Neural correlates of weighted reward prediction error during reinforcement learning classify response to cognitive behavioral therapy in depression.

While cognitive behavioral therapy (CBT) is an effective treatment for major depressive disorder, only up to 45% of depressed patients will respond to it. At present, there is no clinically viable neuroimaging predictor of CBT response. Notably, the lack of a mechanistic understanding of treatment response has hindered identification of predictive biomarkers. To obtain mechanistically meaningful fMRI predictors of CBT response, we capitalize on pretreatment neural activity encoding a weighted reward prediction error (RPE), which is implicated in the acquisition and processing of feedback information during probabilistic learning. Using a conventional mass-univariate fMRI analysis, we demonstrate that, at the group level, responders exhibit greater pretreatment neural activity encoding a weighted RPE in the right striatum and right amygdala. Crucially, using multivariate methods, we show that this activity offers significant out-of-sample classification of treatment response. Our findings support the feasibility and validity of neurocomputational approaches to treatment prediction in psychiatry.