State and Trait Mediated Response to TMS in Substance Use Disorder

OBJECTIVES: The current protocol seeks to develop brain-based intermediate phenotypes of response to transcranial magnetic stimulation (TMS) in chronic substance use disorder (SUD). To date the field has relied on subjective reports, behavioral performance, and long-term clinical outcomes as primary measures of TMS efficacy. While certainly ecologically valid, these observable behaviors lack the sensitivity necessary to fully quantify the effects (or lack thereof) across both individual participants and TMS intervention protocols. This proposed within-subjects design seeks to leverage differences in metaplasticity that is, the context in which stimulation occurs-by studying the response to stimulation in both sated and abstinent states. It is predicted these state manipulations will potentiate response to TMS. When a disruptive allostatic load like chronic nicotine exposure or acute abstinence is placed on the brain, the underlying network becomes less stable and thus more susceptible to TMS intervention. For SUD in general and tobacco use disorder (TUD) in particular, this state dependence of TMS response is a potentially valuable tool to improve a given intervention s clinical efficacy. STUDY POPULATION: Physically and psychiatrically healthy smokers will be recruited. A comparison group of non-smokers will be concurrently enrolled. We estimate we will require n=51/group of completers to have sufficient power to develop the intermediate phenotypes of TMS. DESIGN: The protocol is a two group, between/within subject, fully counterbalanced design. The between-subjects factor is GROUP (smoker/non-smoker) and the within-subjects factor for each GROUP is TMS CONDITION (active/sham). Additionally, and for the smoker group, nicotine STATE (sated/abstinent) is a nested within-subjects factor. Each group will receive single sessions of active and sham intermittent theta burst stimulation to left dorsal lateral prefrontal cortex, followed immediately by an MRI scan to cha