Brief report: attention performance in autism and regional brain metabolic rate assessed by positron emission tomography.
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Biomedical subjects
Publications and source records attributed to M S Buchsbaum.
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EEGs were recorded from 32 channels in 30 normal males, ages 16-22. Delta activity decreased throughout this age range. This decrease was greatest in the left frontal and temporal regions; no occipital lead showed this pattern. Relative EEG amplitude analysis, based on normalized maps, revealed decreases with age across alpha, delta, and theta bands with beta staying the same or increasing. These changes were greatest in the left temporal and left frontal regions. Taken together, these findings suggest that these cortical areas are maturing in the second decade of life. Both delta and theta showed significantly greater decreases with age in the left parietal region than in the right.
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OBJECTIVE: Sleep deprivation is a rapid, nonpharmacologic antidepressant intervention that is effective for a subset of depressed patients. The objective of this study was to identify which brain structures' activity differentiates responders from nonresponders and to study how metabolism in these brain regions changes with mood. METHOD: Regional cerebral glucose metabolism was assessed by positron emission tomography (PET) with [18F]deoxyglucose (FDG) before and after total sleep deprivation in 15 unmedicated awake patients with unipolar major depression and 15 normal control subjects, who did the continuous performance test during FDG uptake. RESULTS: After sleep deprivation, four patients showed a 40% or more improvement on the Hamilton Rating Scale for Depression. Before sleep deprivation the depressed responders had a significantly higher cingulate cortex metabolic rate than the depressed nonresponders, and this normalized after sleep deprivation. The normal control subjects and nonresponding depressed patients showed no change in cingulate metabolic rate after sleep deprivation. CONCLUSIONS: Overactivation of the limbic system as assessed by PET scans may characterize a subset of depressed patients. Normalization of activity with sleep deprivation is associated with a decrease in depression.
Sixteen high-functioning adults with a history of childhood autism and 26 normal control subjects underwent [18F]fluoro-2-deoxyglucose positron-emission tomography to assess regional cerebral glucose metabolic rate (GMR). Autistic patients had a left > right anterior rectal gyrus asymmetry, as opposed to the normal right > left asymmetry in that region. Patients also showed low GMR in the left posterior putamen and high GMR in the right posterior calcarine cortex. Brain regions with GMR > 3 SD from the normal mean were more prevalent in patients than in control subjects. This variable pattern of abnormal activity is consistent with heterogeneous neurophysiological etiology; group differences in striatum and cortex may represent a final common pathway.
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Twelve patients with schizophrenia received positron emission tomography scans with 18F-deoxyglucose before and after 4 to 6 weeks of treatment with clozapine or thiothixene. Both stereotaxic and magnetic resonance image template methods were used to position regions of interest for metabolic rate analysis. Clozapine increased and thiothixene decreased metabolic rates in the basal ganglia; these effects were most marked on the right side. Within the basal ganglia, a superior to inferior gradient in drug effect was found for thiothixene but not clozapine. This gradient resembled in some respects observations on regional differences in D2 receptors in human autoradiography. Baseline metabolic rates also predicted clinical medication response, with right inferior caudate metabolic rates differentiating clozapine and thiothixene responders. Larger sample studies are needed to replicate and extend these initial findings.
Positron emission tomography (PET) measurements of cerebral glucose use were made in 18 patients with generalized anxiety disorder (GAD) during a passive viewing task off medication, and an active vigilance viewing task before and after medication or placebo treatment. In the passive viewing task, patients with GAD were compared with 15 normal controls. A significant difference in pattern of absolute brain metabolism was found. Patients showed lower absolute metabolic rates in basal ganglia and white matter. Relative metabolism was increased in the left inferior area 17 in the occipital lobe, right posterior temporal lobe, and the right precentral frontal gyrus. Significant left-right asymmetry of the parahippocampal gyri was not found in patients with GAD. An active vigilance task resulted in activation of relative basal ganglia metabolism in patients. Benzodiazepine therapy resulted in decreases in absolute metabolic rates for cortical surface, limbic system, and basal ganglia and was not associated with normalization of patterns of glucose metabolism. Change in anxiety scores was significantly correlated with change in limbic system and basal ganglia for the placebo group. The normal-anxious difference in the basal ganglia and the change seen in this region after benzodiazepine treatment are suggestive of a role in anxiety for this structure.
Ten normal male subjects were injected with D-[18F]deoxyglucose during REM sleep, and 32-45 min later they were aroused and reported their dreams as well as free associations to these dreams. Nonparametric correlations between the anxiety scores derived from the typescripts of these verbal reports by the Gottschalk-Gleser content analysis method and localized cerebral glucose metabolic rates obtained from PET scans revealed significant positive correlations in lateral parietal and medial frontal cortex and negative correlations in adjacent white matter.
Positron emission tomography with fludeoxyglucose F 18 was used to assess cortical metabolic rate during an olfactory memory task in six patients with dementia of the Alzheimer type. Metabolic activity was compared with that of both age-matched controls performing the olfactory task and controls resting with their eyes closed. Patients had lower metabolic rates in the anterior portion of the medial-temporal cortex than did controls, and the difference was greatest between patients and the controls performing the memory task. This region is known to receive a large olfactory input and has been implicated in the encoding of human memory. Normal controls resting with their eyes closed had significantly lower metabolic rates in this area when compared with normal controls performing the task. Our results are consistent with those of earlier reports of temporal lobe decreases in metabolic rate and extend them through the examination of areas salient to the behavioral loss.
Neuropsychological measures of memory and cognition and topographical quantitative EEG were obtained on 35 healthy, non-demented, right-handed, elderly subjects aged 60-81. All were free of medications which impair cognition. They were divided into a left temporal slow abnormality group (n = 9) and a control group (n = 26) on the basis of topographically normalized measures of both delta and theta activity for the left temporal lead T3. The group with left temporal slow activity was significantly deficient on measures of memory savings and memory losses derived from the Logical Memory (Story Recall) Test in the Wechsler Memory Scale--Revised. There were no significant differences between these two groups on the non-memory cognitive tasks. This predominant verbal recent memory deficit profile is reasonably similar to the neuropsychological deficit profile of very mildly demented Alzheimer patients. Because left temporal slow EEG activity is also the predominant EEG abnormality in mild Alzheimer patients, a prospective study should be done to determine if this abnormality in non-demented elderly subjects is most often a preclinical sign of Alzheimer's disease.
The authors examined correlations between anxiety and hostility levels experienced during wakefulness, rapid eye movement (REM) dreaming, nonrapid eye movement (NREM) mentation (as assessed by the Gottschalk-Gleser Content Analysis Scales), and cerebral glucose metabolism as measured by positron-emission tomography (PET) in 30 normal volunteers. Different cerebral areas showed significant correlations for anxiety and six anxiety subscales, hostility outward, hostility inward, and ambivalent hostility, as assessed by the patterns of significant positive or negative correlations found with the activation of these emotions. Significant correlations occurred more often in waking and REM dreaming subjects than NREM subjects and were more common in the frontal, parietal, and temporal lobes than in the occipital lobe. Correlations tended to be positive for waking subjects and negative for REM subjects.
Multiple studies have demonstrated prefrontal dysfunction among schizophrenics. The prefrontal cortex does not function in isolation, but instead relies on extensive connections with other brain areas. Functional relationships between cortical areas were assessed by calculating the coherences between different scalp electroencephalogram (EEG) signals recorded from 13 unmedicated male patients with schizophrenia and 9 normal male subjects. Alpha-band coherences linked to prefrontal areas in schizophrenic patients were about the same as those of normal controls when subjects were cognitively "at rest," but they were reduced for certain electrode pairs in the former group when performing the degraded-stimulus continuous performance test. Most of these findings were not accounted for by changes in alpha power, suggesting that "cortical circuits" extending beyond prefrontal areas may be disrupted in schizophrenia.
This study is the first report on the effects of total sleep deprivation (about 32 h) on regional cerebral glucose metabolism during wakefulness in man, using positron emission tomography (PET) with F-18 deoxyglucose (FDG). Sleep deprivation leads to a significant reorganization of regional cerebral metabolic activity, with relative decreases in the temporal lobes and increases in visual cortex. Absolute glucose metabolic measurements indicate a decrease in thalamus, basal ganglia, white matter, and cerebellum. No overall decrease in whole brain metabolism was noted after sleep deprivation. As expected, sleep deprivation significantly reduced visual vigilance as assessed by the continuous performance test and this decrease was correlated significantly with reduced metabolic rate in thalamic, basal ganglia, and limbic regions.
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Women with bulimia often present with symptoms of depression in addition to bingeing and purging behavior. Brain metabolism in eight women with bulimia nervosa was compared to that in eight women with major affective disorder and eight normal women, using positron emission tomography and 18-fluoro-2-deoxyglucose. Normal women have higher right than left cortical metabolic rates and active basal ganglia. Bulimics lost the normal right activation in some areas, but maintained basal ganglia activity. Depressives retained right hemisphere activation, but had decreased metabolism in basal ganglia. This suggests that although women with bulimia frequently present with symptoms of depression, the pathophysiologic changes associated with bulimia differ from major effective disorder.
Resting 32-channel topographical measures of EEG slow activity were compared in 12 elderly controls and 12 patients with senile dementia of the Alzheimer type. The patients had higher amplitude delta and theta than controls, especially in the left temporal regions. This greater amount of low frequency EEG activity in the left temporal area is consistent with recent EEG, neuropsychological assessment, and positron emission tomography findings in SDAT patients. Five patients with mild-to-moderate dementia (as determined by the Folstein Mini-Mental State scale) primarily exhibited focal, abnormal slow activity in the left temporal regions. Seven patients with severe dementia exhibited increased slow activity across the head, which was still most abnormal in the left temporal regions.
This special issue of the Schizophrenia Bulletin focuses on three brain areas hypothesized to play a role in the etiology of schizophrenia--the frontal lobes, the basal ganglia, and the temporal lobes. Contributors to the issue review evidence from brain-imaging, post-mortem, and psychopharmacological studies that support the involvement of each of these important brain areas in schizophrenia. It is concluded that theories emphasizing cortical/subcortical interconnections rather than a single brain area provide the greatest challenge, and also the greatest promise, to schizophrenia researchers.