The Prefrontal Cortex, Fifth Edition, provides users with a thoroughly updated version of this comprehensive work that has historically served as the classic reference on this part of the brain. The book offers a unifying, interdisciplinary perspective that is lacking in other volumes written about the frontal lobes, and is, once again, written by the award-winning author who discovered "memory cells," the physiological substrate of working memory. The fifth edition constitutes a comprehensive update, including all the major advances made on the physiology and cognitive neuroscience of the region since publication in 2008. All chapters have been fully revised, and the overview of prefrontal functions now interprets experimental data within the theoretical framework of the new paradigm of cortical structure and dynamics (the Cognit Paradigm), addressing the accompanying social, economic, and cultural implications. * Provides a distinctly interdisciplinary view of the prefrontal cortex, covering all major methodologies, from comparative anatomy to modern imaging* Unique analysis and synthesis of a large body of basic and clinical data on the subject (more than 2000 references)* Written by an award-winning author who discovered "memory cells," the physiological substrate of working memory* Synthesizes evidence that the prefrontal cortex constitutes a complex pre-adaptive system* Incorporates emerging study of the role of the frontal lobes in social, economic, and cultural adaptation

The prefrontal cortex

• To evaluate dorsolateral prefrontal cortex (DLPFC) physiology and function simultaneously, 20 medication-free patients with chronic schizophrenia and 25 normal controls underwent three separate xenon Xe 133 inhalation procedures for determination of regional cerebral blood flow (rCBF): first at rest, then while performing an automated version of the Wisconsin Card Sort (WCS), a DLPFC-specific cognitive test, and while peforming a simple number-matching (NM) test. During rest, patients had significantly reduced relative, but not absolute, rCBF to DLPFC. During NM, no specific region differentiated patients from controls. During WCS, however, both absolute and relative rCBF to DLPFC significantly distinguished patients from controls. While controls showed a clear increase in DLPFC rCBF, patients did not. The changes were regionally specific, involving only DLPFC. Furthermore, in patients, DLPFC rCBF correlated positively with WCS cognitive performance, suggesting that the better DLPFC was able to function, the better patients could perform. Autonomic arousal measures, the pattern of WCS errors, and results of complementary studies suggest that the DLPFC finding is linked to regionally specific cognitive function and is not a nonspecific epiphenomenon.

Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. I. Regional cerebral blood flow evidence.

We performed a quantitative review of associations between the higher order personality traits in the Big Three and Big Five models (i.e., neuroticism, extraversion, disinhibition, conscientiousness, agreeableness, and openness) and specific depressive, anxiety, and substance use disorders (SUD) in adults. This approach resulted in 66 meta-analyses. The review included 175 studies published from 1980 to 2007, which yielded 851 effect sizes. For a given analysis, the number of studies ranged from three to 63 (total sample size ranged from 1,076 to 75,229). All diagnostic groups were high on neuroticism (mean Cohen's d = 1.65) and low on conscientiousness (mean d = -1.01). Many disorders also showed low extraversion, with the largest effect sizes for dysthymic disorder (d = -1.47) and social phobia (d = -1.31). Disinhibition was linked to only a few conditions, including SUD (d = 0.72). Finally, agreeableness and openness were largely unrelated to the analyzed diagnoses. Two conditions showed particularly distinct profiles: SUD, which was less related to neuroticism but more elevated on disinhibition and disagreeableness, and specific phobia, which displayed weaker links to all traits. Moderator analyses indicated that epidemiologic samples produced smaller effects than patient samples and that Eysenck's inventories showed weaker associations than NEO scales. In sum, we found that common mental disorders are strongly linked to personality and have similar trait profiles. Neuroticism was the strongest correlate across the board, but several other traits showed substantial effects independent of neuroticism. Greater attention to these constructs can significantly benefit psychopathology research and clinical practice.

Linking "big" personality traits to anxiety, depressive, and substance use disorders: a meta-analysis.

Objective: The initial hypothesis that schizophrenia is a manifestation of hyperdopaminergia has recently been faulted. However, several new findings suggest that abnormal, although not necessarily excessive, dopamine activity is an important factor in schizophrenia. The authors discuss these findings and their implications. Method: All published studies regarding dopamine and schizophrenia and all studies on the role of dopamine in cognition were reviewed. Attention has focused on post-mortem studies, positron emission tomography, neuroleptic drug actions, plasma levels of the dopamine metabolite homovanillic acid (HVA), and cerebral blood flow. Results: Evidence, particularly from intracellular recording studies in animals and plasma HVA measurements, suggests that neuroleptics act by reducing dopamine activity in mesolimbic dopamine neurons. Post-mortem studies have shown high dopamine and HVA concentrations in various subcortical brain regions and greater than normal dopamine receptor densities in the brains of schizophrenic patients. On the other hand, the negative/deficit symptom complex of schizophrenia may be associated with low dopamine activity in the prefrontal cortex. Recent animal and human studies suggest that prefrontal dopamine neurons inhibit subcortical dopamine activity. The authors hypothesize that schizophrenia is characterized by abnormally low prefrontal dopamine activity (causing deficit symptoms) leading to excessive dopamine activity in mesolimbic dopamine neurons (causing positive symptoms). Conclusions: The possible co-occurrence of high and low dopamine activity in schizophrenia has implications for the conceptualization of dopamine ‘s role in schizophrenia. It would explain the concurrent presence of negative and positive symptoms. This hypothesis is testable and has important implications for treatment of schizophrenia and schizophrenia spectrum disorders.

Dopamine in Schizophrenia: A Review and Reconceptualization

The sections in this article are:


1
Essence of Prefrontal Function: Regulation of Behavior by Representational Knowledge
11
Subdivisions of Prefrontal Cortex

12
Global Nature of Prefrontal Syndrome in Humans

13
Animal Model for Prefrontal Function in Humans

14
Delayed-Response Tests and Varying Interpretations of Their Functional Significance

15
Distractability and Perseveration: Secondary Consequences of Basic Defect in Representational Memory

16
Representational Memory in Wisconsin Card Sort and Other Diagnostic Tests of Prefrontal Function in Humans

17
Localization of Delayed-Response Function: Principal Sulcus

18
Circuit Basis of Visuospatial Functions




2
Accessing and “On-Line” Processing of Representations in Visuospatial Domain: Parietal-Prefrontal Connections
21
Visuospatial Representational Memory in Humans

22
Spatial-Mnemonic Nature of Delayed-Response Deficit: Domain-Specific Memory Loss

23
Topography of Representational Memory in Prefrontal Cortex

24
Electrophysiological Evidence of Spatial-Mnemonic Processes in Principal Sulcus

25
Parietal-Prefrontal Connectivity

26
Columnar and Laminar Framework for Feedforward and Feedback Mechanisms

27
Functional Significance of Parietal-Prefrontal Collaboration




3
Long-Term Memory and “Off-Line” Processing: Prefrontal-Limbic Connections
31
Role of Hippocampus in Spatial Memory

32
Multiple Connections Between Principal Sulcus and Hippocampal Formation

33
Quadripartite Neural Network: Parietal-Temporal-Cingulate-Prefrontal Circuit

34
Limbic Contribution to Spatial Memory




4
Response Initiation and Inhibition: Projections to Striatum, Tectum, Thalamus, and Premotor Cortex
41
Motor-Control Functions of Prefrontal Cortex

42
Cortical-Striatal Pathway and Related Feedback Loops

43
Cortical-Tectal Pathway

44
Thalamic-Cortical Systems

45
Prefrontal-Premotor Connections: Anterior Supplementary Motor Cortex Relays

46
Functional Speculations




5
Modulatory Mechanisms: Brain Stem Catecholamine Projections
51
Activation of Cognitive Machinery

52
Concentration and Synthesis of Catecholamines in Primate Cortex

53
Brain Stem Innervation of Prefrontal Cortex

54
Delayed-Response Deficits and Recovery Produced by Catecholamine Loss and Replacement in Prefrontal Cortex

55
Circuit Basis for Neuromodulation in Principal Sulcus




6
Multiple Subsystems of Prefrontal Cortex: Unity or Diversity of Function
61
Unity or Diversity of Prefrontal Function

62
Frontal Eye Fields

63
Inferior Convexity

64
Orbital Prefrontal Cortices

65
Problem of Integration




7
Diseases Affecting Prefrontal Cortex
71
Schizophrenia: Loss of Corticocortical Processing and Regulation of Behavior by Representational Knowledge

72
Wernicke-Korsakoff Syndrome: Loss of Thalamocortical and Brain Stem Modulatory Mechanisms

73
Huntington's Chorea and Parkinson's Disease: Loss of Prefrontal-Striatal Mechanisms and Initiation or Inhibition of Motor Response

74
Overview of Neurobiology of Disease




8
Summary

Circuitry of Primate Prefrontal Cortex and Regulation of Behavior by Representational Memory

Background Blinding reviewers to applicant identity has been proposed to reduce bias in peer review. Methods This experimental test used 1200 NIH grant applications, 400 from Black investigators, 400 matched applications from White investigators, and 400 randomly selected applications from White investigators. Applications were reviewed by mail in standard and redacted formats. Results Redaction reduced, but did not eliminate, reviewers' ability to correctly guess features of identity. The primary, preregistered analysis hypothesized a differential effect of redaction according to investigator race in the matched applications. A set of secondary analyses (not preregistered) used the randomly selected applications from White scientists and tested the same interaction. Both analyses revealed similar effects: Standard format applications from White investigators scored better than those from Black investigators. Redaction cut the size of the difference by about half (e.g. from a Cohen's d of 0.20-0.10 in matched applications); redaction caused applications from White scientists to score worse but had no effect on scores for Black applications. Conclusions Grant-writing considerations and halo effects are discussed as competing explanations for this pattern. The findings support further evaluation of peer review models that diminish the influence of applicant identity. Funding Funding was provided by the NIH.

An experimental test of the effects of redacting grant applicant identifiers on peer review outcomes

Improving Psychiatric Consultation to Nonpsychiatrist Physicians

Spinal fluid studies in schizophrenia have not led to the discovery of consistent differences from normals and other comparison groups (Berger et al 1980; Post et al 1975) The frequently observed increased variance in the CSF of schizophrenic patients has been explained by the heterogeneous nature of this illness Attempts to subgroup schizophrenic patients on the basis of CSF has led to associations between reduced homo vanillic acid (HVA) accumulations after probenecid and patients with a poor prognosis (Bowers 1973), decreased HVA and remitted acute schizophrenics (Post et al 1975), and elevated norepinephrine (NE) and paranoid patients (Lake et al 1980) Post et al (1975) found a correlation between 5-hydroxyindoleacetic acid (5-HIAA) concentrations and Schneiderian first-rank symptoms in acutely ill schizophrenics, and we recently found low 5-HIAA in a small group of schizophrenics with a history of successful or serious suicide attempts (Ninan et al 1984)

Lee S. Mann

Papers

An experimental test of the effects of redacting grant applicant identifiers on peer review outcomes

Improving Psychiatric Consultation to Nonpsychiatrist Physicians

Decreased Spinal Fluid Monoamine Metabolites and Norepinephrine in Schizophrenic Patients with Brain Atrophy

Borderline patients' view of their parents.

Sonnet for a Grecian