rTMS effects on urges and severity of tobacco use disorder operate independently of a retrieval-extinction component and involve frontal-striatal pathways

Abstract

Background: Although smoking remains a leading cause of preventable disease, the treatment options for smoking are limited. The present study evaluated the neural features underlying effects of repetitive transcranial magnetic stimulation (rTMS) for reducing smoking cravings. In addition, the efficacy of a simulated retrieval-extinction procedure to augment rTMS efficacy was examined.

Methods: Sixty-one individuals with tobacco use disorder (TUD) were randomized into three groups: classic rTMS, retrieval rTMS (viewed smoking videos before rTMS), and sham rTMS. rTMS was performed on the left dorsolateral prefrontal cortex (DLPFC) over 5 days using a standard figure-8 coil. Smoking cravings and brain responses to smoking cues were measured before and after rTMS treatment. Changes in functional connectivity (FC) among different brain regions were calculated.

Results: rTMS reduced smoking urges in TUD. Both active-rTMS groups demonstrated greater activations of the DLPFC, caudate, and bilateral insula relative to the sham group. Increased FC was observed between executive and reward network brain regions, and decreased FC was observed within reward network regions. Compared with standard rTMS, retrieval-extinction rTMS demonstrated similar outcomes and was associated with less activation of the medial frontal gyrus.

Conclusions: rTMS increased activations in brain regions implicated in executive control and reward processing. Strengthened prefrontal-striatal pathway suggests that rTMS enhanced top-down control over smoking cravings. The retrieval-extinction process, although associated with some different and multiple similar neural correlates as the standard rTMS, did not enhance cessation outcomes.

Keywords: Craving; DLPFC; Retrieval–extinction; TUD; rTMS.