Changes in neuronal activation in patients with bipolar disorder during performance of a working memory task

Objectives: Several lines of evidence suggest that deficits in cognition persist in bipolar patients during periods of euthymia. Working memory impairment has been observed in euthymic bipolar patients and noted to be a significant source of functional deficits in psychiatric disorders. Functional changes associated with these cognitive deficits however, remain poorly understood. We hypothesized that patients with bipolar disorder would demonstrate changes in neuronal activation in specific regions forming part of the working memory network. Methods: Fifteen euthymic bipolar patients and fifteen age- and gender-matched healthy controls were recruited. Subjects participated in fMRI scans during which a two-back working memory task alternated with a zero-back control/attention task using a block-design paradigm. Groups were analyzed separately, and intergroup comparisons were made using an exploratory, voxel-by-voxel analysis. Results: Bipolar patients performed more poorly on the cognitive tasks than did healthy controls (F = 3.77, p = 0.04). After covarying for task performance and reaction time, bipolar patients demonstrated significantly greater activation than healthy subjects in several regions including the fronto-polar prefrontal cortex, temporal cortex, basal ganglia, thalamus, and posterior parietal cortex. No areas showed a significant decrease in activation, compared with healthy controls. Conclusions: Our findings suggest that decreased working memory performance in bipolar patients reflects specific neurofunctional deficits. These deficits may represent primary areas of neuropathology or be secondary to neuropathology elsewhere in the working memory network. Continued research utilizing other imaging modalities may further clarify the underlying neuropathology involved in these cognitive deficits.