Biomedical subjects

Thomas W Weickert

Publications and source records attributed to Thomas W Weickert.

6 recordsLinked to original sources

PubMed2005

Neural mechanisms underlying probabilistic category learning in normal aging.

Probabilistic category learning engages neural circuitry that includes the prefrontal cortex and caudate nucleus, two regions that show prominent changes with normal aging. However, the specific contributions of these brain regions are uncertain, and the effects of normal aging have not been examined previously in probabilistic category learning. In the present study, using a blood oxygenation level-dependent functional magnetic resonance imaging block design, 18 healthy young adults (mean age, 25.5 +/- 2.6 years) and 15 older adults (mean age, 67.1 +/- 5.3 years) were assessed on the probabilistic category learning "weather prediction" test. Whole-brain functional images acquired using a 1.5T scanner (General Electric, Milwaukee, WI) with gradient echo, echo planar imaging (3/1 mm; repetition time, 3000 ms; echo time, 50 ms) were analyzed using second-level random-effects procedures [SPM99 (Statistical Parametric Mapping)]. Young and older adults displayed equivalent probabilistic category learning curves, used similar strategies, and activated analogous neural networks, including the prefrontal and parietal cortices and the caudate nucleus. However, the extent of caudate and prefrontal activation was less and parietal activation was greater in older participants. The percentage correct and reaction time were mainly positively correlated with caudate and prefrontal activation in young individuals but positively correlated with prefrontal and parietal cortices in older individuals. Differential activation within a circumscribed neural network in the context of equivalent learning suggests that some brain regions, such as the parietal cortices, may provide a compensatory mechanism for healthy older adults in the context of deficient prefrontal cortex and caudate nuclei responses.

Adult↗

PubMed2005

First- and second-generation antipsychotic medication and cognitive processing in schizophrenia.

Schizophrenia has been consistently characterized by deficits in the cognitive domains of executive function, working memory, attention, and episodic memory. Although some cognitive abnormalities, such as motor slowing, may be associated with antipsychotic medication administration, generally the cognitive deficits shown by patients with schizophrenia can be attributed at least in part to the disease process. Modulation of the dopamine neurotransmitter system, notably through D2 receptor blockade, has been associated with psychotic symptom reduction and cognitive performance improvements in patients with schizophrenia. Although first-generation antipsychotic medication treatment initially was thought not to result in cognitive improvement, recent studies comparing second-generation antipsychotics to low doses of first-generation antipsychotic medication showed cognitive benefits for first-generation drugs, although perhaps not as great as that found after treatment with second-generation medication. Cognitive improvement associated with administration of antipsychotic medication may be a manifestation of improvement in general cortical information processing. Recent work has shown that specific genetic polymorphisms may interact with antipsychotic medication treatment to influence the degree to which cognitive abilities display improvement after treatment. In particular, the catechol-O-methyltransferase val108/158met polymorphism has been shown to predict working memory improvement after administration of antipsychotic medication to patients with schizophrenia.

Antipsychotic Agents↗

PubMed2004

Catechol-O-methyltransferase val108/158met genotype predicts working memory response to antipsychotic medications.

BACKGROUND: The gene encoding catechol-O-methyltransferase (COMT), an enzyme that regulates prefrontal cortex dopamine, contains a common functional polymorphism (val(108/158)met) that influences prefrontal cortex function in an allelic dose-dependent manner. A recent study reported that the COMT val(108/158)met polymorphism influences cognitive- and physiologic-related prefrontal cortex responses to antipsychotic treatment. The present study tested the effects of several COMT polymorphisms on the cognitive response to antipsychotic medication in patients with schizophrenia. METHODS: Twenty inpatients with schizophrenia or schizoaffective disorder (5 with the val-val genotype, 11 with val-met, and 4 with met-met) were administered cognitive tests at two time points: once after 4 weeks of treatment with antipsychotic medication and once after 4 weeks of placebo administration, according to a counterbalanced, double-blind, within-subject study design. RESULTS: Patients homozygous for the COMT met allele displayed significant improvement on the working memory task after treatment. Patients homozygous for the COMT val allele did not show working memory improvement with treatment. Other COMT polymorphisms were not associated with significant differences between treatment and placebo conditions. CONCLUSIONS: These results support other data suggesting that the COMT val(108/158)met polymorphism might be an important factor in the cognitive response to antipsychotic medication.

Adult↗

PubMed2004

Lack of false recognition in schizophrenia: a consequence of poor memory?

The tendency to falsely recognize items as ones previously presented is increased in patients with frontal lesions and in older participants, whereas patients with medial temporal lobe damage may display such poor memory that they are not especially susceptible to false recognition. Since patients with schizophrenia are often compared to these groups neurocognitively, we explored the extent to which they are more susceptible to false memory. Participants were presented with word lists along a semantic theme, such as "bread". After list presentation, recognition tasks were administered which contained both the studied words as well as unstudied words. Some of the unstudied words were related to the theme of the previously studied words, but never actually presented (e.g. semantic "lures"). In a separate test, free recall of these lists of words was assessed. Interestingly, it was control participants who made more errors at recall, and were especially susceptible to intrusions of the semantic lures. Patients with schizophrenia did not make more false recognition errors in general, and surprisingly they made disproportionately fewer false recognition errors to semantic lures specifically. We conclude that despite poor memory, patients with schizophrenia are not especially susceptible to interference from previous tasks and are not particularly prone to false recollections.

Adult↗

PubMed2003

Comparison of cognitive performances during a placebo period and an atypical antipsychotic treatment period in schizophrenia: critical examination of confounds.

Although previous studies report cognitive improvement following atypical antipsychotic administration in schizophrenia (SC), few placebo-controlled within-subject studies with examination of confounds (symptom reduction, cooperation, learning, and outliers) have been reported. The present study examines the effects of atypicals and confounds upon cognition in SC. The hypothesis tested was that relative to placebo, atypicals as a general class of medication would elicit cognitive improvement in SC. In all, 19 patients with SC (15 males) completed the double-blind, counterbalanced, randomized within-subject study of the effects of atypical antipsychotics (risperidone, clozapine, olanzapine, or quetiapine) vs placebo administration upon cognitive performance in the domains of executive function, attention, memory, language, visual perception, and general intellect. Significant cognitive improvement during atypical antipsychotic administration relative to placebo withdrawal occurred in most cognitive domains with robust improvements in intelligence (p=0.001), memory (p=0.0009), and fluency (p <0.002) even after outliers and unmotivated performances were excluded. These findings suggest that relative to placebo withdrawal, atypicals improve cognitive performance in SC. However, this finding may not be specific to atypicals, since analogous studies of typicals have not been performed.

Adult↗

PubMedDate not supplied

Habit and skill learning in schizophrenia: evidence of normal striatal processing with abnormal cortical input.

Different forms of nondeclarative learning involve regionally specific striatal circuits. The motor circuit (involving the putamen) has been associated with motor-skill learning and the dorsolateral prefrontal cortex (DLPFC) circuit (involving the caudate) has been associated with cognitive-habit learning. Efforts to differentiate functional striatal circuits within patient samples have been limited. Previous studies have provided mixed results regarding striatal-dependent nondeclarative learning deficits in patients with schizophrenia. In this study, a cognitive-habit learning task (probabilistic weather prediction) was used to assess the DLPFC circuit and a motor-skill learning task (pursuit rotor) was used to assess the motor circuit in 35 patients with schizophrenia and 35 normal controls. Patients with schizophrenia displayed significant performance differences from controls on both nondeclarative tasks; however, cognitive-habit learning rate in patients did not differ from controls. There were performance and learning-rate differences on the motor-skill learning task between the whole sample of patients and controls, however, analysis of a subset of patients and controls matched on general intellectual level eliminated learning rate differences between groups. The abnormal performance offset between patients with schizophrenia and controls in the absence of learning rate differences suggests that abnormal cortical processing provides altered input to normal striatal circuitry.

Adult↗