Functional connectivity reconfigurations in risk for alcohol use disorders

项目摘要 酒精使用障碍(AUD)遗传风险的一个重要方面是执行功能低下和适应性低 行为控制。新出现的研究表明，这种执行能力与活动引发的变化有关 在大脑网络功能连接(FC)中。我们对遗传的AUD风险如何影响 支持执行功能的大型网络FC，而现有的小主体研究没有研究 网络如何动态适应不断变化的需求。 我们实验室的长期目标是了解AUD的遗传性大脑脆弱性。此应用程序的 目的是确定AUD风险如何在精神状态下影响大脑网络FC重新配置 过渡。根据我们已发表的初步发现，我们的中心假设是：(I)遗传 AUD风险涉及认知和奖励极端之间转换的低效FC重新配置 参与，以及(2)这些过渡性重新配置与关键澳元风险的自适应控制有关 域名。因此，我们的具体目标是： 目标1：确定认知参与和低水平转换过程中的FC重构 认知负荷(“休息”)与AUD风险因素有关。 目标2：确定在酒精-线索刺激(“食欲”)之间的转换过程中FC的重新配置 参与度“)和休息与澳元风险因素有关。 目标3：确定FC重组与饮酒和酒精相关问题的关系。 探索性目标：测试(A)联合食欲和认知任务网络重构效应； 对饮酒的多重调节作用，以及(C)与失控饮酒有关的影响。 我们提出的工作使用了一种新的范式和分析来描述REST和状态之间的转换 认知控制和酒精暗示暴露。因此，这项工作有望发现新的基本原理 关于灵活和适应性行为调节所需的大脑网络交互作用的知识。是这样的 数据对于理解澳元汇率风险的机制至关重要。这些发现也将被用来开发 “疾病网络”的生物标记物，可以在治疗研究中监测以实现正常化，或者可以 预测治疗反应。

Project Summary An important aspect of inherited risk for alcohol use disorder (AUD) is low executive function and adaptive behavioral control. Emerging work shows that such executive abilities are related to activity-induced changes in brain network functional connectivity (FC). We know very little about how inherited AUD risk affects the large-scale network FC supporting executive functions, and the small body of extant research does not study how networks dynamically adapt to changing demands. Our lab’s long-term goal is to understand inherited brain vulnerabilities for AUD. This application’s objective is to determine how AUD risks affect brain network FC reconfiguration during mental state transitions. As informed by our published preliminary findings, our central hypotheses are that (i) inherited AUD risk involves inefficient FC reconfiguration in transitioning between extremes of cognitive and reward engagement, and that (ii) these transitional reconfigurations relate to adaptive control in the key AUD risk domains. Our specific aims are therefore to: Aim 1: Determine how FC reconfiguration during transitions between cognitive engagement and low cognitive load (“rest”) relates to AUD risk factors. Aim 2: Determine how FC reconfiguration during transitions between alcohol-cue stimulation (“appetitive engagement”) and rest relates to AUD risk factors. Aim 3: Determine how FC reconfiguration relates to drinking and alcohol-related problems. Exploratory Aims: Test for (A) joint appetitive and cognitive task network reconfiguration effects; B) multiple mediation effects on drinking, and (C) effects related to loss of control drinking. Our proposed work uses a novel paradigm and analyses to characterize transitions between rest and states of cognitive control and alcohol cue exposure. The work is thus poised to discover new fundamental knowledge about brain network interactions necessary for flexible and adaptive behavioral regulation. Such data are critical to understanding mechanisms of AUD risk. The findings will also be used to develop biomarkers of “disease networks” that can be monitored in treatment research for normalization, or that can predict therapeutic response.