Identifying circuit-level neuromarkers of smoking dependence that change in response to intervention

Abstract Although half of the 37 million adult smokers in the US attempt to quit each year, only an estimated 3% are successful. Smoking is associated with changes in brain circuitry that drive incentive salience valuation and executive control. Over time, the incentive salience of smoking cues become enhanced, while the salience of non-smoking rewards are diminished. Further, executive control over smoking motivation and drives becomes impaired. While functional magnetic resonance imaging (fMRI) has identified brain circuitry associated with incentive salience valuation and executive control, we currently have a limited understanding of how this brain circuitry changes with cessation treatment and reductions in dependence. Characterizing changes in neurocircuitry during smoking cessation has the potential to inform the development of targeted neuropharmacological, behavioral, and brain stimulation cessation interventions. This proposal aims to provide the candidate with training and research to address this critical gap in our identification of modifiable neuromarkers of smoking dependence. The candidate will conduct a double-blind, 6-week, randomized trial of very low nicotine content cigarettes among smokers while collecting longitudinal fMRI measures over 3 time- points. The MRI tasks will engage incentive salience valuation of smoking and non-smoking rewards and executive control through inhibition and decision making. These tasks will include a respiration-triggered-event- related sequence to measure smoking odor cue reactivity, an understudied, but potentially potent secondary smoking reinforcer. With a mentorship team of experts in tobacco use, human olfaction, fMRI, and longitudinal analysis and the support of the Penn State Tobacco Center of Regulatory Science, the candidate will emerge as a patient-oriented clinical researcher contributing to our neurobehavioral understanding of smoking dependence and tobacco use.