Convergence of TMS Sites and Lesion Locations Associated With Nicotine Addiction Improvement on a Common Brain Circuit

OBJECTIVE: Transcranial magnetic stimulation (TMS) is cleared by the U.S. Food and Drug Administration for smoking cessation, yet the optimal neuroanatomical stimulation target remains unclear. Lesion locations causally linked to nicotine addiction remission have recently been used to identify a candidate brain circuit; however, this circuit has not yet been tested in relation to TMS outcomes. The authors evaluated whether TMS sites more connected to this lesion-derived brain circuit are associated with greater reductions in nicotine addiction. METHODS: Seventy-two participants with tobacco use disorder abstained from smoking for ≥12 hours and received TMS targeting four neuroanatomical regions in the left hemisphere (the dorsolateral prefrontal cortex, superior frontal gyrus, posterior parietal cortex, and visual cortex) across separate sessions, yielding a total of 243 stimulation sites. Nicotine withdrawal was assessed before and after each session using the Shiffman-Jarvik Withdrawal Scale. Functional connectivity between each TMS site and the lesion-based addiction remission circuit was estimated using a normative connectome derived from 1,000 healthy individuals. The authors examined whether TMS site connectivity to this circuit predicted improvements in withdrawal symptoms. RESULTS: TMS site connectivity to the lesion-based addiction remission circuit was significantly associated with percentage improvement in withdrawal symptoms. This relationship remained significant after adjusting for sex, baseline nicotine dependence scores, or both covariates simultaneously. A data-driven TMS circuit for withdrawal improvement closely matched the topography of the lesion-based remission circuit (Pearson's r=-0.74). Integration of lesion and TMS data identified neuroanatomical targets in the frontopolar cortex, posterior parietal cortex, lateral temporal lobe, and superior frontal gyrus. CONCLUSIONS: TMS sites and lesion locations associated with nicotine addiction improvement converge on a common brain circuit. This circuit offers a testable target that may enhance therapeutic outcomes in future TMS interventions for nicotine addiction.