The design is primarily a randomized control-trial design (3 sessions), comparing the effects 10-Hz rTMS applied to four prefrontal TMS targets based on fMRI, cortical thickness (CT), diffusion-weighted imaging (DWI) and resting state functional connectivity (RSFC) on reward processing across two groups of smokers - Active TMS group and Sham TMS group. For Session A, participants will be scanned using a 3 Tesla MRI system and will receive a structural (T1), fMRI, DWI, and resting-state FC scan. Following Session A, all participants will be asked to complete two Ri-TMS sessions within two weeks and will be instructed to abstain from smoking for 4 hours before the start of each scheduled session. Session B and C: Distinct prefrontal target regions will be identified for each subject based on CT, fMRI, DWI, and RSFC data. At the start of Session B, a target will be randomly assigned to each subject using a random permuted block method. For Sessions B and C, participants will be asked to provide their consent, CO levels, and complete the craving questionnaire (TCQ). At the start of Session B, participants will be fitted with an EEG cap and engage in a virtual T-maze feedback task. The task will be divided into two blocks (200 trials per block: 10 minutes per block). At the start of Block 1, the robotic arm will position the TMS coil <1 cm over Target 1. Next, 50 rTMS pulses will be delivered at 110% of participants' rMT at 10- Hz continuously over Target 1 immediately before every 10 trials of the T-maze (5 seconds of TMS, 30 seconds of task). A total of 1000 pulses will be delivered to Target 1 and 200 T-maze trials completed (duration 10-15 minutes). Immediately after, subjects will be asked to complete a probabilistic selection task (PST) to measure post-stimulation effects on decision-making performance (duration, 15 minutes). Following the completion of the PST, subjects will be given a 5 minute rest-break and participants will be asked to fill out the TCQ. At the start of Block 2, the robotic arm will position the TMS coil <1 cm over Target 2, and 50 rTMS pulses will be delivered immediately before every 10 trials of the T-maze task. A total of 1000 pulses will be delivered to Target 2 and 200 T-maze trials completed (duration 10 minutes). Following Target 2 stimulation, subjects will be asked to complete the PST (duration, 15 minutes) and asked to fill out the TCQ. At the end of the Session B, participants will be scheduled to return to the laboratory to complete Session C on a separate day. An identical protocol will be applied to Session C with the exception that TMS pulses will be deliver to Target 3 and Target 4.
Our primary goal will be to identify the optimal prefrontal-cingulate target by systematically measuring the efficacy of various image-based targeting techniques to increase the reward positivity using the 10-Hz TMS protocol in dependent smokers. Our secondary objective will be to measure the targets' effectiveness to increase decision-making capacity using the probabilistic selection task (PST). Our third objective will be to specifically assess whether the TMS targets has a differential impact on state levels of craving relative to baseline (Tobacco Craving Questionnaire [TCQ]. We plan to accomplish these three objectives using a randomized, controlled experiment involving 3 sessions.