Repetitive transcranial magnetic stimulation reduces smoking cravings by decreasing cerebral blood flow in the dorsolateral prefrontal cortex.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation method that has been increasingly used to treat psychiatric disorders, including tobacco use disorder. However, the neural mechanisms underlying the effects of rTMS remain unclear. This study aimed to examine the effectiveness of rTMS in smoking cessation and to explore the underlying neural mechanism of the treatment effect. In Experiment 1, we recruited 60 participants who smoked cigarettes and 60 healthy controls and used their baseline cerebral blood flow (CBF) measured by arterial spin labelling perfusion to determine the group-level difference in CBF. In Experiment 2, we used the left dorsolateral prefrontal cortex (DLPFC) as the target for subsequent 5-day rTMS treatment at a frequency of 10 Hz with 2000 pulses to observe the impact of rTMS on CBF, Fagerström test for nicotine dependence scores and Tiffney questionnaire on smoking urges scores. In Experiment 3, we measured functional connectivity to monitor the functional changes induced by rTMS and assessed their associations with smoking cravings and nicotine dependence scores. In Experiment 1, participants who smoked cigarettes presented significantly higher CBF in the left DLPFC and bilateral anterior cingulate cortex than healthy controls. In Experiment 2, rTMS significantly decreased CBF in the DLPFC and reduced Fagerström test for nicotine dependence scores and Tiffney questionnaire on smoking urges scores. In Experiment 3, rTMS increased functional connectivity between the left DLPFC and the bilateral superior frontal gyrus, right DLPFC, bilateral precuneus and bilateral parahippocampus in participants, who smoked cigarettes. Regional CBF is a tool to identify tobacco use disorder-related regional brain markers and targets for reducing nicotine dependence and smoking cravings through rTMS. A neural mechanism of left DLPFC rTMS may involve a reduction in CBF in the target area and an increase in functional connectivity between the target area and the DLPFC-striatal pathways.