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Biomedical subjects

Trevor Robbins

Publications and source records attributed to Trevor Robbins.

9 recordsLinked to original sources

Intra-dimensional/extra-dimensional set-shifting performance in schizophrenia: impact of distractors.

BACKGROUND: We sought to determine if a representative group of young chronic patients with schizophrenia would demonstrate selective impairments in set shifting processes of the CANTAB Intra-dimensional/extra-dimensional (IDED) task. We predicted that patients would have prominent difficulties with Compound Discrimination (C_D) (stage of the task in which irrelevant stimuli are introduced) and Extra-Dimensional Shifting (EDS) (stage of the task in which a new stimulus dimension must be attended) on the basis of the results of cortical hypodopaminergic states in subhuman primates (for C_D) and effects of dorsolateral prefrontal cortical lesions on set shifting and prior results in schizophrenia (for EDS). METHODS: We administered the IDED to 36 patients and 26 healthy controls. Additionally, we administered the Wisconsin Card Sorting Test (WCST), another test of set shifting, and a Continuous Performance Test (CPT) type task of attention to patients with schizophrenia in order to investigate which cognitive components accounted for performance difficulties at different stages of the IDED task. RESULTS: Patients had selective difficulties on C_D and EDS stages of the task. In schizophrenic patients early stages of the task involving the introduction and establishment of attentional set were correlated to CPT performance, while later set shifting stages were correlated with WCST categories attained. CONCLUSION: We found evidence that patients with schizophrenia were susceptible to introduction of unreinforced irrelevant stimuli at the C_D stage, such that the previously rewarded target stimuli no longer held hegemony as a representation. This type of processing failure may reflect difficulties in stabilizing a representation and is consistent with effects of prefrontal hypodopaminergia in primates. Secondly, "survivors" of this stage experienced marked difficulties on EDS-stage, suggestive of classic prefrontal failures.

Adult↗

Cognitive function and nigrostriatal markers in abstinent methamphetamine abusers.

OBJECTIVE: Preclinical investigations have established that methamphetamine (MA) produces long-term changes in dopamine (DA) neurons in the striatum. Human studies have suggested similar effects and correlated motor and cognitive deficits. The present study was designed to further our understanding of changes in brain function in humans that might result from chronic high dose use of MA after at least 3 months of abstinence. METHOD: Brain function in abstinent users was compared to controls using neuroimaging of monoamine transporters and cognitive assessment. Striatal levels of DA transporter (DAT) and vesicular monoamine transporter type-2 (VMAT2) were determined using [11C]methylphenidate and [11C]dihydrotetrabenazine positron emission tomography, respectively. Cognitive function was evaluated using tests of motor function, memory, learning, attention, and executive function. RESULTS: Striatal DAT was approximately 15% lower and VMAT2 was 10% lower in MA abusers across striatal subregions. The MA abusers performed within the normal range but performed more poorly compared to controls on three of the 12 tasks. CONCLUSIONS: Failure to find more substantial changes in transporter levels and neurocognitive function may be attributed to the length of time that MA users were abstinent (ranging from 3 months to more than 10 years, mean 3 years), although there were no correlations with length of abstinence. Persistent VMAT2 reductions support the animal literature indicating a toxic effect of MA on nigrostriatal nerve terminals. However, the magnitude of the MA effects on nigrostriatal projection integrity is sufficiently small that it is questionable whether clinical signs of DA deficiency are likely to develop.

Adolescent↗

Risk taking during decision-making in normal volunteers changes with age.

Risk taking in a large cohort of adults (N = 177; ages 17-73) decreased with age, demonstrated by performance on a computer based gambling task, which has previously been shown to be sensitive to certain pharmacological manipulations including tryptophan depletion, lesions of the orbitofrontal cortex and neuropsychiatric disorders such as mania. Aging was also associated with longer deliberation times, poorer decision making, reduced risk taking, but no significant change in delay aversion. Subjects with a higher (NART-estimated) IQ were faster to make decisions and showed a greater modulation of risk-taking. Both sexes showed similar patterns of decision making, although male participants exhibited a greater modulation of risk-taking in response to the probability of winning. The Decision-Gamble task provides a variety of behavioral measures, corresponding to different aspects of impulsivity. Factor analysis of these measures suggested that two independent traits underlies performance on the task in normal individuals: one associated with risk tolerance, and a second associated with delay aversion. Age was related to decreases in the risk tolerance factor, but unrelated to the delay aversion; neither factor was significantly related to verbal IQ. This study thus provides support for the concept that impulsivity can be fractionated into 2 or more components.

Adolescent↗

Preclinical models: status of basic research in depression.

Approximately one half-century ago several classes of medications, discovered by serendipity, were introduced for the treatment of depression and bipolar disorder. These highly effective medications revolutionized our approach to mood disorders and helped launch the modern era of psychiatry. Yet our progress since those serendipitous discoveries has been disappointing. We still do not understand with certainty how those medications produce their desired clinical effects. We have not introduced newer medications with fundamentally different mechanisms of action than the older agents. We have not identified the genetic and neurobiological mechanisms underlying depression and mania, nor do we understand the mechanisms by which nongenetic factors influence these disorders. We have only a rudimentary understanding of the circuits in the brain responsible for the normal regulation of mood and affect, and of those circuits that function abnormally in mood disorders. In approaching these gaps in our knowledge, this workgroup highlighted four major areas for future investment. These include developing better animal models of mood disorders; identifying genetic determinants of normal and abnormal mood in humans and animals; discovering novel targets and biomarkers of mood disorders and treatments; and increasing the recruitment of investigators from diverse backgrounds to mood disorders research.

Animals↗

Decision-making deficits in drug addiction.

Core aspects of addictive behaviour can be explained in terms of abnormal decision-making. Using recording of autonomic function during performance of two gambling tasks, Bechara et al. have recently identified three distinct neuropsychological subtypes in individuals with substance dependence. These subtypes may reflect dissociable patterns of disruption in limbic brain circuitry.

Journal Article↗

Decision-making processes following damage to the prefrontal cortex.

Recent work has suggested an association between the orbitofrontal cortex in humans and practical decision making. The aim of this study was to investigate the profile of cognitive deficits, with particular emphasis on decision-making processes, following damage to different sectors of the human prefrontal cortex. Patients with discrete orbitofrontal (OBF) lesions, dorsolateral (DL) lesions, dorsomedial (DM) lesions and large frontal lesions (Large) were compared with matched controls on three different decision-making tasks: the Iowa Gambling Task and two recently developed tasks that attempt to fractionate some of the cognitive components of the Iowa task. A comprehensive battery including the assessment of recognition memory, working memory, planning ability and attentional set-shifting was also administered. Whilst combined frontal patients were impaired on several of the tasks employed, distinct profiles emerged for each patient group. In contrast to previous data, patients with focal OBF lesions performed at control levels on the three decision-making tasks (and the executive tasks), but showed some evidence of prolonged deliberation. DL patients showed pronounced impairment on working memory, planning, attentional shifting and the Iowa Gambling Task. DM patients were impaired at the Iowa Gambling Task and also at planning. The Large group displayed diffuse impairment, but were the only group to exhibit risky decision making. Methodological differences from previous studies of OBF patient groups are discussed, with particular attention to lesion laterality, lesion size and psychiatric presentation. Ventral and dorsal aspects of prefrontal cortex must interact in the maintenance of rational and 'non-risky' decision making.

Adult↗

Executive dysfunction in first-episode schizophrenia and relationship to duration of untreated psychosis: the West London Study.

BACKGROUND: Many studies have demonstrated early generalised cognitive impairment in schizophrenia. AIMS: To examine executive function in first-episode schizophrenia, characterise the nature of the impairment and specify any relationships with symptoms and duration of untreated psychosis (DUP). METHOD: Patients (n = 136) and normal controls (n = 81) were assessed with the Cambridge Automated Neuropsychological Test Battery, National Adult Reading Test IQ, and Scales for the Assessment of Positive and Negative Symptoms. RESULTS: Memory and executive impairments in patients were independent of IQ level. Spatial working memory was impaired because of inadequate strategy use. On a planning task, patients showed reduced planning times and suboptimal problem-solving. On an attentional set-shifting task, 75% of patients were able to perform an extra-dimensional shift thought to be a core attribute of prefrontal cortex function. Those who failed had significantly longer DUP. CONCLUSIONS: Prefrontal cortex function deteriorates at the onset of psychosis and continues to worsen over time.

Adolescent↗

Impulsivity in patients with borderline personality disorder.

This study investigated features of impulsivity in patients with borderline personality disorder (BPD) using the self-report Attention-Deficit Scales for Adults (ADSA) and computer-administered neurocognitive tasks. Forty-one patients with DSM-III-R BPD and 35 nonclinical control subjects were assessed by the ADSA, the National Adult Reading Test, and two computerized tasks mediated by the frontal lobes. Mean scores for seven ADSA scales (six of which relate to aspects of impulsivity) were significantly higher in the patient group compared with the control group. Also, the ADSA ratings for impaired coordination were increased in the BPD patients. The findings indicate that a range of aspects of impulsivity, as well as impaired coordination, are associated with patients selected on the basis of BPD. Also, in the patient group, but not in the control group, associations of the neurocognitive tasks indicated that, first, performance on a planning task related to dorsolateral frontal lobe functioning is correlated with aspects of impulsivity reflected by ADSA scale III ratings (involving disorganisation and lack of perseverance) and, second, performance on a decision-making task related to orbitofrontal functioning is correlated with ratings of impaired coordination. Further work is needed to establish the specificity of the findings.

Adolescent↗