PROJECT SUMMARY. Young adults with opioid use disorders (OUD) are disproportionately affected by the current opioid crisis and have poorer treatment engagement and adherence compared to their older counterparts with catastrophic consequences. As such, the identification of neural networks and behavioral predictors of treatment adherence and abstinence outcomes related to relapse prevention medication treatment for OUD (termed MOUD) in young adults is of great importance and may enhance treatment refinement efforts and improve precision and efficacy of treatment matching. The purpose of this administrative supplement to NIDA R33DA056230 is to identify neurobehavioral features (brain activity, functional connectivity (FC), and cognition and social/emotional processes) at baseline that are related to medication adherence and opioid relapse (Aim 1) in young adults with OUD receiving extended-release injectable naltrexone (XR-NTX) or buprenorphine (XR-BUP) medication treatment, and investigate how these neurobehavioral features change during treatment (Aim 2). The supplement will use a mechanism-focused prospective ‘add-on’ pre-to-post-treatment study design linked to the parent grant’s randomized controlled trial (RCT) testing the efficacy of enhanced recovery support through the Youth Opioid Recovery Support (YORS) program, a developmentally-informed intervention that incorporates home delivery of MOUD, family engagement, assertive outreach, and contingency management to promote medication adherence. The parent RCT will randomize N=120 young adults ages 18-28 seeking treatment for OUD with XR-NTX or XR-BUP to either the YORS intervention or treatment as usual (TAU) for a 6-month course of MOUD treatment. In the supplement project, N=65 young adults from the parent treatment grant (estimated N=32 each choosing XR- NTX and XR-BUP) who meet MRI eligibility criteria and are randomized to receive the YORS intervention will complete pretreatment and week-12 fMRI scan visits and a pre-treatment ‘deep’ behavioral phenotyping assessment visit. During scan visits, participants will complete fMRI scans during rest, opioid cue exposure, emotional faces presentation, and reward. Data on opioid addiction severity, withdrawal, cravings, impulsivity, mood/anxiety, cognitive regulation skills, decision making, and psychiatric diagnoses will be collected during the behavioral assessment visit. Integrated aspects of the fMRI/phenotyping supplement project and main YORS study will allow for investigation of how resting-state and task-related brain activity and connectivity, and cognitive and social/emotional processes relate to opioid relapse and medication adherence and change during treatment in young adults receiving MOUD treatment. It will also allow for exploratory, albeit underpowered, analyses examining mediating effects of medication choice (XR-BUP versus XR-NTX) on relationships identified in the primary analyses between brain connectivity, opioid relapse, and...