Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex reduces resting-state insula activity and modulates functional connectivity of the orbitofrontal cortex in cigarette smokers

Drug Alcohol Depend. 2017 May 1;174:98-105. doi: 10.1016/j.drugalcdep.2017.02.002. Epub 2017 Feb 28.


Background: Previous studies reported that repetitive transcranial magnetic stimulation (rTMS) can reduce cue-elicited craving and decrease cigarette consumption in smokers. The mechanism of this effect however, remains unclear. We used resting-state functional magnetic resonance imaging (rsfMRI) to test the effect of rTMS in non-treatment seeking smokers.

Methods: We used a single blinded, sham-controlled, randomized counterbalanced crossover design where participants underwent two visits separated by at least 1 week. Participants received active rTMS over the left dorsolateral prefrontal cortex (DLPFC) during one of their visits, and sham rTMS during their other visit. They had two rsFMRI scans before and after each rTMS session. We used the same rTMS stimulation parameters as in a previous study (10Hz, 5s-on, 10s-off, 100% resting motor threshold, 3000 pulses).

Results: Ten non-treatment-seeking, nicotine-dependent, cigarette smokers (6 women, an average age of 39.72 and an average cigarette per day of 17.30) finished the study. rsFMRI results demonstrate that as compared to a single session of sham rTMS, a single session of active rTMS inhibits brain activity in the right insula and thalamus in fractional amplitude of low frequency fluctuation (fALFF). For intrinsic brain connectivity comparisons, active TMS resulted in significantly decreased connectivity from the site of rTMS to the left orbitomedial prefrontal cortex.

Conclusions: This data suggests that one session of rTMS can reduce activity in the right insula and right thalamus as measured by fALFF. The data also demonstrates that rTMS can reduce rsFC between the left DLPFC and the medial orbitofrontal cortex.

Keywords: DLPFC; Nicotine dependence; Resting-state fMRI; Reward circuit; Transcranial magnetic stimulation.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Craving / physiology*
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Nerve Net / diagnostic imaging
  • Nerve Net / physiopathology*
  • Nicotine
  • Prefrontal Cortex / diagnostic imaging
  • Prefrontal Cortex / physiopathology*
  • Rest
  • Single-Blind Method
  • Smoking / physiopathology
  • Smoking / therapy*
  • Tobacco Use Disorder / diagnostic imaging
  • Tobacco Use Disorder / physiopathology
  • Tobacco Use Disorder / therapy*
  • Transcranial Magnetic Stimulation / methods*
  • Treatment Outcome


  • Nicotine