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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
PubMed1997

Visuospatial working memory in patients with schizophrenia.

Recent investigations have documented abnormalities in working memory related processes in schizophrenics on tasks assessing the central executive component of this cognitive model. This preliminary study investigated the function of another component of the working memory system, the visuospatial scratch pad in schizophrenia. The "scratch pad's" passive visual store--responsible for the temporary retention of visual material--was assessed via a computerized spatial delayed response task, whereas its active spatial rehearsal subsystem--specialized for retaining the temporal properties--was explored through visual block span. To assess elemental visual spatial abilities we used the Judgment of Line Orientation test. Thirty-two schizophrenics and 27 controls were tested. Although we discovered the basic perceptual abilities of patients to be intact, we determined that whenever memory was necessitated on spatial tasks, patients demonstrated marked deficits. This pattern of cognitive dysfunction is consistent with impairments in a neural network involving prefrontal and/or posterior brain regions in schizophrenia.

Adult↗
PubMed1996

Different side effect profiles of risperidone and clozapine in 20 outpatients with schizophrenia or schizoaffective disorder: a pilot study.

OBJECTIVE: The purpose of this study was to compare the side effect +profiles of clozapine and risperidone. METHOD: The subjects were 20 outpatients with schizophrenia or schizoaffective disorder who were clinically stable on a regimen of clozapine at the time of screening. They underwent a randomized-order crossover comparison of 6 weeks of risperidone treatment and 6 weeks of clozapine treatment. Clinical and neurocognitive variables were assessed by raters blind to medication status, and severity of side effects was determined from patients' self-reports. RESULTS: Side effect measures, but not clinical ratings, were significantly different after 6 weeks of treatment with the two drugs. Patients required more benztropine for motor effects and complained of more insomnia with risperidone and more sedation with clozapine. Body weight was higher at the end of clozapine treatment than at the end of risperidone treatment. CONCLUSIONS: In this exploratory study, the side effect profiles of clozapine and risperidone were consistent with the different pharmacodynamic profiles of the two drugs.

Akathisia, Drug-Induced↗
PubMed1996

Effects of neuroleptic medications on the cognition of patients with schizophrenia: a review of recent studies.

In this review, we have examined the effects of neuroleptic medications on neurocognitive functions in articles published since 1990. Based on recent work and reviews of older studies, neuroleptics do not appear to have marked positive or negative effects on working memory or secondary memory. In contrast, neuroleptic medications appear to have a salutary effect on sustained vigilance or response readiness. The relationship or lack thereof between changes in cognition and changes in clinical state (produced by neuroleptics) is also discussed.

Antipsychotic Agents↗
PubMed1995

Verbal working memory dysfunction in schizophrenia: use of a Brown-Peterson paradigm.

Recent studies of schizophrenia have implicated deficits in processes related to working memory, but the cognitive features of these deficits have been incompletely characterized. We used a modified Brown-Peterson paradigm to compare working memory in patients with schizophrenia and in normal control subjects. Distractor conditions differed in processing demand, increasing in complexity from no distractor to counting backwards (serial threes). We found significant effects of group, of distractor condition, and of a group x distractor condition interaction. The significant interaction was the result of a more rapid decline in the performance of schizophrenic patients with concurrent articulation. In addition, the schizophrenic group also made significantly more intrusion errors. The study suggests that schizophrenic patients exhibit dysfunction of the verbal working memory system due to a diminution in its overall processing resources.

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↗
PubMed1995

Memory and intelligence in lateralized temporal lobe epilepsy and schizophrenia.

Recent neuroimaging studies of patients with schizophrenia have suggested structural and functional abnormalities of mesial temporal lobe structures. We compared the intelligence and memory test performance of 70 patients with schizophrenia and 72 patients with focal, lateralized temporal lobe epilepsy (30 left, 42 right temporal lobe) in order to examine the adequacy of a temporal lobe model of schizophrenic cognitive deficits. The groups did not differ in age, education, or Full Scale IQ. The right temporal lobe group had better overall memory performance than either the left temporal or schizophrenic patients. Unlike the schizophrenic patients, the memory impairment of the left temporal group was most evident with verbal materials and was amplified by delayed testing. Both epilepsy groups had better visual memory than the schizophrenic group. The clear differences in performance pattern between groups suggests that lateralized temporal lobe dysfunction does not by itself provide an adequate model of schizophrenic cognitive impairment.

Adult↗
PubMed1995

Genetic risk of neuropsychological impairment in schizophrenia: a study of monozygotic twins discordant and concordant for the disorder.

We used a paradigm involving monozygotic (MZ) twin pairs discordant for schizophrenia (n = 20) and concordant for schizophrenia (n = 8), as well as normal MZ twin pairs (n = 7) in order to study cognitive measures of genetic risk in schizophrenia. A comparison between the unaffected twins from the discordant sample and the normal twins indicated subtle attenuations in some aspects of memory and executive functioning in the unaffected group and thus provided evidence for cognitive markers of a genetic component in schizophrenia. A comparison of the affected twins from the discordant pairs and the concordant twins yielded virtually no differences, suggesting that a distinction between familial and sporadic cases is not valid in this sample. Large differences between unaffected and affected members of discordant pairs on a wide variety of variables, including IQ, attention, memory, and executive function, highlighted the magnitude of disease-specific factors.

Adult↗
PubMed1995

A case against subtyping in schizophrenia.

In this paper we consider the generally accepted view that schizophrenia is 'heterogeneous'. We point out that the view derives from prima facie evidence from clinical presentation, studies of course, and factor analysis. However, upon closer examination internal contradictions are apparent, e.g., subtypes change, different groupings of symptoms cooccur in the same individual. Another type of paradigm, depending on careful study of case controls (e.g., monozygotic twins discordant for schizophrenia) and distributions, indicates that abnormalities in neurocognition, regional cerebral blood flow, and regional neuroanatomy may be present in nearly every patient, irrespective of absolute level or diagnostic subtype. These results suggest that a simple model in which patients vary along a severity dimension might parsimoniously explain much of the variance. Thus, while it is possible and even probable that schizophrenia may have many etiologies, phenocopies may represent the expression of a unitary pathogenesis of greater or lesser impact.

Case-Control Studies↗
PubMed1995

Thought disorder, working memory and attention: interrelationships and the effects of neuroleptic medications.

Impairments in attention and vigilance, working memory and organization of speech (thought disorder) have been reliably observed in patients with schizophrenia. The response in these cognitive parameters to neuroleptic medications can be used to sharpen their characterization in neuropsychological terms. In particular, a review of the literature suggests that while working memory is relatively insensitive to neuroleptics, attention and thought disorder may improve with neuroleptic administration. On the basis of the response to typical and atypical neuroleptics, attention as deployed in the Continuous Performance Test may reflect response readiness rather than actual vigilance. Thought disorder, which is often assumed to be the result of impaired discourse planning due to a reduced capacity for working memory, does not covary with working memory, and the two parameters show different responses to neuroleptic medications. Rather, cognitive studies suggest that thought disorder may arise from abnormalities within the semantic system itself.

Antipsychotic Agents↗
PubMed1995

Lack of sex differences in the neuropsychological performance of patients with schizophrenia.

OBJECTIVE: While a number of studies have suggested that women with schizophrenia have a less severe form of the disorder than men, the issue has been examined with neuropsychological measures only infrequently. METHOD: The authors compared neuropsychological test performances of men and women from four independent schizophrenic cohorts: two groups of inpatients with chronic courses at a research hospital (N = 128 and N = 63), one group of consecutive admissions to a private psychiatric hospital (N = 57), and one group of schizophrenic twins from discordant monozygotic pairs (N = 20). Nearly 100 comparisons of neuropsychological test performances were made between men and women. RESULTS: Not one comparison significantly favored women, and few were even significantly different between the sexes. CONCLUSIONS: It cannot be ruled out that the disproportionate number of men in the chronic cohorts may have reflected either more frequent intellectual deterioration in men or a bias toward more severely impaired women. Yet, men and women in all groups performed similarly, including the groups in which the sex ratios were nearly equal and were not skewed toward chronicity. These results provide little support for the hypothesis that gender is associated with a unique pathogenesis of schizophrenia or is a marker for a distinct subtype of schizophrenia, at least to the extent that cognitive impairment is a primary manifestation of the underlying disease process. However, given the lack of female patients with later ages at onset and more affective symptoms, the results in this study should be considered relevant only for chronic patients with onset of schizophrenia before age 30.

Adult↗
PubMed1995

Neuropsychological effects of amphetamine may correlate with personality characteristics.

Although the stimulant properties of amphetamine are well established, its effects on cognitive test performance in unfatigued normal adults are poorly documented. Seventeen healthy individuals received a single oral dose of dextroamphetamine (0.25 mg/kg) in a double-blind, placebo-controlled, crossover study. Neurocognitive tests, motor tests, and behavioral observations were performed. Personality information, based on the Tridimensional Personality Questionnaire (TPQ) was also gathered to explore a relationship between personality factors and response to the stimulant. With the exception of two measures of reaction time, there were no overall changes in performance on measures of memory or other cognitive functions. There was decreased reaction time on the continuous performance task (CPT) and increased accuracy of performance under minimal delay conditions in the spatial delay response task while subjects were receiving amphetamine. In addition, the novelty-seeking subscale was found to correlate with a measure of verbal memory. Individuals with higher scores on the novelty-seeking scale deteriorated under amphetamine, while those who had lower scores improved. These results suggest that some cognitive abilities of persons who may have relatively high dopaminergic tone are disrupted by amphetamine, while those with relatively low dopaminergic tone may have their performance enhanced.

Administration, Oral↗
PubMed1994

Schizophrenia and temporal lobe epilepsy. A neuropsychological analysis.

BACKGROUND: Recent neuroimaging studies have reported structural abnormalities of mesial temporal lobe structures in schizophrenia. This study compared the neuropsychological performance of patients with schizophrenia with patients with either left or right temporal lobe epilepsy to determine if lateralized, developmental temporal lobe dysfunction provides a model of the cognitive impairments observed in schizophrenia. METHODS: A total 66 patients with schizophrenia and 101 patients with medically intractable focal temporal lobe epilepsy (48 left temporal, 53 right temporal) received a comprehensive neuropsychological battery. RESULTS: The three groups did not differ on age, years of education, or Full-Scale IQ. However, clear differences were noted in performance profiles. Patients with schizophrenia scored significantly higher than either epilepsy group on a measure of word reading thought to reflect premorbid competence. Patients with schizophrenia demonstrated greater attentional impairment and motor slowing than either epilepsy group. The patients with schizophrenia had superior semantic knowledge and verbal memory compared with the left temporal lobe group. On the Wisconsin Card Sorting Test the patients with schizophrenia obtained significantly fewer categories than either temporal lobe group, but were not significantly more perseverative. CONCLUSIONS: Data suggest lateralized temporal lobe dysfunction does not provide an adequate model of the cognitive impairments seen in schizophrenia. The disorders seem to follow different developmental paths: In early-onset epilepsy, the acquisition of cognitive skills and academic knowledge is compromised, while in schizophrenia cognitive functions are lost. Extratemporal pathologic features, most likely of the frontal lobe, are implicated in the cognitive dysfunction of schizophrenia.

Adult↗
PubMed1994

Cerebral ventricular enlargement in schizophreniform disorder does not progress. A seven year follow-up study.

Ten patients, who underwent computerized tomography (CT) study during evaluation for first episode schizophreniform psychosis were restudied an average of 7 years later. Of the 10 patients, 7 were found to carry a diagnosis of schizophrenia at follow-up. In this subgroup, there was no significant change in the mean ventricular brain ratio measure of cerebral ventricular size between the index and follow-up scans. These findings are consistent with the hypothesis that ventricular enlargement is present at the onset of schizophrenia and does not progress with duration of illness or treatment.

Adolescent↗
PubMed1994

Schizophrenia, training paradigms, and the Wisconsin Card Sorting Test redux.

The question of whether and to what extent poor performance on the Wisconsin Card Sorting Test (WCST) in patients with schizophrenia can be improved with coaching has been controversial. We review relevant studies with particular reference to the following issues: (1) can improvement occur? (2) if improvement does occur, what is its significance? and (3) what is the association between performance and neurophysiology? The studies indicate that in patients with schizophrenia performance can frequently be improved, but usually remains in the abnormal range. Similar results for memory measures have been reported in patients with amnesias or dementias of known neurological origin. This suggests that simple dichotomies between neurologic and psychological explanations of cognitive impairment and potential amelioration of such impairment may be inadequate. Comparisons of the results of studies using the WCST as a clinical tool with binary cut-off scores to define normal and abnormal, as a measure of neuropsychological function along a continuum, and as an activation stimulus to probe neurophysiology suggest that absolute WCST scores may not always accurately gauge the functional integrity of neural systems dedicated to the task. This situation may arise because of individual differences in endowment and in the capacity for neuronal compensation, as well as measurement error. Given these issues, caution is advised in the interpretation of WCST scores, which are best understood as representing a final common cognitive pathway that can be the product of diverse psychological, physiological, and neuroanatomic mechanisms.

Attention↗
PubMed1994

WAIS-R short forms in chronic schizophrenia.

Short forms of the WAIS-R provide a relatively quick screen of an individual's general cognitive ability. This study attempted to measure the merit of three WAIS-R short forms developed by Kaufman (1990) in a group of 114 chronic schizophrenic patients. The results suggest that the four-subtest short form provided the most reliable estimation of Full Scale IQ. The implications of these findings for research screening of schizophrenic patients is discussed.

Adult↗
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↗