FMRI activation during executive function predicts response to cognitive behavioral therapy in older, depressed adults.

OBJECTIVES To test our hypothesis that pre-treatment executive function and brain regional activation during executive function would discriminate between responders and non-responders to cognitive behavioral therapy (CBT) in elderly depressed outpatients. DESIGN Clinical cohort study. SETTING University-affiliated hospital. PARTICIPANTS Sixty outpatients (age 59 years and older) completed 12 weeks of CBT between July 2010 and December 2011. Forty-four completed fMRI procedures. MEASUREMENTS The main outcome consisted of a conversion from a clinical diagnosis (Mini-International Neuropsychiatric Interview) of depression to no clinical diagnosis of depression or a significant improvement in diagnostic criteria. Brain activation measured by functional magnetic resonance imaging during the Wisconsin Card Sorting task (WCST) was the primary predictor variable. RESULTS 67% of patients had a positive response to CBT. Decreased activation in the left inferior frontal triangle and right superior frontal gyrus as well as increased activity in the right middle frontal gyrus and left superior frontal gyrus predicted a positive response to CBT. Demographic and neurocognitive measures of WCST performance were not significant predictors of a positive CBT outcome, whereas the measure of WCST-induced activity in the prefrontal cortex was a significant predictor. CONCLUSIONS These data are among the first to suggest that measures of prefrontal brain activation during executive functioning predict response to CBT in older adults. Further exploration of the specific underlying processes that these prefrontal cortical regions are engaging that contributes to better CBT outcomes is warranted in larger, randomized studies.