and (d) the development of retrieval.
    BibTeX:
    @article{REYNA1995,
      author = {REYNA, VF and BRAINERD, CJ},
      title = {FUZZY-TRACE THEORY - AN INTERIM SYNTHESIS},
      journal = {LEARNING AND INDIVIDUAL DIFFERENCES},
      year = {1995},
      volume = {7},
      number = {1},
      pages = {1-75}
    }
    
    Rezvani, A. & Levin, E. Cognitive effects of nicotine {2001} BIOLOGICAL PSYCHIATRY
    Vol. {49}({3}), pp. {258-267} 
    article  
    Abstract: Nicotine and other nicotinic agonists have been found to improve performance on attention and memory tasks. Clinical studies using nicotine skin patches have demonstrated the efficacy of nicotine in treating cognitive impairments associated with Alzheimer's disease, schizophrenia, and attention-deficit/hyperactivity disorder. Experimental animal studies have demonstrated the persistence of nicotine-induced working memory improvement with chronic exposure, in addition to the efficacy of a variety of nicotinic agonists. Mechanistic studies have found that alpha7 and alpha4 beta2 nicotinic receptors in the hippocampus are critical for nicotinic involvement in cognitive function. Clinical and experimental animal studies provide mutually supporting information for the development of novel nicotinic therapies for cognitive dysfunction. (C) 2001 Society of Biological Psychiatry.
    BibTeX:
    @article{Rezvani2001,
      author = {Rezvani, AH and Levin, ED},
      title = {Cognitive effects of nicotine},
      journal = {BIOLOGICAL PSYCHIATRY},
      year = {2001},
      volume = {49},
      number = {3},
      pages = {258-267},
      note = {Symposium on Nicotine Mechanisms in Alzheimers Disease, FAJARKO, PR, MAR 16-18, 2000}
    }
    
    Ridderinkhof, K., van den Wildenberg, W., Segalowitz, S. & Carter, C. Neurocognitive mechanisms of cognitive control: The role of prefrontal cortex in action selection, response inhibition, performance monitoring, and reward-based learning {2004} BRAIN AND COGNITION
    Vol. {56}({2}), pp. {129-140} 
    article DOI  
    Abstract: Convergent evidence highlights the differential contributions of various regions of the prefrontal cortex in the service of cognitive control, but little is understood about how the brain determines and communicates the need to recruit cognitive control, and how such signals instigate the implementation of appropriate performance adjustments. Here we review recent progress from cognitive neuroscience in examining some of the main constituent processes of cognitive control as involved in dynamic decision making: goal-directed action selection, response activation and inhibition, performance monitoring, and reward-based learning. Medial frontal cortex is found to be involved in performance monitoring: evaluating outcome vis-A-vis expectancy, and detecting performance errors or conflicting response tendencies. Lateral and orbitofrontal divisions of prefrontal cortex are involved in subsequently implementing appropriate adjustments. (C) 2004 Elsevier Inc. All rights reserved.
    BibTeX:
    @article{Ridderinkhof2004,
      author = {Ridderinkhof, KR and van den Wildenberg, WPM and Segalowitz, SJ and Carter, CS},
      title = {Neurocognitive mechanisms of cognitive control: The role of prefrontal cortex in action selection, response inhibition, performance monitoring, and reward-based learning},
      journal = {BRAIN AND COGNITION},
      year = {2004},
      volume = {56},
      number = {2},
      pages = {129-140},
      doi = {{10.1016/j.bandc.2004.09.016}}
    }
    
    Riedel, G., Platt, B. & Micheau, J. Glutamate receptor function in learning and memory {2003} BEHAVIOURAL BRAIN RESEARCH
    Vol. {140}({1-2}), pp. {1-47} 
    article  
    Abstract: The contribution of glutamate to synaptic transmission, plasticity and development is well established; current evidence is based on diverse approaches to decipher function and malfunction of this principal transmitter. With respect to learning and memory, we are now able to identify more specifically the role played by the three main glutamate receptor classes in learning and memory: centre stage is clearly the NMDA receptor, with overwhelming evidence proving its involvement in the actual learning process (encoding), throughout the animal kingdom. This is discussed with respect to many different types of learning. Evidence for the contribution of the AMPA receptors (AMPARs) is less clear-cut due to the general problem of specificity: block of AMPARs will shutdown neuronal communication, and this will affect various components essential for learning. Therefore, the role of AMPARs cannot be established in isolation. Problems of interpretation are outlined and a specific involvement of AMPARs in the regulation of neuronal excitation related to learning is proposed. Metabotropic glutamate receptors (mGluRs) may contribute very little to the actual acquisition of new information. However, memory formation appears to require mGluRs, through the modulation of consolidation and/or recall. Overall, mGluR functions seem variable and dependent on brain structure and learning task. (C) 2002 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{Riedel2003,
      author = {Riedel, G and Platt, B and Micheau, J},
      title = {Glutamate receptor function in learning and memory},
      journal = {BEHAVIOURAL BRAIN RESEARCH},
      year = {2003},
      volume = {140},
      number = {1-2},
      pages = {1-47}
    }
    
    Robbins, T. Chemical neuromodulation of frontal-executive functions in humans and other animals {2000} EXPERIMENTAL BRAIN RESEARCH
    Vol. {133}({1}), pp. {130-138} 
    article  
    Abstract: Neuromodulation of frontal-executive function is reviewed in the context of experiments on rats, monkeys and human subjects. The different functions of the chemically identified systems of the reticular core are analysed from the perspective of their possible different interactions with the prefrontal cortex. The role of dopamine in spatial working memory is reviewed, taking account of its deleterious as well as facilitatory effects. Baseline-dependent effects of dopaminergic manipulation are described in rats on an attentional task, including evidence of enhanced function following infusions of D1 receptor agonists into the prefrontal cortex. The precise nature of the cognitive task under study is shown to be a powerful determinant of the effects of mesofrontal dopamine depletion in monkeys. Parallels are identified in human subjects receiving drugs such as the indirect catecholamine agonists L-dopa, methylphenidate and the dopamine D2 receptor blocker sulpiride. The effects of these drugs on different types of cognitive function sensitive to frontal lobe dysfunction are contrasted with those of a manipulation of 5-HT function, dietary tryptophan depletion. Hypotheses are advanced that accord the ascending systems a greater deal of specificity in modulating prefrontal cortical function than has hitherto been entertained, and clinical and theoretical implications of this hypothesis are discussed.
    BibTeX:
    @article{Robbins2000,
      author = {Robbins, TW},
      title = {Chemical neuromodulation of frontal-executive functions in humans and other animals},
      journal = {EXPERIMENTAL BRAIN RESEARCH},
      year = {2000},
      volume = {133},
      number = {1},
      pages = {130-138},
      note = {Workshop on Executive Control and the Frontal Lobe, DELMENHORST, GERMANY, DEC 01-03, 1998}
    }
    
    Robbins, T. Dissociating executive functions of the prefrontal cortex {1996} PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
    Vol. {351}({1346}), pp. {1463-1470} 
    article  
    Abstract: An analysis is provided of three distinct paradigms that have been used to study executive functions of the prefrontal cortex involving planning, self-ordered memory or attentional set-shifting. Psychological and anatomical dissociations are sought from the perspective of studies of patients with frontal lobe lesions, functional neuroimaging, psychometric studies in normal volunteers and experimental studies in non-human primates. Particular attention is paid to attempts to dissociate mnemonic from other executive capacities. Thus, patients with frontal damage are shown to have deficits in their (1) use of strategies to improve performance in a spatial working memory task and (2) capacity to make an extra-dimensional shift due to a high-order failure of inhibition in an attentional set-shifting paradigm. These results are discussed in terms of anatomical and neuropharmacological dissociations of different aspects of executive function within the prefrontal cortex shown in monkeys.
    BibTeX:
    @article{Robbins1996,
      author = {Robbins, TW},
      title = {Dissociating executive functions of the prefrontal cortex},
      journal = {PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES},
      year = {1996},
      volume = {351},
      number = {1346},
      pages = {1463-1470}
    }
    
    ROBBINS, T., JAMES, M., OWEN, A., SAHAKIAN, B., MCINNES, L. & RABBITT, P. CAMBRIDGE NEUROPSYCHOLOGICAL TEST AUTOMATED BATTERY (CANTAB) - A FACTOR-ANALYTIC STUDY OF A LARGE-SAMPLE OF NORMAL ELDERLY VOLUNTEERS {1994} DEMENTIA
    Vol. {5}({5}), pp. {266-281} 
    article  
    Abstract: The CANTAB battery was administered to a large group (n = 787) of elderly volunteers in the age range from 55 to 80 years. This battery, which is based on tests used to identify the neural substrates of learning and memory in nonhuman primates, has now been extensively used in the assessment of various forms of dementia and also validated on patients with neurosurgical lesions of the frontal and temporal lobes. The tests employed were pattern and spatial recognition, simultaneous and delayed matching to sample, learning of visuospatial paired associates, a matching to sample, reaction time task and a test of spatial working memory. The sample was banded into different IQ bands based on performance on 5 standard tests of intelligence. The MMSE was also administered to exclude cases of possible dementia (n = 16) in the normal sample. In general, performance declined with age and IQ, but these factors did not interact. A factor analysis (with varimax rotation) identified 4 factors with eigenvalues greater than 1, which accounted for over 60% ofthe variance. Factor 1 was equated with general learning and memory ability and loaded significantly with the Intelligence scores; factor 2 was related to speed of responding and loaded most heavily with Age, Comparisons were also made of performance on CANTAB of those subjects with dementing scores on the MMSE and the lowest 5th percentile of the population sample. The results are discussed in terms of the utility of the CANTAB battery for the assessment of dementia and of the implications for theories of changes in cognitive function during normal aging.
    BibTeX:
    @article{ROBBINS1994,
      author = {ROBBINS, TW and JAMES, M and OWEN, AM and SAHAKIAN, BJ and MCINNES, L and RABBITT, P},
      title = {CAMBRIDGE NEUROPSYCHOLOGICAL TEST AUTOMATED BATTERY (CANTAB) - A FACTOR-ANALYTIC STUDY OF A LARGE-SAMPLE OF NORMAL ELDERLY VOLUNTEERS},
      journal = {DEMENTIA},
      year = {1994},
      volume = {5},
      number = {5},
      pages = {266-281}
    }
    
    ROBERTS, R., HAGER, L. & HERON, C. PREFRONTAL COGNITIVE-PROCESSES - WORKING-MEMORY AND INHIBITION IN THE ANTISACCADE TASK {1994} JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL
    Vol. {123}({4}), pp. {374-393} 
    article  
    Abstract: Recent research suggests 2 principal processes are assessed in many neuropsychological tests of prefrontal functioning: the ability to keep transient information on-line (working memory) and the ability to inhibit prepotent, but incorrect, responses. The current studies examined the hypothesis that taxing working memory beyond some threshold can result in decreased inhibition, resembling the errors committed by patients with prefrontal dysfunctions. Across 3 studies, 70 nonpatient subjects were tested on the antisaccade (AS) task (D. Guitton, H. A. Buchtel, & R. M. Douglas, 1985)-a task sensitive to inhibitory deficits. Subjects were required to look in the opposite direction of a flashed cue, inhibiting the reflexive tendency to saccade to the cue. Subjects performed concurrent tasks that varied working-memory load. The results indicated that conditions with the highest working-memory load produced inhibitory errors comparable to patients with prefrontal dysfunctions. The findings are discussed in terms of the interaction between working memory and the inhibition of prepotent responses.
    BibTeX:
    @article{ROBERTS1994,
      author = {ROBERTS, RJ and HAGER, LD and HERON, C},
      title = {PREFRONTAL COGNITIVE-PROCESSES - WORKING-MEMORY AND INHIBITION IN THE ANTISACCADE TASK},
      journal = {JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL},
      year = {1994},
      volume = {123},
      number = {4},
      pages = {374-393}
    }
    
    Rogers, R., Owen, A., Middleton, H., Williams, E., Pickard, J., Sahakian, B. & Robbins, T. Choosing between small, likely rewards and large, unlikely rewards activates inferior and orbital prefrontal cortex {1999} JOURNAL OF NEUROSCIENCE
    Vol. {19}({20}), pp. {9029-9038} 
    article  
    Abstract: Patients sustaining lesions of the orbital prefrontal cortex (PFC) exhibit marked impairments in the performance of laboratory-based gambling, or risk-taking, tasks, suggesting that this part of the human PFC contributes to decision-making cognition. However, to date, little is known about the particular regions of the orbital cortex that participate in this function. In the present study, eight healthy volunteers were scanned, using H-2 O-15 PET technology, while performing a novel computerized risk-taking task. The task involved predicting which of two mutually exclusive outcomes would occur, but critically, the larger reward (and penalty) was associated with choice of the least likely outcome, whereas the smallest reward (and penalty) was associated with choice of the most likely outcome. Resolving these ``conflicting'' decisions was associated with three distinct foci of regional cerebral blood flow increase within the right inferior and orbital PFC: laterally, in the anterior part of the middle frontal gyrus [Brodmann area 10 (BA 10)], medially, in the orbital gyrus (BA 11), and posteriorly, in the anterior portion of the inferior frontal gyrus (BA 47). By contrast, increases in the degree of conflict inherent in these decisions was associated with only limited changes in activity within orbital PFC and the anterior cingulate cortex. These results suggest that decision making recruits neural activity from multiple regions of the inferior PFC that receive information from a diverse set of cortical and limbic inputs, and that the contribution of the orbitofrontal regions may involve processing changes in reward-related information.
    BibTeX:
    @article{Rogers1999,
      author = {Rogers, RD and Owen, AM and Middleton, HC and Williams, EJ and Pickard, JD and Sahakian, BJ and Robbins, TW},
      title = {Choosing between small, likely rewards and large, unlikely rewards activates inferior and orbital prefrontal cortex},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1999},
      volume = {19},
      number = {20},
      pages = {9029-9038}
    }
    
    Romo, R., Brody, C., Hernandez, A. & Lemus, L. Neuronal correlates of parametric working memory in the prefrontal cortex {1999} NATURE
    Vol. {399}({6735}), pp. {470-473} 
    article  
    Abstract: Humans and monkeys have similar abilities to discriminate the difference in frequency between two mechanical vibrations applied sequentially to the fingertips(1-3). A key component of this sensory task is that the second stimulus is compared with the trace left by the first (base) stimulus, which must involve working memory,Where and how is this trace held in the brain? This question was investigated by recording from single neurons in the prefrontal cortex of monkeys while they performed the somatosensory discrimination task, Here we describe neurons in the inferior convexity of the prefrontal cortex whose discharge rates varied, during the delay period between the two stimuli, as a monotonic function of the base stimulus frequency. We describe this as `monotonic stimulus encoding: and we suggest that the result may generalize: monotonic stimulus encoding may be the basic representation of one-dimensional sensory stimulus quantities in working memory. Thus we predict that other behavioural tasks that require ordinal comparisons between scalar analogue stimuli would give rise to monotonic responses similar to those reported here.
    BibTeX:
    @article{Romo1999,
      author = {Romo, R and Brody, CD and Hernandez, A and Lemus, L},
      title = {Neuronal correlates of parametric working memory in the prefrontal cortex},
      journal = {NATURE},
      year = {1999},
      volume = {399},
      number = {6735},
      pages = {470-473}
    }
    
    Roozendaal, B. Stress and memory: Opposing effects of glucocorticoids on memory consolidation and memory retrieval {2002} NEUROBIOLOGY OF LEARNING AND MEMORY
    Vol. {78}({3}), pp. {578-595} 
    article DOI  
    Abstract: It is well established that glucocorticoid hormones, secreted by the adrenal cortex after a stressful event, influence cognitive performance. Some studies have found glucocorticoid-induced memory enhancement. However, many studies have reported impairing effects of glucocorticoids on memory function. This paper reviews recent findings from this laboratory on the acute effects of glucocorticoids in rats on specific memory phases, i.e., memory consolidation and memory retrieval. The evidence suggests that the consequences of glucocorticoid activation on cognition depend largely on the different memory phases investigated. Posttraining activation of glucocorticoid-sensitive pathways involving glucocorticoid receptors enhances memory consolidation in a pattern highly similar to that previously described for adrenal catecholamines. Also, similar to catecholamine effects on memory consolidation, glucocorticoid influences on memory consolidation depend on noradrenergic activation of the basolateral complex of the amygdala and interactions with other brain regions. By contrast, memory retrieval processes are usually impaired with high circulating levels of glucocorticoids or following infusions of glucocorticoid receptor agonists into the hippocampus. The hypothesis is proposed that these apparently dual effects of glucocorticoids on memory consolidation and memory retrieval might be related and that the basolateral complex of the amygdala is a key structure in a memory-modulatory system that regulates, in concert with other brain regions, stress and glucocorticoid effects on both memory consolidation and memory retrieval. (C) 2002 Elsevier Science (USA).
    BibTeX:
    @article{Roozendaal2002,
      author = {Roozendaal, B},
      title = {Stress and memory: Opposing effects of glucocorticoids on memory consolidation and memory retrieval},
      journal = {NEUROBIOLOGY OF LEARNING AND MEMORY},
      year = {2002},
      volume = {78},
      number = {3},
      pages = {578-595},
      note = {7th Conference on the Neurobiology of Learning and Memory, IRVINE, CALIFORNIA, NOV 07-09, 2001},
      doi = {{10.1006/nlme.2002.4080}}
    }
    
    Roth, B., Sheffler, D. & Kroeze, W. Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia {2004} NATURE REVIEWS DRUG DISCOVERY
    Vol. {3}({4}), pp. {353-359} 
    article DOI  
    Abstract: Most common central nervous system disorders-such as depression, bipolar disorder and schizophrenia-seem to be polygenic in origin, and the most effective medications have exceedingly complex pharmacologies. Attempts to develop more effective treatments for diseases such as schizophrenia and depression by discovering drugs selective for single molecular targets (that is, `magic bullets') have, not surprisingly, been largely unsuccessful. Here we propose that designing selectively non-selective drugs (that is, `magic shotguns') that interact with several molecular targets will lead to new and more effective medications for a variety of central nervous system disorders.
    BibTeX:
    @article{Roth2004,
      author = {Roth, BL and Sheffler, DJ and Kroeze, WK},
      title = {Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia},
      journal = {NATURE REVIEWS DRUG DISCOVERY},
      year = {2004},
      volume = {3},
      number = {4},
      pages = {353-359},
      doi = {{10.1038/nrd1346}}
    }
    
    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., 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}}
    }
    
    Rypma, B. & D'Esposito, M. Isolating the neural mechanisms of age-related changes in human working memory {2000} NATURE NEUROSCIENCE
    Vol. {3}({5}), pp. {509-515} 
    article  
    Abstract: Working memory (WM), the process by which information is coded into memory, actively maintained and subsequently retrieved, declines with age. To test the hypothesis that age-related changes in prefrontal cortex (PFC) may mediate this WM decline, we used functional MRI to investigate age differences in PFC activity during separate WM task components (encoding, maintenance, retrieval). We found greater PFC activity in younger than older adults only in dorsolateral PFC during memory retrieval. Fast younger subjects showed less dorsolateral PFC activation during retrieval than slow younger subjects, whereas older adults showed the opposite pattern. Thus age-related changes in dorsolateral PFC and not ventrolateral PFC account for WM decline with normal aging.
    BibTeX:
    @article{Rypma2000,
      author = {Rypma, B and D'Esposito, M},
      title = {Isolating the neural mechanisms of age-related changes in human working memory},
      journal = {NATURE NEUROSCIENCE},
      year = {2000},
      volume = {3},
      number = {5},
      pages = {509-515}
    }
    
    Rypma, B. & D'Esposito, M. The roles of prefrontal brain regions in components of working memory: Effects of memory load and individual differences {1999} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {96}({11}), pp. {6558-6563} 
    article  
    Abstract: Using an event-related functional MRI design, we explored the relative roles of dorsal and ventral prefrontal cortex (PFC) regions during specific components (Encoding, Delay, Response) of a working memory task under different memory-load conditions. In a group analysis, effects of increased memory load were observed only in dorsal PFC in the encoding period. Activity was lateralized to the right hemisphere in the high but not the low memory-load condition. Individual analyses revealed variability in activation patterns across subjects. Regression analyses indicated that one source of variability was subjects' memory retrieval rate. It was observed that dorsal PFC plays a differentially greater role in information retrieval for slower subjects, possibly because of inefficient retrieval processes or a reduced quality of mnemonic representations. This study supports the idea that dorsal and ventral PFC play different roles in component processes of working memory.
    BibTeX:
    @article{Rypma1999a,
      author = {Rypma, B and D'Esposito, M},
      title = {The roles of prefrontal brain regions in components of working memory: Effects of memory load and individual differences},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1999},
      volume = {96},
      number = {11},
      pages = {6558-6563}
    }
    
    Rypma, B., Prabhakaran, V., Desmond, J., Glover, G. & Gabrieli, J. Load-dependent roles of frontal brain regions in the maintenance of working memory {1999} NEUROIMAGE
    Vol. {9}({2}), pp. {216-226} 
    article  
    Abstract: Brain imaging studies have suggested a critical role for prefrontal cortex in working memory (WM) tasks that require both maintainenance and manipulation of information over time in delayed-response WM tasks. In the present study, functional magnetic resonance imaging (fMRI) was used to examine whether prefrontal areas are activated when only maintenance is required in a delayed-response WM task, without the overt requirement to manipulate the stored information, In two scans, six subjects performed WM tasks in which, on each trial, they (1) encoded 1, 3, or 6 to-be remembered letters, (2) maintained these letters across a 5-second unfilled delay, and (3) determined whether a single probe letter was or was not part of the memory set. Activation of left caudal inferior frontal gyrus was observed, relative to the 1-letter task, when subjects were required to maintain 3 letters in WM. When subjects were required to maintain 6 letters in WM, additional prefrontal areas, most notably middle and superior frontal gyri, were activated bilaterally. Thus, increasing the amount of to-be-maintained information, without any overt manipulation requirement, resulted in the recruitment of wide-spread frontal-lobe regions. Inferior frontal gyrus activation was left-hemisphere dominant in both the 3- and 6-letter conditions, suggesting that such activation reflected material-specific verbal processes. Activation in middle and superior frontal gyri appeared only in the 8-letter condition and was right-hemisphere dominant, suggesting that such activation reflected material-independent executive processes, (C) 1999 Academic Press.
    BibTeX:
    @article{Rypma1999,
      author = {Rypma, B and Prabhakaran, V and Desmond, JE and Glover, GH and Gabrieli, JDE},
      title = {Load-dependent roles of frontal brain regions in the maintenance of working memory},
      journal = {NEUROIMAGE},
      year = {1999},
      volume = {9},
      number = {2},
      pages = {216-226}
    }
    
    Saint-Cyr, J., Trepanier, L., Kumar, R., Lozano, A. & Lang, A. Neuropsychological consequences of chronic bilateral stimulation of the subthalamic nucleus in Parkinson's disease {2000} BRAIN
    Vol. {123}({Part 10}), pp. {2091-2108} 
    article  
    Abstract: The aim of this study was to examine possible neuropsychological changes in patients with advanced idiopathic Parkinson's disease treated with bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN). Eleven patients (age = 67 +/- 8 years, years with Parkinson's disease = 15 +/- 3, verbal IQ = 114 +/- 12) were evaluated (in their best `on state') with tests assessing processes reliant on the functional integrity of frontal striatal circuitry, prior to the procedure (n = 11), at 3-6 months (n = 11) and at 9-12 months (n =10) postoperatively. Six of these patients were older than 69 years. Despite clinical motor benefits at 3-6 months postoperative, significant declines were noted in working memory, speed of mental processing, bimanual motor speed and co-ordination, set switching, phonemic fluency, long-term consolidation of verbal material and the encoding of visuospatial material. Declines were more consistently observed in patients who were older than 69 years, leading to a mental state comparable with progressive supranuclear palsy. `Frontal' behavioural dyscontrol without the benefit of insight was also reported by half (three of six) of the caregivers of the elderly subgroup. At 9-12 months postoperative, only learning based on multiple trials had recovered. Tasks reliant on the integrity of frontal striatal circuitry either did not recover or gradually worsened over time. Bilateral STN DBS can have a negative impact on various aspects of frontal executive functioning, especially in patients older than 69 years. Future studies will evaluate a larger group of patients and examine the possible reversibility of these effects by turning the DBS off.
    BibTeX:
    @article{Saint-Cyr2000,
      author = {Saint-Cyr, JA and Trepanier, LL and Kumar, R and Lozano, AM and Lang, AE},
      title = {Neuropsychological consequences of chronic bilateral stimulation of the subthalamic nucleus in Parkinson's disease},
      journal = {BRAIN},
      year = {2000},
      volume = {123},
      number = {Part 10},
      pages = {2091-2108}
    }
    
    Sakai, K., Hikosaka, O., Miyauchi, S., Takino, R., Sasaki, Y. & Putz, B. Transition of brain activation from frontal to parietal areas in visuomotor sequence learning {1998} JOURNAL OF NEUROSCIENCE
    Vol. {18}({5}), pp. {1827-1840} 
    article  
    Abstract: We studied the neural correlates of visuomotor sequence learning using functional magnetic resonance imaging (fMRI). In the test condition, subjects learned, by trial and error, the correct order of pressing two buttons consecutively for 10 pairs of buttons (2 x 10 task); in the control condition, they pressed buttons in any order. Comparison between the test condition and the control condition revealed four brain areas specifically related to learning: the dorsolateral prefrontal cortex (DLPFC), the presupplementary motor area (pre-SMA), the precuneus, and the intraparietal sulcus (IPS). We found that the time course of activation during learning was different between these areas. To normalize the individual differences in the speed of learning, we classified the performance of each subject into three learning stages: early, intermediate, and advanced stages. Both the relative increase of signal intensity and the number of activated pixels within the four areas showed significant changes across the learning stages, with different time courses. The two frontal areas, DLPFC and pre-SMA, were activated in the earlier stages of learning, whereas the two parietal areas, precuneus and IFS, were activated in the later stages. Specifically, DLPFC, pre-SMA, precuneus, and IFS were most highly activated in the early stage, in both the early and intermediate stages, in the intermediate stage, and in both the intermediate and advanced stages, respectively. The results suggest that the acquisition of visuomotor sequences requires frontal activation, whereas the retrieval of visuomotor sequences requires parietal activation, which might reflect the transition from the declarative stage to the procedural stage.
    BibTeX:
    @article{Sakai1998,
      author = {Sakai, K and Hikosaka, O and Miyauchi, S and Takino, R and Sasaki, Y and Putz, B},
      title = {Transition of brain activation from frontal to parietal areas in visuomotor sequence learning},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1998},
      volume = {18},
      number = {5},
      pages = {1827-1840}
    }
    
    SALAME, P. & BADDELEY, A. DISRUPTION OF SHORT-TERM-MEMORY BY UNATTENDED SPEECH - IMPLICATIONS FOR THE STRUCTURE OF WORKING MEMORY {1982} JOURNAL OF VERBAL LEARNING AND VERBAL BEHAVIOR
    Vol. {21}({2}), pp. {150-164} 
    article  
    BibTeX:
    @article{SALAME1982,
      author = {SALAME, P and BADDELEY, A},
      title = {DISRUPTION OF SHORT-TERM-MEMORY BY UNATTENDED SPEECH - IMPLICATIONS FOR THE STRUCTURE OF WORKING MEMORY},
      journal = {JOURNAL OF VERBAL LEARNING AND VERBAL BEHAVIOR},
      year = {1982},
      volume = {21},
      number = {2},
      pages = {150-164}
    }
    
    Salthouse, T. The processing-speed theory of adult age differences in cognition {1996} PSYCHOLOGICAL REVIEW
    Vol. {103}({3}), pp. {403-428} 
    article  
    Abstract: A theory is proposed to account for some of the age-related differences reported in measures of Type A or fluid cognition. The central hypothesis in the theory is that increased age in adulthood is associated with a decrease in the speed with which many processing operations can be executed and that this reduction in speed leads to impairments in cognitive functioning because of what are termed the limited time mechanism and the simultaneity mechanism. That is, cognitive performance is degraded when processing is slow because relevant operations cannot be successfully executed (limited time) and because the products of early processing may no longer be available when later processing is complete (simultaneity). Several types of evidence, such as the discovery of considerable shared age-related variance across various measures of speed and large attenuation of the age-related influences on cognitive measures after statistical control of measures of speed, are consistent with this theory.
    BibTeX:
    @article{Salthouse1996,
      author = {Salthouse, TA},
      title = {The processing-speed theory of adult age differences in cognition},
      journal = {PSYCHOLOGICAL REVIEW},
      year = {1996},
      volume = {103},
      number = {3},
      pages = {403-428}
    }
    
    SALTHOUSE, T. MEDIATION OF ADULT AGE-DIFFERENCES IN COGNITION BY REDUCTIONS IN WORKING MEMORY AND SPEED OF PROCESSING {1991} PSYCHOLOGICAL SCIENCE
    Vol. {2}({3}), pp. {179-183} 
    article  
    BibTeX:
    @article{SALTHOUSE1991a,
      author = {SALTHOUSE, TA},
      title = {MEDIATION OF ADULT AGE-DIFFERENCES IN COGNITION BY REDUCTIONS IN WORKING MEMORY AND SPEED OF PROCESSING},
      journal = {PSYCHOLOGICAL SCIENCE},
      year = {1991},
      volume = {2},
      number = {3},
      pages = {179-183}
    }
    
    SALTHOUSE, T. & BABCOCK, R. DECOMPOSING ADULT AGE-DIFFERENCES IN WORKING MEMORY {1991} DEVELOPMENTAL PSYCHOLOGY
    Vol. {27}({5}), pp. {763-776} 
    article  
    BibTeX:
    @article{SALTHOUSE1991,
      author = {SALTHOUSE, TA and BABCOCK, RL},
      title = {DECOMPOSING ADULT AGE-DIFFERENCES IN WORKING MEMORY},
      journal = {DEVELOPMENTAL PSYCHOLOGY},
      year = {1991},
      volume = {27},
      number = {5},
      pages = {763-776}
    }
    
    Sanchez-Vives, M. & McCormick, D. Cellular and network mechanisms of rhythmic recurrent activity in neocortex {2000} NATURE NEUROSCIENCE
    Vol. {3}({10}), pp. {1027-1034} 
    article  
    Abstract: The neocortex generates periods of recurrent activity, such as the slow (0.1-0.5 Hz) oscillation during slow-wave sleep. Here we demonstrate that slices of ferret neocortex maintained in vitro generate this slow (< 1 Hz) rhythm when placed in a bathing medium that mimics the extracellular ionic composition in situ. This slow oscillation seems to be initiated in layer 5 as an excitatory interaction between pyramidal neurons and propagates through the neocortex. Our results demonstrate that the cerebral cortex generates an `up' or depolarized state through recurrent excitation that is regulated by inhibitory networks, thereby allowing local cortical circuits to enter into temporarily activated and self-maintained excitatory states. The spontaneous generation and failure of this self-excited state may account for the generation of a subset of cortical rhythms during sleep.
    BibTeX:
    @article{Sanchez-Vives2000,
      author = {Sanchez-Vives, MV and McCormick, DA},
      title = {Cellular and network mechanisms of rhythmic recurrent activity in neocortex},
      journal = {NATURE NEUROSCIENCE},
      year = {2000},
      volume = {3},
      number = {10},
      pages = {1027-1034}
    }
    
    Sarnthein, J., Petsche, H., Rappelsberger, P., Shaw, G. & von Stein, A. Synchronization between prefrontal and posterior association cortex during human working memory {1998} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {95}({12}), pp. {7092-7096} 
    article  
    Abstract: We measured coherence between the electroencephalogram at different scalp sites while human subjects performed delayed response tasks. The tasks required the retention of either verbalizable strings of characters or abstract line drawings. In both types of tasks, a significant enhancement in coherence in the theta range (4-7 Hz) was found between prefrontal and posterior electrodes during 4-s retention intervals. During 6-s perception intervals, far fewer increases in theta coherence were found. Also in other frequency bands, coherence increased; however, the patterns of enhancement made a relevance for working memory processes seem unlikely. Our results suggest that working memory involves synchronization between prefrontal and posterior association cortex by phase-locked, low frequency (4-7 Hz) brain activity.
    BibTeX:
    @article{Sarnthein1998,
      author = {Sarnthein, J and Petsche, H and Rappelsberger, P and Shaw, GL and von Stein, A},
      title = {Synchronization between prefrontal and posterior association cortex during human working memory},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1998},
      volume = {95},
      number = {12},
      pages = {7092-7096}
    }
    
    Sarter, M. & Bruno, J. Cognitive functions of cortical acetylcholine: Toward a unifying hypothesis {1997} BRAIN RESEARCH REVIEWS
    Vol. {23}({1-2}), pp. {28-46} 
    article  
    Abstract: Previous efforts aimed at attributing discrete behavioral functions to cortical cholinergic afferents have not resulted in a generally accepted hypothesis about the behavioral functions mediated by this system, Moreover, attempts to develop such a unifying hypothesis have been presumed to be unproductive considering the widespread innervation of the cortex by basal forebrain cholinergic neurons. In contrast to previous descriptions of the rule of cortical acetylcholine (ACh) in specific behavioral phenomena (e.g., mediation of the behavioral effects of reward loss) or mnemonic entities (e.g., working or reference memory), conical ACh is hypothesized to modulate the general efficacy of the cortical processing of sensory or associational information. Specifically, cortical cholinergic inputs mediate the subjects' abilities to detect and select stimuli and associations for extended processing and to allocate the appropriate processing resources to these functions. in addition to evidence from electrophysiological and behavioral studies on the role of cortical ACh in sensory information processing and attention, this hypothesis is consistent with proposed functions of the limbic and paralimbic networks in regulating the activity of the basal forebrain cholinergic neurons, Finally, while the proposed hypothesis implies that changes in activity in cortical ACh simultaneously occur throughout the cortex, the selectivity and precision of the functions of cholinergic function is due to its coordinated interactions with the activity of converging sensory or associational inputs. Finally, the dynamic, escalating consequences of alterations in the activity of cortical ACh (hypo- and hyperactivity) on cognitive functions are evaluated.
    BibTeX:
    @article{Sarter1997,
      author = {Sarter, M and Bruno, JP},
      title = {Cognitive functions of cortical acetylcholine: Toward a unifying hypothesis},
      journal = {BRAIN RESEARCH REVIEWS},
      year = {1997},
      volume = {23},
      number = {1-2},
      pages = {28-46}
    }
    
    SAVE, E., POUCET, B., FOREMAN, N. & BUHOT, M. OBJECT EXPLORATION AND REACTIONS TO SPATIAL AND NONSPATIAL CHANGES IN HOODED RATS FOLLOWING DAMAGE TO PARIETAL CORTEX OR HIPPOCAMPAL-FORMATION {1992} BEHAVIORAL NEUROSCIENCE
    Vol. {106}({3}), pp. {447-456} 
    article  
    Abstract: Hooded rats with bilateral lesions of the anterior part of the hippocampal formation (HIP), anterior region of the posterior parietal cortex (APC), or posterior region of the posterior parietal cortex (PPC) were compared with controls for their exploration of 5 objects in an open field, habituation of locomotion and object investigation, and response to spatial and nonspatial change. First, all groups displayed habituation of both locomotor and exploratory activity. Second, controls selectively reexplored displaced objects, and APC-lesioned rats reexplored all objects, whereas PPC- and HIP-lesioned Tats failed to react to the spatial change. Third, a novel object induced reexploration in all groups. The results are consistent with the roles of the HIP and PPC in spatial information processing. Moreover, the APC and PPC are involved in attentional effortful processing and visuospatial information processing necessary for spatial representation, respectively.
    BibTeX:
    @article{SAVE1992,
      author = {SAVE, E and POUCET, B and FOREMAN, N and BUHOT, MC},
      title = {OBJECT EXPLORATION AND REACTIONS TO SPATIAL AND NONSPATIAL CHANGES IN HOODED RATS FOLLOWING DAMAGE TO PARIETAL CORTEX OR HIPPOCAMPAL-FORMATION},
      journal = {BEHAVIORAL NEUROSCIENCE},
      year = {1992},
      volume = {106},
      number = {3},
      pages = {447-456}
    }
    
    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}
    }
    
    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}
    }
    
    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., 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., 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{Schultz2000,
      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}
    }
    
    Seamans, J., Floresco, S. & Phillips, A. D-1 receptor modulation of hippocampal-prefrontal cortical circuits integrating spatial memory with executive functions in the rat {1998} JOURNAL OF NEUROSCIENCE
    Vol. {18}({4}), pp. {1613-1621} 
    article  
    Abstract: Dopamine (DA) within the prefrontal cortex (PFC) plays an important role in modulating the short-term retention of information during working memory tasks. In contrast, little is known about the role of DA in modulating other executive aspects of working memory such as the use of short-term memory to guide action. The present study examined the effects of D-1 and D-2 receptor blockade in the PFC on foraging by rats on a radial arm maze under two task conditions: (1) a delayed task in which spatial information acquired during a training phase was used 30 min later to guide prospective responses, and (2) a nondelayed task that was identical to the test phase of the delayed task but lacked a training phase, thereby depriving rats of previous information about the location of food on the maze. In experiment 1, microinjections of the D-1 antagonist SCH-23390 (0.05, 0.5, or 5 mu g/mu l), but not the D-2 anatagonist sulpiride (0.05, 0.5, or 5 mu g/mu l), into the prelimbic region of the PFC before the test phase disrupted performance of the delayed task without affecting response latencies. In contrast, neither drug affected performance of the nondelayed task. In the present study, we also investigated the role of D-1 receptors in modulating activity in hippocampal-PFC circuits during delayed responding. Unilateral injections of SCH-23390 into the PFC in the hemisphere contralateral to a microinjection of lidocaine into the hippocampus severely disrupted performance of the delayed task. Thus, the ability to use previously acquired spatial information to guide responding 30 min later on a radial arm maze requires D-1 receptor activation in the PFC and D-1 receptor modulation of hippocampal inputs to the PFC. These data suggest that D-1 receptors in the PFC are involved in working memory processes other than just the short-term active retention of information and also provide direct evidence for DA modulation of limbic-PFC circuits during behavior.
    BibTeX:
    @article{Seamans1998,
      author = {Seamans, JK and Floresco, SB and Phillips, AG},
      title = {D-1 receptor modulation of hippocampal-prefrontal cortical circuits integrating spatial memory with executive functions in the rat},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {1998},
      volume = {18},
      number = {4},
      pages = {1613-1621}
    }
    
    Seamans, J., Gorelova, N., Durstewitz, D. & Yang, C. Bidirectional dopamine modulation of GABAergic inhibition in prefrontal cortical pyramidal neurons {2001} JOURNAL OF NEUROSCIENCE
    Vol. {21}({10}), pp. {3628-3638} 
    article  
    Abstract: Dopamine regulates the activity of neural networks in the prefrontal cortex that process working memory information, but its precise biophysical actions are poorly understood. The present study characterized the effects of dopamine on GABAergic inputs to prefrontal pyramidal neurons using whole- cell patch-clamp recordings in vitro. In most pyramidal cells, dopamine had a temporally biphasic effect on evoked IPSCs, producing an initial abrupt decrease in amplitude followed by a delayed increase in IPSC amplitude. Using receptor subtype- specific agonists and antagonists, we found that the initial abrupt reduction was D2 receptor- mediated, whereas the late, slower developing enhancement was D1 receptor- mediated. Linearly combining the effects of the two agonists could reproduce the biphasic dopamine effect. Because D1 agonists enhanced spontaneous (sIPSCs) but did not affect miniature (mIPSCs) IPSCs, it appears that D1 agonists caused larger evoked IPSCs by increasing the intrinsic excitability of interneurons and their axons. In contrast, D2 agonists had no effects on sIPSCs but did produce a significant reduction in mIPSCs, suggestive of a decrease in GABA release probability. In addition, D2 agonists reduced the postsynaptic response to a GABA(A) agonist. D1 and D2 receptors therefore regulated GABAergic activity in opposite manners and through different mechanisms in prefrontal cortex (PFC) pyramidal cells. This bidirectional modulation could have important implications for the computational properties of active PFC networks.
    BibTeX:
    @article{Seamans2001,
      author = {Seamans, JK and Gorelova, N and Durstewitz, D and Yang, CR},
      title = {Bidirectional dopamine modulation of GABAergic inhibition in prefrontal cortical pyramidal neurons},
      journal = {JOURNAL OF NEUROSCIENCE},
      year = {2001},
      volume = {21},
      number = {10},
      pages = {3628-3638}
    }
    
    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}}
    }
    
    SEGER, C. IMPLICIT LEARNING {1994} PSYCHOLOGICAL BULLETIN
    Vol. {115}({2}), pp. {163-196} 
    article  
    Abstract: Implicit learning is nonepisodic learning of complex information in an incidental manner, without awareness of what has been learned. Implicit learning experiments use 3 different stimulus structures (visual, sequence, and function) and 3 different dependent measures or response modalities (conceptual fluency, efficiency, and prediction and control). Implicit learning may require a certain minimal amount of attention and may depend on attentional and working memory mechanisms. The result of implicit learning is implicit knowledge in the form of abstract (but possibly instantiated) representations rather than verbatim or aggregate representations. Implicit learning shows biases and dissociations in learning different stimulus structures. The dependence of implicit learning on particular brain areas is discussed, some conclusions are drawn for modeling implicit learning, and the interaction of implicit and explicit learning is considered.
    BibTeX:
    @article{SEGER1994,
      author = {SEGER, CA},
      title = {IMPLICIT LEARNING},
      journal = {PSYCHOLOGICAL BULLETIN},
      year = {1994},
      volume = {115},
      number = {2},
      pages = {163-196}
    }
    
    Selemon, L., Rajkowska, G. & Goldman-Rakic, P. Elevated neuronal density in prefrontal area 46 in brains from schizophrenic patients: Application of a three-dimensional, stereologic counting method {1998} JOURNAL OF COMPARATIVE NEUROLOGY
    Vol. {392}({3}), pp. {402-412} 
    article  
    Abstract: Neuropsychologic testing in schizophrenic patients has underscored the prominence of dysfunction in cognitive processes associated with the dorsolateral prefrontal cortex. Quantitative cytometric analysis of area 46 was undertaken in brains from schizophrenic patients to determine whether there are morphologic changes underlying these cognitive deficits. Postmortem brain specimens from 9 schizophrenic patients, 10 normal subjects, and 8 Huntington's diseased patients were fixed in formalin and celloidin embedded. A direct, three-dimensional counting method was used to determine cell density and cortical thickness in Nissl-stained sections of area 46. Overall neuronal density was 21% greater in brains from schizophrenic patients in comparison to normal controls. Significant elevations in neuronal density were observed in layers II, III, IV, and VI. The cortical ribbon was slightly (8 but not significantly thinner However, layer II exhibited disproportionate thinning compared with all other layers. In brains from Huntington's diseased patients, increases in neuronal(35 and glial (61 density with substantial cortical thinning (30 were observed. The neuropathology of area 46 in schizophrenia is similar in direction and magnitude to that previously described in area 9 (Selemon et al. [1995] Arch. Gen. Psychiatry 52:805-818), except for the abnormalities in layer II, which are specific to area 46. In contrast to Huntington's disease, in which cortical atrophy and gliosis are present, no evidence for cortical cell loss was uncovered in the schizophrenic cohort. The observed elevation in neuronal density suggests that a reduction in interneuronal neuropil may constitute the anatomical substrate for prefrontal cortical dysfunction in schizophrenia. (C) 1998 Wiley-Liss, Inc.
    BibTeX:
    @article{Selemon1998,
      author = {Selemon, LD and Rajkowska, G and Goldman-Rakic, PS},
      title = {Elevated neuronal density in prefrontal area 46 in brains from schizophrenic patients: Application of a three-dimensional, stereologic counting method},
      journal = {JOURNAL OF COMPARATIVE NEUROLOGY},
      year = {1998},
      volume = {392},
      number = {3},
      pages = {402-412}
    }
    
    Sereno, M., Pitzalis, S. & Martinez, A. Mapping of contralateral space in retinotopic coordinates by a parietal cortical area in humans {2001} SCIENCE
    Vol. {294}({5545}), pp. {1350-1354} 
    article  
    Abstract: The internal organization of a higher level visual area in the human parietal cortex was mapped. Functional magnetic resonance images were acquired while the polar angle of a peripheral target for a delayed saccade was gradually changed. A region in the superior parietal cortex showed robust retinotopic mapping of the remembered target angle. The map reversed when the direction of rotation of the remembered targets was reversed and persisted unchanged when study participants detected rare target reappearances while maintaining fixation, or when the eccentricity of successive remembered targets was unpredictable. This region may correspond to the lateral intraparietal area in macaque monkeys.
    BibTeX:
    @article{Sereno2001,
      author = {Sereno, MI and Pitzalis, S and Martinez, A},
      title = {Mapping of contralateral space in retinotopic coordinates by a parietal cortical area in humans},
      journal = {SCIENCE},
      year = {2001},
      volume = {294},
      number = {5545},
      pages = {1350-1354}
    }
    
    Sergeant, J., Geurts, H. & Oosterlaan, J. How specific is a deficit of executive functioning for Attention-Deficit/Hyperactivity Disorder? {2002} BEHAVIOURAL BRAIN RESEARCH
    Vol. {130}({1-2, Sp. Iss. SI}), pp. {3-28} 
    article  
    Abstract: A selective review of research in the executive functioning (EF) is given for attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), conduct disorder (CD), higher functioning autism (HFA) and Tourette syndrome. The review is restricted due to changes in the classification of the disorder in recent years and secondly the heterogeneity of EF is restricted to five key areas of concern, inhibition, set shifting, working memory, planning, and fluency. The review makes clear that there are strong differences between child psychopathological groups and controls on these EFs. However, future research will be needed to identify an EF deficit or profile, which is specific for these disorders. (C) 2002 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{Sergeant2002,
      author = {Sergeant, JA and Geurts, H and Oosterlaan, J},
      title = {How specific is a deficit of executive functioning for Attention-Deficit/Hyperactivity Disorder?},
      journal = {BEHAVIOURAL BRAIN RESEARCH},
      year = {2002},
      volume = {130},
      number = {1-2, Sp. Iss. SI},
      pages = {3-28},
      note = {Symposium on Dopamine Hypothesis of ADHD, CASTILLA LA MANCHA, SPAIN, FEB 14-25, 2000}
    }
    
    Shah, P. & Miyake, A. The separability of working memory resources for spatial thinking and language processing: An individual differences approach {1996} JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL
    Vol. {125}({1}), pp. {4-27} 
    article  
    Abstract: The current study demonstrates the separability of spatial and verbal working memory resources among college students. In Experiment 1, we developed a spatial span task that taxes both the processing and storage components of spatial working memory. This measure correlates with spatial ability (spatial visualization) measures, but not with verbal ability measures. In contrast, the reading span test, a common test of verbal working memory, correlates with verbal ability measures, but not with spatial ability measures. Experiment 2, which uses an interference paradigm to cross the processing and storage demands of span tasks, replicates this dissociation and further demonstrates that both the processing and storage components of working memory tasks are important for predicting performance on spatial thinking and language processing tasks.
    BibTeX:
    @article{Shah1996,
      author = {Shah, P and Miyake, A},
      title = {The separability of working memory resources for spatial thinking and language processing: An individual differences approach},
      journal = {JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL},
      year = {1996},
      volume = {125},
      number = {1},
      pages = {4-27},
      note = {35th Annual Meeting of the Psychonomic-Society, ST LOUIS, MO, NOV 11-13, 1994}
    }
    
    Shallice, T. & Burgess, P. The domain of supervisory processes and temporal organization of behaviour {1996} PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
    Vol. {351}({1346}), pp. {1405-1411} 
    article  
    Abstract: The possibility that the supervisory system of Norman & Shallice (1986) can be fractionated into different subprocesses is discussed. It is argued that confronting a novel situation effectively requires a variety of different types of process. It is then argued that evidence of separability of different processes may be obtained by the observation of very low correlations across patients on more than one measure on each of which frontal patients show a performance deficit. Examples of this are provided by examining the Hayling sentence completion and the Brixton spatial anticipation tasks. Finally, differential localization of the subprocesses and hence the conclusion that they are separable is discussed with respect to the localization of monitoring and verification processes in memory.
    BibTeX:
    @article{Shallice1996,
      author = {Shallice, T and Burgess, P},
      title = {The domain of supervisory processes and temporal organization of behaviour},
      journal = {PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES},
      year = {1996},
      volume = {351},
      number = {1346},
      pages = {1405-1411}
    }
    
    SHASTRI, L. & AJJANAGADDE, V. FROM SIMPLE ASSOCIATIONS TO SYSTEMATIC REASONING - A CONNECTIONIST REPRESENTATION OF RULES, VARIABLES AND DYNAMIC BINDINGS USING TEMPORAL SYNCHRONY {1993} BEHAVIORAL AND BRAIN SCIENCES
    Vol. {16}({3}), pp. {417-451} 
    article  
    Abstract: Human agents draw a variety of inferences effortlessly, spontaneously, and with remarkable efficiency - as though these inferences were a reflexive response of their cognitive apparatus. Furthermore, these inferences are drawn with reference to a large body of background knowledge. This remarkable human ability seems paradoxical given the complexity of reasoning reported by researchers in artificial intelligence. It also poses a challenge for cognitive science and computational neuroscience: How can a system of simple and slow neuronlike elements represent a large body of systemic knowledge and perform a range of inferences with such speed? We describe a computational model that takes a step toward addressing the cognitive science challenge and resolving the artificial intelligence paradox. We show how a connectionist network can encode millions of facts and rules involving n-ary predicates and variables and perform a class of inferences in a few hundred milliseconds. Efficient reasoning requires the rapid representation and propagation of dynamic bindings. Our model (which we refer to as SHRUTI) achieves this by representing (1) dynamic bindings as the synchronous firing of appropriate nodes, (2) rules as interconnection patterns that direct the propagation of rhythmic activity, and (3) long-term facts as temporal pattern-matching subnetworks. The model is consistent with recent neurophysiological evidence that synchronous activity occurs in the brain and may play a representational role in neural information processing. The model also makes specific psychologically significant predictions about the nature of reflexive reasoning. It identifies constraints on the form of rules that may participate in such reasoning and relates the capacity of the working memory underlying reflexive reasoning to biological parameters such as the lowest frequency at which nodes can sustain synchronous oscillations and the coarseness of synchronization.
    BibTeX:
    @article{SHASTRI1993,
      author = {SHASTRI, L and AJJANAGADDE, V},
      title = {FROM SIMPLE ASSOCIATIONS TO SYSTEMATIC REASONING - A CONNECTIONIST REPRESENTATION OF RULES, VARIABLES AND DYNAMIC BINDINGS USING TEMPORAL SYNCHRONY},
      journal = {BEHAVIORAL AND BRAIN SCIENCES},
      year = {1993},
      volume = {16},
      number = {3},
      pages = {417-451}
    }
    
    Shaywitz, S., Shaywitz, B., Pugh, K., Fulbright, R., Skudlarski, P., Mencl, V., Constable, R., Naftolin, F., Palter, S., Marchione, K., Katz, L., Shankweiler, D., Fletcher, J., Lacadie, C., Keltz, M. & Gore, J. Effect of estrogen on brain activation patterns in postmenopausal women during working memory tasks {1999} JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
    Vol. {281}({13}), pp. {1197-1202} 
    article  
    Abstract: Context Preclinical studies suggest that estrogen affects neural structure and function in mature animals; clinical studies are less conclusive with many, but not all, studies showing a positive influence of estrogen on verbal memory in postmenopausal women. Objective To investigate the effects of estrogen on brain activation patterns in postmenopausal women as they performed verbal and nonverbal working memory tasks. Design Randomized, double-blind, placebo-controlled, crossover trial from 1996 through 1998. Setting Community volunteers tested in a hospital setting. Patients Forty-six postmenopausal women aged 33 to 61 years (mean [SD] age, 50.8 [4.7] years). intervention Twenty-one-day treatment with conjugated equine estrogens, 1.25 mg/d, randomly crossed over with identical placebo and a 14-day washout between treatments. Main Outcome Measures Brain activation patterns measured using functional magnetic resonance imaging during tasks involving verbal and nonverbal working memory. Results Treatment with estrogen increased activation in the inferior parietal lobule during storage of verbal material and decreased activation in the inferior parietal lobule during storage of nonverbal material. Estrogen also increased activation in the right superior frontal gyrus during retrieval tasks, accompanied by greater left-hemisphere activation during encoding. The latter pattern represents a sharpening of the hemisphere encoding/retrieval asymmetry (HERA) effect. Estrogen did not affect actual performance of the verbal and nonverbal memory tasks. Conclusions Estrogen in a therapeutic dosage alters brain activation patterns in postmenopausal women in specific brain regions during the performance of the sorts of memory function that are called upon frequently during any given day. These results suggest that estrogen affects brain organization for memory in postmenopausal women.
    BibTeX:
    @article{Shaywitz1999,
      author = {Shaywitz, SE and Shaywitz, BA and Pugh, KR and Fulbright, RK and Skudlarski, P and Mencl, VE and Constable, RT and Naftolin, F and Palter, SF and Marchione, KE and Katz, L and Shankweiler, DP and Fletcher, JM and Lacadie, C and Keltz, M and Gore, JC},
      title = {Effect of estrogen on brain activation patterns in postmenopausal women during working memory tasks},
      journal = {JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION},
      year = {1999},
      volume = {281},
      number = {13},
      pages = {1197-1202}
    }
    
    SIEGEL, L. & RYAN, E. THE DEVELOPMENT OF WORKING MEMORY IN NORMALLY ACHIEVING AND SUBTYPES OF LEARNING-DISABLED CHILDREN {1989} CHILD DEVELOPMENT
    Vol. {60}({4}), pp. {973-980} 
    article  
    BibTeX:
    @article{SIEGEL1989,
      author = {SIEGEL, LS and RYAN, EB},
      title = {THE DEVELOPMENT OF WORKING MEMORY IN NORMALLY ACHIEVING AND SUBTYPES OF LEARNING-DISABLED CHILDREN},
      journal = {CHILD DEVELOPMENT},
      year = {1989},
      volume = {60},
      number = {4},
      pages = {973-980}
    }
    
    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. Dissociating verbal and spatial working memory using PET {1996} CEREBRAL CORTEX
    Vol. {6}({1}), pp. {11-20} 
    article  
    Abstract: Three experiments used position emission tomography (PET) to study the neural basis of human working memory, These studies ask whether different neural circuits underly verbal and spatial memory. In Experiment 1, subjects had to retain for 3 sec. either the names of four letters (verbal memory) or the positions of three dots (spatial memory). The PET results manifested a clear cut double dissociation, as the verbal task activated primarily left-hemisphere regions whereas the spatial task activated only right-hemisphere regions, In Experiment 2, the identical sequence of letters was presented in all conditions, and what varied was whether subjects had to remember the names of the letters (verbal memory) or their positions in the display (spatial memory). In the verbal task, activation was concentrated more in the left than the right hemisphere; in the spatial task, there was substantial activation in both hemispheres, though in key regions, there was more activation in the right than the left hemisphere. Experiment 3 studied only verbal memory, and showed that a continuous memory task activated the same regions as the discrete verbal task used in Experiment 1. Taken together, these results indicate that verbal and spatial working memory are implemented by different neural structures.
    BibTeX:
    @article{Smith1996,
      author = {Smith, EE and Jonides, J and Koeppe, RA},
      title = {Dissociating verbal and spatial working memory using PET},
      journal = {CEREBRAL CORTEX},
      year = {1996},
      volume = {6},
      number = {1},
      pages = {11-20}
    }
    
    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}
    }
    
    Smith, E., Jonides, J., Marshuetz, C. & Koeppe, R. Components of verbal working memory: Evidence from neuroimaging {1998} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {95}({3}), pp. {876-882} 
    article  
    Abstract: We review research on the neural bases of verbal working memory, focusing on human neuroimaging studies, We first consider experiments that indicate that verbal working memory is composed of multiple components, One component involves the subvocal rehearsal of phonological information and is neurally implemented by left-hemisphere speech areas, including Broca's area, the premotor area, and the supplementary motor area, Other components of verbal working memory may be devoted to pure storage and to executive processing of the contents of memory, These studies rest on a subtraction logic, in which two tasks are imaged, differing only in that one task presumably has an extra process, and the difference image is taken to reflect that process, We then review studies that show that the previous results can be obtained with experimental methods other than subtraction, We focus on the method of parametric variation, in which a parameter that presumably reflects a single process is varied, In the last section, we consider the distinction between working memory tasks that require only storage of information vs, those that require that the stored items be processed in some way, These experiments provide some support for the hypothesis that, when a task requires processing the contents of working memory, the dorsolateral prefrontal cortex is disproportionately activated.
    BibTeX:
    @article{Smith1998a,
      author = {Smith, EE and Jonides, J and Marshuetz, C and Koeppe, RA},
      title = {Components of verbal working memory: Evidence from neuroimaging},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {1998},
      volume = {95},
      number = {3},
      pages = {876-882},
      note = {Colloquium on Neuroimaging of Human Brain Function, IRVINE, CALIFORNIA, MAY 29-31, 1997}
    }
    
    Sohn, M., Ursu, S., Anderson, J., Stenger, V. & Carter, C. The role of prefrontal cortex and posterior parietal carter in task switching {2000} PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
    Vol. {97}({24}), pp. {13448-13453} 
    article  
    Abstract: Human ability to switch from one cognitive task to another involves both endogenous preparation without an external stimulus and exogenous adjustment in response to the external stimulus. In an event-related functional MRI study, participants performed pairs of two tasks that are either the same (task repetition) or different (task switch) from each other. On half of the trials, foreknowledge about task repetition or task switch was available. On the other half, it was not. Endogenous preparation seems to involve lateral prefrontal cortex (BA 46/45) and posterior parietal cortex (BA 40), During preparation, higher activation increases in inferior lateral prefrontal cortex and superior posterior parietal cortex were associated with foreknowledge than with no foreknowledge. Exogenous adjustment seems to involve superior prefrontal cortex (BA 8) and posterior parietal cortex (BA 39/40) in general. During a task switch with no foreknowledge, activations in these areas were relatively higher than during a task repetition with no foreknowledge. These results suggest that endogenous preparation and exogenous adjustment for a task switch may be independent processes involving different brain areas.
    BibTeX:
    @article{Sohn2000,
      author = {Sohn, MH and Ursu, S and Anderson, JR and Stenger, VA and Carter, CS},
      title = {The role of prefrontal cortex and posterior parietal carter in task switching},
      journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
      year = {2000},
      volume = {97},
      number = {24},
      pages = {13448-13453}
    }
    
    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}
    }
    
    Sousa, N., Lukoyanov, N., Madeira, M., Almeida, O. & Paula-Barbosa, M. Reorganization of the morphology of hippocampal neurites and synapses after stress-induced damage correlates with behavioral improvement {2000} NEUROSCIENCE
    Vol. {97}({2}), pp. {253-266} 
    article  
    Abstract: We recently demonstrated that stress-induced cognitive deficits in rats do not correlate with hippocampal neuronal loss. Working on the premise that subtle structural changes may however be involved, we here evaluated the effects of chronic stress on hippocampal dendrite morphology, the volume of the mossy fiber system, and number and morphology of synapses between mossy fibers and CA3 dendritic excrescences. To better understand the mechanisms by which stress exerts its structural effects, we also studied these parameters in rats given exogenous corticosterone. Further, to search for signs of structural reorganization following the termination of the stress and corticosterone treatments, we analysed groups of rats returned to treatment-free conditions. All animals were assessed for spatial learning and memory performance in the Morris water maze. Consistent with previous findings, dendritic atrophy was observed in the CA3 hippocampal region of chronically stressed and corticosterone-treated rats; in addition, we observed atrophy in granule and CA1 pyramidal cells following these treatments. Additionally, profound changes in the morphology of the mossy fiber terminals and significant loss of synapses were detected in both conditions. These alterations were partially reversible following rehabilitation from stress or corticosterone treatments. The fine structural changes, which resulted from prolonged hypercortisolism, were accompanied by impairments in spatial learning and memory; the latter were undetectable following rehabilitation. We conclude that there is an intimate relationship between corticosteroid levels, hippocampal neuritic structure and hippocampal-dependent learning and memory. (C) 2000 IBRO. Published by Elsevier Science Ltd.
    BibTeX:
    @article{Sousa2000,
      author = {Sousa, N and Lukoyanov, NV and Madeira, MD and Almeida, OFX and Paula-Barbosa, MM},
      title = {Reorganization of the morphology of hippocampal neurites and synapses after stress-induced damage correlates with behavioral improvement},
      journal = {NEUROSCIENCE},
      year = {2000},
      volume = {97},
      number = {2},
      pages = {253-266}
    }
    
    Spencer, W. & Raz, N. Differential effects of aging on memory for content and context: A meta-analysis {1995} PSYCHOLOGY AND AGING
    Vol. {10}({4}), pp. {527-539} 
    article  
    Abstract: The authors reviewed the evidence of age differences in episodic memory for content of a message and the context associated with it. Specifically, the authors tested a hypothesis that memory for context is more vulnerable to aging than memory for content. In addition, the authors inquired whether effort at encoding and retrieval and type of stimulus material moderate the magnitude of age differences in both memory domains. The results of the meta-analysis of 46 studies confirmed the main hypothesis: Age differences in context memory are reliably greater than those in memory for content. Tasks that required greater effort during retrieval yielded larger age differences in content but not in context memory. The greatest magnitude of age differences in context memory was observed for those contextual features that were more likely to have been encoded independently from content. Possible mechanisms that may underlie age differences in context memory-attentional deficit, reduced working memory capacity, and failure of inhibitory processing are discussed.
    BibTeX:
    @article{Spencer1995,
      author = {Spencer, WD and Raz, N},
      title = {Differential effects of aging on memory for content and context: A meta-analysis},
      journal = {PSYCHOLOGY AND AGING},
      year = {1995},
      volume = {10},
      number = {4},
      pages = {527-539}
    }
    
    SQUIRE, L. MEMORY AND THE HIPPOCAMPUS - A SYNTHESIS FROM FINDINGS WITH RATS, MONKEYS, AND HUMANS {1992} PSYCHOLOGICAL REVIEW
    Vol. {99}({2}), pp. {195-231} 
    article  
    Abstract: This article considers the role of the hippocampus in memory function. A central thesis is that work with rats, monkeys, and humans-which has sometimes seemed to proceed independently in 3 separate literatures-is now largely in agreement about the function of the hippocampus and related structures. A biological perspective is presented, which proposes multiple memory systems with different functions and distinct anatomical organizations. The hippocampus (together with anatomically related structures) is essential for a specific kind of memory, here termed declarative memory (similar terms include explicit and relational). Declarative memory is contrasted with a heterogeneous collection of nondeclarative (implicit) memory abilities that do not require the hippocampus (skills and habits, simple conditioning, and the phenomenon of priming). The hippocampus is needed temporarily to bind together distributed sites in neocortex that together represent a whole memory.
    BibTeX:
    @article{SQUIRE1992,
      author = {SQUIRE, LR},
      title = {MEMORY AND THE HIPPOCAMPUS - A SYNTHESIS FROM FINDINGS WITH RATS, MONKEYS, AND HUMANS},
      journal = {PSYCHOLOGICAL REVIEW},
      year = {1992},
      volume = {99},
      number = {2},
      pages = {195-231}
    }
    
    SQUIRE, L. & ZOLAMORGAN, S. THE MEDIAL TEMPORAL-LOBE MEMORY SYSTEM {1991} SCIENCE
    Vol. {253}({5026}), pp. {1380-1386} 
    article  
    Abstract: Studies of human amnesia and studies of an animal model of human amnesia in the monkey have identified the anatomical components of the brain system for memory in the medial temporal lobe and have illuminated its function. This neural system consists of the hippocampus and adjacent, anatomically related cortex, including entorhinal, perirhinal, and parahippocampal cortices. These structures, presumably by virtue of their widespread and reciprocal connections with neocortex, are essential for establishing long-term memory for facts and events (declarative memory). The medial temporal lobe memory system is needed to bind together the distributed storage sites in neocortex that represent a whole memory. However, the role of this system is only temporary. As time passes after learning, memory stored in neocortex gradually becomes independent of medial temporal lobe structures.
    BibTeX:
    @article{SQUIRE1991,
      author = {SQUIRE, LR and ZOLAMORGAN, S},
      title = {THE MEDIAL TEMPORAL-LOBE MEMORY SYSTEM},
      journal = {SCIENCE},
      year = {1991},
      volume = {253},
      number = {5026},
      pages = {1380-1386}
    }
    
    STECKLER, T. & SAHGAL, A. THE ROLE OF SEROTONERGIC CHOLINERGIC INTERACTIONS IN THE MEDIATION OF COGNITIVE-BEHAVIOR {1995} BEHAVIOURAL BRAIN RESEARCH
    Vol. {67}({2}), pp. {165-199} 
    article  
    Abstract: Cholinergic systems have been linked to cognitive processes such as attention, learning and mnemonic function. However, other neurotransmitter systems, such as the serotonergic one, which may have only minor effects on cognitive function on their own, interact with cholinergic function and their combined effects may have marked behavioural actions. Some studies have dealt with serotonergic-cholinergic interactions, but it is unclear whether both systems affect cognition directly or whether interactions at a behavioural level result from additional alterations in non-cognitive factors. This distinction is difficult, since it is possible that the diverse cholinergic and serotonergic systems serve different roles in the mediation of cognitive processes, both at the neuroanatomical and neurochemical level. Nevertheless, it is possible that cholinergic systems primarily alter accuracy in cognitive tasks, whereas serotonergic neurotransmission modulates behaviour by altering bias (motivation, motor processes). Whether serotonin alters accuracy or bias, however, may also depend on the cognitive process under investigation: it is suggested that attention, stimulus processing and/or arousal can be influenced by both cholinergic and serotonergic systems independently from each other. Cholinergic and serotonergic projections to cortex and thalamus may be of importance in the mediation of these cognitive processes. Serotonergic-cholinergic interactions could also be of importance in the mediation of learning processes and trial-by-trial working memory. The data available do not allow an unambiguous conclusion about the role of these interactive processes in the mediation of long-term reference memory. These processes may rely on serotonergic-cholinergic interactions at the hippocampal level. It is concluded that serotonergic-cholinergic interactions play an important role in the mediation of behavioural, including cognitive, performance, but that further studies are necessary in order to elucidate the exact nature of these interactions.
    BibTeX:
    @article{STECKLER1995,
      author = {STECKLER, T and SAHGAL, A},
      title = {THE ROLE OF SEROTONERGIC CHOLINERGIC INTERACTIONS IN THE MEDIATION OF COGNITIVE-BEHAVIOR},
      journal = {BEHAVIOURAL BRAIN RESEARCH},
      year = {1995},
      volume = {67},
      number = {2},
      pages = {165-199}
    }
    
    Steele, R. & Morris, R. Delay-dependent impairment of a matching-to-place task with chronic and intrahippocampal infusion of the NMDA-Antagonist D-AP5 {1999} HIPPOCAMPUS
    Vol. {9}({2}), pp. {118-136} 
    article  
    Abstract: We investigated the role of NMDA receptors in memory encoding and retrieval. A delayed matching-to-place (DMP) paradigm in the watermaze was used to examine 1-trial spatial memory in rats. Over periods of up to 21 days, 4 daily trials were given to an escape platform hidden in a new location each day, with the memory interval (ITI) varying from 15 sec to 2 hours between trials 1 and 2, but always at 15 sec for the remaining ITIs. Using chronic i.c.v. infusions of D-AP5, acute intrahippocampal infusions, ibotenate hippocampus + dentate lesions and relevant aCSF or sham surgery control groups, we established: (1) the DMP task is hippocampal-dependent; (2) D-AP5 causes a delay-dependent impairment of memory in which the Groups x Delay interaction was significant on two separate measures of performance; (3) this memory impairment also occurs with acute intrahippocampal infusions; (4) the impairment occurs irrespective of whether the animals stay in or are removed from the training context during the memory delay interval; and (5) D-AP5 affects neither the retrieval of information about the spatial layout of the environment, nor memory of where the escape platform had been located on the last day before the start of chronic D-AP5 infusion. LTP in vivo in the dentate gyrus was blocked in the chronically-infused D-AP5 rats and HPLC measurements at sacrifice revealed appropriate intrahippocampal levels. Acute intrahippocampal infusion of radiolabelled D-AP5 revealed relatively restricted diffusion and was used to estimate whole-tissue hippocampal drug concentrations. These results indicate that (1) short-term memory for spatial information is independent of NMDA receptors; (2) the rapid consolidation of spatial information into long-term memory requires activation of hippocampal NMDA receptors; (3) NMDA receptors are not involved in memory retrieval; and (4) the delay-related effects of NMDA receptor antagonists on performance of this task cannot be explained in terms of sensorimotor disturbances. The findings relate to the idea that hippocampal synaptic plasticity is involved in event-memory (Morris and Frey, Phil Trans R Soc Lend B 1997;352:1489-1503) and to a computational model of one-trial DMP performance of Foster et al. (unpublished data). Hippocampos 9:118-136, 1999. (C) 1999 Wiley-Liss, Inc.
    BibTeX:
    @article{Steele1999,
      author = {Steele, RJ and Morris, RGM},
      title = {Delay-dependent impairment of a matching-to-place task with chronic and intrahippocampal infusion of the NMDA-Antagonist D-AP5},
      journal = {HIPPOCAMPUS},
      year = {1999},
      volume = {9},
      number = {2},
      pages = {118-136}
    }
    
    von Stein, A. & Sarnthein, J. Different frequencies for different scales of cortical integration: from local gamma to long range alpha/theta synchronization {2000} INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY
    Vol. {38}({3}), pp. {301-313} 
    article  
    Abstract: Cortical activity and perception are not driven by the external stimulus alone; rather sensory information has to be integrated with various other internal constraints such as expectations, recent memories, planned actions, etc. The question is how large scale integration over many remote and size-varying processes might be performed by the brain. We have conducted a series of EEG recordings during processes thought to involve neuronal assemblies of varying complexity. While local synchronization during visual processing evolved in the gamma frequency range, synchronization between neighboring temporal and parietal cortex during multimodal semantic processing evolved in a lower, the beta1 (12-18 Hz) frequency range, and long range fronto-parietal interactions during working memory retention and mental imagery evolved in the theta and alpha (4-8 Hz, 8-12 Hz) frequency range. Thus, a relationship seems to exist between the extent of functional integration and the synchronization-frequency. In particular, long-range interactions in the alpha and theta ranges seem specifically involved in processing of internal mental context, i.e, for top-down processing. We propose that large scale integration is performed by synchronization among neurons and neuronal assemblies evolving in different frequency ranges. (C) 2000 Elsevier Science B.V. All rights reserved.
    BibTeX:
    @article{Stein2000,
      author = {von Stein, A and Sarnthein, J},
      title = {Different frequencies for different scales of cortical integration: from local gamma to long range alpha/theta synchronization},
      journal = {INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY},
      year = {2000},
      volume = {38},
      number = {3},
      pages = {301-313}
    }
    
    STERN, Y., ANDREWS, H., PITTMAN, J., SANO, M., TATEMICHI, T., LANTIGUA, R. & MAYEUX, R. DIAGNOSIS OF DEMENTIA IN A HETEROGENEOUS POPULATION - DEVELOPMENT OF A NEUROPSYCHOLOGICAL PARADIGM-BASED DIAGNOSIS OF DEMENTIA AND QUANTIFIED CORRECTION FOR THE EFFECTS OF EDUCATION {1992} ARCHIVES OF NEUROLOGY
    Vol. {49}({5}), pp. {453-460} 
    article  
    Abstract: A brief diagnostic battery of neuropsychological tests was developed for a large-scale epidemiological study of dementia. We operationally defined dementia as defective memory and defective performance in at least two other areas, including orientation, abstract reasoning, construction, and language. Criterion scores for defining defective performance on each test were developed. In a pilot study that used 51 different subjects with a working diagnosis based on physicians' assessment (ie, 32 demented and 29 nondemented subjects), the test-based diagnosis agreed with the working diagnosis in all but two cases. The test battery was then applied to 430 healthy elderly subjects. Eighteen percent of those with 8 or less years of education met criteria for dementia compared with 5% of those with more than 8 years of education. We computed education-corrected scores for each test with the use of residuals from the regression of each test score on education. Based on corrected scores, 12 subjects were reclassified as nondemented and 11 as demented. Subjects who were reclassified as demented were significantly more impaired in activities of daily living than nondemented subjects who were not reclassified. Activities of daily living in subjects who were reclassified as nondemented did not differ from those in demented subjects who were not reclassified. These findings suggest that the neuropsychological battery may have utility in the diagnosis of dementia. However, neuropsychological performance may be influenced by education, and some form of adjustment, such as correction for activities of daily living, may be required in epidemiological studies.
    BibTeX:
    @article{STERN1992,
      author = {STERN, Y and ANDREWS, H and PITTMAN, J and SANO, M and TATEMICHI, T and LANTIGUA, R and MAYEUX, R},
      title = {DIAGNOSIS OF DEMENTIA IN A HETEROGENEOUS POPULATION - DEVELOPMENT OF A NEUROPSYCHOLOGICAL PARADIGM-BASED DIAGNOSIS OF DEMENTIA AND QUANTIFIED CORRECTION FOR THE EFFECTS OF EDUCATION},
      journal = {ARCHIVES OF NEUROLOGY},
      year = {1992},
      volume = {49},
      number = {5},
      pages = {453-460}
    }
    
    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 dorsolateral lesion patients had difficulty only on versions of the tasks that placed demands on working memory.
    BibTeX:
    @article{Stone1998,
      author = {Stone, VE and Baron-Cohen, S and Knight, RT},
      title = {Frontal lobe contributions to theory of mind},
      journal = {JOURNAL OF COGNITIVE NEUROSCIENCE},
      year = {1998},
      volume = {10},
      number = {5},
      pages = {640-656}
    }
    
    Stromswold, K., Caplan, D., Alpert, N. & Rauch, S. Localization of syntactic comprehension by positron emission tomography {1996} BRAIN AND LANGUAGE
    Vol. {52}({3}), pp. {452-473} 
    article  
    Abstract: Positron Emission Tomography (PET) was used to determine regional cerebral blood flow (rCBF) when eight normal right-handed males read and made acceptability judgments about sentences. rCBF was greater in Broca's area (particularly in the pars opercularis) when subjects judged the semantic plausibility of syntactically more complex sentences as compared to syntactically less complex sentences. rCBF was greater in left perisylvian language areas when subjects had to decide whether sentences were semantically plausible than when subjects had to decide whether syntactically identical sentences contained a nonsense word. The results of this experiment suggest that overall sentence processing occurs in regions of the left perisylvian association cortex. The results also provide evidence that one particular aspect of sentence processing (the process that corresponds to the greater difficulty of comprehending center-embedded than right-branching relative clause sentences) is centered in the pars opercularis of Broca's area. This process is likely to be related to the greater memory load associated with processing center-embedded sentences. (C) 1996 Academic Press, Inc.
    BibTeX:
    @article{Stromswold1996,
      author = {Stromswold, K and Caplan, D and Alpert, N and Rauch, S},
      title = {Localization of syntactic comprehension by positron emission tomography},
      journal = {BRAIN AND LANGUAGE},
      year = {1996},
      volume = {52},
      number = {3},
      pages = {452-473}
    }
    
    Stuss, D. & Levine, B. Adult clinical neuropsychology: Lessons from studies of the frontal lobes {2002} ANNUAL REVIEW OF PSYCHOLOGY
    Vol. {53}, pp. {401-433} 
    article  
    Abstract: Clinical neuropsychologists have adopted numerous (and sometimes conflicting) approaches to the assessment of brain-behavior relationships. We review the historical development of these approaches and we advocate an approach to clinical neuropsychology that is informed by recent findings from cognitive neuroscience. Clinical assessment of executive and emotional processes associated with the frontal lobes of the human brain has yet to incorporate the numerous experimental neuroscience findings on this topic. We review both standard and newer techniques for assessment of frontal lobe functions, including control operations involved in language, memory, attention, emotions, self-regulation, and social functioning. Clinical and experimental research has converged to indicate the fractionation of frontal subprocesses and the initial mapping of these subprocesses to discrete frontal regions. One anatomical distinction consistent in the literature is that between dorsal and ventral functions, which can be considered cognitive and affective, respectively. The frontal lobes, in particular the frontal poles, are involved in uniquely human capacities, including self-awareness and mental time travel.
    BibTeX:
    @article{Stuss2002,
      author = {Stuss, DT and Levine, B},
      title = {Adult clinical neuropsychology: Lessons from studies of the frontal lobes},
      journal = {ANNUAL REVIEW OF PSYCHOLOGY},
      year = {2002},
      volume = {53},
      pages = {401-433}
    }
    
    Sweeney, J., Mintun, M., Kwee, S., Wiseman, M., Brown, D., Rosenberg, D. & Carl, J. Positron emission tomography study of voluntary saccadic eye movements and spatial working memory {1996} JOURNAL OF NEUROPHYSIOLOGY
    Vol. {75}({1}), pp. {454-468} 
    article  
    Abstract: 1. The purpose of this study is to define the cortical regions that subserve voluntary saccadic eye movements and spatial working memory in humans. 2. Regional cerebral blood flow (rCBF) during performance of oculomotor tasks was measured with [O-15]-H2O positron emission tomography (PET). Eleven well-trained, healthy young adults performed the following tasks: visual fixation, visually guided saccades, antisaccades (a task in which subjects made saccades away from rather than toward peripheral targets), and either an