Table 3_Speech paired vagus nerve stimulation restores neural sound processing in a rat model of autism.xlsx

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.

引言
产前暴露于丙戊酸（valproic acid, VPA）是引发自闭症谱系障碍（autism spectrum disorder, ASD）的常见环境因素，常导致个体出现表达性与接受性语言障碍。自闭症谱系障碍患者的类似交流困难，往往与皮层下及皮层听觉加工异常相关。产前暴露于VPA的啮齿类动物，其皮层对语音的反应会出现受损，且行为层面辨别语音的能力也会出现障碍。

方法
本研究旨在探究配对式迷走神经刺激（vagus nerve stimulation, VNS）是否能够修复听觉加工功能。第一项实验中，我们评估了配对声音的VNS是否会改变听觉前区对纯音、噪声爆发序列以及语音的在体胞外多单元反应。后续实验则旨在验证，神经听觉加工的改善是否能带来听觉辨别能力的提升。第二项实验中，我们让大鼠接受Go/NoGo听觉辨别任务测试，在该任务中，VNS会与正确试次进行配对。

结果
我们发现，与暴露于生理盐水的对照组大鼠相比，暴露于VPA的大鼠其频谱、时域以及语音听觉加工均出现受损。接受配对声音VNS的VPA暴露大鼠，其对各类声音的加工能力得到了部分或完全恢复。然而，在多项听觉辨别任务中，我们并未观察到产前VPA暴露或VNS干预会对大鼠的行为表现产生影响。

讨论
本研究首次证实，配对语音的VNS能够对各类声音的皮层听觉加工产生普遍性改善，挽救了VPA暴露大鼠的神经加工功能。上述研究结果为未来开发基于VNS的语言交流障碍干预手段提供了理论框架。