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

Award Number: R01DC017480
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Enhancing Speech Processing In A Rat Model Of Autism Using Vagus Nerve Stimulation - 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 and lay the groundwork for more comprehensive future studies, with the goal of translating these critical first-in-animal preclinical experiments to a clinical therapy that could provide significant, tangible improvements in the lives of individuals with ASD.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = -$56 )
2025	2023	UNIVERSITY OF TEXAS AT DALLAS	800 WEST CAMPBELL RD.	RICHARDSON	TX	75080	DALLAS	USA	Research Related to Deafness and Communication Disorders	001	5	3/31/2025	SUPPLEMENT FOR EXPANSION	-$7
2025	2023	UNIVERSITY OF TEXAS AT DALLAS	800 WEST CAMPBELL RD.	RICHARDSON	TX	75080	DALLAS	USA	Research Related to Deafness and Communication Disorders	000	5	3/31/2025	NON-COMPETING CONTINUATION	-$49
														Subtotal = -$56

Issue Date FY: 2023 ( Subtotal = $439,713 )
2023	2023	UNIVERSITY OF TEXAS AT DALLAS	800 WEST CAMPBELL RD.	RICHARDSON	TX	75080	DALLAS	USA	Research Related to Deafness and Communication Disorders	000	5	11/18/2022	NON-COMPETING CONTINUATION	$344,250
2023	2023	UNIVERSITY OF TEXAS AT DALLAS	800 WEST CAMPBELL RD.	RICHARDSON	TX	75080	DALLAS	USA	Research Related to Deafness and Communication Disorders	001	5	1/20/2023	NON-COMPETING CONTINUATION	$38,250
2023	2023	UNIVERSITY OF TEXAS AT DALLAS	800 WEST CAMPBELL RD.	RICHARDSON	TX	75080	DALLAS	USA	Research Related to Deafness and Communication Disorders	002	5	7/19/2023	SUPPLEMENT FOR EXPANSION	$57,213
														Subtotal = $439,713

Issue Date FY: 2022 ( Subtotal = $415,787 )
2022	2022	UNIVERSITY OF TEXAS AT DALLAS	800 W CAMPBELL RD	RICHARDSON	TX	75080	DALLAS	USA	Research Related to Deafness and Communication Disorders	002	4	7/11/2022	SUPPLEMENT FOR EXPANSION	$33,287
2022	2022	UNIVERSITY OF TEXAS AT DALLAS	800 W CAMPBELL RD	RICHARDSON	TX	75080	DALLAS	USA	Research Related to Deafness and Communication Disorders	001	4	4/20/2022	NON-COMPETING CONTINUATION	$38,250
2022	2022	UNIVERSITY OF TEXAS AT DALLAS	800 W CAMPBELL RD	RICHARDSON	TX	75080	DALLAS	USA	Research Related to Deafness and Communication Disorders	000	4	11/22/2021	NON-COMPETING CONTINUATION	$344,250
														Subtotal = $415,787

Issue Date FY: 2021 ( Subtotal = $382,500 )
2021	2021	UNIVERSITY OF TEXAS AT DALLAS	800 W CAMPBELL RD	RICHARDSON	TX	75080	DALLAS	USA	Research Related to Deafness and Communication Disorders	000	3	11/30/2020	NON-COMPETING CONTINUATION	$344,250
2021	2021	UNIVERSITY OF TEXAS AT DALLAS	800 W CAMPBELL RD	RICHARDSON	TX	75080	DALLAS	USA	Research Related to Deafness and Communication Disorders	001	3	1/8/2021	NON-COMPETING CONTINUATION	$38,250
														Subtotal = $382,500

Issue Date FY: 2020 ( Subtotal = $382,500 )
2020	2020	UNIVERSITY OF TEXAS AT DALLAS	800 W CAMPBELL RD	RICHARDSON	TX	75080	DALLAS	USA	Research Related to Deafness and Communication Disorders	001	2	11/7/2019	NON-COMPETING CONTINUATION	$34,425
2020	2020	UNIVERSITY OF TEXAS AT DALLAS	800 W CAMPBELL RD	RICHARDSON	TX	75080	DALLAS	USA	Research Related to Deafness and Communication Disorders	000	2	11/4/2019	NON-COMPETING CONTINUATION	$309,825
2020	2020	UNIVERSITY OF TEXAS AT DALLAS	800 W CAMPBELL RD	RICHARDSON	TX	75080	DALLAS	USA	Research Related to Deafness and Communication Disorders	002	2	1/15/2020	NON-COMPETING CONTINUATION	$38,250
														Subtotal = $382,500

Issue Date FY: 2019 ( Subtotal = $382,500 )
2019	2019	UNIVERSITY OF TEXAS AT DALLAS	800 W CAMPBELL RD	RICHARDSON	TX	75080	DALLAS	USA	Research Related to Deafness and Communication Disorders	000	1	11/8/2018	NEW	$382,500
														Subtotal = $382,500

Grand Total All Awards = $2,002,944

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

Award Number: R01DC017480

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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