Author
Ronald G. Manning
Bio: Ronald G. Manning is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Ionization chamber & Cerebral blood flow. The author has an hindex of 6, co-authored 7 publications receiving 1279 citations.
Papers
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TL;DR: Local cerebral uptake of deoxyglucose labeled with fluorine 18 was measured by positron-emission tomography in eight patients with schizophrenia and in six age-matched normal volunteers, indicating relatively lower glucose use than normal control subjects.
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.
509 citations
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TL;DR: The results indicate that brain oxidative metabolism, when measured under resting conditions with reduced sensory input, is not reduced in relation to age in healthy men and no significant relations between intelligence and resting cerebral metabolism are evident.
Abstract: Brain oxidative metabolism was examined with positron emission tomography and [18F]2-deoxy-D-glucose in 40 healthy men aged 21 to 83 years, under conditions of reduced visual and auditory stimulation. The mean cerebral metabolic rate for glucose (CMRglc) equaled 4.6 to 4.7 mg X 100 gm-1 X min-1 and did not correlate significantly with age (p greater than 0.05). Regional cerebral metabolic rates for glucose (rCMRglc) and Q ratios (rCMRglc/CMRglc), which had lower coefficients of variation than did rCMRglc, also did not correlate with age. Hyperfrontality of cerebral metabolism was absent at all ages. Age decrements were demonstrated in the error score on the Benton Revised Visual Retention Test and in the Performance Subtest scaled score of the Wechsler Adult Intelligence Scale (WAIS) but not in the Verbal Subtest scaled score of the WAIS. The cognitive test scores did not correlate with brain metabolic rates. The results indicate that brain oxidative metabolism, when measured under resting conditions with reduced sensory input, is not reduced in relation to age in healthy men. Furthermore, no significant relations between intelligence and resting cerebral metabolism are evident.
272 citations
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TL;DR: The results indicate that the cerebral metabolic rate for glucose is not correlated with age in healthy men.
Abstract: Positron emission tomography (PET) scanning with 18F-2-deoxy-D-glucose was employed to examine hemispheric and regional rates of cerebral glucose utilization in 21 resting healthy men between the ages of 21 and 83 years. The eyes of the subjects were covered and the external auditory canals were plugged with cotton in the 45 minutes following injection of tracer. Mean hemispheric cerebral metabolic rates for glucose (CMRglc) averaged 4.3 to 4.4 mg x 100 g-1 X min-1, and mean hemispheric grey matter glucose utilization, (CMRglc)grey, averaged 5.2 to 5.3 mg x 100 g-1 X min-1. Neither parameter was correlated significantly with age, nor were their right/left ratios correlated with age (P greater than 0.05). The mean ratios, furthermore, did not differ significantly from 1. Regional cerebral metabolic rates for glucose, rCMRglc, at each of 31 identified midline and bilateral structures also were not correlated significantly with age. Mean rCMRglc ranged from 2.6 mg X 100 g-1 X min-1 at the centrum semiovale to 6.2 mg . 100 g-1 X min-1 at the precentral gyrus of the frontal lobe and precuneus of the parietal lobe. The results indicate that the cerebral metabolic rate for glucose is not correlated with age in healthy men.
246 citations
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TL;DR: Positron emission tomography with simultaneous electroencephalographic monitoring was performed with {18F}fluorodeoxyglucose in 20 patients with complex partial seizures who had normal computed tomographic scans, finding a tendency for patients to have higher overall metabolic rates when taking less medication.
Abstract: Positron emission tomography with simultaneous electroencephalographic monitoring was performed with [18F]fluorodeoxyglucose in 20 patients with complex partial seizures who had normal computed tomographic scans. Seven patients had only unilateral epileptiform discharges on the electroencephalogram, 3 had predominantly unilateral discharges, and 10 had nonlocalized epileptiform abnormalities. Positron emission tomography showed a hypometabolic lesion in 16 of the 20 patients. Pathological changes in the hypometabolic region were found in postoperative specimens in 4 of 5 patients studied. Positron emission tomography was unaffected by the seizure frequency, state of alertness, or number of spike discharges during the scan. There was a tendency for patients to have higher overall metabolic rates when taking less medication. Seizures occurring during [18F]fluorodeoxyglucose uptake in 3 patients produced a hypermetabolic area at the interictal hypometabolic focus. Positron emission tomography sometimes showed more widespread hypometabolism than suspected on the basis of the scalp-recorded electroencephalogram. The frontal lobe showed a greater degree of hypometabolism than the temporal lobe in 3 patients. Focal lesions may be identified by positron emission tomography even if the electroencephalographic abnormality is not well localized.
239 citations
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01 Jan 1983
TL;DR: The development of the 18F-labeled 2-fluorodeoxyglucose (218FDG) method has produced a powerful tool for studying cerebral energy metabolism with positron tomography in resting subjects and schizophrenic subjects at rest and off medication.
Abstract: The ability to study patterns of cerebral metabolism in humans noninvasively is clearly one of the great advantages of positron tomography. The development of the 18F-labeled 2-fluorodeoxyglucose (218FDG) method has produced a powerful tool for studying cerebral energy metabolism with positron tomography (Huang et al. 1980). Given the tight coupling normally existing between cerebral function and energy metabolism (Sokoloff 1977, 1981), 218FDG has been used to study resting patterns of metabolism in resting subjects (Mazziotta et al. 1981), subjects undergoing neuropsychological activations (Greenberg et al. 1981), and schizophrenic subjects at rest and off medication (Buchsbaum et al. 1982).
12 citations
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01 Jan 1997
TL;DR: 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.
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
2,589 citations
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TL;DR: 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.
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.
2,066 citations
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TL;DR: The frontal lobe hypothesis of cognitive aging is found to perform well, with the exception of an inability to account for age-related declines in item recall and recognition memory, possibly a result of age- related declines in medial temporal function.
Abstract: The purpose of this review is to extend the existing application of the frontal lobe hypothesis of cognitive aging beyond the limited work on inhibitory control (F. N. Dempster, 1992) to include memory processes supported by the prefrontal cortex. To establish a background for this analysis, I review existing models of prefrontal cortex function and present a synthesized model that includes a general function of temporal integration, supported by 4 specific processes: prospective memory, retrospective memory, interference control, and inhibition of prepotent responses. I found the frontal lobe hypothesis to perform well, with the exception of an inability to account for age-related declines in item recall and recognition memory, possibly a result of age-related declines in medial temporal function.
1,979 citations
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TL;DR: The sections in this article are: Essence of Prefrontal Function: Regulation of Behavior by Representational Knowledge, Multiple Subsystems of Pre Frontal Cortex: Unity or Diversity of Function, and Functional Speculations.
Abstract: The sections in this article are:
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Essence of Prefrontal Function: Regulation of Behavior by Representational Knowledge
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Subdivisions of Prefrontal Cortex
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Global Nature of Prefrontal Syndrome in Humans
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Animal Model for Prefrontal Function in Humans
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Delayed-Response Tests and Varying Interpretations of Their Functional Significance
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Distractability and Perseveration: Secondary Consequences of Basic Defect in Representational Memory
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Representational Memory in Wisconsin Card Sort and Other Diagnostic Tests of Prefrontal Function in Humans
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Localization of Delayed-Response Function: Principal Sulcus
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Circuit Basis of Visuospatial Functions
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Accessing and “On-Line” Processing of Representations in Visuospatial Domain: Parietal-Prefrontal Connections
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Visuospatial Representational Memory in Humans
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Spatial-Mnemonic Nature of Delayed-Response Deficit: Domain-Specific Memory Loss
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Topography of Representational Memory in Prefrontal Cortex
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Electrophysiological Evidence of Spatial-Mnemonic Processes in Principal Sulcus
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Parietal-Prefrontal Connectivity
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Columnar and Laminar Framework for Feedforward and Feedback Mechanisms
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Functional Significance of Parietal-Prefrontal Collaboration
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Long-Term Memory and “Off-Line” Processing: Prefrontal-Limbic Connections
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Role of Hippocampus in Spatial Memory
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Multiple Connections Between Principal Sulcus and Hippocampal Formation
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Quadripartite Neural Network: Parietal-Temporal-Cingulate-Prefrontal Circuit
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Limbic Contribution to Spatial Memory
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Response Initiation and Inhibition: Projections to Striatum, Tectum, Thalamus, and Premotor Cortex
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Motor-Control Functions of Prefrontal Cortex
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Cortical-Striatal Pathway and Related Feedback Loops
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Cortical-Tectal Pathway
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Thalamic-Cortical Systems
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Prefrontal-Premotor Connections: Anterior Supplementary Motor Cortex Relays
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Functional Speculations
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Modulatory Mechanisms: Brain Stem Catecholamine Projections
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Activation of Cognitive Machinery
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Concentration and Synthesis of Catecholamines in Primate Cortex
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Brain Stem Innervation of Prefrontal Cortex
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Delayed-Response Deficits and Recovery Produced by Catecholamine Loss and Replacement in Prefrontal Cortex
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Circuit Basis for Neuromodulation in Principal Sulcus
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Multiple Subsystems of Prefrontal Cortex: Unity or Diversity of Function
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Unity or Diversity of Prefrontal Function
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Frontal Eye Fields
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Inferior Convexity
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Orbital Prefrontal Cortices
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Problem of Integration
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Diseases Affecting Prefrontal Cortex
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Schizophrenia: Loss of Corticocortical Processing and Regulation of Behavior by Representational Knowledge
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Wernicke-Korsakoff Syndrome: Loss of Thalamocortical and Brain Stem Modulatory Mechanisms
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Huntington's Chorea and Parkinson's Disease: Loss of Prefrontal-Striatal Mechanisms and Initiation or Inhibition of Motor Response
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Overview of Neurobiology of Disease
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Summary
1,923 citations
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TL;DR: In this paper, a novel mechanism for regulating dopamine activity in subcortical sites and its possible relevance to schizophrenia is proposed, which is based on the regulation of dopamine release into sub cortical regions occurring via two independent mechanisms: (1) transient or phasic dopamine release caused by dopamine neuron firing, and (2) sustained, "background" tonic release regulated by prefrontal cortical afferents.
1,771 citations