Atypical Late Neurodevelopment in Autism: A Longitudinal MRI and DTI Study

描述（由申请人提供）：除了努力描述自闭症的早期迹象外，继续努力了解自闭症的大脑基础，它如何随时间变化，以及它如何与儿童和成人疾病变化的表现相关，这一点至关重要。已经患病的自闭症患者数量庞大，而且还在不断增长。很明显，这些个体的自闭症是一种动态障碍，而且相当大比例的受影响个体随着年龄的增长而恶化而不是改善。损伤不随时间恶化的人生活在稳定但严重的终身残疾中。本研究的目的是了解自闭症儿童到成年的纵向脑机制，以及大脑动态变化与临床表型变化之间的关系。这项研究将为开发新的治疗方法和二级和三级预防干预措施提供重要的新信息。该项目的具体目标是收集时间3和时间4的纵向结构和弥散张量神经成像3 Telsa以及临床和神经心理学数据，这些数据来自一大群患有自闭症的儿童和成人以及典型发展个体。时间1和时间2数据的收集是由美国国立卫生研究院自闭症卓越合作项目资助的。这是一项对100名自闭症男性和72名正常对照者的病例对照纵向研究。队列中的受试者平均分为4个年龄组。时间1时，他们的年龄分别为3- 6,7 - 11,12 -17和18-35岁。时间2时，他们大了2岁。在第3次和第4次，他们会大4岁和6岁。3在时间1和时间2收集了Telsa结构和扩散张量成像数据，并将在时间1和时间2使用的同一台扫描仪上在时间3和时间4收集数据。确定了3个主要和次要特征值和特征向量，并计算了分数各向异性、平均扩散率、轴向和径向扩散率，用于定量评估白质完整性。对结构和扩散张量成像数据进行感兴趣区域和基于全脑体素的分析，以及神经束成像。收集了所有受试者的详细临床和神经心理学数据，并研究了动态脑-行为关系。该项目是犹他大学、威斯康星大学和杨百翰大学之间的合作成果，犹他大学对所有受试者进行确定、评估和扫描，威斯康星大学对所有扩散张量成像数据进行处理和分析，杨百翰大学对所有结构数据进行处理和分析。自2002年以来，这个协作小组一直在有效和富有成效地共同开展这项纵向研究。

DESCRIPTION (provided by applicant): In addition to efforts to describe the earliest signs of autism, it is critical to continue efforts to understand the brain-basis of autism, how it changes over time, and how it is related to the changing manifestations of the disorder in children and adults. The population of already-affected individuals with autism is huge and growing. It has become clear that autism in these individuals is a dynamic disorder and that a sizeable proportion of affected individuals worsen rather than improve as they grow older. Individuals whose impairment does not worsen over time live with stable but significant lifelong disability. The objective of this research is to understand longitudinal brain mechanisms from childhood into adulthood in autism and how dynamic brain and clinical phenotype changes are related. This research will result in new information important for the development of new treatments and secondary and tertiary preventive interventions. The specific aims of this project are to collect time 3 and time 4 longitudinal structural and diffusion tensor neuroimaging at 3 Telsa along with clinical and neuropsychological data on a large cohort of children and adults with autism and typically developing individuals. The collection of time 1 and time 2 data was funded by the NIH Collaborative Program of Excellence in Autism. This is a case-control longitudinal study of the original cohort of 100 males with autism and 72 matched normal controls. Subjects in the cohort are equally divided into 4 age-bins. At time 1 they were 3-6, 7-11, 12-17, and 18-35 years of age. At time 2 they were 2 years older. At times 3 and 4 they will be 4 and 6 years older. 3 Telsa structural and diffusion tensor imaging data were collected at time 1 and time 2 and will be collected at time 3 and 4 on the single, same scanner used for time 1 and 2. The 3 major and minor eigenvalues and eigenvectors are determined and fractional anisotropy, mean diffusivity, and axial and radial diffusivity calculated for quantitative assessment of white matter integrity. Region of interests and whole-brain voxel-based analyses of both structural and diffusion tensor imaging data are performed, along with tractography. Detailed clinical and neuropsychological data are collected on all subjects and dynamic brain-behavior relationships studied. This project is a collaborative effort between the University of Utah, where all subjects are ascertained, assessed, and scanned, the University of Wisconsin, where all diffusion tensor imaging data are processed and analyzed, and Brigham Young University where all structural data are processed and analyzed. This collaborative group has been effectively and productively working together on this longitudinal study since 2002.