Identify the Optimal TMS Target to Modulate Reward Activity

This study uses brain imaging (fMRI) and brain stimulation (repetitive TMS) to identify the best brain target for reducing the overactive reward-seeking behavior that drives nicotine addiction. The brain's reward system is central to addiction — nicotine hijacks it, making smoking feel rewarding and making it hard to stop. By identifying which brain region, when stimulated, most effectively dampens this reward response, researchers hope to optimize non-invasive brain stimulation as a smoking cessation tool. Nicotine-dependent adults aged 18 to 55 who are in stable mental and physical health are eligible. Participants must not have had substance abuse treatment in the past 30 days and, if female, must not be pregnant. Those with contraindications to MRI (such as metal implants or claustrophobia) or TMS (seizure history, brain injury, certain implants), brain lesions on MRI, or a history of major psychiatric disorders including bipolar disorder, schizophrenia, PTSD, or dementia are excluded. Smoking kills millions of people each year, and many smokers are unable to quit despite using available pharmacological treatments. Non-invasive brain stimulation has shown promise as an addiction treatment, but its effectiveness has been limited by uncertainty about the optimal target. This study could identify the precise brain circuit to target — a key step toward developing more powerful, personalized cessation interventions.