Lee S. Mann

Bio: Lee S. Mann is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Homovanillic acid & Toronto Alexithymia Scale. The author has an hindex of 10, co-authored 16 publications receiving 1336 citations.

Cerebral glucography with positron tomography. Use in normal subjects and in patients with schizophrenia.

Abstract: • Local cerebral uptake of deoxyglucose labeled with fluorine 18 was measured by positron-emission tomography in eight patients with schizophrenia who were not receiving medication and in six age-matched normal volunteers. Subjects sat in an acoustically treated, darkened room with eyes closed after injection of 3 to 5 mCi of deoxyglucose18F. After uptake, seven to eight horizontal brain scans parallel to the canthomeatal line were done. Scans were treated digitally, with a 2.3-cm strip peeled off each slice and ratios to whole-slice activity computed. Patients with schizophrenia showed lower ratios in the frontal cortex, indicating relatively lower glucose use than normal control subjects; this was consistent with previously reported studies of regional cerebral blood flow. Patients also showed diminished ratios for a 2.3-cm square that was positioned over central gray-matter areas on the left but not on the right side. These findings are preliminary; issues of control of mental activity, brain structure identification, and biologic and anatomic heterogeneity of schizophrenia remain to be explored.

Computerized tomography and neuropsychological test measures in adolescents with obsessive-compulsive disorder.

Abstract: The authors administered CAT scans and neuropsychological tests to 16 adolescents with obsessive-compulsive disorder (mean age +/- SD = 13.7 +/- 1.6 years) and 16 matched controls. The patients had a mean ventricular-brain ratio (VBR) significantly higher than the controls' and showed spatial-perceptual deficits similar to those found in patients with frontal lobe lesions. Memory, reaction time, and decision time did not differ significantly from controls'. Neurodevelopmental examination of seven patients yielded a high frequency of age-inappropriate synkinesias and left hemibody signs. These results suggest CNS dysfunctioning in children with obsessive-compulsive disorder, with possible right cerebral involvement. However, the patients' neuropsychological test deficits and VBRs were not correlated.

Computed Tomographic Scans in Patients With Schizophrenia, Schizoaffective, and Bipolar Affective Disorder

Abstract: Computed tomographic (CT) scans of 28 chronic schizophrenic patients, 15 chronic schizoaffective patients, and 19 patients with bipolar affective disorder were compared on three measures: ventricular size, sulcal prominence (cortical atrophy), and cerebellar atrophy. Because the patients with bipolar disorder were older, measures were adjusted by controlling for age statistically or excluding patients over age 50 years. After age correction, there were no significant differences across diagnostic groups. Each group contained some subjects with enlarged ventricles, sulcal prominence, and/or cerebellar atrophy. The similarity of CT scan results across the three groups argues against ascribing these abnormalities to any one psychiatric disorder or to a specific drug effect. Sampling effects and the possibility of differential causes of the findings in the different diagnostic groups must be considered. Examination of the correlations of these three CT scan measures found them to be significantly related to each other. Age correlated with all measures when patients over age 50 years were included in the analysis, but not for patients aged 50 years and younger.

Dopamine metabolism in the cerebrospinal fluid of drug-free schizophrenic patients with and without cortical atrophy.

Abstract: • Cortical atrophy measured with computed tomography was observed in ten of 53 schizophrenic patients. Levels of homovanillic acid, dihydroxyphenyl acetic acid (DOPAC), conjugated DOPAC, and dopamine sulfate (DASO 4 ) were measured in the cerebrospinal fluid of these patients during a drug-free evaluation. Patients with cortical atrophy had lower cerebrospinal fluid levels of homovanillic acid, DOPAC, and conjugated DOPAC but higher DASO 4 levels. Combined measures of dopamine utilization were significantly lower in patients with cortical atrophy. We did not find significant clinical or demographic differences between the patients with and without cortical atrophy. Patients without brain atrophy who had dopamine utilization above the mean showed more psychotic symptoms and shorter duration of illness, while those with dopamine below the mean had more negative symptoms. We propose that both state- and trait-dependent variables affect dopamine turnover.

Dopamine-beta-hydroxylase activity and homovanillic acid in spinal fluid of schizophrenics with brain atrophy

Abstract: Schizophrenic patients with high ventricle brain ratios and cortical brain atrophy, as shown by computerized tomography, had decreased spinal fluid concentrations of homovanillic acid and dopamine-beta-hydroxylase activity. These decreased cerebral spinal fluid concentrations in patients with brain atrophy support the proposal of disturbed noradrenaline and dopamine neurotransmission in a subgroup of schizophrenic patients.

The prefrontal cortex

Abstract: 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

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

Abstract: • 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.

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

Abstract: 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.

Dopamine in Schizophrenia: A Review and Reconceptualization

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

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

Abstract: 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