Affective episodes in recently diagnosed patients with bipolar disorder associated with altered working memory-related prefrontal cortex activity: A longitudinal fMRI study

Introduction: Bipolar disorder (BD) is often accompanied by trait-related cognitive impairments, but it is unclear which neurocircuitry abnormalities give rise to these impairments and whether neurocircuitry differences are exacerbated with illness progression. This longitudinal fMRI study of recently diagnosed BD patients investigates whether aberrant working memory (WM) related activity in the cognitive control network is accentuated by new affective episodes. Methods: Forty-seven recently diagnosed BD patients in full or partial remission and 38 healthy controls were assessed with neurocognitive tests and fMRI during the performance of a verbal n-back WM task at baseline and follow-up (15.4 months in average). Results: Patients showed WM-related hypo-activity in dorsal prefrontal cortex (dPFC) and impaired cognitive function within attention and psychomotor speed, WM and executive function, and verbal learning and memory compared to controls at baseline. During the follow-up period, 26 patients experienced at least one affective episode (BD+), while 21 remained in remission (BD-). There was no deterioration in cognitive performance in BD+ compared to BD- patients. Nevertheless, BD+ displayed increased WM-related dPFC activity at follow-up compared with BD- patients. This change in dPFC response was independent of mood symptoms and medication. Limitations: The study did not account for type or frequency of affective episodes. Conclusion: The study identifies cognitive impairment and WM-related hypo-activity in dPFC early during the course of BD. Increased high-load WM related dPFC activity over the follow-up period in BD+ versus BD- patients in the absence of changes in cognitive performance may reflect an episode-related reduction in PFC efficiency.