ABSTRACT Tobacco addiction is a costly and often fatal problem. Even with counseling and nicotine replacement therapy, most smokers relapse following a quit attempt. For many smokers, cigarette smoking is provoked by affective distress. The ability to cope with this distress and remain abstinent may depend on one's level of distress tolerance, which is the ability to persist in a goal-directed activity while experiencing physical or affective discomfort. However, a gap in knowledge exists regarding the neural mechanisms that underlie distress tolerance. Identifying these neural mechanisms and understanding individual differences in distress tolerance holds promise for the development of new therapies and the improvement of cessation success through personalized interventions. Past research has shown that cigarette cravings and other forms of affective distress activate the insula, which may be the neural hub that connects the awareness of affective distress to cognitive control regions that determine the subsequent behavioral response (e.g., smoking a cigarette to relieve cravings). However, there is a significant gap in knowledge concerning whether insula connectivity underlies real-world distress tolerance behavior in the service of smoking cessation. Lab-based measures of distress tolerance provide standardized comparisons across individuals and could be used to identify smokers who would most benefit from interventions. A complementary approach, ecological momentary assessment, can capture temporal relationships among affective distress, craving, and smoking as they occur in smoker's daily lives, in real time. The goal of this research is to test the predictive validity of lab-based measures of distress tolerance against the real-world stress/smoking relationship, and to identify neural differences within smokers that relate to distress tolerance and could predict quit outcomes (i.e., relapsed vs nonrelapsed). To address this gap in knowledge, we will investigate three aims: Aim 1) Associate lab measures of distress tolerance to insula connectivity. Aim 2) Relate lab measures of distress tolerance with real-world stress and smoking using ecological momentary assessment. Aim 3) Explore how insula connectivity relates to real-world stress and smoking. By providing clear evidence of how distress tolerance, brain connectivity, and daily stress relate to quit outcomes, this study will greatly increase our understanding of why some smokers succeed in quitting while others relapse. This research will be generalizable to other drug addictions and psychiatric conditions that are exacerbated by physical or affective distress. Successful completion of this study will inform the development of personalized smoking interventions, as well as identify neural mechanisms that can be targeted by novel therapeutic techniques.

R01DA048948

2019-08-15

2024-05-31