Neural Mechanisms underlying dissociable effects of cTBS in Psychostimulant Abuse

ABSTRACT Nicotine addiction is associated with deficits in prefrontal cortical (PFC) mediated control over inhibiting behavior and regulating appetitive response. We have reported stimulation pattern-dependent dissociable modulatory effects of low-frequency non-invasive brain stimulation (NIBS; cTBS) when applied to the lateral PFC—right inferior frontal gyrus (r.IFG) on inhibitory control, corticolimbic resting state functional connectivity (rsF) and smoking behavior. We further identified a novel pattern showing that dorsomedial PFC (preSMA) rsFC with corticostriatal circuitry predicts regulation of craving efficacy and smoking lapse vulnerability, and that preSMA NIBS modulates corticostriatal rsFC. Our preliminary findings, along with the extant literature also suggest PFC location specific effects of continuous theta burst stimulation cTBS on changing the strength of cortico-limbic- striatal functional connectivity (FC) and reducing the concentration of excitatory neurometabolites in the respective circuitry target by cTBS. The goal of this proposal is to conduct a location control (vertex) crossover study of cTBS to examine the neurocircuitry and neurobiological mechanisms mediating the effects of cTBS to r.IFG and preSMA on inhibitory control and craving regulation, respectively, and evaluate associations between neural outcomes and smoking behavior over the subsequent 24-hours.