Limbic-Executive Network Transitions in Alcohol Use Disorder

项目摘要 酒精使用障碍(AUD)非常普遍，治疗后的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。 在这一点上，AUD可以被概念化为与以下相关的“内部”定向大脑网络之间的冲突 奖赏冲动(边缘模式和默认模式网络)和参与非酒精相关任务的需要 (额顶顶层，“积极任务”网络)。这种紧张在治疗中尤其明显，那些患有 澳元必须学会如何摆脱对酒精的痴迷，转而投身于其他地方。 大多数研究功能性大脑网络组织的工作(无论是在AUD，还是更广泛的)都检查了 特定认知状态下的功能连通性(例如，在“休息”或特定任务期间)。这是最主要的 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间 其他要求。一种新的方法是必要的。 该R21探索性机制的目标是使用一种新的范例来获取初步数据 这反映了康复过程中所需的认知状态变化。具体地说，我们将研究奖励和 高管职能网络，因为他们脱离了酒精饮料品尝所产生的激励突出， 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(激励显著、执行功能、负面 影响)与从酒精相关时期过渡时功能较差的网络重新配置有关 对执行控制的胃口刺激。我们的理论基础是研究这些动态大脑的本质 网络变化将有助于理解导致不同治疗结果的机制。 在很好地检验这种假设之前，我们首先需要初步的数据来证明 连接性的组成部分可以从我们提出的新范式中提取出来。这样做的具体目的是 因此，试探性/开发性赠款申请将用于： 目标1：论证在以下过程中获取网络重新配置组件的可行性 从食欲状态(品尝首选的酒精饮料)转变到认知控制(停止 信号响应抑制)。 目标2：测试AUD受试者和健康社交受试者在网络转换上的差异 酒鬼。 从R21探索机制获得的初步数据将支持R01应用程序进行更多 AUD在执行功能、激励领域的表型变异性的综合研究 显著，情绪与大脑网络的动态相关，因为它们自适应地重新配置。

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.