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Biomedical subjects

T E Goldberg

Publications and source records attributed to T E Goldberg.

At least 19 recordsLinked to original sources

Visual orienting in schizophrenia.

Patients with schizophrenia demonstrate a variety of attentional impairments which have proven difficult to relate to specific neural systems. Posner et al. (1988) reported an asymmetric slowing of right visual field orienting in schizophrenia similar to that observed in patients with parietal lesions. We examined the visual orienting performance of 19 patients and controls using two different versions of the Posner paradigm. In overall ANOVAs we found main effects of group, cue condition, and delay interval. However, we did not observe any main effect of visual field or interactions involving visual field. There was some evidence of an asymmetric cost of invalid cues similar to those reported by Posner et al. The bulk of data suggests bilateral attentional deficits.

Adult

Dichotic listening in monozygotic twins discordant and concordant for schizophrenia.

Emotional and neutral word versions of the fused rhymed words dichotic listening test were administered to members of 18 pairs of monozygotic twins discordant for schizophrenia, 7 pairs concordant for schizophrenia, and 7 pairs of normal twins. In the discordant group, affected twins had smaller right ear advantages than did their unaffected cotwins for neutral words. The difference was completely attenuated with the presentation of emotional words or in less powerful between-group comparisons that included twins concordant for schizophrenia and normal twins. It is unlikely that this finding reflects an abnormality in the lateralized representation of language, both because we did not find a correlation between handedness scores and dichotic listening scores and because emotional stimuli normalized results. The finding may reflect abnormalities in the allocation of attention for priming language centers in the left hemisphere. 'At risk' subjects, i.e., the unaffected members of the discordant pairs, did not differ significantly from normal monozygotic twins on measures of dichotic listening.

Adult

Forms of memory failure in schizophrenia.

Effortful and automatic memory task performances were examined in 36 schizophrenic patients and 18 normal control Ss. Tasks included free recall, recognition, and frequency estimation. Patients demonstrated impairment in recall, in recognition, in semantic encoding, and in frequency estimation. Deficits were observed across tasks despite differences in attentional demands. The results suggest a basic compromise of memory function, which is consistent with recent neuroimaging evidence of structural or physiological abnormalities in frontal and temporal lobe structures in schizophrenia.

Adult

Release from proactive interference: determinants of performance and neuropsychological correlates.

The Wickens (1970) modification of the Brown-Peterson short-term memory task has been used to investigate release from proactive interference (PI) in a number of memory-impaired groups. It has been suggested that failure to release from PI is observed only in patients with compromise of both memory and 'frontal-lobe' functions. The present study examined performance on this paradigm in patients with schizophrenia (SC), a neuropsychiatric disorder which typically includes both frontal and mnemonic impairments. Patients with SC were found to exhibit significantly less release from PI than normal controls. It was determined through correlational analyses that average Trial 1 performance on this task could predict performance on all subsequent trials, indicating that 'release' from PI may measure the same psychological process as the Brown-Peterson task, which does not include a release condition. Trial 1 performance in the SC group was correlated with a wide range of neuropsychological measures, but after the effect of full scale IQ was partialled out, only correlations with measures of memory and measures of frontal-lobe function remained significant. The results support previous formulations of the neuropsychological concomitants of release from PI, but suggest that failure to release on this paradigm may be secondary to a significant compromise of the ability to perform the Brown-Peterson task. It is proposed that the experimental design constraints necessary to elicit a failure to release from PI in any patient group may limit the utility of this measure, and that Brown-Peterson performance may be a more reliable index of the neuropsychological functions involved.

Adult

Neuropsychological and glucose metabolic profiles in asymmetric Parkinson's disease.

Patients with predominantly unilateral parkinsonian signs may provide a unique opportunity to evaluate the cerebral representation of cognitive functions characteristically affected in idiopathic Parkinson's disease. Twenty hemiparkinsonian patients (ten left and ten right) and 10 healthy controls, matched for age and education, were studied with neuropsychological tests and positron emission tomography. Both right and left hemiparkinsonians evidenced impairments in visuospatial and verbal episodic memory function, but had no deficits in executive abilities, compared to controls. None of the neuropsychological test scores distinguished right from left hemiparkinsonians. Glucose metabolic profiles were identical for the three groups in all cortical areas assessed; in the subcortex however, lenticular hypermetabolism contralateral to the predominant side of motor involvement was evident in the left hemiparkinsonian group. Correlational analysis revealed that higher glucose metabolic rates in the basal ganglia of these hemiparkinsonians were associated with lower visuospatial test scores. In frontal and parietal cortex, decreasing glucose metabolism was positively associated with neurobehavioral function; in temporal cortex, measures of attention and memory decreased with increasing glucose metabolic rates.

Adult

Lack of a bimodal distribution of ventricular size in schizophrenia: a Gaussian mixture analysis of 1056 cases and controls.

The finding of clinical and laboratory differences between schizophrenic patients with large and small cerebral ventricles has led to the widespread assumption that large ventricles are a marker that characterizes a subgroup of patients with schizophrenia. We reviewed all published English language ventricle-to-brain ratio (VBR) studies in which individual data points were available (schizophrenics: n = 691, medical controls; n = 205, normal volunteers: n = 160). Using a univariate normal mixture model to examine the distribution of ventricular size in each group, we found no evidence of a mixture of Gaussian distributions (i.e., "bimodality") within any of the three groups. The same analysis was then performed on the combined sample of schizophrenic patients and normal and medical controls, respectively. In each case the improvement in fit of a mixture of normal distributions compared to a single component normal distribution was significant. The data do not support the notion that ventricular enlargement is a discontinuous marker of a subtype of schizophrenia.

Analysis of Variance

Tardive dyskinesia: neuropsychological, computerized tomographic, and psychiatric symptom findings.

Prior studies have suggested that schizophrenic patients with tardive dyskinesia (TD) have an unusual incidence of cognitive impairment, structural brain abnormalities, and negative symptoms. Twenty-seven schizophrenic patients with TD and an equal number of age-, gender-, and education-matched schizophrenic controls were studied. Each patient received neuropsychological testing, psychiatric symptom ratings, and most had cerebral computed tomography (CT) scans. Patients with TD significantly differed from controls on only 1 of 23, cognitive measures, and the overall group performance profiles were highly similar. No differences were observed on symptom ratings. Patients with TD had significantly smaller ventricular-brain ratios (VBRs) than controls. These data fail to support an association of TD with global measures of "organicity." Abnormal movements may result from specific dysfunction within the more purely motor circuits of the basal ganglia without compromising other neural systems involved in cognitive processing.

Adult

Computed tomography measurements of brain density in Schizophrenia.

Although previous studies have reported differences in computed tomography (CT) scan attenuation values between patients with schizophrenia and controls, interpretation of these findings has been hindered by methodological shortcomings such as the failure to control for head size, scanner calibration differences, and other confounding variables. In the present study of CT attenuation values in multiple brain regions in 20 patients with chronic schizophrenia and an equal number of age- and sex-matched normal subjects we controlled for head size and normalized the attenuation values for each scan to an internal standard. No significant differences emerged between the patients with schizophrenia and the controls. However, in the controls only, the mean density of white matter in the left frontal area was significantly higher (t = -2.83, p = 0.01) than that in the right. The results, although possibly suggestive of deviant lateralization in schizophrenia, raise questions about the sensitivity and validity of regional CT attenuation values in detecting subtle anatomic abnormalities in patients with this illness.

Adult

Cognitive and behavioral effects of the coadministration of dextroamphetamine and haloperidol in schizophrenia.

OBJECTIVE: The authors sought to determine if an acute dose of dextroamphetamine might have positive effects on affect and cognition in schizophrenic patients maintained on a regimen of haloperidol and, if so, what variables might predict such improvements. METHOD: Twenty-one patients with chronic schizophrenia who were hospitalized on a research ward received a single oral dose of dextroamphetamine (0.25 mg/kg) in a double-blind, placebo-controlled, crossover study. All patients were receiving 0.4 mg/kg per day of haloperidol. Cognitive tests, motor tests, global ratings, mood ratings, and videotape ratings were used to determine the effect of the coadministration of these drugs. Ventricle-brain ratios derived from CT scans were used to predict response to the coadministration of these drugs. RESULTS: Amphetamine improved performance on a measure of concept formation on the Wisconsin Card Sorting Test but did not result in changes in performance on tests of memory or attention. As a group, the patients were more active and performed psychomotor tests more quickly while receiving amphetamine. Six patients were judged by clinical raters to have improved in terms of affect, cooperation, and engagement with the environment. Improvement was associated with enlarged cerebral ventricles and increases in blink rate from the placebo to the active drug condition. No patient unequivocally worsened. CONCLUSIONS: These results may be consistent with the theory that coadministration of amphetamine and haloperidol produces relatively selective enhancement of cortical dopaminergic activity. However, because of the acute nature of the trial and the specialized research environment in which it was conducted, the authors do not advocate amphetamine as a routine clinical treatment of schizophrenia.

Adult

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

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

The hippocampus and parahippocampus in schizophrenia, suicide, and control brains.

Recent postmortem studies in schizophrenia have shown abnormalities in medial temporal lobe structures, including the hippocampus and parahippocampus. We tried to replicate previous studies and to explore the specificity of this finding to schizophrenia. The anterior hippocampus and parahippocampal cortex were evaluated for area and shape in postmortem tissue from 12 schizophrenic, 17 nonschizophrenic suicide, and 10 nonpsychiatric control brains. No significant differences were found in hippocampal area, but the parahippocampal cortex was significantly smaller in the schizophrenic group than in the control group. When parahippocampi from right and left sides were analyzed separately, both the suicide and schizophrenic groups had smaller parahippocampi on the right side than did the controls [corrected]. The suicide group exhibited greater parahippocampal areas in the left than in the right tissue samples within the group, while such a difference did not exist in the schizophrenic or control groups. This study demonstrated changes in temporal lobe structures in both schizophrenic and nonschizophrenic suicide groups.

Adult

Neuropsychological assessment of monozygotic twins discordant for schizophrenia.

A comparison of monozygotic twins discordant for schizophrenia controls for genetic variance and reduces variance due to environmental circumstances, thus serving to highlight differences due to phenotypic-related variables. In this study, we assessed 16 such twin pairs on a wide range of neuropsychological tests. The affected twins tended to perform worse than their unaffected counterparts on most of the tests. Deficits were especially severe on tests of vigilance, memory, and concept formation, suggesting that dysfunction is greatest in the frontotemporal cortex. While manifest symptoms were not highly associated with neuropsychological scores, global level of functioning was. To address the issue of genetic liability, we also compared the sample of discordant unaffected twins with a sample of seven pairs of normal monozygotic twins. No significant differences between the groups were found for any neuropsychological test. In fact, the results suggest that neuropsychological dysfunction is a consistent feature of schizophrenia and that it is related primarily to the clinical disease process and not to genetic or nonspecific environmental factors.

Adult

Morphometry of the corpus callosum in monozygotic twins discordant for schizophrenia: a magnetic resonance imaging study.

The corpus callosum (CC) has been the focus of several morphometric studies of patients with schizophrenia, but the results of these studies have been contradictory. In an attempt to improve the reliability of morphometric measurements of the corpus callosum, a computerised image analysis system was used to measure the shape, area, thickness and length of the CC on magnetic resonance imaging (MRI) in 12 pairs of monozygotic twins discordant for schizophrenia (SC). No differences in CC area (anterior, middle, posterior thirds and total), length or vertical thickness of the CC body (at three levels) were demonstrated by t test comparisons of the affected SC and unaffected twins. Statistical analysis of a Fourier expansion series suggested differences in shape between normal and SC cotwins in the second harmonic of the anterior and middle segments and effects of gender on posterior CC shape. These results fail to replicate previous findings of altered length, thickness and area in the schizophrenic CC, but implicate disease-related shape differences in the anterior and middle segment of the corpus callosum and gender-related differences in splenium shape. The disease-related shape distortion suggest ventriculomegaly rather than an intrinsic abnormality of the corpus callosum.

Adult

Assessment of procedural learning and problem solving in schizophrenic patients by Tower of Hanoi type tasks.

Two versions of the Tower of Hanoi task were used to investigate different components of learning and problem solving in schizophrenia. Prior studies have suggested that a three-disk version (Tower 3), which involves primarily problem-solving abilities and planning, is preferentially sensitive to frontal lobe lesions and that the more difficult four-disk version (Tower 4), which involves "learning by doing," is sensitive to basal ganglia disease. Schizophrenic patients performed significantly worse than normal subjects on Tower 3 and Tower 4. However, they performed at least as well relatively on Tower 4 as on Tower 3, indicating that level of difficulty per se does not account for their poor performance on these tasks. Moreover, they eventually attained perfect or near-perfect performance after four days of repeated administration. Their relatively stronger performance on Tower 4 may have reflected an ability to acquire a procedure and, as such, suggests greater preservation of basal ganglia function than of prefrontal function.

Adult

Quantitative shape analysis of the temporal and prefrontal lobes of schizophrenic patients: a magnetic resonance image study.

In a recent quantitative neuroimaging study, the authors reported significant reduction in the gray matter volume of both temporal lobes of schizophrenic (SC) patients. In order to better elucidate the nature of this finding (i.e., diffuse vs. focal), we analyzed the shape of the temporal lobes of 17 SC patients and an equal number of age-sex matched controls. Our shape analysis was able to discriminate between a significant number of SC and control patients based on the Fourier harmonic amplitudes of both the middle and posterior levels of the temporal lobes. These results are consistent with bilateral focal or multifocal distortions of the temporal lobes of SC patients. A similar shape analysis of the prefrontal lobes showed no significant conformational differences between the groups. The basis of this quantitative shape analysis (the Fourier expansion series) and the method by which it can be applied are explained in detail.

Atrophy