# Excitatory/Inhibitory Balance and Behavioral Flexibility in Adults with a History of Adolescent Binge Drinking

> **NIH NIH F31** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $38,190

## Abstract

PROJECT SUMMARY/ABSTRACT
 Adolescents tend to consume alcohol less often but at higher volumes than adults do, a pattern referred
to as binge drinking. Because adolescence is a critical period for brain development, excessive exposure to
alcohol is particularly concerning. For example, during adolescence the prefrontal cortex (PFC) GABAergic
system matures from the pre-adolescent state of great excitation to inhibition to reduced, adult-like proportions.
This GABAergic development is disrupted by exposure to alcohol, a GABA agonist, resulting in increased
excitatory/inhibitory (E/I) balance in the PFC that persists into adulthood. One facet of executive function that is
reliant on the PFC and that published data suggest is impacted by adolescent binge drinking is behavioral
flexibility, which describes an individual’s ability to adjust their behavior to changing environmental
circumstances. Indeed, reduced PFC GABA has been associated with both adolescent binge alcohol exposure
and impairments in behavioral flexibility, but no studies to date have evaluated whether reduced GABA, or
more generally, a skewed E/I balance, mediates the association between adolescent alcohol exposure and
behavioral inflexibility in humans. Based on available evidence, we hypothesize that adolescent binge drinking
increases the E/I balance of the PFC. Thus, the proposed study will first assess group differences in E/I
balance amongst adults with and without a history of adolescent binge drinking using a recently described
method in which E/I balance can be derived from the slope of the brain’s electroencephalographic (EEG)
power spectrum (Aim 1). Further, we hypothesize that adults with a history of adolescent binge drinking will
exhibit reduced behavioral flexibility, and that E/I balance will mediate this relationship (Aim 2). To test this, we
will utilize the Hidden Association Between Images Task to assess habitual responding, a metric of inflexible
behavior. To further test the relationship between E/I balance and behavioral flexibility, we will assess whether
bilateral transcranial alternating current stimulation (tACS) of the PFC, which modulates the E/I balance of
stimulated brain regions, alters performance on this task-based measure of behavioral flexibility (Aim 3). We
hypothesize that PFC stimulation which increases the E/I balance of the brain will impair behavioral flexibility.
Together, this proposed research will provide new information regarding persistent neural and behavioral
changes associated with adolescent binge drinking. Given evidence that early alcohol use is associated with
elevated lifetime prevalence of substance use disorders, and that behavioral inflexibility and disruptions in E/I
balance are present in adults with substance use disorders, insight into these relationships could provide a
mechanistic link between early alcohol use and this elevated risk and could thereby aid in the development of
novel therapeutic targets.

## Key facts

- **NIH application ID:** 10260422
- **Project number:** 5F31AA028427-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Madeline Mae Robertson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,190
- **Award type:** 5
- **Project period:** 2020-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10260422

## Citation

> US National Institutes of Health, RePORTER application 10260422, Excitatory/Inhibitory Balance and Behavioral Flexibility in Adults with a History of Adolescent Binge Drinking (5F31AA028427-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10260422. Licensed CC0.

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