Speech Paired Vagus Nerve Stimulation Restores Neural Sound Processing in A Rat Model of Autism

Brendan M Williams^1,2*Yuko Tamaoki^1,2Tanya T Danaphongse²Isabella K Myers^1,2Samantha L Kroon¹Maria P Solano¹Allan A Jacob¹Jonathan Riley²Min Chen³Seth Hays^2,4Crystal T Engineer^1,2*

• ¹Department of Neuroscience, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, United States
• ²The University of Texas at Dallas, Texas Biomedical Device Center, Richardson, Texas, United States
• ³Department of Mathematical Sciences, School of Natural Sciences and Mathematics, University of Texas at Dallas, Richardson, Texas, United States
• ⁴Department of Bioengineering, Erik Jonsson School of Engineering and Computer Science, The University of Texas at Dallas, Richardson, Texas, United States

Prenatal 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. We 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 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. 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. Across several sound discrimination tasks, we did not observe changes in behavioral performance in response to prenatal exposure to VPA or VNS. Our 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.