Personalized 10 Hz left DLPFC rTMS was associated with reduced cigarette consumption in tobacco use disorder
Disclaimer:
This content is intended for healthcare professionals and is provided for educational purposes only. Transcranial magnetic stimulation (TMS) is not approved for the treatment of tobacco use disorder, unless otherwise stated by local regulatory authorities.
A recent study from Li and colleagues investigated whether rTMS targeting different brain circuits could reduce cigarette consumption in adults with tobacco use disorder (TUD). The study compared excitatory 10 Hz stimulation of the left dorsolateral prefrontal cortex (L-DLPFC), a region involved in executive control, with inhibitory 1 Hz stimulation of the left medial orbitofrontal cortex (L-mOFC), a region involved in reward processing, and sham stimulation.
In this double-blind, sham-controlled randomized trial, 46 participants were randomized and 35 completed all 15 treatment sessions and both MRI scans. The analyzed groups included 12 participants receiving 10 Hz L-DLPFC rTMS, 14 receiving 1 Hz L-mOFC rTMS, and 9 receiving sham. Treatment was delivered five days per week for three weeks.
Treatment was personalized using fMRI to identify individual cortical targets and electric-field modeling to personalize stimulation intensity. The L-DLPFC group received 10 Hz rTMS with 3,000 pulses per session. The L-mOFC group received continuous 1 Hz rTMS with 900 pulses per session. Both protocols lasted 15 minutes per session.
The primary outcome was change in cigarettes smoked per day (CPD). The mean reduction was 11.14 CPD with 10 Hz L-DLPFC stimulation, compared with 6.43 with sham and 4.92 with 1 Hz L-mOFC stimulation. The overall treatment-group difference was significant (p < 0.0001), and post hoc comparisons showed greater reductions with 10 Hz L-DLPFC than sham (p < 0.05) or 1 Hz L-mOFC (p < 0.001).
The fMRI findings provided exploratory information about potential mechanisms. After 10 Hz L-DLPFC stimulation, activity increased in the DLPFC during a task requiring participants to resist the urge to smoke and decreased in the mOFC during smoking-cue exposure. Increased DLPFC activity was also correlated with greater reductions in CPD (r = 0.62, p < 0.05 after removal of an outlier).
No serious adverse events occurred. Pain was the most commonly reported side effect, side effects resolved shortly after stimulation, and no participant required treatment for an adverse effect. The authors identified the modest sample size as an important limitation, particularly for secondary and neuroimaging outcomes. They also noted that differences in pulse number between the 10 Hz and 1 Hz protocols constrain frequency-specific interpretation.
Within this study context, the findings suggest that 10 Hz L-DLPFC stimulation was associated with greater reductions in cigarette consumption than either sham or 1 Hz L-mOFC stimulation. The accompanying imaging findings are consistent with the authors’ proposed model involving increased engagement of executive-control circuitry and downstream modulation of reward-related activity. Larger studies using sustained, biologically verified abstinence outcomes are needed to confirm these findings.
Reference:
Li X, Caulfield KA, Carpenter MJ, Ramakrishnan V, Herrmann ES, Dancy M, George MS. DLPFC rTMS is more effective than sham or orbitofrontal stimulation for smoking cessation and alters frontal brain activity: A double-blind, sham-controlled randomized clinical trial. J Psychiatr Res. 2026;197:187-195. doi:10.1016/j.jpsychires.2026.02.053.
https://www.sciencedirect.com/science/article/pii/S0022395626001457?via%3Dihub
