Functional connectivity reconfigurations in risk for alcohol use disorders

酒精使用障碍风险中的功能连接重新配置

• 批准号: 10706470
• 负责人: Mario Dzemidzic
• 金额: $ 54.32万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-20 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10706470
• 关键词: Affect; Alcohols; Attention; Behavior Control; Behavioral; Biological Markers; Brain; Brain region; Cognitive; Data; Desire for food; Disease; Exposure to; Family history of; Goals; Hair; Impulsivity; Inherited; Joints; Knowledge; Mediation; Methods; Monitor; Outcomes Research; Pathway interactions; Pattern; Phenotype; Prediction of Response to Therapy; Prevention Research; Psychopathology; Publishing; Regulation; Research; Rest; Rewards; Risk; Risk Factors; Services; System; Taste Perception; Testing; Work; alcohol cue; alcohol related problem; alcohol risk; alcohol use disorder; biological sex; brain based; cognitive change; cognitive control; cognitive function; cognitive load; cognitive task; connectome; craving; critical period; cue reactivity; discounting; disorder risk; drinking; drinking behavior; executive function; externalizing behavior; flexibility; functional disability; incentive salience; male; mental state; negative affect; novel; problem drinker; response; sample fixation; support network; treatment research; treatment response

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.

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 行为控制新的研究表明，这种执行能力与活动引起的变化有关 大脑网络功能连接（FC）。我们对遗传性澳元风险如何影响 大规模网络FC支持执行功能，而小机构现存的研究并没有研究 网络如何动态地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风险如何影响精神状态期间的脑网络FC重构 过渡。根据我们发表的初步研究结果，我们的中心假设是：（i）遗传性 AUD风险涉及在认知和奖励极端之间过渡时低效的FC重新配置 （ii）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.因此，我们的具体目标是： 目标1：确定在认知参与度和低参与度之间的过渡期间FC如何重新配置 认知负荷（“休息”）与AUD风险因素有关。 目的2：确定在酒精-线索刺激（“食欲”）之间的过渡期间FC如何重新配置 参与度”）和休息与澳元风险因素有关。 目标3：确定FC重新配置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新配置效应; B） 对饮酒的多重中介作用，以及（C）与饮酒失控相关的作用。 我们提出的工作使用一种新的范式和分析来表征休息和状态之间的转换 认知控制和酒精暴露的关系因此，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必需的大脑网络相互作用的知识。等 数据对于理解澳元风险机制至关重要。研究结果还将用于开发 可以在治疗研究中监测的“疾病网络”的生物标志物， 预测治疗反应。