Coherence and Temporal Dynamics in Auditory Cortex of Children with Autism

描述（由申请人提供）：语言和沟通缺陷，尽管有异质表型，但从定义上讲，在某种程度上影响着接近自闭症的个体，这可能是自闭症最具破坏性的特征。我们假设自闭症的语言障碍是由早期的听觉皮质处理异常和早期听觉皮质与语言区域之间的连接减少所驱动的。事实上，现在有几个小组在初级听觉皮层中显示出听觉信息处理的异常，最近的研究也指出自闭症皮层中功能连接的减少。自闭症研究的另一个挑战是建立功能反应参数与解剖学和行为/临床测量之间的联系。因此，拟议项目的目标是(a)表征自闭症的听觉处理缺陷，重点是早期听觉皮层和语言区域的局部时间动态；(b)研究处理听觉信息的大脑区域之间的活动一致性，无论是在大脑半球内部还是在大脑半球之间，作为功能连通性的衡量标准；(c)调查功能性听觉处理障碍的程度与临床确定的语言技能以及自闭症的严重程度之间的相关性；(d)将功能性脑磁图数据与多模态解剖MRI数据共同注册，以便将组织和功能异常联系起来。这样的整合水平对于建立早期诊断的定量生物标志物，以及促进设计专门的、有针对性的治疗干预措施是必要的。为了实现这些目标，7至10岁的健康和自闭症儿童的听觉处理动态将使用MEG记录，并映射到解剖MRI数据上。预期的结果是：(1)两种人群听觉皮质区域反应的时间动态特征；(2)调查自闭症与解剖学相关的功能连接减少的假设；(3)通过功能和解剖成像测量之间的相关性，确定皮层水平的损伤是否确实是自闭症特征的语言和沟通缺陷的临床观察的起源。以及行为衍生的神经认知特征。公共卫生相关性：自闭症是一种复杂和破坏性的疾病，通过三种行为来诊断，目前在175名儿童中约有1人患自闭症。除了影响患有自闭症的个人之外，自闭症还影响到个人的家庭，也影响到学校和社区，因为在公立学校系统中教育自闭症儿童的费用估计在每年5万到8万美元之间，大约是教育健康儿童费用的5倍。该项目旨在整合自闭症的神经基质的功能和神经解剖学研究，以更好地理解导致自闭症的大脑功能障碍，这反过来可能有助于开发更有效的治疗方法，也许是允许生物学方法，而不是行为方法，从而更早地诊断。

DESCRIPTION (provided by applicant): The language and communication deficits that, in spite of the heterogeneous phenotype, by definition affect nearly autistic individuals to some degree, are perhaps the most devastating features of autism. We hypothesize that language impairments in autism are driven by early stage auditory cortical processing abnormalities and reduced connectivity between early auditory cortex and language areas. Indeed, several groups now show abnormal processing of auditory information in primary auditory cortex, and recent studies also point toward reduced functional connectivity in the autistic cortex. Another challenge of autism research is to establish links between functional response parameters, and anatomical and behavioral/clinical measures. The objectives of the proposed project are therefore (a) to characterize auditory processing deficits in autism, with an emphasis on local temporal dynamics in early auditory cortex and in language areas; (b) to study coherence of activity across brain regions that process auditory information, both within and across hemispheres, as a measure of functional connectivity; (c) to investigate the correlations between the extent of functional auditory processing impairments, and clinically determined language skills, as well as severity of the autism; (d) to coregister functional MEG data with multimodal anatomical MRI data in order to correlate tissue and functional abnormalities. Such levels of integration are necessary to establish quantitative biomarkers for early diagnosis, and to facilitate the design of specialized, well- targeted therapeutic interventions. To achieve these goals, auditory processing dynamics in healthy and autistic children ages 7 to 10 will be recorded using MEG, and mapped onto anatomical MRI data. Expected outcomes are (1) characterization of temporal dynamics of responses in auditory cortical areas in both populations (2) investigation of the hypothesis claiming reduced functional connectivity in autism with anatomical correlates, and (3) establishing whether cortical level impairments indeed lie at the origin of clinical observations of language and communication deficits that characterize autism, through correlations between functional and anatomical imaging measures, and behaviorally derived neurocognitive profiles. PUBLIC HEALTH RELEVANCE: Autism is a complex and devastating disorder which is diagnosed through a triad of behaviors and currently has full spectrum prevalence of about 1 in 175 children. In addition to affecting the individuals afflicted with the disorder, autism also affects not only the individual's family, but also the schools and communities, as the estimated cost of educating a child with autism in the public school system ranges from $50,000 to $80,000 per year, approximately 5 times the cost of educating a healthy child. This project aims to integrate functional and neuroanatomical studies of the neural substrates of autism, to better our understanding of the brain dysfunctions that cause autism, which in turn could contribute to the development of more effective treatments and, perhaps, approaches to allow for biological, rather than behavioral, and thus earlier, diagnosis.