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: 7558360
• 负责人: JANET Elizabeth LAINHART
• 金额: $ 34.9万
• 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/7558360
• 关键词: 20 year old; Adolescent; Adult; Age; Area; Arts; Autistic Disorder; Base of the Brain; Behavior; Behavioral; Biological; Biological Neural Networks; Biomedical Computing; Brain; Brain imaging; Characteristics; Child; Childhood; Clinical; Clinical Research; Clinical Trials; Cognitive; Collaborations; Communities; Comorbidity; Computers; Control Groups; Data; Data Set; Databases; Development; Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Early treatment; Education; Evaluation; Genes; Goals; Heterogeneity; Image; Image Analysis; Impairment; Individual; Interdisciplinary Study; Intervention; Knowledge; Language; Length; Life; Location; Magnetic Resonance Imaging; Measures; Medical; Medical Imaging; Mentally Disabled Persons; Methods; Outcome; Persons; Phenotype; Preventive Intervention; Public Health; Research; Research Personnel; Resolution; Resources; Scientist; Severities; Stereotyping; Testing; Thick; Time; United States National Institutes of Health; Universities; Utah; Variant; Work; age related; autism spectrum disorder; base; clinical phenotype; cohort; gray matter; improved; interest; male; morphometry; neurobiological mechanism; neurodevelopment; neuroimaging; neuropathology; neuropsychological; novel; outcome forecast; research clinical testing; social; technology development; time use; tool; white matter

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期最普遍的医疗状况之一。在美国20岁以下的486,000名患有自闭症疾病（ASD）的486,000名患者中，只有一小部分年轻，可以从强化的早期干预中受益。自闭症儿童的总体预后不好。尽管在过去30年中的治疗和教育方面有所改善，但成年结果即使对于非心理智障的人，自闭症患者也没有显着改善。大多数人一生都需要高水平的父母和社区支持。造成这个巨大公共卫生问题的原因之一是，自闭症儿童和成年人的基本缺陷的脑基础尚不清楚。我们建议对自闭症后期神经发育的纵向神经影像学，临床和神经心理学研究与国家医学成像计算联盟（NA-MIC）之间的合作，NIH路线图国家生物医学计算中心之一。该协作将使NA-MIC开发的最先进的大脑成像分析工具进入自闭症临床研究，并组成一个新的高度互动性的多学科研究团队。计算机科学家和临床研究人员共同努力，将使用自闭症中的关键生物学问题来“驱动“ 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期间异常大脑连通性的微观结构基础，以及2）脑微观结构与缺陷，发育轨迹和结果如何相关。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，这些数据已经在单个3tesla扫描仪上收集到的100名男性，具有高功能的自闭症和72个通常发育中的男性。在未来5年内将收集时间3和4数据（MH080826）。我们将使用NA-MIC开发的新型，非缩写的扩散张量图分析方法，以在个人和群体的水平上，在语言，社交和重复性行为神经网络中沿整个白质界面进行微结构特征。我们将将白质分析与皮质和皮质下灰质的结构图像分析相结合。我们将确定微观结构的白质特征，灰质形态计量学特征和临床缺陷如何相互关联，并且在自闭症中随着时间的流逝而变化。自闭症现在是童年最普遍的医学障碍之一。即使是自闭症患有自闭症的年龄较大的儿童和青少年，成人的结果通常仍然很差，对终身临床和社区支持的需求很高。了解这些人的缺陷，疾病病程和结局的大脑基础对于自闭症特异性治疗以及二级预防干预措施的发展至关重要。