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Prefrontal hypoactivation during working memory in bipolar II depression

  • J. O. Brooks (a1), N. Vizueta (a1), C. Penfold (a1), J. D. Townsend (a1), S. Y. Bookheimer (a1) and L. L. Altshuler (a1)...



Patterns of abnormal neural activation have been observed during working memory tasks in bipolar I depression, yet the neural changes associated with bipolar II depression have yet to be explored.


An n-back working memory task was administered during a 3T functional magnetic resonance imaging scan in age- and gender-matched groups of 19 unmedicated, bipolar II depressed subjects and 19 healthy comparison subjects. Whole-brain and region-of-interest analyses were performed to determine regions of differential activation across memory-load conditions (0-, 1- and 2-back).


Accuracy for all subjects decreased with higher memory load, but there was no significant group × memory load interaction. Random-effects analyses of memory load indicated that subjects with bipolar II depression exhibited significantly less activation than healthy subjects in left hemispheric regions of the middle frontal gyrus [Brodmann area (BA) 11], superior frontal gyrus (BA 10), inferior parietal lobule (BA 40), middle temporal gyrus (BA 39) and bilateral occipital regions. There was no evidence of differential activation related to increasing memory load in the dorsolateral prefrontal or anterior cingulate cortex.


Bipolar II depression is associated with hypoactivation of the left medio-frontal and parietal cortex during working memory performance. Our findings suggest that bipolar II depression is associated with disruption of the fronto-parietal circuit that is engaged in working memory tasks, which is a finding reported across bipolar subtypes and mood states.


Corresponding author

* Address for correspondence: J. O. Brooks, Ph.D., M.D., Department of Psychiatry & Biobehavioral Sciences, UCLA Semel Institute for Neuroscience & Human Behavior, 300 Medical Plaza, Suite 2229, Los Angeles, CA 90024, USA. (Email:


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