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: 10494195
• 负责人: DAVID A. KAREKEN
• 金额: $ 19.03万
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10494195
• 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）非常普遍，治疗后复发率仍然居高不下。 因此，了解导致不同治疗结果的大脑机制非常重要。 在这方面，AUD可以被概念化为与以下相关的“向内”定向的大脑网络之间的冲突： 奖励冲动（边缘系统和默认模式网络）和参与非酒精相关任务的需要 （frontoparietal，“task-positive”networks）.这种紧张关系在治疗中尤其明显， AUD必须学会如何从酒精过度到其他地方。 大多数研究功能性大脑网络组织的工作（无论是在AUD中，还是更普遍地）都研究了 特定认知状态内的功能连接（例如，在“休息”或给定任务期间）。这种占主导地位的 这种方法忽略了大脑必须在功能上重新配置和适应的关键过渡时期， 其他要求。必须采取新的办法。 该R21探索机制的目的是使用新的范例获取初步数据 这反映了恢复期间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，因为他们脱离了酒精饮料口味所创造的激励显着性， 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的表型域（激励显著性，执行功能，负 影响）与从酒精相关的时期过渡到功能较少的网络重新配置有关 食欲刺激到执行控制。我们的理论基础是，研究这些动态大脑的性质， 网络变化将有助于理解导致治疗结果可变的机制。 在做好准备检验这一假设之前，我们首先需要初步数据来证明， 可以从我们提出的新范例中提取连通性的组成部分。具体目标是 因此，探索性/发展性赠款申请应： 目标1：演示在网络重构期间获得网络重构组件的可行性。 从食欲状态（品尝优选的酒精饮料）到认知控制（停止）的转变 信号响应抑制）。 目的2：测试AUD受试者和健康社交受试者之间的网络转换差异 酒鬼 从R21探索机制中获得的初步数据将支持R 01应用程序， 全面研究AUD表型变异性在执行功能、激励 显著性和情绪与大脑网络的动态变化有关，因为它们自适应地重新配置。