DIFFUSION TENSOR MRI + HISTOPATHOLOGY OF BRAIN MICROSTRUCTURE + FIBER PATHWAYS

越来越多的证据表明，自闭症是一种大脑连接障碍。内部和内部 半球间白色物质体积/面积和其体积共变的结构簇中， 观察功能性磁共振成像研究已经报道了皮质内激活模式的改变， 皮质下灰质结构和神经网络内部和之间的功能连接减少， 自闭症我们初步的DTT研究表明，高功能自闭症患者在以下方面存在异常： 最近定义的杏仁核和海马体与梭状回中部相互连接的通路; 是，更高的各向异性，表明更小的纤维直径和更致密的纤维堆积，在右边， 而左边的人，在面部处理测试中表现较低。该研究支持 DTT识别自闭症大脑微结构的能力与表型有关。 我们建议研究自闭症患者大脑的解剖连接和微结构异常， 使用扩散张量磁共振成像（DT-MRI或DTI）和扩散张量跟踪（DTT）。我们 将测量连接特定大脑的白色通路的微观结构变化 区域和相关的灰质区域在40个单独匹配的成年人对（年龄18 -35岁）， 30对单独配对的儿童（6-11岁）患有和不患有自闭症。我们将把这些 与这些途径相关的行为测量结果。我们将完成相关的组织病理学检查 皮质内有髓纤维投射到白色物质中并形成联合、投射和 连合（胼胝体）通路。我们将测量灰色和白色物质结构的体积， 与DT-MRI和DTT结果相关。 该项目的结果将提供对大脑微观结构的全面了解， 组织病理学及其与DTI测量的结构连接和功能连接的关系 项目二和项目三将与谁分享主题。该项目还将提供关键的洞察力， 自闭症早期脑发育障碍的结构性后果该项目将解决自闭症 研究矩阵目标6、22、23和34：自闭症的神经病理学以及大脑结构和功能 与自闭症有关。它还开发了DDT方法，用于研究自闭症特有的途径。

A growing body of evidence suggests that autism is a disorder of brain connectivity. Alterations in intra- and inter-hemispheric white matter volume/area and in clusters of structures whose volumes covary have been observed. Functional MRI studies have reported alterations in activation patterns within cortical and subcortical gray structures and reductions in functional connectivity within and between neural networks in autism. Our preliminary DTT studies indicate that subjects with high-functioning autism have abnormalities in a recently defined pathway interconnecting the amygdala and hippocampus with the mid-fusiform gyrus; that is, higher anisotropy, suggesting smaller fiber diameters and denser fiber packing, on the right as compared with the left, that was correlated with lower performanceon face processing tests. This study supports the capacity of DTT for identifying brain microstructure central to autism making links to the phenotype. We propose to study the anatomic connectivity and microstructural abnormalities of the brain in autism by using diffusion tensor magnetic resonance imaging (DT-MRI or DTI) and diffusion tensor tracking (DTT). We will measure microscopic structural changes in white matter pathways that interconnect specific brain regions and the associated gray matter regions in 40 individually-matched pairs of adults (age18-35 yrs)and 30 individually-matched pairs of children (age 6-11 yrs) with and without autism. We will correlate those results with behavioral measures related to these pathways. We will complete a related histopathological study of intracortical myelinated fibers that project into white matter and form association, projection, and commissural (corpus callosal) pathways. We will measure the volumes of gray and white matter structures to correlate with the DT-MRI and DTT findings. The results of this Project will provide a comprehensive understanding of brain microstructure and histopathology and its relation to structural connectivity as measured by DTI and functional connectivity in Projects II and III with whom subjects will be shared. This project will also provide critical insight into the structural outcome of the early disturbances in brain growth in autism. This Project will address Autism Research Matrix goals 6, 22, 23 and 34 on the neuropathology of autism and brain structure and function associated with autism. It also develops DDT methods for the study of pathways specific to autism.