Buprenorphine has emerged as a leading treatment for opioid use disorder (OUD), but recipients have high early relapse rates likely due to varying degrees of dysfunction within craving and cognitive control neuronal networks. Transcranial direct current stimulation (tDCS) may have promise as adjuvant treatment for buprenorphine initiators because considerable work on addictive substances suggests treatment targeted at the dorsolateral prefrontal cortex (DLPFC; region involved in self-regulation) may reduce craving and drug consumption. We will measure behavioral and brain responses following tDCS stimulation to the DLPFC delivered during cognitive control network (CCN) priming. Participants in their first week of prescribed buprenorphine will be assessed twice using FMRI, once prior to tDCS+CCN priming and again at the completion of 5 sessions of tDCS+CCN priming (one week later). Task-based and resting state functional connectivity will be used to examine networks associated with craving (CR) and cognitive control. In the UG3 phase (n=60), FMRI will provide validation of expected changes in these networks following tDCS stimulation. Go/no go criteria for the UH3 phase will be demonstration of greater FMRI change in any node of the CR or CCN networks AND greater change in subjective craving measured prior to (outside FMRI scan) or during an FMRI cue reactivity task following the tDCS+CCN priming intervention compared to sham tDCS+CCN priming. In the UH3 phase (n=100), we will perform a larger RCT (vs. sham control) to address long-term neurobehavioral outcomes, including opioid relapse, craving, and sustained fMRI changes. Because tDCS is safe, inexpensive and portable, if this intervention provides FMRI validation of targeted brain effects and produces clinical response, it could have great impact augmenting the care of persons entering buprenorphine treatment, a population at high risk for treatment failure.

NARRATIVE Early initiators of buprenorphine, a leading treatment for opioid use disorder, are at high risk for early relapse, likely due to dysfunction within craving and cognitive control neuronal networks. This project will test a non- invasive brain stimulation technique, transcranial Direct Current Stimulation, to reduce craving in buprenorphine recipients. If the FMRI provides validation of tDCS-related changes in these neuronal networks as well as clinical efficacy, then this neuromodulation intervention may be an important adjuvant treatment in clinical care of those entering buprenorphine care.