Transdiagnostic Effects of Ventromedial Prefrontal Cortex Transcranial Magnetic Stimulation on Cue Reactivity

Background: Elevated frontal and striatal reactivity to drug cues is a transdiagnostic hallmark of substance use disorders. The goal of these experiments was to determine if it is possible to decrease frontal and striatal reactivity to drug cues in both cocaine users and heavy alcohol users through continuous theta burst stimulation (cTBS) to the left ventromedial prefrontal cortex (VMPFC). Methods: Two single-blinded, within-subject, active sham–controlled experiments were performed wherein neural reactivity to drug/alcohol cues versus neutral cues was evaluated immediately before and after receiving real or sham cTBS (110% resting motor threshold, 3600 pulses, Fp1 location; N = 49: 25 cocaine users [experiment 1], 24 alcohol users [experiment 2]; 196 total functional magnetic resonance imaging scans). Generalized psychophysiological interaction and three-way repeated-measures analysis of variance were used to evaluate cTBS-induced changes in drug cue-associated functional connectivity between the left VMPFC and eight regions of interest: ventral striatum, left and right caudate, left and right putamen, left and right insula, and anterior cingulate cortex. Results: In both experiments, there was a significant interaction between treatment (real/sham) and time (pre/post). In both experiments, cue-related functional connectivity was significantly attenuated following real cTBS versus sham cTBS. There was no significant interaction with region of interest for either experiment. Conclusions: This is the first sham-controlled investigation to demonstrate, in two populations, that VMPFC cTBS can attenuate neural reactivity to drug and alcohol cues in frontostriatal circuits. These results provide an empirical foundation for future clinical trials that may evaluate the efficacy, durability, and clinical implications of VMPFC cTBS to treat addictions.