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Biomedical subjects

J M Gold

Publications and source records attributed to J M Gold.

At least 37 records · Page 2Linked to original sources

Repeatable battery for the assessment of neuropsychological status as a screening test in schizophrenia, II: convergent/discriminant validity and diagnostic group comparisons.

OBJECTIVE: In a companion article in this issue of the Journal, the authors presented data suggesting that the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is sensitive to the types of impairments observed in schizophrenia, correlates highly with standard measures of intelligence and memory, and is related to employment status in a group of patients with schizophrenia drawn from a tertiary care research center. The objectives of the current study were 1) to determine if evidence of the convergent validity of the RBANS could be replicated in a diagnostically heterogeneous sample drawn from a public mental health system, 2) to examine the relationship of the RBANS to a broad neuropsychological battery, and 3) to compare the performance of patients with schizophrenia and patients with bipolar disorder on a neuropsychological battery and the RBANS. METHOD: The RBANS and a standard neuropsychological battery, including the WAIS-III and Wechsler Memory Scale, 3rd ed. (WMS-III), were given to 150 patients drawn from a larger study of vocational rehabilitation. RESULTS: Correlations of RBANS total scores with WAIS-III and WMS-III variables were highly similar across study groups. The RBANS correlated highly with a composite z score derived from 22 standard measures of IQ, memory, language, motor, attention, and executive function. Principal component analyses of the neuropsychological battery resulted in a six-factor solution: the RBANS correlated most highly with a general ability factor and had limited correlations with measures of motor performance, vigilance, and executive function. Patients with schizophrenia demonstrated greater deficits on the neuropsychological battery and the RBANS than patients with bipolar disorder. CONCLUSIONS: These data suggest that the RBANS is a useful screening instrument for assessing the severity of cognitive impairment in psychiatric populations.

Adult↗

Prediction of neuropsychological performance by neurological signs in schizophrenia.

OBJECTIVE: The major purposes of this study were 1) to examine whether neurological signs predict cognitive performance in both schizophrenic patients and healthy subjects and 2) to determine the ability of neurological signs and neuropsychological tests to discriminate schizophrenic patients from healthy subjects. METHOD: Eighty-five patients with a DSM-III-R diagnosis of schizophrenia and 36 normal comparison subjects were included in the study. All subjects were administered a comprehensive neuropsychological test battery, and neurological signs were assessed with the Neurological Evaluation Scale. Stepwise regression analyses were used to predict neuropsychological test performance from the subscale scores on the Neurological Evaluation Scale. Forward stepwise linear discriminant function analyses were used to examine the discriminative ability of neurological subscale scores, neuropsychological test scores, and the two combined. RESULTS: Scores on the Neurological Evaluation Scale predicted the neuropsychological test performance of both patients and comparison subjects. The sensory integration subscale score was the most frequent predictor of neuropsychological test performance. In contrast, the "others" subscale, which includes frontal release signs, abnormalities in eye movements, and short-term memory, was the most highly discriminating subscale, correctly classifying 78.5% of the total study group. The best predictors from the neuropsychological battery (category fluency and Trail Making Test, part A, time test) correctly classified 81.8%. When both sets of variables were used, the Neurological Evaluation Scale "others" subscale entered the discriminant function first. CONCLUSIONS: Neurological signs are reliably related to measures of neuropsychological performance and also reliably discriminate between patients and healthy subjects. However, some neurological signs may be more sensitive to the presence of schizophrenia, while others may be more predictive of neuropsychological performance.

Adolescent↗

Changing patterns of brain activation during maze learning.

Recent research has found that patterns of brain activation involving the frontal cortex during novel task performance change dramatically following practice and repeat performance. Evidence for differential left vs. right frontal lobe activation, respectively, during episodic memory encoding and retrieval has also been reported. To examine these potentially related issues regional cerebral blood flow (rCBF) was measured in 15 normal volunteers using positron emission tomography (PET) during the naive and practiced performance of a maze task paradigm. SPM analysis indicated a largely right-sided, frontal lobe activation during naive performance. Following training and practice, performance of the same maze task elicited a more posterior pattern of rCBF activation involving posterior cingulate and precuneus. The change in the pattern of rCBF activation between novel and practiced task conditions agrees with results found in previous studies using repeat task methodology, and indicates that the neural circuitry required for encoding novel task information differs from that required when the same task has become familiar and information is being recalled. The right-sided preponderance of activation during naive performance may relate to task novelty and the spatially-based nature of the stimuli, whereas posterior areas activated during repeat performance are those previously found to be associated with visuospatial memory recall. Activation of these areas, however, does not agree with previously reported findings of left-sided activation during verbal episodic memory encoding and right-sided activation during retrieval, suggesting different neural substrates for verbal and visuospatial processing within memory.

Adult↗

Uncoupling cognitive workload and prefrontal cortical physiology: a PET rCBF study.

Working memory is a fundamental cognitive building block involved in the short-term maintenance and transformation of information. In neuropsychological studies, working memory has been shown to be of limited capacity; however, the neurophysiological concomitants of this capacity limitation have not been explored. In this study we used the [15O] water PET rCBF technique and statistical parametric mapping to examine normal subjects while they performed two cognitive tasks, both individually and simultaneously. One task was the Wisconsin Card Sorting Test, a complex reasoning task involving working memory, and the other was a rapidly paced auditory verbal shadowing task. When both tasks were performed simultaneously, there were significant decrements in performance compared with the individual task performance scores, indicating that cognitive workload had been increased. Analysis of the rCBF maps showed that when the two tasks were performed together, in contrast to when they were performed separately, there was less prefrontal activation. These results suggest that increases in cognitive workload do not necessarily recruit and then sustain cortical neurophysiological resources to a maximum, but rather may actually be accompanied by a diminution in cortical activity.

Adult↗

The role of negative symptoms and cognitive dysfunction in schizophrenia outcome.

Schizophrenia is a lifelong illness, with symptoms beginning in late adolescence/early adulthood and persisting throughout the rest of the patient's life. Positive psychotic symptoms may fluctuate during the course of the illness, but negative symptoms, especially primary negative symptoms, and cognitive dysfunction are relatively constant. The negative symptoms of schizophrenia are both primary (associated with the illness) and secondary (due to depression, neuroleptic-induced parkinsonism or acute psychosis). While secondary negative symptoms may be reduced by treating the causative agent, primary negative symptoms are viewed as enduring, persisting between psychotic episodes. Conventional antipsychotics treat the positive symptoms of schizophrenia, but they have little effect on primary negative and cognitive symptoms. Primary negative symptoms are often associated with poor premorbid function, the male sex, and low IQ (Intelligence Quotient). In addition, most studies find that negative symptoms are associated with a poor overall outcome. Several studies, including our own, have suggested that primary negative symptoms are functionally localized to the frontal and parietal cortices. These kinds of data raise the possibility that primary negative symptoms may have a pathophysiological basis distinct from positive psychosis. Cognitive impairment also appears to be a relatively independent aspect of schizophrenia. Impairment may be evident in a subtle form from early childhood, and often precedes the development of psychotic symptoms. Additional impairment accrues with the onset of psychotic illness with little evidence, in the vast majority of cases, of progression over the course of the illness. Cognitive impairment is only modestly related to psychotic symptom severity and type. However, the extent, and perhaps specific types of cognitive impairment, appear to be predictive of functional outcome.

Adolescent↗

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↗

Auditory working memory and Wisconsin Card Sorting Test performance in schizophrenia.

BACKGROUND: Impaired Wisconsin Card Sorting Test (WCST) performance has been one critical piece of evidence suggesting frontal lobe dysfunction in schizophrenia. However, the specific cognitive processes underlying impaired performance have not been identified. Impaired WCST performance in schizophrenia might in part reflect a fundamental working memory deficit. METHODS: We examined the performance of 30 normal subjects and 36 patients with schizophrenia on a neuropsychological battery including a novel measure of working memory-letter-number (LN) span. RESULTS: Patients with schizophrenia were impaired on LN span performance, which was also highly correlated with WCST performance (r = 0.74). Between-group WCST differences were eliminated when we covaried LN span. Regression analyses suggested that LN span performance predicted the WCST category achieved score, whereas measures of set shifting, verbal fluency, and attention were predictive of perseveration. CONCLUSION: Working memory may be a critical determinant of one aspect of WCST performance in schizophrenia.

Adult↗

Unnatural practices, unspeakable actions: a study of delayed auditory feedback in schizophrenia.

OBJECTIVE: It has been suggested that auditory hallucinations and delusions of control in persons with schizophrenia could involve a disconnection between an "intention center" and a "monitoring center." METHOD: To test this model directly, the authors used a delayed auditory feedback paradigm in which the subject hears his or her own speech delayed electronically by a fraction of a second. In normal, subjects this produces dysfluency, which is thought to occur because an expectancy about the perceptual arrival of speech, formed in a monitoring center on the basis of corollary discharge from an intention center, is violated. If, however, a disconnection were present in schizophrenia, such an expectancy would not be formed; hence, less dysfluency should occur. Fifteen patients with chronic schizophrenia (10 of whom experienced auditory hallucinations and/or delusions of control) and 19 normal subjects were studied. RESULTS: Rather than exhibiting less dysfluency than the normal subjects, patients with delusions and/or hallucinations exhibited significantly more dysfluency. CONCLUSIONS: These results do not support a cognitive model of disconnection.

Adult↗

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↗

Negative symptoms: diagnosis, treatment and prognosis.

The concept of negative symptoms is derived from Kraeplin's description of the dissolution of the personality in patients with schizophrenia. Negative symptoms may be either primary, or secondary to positive symptoms, antipsychotic side effects, dysphoric affect and environmental deprivation. Primary negative symptoms represent core features of the illness, and have been termed deficit symptoms. The differentiation of primary from secondary negative symptoms has important treatment implications, as treatment approaches vary greatly for the different types of negative symptoms. Specific pharamacological and psychosocial treatments are available for secondary negative symptoms. However, to date, there are no known effective treatments for primary negative symptoms. The importance of developing effective treatments for primary negative symptoms is underscored by the relationship of these symptoms to poor social, occupational, and global outcome.

Antipsychotic Agents↗

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↗

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↗

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↗

Cognitive deficits and the neurobiology of schizophrenia.

Recent research in schizophrenia has demonstrated widespread abnormalities in patients' brain structure, cognitive function, and physiology. These abnormalities are most probably developmental in origin and involve a network of connected frontal-temporal-limbic structures.

Brain↗

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↗

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↗

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↗

Tourette's syndrome in monozygotic twins. Relationship of tic severity to neuropsychological function.

OBJECTIVE: To determine whether there is a relationship between tic severity and neuropsychological function in Tourette's syndrome (TS). DESIGN: The study employed a case-control series involving monozygotic twin pairs, divided into more severe and less severe groups based on tic severity and tested with a neuropsychological battery of tests. SETTING: Twin pairs were recruited nationwide and evaluated in the National Institute of Mental Health Neuropsychiatric Research Hospital. PATIENTS: Twelve twin pairs (mean age, 10.5 years; range, 8 to 16 years) in which at least one member met criteria for a diagnosis of TS. RESULTS: Global neuropsychological performance was significantly worse in the twins with more severe tic symptoms, with significant differences emerging on individual tests of attention, visuospatial perception, and motor function. In each twin pair, the twin with more severe tics had poorer global neuropsychological function. CONCLUSIONS: The results suggest that the nongenetic factors that influence tic severity in TS exert a similar effect on neuropsychological function, and that these two clinical manifestations of TS may share a common pathophysiologic state.

Adolescent↗