Animal Model of Speech Sound Processing in Autism

自闭症言语声音处理的动物模型

• 批准号: 8020907
• 负责人: MICHAEL P KILGARD
• 金额: $ 28.32万
• 依托单位: UNIVERSITY OF TEXAS DALLAS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8020907
• 关键词: Acoustics; Adult; Affect; Animal Model; Animals; Auditory; Auditory area; Auditory system; Autistic Disorder; Behavioral; Cells; Child; Code; Cognitive; Communication; Communication impairment; Control Animal; Cues; Development; Discrimination; Engineering; Environment; Exhibits; Functional Imaging; Heterogeneity; Housing; Human; Image; Imaging Techniques; Impairment; Individual; Inferior Colliculus; Laboratories; Language; Life; Modeling; Neurons; Outcome; Patients; Pattern; Physiology; Population; Process; Rattus; Reporting; Resolution; Sensory; Severities; Social Interaction; Speech; Speech Sound; Techniques; Training; United States; Valproic Acid; Work; base; design; environmental enrichment for laboratory animals; imaging modality; improved; in utero; insight; millisecond; neuromechanism; prenatal exposure; public health relevance; relating to nervous system; response; spatiotemporal

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.

描述（由申请人提供）：在美国，每150人中就有一人患有自闭症。自闭症患者在处理日常交流和社会交往中使用的微妙线索的能力严重受损。最近的功能成像研究显示，自闭症儿童和成人的语音辨别能力严重不足。言语诱发神经反应的潜伏期延长与认知和语言障碍的程度密切相关。不幸的是，人类成像技术的低分辨率掩盖了损伤的神经基础。 我们建议在丙戊酸（VPA）自闭症动物模型中评估语音编码，并量化两种常见自闭症治疗方法的有益效果：听觉训练和环境丰富。语音在正常大鼠中枢听觉系统中引起特定的细胞放电的时空模式。该项目的第一个目的是确定VPA暴露对语音的丘和皮层表征的后果。我们的初步结果表明，在子宫VPA暴露严重降低了精确的时空模式诱发的语音在听觉皮层。与自闭症一样，在我们的动物模型中，语音的潜伏期明显大于音调。 该项目的第二个目的是确定VPA暴露对言语声音辨别的行为后果。如果言语声音的神经时空表征退化，则在VPA处理的大鼠中可能无法区分某些言语声音。因此，我们预测VPA暴露大鼠的语音辨别力将受损。第三个目的是确定言语训练和环境丰富对VPA暴露大鼠言语诱发活动的影响。基于以前的研究，我们预测，语音训练和环境丰富将减轻语音的皮层反应的退化，恢复语音声音的歧视，在VPA治疗大鼠的控制水平。拟议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，以治疗自闭症的沟通障碍，部分原因是语音识别能力下降。 公共卫生关系：虽然自闭症患者有明显的沟通问题，但对造成沟通障碍的神经机制知之甚少。拟议的自闭症动物模型将确定语音辨别障碍的潜在原因，并量化两种常见自闭症疗法的有益效果：听觉训练和环境丰富。更好地理解这些机制可能有助于设计改进的行为和感觉疗法，以减少自闭症的沟通障碍。