Speech paired vagus nerve stimulation restores neural sound processing in a rat model of autism

IntroductionPrenatal exposure to valproic acid (VPA) is a common environmental cause of autism spectrum disorder (ASD) and often leads to expressive and receptive language impairments. Similar communication difficulties among individuals with ASD are often linked to abnormal subcortical and cortical...

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Main Authors: Brendan M. Williams, Yuko Tamaoki, Tanya T. Danaphongse, Isabella K. Myers, Samantha L. Kroon, Maria P. Solano, Allan A. Jacob, Jonathan R. Riley, Min Chen, Seth A. Hays, Crystal T. Engineer
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnins.2025.1600024/full
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author Brendan M. Williams
Brendan M. Williams
Yuko Tamaoki
Yuko Tamaoki
Tanya T. Danaphongse
Isabella K. Myers
Isabella K. Myers
Samantha L. Kroon
Maria P. Solano
Allan A. Jacob
Jonathan R. Riley
Min Chen
Seth A. Hays
Seth A. Hays
Crystal T. Engineer
Crystal T. Engineer
author_facet Brendan M. Williams
Brendan M. Williams
Yuko Tamaoki
Yuko Tamaoki
Tanya T. Danaphongse
Isabella K. Myers
Isabella K. Myers
Samantha L. Kroon
Maria P. Solano
Allan A. Jacob
Jonathan R. Riley
Min Chen
Seth A. Hays
Seth A. Hays
Crystal T. Engineer
Crystal T. Engineer
author_sort Brendan M. Williams
collection DOAJ
description IntroductionPrenatal exposure to valproic acid (VPA) is a common environmental cause of autism spectrum disorder (ASD) and often leads to expressive and receptive language impairments. Similar communication difficulties among individuals with ASD are often linked to abnormal subcortical and cortical sound processing. Rodents prenatally exposed to VPA exhibit degraded cortical responses to speech and an impaired ability to behaviorally discriminate speech sounds.MethodsWe sought to determine whether sound processing could be restored with paired vagus nerve stimulation (VNS). In a first experiment, we evaluated whether sound-paired VNS would alter in vivo extracellular multi-unit responses to tones, noise burst trains, and speech sounds from the anterior auditory field. We next sought to evaluate whether improvements to neural sound processing led to improvements in sound discrimination ability. In a second experiment, rats underwent go/no-go sound discrimination testing where VNS was paired with successful trials.ResultsWe found that VPA-exposed rats had degraded spectral, temporal, and speech sound processing compared to saline-exposed control rats. VPA-exposed rats which received sound-paired VNS exhibited a partial or full restoration of processing across sound types. However, across several sound discrimination tasks, we did not observe changes in behavioral performance in response to prenatal exposure to VPA or VNS.DiscussionOur study is the first to show that speech-paired VNS leads to a generalized improvement in cortical sound processing across sound types, rescuing neural processing among VPA-exposed rats. These results provide a framework for future studies to develop VNS-based interventions for communication disorders.
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spelling doaj-art-069f5b80a4f8450d95ebc465d7c19bd02025-08-20T03:25:49ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-06-011910.3389/fnins.2025.16000241600024Speech paired vagus nerve stimulation restores neural sound processing in a rat model of autismBrendan M. Williams0Brendan M. Williams1Yuko Tamaoki2Yuko Tamaoki3Tanya T. Danaphongse4Isabella K. Myers5Isabella K. Myers6Samantha L. Kroon7Maria P. Solano8Allan A. Jacob9Jonathan R. Riley10Min Chen11Seth A. Hays12Seth A. Hays13Crystal T. Engineer14Crystal T. Engineer15Department of Neuroscience, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, TX, United StatesTexas Biomedical Device Center, The University of Texas at Dallas, Richardson, TX, United StatesDepartment of Neuroscience, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, TX, United StatesTexas Biomedical Device Center, The University of Texas at Dallas, Richardson, TX, United StatesTexas Biomedical Device Center, The University of Texas at Dallas, Richardson, TX, United StatesDepartment of Neuroscience, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, TX, United StatesTexas Biomedical Device Center, The University of Texas at Dallas, Richardson, TX, United StatesTexas Biomedical Device Center, The University of Texas at Dallas, Richardson, TX, United StatesDepartment of Neuroscience, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, TX, United StatesDepartment of Neuroscience, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, TX, United StatesTexas Biomedical Device Center, The University of Texas at Dallas, Richardson, TX, United StatesDepartment of Mathematical Sciences, University of Texas at Dallas, Richardson, TX, United StatesTexas Biomedical Device Center, The University of Texas at Dallas, Richardson, TX, United StatesDepartment of Bioengineering, Erik Jonsson School of Engineering and Computer Science, University of Texas at Dallas, Richardson, TX, United StatesDepartment of Neuroscience, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, TX, United StatesTexas Biomedical Device Center, The University of Texas at Dallas, Richardson, TX, United StatesIntroductionPrenatal exposure to valproic acid (VPA) is a common environmental cause of autism spectrum disorder (ASD) and often leads to expressive and receptive language impairments. Similar communication difficulties among individuals with ASD are often linked to abnormal subcortical and cortical sound processing. Rodents prenatally exposed to VPA exhibit degraded cortical responses to speech and an impaired ability to behaviorally discriminate speech sounds.MethodsWe sought to determine whether sound processing could be restored with paired vagus nerve stimulation (VNS). In a first experiment, we evaluated whether sound-paired VNS would alter in vivo extracellular multi-unit responses to tones, noise burst trains, and speech sounds from the anterior auditory field. We next sought to evaluate whether improvements to neural sound processing led to improvements in sound discrimination ability. In a second experiment, rats underwent go/no-go sound discrimination testing where VNS was paired with successful trials.ResultsWe found that VPA-exposed rats had degraded spectral, temporal, and speech sound processing compared to saline-exposed control rats. VPA-exposed rats which received sound-paired VNS exhibited a partial or full restoration of processing across sound types. However, across several sound discrimination tasks, we did not observe changes in behavioral performance in response to prenatal exposure to VPA or VNS.DiscussionOur study is the first to show that speech-paired VNS leads to a generalized improvement in cortical sound processing across sound types, rescuing neural processing among VPA-exposed rats. These results provide a framework for future studies to develop VNS-based interventions for communication disorders.https://www.frontiersin.org/articles/10.3389/fnins.2025.1600024/fullvalproic acidvagus nerve stimulationspeechanterior auditory fieldautism spectrum disorderpreclinical research
spellingShingle Brendan M. Williams
Brendan M. Williams
Yuko Tamaoki
Yuko Tamaoki
Tanya T. Danaphongse
Isabella K. Myers
Isabella K. Myers
Samantha L. Kroon
Maria P. Solano
Allan A. Jacob
Jonathan R. Riley
Min Chen
Seth A. Hays
Seth A. Hays
Crystal T. Engineer
Crystal T. Engineer
Speech paired vagus nerve stimulation restores neural sound processing in a rat model of autism
Frontiers in Neuroscience
valproic acid
vagus nerve stimulation
speech
anterior auditory field
autism spectrum disorder
preclinical research
title Speech paired vagus nerve stimulation restores neural sound processing in a rat model of autism
title_full Speech paired vagus nerve stimulation restores neural sound processing in a rat model of autism
title_fullStr Speech paired vagus nerve stimulation restores neural sound processing in a rat model of autism
title_full_unstemmed Speech paired vagus nerve stimulation restores neural sound processing in a rat model of autism
title_short Speech paired vagus nerve stimulation restores neural sound processing in a rat model of autism
title_sort speech paired vagus nerve stimulation restores neural sound processing in a rat model of autism
topic valproic acid
vagus nerve stimulation
speech
anterior auditory field
autism spectrum disorder
preclinical research
url https://www.frontiersin.org/articles/10.3389/fnins.2025.1600024/full
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