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Biomedical subjects

K F Berman

Publications and source records attributed to K F Berman.

At least 37 records · Page 2Linked to original sources
PubMed1996

Isolating the mnemonic component in spatial delayed response: a controlled PET 15O-labeled water regional cerebral blood flow study in normal humans.

In this study we attempted to elucidate the neural network involved in maintaining spatial information over short delays by means of the PET 15O-labeled water method for measuring regional cerebral blood flow. To isolate the mnemonic component of delayed response processing we designed a control task isomorphic to the experimental task (in which the subject remembered the location of four targets in an array over a 7 s delay) and controlled for spatial encoding. Fourteen normal subjects participated in the study. Regional cerebral blood flow (rCBF) data were analyzed using statistical parametric mapping, a data-driven approach which canvasses the whole brain for significantly activated pixels in the experimental vis-à-vis the control task, and a hypothesis driven region of interest approach involving comparisons of control and experimental conditions using normalized rCBF data. We found convergent evidence for a spatially distinct but functionally related network in which dorsolateral prefrontal cortex and extrastriate occipital cortex were activated by the experimental task vis-à-vis the control task, as well as evidence for superior parietal and supplementary motor area cortical activation. These findings suggest that anterior components of the network may be involved in mnemonic rehearsal functions, while posterior components may store critical perceptual attributes of the memoranda.

Adult↗
PubMed1996

Cognitive activation during PET: a case study of monozygotic twins discordant for closed head injury.

Using positron emission tomography (PET), we studied physiological changes in a patient with frontal lobe damage resulting from closed head injury by assessing his regional cerebral blood flow (rCBF) pattern relative to that of his uninjured monozygotic (MZ) cotwin and against normal variability between cotwins in 10 comparably-aged, uninjured MZ twin pairs. rCBF was measured during the Wisconsin Card Sorting Test (WCST) and a sensorimotor control task. Differences between the index twins in rCBF activation (WCST-control) in regions determined on coplanar MRIs were compared to within-pair differences in the control group using the Z-statistic. Activation differences between the index twins extending beyond normal variability were found in two regions-relative to his uninjured cotwin, the injured twin showed less activation in the inferior portion of the left inferior frontal gyrus while showing greater activation in the left hippocampus (P < 0.04). This pattern contrasts with that of normal subjects during WCST performance of augmented rCBF in the prefrontal cortex and not in the hippocampus. These rCBF differences appear to reflect the utilization of different neural systems when performing a frontal-lobe task. The use of the hippocampus by the injured twin might reflect an attempt to compensate for compromised frontal lobe functioning.

Adolescent↗
PubMed1996

Functional mapping of human sensorimotor cortex with 3D BOLD fMRI correlates highly with H2(15)O PET rCBF.

Positron emission tomography (PET) functional imaging is based on changes in regional cerebral blood flow (rCBF). Functional magnetic resonance imaging (fMRI) is based on a variety of physiological parameters as well as rCBF. This study is aimed at the cross validation of three-dimensional (3D) fMRI, which is sensitive to changes in blood oxygenation, with oxygen-15-labeled water (H2(15)O) PET. Nine normal subjects repeatedly performed a simple finger opposition task during fMRI scans and during PET scans. Within-subject statistical analysis revealed significant ("activated") signal changes (p < 0.05, Bonferroni corrected for number of voxels) in contralateral primary sensorimotor cortex (PSM) in all subjects with fMRI and with PET. With both methods, 78% of all activated voxels were located in the PSM. Overlap of activated regions occurred in all subjects (mean 43%, SD 26%). The size of the activated regions in PSM with both methods was highly correlated (rho = 0.87, p < 0.01). The mean distance between centers of mass of the activated regions in the PSM for fMRI versus PET was 6.7 mm (SD 3.0 mm). Average magnitude of signal change in activated voxels in this region, expressed as z-values adapted to timeseries, zt, was similar (fMRI 5.5, PET 5.3). Results indicate that positive blood oxygen level-dependent (BOLD) signal changes obtained with 3D principles of echo shifting with a train of observations (PRESTO) fMRI are correlated with rCBF, and that sensitivity of fMRI can equal that of H2(15)O PET.

Adult↗
PubMed1996

Gender differences in cerebral blood flow as a function of cognitive state with PET.

UNLABELLED: This study explored the role of cognitive states in gender-based differences in brain function. METHODS: We used the 15O-water bolus method to measure cerebral blood flow (CBF) in 14 young normal volunteers with PET. Each subject was scanned six times, three during different neuropsychological tasks linked to the prefrontal cortex and three others during customized sensorimotor control tasks. The prefrontal tasks were the Wisconsin Card Sorting (WCS) Test, Delayed Alternation task (DA) and Spatial Delayed Response task (DR). RESULTS: A significant main influence of sex on global CBF (ml/min/100g) was seen, with higher values in women, as viewed across all six conditions (means: 60.9 versus 53.2, ANOVA F = 9.35, p < 0.01). Post-hoc contrasts, however showed that this finding was not uniform in all conditions. Differences between men and women were seen during performance of the frontal lobe tasks, but not during the sensorimotor control tasks. Even within the three frontal lobe tasks, results tended to vary: the differences between the sexes were most significant during the DA and just reached traditional levels of significance during the WCS. Therefore, if we had utilized a single task condition to determine whether men and women have different global CBFs, disparate conclusions would have reached depending upon the task chosen. CONCLUSION: Although clear sex differences in global CBF can be demonstrated, the cognitive state of the subjects must be controlled and considered when interpreting the differences. Also, variations in the cognitive state might explain some of the discrepancies in gender studies in the rCBF and cerebral glucose metabolism literature.

Adult↗
PubMed1995

Physiological activation of a cortical network during performance of the Wisconsin Card Sorting Test: a positron emission tomography study.

To determine the neural circuitry engaged by performance of the Wisconsin Card Sorting Test (WCST), a neuropsychological test traditionally considered to be sensitive to prefrontal lesions, regional cerebral blood flow was measured with oxygen-15 water and positron emission tomography (PET) while young normal subjects performed the test as well as while they performed a specially designed sensorimotor control task. To consider which of the various cognitive operations and other experiential phenomena involved in the WCST PET scan are critical for the pattern of physiological activation and to focus on the working memory component of the test, repeat WCST scans were also performed on nine of the subjects after instruction on the test and practice to criteria. We confirmed that performance of the WCST engages the frontal cortex and also produces activation of a complex network of regions consistently including the inferior parietal lobule but also involving the visual association and inferior temporal cortices as well as portions of the cerebellum. The WCST activation in the dorsolateral prefrontal cortex (DLPFC) remained significant even after training and practice on the test, suggesting that working memory may be largely responsible for the physiological response in DLPFC during the WCST and, conversely, that the DLPFC plays a major role in modulating working memory.

Adolescent↗
PubMed1994

Relations between neuropsychological performance and brain morphological and physiological measures in monozygotic twins discordant for schizophrenia.

Correlational approaches that examine the relation between neuropsychological measures and brain morphology or physiology in schizophrenia have yielded inconsistent results. This may be due in part to difficulties in ascertaining precisely to what degree each measure deviates from its genetically and environmentally determined potential level. We attempted to surmount this problem in a paradigm involving monozygotic twin pairs discordant for schizophrenia. In this paradigm, the difference score between the unaffected member and affected member of a twin pair should represent the degree of pathologic involvement irrespective of actual level. In correlating intrapair difference scores of anatomic structures measured from magnetic resonance imaging (n = 15) and prefrontal regional cerebral blood flow (rCBF) (n = 10) with cognitive abilities (after partialing IQ), we found strong associations between (1) the left hippocampus and a parameter of verbal memory, and (2) prefrontal rCBF with symptom scores and perseveration on the Wisconsin Card Sorting Test. These results support other research implicating medial temporal and prefrontal regions as important in the symptomatic expression and cognitive failures of schizophrenia. Overall, however, there was a relative paucity of significant associations between neuroanatomic and neurocognitive variables. This may have been due to the relatively restricted ranges of hippocampal size or cognitive ability found in this sample.

Adult↗
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↗
PubMed1993

Is the mechanism of prefrontal hypofunction in depression the same as in schizophrenia? Regional cerebral blood flow during cognitive activation.

To test the hypothesis that depressed and schizophrenic patients have a common pathophysiological mechanism for hypofunction of the prefrontal cortex ('hypofrontality'), we measured regional cortical blood flow (rCBF) in ten depressed patients, ten patients with schizophrenia, and 20 age- and sex-matched normal controls. Blood flow was measured during three different cognitive conditions: a resting state, a simple number-matching sensorimotor control task, and the Wisconsin Card Sorting test (WCS). The schizophrenic patients had lower prefrontal rCBF during the WCS. There were no differences in global or regional flow between the depressed patients and the normal subjects during any testing condition. Analysis of rCBF lateralisation showed that during the WCS normal subjects had relatively more left parietal blood flow than depressed patients, who had more right parietal blood flow. Since the testing condition that has most consistently revealed hypofrontality in schizophrenia (i.e. the WCS) was not associated with abnormal rCBF in the depressed patients, these data suggest that the pathophysiological mechanisms underlying prefrontal hypofunction in depression and schizophrenia are different.

Adult↗
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↗