Effects of Hyperdirect Pathway Theta-Burst Transcranial Magnetic Stimulation on Inhibitory Control, Craving, and Smoking in Adults with Nicotine Dependence: A Double-Blind Randomized Crossover Trial.

BACKGROUND: Nicotine dependence is associated with dysregulated hyperdirect pathway (HDP)-mediated inhibitory control (IC). However, there are currently no evidence-based treatments shown to target the HDP to improve IC and reduce cigarette cravings and smoking.

METHODS: Following a baseline non-stimulation control session, this study (N = 37; female: n = 17) utilized a double-blind, randomized crossover design, to examine the behavioral and neural effects of intermittent TBS (iTBS) and continuous TBS (cTBS) to the right inferior frontal gyrus (rIFG) ─ a key cortical node of the HDP. Associations between treatment effects were also explored.

RESULTS: At baseline, HDP IC task-state functional connectivity (tsFC) was positively associated with IC task performance, which confirmed the relevance between HDP circuit function and IC. Relative to iTBS, rIFG cTBS improved IC task performance. Relative to the baseline non-stimulation control session, both TBS conditions reduced cigarette craving and smoking, but although craving and smoking were lower for cTBS, no differences were found between the two active conditions. Additionally, although HDP IC tsFC was greater following cTBS as compared to iTBS, there was no significant difference between conditions. Lastly, cTBS-induced improvement in IC task performance was associated with reduced craving; and cTBS-induced reduction in craving was associated with reduced smoking.

CONCLUSIONS: Findings warrant further investigation into the effects of rIFG cTBS for increasing IC and reducing craving and smoking among individuals with nicotine dependence. Future sham-controlled cTBS studies may further help to elucidate the mechanisms by which rIFG cTBS mediates IC and smoking behavior.

CLINICALTRIALS: gov Identifier: NCT03960138.