Attentional Ability and Resilience to Alcohol Use Disorder: Neurocognitive Mechanisms - PROJECT SUMMARY A family history (FH) of alcohol use disorder (AUD) increases one’s personal risk of AUD by 3-4 fold. Given the large proportion of the burden of AUD endured by these individuals and their families, the development of impactful prevention and treatment strategies should consider focused strategies for those individuals. A compelling approach to accomplish this goal is to augment brain resilience mechanisms to compensate for underlying vulnerabilities, which would have greatest efficacy in those at highest risk for poor outcomes. With this objective in mind, we previously identified candidate neurocognitive mechanisms of resilience to familial risk for AUD by comparing FH-positive young adults with versus those without AUD relative to controls. Using this resilience-centered framework, a well-powered, data-driven analysis identified self-reported attentional ability as the factor that most robustly predicted AUD resilience. We validated this finding in a large, independent sample, demonstrating that at-risk young adults with FH that do not binge drink report heightened attentional ability, not only relative to those that binge drink, but even relative to low-risk, non-binge-drinking young adults, supporting the notion that attentional processes support resilient outcomes to AUD and binge drinking. We now seek to advance these cross-sectional, self-report associations in a rigorous, systematic investigation to identify targetable cognitive processes and brain regions that promote AUD-related resilience. Currently, the mechanisms linking attentional ability to AUD resilience remain undetermined. The proposed studies seek to establish how attentional ability protects against the development of alcohol use disorder in at-risk individuals by combining both observational and experimental methods. In Aim 1, we will examine the role of facets of attention measured with fMRI, EEG, and behavior on alcohol use trajectories in 200 emerging adults, including those at risk (FH-positive) and those not at risk (FH-negative) for AUD. The neural correlates of the relationship between attentional ability and future alcohol use will be examined with computational analyses of fMRI and EEG data acquired during attention tasks. In Aim 2, we will test whether fMRI and EEG markers of attention attenuate neural responses to pictorial alcohol cues as a mechanism of AUD resilience. In these two longitudinal aims, we predict that greater “top-down” neurobehavioral indicators of attentional ability (Aim 1) will promote reduced “bottom up” cue reactivity (Aim 2), resulting in shallower alcohol use trajectories in FH-positive (vs. FH-negative) individuals. Aim 3 will include a subsample of 50 “non-resilient” subjects reporting problematic alcohol use. We will test causal relationships by examining effects of boosting attentional ability with methylphenidate on neural cue reactivity (as a proxy for addiction) in a placebo-controlled, within-subjects study. Successful completion of this project will substantially increase our understanding of the neuroscience of resilience related to addiction. This knowledge will support the development of treatment and preventive strategies that could significantly mitigate alcohol-related problems in the millions of individuals in the US with familial risk.
