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。内部和内部的变化 大脑半球间白质体积/面积以及体积变化较大的结构簇 观察到的。功能磁共振研究报告了大脑皮质和大脑皮质内激活模式的改变。 皮质下灰质结构和神经网络内和神经网络之间的功能连接减少 自闭症。我们的初步DTT研究表明，高功能自闭症患者在 最近定义的一种连接杏仁核和海马体与中梭形回的通路； 更高的各向异性，这意味着更小的纤维直径和更密集的纤维堆积，与右侧相比 对于左撇子来说，这与面孔处理测试中较低的表现有关。这项研究支持 DTT识别自闭症核心脑微结构的能力与表型有关。 我们建议通过以下方法研究自闭症患者大脑的解剖连接和微结构异常 使用弥散张量磁共振成像(DT-MRI或DTI)和弥散张量跟踪(DTT)。我们 将测量连接特定大脑的白质通路的微观结构变化 40对单独配对的成年人(年龄18-35岁)的脑区和相关灰质区域 30对单独配对的患有和不患有自闭症的儿童(6-11岁)。我们会将这些信息关联起来 结果与这些通路相关的行为测量。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质并形成联系、投射和 连合径路。我们将测量灰质和白质结构的体积以 与DT-MRI和DTT表现相关联。 该项目的结果将提供对大脑微观结构和 弥散张量成像测量的组织病理学及其与结构连接和功能连接的关系 将与其分享主题的项目II和III。该项目还将提供对 自闭症患者早期脑发育障碍的结构性结果。该项目将解决自闭症问题 自闭症神经病理学和脑结构与功能研究矩阵目标6、22、23和34 与自闭症有关。它还开发了滴滴涕方法来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.