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Biomedical subjects

M S Buchsbaum

Publications and source records attributed to M S Buchsbaum.

At least 73 records · Page 4Linked to original sources

Glucose metabolic correlates of continuous performance test performance in adults with a history of infantile autism, schizophrenics, and controls.

Twenty-five schizophrenic patients, fourteen adults with a history of infantile autism, and twenty normal controls performed a test of sustained attention, the degraded stimulus continuous performance test (CPT), during the 35 minute 18-fluoro-2-deoxyglucose uptake period preceding positron emission tomographic (PET) scan acquisition. This is the first analysis comparing correlations between glucose metabolic rate (GMR) for selected regions and CPT performance. CPT performance differed in controls and schizophrenics, but autistics did not differ from either group. In controls and schizophrenic patients, task performance correlated with GMR in medial superior frontal gyrus and lateral inferior temporal gyrus, suggesting that activation of those regions is important in the normal performance of the task and that damage to those regions, which also showed low GMR in schizophrenics, contributes to the attentional dysfunction in schizophrenia. Also, schizophrenics showed negative correlations of task performance with anterior cingulate activity suggesting that overactivity of that region, which is involved in mental effort and whose GMR was low in our larger study of schizophrenia, impairs task performance in schizophrenics. Autistic patients showed negative correlations of medial frontal cortical GMR with attentional performance, suggesting that neuronal inefficiency in that region may contribute to poor performance.

Adolescent↗

Localized and lateralized cerebral glucose metabolism associated with eye movements during REM sleep and wakefulness: a positron emission tomography (PET) study.

In order to study the neural substrate for eye movements during rapid eye movement (REM) sleep, we analyzed the positron emission tomography (18Fluorodeoxyglucose positron emission tomography) scan data obtained from normal subjects. Eye movement data were available on nine subjects studied during nighttime REM sleep and six control subjects studied during waking as they periodically moved their eyes. The number of eye movements during REM sleep was positively correlated with glucose metabolic rate in the areas corresponding to (a) the saccadic eye movement system (frontal eye field and dorsolateral prefrontal cortex, statistically significant only on the right side), (b) the midline attentional system (cingulate and medial frontal cortex, precuneus) and (c) the parietal visual spatial attentional system (bilateral superior parietal lobules, right inferior parietal lobule); and negatively correlated with relative metabolic rate in the left inferior parietal lobule. Positive correlations between waking eye movements and metabolic rate were observed in the same areas except inferior parietal lobule. Our results show that the same cortical areas are involved in eye movements in both REM sleep and wakefulness and suggest that REM sleep eye movements are saccadic scans of targets in the dream scene. Our data also suggest right hemispheric specialization in saccadic eye movement control and reciprocal inhibition in the contralateral homologous area during higher cortical functioning.

Attention↗

EEG delta, positron emission tomography, and memory deficit in Alzheimer's disease.

Quantitative scalp EEG from 32 channels and the cerebral glucose metabolic rate from the 32 underlying cortical positions as assessed by positron emission tomography (PET) with 18F-2-deoxyglucose (FDG) were obtained on 36 patients with mild to moderate senile dementia of the Alzheimer type and 17 age- and sex-matched normal control subjects. Subjects performed a verbal memory task during uptake of FDG. There were significant correlations between both delta amplitude and metabolic rate and memory performance during FDG uptake. Patients with Alzheimer's disease had significantly greater left temporal delta amplitude and lower glucose metabolic rates. Both EEG delta in microvolts and metabolic rate had similar diagnostic sensitivity, but PET had fewer false positives among normals. The left amygdala had the highest sensitivity and percent correct diagnosis of any brain area. Temporal lobe EEG delta activity showed higher correlations with hippocampal metabolic rate than metabolic rate directly under the electrode.

Aged↗

Structural and functional correlates of subsyndromes in chronic schizophrenia.

Recent psychopathological studies consistently identified a delusional, a negative, and a disorganized subsyndrome in chronic schizophrenia. The aim of our studies was to investigate the subsyndromes with respect to their underlying cerebral changes using computed tomography (CT) and positron emission tomography (PET). In a CT study 50 DSM III schizophrenics were subgrouped according to four factors identified by a factor analysis of BPRS ratings. This procedure identified three chronic clusters (delusional ideation, negative symptoms, and disorganization) and one cluster with a remitting course of the disorder. Both the negative and the delusional subsyndrome were associated with a widening of the frontal interhemispheric fissure. Disorganization was associated with neurological soft signs, an increased ventricle brain ratio, and width of the 3rd ventricle. The same subgrouping was applied in a 18F-deoxyglucose PET study of 79 neuroleptic free DSM III schizophrenic patients and 47 healthy controls. The delusional subsyndrome was associated with a decreased hippocampal function, while the negative subsyndrome showed a prominent hypofrontality and left temporal cortex changes. Both the delusional and the negative subsyndrome were associated with a decreased activity in the medial frontal gyrus in comparison to the other schizophrenic patients and the healthy controls. The disorganized subsyndrome was characterized by an overactivity in the parietal cortex and motor strip and a decreased activity in the corpus callosum. These findings support the differentiation of three subsyndromes in chronic schizophrenia. The subsyndromes seem to be characterized by deviant patterns of cerebral alterations, rather than deficits in a single location.

Brain↗

Positron emission tomography studies of abnormal glucose metabolism in schizophrenic illness.

Advances in psychopharmacology and neuroscience have brought into view a wide field of competing mechanisms for the etiology of schizophrenia including, but not limited to, deficits in one or more neurotransmitters (dopamine, serotonin, GABA, glutamate, and noradrenaline systems), neurodevelopmental defects in cortical connectivity, and viral infection. Genetic studies suggest heterogeneity in the illness, with multifactorial inheritance. Since cerebral metabolic activity reflects regional brain work for all neurotransmitter systems, imaging studies can provide information on the functional neuroanatomy of a deficit in the individual patient, allowing the grouping of patients for more intensive investigation in more homogeneous groups. Metabolic imaging studies allow psychopharmacological response to be regionally assessed and clinical responders to be identified, even for medications that affect more than one neurotransmitter system or have clinical effects that derive from changes in activity one synapse or more removed from the site of primary action.

Brain↗

Selective reductions in prefrontal glucose metabolism in murderers.

This study tests the hypothesis that seriously violent offenders pleading not guilty by reason of insanity or incompetent to stand trial are characterized by prefrontal dysfunction. This hypothesis was tested in a group of 22 subjects accused of murder and 22 age-matched and gender-matched controls by measuring local cerebral uptake of glucose using positron emission tomography during the continuous performance task. Murderers had significantly lower glucose metabolism in both lateral and medial prefrontal cortex relative to controls. No group differences were observed for posterior frontal, temporal, and parietal glucose metabolism, indicating regional specificity for the prefrontal deficit. Group differences were not found to be a function of raised levels of left-handedness, schizophrenia, ethnic minority status, head injury, or motivation deficits in the murder group. These preliminary results suggest that deficits localized to the prefrontal cortex may be related to violence in a selected group of offenders, although further studies are needed to establish the generalizability of these findings to violent offenders in the community.

Adult↗

Patterns of cortical activity in schizophrenia.

Eighty-three patients with schizophrenia and 47 healthy controls received positron emission tomography (PET) with 18F-2-deoxyglucose uptake while they were executing the Continuous Performance Test (CPT). The entire cortex was divided into 16 regions of interest in each hemisphere, four in each lobe of the brain, and data from corresponding right and left hemispheric regions were averaged. Data from the schizophrenic patients were subjected to a factor analysis, which revealed five factors that explained 80% of the common variance. According to their content, the factors were identified and labelled 'parietal cortex and motor strip', 'associative areas', 'temporal cortex', 'hypofrontality' (which included midfrontal and occipital areas) and 'frontal cortex'. Hemispheric asymmetry was only confirmed for the temporal cortex. Factor weights obtained in the schizophrenic group were applied to the metabolic data of the healthy controls and factors scales computed. Schizophrenics were significantly more hypofrontal than the controls, with higher values on the 'parietal cortex and motor strip' factor and a trend towards higher values in the temporal cortex. A canonical discriminant analysis confirmed that the 'hypofrontality' and 'parietal cortex and motor strip' factors accurately separated the schizophrenic group from the healthy controls. Hemispheric asymmetry was only confirmed for the temporal lobe. Significantly higher factor scores for the left temporal lobe in schizophrenics than in normals were obtained when calculated for the right and left hemisphere separately. Taken together, our results confirm the importance of hypofrontality as a pattern of cortical metabolic rate and point to the potential importance of parietal and motor strip function in schizophrenia.

Adult↗

Clozapine effects on glucose metabolic rate in striatum and frontal cortex.

Eighteen patients with schizophrenia had cerebral metabolic rates assessed with positron emission tomography during a double-blind, placebo-controlled crossover study of clozapine treatment. Relative metabolic rates were increased in the basal ganglia, especially on the right side. In the frontal lobe, metabolic rates were lowered, more on the left than on the right. The anterior nuclei of the thalamus also showed lower metabolic rates after clozapine. We have previously observed patients with schizophrenia to have low metabolic rates in the basal ganglia and to lack the normal right > left asymmetry; in this study, clozapine normalized striatal activity. In the frontal lobe, asymmetry was normalized, but hypofrontal function was, if anything, exaggerated. This effect in the frontal lobe was not observed with haloperidol in earlier studies. The cortical effects of clozapine may be related to its unique clinical properties and suggest important differences between typical and atypical antipsychotic drugs.

Adult↗

Magnetic resonance and positron emission tomography imaging of the corpus callosum: size, shape and metabolic rate in unipolar depression.

Magnetic resonance imaging (MRI) and positron emission tomography (PET) with fluorodeoxyglucose were used to study the size and shape of the corpus callosum in 20 patients with unipolar depressive disorder and 16 normal controls. An automated algorithm outlined the corpus callosum and divided it into quarters. The anterior and posterior quarters of the corpus callosum were larger in depressed patients than in controls, findings similar to most earlier MRI studies of the corpus callosum in schizophrenics. The patient-normal difference was more marked in females than in males. PET glucose metabolic values were higher in patients with thinner or smaller callosums. The presence of marked sex differences makes future larger studies controlling body size and age important.

Adult↗

Olfactory memory in unmedicated schizophrenics.

Previous studies have indicated that schizophrenic patients have olfactory deficits. The question as to whether olfactory deficits are due to chronic effects of medication has not been addressed. This is the first paper to report that never-medicated schizophrenic patients also have olfactory deficits. Twenty four normal subjects and twenty unmedicated schizophrenic patients were examined with two tests of olfactory function: the University of Pennsylvania Smell Identification Test (UPSIT) and a match-to-sample olfactory memory test. Results indicated that schizophrenics did poorly on both the UPSIT and the olfactory match-to-sample memory test relative to sex and age-matched controls. ANCOVA showed that the deficit in performance on the olfactory match-to-sample test was still present even when the variance due to the UPSIT was taken out of the analysis. Deficits in olfactory identification and olfactory memory are consistent with the concept that schizophrenics have dysfunctional limbic systems.

Blood Glucose↗

Reduced regional brain glucose metabolism assessed by positron emission tomography in electrodermal nonresponder schizophrenics: a pilot study.

This pilot study examined whether electrodermal nonresponder and responder subgroups of schizophrenic patients differ in regional brain metabolism assessed by Positron Emission Tomography during a continuous performance test. In comparison to both normal controls (n = 6) and responder schizophrenics (n = 3), the nonresponder schizophrenics (n = 3) showed about a 20% reduction in metabolic rate across the entire brain. Nonresponder schizophrenics tended to have lower absolute metabolic rates than responders in lateral and medial frontal, thalamic, and hippocampal areas. Nonresponders also had significantly lower relative metabolic rates in medial frontal and hippocampal areas as well as the right amygdala. These data suggest that electrodermal subgroups of schizophrenics differ in both regionally specific brain metabolic processes thought to be involved in electrodermal activity and in generalized brain metabolism.

Adult↗

The cerebral neurobiology of hope and hopelessness.

Hope and hopelessness are useful constructs that have been employed by clinicians in theory making regarding the pathogenesis and course of disease and in the application of various psychological and medical treatments to illness. French (1952) and Frank (1968) viewed hope as a necessary motivating force in influencing an individual to try to overcome inner psychological conflicts and seek to resolve a psychoneurosis. Melges and Bowlby (1969) classified the types of hopelessness in psychopathological processes. Perley et al. (1971), using an objective method for content analysis of small samples of speech (Gottschalk 1974), found that elevated hope scores predicted continuation of psychiatric treatment rather than dropping out. Gottschalk et al. (1967, 1969) found that hope scores derived from verbal samples predicted the duration of survival of patients with terminal cancer receiving irradiation treatment (1969) and predicted relatively favorable outcome in psychotherapy (1967).

Attitude↗

Cortical-striatal-thalamic circuits and brain glucose metabolic activity in 70 unmedicated male schizophrenic patients.

OBJECTIVE: The cortical-striatal-thalamic circuit modulates cognitive processing and thus may be involved in the cognitive dysfunction in schizophrenia. The imaging of metabolic rate in the structures making up this circuit could reveal the correlates of schizophrenia and its main symptoms. METHOD: Seventy male schizophrenic patients underwent [18F]-fluorodeoxyglucose positron emission tomography after a period of at least 4 weeks during which they had not received neuroleptic medication and were compared to 30 age-matched male normal comparison subjects. RESULTS: Analyses revealed decreased metabolism in medial frontal cortex, cingulate gyrus, medial temporal lobe, corpus callosum, and ventral caudate and increased metabolism in the left lateral temporal and occipital cortices in the schizophrenic cohort. Consistent with previous studies, the schizophrenic group had lower hypofrontality scores (ratios of lateral frontal to occipital metabolism) than did comparison subjects. The lateral frontal cortical metabolism of schizophrenic patients did not differ from that of comparison subjects, while occipital cortical metabolism was high, suggesting that lateral hypofrontality is due to abnormalities in occipital rather than lateral frontal activity. Hypofrontality was more prominent in medial than lateral frontal cortex. Brief Psychiatric Rating Scale (BPRS) scores, obtained for each schizophrenic patient on the scan day, were correlated with regional brain glucose metabolic rate. Medial frontal cortical and thalamic activity correlated negatively with total BPRS score and with positive and negative symptom scores. Lateral frontal cortical metabolism and hypofrontality scores did not significantly correlate with negative symptoms. Analyses of variance demonstrated a reduced right greater than left asymmetry in the schizophrenic patients for the lateral cortex as a whole, with simple interactions showing this effect specifically in temporal and frontal cortical regions. CONCLUSIONS: Low metabolic rates were confirmed in medial frontal cortical regions as well as in the basal ganglia, consistent with the importance of the cortical-striatal-thalamic pathways in schizophrenia. Loss of normal lateralization patterns was also observed on an exploratory basis. Correlations with negative symptoms and group differences were more prominent in medial than lateral frontal cortex, suggesting that medial regions may be more important in schizophrenic pathology.

Adolescent↗

Regional glucose metabolic changes after learning a complex visuospatial/motor task: a positron emission tomographic study.

Regional cerebral glucose metabolic rate (GMR) quantified with positron emission tomography (PET) with 18-fluoro-2-deoxyglucose (FDG) was measured twice in 8 young men performing a complex visuospatial/motor task (the computer game Tetris), before and after practice. After 4-8 weeks of daily practice on Tetris, GMR in cortical surface regions decreased despite a more than 7-fold increase in performance. Subjects who improved their Tetris performance the most after practice showed the largest glucose metabolic decreases after practice in several areas. These results suggest that learning may result in decreased use of extraneous or inefficient brain areas. Changes in regional subcortical glucose metabolic rate with practice may reflect changes in cognitive strategy that are a part of the learning process.

Adult↗

Cerebral brain metabolism in adult dyslexic subjects assessed with positron emission tomography during performance of an auditory task.

Ten dyslexic adults (aged 33.5 +/- 7.3 years, nine men, one woman) and 10 age-, sex- and handedness-matched control subjects (aged 33.6 +/- 5.8 years) performed an auditory syllable discrimination task during 18-fluoro-2-deoxyglucose uptake, and then underwent positron emission tomographic scans. A second normal control group performed an analogous visual discrimination task. Dyslexic subjects experienced greater difficulty and made significantly more errors in performing the auditory task. There were no differences in brain metabolic rates in lateral cortical areas (frontal, parietal, temporal, and occipital lobes). A significant difference emerged in the medial temporal lobe, with dyslexic subjects having significantly higher absolute and relative brain metabolism along an anterior-posterior gradient than normal adults. These data support the hypothesis of altered cerebral processing of auditory stimuli in patients with dyslexia.

Adult↗

Frontostriatal disorder of cerebral metabolism in never-medicated schizophrenics.

We scanned 18 patients with schizophrenia who had never received neuroleptic medication and 20 age- and sex-matched controls by positron emission tomography with 18-F-fluorodeoxyglucose (fludeoxyglucose F 18) as a tracer of glucose metabolism. Subjects performed the Continuous Performance Test during 18-F-fluorodeoxyglucose uptake. Scan results were converted to metabolic rates, and computer algorithms were used to identify cortical regions. Previous reports of relative hypofrontality in schizophrenia were confirmed, indicating that this finding is not an artifact of previous treatment. Significantly reduced ratios of inferior and medial frontal regions to occipital cortex were found, together with diminished metabolism in the basal ganglia. This suggests the presence of a combined frontostriatal dysfunction in schizophrenia.

Adult↗

Striatal metabolic rate and clinical response to neuroleptics in schizophrenia.

A low metabolic rate in the caudate nucleus and putamen in schizophrenic patients while they were not receiving medication was found to predict a favorable clinical response to haloperidol. Twenty-five patients (21 men and four women) entered a double-blind crossover trial of haloperidol and placebo; to our knowledge, this is the first such trial with positron emission tomography to be reported. Patients received either placebo or medication for the first 5 weeks, and they received the other treatment for the second 5 weeks. Positron emission tomographic scans were obtained at weeks 5 and 10. Patients with low relative metabolic rates in the caudate nucleus and putamen while they were receiving placebo were more likely to show decreases in their Brief Psychiatric Rating Scale scores with haloperidol treatment than individuals with normal or high metabolic rates. Among responders, haloperidol treatment had a "normalizing" effect on metabolic activity in the striatum, with the metabolic rate while they were receiving haloperidol being higher than that while they were receiving placebo. Nonresponders were more likely to show a worsening of hypofrontality while they were receiving medication and an absence of change in the striatum.

Adult↗