Biomedical subjects

T E Goldberg

Publications and source records attributed to T E Goldberg.

At least 19 recordsLinked to original sources

PubMed2003

Duration judgements in patients with schizophrenia.

BACKGROUND: The ability to encode time cues underlies many cognitive processes. In the light of schizophrenic patients' compromised cognitive abilities in a variety of domains, it is noteworthy that there are numerous reports of these patients displaying impaired timing abilities. However, the timing intervals that patients have been evaluated on in prior studies vary considerably in magnitude (e.g. 1 s, 1 min, 1 h etc.). METHOD: In order to obviate differences in abilities in chronometric counting and place minimal demands on cognitive processing, we chose tasks that involve making judgements about brief durations of time (< 1 s). RESULTS: On a temporal generalization task, patients were less accurate than controls at recognizing a standard duration. The performance of patients was also significantly different from controls on a temporal bisection task, in which participants categorized durations as short or long. Although time estimation may be closely intertwined with working memory, patients' working memory as measured by the digit span task did not correlate significantly with their performance on the duration judgement tasks. Moreover, lowered intelligence scores could not completely account for the findings. CONCLUSIONS: We take these results to suggest that patients with schizophrenia are less accurate at estimating brief time periods. These deficits may reflect dysfunction of biopsychological timing processes.

Adolescent↗

PubMed2002

An investigation of the integrity of semantic boundaries in schizophrenia.

Organizing information and knowledge, and hence categorization, requires specifying boundaries between items, concepts and words. Over-inclusiveness in categorization may be seen as looseness of association; over-inclusive thinking was an early description of schizophrenic thinking. Recent studies suggest semantic memory problems in schizophrenia, and that thought disorder is associated with a disorganized semantic network. One such study [Psychol. Med. 24 (1994) 193], using a word categorization task, found patients slowest to respond to items semantically related to, but outside the category, whereas controls were slower responding to items sharing less features of the category (i.e. borderline). The authors suggested that there is an outward shift of semantic category boundaries in schizophrenia. In Experiment 1, we replicated methods, but did not find this qualitative difference in patients (28 patients, 26 controls). We extended this question in Experiment 2 to a more visual domain using pictures that 'morphed' from one entity into another and asked participants to decide when they no longer considered an item to be that item (20 patients, 25 controls). We did not find a difference between patients and controls in their sensitivity to detect boundaries of representations. These two experiments do not support the notion that thought disorder with postulated looseness of association or over-inclusive thinking is related to reduced awareness of boundaries of semantic category membership or entities, and inferentially their featural network. Despite anomalies in the semantic system in schizophrenia, we found aspects to be intact. This specificity of semantic processing is promising, suggesting that research will be informative as to how semantic memory is constructed, and thus how it can selectively break down. Moreover, this study indicates that patients do not 'fail' semantic tasks (e.g. priming) because of globally disorganized decision-making: here their capability to make precise distinctions between representations was intact.

Adult↗

PubMed2002

Semantic clustering in verbal fluency: schizophrenic patients versus control participants.

BACKGROUND: Schizophrenic patients generate fewer words than healthy controls during verbal fluency tasks. The structure of output may explain why patients generate fewer exemplars. METHODS: Twenty-four healthy controls and 24 patients with schizophrenia participated in six, 3 min semantic fluency tasks. In a subsequent session, participants were given cards, each printed with one of their own words generated from previous fluency tasks. Participants were to sort the cards into categories (e.g. subcategories of 'animals'), thus defining their own semantic subcategories of words, and thereby eliminating experimenter assumptions about word relatedness. These clusters were matched with fluency output of each participant. The time spent searching through semantic networks within clusters and switching to other clusters when locating and producing associated words were measured. RESULTS: Patients produced fewer words and spent more time switching to words within clusters and to different clusters than controls, but otherwise response profiles were similar. Although controls returned more frequently to clusters and consequently made more switches between these clusters than patients, this group difference disappeared when the total number of words produced was covaried. CONCLUSIONS: Consistent with previous literature, patients produced fewer words and made more errors than controls. The absence of a group difference in number of different clusters or mean number of items per cluster suggests that patients are similar to controls with respect to number of ideas in their semantic network. Patients' longer between-cluster switching times indicate a general slowness that may be attributed to difficulties finding new words within a semantic field.

Adult↗

PubMed2001

Prefrontal neurons and the genetics of schizophrenia.

This article reviews prefrontal cortical biology as it relates to pathophysiology and genetic risk for schizophrenia. Studies of prefrontal neurocognition and functional neuroimaging of prefrontal information processing consistently reveal abnormalities in patients with schizophrenia. Abnormalities of prefrontal information processing also are found in unaffected individuals who are genetically at risk for schizophrenia, suggesting that genetic polymorphisms affecting prefrontal function may be susceptibility alleles for schizophrenia. One such candidate is a functional polymorphism in the catechol-o-methyl transferase (COMT) gene that markedly affects enzyme activity and that appears to uniquely impact prefrontal dopamine. The COMT genotype predicts performance on prefrontal executive cognition and working memory tasks. Functional magnetic resonance imaging confirms that COMT genotype affects prefrontal physiology during working memory. Family-based association studies have revealed excessive transmission to schizophrenic offspring of the allele (val) related to poorer prefrontal function. These various data provide convergent evidence that the COMT val allele increases risk for schizophrenia by virtue of its effect on dopamine-mediated prefrontal information processing-the first plausible mechanism for a genetic effect on normal human cognition and risk for mental illness.

Alleles↗

PubMed2001

A comparison of verbal fluency tasks in schizophrenic patients and normal controls.

Previous studies have reported significant impairment on verbal fluency tasks (semantic and letter) among schizophrenic subjects. However, the possibility of specific categorical deficits has not been adequately investigated. Nor have the effects of task duration, the stability between testing sessions, and the relationship between intelligence and performance on fluency been thoroughly studied. We performed a series of 3 min fluency tasks (semantic/syntactic and letter) to determine whether duration specific or category-specific differences exist between schizophrenic subjects and normal controls. Each subject was tested at three different times as a means of estimating word pool and assessing the stability of fluency output. Subjects were asked to generate exemplars from each of four semantic/syntactic categories (animals, tools, common nouns and verbs) and three letters (G, E and T). Data from 13 schizophrenic subjects and 15 sex-, age- and pre-morbid-IQ-matched control subjects revealed that patients' overall performance on both the semantic and letter fluency tasks was impaired. While differential impairment on specific semantic categories was noted between groups, no differential effects relating to task duration or testing session were present. Further, by comparing the number of novel words produced in the three testing sessions, we found the groups to be equivalent, a finding we take to suggest that schizophrenic patients' lexicon is intact. Covarying current IQ eliminated the group difference robustly for letter fluency, while only marginally for semantic fluency. Our data revealed the presence of impairment in semantic and letter fluency tasks in schizophrenic patients consistent with previous reports, and also that patients were differentially impaired on semantic categories.

Adult↗

PubMed2001

Relative risk for cognitive impairments in siblings of patients with schizophrenia.

BACKGROUND: Patients with schizophrenia have impairments in several domains of cognition, including working memory/executive function, verbal memory, language, oculomotor scanning/psychomotor speed, and general intelligence. Impairments have also been found in unaffected siblings, suggesting they could be heritable. To assess the suitability of cognitive dysfunction for use in genetic studies, we estimated relative risk (lambda) in a large cohort of siblings. METHODS: One hundred forty-seven patients with schizophrenia, 193 of their siblings, and 47 control subjects were studied using a neuropsychological test battery, which included intelligence quotient (IQ), Wide Range Achievement Test, Wisconsin Card Sort, Wechsler Memory Scale (revised), California Verbal List Test, Trails A and B, and Letter and Category Fluency. Relative risk was estimated using a cutoff score of 1 SD below the control mean. RESULTS: As expected, patients performed markedly worse than control subjects on all tests except the Wide Range Achievement Test. Siblings had impaired performance on the Wisconsin Card Sort and Trails B, with trends for reduction (p = .01-.05) on the California Verbal List Test and Letter Fluency. Relative risk to siblings was elevated on the Trails B (lambda = 4.0) and California Verbal List Test (lambda = 2.8). Trends (p = .01-.05) for increased lambda were also seen for Wisconsin Card Sort, Letter Fluency, Wechsler Memory Scale and decline in IQ (lambda = 1.74-2.4). Correlations between tests of different cognitive functions were weak, indicating they measure relatively independent processes. CONCLUSION: Unselected siblings of patients with schizophrenia have impairments in several cognitive domains. Relative risk scores were in the moderate range, suggesting a significant genetic component. Impairments on one test only weakly predicted impairments on other tests. Thus, cognitive phenotypes identify distinct, familial traits associated with schizophrenia. Using this dimensional approach to subdividing schizophrenia may reduce the clinical and genetic heterogeneity of schizophrenia and improve the power of genetic studies.

Adult↗

PubMed2001

Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia.

Abnormalities of prefrontal cortical function are prominent features of schizophrenia and have been associated with genetic risk, suggesting that susceptibility genes for schizophrenia may impact on the molecular mechanisms of prefrontal function. A potential susceptibility mechanism involves regulation of prefrontal dopamine, which modulates the response of prefrontal neurons during working memory. We examined the relationship of a common functional polymorphism (Val(108/158) Met) in the catechol-O-methyltransferase (COMT) gene, which accounts for a 4-fold variation in enzyme activity and dopamine catabolism, with both prefrontally mediated cognition and prefrontal cortical physiology. In 175 patients with schizophrenia, 219 unaffected siblings, and 55 controls, COMT genotype was related in allele dosage fashion to performance on the Wisconsin Card Sorting Test of executive cognition and explained 4% of variance (P = 0.001) in frequency of perseverative errors. Consistent with other evidence that dopamine enhances prefrontal neuronal function, the load of the low-activity Met allele predicted enhanced cognitive performance. We then examined the effect of COMT genotype on prefrontal physiology during a working memory task in three separate subgroups (n = 11-16) assayed with functional MRI. Met allele load consistently predicted a more efficient physiological response in prefrontal cortex. Finally, in a family-based association analysis of 104 trios, we found a significant increase in transmission of the Val allele to the schizophrenic offspring. These data suggest that the COMT Val allele, because it increases prefrontal dopamine catabolism, impairs prefrontal cognition and physiology, and by this mechanism slightly increases risk for schizophrenia.

Adult↗

PubMed2001

Short-term memory for serial order in schizophrenia: a detailed examination of error types.

Cognitive deficits in schizophrenia have been associated with working memory problems. Schizophrenic patients (n = 24) and controls (n = 29) participated in simple short-term memory tasks, recalling a list of letters from the first to last item in the order of presentation. The authors hypothesized that deficient sequential representations would increase movement errors (e.g., ABCD being recalled as ABDC) or intrusion errors (e.g., ABCD being recalled as ABCX), whereas simple trace decay would lead to omission errors (e.g., ABCD being recalled as ABC_). Patients made disproportionately more omissions toward the end of 6-item lists. There were no group differences in movements or intrusions as a function of serial position. Schizophrenic patients' limited short-term memory span may be due to greater forgetting during recall and not to a selective deficit in the mechanisms responsible for maintaining serial order information.

Adult↗

PubMed2001

Associating semantic space abnormalities with formal thought disorder in schizophrenia: use of triadic comparisons.

Recent studies of schizophrenia have suggested that thought disorder results from abnormalities in semantic processing. In the following pilot study, the cognitive system used for organizing and associating concepts was examined using a triadic comparison task. The semantic maps of schizophrenia patients with high thought disorder (N = 5) were compared to that of schizophrenia patients with low levels of thought disorder (N = 5) and normal controls (N = 10) with multidimensional scaling analysis. At initial testing and at retest, patients with high levels of thought disorder exhibited consistently lower semantic goodness of fit scores and failed to map results of triadic comparisons along well-defined dimensions. Results suggest that thought disorder in schizophrenia is related to a disturbance in the organization of semantic networks.

Adult↗

PubMed2001

Relative risk of neurological signs in siblings of patients with schizophrenia.

OBJECTIVE: First-degree relatives of patients with schizophrenia appear to have subtle neurological signs, suggesting that these measures could serve as intermediate phenotypes in genetic studies of schizophrenia. The strength of a possible genetic component is unknown, however, leaving it uncertain whether such traits could increase the power to find schizophrenia susceptibility loci. The authors' goal was to investigate the strength of this possible genetic component. METHOD: They estimated the relative risk of neurological impairments in a large group of siblings of patients with schizophrenia. Two standard neurological scales (the Neurological Evaluation Scale and the Woods Scale) were used to examine 115 patients, 185 of their siblings, and 88 normal comparison subjects. RESULTS: There were significant differences between the siblings of patients with schizophrenia and the normal comparison subjects only on the Woods Scale. Relative risk of neurological impairment was significantly increased in the sibling group, but the significance was weak to moderate. Neurological impairment was not redundant with several other intermediate phenotypic measures based on cognitive impairment. CONCLUSIONS: These data suggest that neurological signs cluster in patients with schizophrenia and their families and could possibly identify a unique component of genetic variance for risk of schizophrenia. However, the fairly low relative risk and the uncertain pathophysiology of such signs may limit their usefulness.

Adult↗

PubMed2000

Memory for temporal order in patients with schizophrenia.

There is some evidence that memory for temporal order is a process that may be impaired independently of other forms of memory. For example, patients with Korsakoff's syndrome have been shown to have poorer temporal-order memory than other amnesic patients, despite item memory being equivalent. Patients with schizophrenia have been reported to have a variety of memory problems, although memory for the order of events has not been examined very frequently. In this study, we tested memory for temporal order in patients with schizophrenia and in control subjects. Subjects were presented with two lists of 15 words (at two different times) and were later asked to reproduce the order of each list from a random array of the words. In both versions of the test, patients with schizophrenia were impaired in placing the items in the correct temporal order. Recall and recognition of the actual words used to comprise the lists were also impaired in the schizophrenic patients. However, when recall measures were covaried, and when patients were matched with controls for recall, post-hoc group differences in temporal memory were eliminated. In contrast, covarying recognition (indexed by d' or matching for recognition) did not eliminate group differences. Therefore, although memory for temporal order is compromised in patients with schizophrenia, this deficit is highly correlated with generally poorer item-specific memory retrieval (i.e., recall). It is possible that both impairments are due to some third process that underlies and aids in the reconstruction of episodes.

Adolescent↗

PubMed2000

Cognitive impairments in patients with schizophrenia displaying preserved and compromised intellect.

BACKGROUND: Although intellectual and neurocognitive deficits accompany schizophrenia, there are inconsistencies in the literature concerning issues of intellectual decline, premorbid deficits, a modal deficit pattern, and preserved abilities. METHODS: A battery of neuropsychological tests was administered once to 117 consecutively admitted patients with chronic schizophrenia and a group of 27 healthy control subjects to examine patterns of premorbid and current intellect (measured by means of reading scores and IQ, respectively) and the attendant cognitive profiles in schizophrenia using classification methods based on clinically derived (IQ levels) and atheoretical (cluster) techniques. RESULTS: Sixty patients (51%) with schizophrenia who displayed a general intellectual decline of 10 points or greater from estimated premorbid levels also exhibited deficits of executive function, memory, and attention. Twenty-eight patients (23%) with consistently low estimated premorbid intellect and current intellectual levels who displayed no evidence of IQ decline exhibited language and visual processing deficits in addition to deficits present in the intellectually declining group. The remaining 29 patients (25%) who displayed average estimated premorbid intellectual levels did not show IQ decline and exhibited a cognitive profile similar to normal, with the exception of executive function and attention impairment. Atheoretical analyses support the findings from clinically derived subgroups. CONCLUSIONS: These results suggest that IQ decline, although modal in schizophrenia, is not universally characteristic and that executive function and attention deficits may be core features of schizophrenia, independent of IQ variations.

Adult↗

PubMed2000

Effects of dextroamphetamine on cognitive performance and cortical activation.

Monoaminergic neurotransmitters are known to have modulatory effects on cognition and on neurophysiological function in the cortex. The current study was performed with BOLD fMRI to examine physiological correlates of the effects of dextroamphetamine on working-memory performance in healthy controls. In a group analysis dextroamphetamine increased BOLD signal in the right prefrontal cortex during a task with increasing working-memory load that approached working-memory capacity. However, the effect of dextroamphetamine on performance and on signal change varied across individuals. Dextroamphetamine improved performance only in those subjects who had relatively low working-memory capacity at baseline, whereas in the subjects who had high working-memory capacity at baseline, it worsened performance. In subjects whose performance deteriorated, signal change was greater than that in subjects who had an improvement in performance, and these variations were correlated (Spearman rho = 0.89, P<0.02). These data shed light on the manner in which monoaminergic tone, working memory, and prefrontal function interact and, moreover, demonstrate that even in normal subjects the behavioral and neurophysiologic effects of dextroamphetamine are not homogeneous. These heterogeneic effects of dextroamphetamine may be explained by genetic variations that interact with the effects of dextroamphetamine.

Adult↗

PubMed2000

Paired-associate learning and memory interference in schizophrenia.

Patients with frontal lobe damage have been shown to exhibit disproportionate impairments of second list learning as a result of interference effects. Based upon the assumption that schizophrenia is associated with frontal dysfunction, we attempted to explore how various manipulations of paired-associate learning tasks would interfere with schizophrenic patients' memory performance. Patients with schizophrenia were administered four tests of paired-associate learning, in which cue and response words were manipulated to increase interference across two study lists. In two tests of paired-associate learning (AB-AC test), cue words used in one list were repeated in a second list but were associated with different response words (e.g. lion-hunter, lion-circus). One version of this test employed moderately related word pairs and the other version employed unrelated word pairs. In the other two tests (AB-ABr test), all words used in one list were repeated in a second list but were rearranged to form new pairs. Again, one version of this test used moderately related word pairs and the other version used unrelated word pairs. We hypothesized that patients with schizophrenia would exhibit disproportionate impairment of second-list learning as a result of interference effects and that they would do especially poorly in the AB-ABr task, where the word pairs were unrelated. However, these predictions were not supported. Furthermore, it was difficult to tease apart a specific problem in list discrimination from the generally poor memory of the schizophrenic patients. We suggest that the susceptibility to these interference effects in patients with schizophrenia is not a specific problem in cognition, but rather one that is confounded by general memory problems.

Adolescent↗

PubMed2000

Effects of neuroleptic medications on speech disorganization in schizophrenia: biasing associative networks towards meaning.

BACKGROUND: While some cognitive accounts of disorganized speech, or thought disorder, in schizophrenia have emphasized failures in working memory/discourse planning or selective attention, we have suggested that thought disorder resides in the semantic system. In this study we assessed the effect of neuroleptic medication on thought disorder and semantic processing. METHODS: Seventeen patients with schizophrenia were assessed while receiving neuroleptic medications and in crossover fashion, placebo. A number of measures were obtained: clinically rated thought disorder (using the Thought, Language and Communication Scale); working memory letter number span); lexical integrity (naming and receptive vocabulary); and, semantic priming of intracategorical word pairs. RESULTS: Semantic priming measures improved with neuroleptic medication, as did clinically rated thought disorder. No other measure changed significantly. Priming selectively covaried with changes in thought disorder. CONCLUSION: Changes in spreading semantic activation, measured in a semantic priming paradigm and presumably brought about by neuroleptics' influence on dopaminergic neuromodulatory systems, might reflect changes in the biases of pre-existing associative networks that favour or increase the accessibility of representations related by shared features. This study also has implications for the architecture of normal language in that a dissociation between the lexical and semantic levels was observed, due to the selective compromise of tasks demanding semantic processing.

Adult↗

PubMed2000

A comparison of rCBF patterns during letter and semantic fluency.

To evaluate the functional neuroanatomies underlying letter and category fluency, 18 normal controls were studied with oxygen-15 water regional cerebral blood flow positron emission tomography. Three counterbalanced conditions each consisted of 6 trials (45 s each): letter fluency (generating words when cued with a particular letter), semantic fluency (generating words when cued with a particular category), and a control condition (generating days of the week and months of the year). Relative to the control, participants activated similar brain regions during both fluency tasks, including the anterior cingulate, left prefrontal regions, thalamus, and cerebellum; reductions were found in parietal and temporal regions. In a direct comparison of the 2 fluency tasks, inferior frontal cortex and temporoparietal cortex (hypothesized to participate in a phonologic loop for accessing word pronunciation) were activated more during letter than semantic fluency, whereas left temporal cortex (associated with access to semantic storage) was activated more during semantic than letter fluency. This study identifies subtle differences in the neural networks underlying letter and semantic fluency that may underlie the dissociation of these abilities in patients.

Adult↗

PubMed2000

Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited.

Evidence implicates subtle neuronal pathology of the prefrontal cortex (PFC) in schizophrenia, but how this pathology is reflected in physiological neuroimaging experiments remains controversial. We investigated PFC function in schizophrenia using functional magnetic resonance imaging (fMRI) and a parametric version of the n-back working memory (WM) task. In a group of patients who performed relatively well on this task, there were three fundamental deviations from the 'healthy' pattern of PFC fMRI activation to varying WM difficulty. The first characteristic was a greater magnitude of PFC fMRI activation in the context of slightly impaired WM performance (i.e. physiological inefficiency). The second was that the significant correlations between behavioral WM performance and dorsal PFC fMRI activation were in opposite directions in the two groups. Third, the magnitude of the abnormal dorsal PFC fMRI response was predicted by an assay of N-acetylaspartate concentrations (NAA) in dorsal PFC, a measure of neuronal pathology obtained using proton magnetic resonance spectroscopy. Patients had significantly lower dorsal PFC NAA than controls and dorsal PFC NAA inversely predicted the fMRI response in dorsal PFC (areas 9, 46) to varying WM difficulty - supporting the assumption that abnormal PFC responses arose from abnormal PFC neurons. These data suggest that under certain conditions the physiological ramifications of dorsal PFC neuronal pathology in schizophrenia includes exaggerated and inefficient cortical activity, especially of dorsal PFC.

Adolescent↗

PubMed2000

Continuous performance test and schizophrenia: a test of stimulus-response compatibility, working memory, response readiness, or none of the above?

OBJECTIVE: Abnormalities of attention are considered the fundamental deficits in cognitive function manifested by patients with schizophrenia. The authors administered variations of two types of cognitive tasks to patients with schizophrenia (N=20) and normal comparison subjects (N=30) to test four possible cognitive mechanisms that might account for such abnormalities. METHOD: Variations of the Continuous Performance Test were used to test the four mechanisms. Stimulus-response mapping was explored by comparing results on a task in which subjects were to make a response if the word "nine" was preceded by the word "one" with results on a task in which the required response was made explicit by the stimulus (the word "ready" followed by the word "press"). The building up of a prepotent response tendency was tested by manipulating the probability with which the cue and imperative stimulus appeared (17% or 50%). The amount of working memory required to maintain contextual information was tested by using different delay intervals (1000 msec and 3000 msec). The extent to which problems in vigilance might be attributable to problems in the "motoric" component of response readiness was operationalized by having subjects perform a secondary motor task concurrent with the attentional task. RESULTS: Patients with schizophrenia performed significantly worse than the normal comparison subjects on all tasks. However, none of the four manipulations of the Continuous Performance Test tasks had a differential impact on the patients' performance speed or accuracy. In contrast, there was a significant interaction of group, delay interval, and target probability in which patients made disproportionately more omission errors at short delay intervals and at low target probabilities. CONCLUSIONS: The findings may call into question the explanatory power of certain well-known contemporary mechanistic accounts of performance on the Continuous Performance Test in patients with schizophrenia. The findings suggest that a difficulty in rapidly encoding information (i.e., constructing a representation) in certain "unengaging" situations may be at the core of deficits on tasks associated with this attentional test.

Adult↗