Images in neuroscience. Neuroimaging, II. Regional cerebral blood flow with H2(15)O.
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Brain↗
Biomedical subjects
H H Holcomb
Publications and source records attributed to H H Holcomb.
Images in neuroscience. Cortex, VI. Auditory cortical function.
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Acoustic Stimulation↗
Glutamate pharmacology and the treatment of schizophrenia: current status and future directions.
Glutamate-containing neuronal terminals are ubiquitous in the central nervous system and their functional importance in mental activity is considerable. Therefore, the involvement of this neurotransmitter in the pathology of schizophrenia is being studied. Biochemical evidence has suggested that glutamatergic transmission may be regionally reduced in schizophrenia, although this evidence has never been completely consistent nor fully replicable. More striking has been the behavioral effects in humans of the antiglutamatergic drugs phencyclidine (PCP) and its congener ketamine. By historical report, PCP produces a 'schizophrenia-like' psychosis in normal humans and aggravates the psychosis in schizophrenics. More recently, ketamine has been shown to produce a mild psychotomimetic effect in normal volunteers, which has some schizophrenia-like features. We have studied the effects of ketamine in schizophrenic patients. Here, ketamine intensified each patient's specific underlying psychosis, an effect not blocked by haloperidol. Moreover, ketamine selectively increased cerebral blood flow (CBF) in the anterior cingulate cortex and reduced CBF in hippocampus and lingual gyrus. These data may be pertinent to the subject's psychosis exacerbation, especially because both cingulate and hippocampus have been previously implicated in schizophrenic psychosis. In addition, ketamine produced a distinctive dynamic time-course of regional CBF changes in different anatomic regions, with immediate (5-10 min) changes in cingulate, but somewhat more delayed changes (20-40 min) in the thalamus and cerebellum. Our immediate early gene (IEG) time-course data with c-fos and zif268 in rats following PCP suggest that a single dose of this antiglutamatergic compound can have an effect in some brain areas which lasts beyond 48 h, an effect which is distinct by IEG and by region. Together, these data suggest that glutamate-mediated neurotransmission has a strong influence in schizophrenia, although the specifics of this involvement have yet to be articulated.
Autoradiography↗
Increased temporal lobe glucose use in chronic schizophrenic patients.
Temporal lobe glucose metabolic rate was assessed in 21 off-medication patients with schizophrenia and 19 normal controls by positron emission tomography with 18F-deoxyglucose. Patients with schizophrenia had significantly greater metabolic activity in the left than the right anterior temporal lobe, and the extent of this lateralization was in proportion to the severity of psychopathology.
Adult↗
Local cerebral glucose abnormalities in mild closed head injured patients with cognitive impairments.
Mild-moderate closed head injury (CHI) can be followed by neuropsychological impairments in recent memory and attention, despite the absence of discernible structural abnormalities in a significant number of patients. To determine whether CHI may result in cerebral glucose metabolic abnormalities, we used fluorodeoxyglucose (FDG) technique with PET imaging to measure local cerebral metabolic rates for glucose (LCMRGlu) in three CHI patients and three matched normal controls. The CHI patients were between 3-12 months post-injury. All had deficits in attention and recent memory shown by neuropsychological testing. CT, MRI, EEG and drug screens were negative at the time of PET scanning. Subjects were engaged in a vigilance task throughout the initial 30 min following FDG administration. Group comparisons were made using t tests. There were no significant group differences found in global glucose metabolic rate. Nevertheless, the CHI group exhibited significantly decreased LCMRGLu in medial temporal, posterior temporal, and posterior frontal cortices, as well as in the left caudate nucleus. LCMRGlu was significantly increased, relative to controls, in anterior temporal and anterior frontal cortices. These results suggest that CHI patients can have regional glucose metabolic abnormalities, indicative of altered neuronal function, despite the absence of discernible anatomic abnormalities.
Brain↗
Effect of 5-hydroxytryptophan on H-reflex recovery curves in normal subjects and patients with affective disorders.
The effect of the serotonin precursor DL-5-hydroxytryptophan (5-HTP) on the Hoffmann reflex recovery curve (HRRC) was studied in normal subjects and patients with affective illness. 5-HTP significantly decreased the HRRC in normal controls and in depressed and manic patients receiving treatment with lithium or antidepressants. 5-HTP increased the HRRC in unmedicated depressed and manic patients. These results provide further evidence for a serotonergic abnormality in the affective disorders.
5-Hydroxytryptophan↗
The effect of neuroleptics on dysfunction in a prefrontal substrate of sustained attention in schizophrenia.
Regional brain metabolism was measured in patients with schizophrenia during the performance of auditory discrimination to evaluate the effect of neuroleptic medication on the middle prefrontal cortex, an area that appears to be an important biological determinant of the sustained attention required of subjects in this task. While unmedicated patients with schizophrenia have lower than "normal" metabolic rates in this cortical area that are unrelated to performance, patients receiving neuroleptics appear to have this metabolic deficit attenuated with higher metabolism in this area associated with greater accuracy of performance. This change occurs in the context of differential neuroleptic effects on the cortical regions of the frontal cortex, increased metabolism in the basal ganglia, thalamus and temporal lobes, and no apparent effect in the parietal and occipital cortices. The findings suggest that only part of the abnormality in the prefrontal cortex determination of sustained attention in schizophrenia is sensitive to neuroleptic treatment.
Adult↗
Dysfunction in a prefrontal substrate of sustained attention in schizophrenia.
Regional brain metabolism was measured in normal subjects and patients with schizophrenia while they performed an auditory discrimination task designed to emphasize sustained attention. A direct relationship was found in the normal subjects between metabolic rate in the middle prefrontal cortex and accuracy of performance. The metabolic rate in the middle prefrontal cortex of patients with schizophrenia, even those who performed as well as normals, was found to be significantly lower than normal and unrelated to performance. The findings point to a role of the mid-prefrontal region in sustained attention and to dysfunction of this region in schizophrenia.
Adult↗
Positron emission tomography studies of basal ganglia and somatosensory cortex neuroleptic drug effects: differences between normal controls and schizophrenic patients.
Glucose metabolic rate in the basal ganglia, thalamus, and somatosensory cortex was examined in eight patients with schizophrenia before and after receiving neuroleptic medication. Basal ganglia metabolic rates were increased with medication: more on the right than on the left and more in putamen than caudate. The cortical anteroposterior ratio, an index of relative hypofrontality, was not affected by neuroleptics. The brain areas that were found to be altered by neuroleptics were selected for comparison between off-medication schizophrenics and controls. Metabolic rates in the basal ganglia tended to be low in patients with schizophrenia in comparison to 24 age- and sex-matched controls.
Adolescent↗
Glucose utilization in the temporal cortex of affectively ill patients: positron emission tomography.
As temporal lobe dysfunction has been postulated in the affective disorders, the authors investigated glucose utilization in the temporal lobes of 13 affectively ill patients in comparison with 18 normal volunteer controls and 17 previously reported schizophrenic patients, following injections of fluorine 18-2-deoxy-D-glucose (FDG) during somatosensory stimulation to the right forearm. Using a boundary-finding algorithm to outline each temporal lobe, maximum glucose use relative to maximums elsewhere in the same positron emission tomography (PET) slice were calculated. In a small group of moderately to severely depressed patients, this relative measure was significantly reduced in the right (with a similar trend in the left) temporal lobe compared to normal volunteers and the other comparison groups. The lack of a significant increase in glucose utilization, measured either as a maximum or in relation to other areas in the PET scan slice, suggests that a temporal lobe activation or a seizure-like process is not generally occurring during active depressive phases of the illness.
Affective Disorders, Psychotic↗
Topographic differences between normals and schizophrenics: the N120 evoked potential component.
Topographic differences in evoked potentials were measured in 20 off-medication chronic schizophrenics and 24 normal controls. Four intensities of brief electrical shocks were administered to the subject's right forearm in a random order at 1-second intervals. Evoked potentials (EPs) were recorded from the scalp over the left hemisphere. The EP data from 16 left hemisphere leads were used to generate EP maps of brain response for individual subjects. The maps were normalized by z transformation. Group mean maps of EP activity and unpaired t tests were then computed. Normals showed strongly localized activity in the pre- and postcentral gyri, with increasing intensity resulting in the attenuation of parietal response. Schizophrenics showed more diffuse EP activity which did not vary with intensity. Significant differences between normals and schizophrenics were found for all four intensities in posterior frontal and anterior parietal cortex. This is consistent with the findings of small EPs reported by others in the somatosensory, visual and auditory modalities.
Adult↗
Alterations of local cerebral glucose utilization during chronic dehydration in rats.
The quantitative autoradiographic deoxyglucose method was used to study changes in local cerebral glucose utilization in conscious dehydrated rats. Animals were either given saline to drink or were deprived of water for 5 days. Saline ingestion did not alter the rates of glucose metabolism in any brain region when compared to the rates of glucose metabolism in animals which had free access to water. Glucose utilization was increased by 140%, however, in the pituitary neural lobe. Water deprivation produced both increases and decreases in glucose metabolism, depending on the particular structure. In 20 of 44 brain structures analyzed, there were significant decreases from -18 to -34% in glucose utilization. Four forebrain structures, the subfornical organ, septal triangular nucleus, and hypothalamic paraventricular and supraoptic nuclei, had increases in glucose utilization of 30-73%. The rate of glucose utilization in the pituitary neural lobe was increased by 367% in water-deprived rats. The results demonstrate that metabolic activity is stimulated in some, but not all, of the structures participating in fluid regulation during an intense thirst challenge. Many brain regions have depressed metabolism in chronic severe dehydration.
Animals↗
Positron emission tomography in schizophrenic patients with and without neuroleptic medication.
Positron emission tomography using [18F]2-fluoro-2-deoxy-D-glucose was performed in nine chronic schizophrenic patients both when medication-free and when medicated with neuroleptics. Total brain cortex, temporal cortex, and basal ganglia glucose use was significantly increased with medication; however, there was no change in anterior/posterior metabolic gradients.
Adolescent↗
Clinical correlates of decreased anteroposterior metabolic gradients in positron emission tomography (PET) of schizophrenic patients.
The finding in schizophrenic patients of a reversal of the normal frontal to posterior pattern of brain metabolic activity with positron emission tomography (PET) is of interest, but its relevance to psychopathology is unknown. Using PET, the authors studied 21 patients with chronic schizophrenia and 21 age- and sex-matched control subjects. Although eight of the 21 patients and only one of the control subjects showed a relatively lower anteroposterior metabolic gradient, no clinical correlates of this finding were noted. In addition, cerebral atrophy, as determined by CAT scan, was not associated with this aberrant metabolic pattern.
Adolescent↗
Anteroposterior gradients in cerebral glucose use in schizophrenia and affective disorders.
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.
Adult↗
Correlational methods for determining regional coupling of cerebral glucose metabolism: a pilot study.
The current study presents an alternate method of analyzing PET data by means of a correlational approach. Correlational or coupling patterns of regional cerebral glucose metabolism were found for normal subjects and patients with schizophrenia under electric shock stimulation. At two levels (91 mm and 78 mm) significant differences were found between the coupling patterns of normal subjects and patients with schizophrenia. For the normals, the obtained correlational maps were consistent with the sensory input. However, such patterns were not found for the patients with schizophrenia. Therefore it is suggested that the outlined analysis procedure may complement the standard approach of comparing the mean metabolic rates.
Adolescent↗
Elevated glucose utilization in subfornical organ and pituitary neural lobe of the Brattleboro rat.
Homozygous Brattleboro rats have a genetic inability to synthesize vasopressin and therefore manifest the signs and symptoms of diabetes insipidus. Measurement of local cerebral glucose utilization in these rats has revealed increases specifically localized to the subfornical organ and pituitary neural lobe. Vasopressin replacement reverses the increased glucose utilization only in the subfornical organ. The results suggest that vasopressin regulates the rate of glucose metabolism in the subfornical organ.
Animals↗
Cerebral metabolic consequences of electrical cutaneous stimulation in normal individuals.
Local cerebral uptake of deoxyglucose labeled with fluorine (FDG) was measured by positron emission tomography in 21 normal adult controls. Seven subjects received FDG while resting in a dark room and fourteen while receiving unpleasant electrical stimulation of their right forearm in a dark room. All subjects showed greater glucose use in the anterior than in the posterior cerebral cortex. Electrical stimulation of the right forearm was associated with greater left than right glucose use in the region of the postcentral, but not precentral gyrus. The antero-posterior gradient in glucose use was increased at the level of the inferior frontal gyrus by the electrical stimulation. The data are consistent with the hyperfrontal pattern reported for regional cerebral blood flow and suggest that glucose use gradients across large brain areas are sensitive to sensory stimulation.
Adolescent↗