7. Project Summary/Abstract Lung cancer is the leading major cause of preventable death in the United States, and cigarette smoking is a contributor to lung cancer in 80%–90% of cases. Though adult cigarette smoking rates have declined substantially during the past 50 years, they remain as high as 30% in certain groups, such as individuals living in poverty. Quitting is difficult: a given quit attempt results in cessation in fewer than 10% of cases, and most adult cigarette smokers have attempted and failed to quit, and often many times. What is urgently needed are novel interventions for cigarette smoking cessation that operate through different mechanisms from those targeted by existing interventions, which are likely to have been unsuccessful for persistent smokers. A barrier to progress is that the mechanisms of action of most treatments are not known, which makes it difficult to know which treatment will work best for whom. We turn to affective science to identify a candidate technique that could serve as the basis for a novel intervention. Research on affect regulation typically focuses on down- regulation of affective states, such as craving for cigarettes, using effortful strategies such as cognitive reappraisal. However, a new insight in affect regulation is that people can construe, or subjectively understand, events with varying levels of abstraction, and that construing health-related behaviors in high- versus low-level terms promotes health behavior in several domains. For example, smokers who want to quit are more likely to resist a cigarette when they construe the same event (e.g., “abstinence”) in more abstract, high-level terms (e.g., “becoming a better me”) versus more concrete, low-level terms (e.g., “not smoking this cigarette”). There is some evidence that high-level construal might rely on distinct mechanisms from traditional affect regulation and smoking reduction interventions, but its mechanisms of action are unknown. Directly comparing its mechanisms to those of alternative affect regulation strategies and developing tools to induce high-level construal are the next steps on the path toward developing a novel intervention. Also, establishing individual differences in the effects of high-level construal will allow future interventions to be targeted to the individuals for whom they will be maximally effective. We identified two candidate mechanisms through which high-level construal might operate: down-regulation of craving and up-regulation of goal energization (i.e., motivation to quit). Functional magnetic resonance imaging (fMRI) revealed the neural systems engaged by those processes to be distinct. So, we will use multivariate analyses of fMRI data to quantify the similarity of high-level construal to each candidate (Aim 1). This will be done in a longitudinal translational experiment with 4 conditions—high- level construal, down-regulation of craving, up-regulation of goal energization, and treatment-as-usual—in a s...