Structural and Functional Neural Targets of Addiction Treatment in Adolescents and Young Adults: A Systematic Review and Meta-Analysis

Objective: Addictive disorders start during adolescence for most individuals, and developmental differences in brain maturation and response to treatments are present. Recent studies in adults have identified associations between addiction treatment response and regional and circuit specific brain dysfunction, suggesting candidate neural treatment targets. The purpose of this systematic review and meta-analysis was to qualitatively and quantitatively summarize findings from structural and functional neuroimaging studies that examine neural correlates of treatment response in adolescents and young adults with addictive disorders. Methods: A systematic review and meta-analysis of peer-reviewed studies was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies were selected if they included individuals aged 13-26 with a DSM-IV or DSM-5 (Diagnostic and Statistical Manual, Fourth and Fifth Edition) addictive disorder diagnosis, used neuroimaging, administered a treatment/intervention, and reported within- or between-subject contrasts in brain structure or activity across treatment/intervention and a control condition or brain-behavior correlations with treatment-outcome variables. Quantitative meta-analyses used an activation-likelihood estimation (ALE) approach. Results: Out of 3177 citations, 27 studies were included in the qualitative analysis. Qualitative analyses revealed anatomical, connectivity, and functional brain-behavior associations with response to addiction interventions across a broad array of cortical and subcortical brain regions and associated networks. Eighteen functional magnetic resonance imaging studies involving 354 participants and 88 brain foci were included in the ALE meta-analysis. Despite significant heterogeneity in study design and methods, six ALE activation clusters localized to the anterior cingulate cortex, inferior frontal gyrus, supramarginal gyrus, middle temporal gyrus, precuneus, and putamen showed consistent brain-behavior associations with treatment-outcome variables. Conclusions: Cortical and subcortical brain regions involved in cognition, emotion regulation, decision-making, reward, and self-reference are associated with treatment response in addicted youth. These results are consistent with findings in the adult literature and suggest overlapping neural treatment targets across developmental stages.