Smoking is the greatest preventable cause of mortality and a significant economic burden. Even with the best available treatments, most smokers relapse within days or weeks after a quit attempt. To improve quit rates significantly, we need a more refined mechanistic understanding of why so many smokers who attempt to quit will relapse quickly. The proposed functional magnetic resonance imaging (fMRI) study integrates concepts and tools from the fields of cognitive neuroscience and behavioral science to determine how brain states in early abstinence influence clinical outcomes among treatment-seeking smokers. The primary aims of this hypothesis-driven study are: (1) to identify brain mechanisms that increase vulnerability to smoking relapse, and (2) to test an integrated brain-behavior model of smoking relapse. Using our validated fMRI-based abstinence challenge paradigm, 200 treatment-seeking smokers will complete two 1-hour pre- treatment fMRI scans: after smoking satiety and after 24 hours of confirmed abstinence. We will examine neural and behavioral responses during performance of validated tasks probing working memory, cue reactivity, and stress response as well as resting state functional connectivity. Participants will then set a target quit date, receive smoking cessation counseling, and be monitored for 6-months to assess time (days) to relapse, using a validated smoking relapse protocol. The primary outcome is time to relapse. Secondary outcomes include abstinence symptoms and smoking status at 30 days. For human subjects reasons, relapsing smokers will be offered an opportunity to receive 8 weeks of nicotine patch treatment and counseling free of charge following study completion. Although neuroimaging is not likely to become a standard pre- cessation assessment the near future, this study will elucidate pathological neurobehavioral processes and specific neurocognitive domains that can be targeted in new treatments to aid smoking cessation.
