Author
R. M. Kessler
Other affiliations: University of California, Irvine
Bio: R. M. Kessler is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Positron emission tomography & Fluorodeoxyglucose. The author has an hindex of 15, co-authored 21 publications receiving 2850 citations. Previous affiliations of R. M. Kessler include University of California, Irvine.
Papers
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TL;DR: A correlation between rate of glycolysis and malignancy in primary cerebral tumors is found and Cerebral cortical glucose utilization was often depressed in areas adjacent to or neurally connected to the tumor site, and there was focal irregular delta wave EEG activity in these areas.
Abstract: Positron emission tomography was used to measure local cerebral glucose utilization by the 2-[ 18 F]fluoro-2-deoxy-D-glucose technique in 23 patients with cerebral gliomas. All 10 high-grade (III and IV) astrocytomas demonstrated a region of high activity with a glucose consumption of 7.4 ± 3.5 (SD) mg/100 gm per minute. The 13 low-grade (I and II) gliomas had a glucose metabolic rate of 4.0 ± 1.8 mg/100 gm per minute, with no distinctly visible hot spot. Thus, we found a correlation between rate of glycolysis and malignancy in primary cerebral tumors. Cerebral cortical glucose utilization was often depressed in areas adjacent to or neurally connected to the tumor site, and there was focal irregular delta wave EEG activity in these areas.
754 citations
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TL;DR: Local cerebral uptake of deoxyglucose labeled with fluorine 18 was measured by positron emission tomography in patients with schizophrenia and patients with affective disorder, sharing a lack of diagnostic specificity with many biologic measures.
Abstract: • Local cerebral uptake of deoxyglucose labeled with fluorine 18 was measured by positron emission tomography in 16 patients with schizophrenia and 11 patients with affective disorder. Patients received no medication a minimum of 14 days and an average of 39.8 days. The subjects were administered the deoxyglucose 18F just before receiving a 34-minute 1/s series of unpleasant electrical stimuli to the right forearm while resting with eyes closed in a darkened, acoustically attenuated psychophysiologic testing chamber. Following monitored stimulation in the controlled environment, subjects were scanned and images converted to values of glucose use in micromoles per 100 g per minute according to Sokoloff's model. Data were analyzed with a four-way analysis of variance (ANOVA) with independent groups (normals, schizophrenics, and affectives) and repeated measures for slice level (supraventricular, midventricular, and infraventricular), hemisphere (right, left), and anteroposterior position (four sectors). Both normal subjects and patients showed a significant anteroposterior gradient in glucose use with highest values in the frontmost sector. Patients both with schizophrenia and with affective illness showed less of an anteroposterior gradient especially at superior levels, which was statistically confirmed by ANOVA. Absolute glucose levels in patients, which were actually higher in posterior regions rather than lower in frontal regions, were the largest contributors to the effect. Neither group differences in whole brain glucose use nor left-right asymmetries reached statistical significance. These results are consistent with our earlier reports of a relative hypofrontal function in schizophrenia compared with controls. This report extends this finding to affective illness, sharing a lack of diagnostic specificity with many biologic measures.
366 citations
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TL;DR: Five patients who had undergone radiation therapy for cerebral tumors and whose conditions were deteriorating were examined by means of positron emission tomography (PET) with [18F] fluorodeoxyglucose and the two cases of radiation necrosis were distinguished from the three recurrent tumors.
Abstract: Five patients who had undergone radiation therapy for cerebral tumors and whose conditions were deteriorating were examined by means of positron emission tomography (PET) with [18F] fluorodeoxyglucose. All five cases had similar clinical and computed tomographic findings. Using the PET technique the two cases of radiation necrosis were distinguished from the three recurrent tumors. In the two cases of radiation necrosis the rate of glucose utilization in the lesion was markedly reduced compared with the normal brain parenchyma. In the recurrent gliomas, however, the glucose metabolic rate was elevated. All five diagnoses were confirmed by biopsy or autopsy.
270 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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TL;DR: Current knowledge of blood flow and perfusion-related parameters, which usually go hand in hand and in turn define the cellular metabolic microenvironment of human malignancies, are summarized for predicting the acute and/or long-term response of tumors to therapy.
Abstract: The objective of this review article is to summarize current knowledge of blood flow and perfusion-related parameters, which usually go hand in hand and in turn define the cellular metabolic microenvironment of human malignancies. A compilation of available data from the literature on blood flow, oxygen and nutrient supply, and tissue oxygen and pH distribution in human tumors is presented. Whenever possible, data obtained for human tumors are compared with the respective parameters in normal tissues, isotransplanted or spontaneous rodent tumors, and xenografted human tumors. Although data on human tumors in situ are scarce and there may be significant errors associated with the techniques used for measurements, experimental evidence is provided for the existence of a compromised and anisotropic blood supply to many tumors. As a result, O2-depleted areas develop in human malignancies which coincide with nutrient and energy deprivation and with a hostile metabolic microenvironment (e.g., existence of severe tissue acidosis). Significant variations in these relevant parameters must be expected between different locations within the same tumor, at the same location at different times, and between individual tumors of the same grading and staging. Furthermore, this synopsis will attempt to identify relevant pathophysiological parameters and other related areas future research of which might be most beneficial for designing individually tailored treatment protocols with the goal of predicting the acute and/or long-term response of tumors to therapy.
3,379 citations
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TL;DR: It is revealed that EF deficits are consistently found in both ADHD and autism but not in CD (without ADHD) or in TS, and both the severity and profile of EF deficits appears to differ across ADHD and Autism.
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.
3,108 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