Coherence and Temporal Dynamics in Auditory Cortex of Children with Autism

自闭症儿童听觉皮层的连贯性和时间动态

• 批准号: 7631322
• 负责人: Tal Kenet
• 金额: $ 8.83万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-04 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7631322
• 关键词: 10 year old; Address; Affect; Age; Area; Auditory; Auditory area; Autistic Disorder; Behavior; Behavioral; Biological; Biological Markers; Brain; Brain region; Child; Choline; Clinical; Collaborations; Communication; Communication impairment; Communities; Complement; Complex; Corpus Callosum; Creatine; Data; Data Sources; Development; Diagnosis; Disease; Distant; Early Diagnosis; Electroencephalography; Environment; Family; Fascicle; Fiber; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Homologous Gene; Image; Impairment; Individual; Investigation; Language; Life; Link; Literature; MRI Scans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Maps; Measures; Motivation; Neuroanatomy; Neurobiology; Neurocognitive; Neurons; Outcome; Participant; Pathway interactions; Phenotype; Population; Prevalence; Process; Recruitment Activity; Research; Resource Sharing; Schools; Sensory Process; Severities; Source; Staging; System; Testing; Therapeutic Intervention; Time; Tissues; Triad Acrylic Resin; Work; autistic children; base; bioimaging; boys; capsule; cognitive function; cost; design; effective therapy; experience; interest; public health relevance; relating to nervous system; response; skills; stem; white matter; white matter change

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.

描述（由申请人提供）：语言和沟通缺陷，尽管异质性表型，根据定义，在某种程度上影响近自闭症个体，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听觉皮层处理异常和早期听觉皮层与语言区之间连接减少所驱动的。事实上，现在有几组人在初级听觉皮层中表现出异常的听觉信息处理，最近的研究也指出自闭症皮层的功能连接减少。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）确定孤独症听觉处理缺陷的特征，重点是早期听觉皮层和语言区的局部时间动态;（B）研究处理听觉信息的大脑区域活动的连贯性，包括半球内部和半球之间的活动，作为功能连接的衡量标准;（c）研究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严重程度之间的相关性;（d）将功能性MEG数据与多模态解剖MRI数据配准，以关联组织和功能异常。这种整合水平对于建立用于早期诊断的定量生物标志物以及促进专门的、靶向良好的治疗干预的设计是必要的。为了实现这些目标，将使用MEG记录7至10岁健康和自闭症儿童的听觉处理动态，并映射到解剖MRI数据上。预期的结果是（1）表征两个人群中听觉皮层区域反应的时间动态（2）调查声称自闭症功能连接减少的假设与解剖学相关性，以及（3）确定皮层水平损伤是否确实是自闭症特征语言和沟通缺陷临床观察的起源，通过功能和解剖成像测量之间的相关性，以及行为衍生的神经认知概况。公共卫生相关性：孤独症是一种复杂的和毁灭性的疾病，通过三重行为诊断，目前全谱患病率约为1/175儿童。除了影响患有自闭症的个人之外，自闭症还不仅影响个人的家庭，而且影响学校和社区，因为在公立学校系统中教育自闭症儿童的估计费用每年在50 000美元至80 000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神经基质的功能和神经解剖学研究，以更好地了解导致自闭症的大脑功能障碍，这反过来又有助于开发更有效的治疗方法，也许，允许生物学方法，而不是行为，从而更早地诊断。