Fronto-temporal dysregulation in remitted bipolar patients: an fMRI delayed-non-match-to-sample (DNMS) study

Autor: Carrie E. Bearden, Sophia Frangou, Dawn I. Velligan, E. Serap Monkul, Diana Tordesillas-Gutiérrez, David C. Glahn, Jennifer L. Robinson
Rok vydání: 2009
Předmět:
Zdroj: Bipolar Disorders. 11:351-360
ISSN: 1399-5618
1398-5647
DOI: 10.1111/j.1399-5618.2009.00703.x
Popis: There is growing evidence that at least a proportion of patients with bipolar disorder have significant cognitive impairments, even during periods of symptomatic remission (1–5). Working memory—defined as the temporary maintenance and manipulation of information—is among the most severely affected cognitive domains (1, 6, 7), with the level of deficit rising with increasing task difficulty (8). Both structural and functional abnormalities have been reported in bipolar patients in brain regions relevant for working memory function, including the dorsolateral prefrontal cortex (PFC), anterior cingulate cortex (ACC), and medial temporal lobe (MTL) (9–11). Most theoretical models of working memory distinguish between manipulation and maintenance processes, highlighting that these processes are differentially served by prefrontal regions, with dorsolateral prefrontal regions and superior parietal regions being differentially involved in the manipulation of information (12–14), and ventrolateral prefrontal regions in the maintenance of information (14). Recently, we developed a novel delayed-non-match-to-sample (DNMS) working memory task that highlights maintenance processes with separate conditions requiring the use of distinct mnemonic strategies to facilitate performance. Specifically, the task includes a condition that emphasizes the use of contextual information to organize familiar stimuli (‘familiarity condition’) and a condition where using holistic representations of novel stimuli (‘novelty condition’) is advantageous. While the former has been linked to prefrontal activation (15–17), the latter is thought to be associated more closely with MTL function (18). Previously, we employed this task behaviorally in a moderately symptomatic sample of patients with bipolar disorder and found that bipolar patients had deficits consistent with organizational dysfunction and poor detection of novel information relative to healthy controls (19). Although these results imply prefrontal and medial temporal dysfunction in bipolar disorder, direct assessment of neurophysiologic differences during task performance is necessary. In the current experiment, we used functional magnetic resonance imaging (fMRI) to examine activity in remitted patients with bipolar I disorder and demographically matched healthy comparison subjects while performing our working memory task (19). We focused on patients in symptomatic remission to ensure that between-group neurophysiologic differences during task performance were not due to confounding effects of current mood symptoms. Thus, the present design allowed assessment of trait-related functional abnormalities within prefrontal and medial temporal regions. Consistent with the notion of working memory network dysfunction, particularly with regard to maintenance processes, implied by our prior behavioral findings utilizing this paradigm (19), we hypothesized that remitted patients with bipolar disorder would exhibit reduced neural activity compared to healthy subjects in prefrontal regions during the familiarity condition, and in MTL regions during the novelty condition.
Databáze: OpenAIRE
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