# Exploring the role of inhibitory dysfunction in age-related cognitive impairments

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $20,726

## Abstract

PROJECT SUMMARY
Aging is associated with substantial cognitive decline across many domains. One factor that may play a role is
age-related changes in neural distinctiveness–the extent to which neural activation patterns evoked by different
stimuli are different. Our research group and others have found that neural distinctiveness tends to decline with
age, and that older adults who maintain more distinctive neural representations perform better on a range of
cognitive tasks. Previous animal work has found that levels of GABA (the brain’s major inhibitory
neurotransmitter) decline with age and that pharmacological manipulations of GABA cause changes in neural
distinctiveness. Based on this work, we hypothesize that age-related changes in cortical inhibition contribute to
age-related declines in neural distinctiveness, which in turn contribute to behavioral impairments. We propose
to test this model in humans. Specifically, we propose to investigate whether individual differences in cortical
inhibition and GABA concentration in visual and motor cortex are associated with individual differences in neural
distinctiveness and cognitive performance. We will recruit a large sample of older and younger adults and will
then use transcranial magnetic stimulation to measure cortical inhibition, Magnetic Resonance Spectroscopy
to measure GABA levels, functional MRI to measure neural distinctiveness, and a battery of validated tasks to
measure cognitive performance. We will then test whether cortical inhibition and GABA levels are reduced in
older vs. younger adults (Aim 1). We will also test whether individual differences in neural distinctiveness are
associated with individual differences in cortical inhibition/GABA concentration (Aim 2). Finally, we will test
whether individual differences in neural distinctiveness, in GABA, and in cortical inhibition are associated with
individual differences in behavior (Aim 3). The proposed studies offer the hope of shedding light on the
underlying causes of age-related impairments. Such an understanding is the first step in designing interventions
that could slow, or conceivably even prevent, the behavioral impairments associated with healthy aging.

## Key facts

- **NIH application ID:** 9992457
- **Project number:** 1F31AG067705-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Dalia Khammash
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $20,726
- **Award type:** 1
- **Project period:** 2020-05-01 → 2020-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9992457

## Citation

> US National Institutes of Health, RePORTER application 9992457, Exploring the role of inhibitory dysfunction in age-related cognitive impairments (1F31AG067705-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9992457. Licensed CC0.

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