Fronto-temporal dysregulation in asymptomatic bipolar I patients: a paired associate functional MRI study

Bipolar disorder is associated with persistent declarative memory disturbances, but the neural basis of these deficits is not well understood. We used fMRI to investigate brain activity during performance on a face-name paired associate task, which allows for the dissociation of encoding and recall-related memory processes. Fifteen clinically remitted bipolar I disorder patients and 24 demographically matched healthy comparison subjects were scanned during task performance. At the voxel level, bipolar patients showed reduced cortical activation, relative to controls, in multiple task-related brain regions during encoding. During recognition, bipolar patients under-activated left hippocampal and parahippocampal regions, despite adequate task performance. Region of interest analyses indicated that, during encoding, bipolar patients had greater bilateral dorsolateral prefrontal (DLPFC) activity than healthy subjects. In contrast, during recognition patients showed hypo-activation relative to controls in the right, but not the left, DLPFC. Although hippocampal activity did not differ between groups during encoding, bipolar patients failed to activate hippocampal regions to the same extent as healthy subjects during recognition. Finally, while better task performance was associated with recognition-related hippocampal activity in healthy subjects, bipolar patients showed an inverse relationship between task performance and hippocampal activity. Remitted bipolar patients over-engaged dorsolateral prefrontal regions when learning face-name pairs, but relative hypoactivation in both prefrontal and medial temporal regions during recognition. These findings suggest a neural basis for the long-term memory deficits consistently observed in patients with bipolar disorder; further, as these patterns appear in symptomatically remitted patients, they are unlikely to be an artifact of mood symptoms.