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

Abstract

BackgroundNicotine dependence is associated with dysregulated hyperdirect pathway (HDP)–mediated inhibitory control (IC). However, there are currently no evidence-based treatments that have been shown to target the HDP to improve IC and reduce cigarette cravings and smoking. MethodsFollowing a baseline nonstimulation control session, this study (N = 37; female: n = 17) used a double-blind, randomized crossover design to examine the behavioral and neural effects of intermittent theta burst stimulation (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. ResultsAt baseline, HDP IC task-state functional connectivity was positively associated with IC task performance, which confirmed the association between HDP circuit function and IC. Compared with iTBS, rIFG cTBS improved IC task performance. Compared with the baseline nonstimulation control session, both TBS conditions reduced cigarette craving and smoking; however, although craving and smoking were lower for cTBS, no differences were found between the two active conditions. In addition, although HDP IC task-state functional connectivity was greater following cTBS than iTBS, there was no significant difference between conditions. Finally, cTBS-induced improvement in IC task performance was associated with reduced craving, and cTBS-induced reduction in craving was associated with reduced smoking. ConclusionsThese 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 help further elucidate the mechanisms by which rIFG cTBS mediates IC and smoking behavior.