The Microstructural Basis of Abnormal Connectivity in Autism

自闭症异常连接的微观结构基础

• 批准号: 7795043
• 负责人: JANET Elizabeth LAINHART
• 金额: $ 33.64万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7795043
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DESCRIPTION (provided by applicant): Autism spectrum disorders are now among the most prevalent medical conditions of childhood. Only a small fraction of the 486,000 individuals under 20 years of age with an autism-spectrum disorder (ASD) in the U.S are young enough to benefit from intensive early intervention. Overall prognosis for the older children with autism is not good. Despite improvements in treatment and education over the past 30 years, adult outcome even for non-mentally retarded individuals with autism has not significantly improved. The majority continue to need high levels of parental and community support throughout their lives. One reason for this huge public health problem is that the brain-basis of fundamental deficits in older children and adults with autism is not well understood. We propose collaboration between a longitudinal neuroimaging, clinical, and neuropsychological study of late neurodevelopment in autism and the National Alliance for Medical Imaging Computing (NA- MIC), one of the NIH Roadmap National Centers for Biomedical Computing. The collaboration will bring state-of-the-art brain imaging analysis tools developed by NA-MIC into autism clinical research and form a new highly interactive multidisciplinary research team. Working together, the computer scientists and clinical researchers will use critical biological questions in autism to "drive" the development of NA-MIC "tools". The critical biological questions are 1) what is the microstructural basis of abnormal brain connectivity during late neurodevelopment in autism, and 2) how is brain microstructure related to deficits, developmental trajectory, and outcome. We will use Time 1 and Time 2 high-resolution MRI and diffusion tensor imaging data that have already been collected on a single 3Tesla scanner on a cohort of 100 males with high-functioning autism and 72 typically developing males. Time 3 and 4 data are being collected over the next 5 years (MH080826). We will use novel, non-tractography-based, diffusion tensor image analysis methods developed by NA-MIC to compare, at the level of both individuals and groups, microstructural features along entire white matter tracts in language, social, and repetitive behavior neural networks. We will integrate the white matter analysis with structural image analysis of cortical and subcortical gray matter. We will determine how microstructural white matter features, gray matter morphometric features, and clinical deficits are related to each other and change over time in autism. Autism is now one of the most prevalent medical disorders of childhood. Adult outcome for even high-functioning older children and adolescents with autism is still usually poor, with a high need for lifelong clinical and community support. Understanding the brain- basis of deficits, disease course, and outcome in these individuals is critical for development of autism-specific treatments as well as secondary and tertiary preventive interventions.

描述（由申请人提供）：自闭症谱系障碍现在是儿童时期最普遍的疾病之一。在美国，486,000 名 20 岁以下患有自闭症谱系障碍 (ASD) 的人中，只有一小部分足够年轻，可以从强化早期干预中受益。年龄较大的自闭症儿童的总体预后并不好。尽管过去 30 年治疗和教育有所改善，但即使是非智障自闭症患者的成年结局也没有显着改善。大多数人一生都需要父母和社区的高水平支持。造成这一巨大公共卫生问题的原因之一是，对于年龄较大的自闭症儿童和成人的基本缺陷的大脑基础尚不清楚。我们建议对自闭症晚期神经发育的纵向神经影像、临床和神经心理学研究与国家医学影像计算联盟 (NA-MIC) 进行合作，该联盟是 NIH 路线图国家生物医学计算中心之一。此次合作将把 NA-MIC 开发的最先进的脑成像分析工具引入自闭症临床研究中，并组建一个新的高度互动的多学科研究团队。计算机科学家和临床研究人员将共同利用自闭症的关键生物学问题来“推动”NA-MIC“工具”的开发。关键的生物学问题是：1）自闭症晚期神经发育过程中大脑连接异常的微观结构基础是什么，2）大脑微观结构如何与缺陷、发育轨迹和结果相关。我们将使用时间 1 和时间 2 高分辨率 MRI 和扩散张量成像数据，这些数据已经在一台 3Tesla 扫描仪上收集到，对 100 名高功能自闭症男性和 72 名正常发育男性进行了研究。未来 5 年将收集时间 3 和时间 4 的数据 (MH080826)。我们将使用 NA-MIC 开发的新型非纤维束成像扩散张量图像分析方法，在个体和群体水平上比较语言、社交和重复行为神经网络中整个白质纤维束的微观结构特征。我们将把白质分析与皮质和皮质下灰质的结构图像分析结合起来。我们将确定自闭症患者的白质微观结构特征、灰质形态特征和临床缺陷如何相互关联以及如何随时间变化。自闭症现在是儿童时期最普遍的疾病之一。即使是高功能的年龄较大的自闭症儿童和青少年的成人结局通常仍然很差，非常需要终生的临床和社区支持。了解这些个体的缺陷、病程和结果的大脑基础对于开发自闭症特异性治疗以及二级和三级预防干预措施至关重要。