The Microstructural Basis of Abnormal Connectivity in Autism

描述(由申请人提供)：自闭症谱系障碍现在是最普遍的儿童疾病之一。在美国486,000名20岁以下的自闭症谱系障碍(ASD)患者中，只有一小部分人足够年轻，可以从强化的早期干预中受益。自闭症年龄较大的儿童总体预后不佳。尽管过去30年在治疗和教育方面有所改进，但即使是患有自闭症的非智力障碍患者的成人结果也没有显著改善。大多数人在他们的一生中仍然需要父母和社区的高度支持。造成这一巨大公共卫生问题的一个原因是，自闭症患者年龄较大的儿童和成人的基本缺陷的大脑基础还没有得到很好的理解。我们建议对自闭症晚期神经发育的纵向神经成像、临床和神经心理学研究与国家医学成像计算联盟(NA-MIC)合作，NA-MIC是NIH路线图国家生物医学计算中心之一。这项合作将把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，并形成一个新的高度互动的多学科研究团队。通过合作，计算机科学家和临床研究人员将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脑连接异常的微结构基础是什么，以及2)脑微结构与缺陷、发育轨迹和结果是如何联系的。我们将使用Time 1和Time 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，对象是100名高功能自闭症男性和72名典型发育中的男性。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开发的新的、非基于脑束成像的扩散张量图像分析方法，在个人和群体的水平上比较语言、社会和重复行为神经网络中整个白质束的微结构特征。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脑白质微结构特征、灰质形态计量学特征和临床缺陷是如何相互联系和随时间变化的。自闭症现在是儿童时期最普遍的疾病之一。即使是患有自闭症的高功能大龄儿童和青少年的成人结局通常也很差，非常需要终身的临床和社区支持。了解这些人的缺陷、病程和结果的大脑基础对于开发针对自闭症的治疗以及二级和三级预防干预措施至关重要。

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.