Neural responses to negative outcomes predict success in community-based substance use treatment

Patterns of brain activation have demonstrated promise as prognostic indicators in substance dependent individuals (SDIs) but have not yet been explored in SDIs typical of community-based treatment settings.

Prospective clinical outcome design, evaluating baseline functional magnetic resonance imaging data from the Balloon Analogue Risk Task (BART) as a predictor of 3-month substance use treatment outcomes.

Community-based substance use programs in Bloomington, Indiana, USA.

Twenty-three SDIs (17 male, aged 18-43 years) in an intensive outpatient or residential treatment program; abstinent 1-4 weeks at baseline.

Event-related brain response, BART performance and self-report scores at treatment onset, substance use outcome measure (based on days of use).

Using voxel-level predictive modeling and leave-one-out cross-validation, an elevated response to unexpected negative feedback in bilateral amygdala and anterior hippocampus (Amyg/aHipp) at baseline successfully predicted greater substance use during the 3-month study interval (P ≤ 0.006, cluster-corrected). This effect was robust to inclusion of significant non-brain-based covariates. A larger response to negative feedback in bilateral Amyg/aHipp was also associated with faster reward-seeking responses after negative feedback (r₍₂₃₎  = -0.544, P = 0.007; r₍₂₃₎  = -0.588, P = 0.003). A model including Amyg/aHipp activation, faster reward-seeking after negative feedback and significant self-report scores accounted for 45% of the variance in substance use outcomes in our sample.

An elevated response to unexpected negative feedback in bilateral amygdala and anterior hippocampus (Amyg/aHipp) appears to predict relapse to substance use in people attending community-based treatment.