PROJECT SUMMARY/ABSTRACT The use of electronic nicotine delivery systems (ENDS) is on the rise, particularly among young people, and has been linked to nicotine dependence. Abuse of ENDS is associated with a variety of adverse consequences, but as is frequently observed with substance dependence, these adverse consequences are often insufficient to motivate and sustain quitting attempts. Nicotine dependence remains a significant public health burden. New approaches to facilitate quitting and sustain abstinence are needed, which will require novel insights into why a nicotine addiction remains so difficult to overcome. Attention has long been understood to play an important role in the addiction process, including nicotine addiction. Attention selects which aspects of sensory input receive cognitive processing and thereby influence behavior. A substantial body of research has been devoted to investigating the mechanisms by which smoking-related cues draw attention through reward-mediated processes and the degree to which these biases predict quitting, along with developing attentional bias modification techniques intended to facilitate quitting. These efforts have been largely unsuccessful and therefore appear to fall short of accounting for the full range of information processing biases responsible for the maintenance of a nicotine addiction. In the pursuit of a more comprehensive account of these biases, the influence of aversive outcomes on attention offers promise. Interest in how aversive outcomes influence the control of attention has grown in recent years, and robust biases towards aversively- conditioned stimuli have been identified in non-clinical samples. However, how aversive conditioning influences attention in the context of addiction remains unexplored. This is especially pertinent to the issue of why individuals often maintain an addiction in spite of repeated exposure to its harmful effects. To address this gap in understanding, the proposed research seeks to identify how nicotine-dependent ENDS users and non-users differ with respect to the manner in which their attention systems are influenced by aversive outcomes. In Specific Aim 1, attentional biases towards aversively conditioned stimuli in ENDS users and matched non- users will be measured, probing the strength of threat-related attentional biases. In Specific Aim 2, differences between users and non-users with respect to the relative influences of threat detection and negative reinforcement on the control of attention will be examined, which together with Specific Aim 1 will provide a comprehensive picture of whether and how aversive information processing differs between ENDS users and non-users. The overarching goal of the proposed research is to more fully characterize how biases in the orienting of attention are related to nicotine addiction, offering unique insights into why users are often undeterred by the adverse effects of their habit. Knowledge gained from the pr...