# Limbic-Executive Network Transitions in Alcohol Use Disorder

> **NIH NIH R21** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $239,933

## Abstract

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.

## Key facts

- **NIH application ID:** 10317609
- **Project number:** 1R21AA029614-01
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** DAVID A. KAREKEN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $239,933
- **Award type:** 1
- **Project period:** 2021-09-25 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10317609

## Citation

> US National Institutes of Health, RePORTER application 10317609, Limbic-Executive Network Transitions in Alcohol Use Disorder (1R21AA029614-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10317609. Licensed CC0.

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