# Multimodal Neuroimaging of Alcohol Withdrawal: The Role of Glutamate in Neural Reorganization

> **NIH NIH K01** · YALE UNIVERSITY · 2020 · $178,243

## Abstract

PROJECT ABSTRACT
This Mentored Research Scientist Development Award application proposes support for Ansel Hillmer, Ph.D.,
in his transition to independent research using neuroimaging to study alcohol use disorders in humans.
Glutamate's role in both alcohol dependence and neuroplasticity make it a critical system to examine the
neurochemical underpinnings of dynamic changes in brain structure and function in alcohol dependence and
withdrawal. The goal of this proposed research is to study the role of the metabotropic glutamate 5 receptor
(mGluR5), a promising target for alcohol dependence therapeutics, in neural reorganization during alcohol
withdrawal. Specific focus is given to examining relationships between neurochemical changes and clinical
correlates of alcohol dependence throughout the course of withdrawal. We propose to perform longitudinal
neuroimaging in 40 alcohol dependent patients during withdrawal at 7-10 days abstinence and 4 weeks
abstinence, and single sessions in 30 matched healthy controls. The recruitment and evaluation of alcohol
dependent patients will be mentored by Kelly Cosgrove, Ph.D. and Stephanie O'Malley, Ph.D. Neuroimaging
sessions will feature 18F-FPEB PET scans to measure mGluR5 availability, and resting state fMRI connectivity
to examine neural organization. First, we will assess differences in both mGluR5 availability and resting state
connectivity in patients longitudinally and relative to controls. Next, we will determine relationships of
neuroimaging measures with clinical and cognitive correlates of alcohol dependence. The acquisition and
analysis of mGluR5-specific PET data will be mentored by Dr. Cosgrove and Richard Carson, Ph.D.; while
acquisition and analysis of connectivity measures will be mentored by Todd Constable, Ph.D. Finally, we will
develop analysis methods, using techniques such as parallel Independent Component Analysis, to analyze
multimodal mGluR5 PET and whole-brain connectivity data in synergy. This work will be co-mentored by Drs.
Carson, Constable, and Godfrey Pearlson, Ph.D. These proposed experiments will provide insight into possible
uses of mGluR5 therapeutics for alcohol dependence, examine how clinical correlates of dependence change
during withdrawal in relation to mGluR5 function and neural organization, and develop analysis methods
evaluating neurotransmitter-specific function in neuronal connectivity. The research experience will be
supported by a complementary training plan providing scientific development in four key areas: clinical alcohol
research, functional Magnetic Resonance neuroimaging (fMRI), Positron Emission Tomography (PET)
neuroimaging, and responsible conduct of research. Thus this K01 award will advance the field's
understanding of evolving brain function during alcohol withdrawal, and supply a uniquely qualified scientist
blending innovative techniques from clinical alcohol research and neuroimaging to advance future
understanding of brain dysfunction in alcoh...

## Key facts

- **NIH application ID:** 9858199
- **Project number:** 5K01AA024788-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Ansel Hillmer
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $178,243
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858199

## Citation

> US National Institutes of Health, RePORTER application 9858199, Multimodal Neuroimaging of Alcohol Withdrawal: The Role of Glutamate in Neural Reorganization (5K01AA024788-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9858199. Licensed CC0.

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