Repetitive transcranial magnetic stimulation (rTMS) shows promise for smoking cessation, but its neural mechanisms remain unclear. It is unknown whether rTMS reduces smoking by enhancing executive control or suppressing reward-related brain activity. This study aimed to address this gap by comparing excitatory and inhibitory rTMS targeting distinct cortical circuits implicated in tobacco use disorder (TUD). In a double-blind, sham-controlled design, treatment-seeking individuals with TUD were randomized to 15 sessions of personalized, fMRI-guided, E-field–dosed rTMS: (1) sham rTMS, (2) excitatory 10 Hz rTMS over the left dorsolateral prefrontal cortex (L-DLPFC; 3,000 pulses/session), or (3) inhibitory 1 Hz rTMS over the left medial orbitofrontal cortex (L-mOFC; 900 pulses/session). fMRI scans were conducted pre- and post- 15 sessions of rTMS. Primary outcomes were reductions in cigarettes per day (CPD) and changes in blood-oxygen-level–dependent (BOLD) activity. Thirty-five of 46 participants completed the study (sham = 9; 10 Hz L-DLPFC = 12; 1 Hz L-mOFC = 14). The 10 Hz L-DLPFC group showed a significantly greater CPD reduction than 1 Hz L-mOFC and sham (–11.14 vs. –4.92 and –6.43, respectively; p < 0.0001, partial η 2 = 0.135). rTMS to the L-DLPFC also increased prefrontal activity and decreased orbitofrontal activity (p < 0.05), with the degrees of CPD reduction correlating with enhanced activation in L-DLPFC (p<0.05). Enhancing executive control via 10 Hz rTMS over the L-DLPFC was more effective for smoking reduction than suppressing reward circuitry with 1 Hz rTMS over the L-mOFC. Findings suggest that strengthening prefrontal regulation of reward processing is a key mechanism by which rTMS promotes smoking cessation. clinicaltrials.gov Identifier: NCT 04903028 • Multiple sessions of daily MRI-guided rTMS to the left DLPFC aided smoking cessation. • 10 Hz DLPFC for three weeks is superior to 1 Hz mOFC and sham treatment. • 3-week daily 10 Hz rTMS over the left DLPFC increased prefrontal cortex activity and decreased medial frontal cortex activity.
Li et al. (Sun,) studied this question.