Neural and Mobile Assessment of Behavior Change Among Problem Drinkers

在美国，酗酒是可预防死亡的第三大原因，也是导致死亡的第二大原因。 然而，在24-44岁的成年人中，目前的知识有两个重要的差距：1） 不太严重的AUD形式（如问题饮酒（PD））的潜在机制知之甚少，2） PD行为改变的潜在机制，包括自发（非治疗）行为 短期干预（BI）导致的改变和行为改变，这在PD中特别有效。 在这里，我们解决了第一个差距，假设PD有提高激励显着性酒精线索 （反应）和受损的能力，以调节激励显着性（监管）相比，社会饮酒者（SD）。 我们将在实验室中使用功能性MRI（fMRI）在神经和行为水平上测试这一假设， 自然环境生态瞬时评价（EMA）。我们解决第二个差距的假设， 而PD中的自发行为变化主要取决于反应性过程， 对BI的响应变化主要取决于监管过程。为此，我们将招募100名 PD和50名社交饮酒者（SD）。在基线时，所有参与者将完成两周的EMA， 在fMRI扫描期间进行酒精调节渴望（ROC）任务，然后再完成3周的EMA。的 ROC任务提供了反应性的行为和fMRI测量（例如腹侧纹状体活动增加， 线索诱导的酒精渴望的报告）调节（例如，控制相关的前额叶活动和减少 渴望）。这些分析将测试基线神经和环境指标的组间差异， 反应性和调节。接下来，PD将随机接受立即接受BI或接受BI 6个月后，测量结果后（延迟干预对照组，或DIC组）。BI和DIC 各组将在分配后三周内完成EMA方案。饮酒的结果将是 在3个月和6个月时进行评估。我们预计，相对于SD，PD将显示出更高的神经测量值， 反应性（例如，在被动观察条件下，腹侧纹状体（VS）对酒精提示的激活升高），以及 调节的神经测量减少（例如，调节期间前额控制区的活动减少 （目标1）。与此同时，PD将报告更高水平的反应性和更低水平的EMA监管 与SD相比，SD将与fMRI测量相关（目标2）。我们预测，在BI中， 组，减少酒精使用将缓和神经系统的功能调节（例如， 背外侧PFC），而在DIC组中，持续使用酒精将受到功能的调节。 神经系统的反应性（例如VS）（目标3）。最后，我们预测，在BI组中， 使用将通过EMA调节措施的变化介导，并通过以下治疗前指标预测 在ROC任务中，酒精使用的变化将通过以下因素的变化来介导： 反应性的EMA测量，并通过ROC任务中的反应性的预处理测量进行预测（目标4）。

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).