BRAIN MICROSTRUCTURE & BEHAVIOR IN NEWLY-DIAGNOSED TODDLERS/PRESCHOOLERS WITH ASD

 描述(由申请者提供)：自闭症谱系障碍是一个主要的世界性公共卫生问题，在美国每88个儿童和成年人中就有一个受到影响。自闭症是一种终生衰弱的发育性大脑疾病，其特征是社交和交流障碍。我们之前使用磁共振扩散张量跟踪(DTT)对自闭症成年人进行了研究，发现用于识别面孔和面孔情绪(社交和非语言交流的关键方面)的脑白质通路发生了独特的变化。这些大脑变化与儿童早期行为之间存在关系，这表明这些大脑变化可能发生在儿童早期，可能代表着面孔加工路径缺乏大脑半球的专门化。在同一批成年人中，我们还发现了胼胝体的大脑变化，这是一种允许信息在大脑右半球和左半球之间流动的大脑结构。这些变化可能导致了人脸加工和语言功能的某些特征。然而，为了更好地了解自闭症的神经生物学，有必要对被诊断为自闭症的非常年幼的儿童进行这些大脑变化的测试，因为成人大脑的变化可能是由于许多其他因素造成的，这些因素几十年来积累起来。为了确定这些变化是否是自闭症发生在发展早期的、在诊断时就存在的基本的、原发的异常，我们将使用DTT来：1)测试幼儿和最近诊断为自闭症的学龄前儿童同一脸部加工路径中的水扩散变化，2)测试语言路径的变化，以及3)测试胼胝体的变化。结果将与面部感知和语言处理的测量进行比较，以确定大脑变化的功能意义。我们计划研究20名患有自闭症的幼儿/学龄前儿童(2-5岁)和20名单独匹配的对照儿童，这两组儿童都被明确诊断为患有自闭症或发育正常。这一结果将决定自闭症成人的大脑变化在确诊后不久的儿童早期是更严重、相似还是不那么严重。我们的长期目标是：1)更好地了解自闭症的潜在生物学机制和病因；2)改进自闭症的早期诊断、筛查、风险评估以及早期治疗和干预的设计/计划；以及3)提供安全、非侵入性的措施(生物标记物)，可用于辅助诊断和指导寻找自闭症的遗传/免疫/环境因素。

 DESCRIPTION (provided by applicant): Autism spectrum disorder is a major worldwide public health problem affecting 1 in 88 children and adults in the U.S. Autism is a lifelong debilitating developmental brain disorder characterized by impairments in social interaction and communication. We previously studied adults with autism using MRI diffusion tensor tracking (DTT), and found unique changes in white matter pathways used for recognizing faces and face emotions (critical aspects of social interaction and non-verbal communication). There was a relationship between these brain changes and early-childhood behaviors, suggesting that these brain changes may occur early in childhood, and may represent a lack of hemispheric specialization of face-processing pathways. In the same adults, we also found brain changes in the corpus callosum, a brain structure that allows information to flow between the brain's right and left hemisphere. Some characteristics of face processing and language function may be caused by such changes in the corpus callosum. However, to better understand the neurobiology of autism, it is necessary to test for these brain changes in very young children diagnosed with autism, because the changes in the adult brain could be due to many other factors that accumulate over decades. To determine whether such changes are a fundamental, primary abnormalities in autism that occur early in development, and that are present at the time of diagnosis, we will use DTT to: 1) test for water diffusion changes in the same face processing pathways in toddlers and preschoolers recently diagnosed with autism, 2) test for changes in language pathways, and 3) test for changes in the corpus callosum. The results will be compared to measures of face perception and language processing to determine the functional significance of the brain changes. We plan to study 20 toddlers/preschoolers with autism (2-5 years of age) and 20 individually-matched comparison children, where both groups have been clearly diagnosed and tested as either having autism or having normal development. The results will determine if the brain changes seen in adults with autism are more severe, similar, or less severe in early childhood soon after diagnosis. Our long- term goals are to: 1) provide a better understanding of the underlying biological mechanisms and causes of autism; 2) improve the early diagnosis, screening, risk assessment, and design/planning of early treatments and interventions; and 3) provide safe, non-invasive measures (biomarkers) that can be used to aid diagnosis and guide the search for genetic/immunological/environmental factors in autism.