Animal Model of Speech Sound Processing in Autism

描述（由申请人提供）：在美国，每150人中就有1人患有自闭症。自闭症患者在处理日常交流和社会互动中使用的微妙线索的能力上严重受损。最近的功能成像研究揭示了自闭症儿童和成人在语音识别方面的严重缺陷。言语诱发神经反应的潜伏期增加与认知和语言障碍程度密切相关。不幸的是，人类成像技术的低分辨率模糊了损伤的神经基础。我们建议在丙戊酸（VPA）自闭症动物模型中评估语音编码，并量化两种常见的自闭症治疗方法：听觉训练和环境富集的有益效果。语音唤起了正常大鼠中枢听觉系统中特定的细胞放电时空模式。该项目的第一个目的是确定VPA暴露对语音的丘状和皮层表征的影响。我们的初步结果表明，子宫内VPA暴露严重降低了听觉皮层中语音诱发的精确时空模式。就像自闭症一样，在我们的动物模型中，语音的潜伏期比音调的潜伏期要长得多。该项目的第二个目的是确定VPA暴露对语音歧视的行为后果。如果语音的神经时空表征退化，那么VPA治疗的大鼠可能无法区分某些语音。因此，我们预测VPA暴露大鼠的语音辨别能力将受损。第三个目的是确定言语训练和环境富集对VPA暴露大鼠言语诱发活动的影响。在前人研究的基础上，我们预测语音训练和环境丰富都能缓解VPA治疗大鼠皮层对语音反应的退化，并使语音识别恢复到控制水平。所提出的研究结果将增加我们对与语音编码相关的神经机制的理解。从这些研究中获得的见解可能会影响新的行为和感觉技术的发展，以治疗自闭症中的交流障碍，这些障碍部分是由于语音辨别能力下降造成的。

DESCRIPTION (provided by applicant): One out of every 150 people in the United States is affected by autism. Autistic individuals are severely impaired in their ability to process the subtle cues used in everyday communication and social interactions. Recent functional imaging studies have revealed serious deficits in speech sound discrimination in both children and adults with autism. The latency increase of speech evoked neural responses is well correlated with the degree of cognitive and language impairments. Unfortunately, the poor resolution of human imaging techniques obscures the neural basis of the impairment. We propose to evaluate speech sound coding in the valproic acid (VPA) animal model of autism, and quantify the beneficial effects of two common autism therapies: auditory training and environmental enrichment. Speech sounds evoke specific spatiotemporal patterns of cell firing in the central auditory system of normal rats. The first aim of the project is to determine the consequence of VPA exposure on the collicular and cortical representations of speech sounds. Our preliminary results indicate that in utero VPA exposure severely degrades the precise spatiotemporal patterns evoked by speech sounds in auditory cortex. As in autism, the longer latency in our animal model is significantly greater for speech sounds compared to tones. The second aim of the project is to determine the behavioral consequences of VPA exposure on speech sound discrimination. If the neural spatiotemporal representations of speech sounds are degraded, then it is possible that certain speech sounds may not be distinguishable in VPA treated rats. We therefore predict that speech sound discrimination will be impaired in VPA exposed rats. The third aim is to determine the effects of speech training and environmental enrichment on speech evoked activity in VPA exposed rats. Based on previous studies, we predict that both speech training and environmental enrichment will relieve the degradation of the cortical responses to speech sounds and restore speech sound discrimination to control levels in VPA treated rats. The results of the proposed studies will add to our understanding of the neural mechanisms that are associated with speech sound coding. Insights derived from these studies may influence the development of new behavioral and sensory techniques to treat the communication impairments in autism that result in part from degraded speech sound discrimination. PUBLIC HEALTH RELEVANCE: Although individuals with autism are known to have significant communication problems, the neural mechanisms responsible for impaired communication are poorly understood. The proposed animal model for autism will identify a potential cause of speech sound discrimination impairments and quantify the beneficial effects of two common autism therapies: auditory training and environmental enrichment. A better understanding of these mechanisms may aid the design of improved behavioral and sensory therapies to reduce communication impairments in autism.