BRAIN CONNECTIVITY AND THE ROLE OF MYELIN IN AUTISM SPECTRUM DISORDERS

孤独症谱系障碍的脑连接和髓鞘的作用 摘要 髓鞘的成熟是人类大脑发育和功能的基石。髓鞘形成 在建立和维持离散大脑之间的有效通信方面起着关键作用 区域（即大脑连接），并被认为是各种神经和精神疾病的基础。 自闭症谱系障碍（ASD）。然而，目前对ASD中髓鞘的理解是 非常有限。因此，这项拟议研究的目标是研究是否存在差异， 有髓鞘白色物质微结构存在于个体ASD和典型发育之间， 研究有髓鞘的白色物质及其发育影响结构和 这两个群体的功能连接。我们的目标是通过两个坚实的步骤实现这一目标。在第一阶段 (K99)，我们将利用正在进行的纵向磁共振成像研究来测量两种结构 40名被诊断为自闭症谱系的个体大脑中的功能连接特征 疾病和40个典型发育受试者。我们还将利用该领域的进步， 定量MRI，以实现和获取髓鞘水分数的测量，这是一种替代测量， 髓磷脂含量。这些数据将使我们能够进行第一次调查， 髓鞘在自闭症谱系障碍中的作用，并使我们能够研究髓鞘如何影响 结构和功能的大脑连接。在下一阶段（R 00），我们测量和询问大脑 在自闭症风险较高的婴儿早期大脑发育过程中的微观结构。我们将 检查大脑连接和髓鞘含量的横截面神经发育轨迹， 提供有关神经发育机制的知识和新的见解， 不断升级的紊乱我们希望，这一详细的分析将导致宝贵的信息， 大脑的结构-功能关系，以及提供新的理解到的关键作用， 有髓鞘的白色物质对介导大脑的连接关系有重要作用。我们的结果将揭示新的 自闭症发病机制的神经生物学机制，并促进我们对自闭症最早发病机制的理解 这是一种损害性疾病的表现。因此，拟议项目的结果对新的 了解自闭症谱系障碍的脑成像表型，并将直接影响 制定早期和有针对性的干预战略。

BRAIN CONNECTIVITY AND THE ROLE OF MYELIN IN AUTISM SPECTRUM DISORDERS ABSTRACT The maturation of the myelin sheath is a cornerstone to human brain development and function. Myelination plays a critical role in the establishment and maintenance of efficient communication between discrete brain regions (i.e. brain connectivity) and is additionally believed to underlie a variety of neurological and psychiatric disorders, including autism spectrum disorder (ASD). However, the current understanding of myelin in ASD is exceptionally limited. Thus, the goal of this proposed research is to examine whether differences in the myelinated white matter microstructure exist between individuals ASD and typical development and to investigate the extent to which the myelinated white matter and its development influences structural and functional connectivity in these two groups. We aim to achieve this goal in two solid steps. In the first phase (K99), we will leverage an ongoing longitudinal magnetic resonance imaging study to measure both structural and functional connectivity characteristics in the brain of 40 individuals diagnosed with autism spectrum disorder and 40 typically developing subjects. We will additionally utilize advancements in the field of quantitative MRI to implement and acquire measurements of the myelin water fraction, a surrogate measure of myelin content, from these subjects. This data will allow us to perform the first investigation about the role of myelin in autism spectrum disorders and allow us to examine how myelin influences the relationships between structural and functional brain connectivity. In the next phase (R00), we measure and interrogate brain microstructure during early brain development in infants at heightened risk for developing autism. We will examine the cross-sectional neurodevelopmental trajectories of brain connectivity and myelin content in order to provide knowledge and new insights regarding the neurodevelopmental mechanisms that underlie this escalating disorder. We expect that this detailed analysis will result in invaluable information about the structure-function relationships of the brain as well as provide new understanding into the critical role that myelinated white matter has on mediating connectivity relationships of the brain. Our results will reveal new neurobiological mechanisms of the pathogenesis of autism and advance our comprehension about the earliest manifestations of this impairing disorder. The results from the proposed project are thus significant to new understanding of brain imaging phenotypes of autism spectrum disorders and will have direct implications for the development of earlier and targeted intervention strategies.