Bipolar depressed patients show both failure to activate and failure to de-activate during performance of a working memory task

Background: Bipolar depression has been found to be associated with changes in prefrontal cortex activity during performance of cognitive tasks. However, the role of task-related de-activations has been little investigated. Method: Forty-one bipolar depressed patients and 41 matched normal controls underwent fMRI scanning while performing baseline, 1-back and 2-back versions of the n-back task. Linear models were used to obtain maps of within-group activations and areas of differential activation between the groups. Results: The bipolar depressed patients showed reduced activation in the dorsolateral prefrontal cortex (DLPFC) bilaterally and several other regions. After controlling for differences in task performance only differences in the DLPFC and cerebellum remained. Left DLPFC activation was inversely correlated with Hamilton and MADRS scores. The patients showed failure to de-activate in the medial prefrontal cortex, an area corresponding to the anterior medial node of the default mode network. Limitations: To confirm default mode network dysfunction demonstration of resting-state connectivity abnormalities would also be required. The study was carried out on treated patients, and did not assess for presence of depressive symptoms in the healthy controls. Conclusions: Both prefrontal cortical and default mode network dysfunction appear to characterise bipolar depression. The former, but not the latter, is associated with symptom severity. (c) 2012 Elsevier B.V. All rights reserved.