Time for a paradigm shift: The adolescent brain in addiction treatment

•This study integrates fMRI with a behavioral randomized controlled trial with youth.•Our fMRI paradigm assessed adolescent brain response to therapist language.•MI youth demonstrated significantly better treatment outcomes than BAM youth at 12 months•Youth showed brain change in response to complex reflection vs. mindful and complex reflection vs. confront (e.g., precuneus; postcentral gyrus).•Youth brain change to therapist language was associated with outcomes. One route to improve adolescent addiction treatment outcomes is to use translational approaches to help identify developmental neuroscience mechanisms that undergird active treatment ingredients and advance adolescent behavior change. This sample included 163 adolescents (ages 15–19) randomized to motivational interviewing (MI) vs. brief adolescent mindfulness (BAM). Youth completed an fMRI paradigm assessing adolescent brain response to therapist language (complex reflection vs. mindful; complex reflection vs. confront; mindful vs. confront) at pre- (prior to the completion of the full intervention) and post-treatment (at 3-month follow-up) and behavioral measures at 3, 6 and 12 months. Youth in both treatment groups showed significant problem drinking reductions at 3 and 6 months, but MI youth demonstrated significantly better treatment outcomes than BAM youth at 12 months. We observed several significant treatment group differences (MI > BAM) in neural response to therapist language, including at pre-treatment when examining complex reflection vs. mindful, and complex reflection vs. confront (e.g., superior temporal gyrus, lingual gyrus); and at post-treatment when examining mindful vs. confront (e.g., supplementary motor area; middle frontal gyrus). When collapsed across treatment groups (MI + BAM), we observed significant differences by time, with youth showing a pattern of brain change in response to complex reflection vs. mindful, and complex reflection vs. confront (e.g., precuneus; postcentral gyrus). There was no evidence of a significant group × time interaction. However, brain change in response to therapist language (complex reflection vs. confront) in regions such as middle frontal gyrus, was associated with reductions in problem drinking at 12 months. Yet, few treatment group differences were observed. These data underscore the need to better understand therapist language and it's impact on the developing brain, in order to inform and aggregate the most impactful elements of addict