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

Objectives: Bipolar disorder is associated with working memory (WM) impairments that persist during periods of symptomatic remission. However, the neural underpinnings of these deficits are not well understood. Methods: Fifteen clinically remitted bipolar patients and 15 demographically matched healthy controls underwent functional magnetic resonance imaging while performing a novel delayed-non-match-to-sample (DNMS) task. This nonverbal DNMS task involves two conditions, one requiring the organization of existing memory traces ('familiarity'), and one involving the formation of new memory traces ('novelty'). These processes are thought to differentially engage the prefrontal cortex and medial temporal lobe, respectively. Results: Although behavioral performance did not differ between groups, bipolar patients and controls exhibited significantly different patterns of neural activity during task performance. Patients showed relative hyperactivation in the right prefrontal gyrus and relative hypoactivation in visual processing regions compared to healthy subjects across both task conditions. During the novelty condition, patients showed a pattern of hypoactivation relative to controls in medial temporal regions, with relative hyperactivation in the anterior cingulate. Conclusions: These findings suggest that disruption in fronto-temporal neural circuitry may underlie memory difficulties frequently observed in patients with bipolar disorder.