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

ABSTRACT: 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.

SUBMITTER: Queirazza F

PROVIDER: S-EPMC6669013 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Queirazza Filippo F Fouragnan Elsa E Steele J Douglas JD Cavanagh Jonathan J Philiastides Marios G MG

Science advances 20190731 7

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 re ...[more]

PMID: 31392266

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Project description:ImportanceMajor depressive disorder is prevalent and impairing. Parsing neurocomputational substrates of reinforcement learning in individuals with depression may facilitate a mechanistic understanding of the disorder and suggest new cognitive therapeutic targets.ObjectiveTo determine associations among computational model-derived reinforcement learning parameters, depression symptoms, and symptom changes after treatment.Design, setting, and participantsIn this mixed cross-sectional-cohort study, individuals performed reward and loss variants of a probabilistic learning task during functional magnetic resonance imaging at baseline and follow-up. A volunteer sample with and without a depression diagnosis was recruited from the community. Participants were assessed from July 2011 to February 2017, and data were analyzed from May 2017 to May 2021.Main outcomes and measuresComputational model-based analyses of participants' choices assessed a priori hypotheses about associations between components of reward-based and loss-based learning with depression symptoms. Changes in both learning parameters and symptoms were then assessed in a subset of participants who received cognitive behavioral therapy (CBT).ResultsOf 101 included adults, 69 (68.3%) were female, and the mean (SD) age was 34.4 (11.2) years. A total of 69 participants with a depression diagnosis and 32 participants without a depression diagnosis were included at baseline; 48 participants (28 with depression who received CBT and 20 without depression) were included at follow-up (mean [SD] of 115.1 [15.6] days). Computational model-based analyses of behavioral choices and neural data identified associations of learning with symptoms during reward learning and loss learning, respectively. During reward learning only, anhedonia (and not negative affect or arousal) was associated with model-derived learning parameters (learning rate: posterior mean regression β = -0.14; 95% credible interval [CrI], -0.12 to -0.03; outcome sensitivity: posterior mean regression β = 0.18; 95% CrI, 0.02 to 0.37) and neural learning signals (moderation of association between striatal prediction error and expected value signals: t97 = -2.10; P = .04). During loss learning only, negative affect (and not anhedonia or arousal) was associated with learning parameters (outcome shift: posterior mean regression β = -0.11; 95% CrI, -0.20 to -0.01) and disrupted neural encoding of learning signals (association with subgenual anterior cingulate prediction error signals: r = -0.28; P = .005). Symptom improvement following CBT was associated with normalization of learning parameters that were disrupted at baseline (reward learning rate: posterior mean regression β = 0.15; 90% CrI, 0.001 to 0.41; loss outcome shift: posterior mean regression β = 0.42; 90% CrI, 0.09 to 0.77).Conclusions and relevanceIn this study, the mapping of reinforcement learning components to symptoms of major depression revealed mechanistic features associated with these symptoms and points to possible learning-based therapeutic processes and targets.

Dataset Information

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

Publications

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

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