# Connectivity between the BNST and insula during prolonged alcohol withdrawal inhumans

> **NIH NIH F30** · VANDERBILT UNIVERSITY · 2021 · $2,500

## Abstract

Project Summary
Alcohol use disorder (AUD) affects more than 16 million Americans, causing a substantial burden on those
affected, the health care system, and the economy. Despite effective treatments, the majority of patients
relapse and are unable to achieve long-term treatment success. Given the high rates of relapse, interventions
that aim to prevent relapse have high potential impact. Research in both animal models and humans shows
that early stages of sobriety are characterized by hyperarousal, anxiety, and depression. These symptoms are
thought to result from the neuroadaptive changes that occur in response to chronic alcohol use and can persist
after the initial detoxification into a stage known as prolonged withdrawal (PW). During PW, relapse is often
driven by negative reinforcement, where drinking is reinforced by the removal of negative affect. Thus, PW is a
high-risk period of recovery because it couples negative reinforcement with hyperarousal, anxiety, and high
susceptibility to stress. In rodents, the bed nucleus of the stria terminalis (BNST) has been identified as a
crucial brain region for both anxiety and stress-sensitivity, especially during prolonged withdrawal. New
findings in an animal model of prolonged withdrawal suggest that insula projections to the BNST underlie the
anxiety and depression phenotype typically observed during this withdrawal period. Our preliminary data show
that the insula and BNST are also connected in humans. The insula is a complex, heterogeneous region.
Findings to date show that the anterior insula is involved in emotion and reward while the posterior insula is
involved in the perception of autonomic activity. Further, the anterior and posterior insula have distinct
neurocircuits. The goal of the current project is to determine the extent to which BNST-insula connectivity is
altered in humans during prolonged withdrawal. Three inter-related aims are proposed to achieve this goal.
Specific Aim 1 will establish the normative pattern of BNST-insula structural connectivity (diffusion tensor
imaging) and resting-state functional connectivity in healthy humans. An anterior and posterior division of the
insula will be used to identify more precise patterns of BNST-insula connectivity. Specific Aims 2 and 3 will
compare patients with AUD who are 30-180 abstinent (PW) to healthy controls (HC). Specific Aim 2 will test for
alterations in BNST-insula structural and resting-state functional connectivity in the PW group compared to HC.
Specific Aim 3 will investigate BNST-insula task-based functional connectivity during a mildly stressful task in
the PW group compared to HC. The hypotheses are 1) that the anterior insula will have stronger structural and
functional connectivity with the BNST than the posterior insula and 2) that BNST-anterior insula connectivity
will be stronger in the PW group compared to HC. The results of this study will fill a critical knowledge gap, by
elucidating the neural mechanisms in...

## Key facts

- **NIH application ID:** 10387505
- **Project number:** 3F30AA027418-02S1
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Elizabeth Flook
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,500
- **Award type:** 3
- **Project period:** 2021-06-15 → 2022-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10387505

## Citation

> US National Institutes of Health, RePORTER application 10387505, Connectivity between the BNST and insula during prolonged alcohol withdrawal inhumans (3F30AA027418-02S1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10387505. Licensed CC0.

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