Limbic-Executive Network Transitions in Alcohol Use Disorder

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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.