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Biomedical subjects

K F Berman

Publications and source records attributed to K F Berman.

At least 19 recordsLinked to original sources
PubMed1994

The frontal lobes and schizophrenia.

Many patients with schizophrenia show clinical signs of frontal lobe dysfunction, including blunted affect, difficulty with problem solving, and impoverished thinking. The authors present cytoarchitectural, neuropsychological, and functional neuroanatomical evidence of frontal abnormalities from recent studies of frontal dysfunction in schizophrenia. It is suggested that the failure of intracortical connectivity of the prefrontal cortex accounts for both cognitive and psychotic manifestations of this illness.

Brain Mapping↗
PubMed1992

Probes for narcotic receptor mediated phenomena. 18. Epimeric 6 alpha- and 6 beta-iodo-3,14-dihydroxy-17-(cyclopropylmethyl)-4,5 alpha-epoxymorphinans as potential ligands for opioid receptor single photon emission computed tomography: synthesis, evaluation, and radiochemistry of [125I]-6 beta-iodo-3,14-dihydroxy-17-(cyclopropylmethyl)-4,5 alpha-epoxymorphinan.

The epimeric 6 beta- and 6 alpha-iodo-3,14-dihydroxy-17-(cyclopropylmethyl)-4,5 alpha-epoxymorphinans (1, ioxy) and (2, epioxy), respectively, were each synthesized in five steps starting with naltrexone. The configuration of the 6-iodo group of 1 was unequivocally determined to be beta-based on single crystal X-ray analysis of its precursor 3-acetoxy-6 beta-iodo-14-hydroxy-17-(cyclopropylmethyl)-4,5 alpha-epoxymorphinan (10). Both 1 and 2 as well as their corresponding 3-O-acetates 10 and 11 were found to readily cross the blood-brain barrier and completely reverse the analgesic effects of a 10 mg/kg intraperitoneal dose of morphine sulfate as determined by the paw withdrawal latency test. Compounds 1 and 2 were found to bind with high affinity to mu, delta, and kappa receptors in vitro. In general, 1 and 2 exhibited higher affinity for mu and kappa receptors than naltrexone while the 6 beta-iodo epimer 1 (ioxy) was more potent than its epimer 2. In a comparison of the 6 beta-halogen substituent on binding affinity across opioid receptor subtypes, it was generally found that I greater than Br greater than F. On the basis of the results of in vitro and in vivo testing, 1 was selected as a target for radioiodination and evaluation as a potential single photon emission computed tomography imaging agent for opioid receptors. Carrier-free [125I]-1 was synthesized in near quantitative yield by the sequence of reaction of excess 3-acetoxy-6 alpha-[[(trifluoromethyl)sulfonyl]oxy]-14-hydroxy-17- (cyclopropylmethyl)-4,5 alpha-epoxymorphinan (8) with anhydrous Na125I in dry acetonitrile for 90 min at 76 degrees C followed by deacetylation of the product with 1:1 aqueous ammonia/acetonitrile at 25 degrees C. The potential of [125I]-1 as an in vivo imaging agent for opioid receptors is evaluated and discussed.

Animals↗
PubMed1992

Regional cerebral blood flow in monozygotic twins discordant and concordant for schizophrenia.

We addressed several questions regarding hypofunction of the prefrontal cortex ("hypofrontality") in schizophrenia by measuring regional cerebral blood flow during three different cognitive conditions in monozygotic twins who were discordant or concordant for schizophrenia or who were both normal. These questions included the prevalence of hypofrontality, the importance of genetic predisposition, and the role of long-term neuroleptic treatment. Significant differences between affected and unaffected discordant twins were found only during a task linked to the prefrontal cortex, the Wisconsin Card Sorting Test. During this condition, all of the twins with schizophrenia were hypofrontal compared with their unaffected co-twins, suggesting that, if appropriate cognitive conditions and control groups are used, hypofrontality can be demonstrated in the majority of, if not all, patients with schizophrenia. When unaffected co-twins of patients with schizophrenia were compared with twins who were both normal, no differences were observed, suggesting that nongenetic factors are important in the cause of the prefrontal physiologic deficit that appears to characterize schizophrenia. When concordant twins with a high- vs a low-dose lifetime history of neuroleptic treatment were compared, the twin receiving the higher dose was more hyperfrontal in six of eight pairs, suggesting that long-term neuroleptic treatment does not play a major role in hypofrontality.

Adult↗
PubMed1992

Evidence of dysfunction of a prefrontal-limbic network in schizophrenia: a magnetic resonance imaging and regional cerebral blood flow study of discordant monozygotic twins.

OBJECTIVE: The authors previously reported that in monozygotic twins discordant for schizophrenia the affected twin almost invariably had a smaller anterior pes hippocampus, measured with magnetic resonance imaging (MRI), and invariably had less regional cerebral blood flow (rCBF) in the dorsolateral prefrontal cortex during performance of the Wisconsin Card Sorting Test. The present study was an investigation of the relationship between hippocampal pathology and prefrontal hypofunction in the same twin pairs. METHOD: Nine pairs of monozygotic twins discordant for schizophrenia underwent MRI scanning for determination of anterior hippocampal volume and xenon-inhalation rCBF testing for determination of prefrontal physiological activation associated with the Wisconsin Card Sorting Test. RESULTS: The differences within twin pairs on the MRI and rCBF measures were strongly and selectively correlated. Specifically, the more an affected twin differed from the unaffected twin in left hippocampal volume, the more they differed in prefrontal physiological activation during the Wisconsin Card Sorting Test. In the affected twins as a group, prefrontal activation was strongly related to both left and right hippocampal volume. These relationships were not found in the group of unaffected twins. CONCLUSIONS: This finding is consistent with the notion that schizophrenia involves pathology of and dysfunction within a widely distributed neocortical-limbic neural network that has been implicated in, among other activities, the performance of cognitive tasks requiring working memory.

Adult↗
PubMed1992

Neurologic outcome of patients with dorsolateral prefrontal leukotomy.

Few controlled studies of neurologic function in frontal leukotomy patients have been done. The authors compared neurologic examinations of patients who had bilateral leukotomies with those of psychiatric control subjects matched for age, diagnosis, and duration of illness. Cranial nerve dysfunction, abnormal involuntary movements, and primitive reflexes were common. No significant differences between the two patient groups were found. The leukotomized patients were less irritable than control subjects and had statistically higher seizure and death rates. Neurologic abnormalities are, thus, common in elderly chronic psychiatric patients. Surprisingly, patients with bilateral prefrontal leukotomy do not differ from well-matched psychiatric controls on most clinical tests of neurologic function.

Aged↗
PubMed1992

A comparison of xenon-133 and xenon-127 for the determination of regional cerebral blood flow measured by dynamic SPECT.

Phantom studies and cerebral blood flow (CBF) measurements in 11 normal subjects at rest were performed by single photon emission tomography (SPECT) with Xe-133 (16 mm full-width at half-maximum [FWHM] collimation) and Xe-127 (16 mm, 12 mm, and 9 mm FWHM collimation). The phantom results clearly illustrated the feasibility of Xe-127 studies and the advantage of Xe-127 over Xe-133 for equivalent patient dose exposures. CBF values obtained with Xe-127 were comparable to those of Xe-133 for the 16 mm collimator, although higher flow values were found with the better resolution, probably because of reduced partial volume effects. The correlations between the various groups of examinations were high, except for the Xe-133 and Xe-127 16 mm collimator groups. Xe-127 allows a considerable increase in the resolution of the images, while exposing the patient to a lower radiation dose. Potential limitations because of higher energy penetrating photons from Xe-127 were not observed in this specially shielded equipment.

Adolescent↗
PubMed1991

The distribution of cerebral muscarinic acetylcholine receptors in vivo in patients with dementia. A controlled study with 123IQNB and single photon emission computed tomography.

A high-affinity muscarinic receptor antagonist, 123IQNB (3-quinuclidinyl-4-iodobenzilate labeled with iodine 123), was used with single photon emission computed tomography to image muscarinic acetylcholine receptors in 14 patients with dementia and in 11 healthy controls. High-resolution single photon emission computed tomographic scanning was performed 21 hours after the intravenous administration of approximately 5 mCi of IQNB. In normal subjects, the images of retained ligand showed a consistent regional pattern that correlated with postmortem studies of the relative distribution of muscarinic receptors in the normal human brain, having high radioactivity counts in the basal ganglia, occipital cortex, and insular cortex, low counts in the thalamus, and virtually no counts in the cerebellum. Eight of 12 patients with a clinical diagnosis of Alzheimer's disease had obvious focal cortical defects in either frontal or posterior temporal cortex. Both patients with a clinical diagnosis of Pick's disease had obvious frontal and anterior temporal defects. A region of interest statistical analysis of relative regional activity revealed a significant reduction bilaterally in the posterior temporal cortex of the patients with Alzheimer's disease compared with controls. This study demonstrates the practicability of acetylcholine receptor imaging with 123IQNB and single photon emission computed tomography. The data suggest that focal abnormalities in muscarinic binding in vivo may characterize some patients with Alzheimer's disease and Pick's disease, but further studies are needed to address questions about partial volume artifacts and receptor quantification.

Adult↗
PubMed1991

The effect of amphetamine on regional cerebral blood flow during cognitive activation in schizophrenia.

To explore the role of monoamines on cerebral function during specific prefrontal cognitive activation, we conducted a double-blind placebo-controlled crossover study of the effects of 0.25 mg/kg oral dextroamphetamine on regional cerebral blood flow (rCBF) as determined by 133Xe dynamic single-photon emission-computed tomography (SPECT) during performance of the Wisconsin Card Sorting Test (WCST) and a sensorimotor control task. Ten patients with chronic schizophrenia who had been stabilized for at least 6 weeks on 0.4 mg/kg haloperidol participated. Amphetamine produced a modest, nonsignificant, task-independent, global reduction in rCBF. However, the effect of amphetamine on task-dependent activation of rCBF (i.e., WCST minus control task) was striking. Whereas on placebo no significant activation of rCBF was seen during the WCST compared with the control task, on amphetamine significant activation of the left dorsolateral prefrontal cortex (DLPFC) occurred (p = 0.0006). Both the mean number of correct responses and the mean conceptual level increased (p less than 0.05) with amphetamine relative to placebo. In addition, with amphetamine, but not with placebo, a significant correlation (p = -0.71; p less than 0.05) emerged between activation of DLPFC rCBF and performance of the WCST task. These findings are consistent with animal models in which mesocortical catecholaminergic activity modulates and enhances the signal-to-noise ratio of evoked cortical activity.

Adult↗
PubMed1990

Regional cerebral blood flow and cognitive function in Huntington's disease and schizophrenia. A comparison of patients matched for performance on a prefrontal-type task.

Matching patients with etiologically distinct but clinically overlapping cognitive disorders on performance of a regionally specific neuropsychological task is a novel and potentially powerful approach to highlighting differences in the pathophysiological mechanisms of impaired cognition. We used this strategy to compare patients with Huntington's disease (HD) and schizophrenia (SC), disorders that share similarities in cognitive impairment. Patients were matched on the basis of performance on the Wisconsin Card Sorting test of "prefrontal" function, after which neuropsychological test data and regional cerebral blood flow data were determined while patients who performed the Wisconsin Card Sorting test were examined. Patients with HD performed worse on visuospatial tasks and recall memory than did patients with SC, although Wechsler Adult Intelligence Scales-Revised IQ and Wechsler Memory Scale memory quotients were equivalent. These differences could not be attributed to differences on the index task, the Wisconsin Card Sorting Test. Patients with HD and SC exhibited a double dissociation in regional cerebral blood flow. The patients with SC had relatively low frontal and high parietal flows, while patients with HD exhibited the reverse of this pattern. Thus, the regional cerebral blood flow and neuropsychological findings in this study appeared to demonstrate that the single final common cognitive impairment of executive function in HD and SC is associated with two markedly dissimilar pathophysiological states.

Adult↗
PubMed1990

Lateralisation of cortical function during cognitive tasks: regional cerebral blood flow studies of normal individuals and patients with schizophrenia.

To assess cognitively-related regional asymmetries of brain function, regional cerebral blood flow (rCBF) was determined by the xenon inhalation method while normal subjects performed 10 different tasks and also while they were at rest. In addition to healthy subjects, patients with schizophrenia were also studied. A total of 447 rCBF studies were carried out during the following conditions: the Wisconsin Card Sort Test, a numbers matching test, a symbols matching test, Raven's Progressive Matrices, an auditory discrimination test, an auditory control task, two versions of a visual continuous performance task, line orientation, semantic classification, and resting. On the whole, those tasks that seem to require or allow for internal verbalisation resulted in the greatest activation of the left hemisphere compared with the right; right hemisphere activation predominated only in the two tasks primarily involving attention and vigilance. Furthermore, a consistent regional topography of normal cerebral functional laterality was seen: under most conditions left prefrontal cortical activity exceeded that of right prefrontal cortex; during all non-auditory tasks, parieto-occipital cortical activity had an opposite pattern-greater right than left. During most conditions the schizophrenic patients displayed the same pattern. While several cognitively specific between-group differences were found, no single cortical region was consistently implicated and no specific direction of abnormal asymmetry predominated. These data suggest that there is a predominant task-independent functional pattern of cortical activity emphasising relatively greater left anterior and right posterior activation. This pattern may reflect the verbal and attentional primacy of these areas, respectively.

Adult↗
PubMed1989

Anxiety and cerebral blood flow during behavioral challenge. Dissociation of central from peripheral and subjective measures.

To investigate the relationship between anxiety and regional cerebral blood flow, we administered behavioral challenges to 10 patients with obsessive-compulsive disorder while measuring regional cerebral blood flow with the xenon 133 inhalation technique. Each patient was studied under three conditions: relaxation, imaginal flooding, and in vivo (actual) exposure to the phobic stimulus. Subjective anxiety, obsessive-compulsive ratings, and autonomic measures (heart rate, blood pressure) increased significantly, but respiratory rate and PCO2 did not change across the three conditions. Regional cerebral blood flow increased slightly (in the temporal region) during imaginal flooding, but decreased markedly in several cortical regions during in vivo exposure, when anxiety was highest by subjective and peripheral autonomic measures. These results demonstrate that intense anxiety can be associated with decreased rather than increased cortical perfusion and that ostensibly related states of anxiety (eg, anticipatory and obsessional anxiety) may be associated with opposite effects on regional cerebral blood flow.

Adult↗
PubMed1989

Behavioral and electroencephalographic effects of the adenosine1 agonist, L-PIA.

The effects of N6-(L-2-phenylisopropyl)-adenosine (L-PIA), an A1 agonist, were measured on both spontaneous locomotor activity and electroencephalographic (EEG) measures of sleep in rats. L-PIA strongly inhibited motor activity at 100 micrograms/kg intraperitoneally (IP), a dose which had no statistically significant effects on EEG-defined sleep. A higher dose of L-PIA (200 micrograms/kg) increased the latency to sleep initiation and inhibited later REM sleep. These results demonstrate that L-PIA can produce a state of apparent behavioral quiescence in the presence of EEG-defined arousal.

Adenosine↗
PubMed1989

The effect of apomorphine on regional cerebral blood flow in schizophrenia.

A double-blind, placebo-controlled crossover study of the effects of apomorphine on regional cerebral blood flow (rCBF) during a prefrontal cortex activation task was undertaken to explore the role of dopamine on cortical function. The subjects were eight drug-free, chronically psychotic patients; six patients had schizophrenia. In each, apomorphine increased the relative prefrontal flow. The results suggest that enhanced prefrontal dopamine activity may reverse deficits in prefrontal cortex metabolism in schizophrenia.

Adult↗
PubMed1988

Met5-enkephalin-Arg6-Gly7-Leu8 immunoreactivity in rat and human cerebrospinal fluid: influence of neuroleptic drugs and electroconvulsive shock.

Met5-Enkephalin-Arg6-Gly7-Leu8 immunoreactivity was quantitated in both rat and human cerebrospinal fluid (CSF) by radioimmunoassay with a carboxy-terminal directed antiserum. The immunoreactivity in CSF was chromatographically characterized in both species and was found to consist almost exclusively of high molecular weight forms. In human CSF there was approximately 300 fmol/ml and in the rat 1,500 fmol/ml of immunoreactivity. The possibility of a rostro-caudal gradient was examined in the human by analyzing the first and the twenty-fifth ml of CSF drawn during a lumbar puncture: none was found. The immunoreactivity was fairly stable; no loss of immunoreactivity was observed after 24 h of incubation of rat CSF at 37 degrees C. Electroconvulsive shock (ECS) produced a significant elevation in CSF content but only after a course of chronic administration; a single acute ECS produced no increase. Human subjects with schizophrenia who were being treated with antipsychotic drugs had elevated levels of immunoreactivity in comparison to non-mediated patients and normals. The high levels of this immunoreactivity in CSF, its stability and the evidence that the content can change with physiological and pharmacological manipulation indicate that Met5-Enkephalin-Arg6-Gly7-Leu8 immunoreactivity can serve as a new and useful CSF marker for investigating the CNS enkephalin system in neurological or psychiatric disorders.

Animals↗