Brain Activity and Smoking Cessation

Our previous work demonstrated that, among non-treatment seeking smokers, regional cerebral blood flow (rCBF) is increased following 14 hours of overnight abstinence, as compared to smoking as usual. Specifically, increased rCBF was observed in the anterior cingulate, medial and left orbitofrontal cortex. Two smoking urges items ("cravings for a cigarette" and "urges to smoke at this time") that predict relapse were strongly correlated with CBF increases in several regions that comprise the brain's reward and visual circuitry (Wang et al., 2007). In addition, two other studies by our group using BOLD fMRI showed that smokers with genotypes associated with smoking relapse exhibit a reduction in BOLD signal in the bilateral dorsolateral PFC and MF/CG during nicotine withdrawal as well as impairments in working memory at high levels of task difficulty (Loughead et al., 2009). In a follow-up experiment, it was found that the smoking cessation medication varenicline reverses this deficit (Loughead et al., in press). In the current study, we propose to extend these findings in a smoking cessation treatment population by testing: (1) whether brain activation and connectivity in a resting state, assessed by ASL perfusion MRI, BOLD fMRI, and diffusion tensor imaging (DTI) predicts smoking relapse, and (2) whether brain activation, assessed by BOLD fMRI during performance of neurobehavioral probes for executive cognitive function, stress and cue reactivity, predicts smoking relapse. Following eligibility screening (week 0), 100 treatment-seeking smokers will complete two 1.5 hour pre-quit neuroimaging assessments (one following 24 hours of overnight abstinence and the other after smoking-as-usual (weeks 1 and weeks 2-3; order counterbalanced). All will receive standardized behavioral smoking cessation counseling (week 4) to prepare for a scheduled quit attempt (week 5). They will make brief visits to the Center (weeks 5, 6, 7, 8 \& 9) to receive booster counseling and assess smoking status. The primary endpoints for assessing quitting success are: 8 weeks post-target quit date (week 13) and 24-weeks post target quit date (week 29). At the 8-week post-target quit date all participants will be contacted for a telephone survey and those who self-report not smoking for the past 7 days will be asked to come to the Center for biochemical confirmation. Lastly, a subset of participants (15 smokers who report having been abstinent for at least the past 7 days and 15 smokers who relapsed within the first few weeks of the TQD) will be asked to complete a third MRI scan to examine changes in brain activity related to cessation. Only those participants reporting being quit at this time point will be contacted again at 24 weeks. Identification of the neural substrates of relapse following a quit attempt could inform the development of novel medications. Further, the identification of a "brain signature" that predicts relapse may allow for the use of fMRI to screen novel medications and identify those that reverse the liability profile.