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Psychiatry Res. 2013 Oct 30;214(1):56-65. doi: 10.1016/j.pscychresns.2013.05.002. Epub 2013 Aug 17.

A developmental study on the neural circuitry mediating response flexibility in bipolar disorder.

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Section on Bipolar Spectrum Disorders, Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, USA.


Cross-sectional neuroimaging studies are an important first step in examining developmental differences in brain function between adults and youth with bipolar disorder (BD). Impaired response flexibility may contribute to reduced ability to modify goal-directed behavior in BD appropriately. We compared neural circuitry mediating this process in child (CBD) vs. adult BD (ABD) and age-matched healthy subjects. fMRI data from 15 CBD, 23 ABD, 20 healthy children, and 27 healthy adults were acquired during a response flexibility paradigm, a task where subjects inhibit a prepotent response and execute an alternative response. When successfully executing an alternate response, CBD showed frontal, parietal, and temporal hyperactivation relative to healthy children and ABD, while ABD hypoactivated these regions relative to healthy adults. Previous studies of response flexibility in healthy volunteers revealed frontal, temporal, and parietal cortex hyperactivation in children and hypoactivation in adults. Relative to age-matched healthy subjects, we found hyperactivation in these regions in CBD and hypoactivation in ABD. This suggests that our findings in patients may represent the extreme extension of the age-related response flexibility activation differences found in healthy subjects. Future studies should use longitudinal fMRI to examine the developmental trajectory of the neural circuitry mediating response flexibility in BD.


Bipolar disorder; Cross-sectional; Neuroimaging; Response flexibility; Stop-change task

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