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

Abstract

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.

Copyright © 2017 Elsevier B.V. All rights reserved.

Figures

Figure 1

Study design

Figure 2

One session of rTMS of 3000 pulse over the left DLPFC reduced brain activity in (A) right insula (p<0.05, AlphaSim corrected); (B) The bar graph shows the mean fALFF of insula (33, −24, 18); (C) right thalamus (p<0.05, AlphaSim corrected); (D) The bar graph shows the mean fALFF of right thalamus (15, −24, 3). * p<.05, **p<.01

Figure 3

The comparison of the connectivity of the DLPFC and the orbital medial prefrontal cortex (OMPFC) between active and sham-TMS (A). The connectivity of DLPFC (−42, 34, 30) and OMPFC (−39, 45, −9) (B). The bar graph shows the mean functional connectivity (FC) in sham and active TMS treatment. * p<.05, **p<.01