# Enhancing Speech Processing In A Rat Model Of Autism Using Vagus Nerve Stimulation

> **NIH NIH R01** · UNIVERSITY OF TEXAS DALLAS · 2022 · $382,500

## Abstract

One of the major obstacles facing individuals with autism is the inability to communicate effectively. While there
are many reasons for this inability, an important component appears to be a serious deficit in the ability to process
speech sounds effectively. Expensive, time-consuming behavioral interventions can improve behavioral
outcomes, but many individuals undergo these interventions and still experience deficits. The development of
adjunctive interventions that can increase the benefit of rehabilitation therapies is essential to improve the lives
of individuals with autism spectrum disorders (ASD). We have developed a novel technique to drive robust
neuroplasticity and enhance the benefits of rehabilitation. Vagus nerve stimulation (VNS) paired with the
presentation of a sound triggers rapid, phasic release of plasticity promoting neuromodulators, which potentiate
plasticity in the auditory network. Recent preclinical and clinical findings indicate that VNS paired with sensory
or motor rehabilitative therapies can significantly enhance functional recovery compared to rehabilitative therapy
alone. This proposal will evaluate whether VNS paired with auditory training can enhance the efficacy of
rehabilitation in the context of autism. In utero valproic acid (VPA) exposure is a well-documented cause of
autism in humans. Similar to individuals with autism, both speech discrimination ability and auditory cortical
responses are impaired in VPA exposed rats. The objective of this proposal is to determine whether VNS paired
with auditory training can reverse the neural and behavioral auditory processing deficits observed in VPA
exposed rats. In Aim 1, we test the ability of both implanted and non-invasive VNS paired with auditory training
to improve discrimination ability after prenatal VPA exposure. VPA exposed rats are significantly impaired at
discriminating between speech sounds. We will evaluate discrimination accuracy in VPA or saline exposed rats
undergoing VNS paired auditory training. In Aim 2, we evaluate awake behaving neurophysiological responses
in auditory cortex to evaluate the VNS-dependent neural plasticity that may underlie improved auditory
processing. VPA exposed rats exhibit altered auditory cortex responses compared to control rats. Previous
results suggest that VNS pairing may strengthen auditory cortex responses more rapidly and to a greater degree
than training alone. In Aim 3, we test the role of two neuromodulatory networks in the VNS-dependent
enhancement of plasticity and sound discrimination ability in the context of VPA exposure. We will deplete
cholinergic or noradrenergic afferents specifically to the auditory cortex to determine whether acetylcholine or
norepinephrine depletion impairs VNS-related improvements in auditory processing. In addition to proof-of-
concept evidence for clinical translation, this proposal will provide insight into the ability of plasticity-based
therapies to be effective in treating ASD a...

## Key facts

- **NIH application ID:** 10310404
- **Project number:** 5R01DC017480-04
- **Recipient organization:** UNIVERSITY OF TEXAS DALLAS
- **Principal Investigator:** Crystal T Engineer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $382,500
- **Award type:** 5
- **Project period:** 2018-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10310404

## Citation

> US National Institutes of Health, RePORTER application 10310404, Enhancing Speech Processing In A Rat Model Of Autism Using Vagus Nerve Stimulation (5R01DC017480-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10310404. Licensed CC0.

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