Limbic-Executive Network Transitions in Alcohol Use Disorder

酒精使用障碍中的边缘-执行网络转变

• 批准号: 10317609
• 负责人: DAVID A. KAREKEN
• 金额: $ 23.99万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-25 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10317609
• 关键词: Aftercare; Alcohols; Applications Grants; Area; Behavioral; Behavioral inhibition; Biological Markers; Brain; Cognitive; Conflict (Psychology); Data; Desire for food; Emotions; Executive Dysfunction; Exploratory/Developmental Grant; Family; Goals; Image; Knowledge; Lead; Learning; Methods; Modeling; Nature; Outcomes Research; Patients; Performance; Phenotype; Positioning Attribute; Publishing; Recovery; Regulation; Relapse; Rest; Rewards; Risk; Risk Factors; Signal Transduction; Taste Perception; Testing; Time; Treatment outcome; Work; alcohol use disorder; cognitive control; cohort; executive function; flexibility; improved; incentive salience; male; mental state; negative affect; novel; novel strategies; problem drinker; response; sample fixation; sex; social

Project Summary Alcohol use disorders (AUD) are highly prevalent and post-treatment relapse remains stubbornly elevated. Understanding the brain mechanisms that contribute to varied treatment outcomes is thus of great importance. In this regard, AUD can be conceptualized as a conflict between “inwardly” directed brain networks related to reward urges (limbic and default-mode networks) and the need to engage in non-alcohol-related tasks (frontoparietal, “task-positive” networks). Such a tension is particularly evident in treatment, where those with AUD must learn how to transition away from alcohol preoccupation to engage elsewhere. Most work that examines functional brain network organization (both in AUD, and more generally) examines functional connectivity within particular cognitive states (e.g., during “rest” or a given task). This predominant approach ignores critical times of transition when the brain must functionally reconfigure and adapt to other demands. A new approach is necessary. The objective of this R21 exploratory mechanism is to acquire preliminary data using a novel paradigm that mirrors the cognitive state changes needed during recovery. Specifically, we will study reward and executive functional networks as they disengage from the incentive salience created by alcoholic drink tastes, and transition into periods requiring cognitive control and behavioral inhibition. Our central hypothesis is that phenotypic domains of AUD (incentive salience, executive function, negative affect) are related to less functional network reconfiguration when transitioning from periods of alcohol-related appetitive stimulation to executive control. Our rationale is that studying the nature of these dynamic brain network changes will help to understand the mechanisms that lead to variable treatment outcomes. Prior to being well-positioned to test such a hypothesis, we first require preliminary data demonstrating that components of connectivity can be extracted from our proposed novel paradigm. The specific aims of this exploratory/developmental grant application are therefore to: Aim 1: Demonstrate the feasibility of obtaining network reconfiguration components during the transition from an appetitive state (tasting a preferred alcoholic drink) to cognitive control (stop signal response inhibition). Aim 2: Test for differences in network transitions between subjects with AUD and healthy social drinkers. Preliminary data derived from this R21 exploratory mechanism will then support an R01 application for a more comprehensive study of how AUD phenotypic variability in the domains of executive function, incentive salience, and emotion relates to the dynamics of brain networks as they adaptively reconfigure.

项目摘要 酒精使用障碍（AUD）高度普遍，治疗后继电器仍然顽固地升高。 因此，了解导致各种治疗结果的大脑机制至关重要。 在这方面，AUD可以被概念化为“向内”定向的大脑网络之间的冲突 奖励冲动（边缘和默认模式网络）以及参与与酒精相关的任务的需求 （Frontoparietal，“任务阳性”网络）。这种紧张局势在治疗中尤其是 AUD必须学习如何从饮酒过渡到其他地方参与。 大多数检查功能性脑网络组织（在AUD和更广泛）检查的工作 特定认知状态内的功能连接性（例如，在“休息”或给定的任务期间）。这主要 当大脑必须重新配置并适应大脑时，方法忽略过渡的关键时期 其他要求。需要一种新的方法。 这种R21探索机制的目的是使用新型范式获取初步数据 这反映了恢复过程中所需的认知状态变化。具体来说，我们将研究奖励和 执行功能网络与酒精饮料品味产生的激励显着性相关， 并过渡到需要认知控制和行为抑制的时期。 我们的中心假设是AUD的表型领域（激励显着性，执行功能，负面 情感）与从酒精相关的周期过渡时，与功能网络重新配置较低有关 对执行控制的开胃刺激。我们的理由是研究这些动态大脑的性质 网络变化将有助于了解导致可变治疗结果的机制。 在拟合良好以检验这种假设之前，我们首先需要初步数据，以表明 连通性的组成部分可以从我们提出的新型范式中提取。这个特定的目的 因此 目标1：证明在此期间获得网络重新配置组件的可行性 从食欲（品尝首选酒精饮料）过渡到认知控制（停止 信号响应抑制）。 目标2：测试AUD和健康社交受试者之间网络过渡的差异 饮酒者。 然后，从该R21探索机制得出的初步数据将支持更多的R01应用程序 关于执行功能领域的AUD表型变异性如何，激励性的全面研究 显着性和情感与大脑网络的动态相关，它们可以适应重新配置。