Heavy drinking is the third leading cause of preventable death in the U.S. and is the second leading cause of disability among adults aged 24-44, however, there are two important gaps in current knowledge: 1) the mechanisms underlying less severe forms of AUD, like problem drinking (PD), are poorly understood, as are 2) the mechanisms underlying behavior change in PD, including both spontaneous (non-treatment) behavior change and behavior change that results from brief interventions (BI), which are particularly effective in PD . Here, we address the first gap by positing that PD have heightened incentive salience to alcohol cues (reactivity) and impaired ability to regulate incentive salience (regulation), compared to social drinkers (SD). We will test this hypothesis at a neural and behavioral level in the lab using functional MRI (fMRI) and in the natural environment ecological momentary assessment (EMA). We address the second gap by positing that whereas spontaneous behavior change in PD depends primarily upon the reactivity processes, behavior change in response to a BI depends primarily upon regulation processes. To these ends, we will recruit 100 PDs and 50 social drinkers (SD). At baseline, all participants will complete two weeks of EMA, perform an alcohol regulation of craving (ROC) task during fMRI scanning, and then complete 3 more weeks of EMA. The ROC task provides behavioral and fMRI measures of reactivity (e.g. increased ventral striatum activity and reports of cue-induced alcohol craving) regulation (e.g. control-related prefrontal activity and diminished craving). The analyses will test for group differences in baseline neural and environmental measures of reactivity and regulation. Next, PDs will be randomized to receive either a BI immediately or to receive the BI after 6 months, after outcomes are measured (the delayed intervention control, or DIC group). Both BI and DIC groups will complete an EMA protocol for the three weeks following assignment. Drinking outcomes will be assessed at 3 and 6 months. We expect that relative to SDs, PDs will show heightened neural measures of reactivity (e.g. elevated ventral striatum (VS) activation to alcohol cues in passive viewing conditions), and reduced neural measures of regulation (e.g. reduced activity in prefrontal control regions during regulation conditions) (Aim 1). In parallel, PDs will report higher levels of reactivity and lower levels of regulation in EMA measures, compared to SD, which will be correlated with fMRI measures (Aim 2). We predict that in the BI group, reduction in alcohol use will be moderated by the functioning of neural systems for regulation (e.g. dorsolateral PFC), whereas in the DIC group a persistence of alcohol use will be moderated by the functioning of neural systems for reactivity (e.g. VS) (Aim 3). Finally, we predict that in the BI group, changes in alcohol use will be mediated by changes in EMA measures of regulation and predicted by pre-treatment indices of regulation in the ROC task, whereas in the DIC group, changes in alcohol use will be mediated by changes in EMA measures of reactivity and predicted by pre-treatment measures of reactivity in the ROC task (Aim 4).
Although problem drinkers (PD) are a less severe, highly prevalent sub-type of alcohol use disorder (AUD) who are more likely to undergo reductions in alcohol use, compared to more severe AUD, the underlying mechanisms that maintain PD, as well as the mechanisms that underlie both spontaneous and treatment- related behavior change in this population, are not well understood. This proposal takes a lab to life approach by combining functional neuroimaging (fMRI), ecological momentary assessment (EMA), and brief interventions (BI) in non-treatment seeking PD to test whether heightened incentive salience (reactivity) to alcohol cues and impaired ability to regulate cue-induce craving are the mechanisms that characterize PD, and play a role in behavior change vs. persistence of behavior. Identifying these mechanisms is critical for testing and understanding treatments and uncovering who is most likely to respond to interventions.
