BRAIN CONNECTIVITY AND THE ROLE OF MYELIN IN AUTISM SPECTRUM DISORDERS

大脑连接和髓磷脂在自闭症谱系障碍中的作用

• 批准号: 9978615
• 负责人: Douglas Carl Dean III
• 金额: $ 24.8万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-21 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9978615
• 关键词: Adult; Algorithms; Anatomy; Anisotropy; Architecture; Area; Axon; Behavioral; Brain; Brain imaging; Brain region; Characteristics; Child; Clinical; Cognitive; Communication; Comprehension; Corpus Callosum; Data; Defect; Development; Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Functional Magnetic Resonance Imaging; Goals; Human; Image; Impairment; Individual; Infant; Injury; Intervention; Intervention Studies; Investigation; Knowledge; Life; Lipids; Longevity; Magnetic Resonance Imaging; Maintenance; Maps; Measurement; Measures; Mediating; Mediation; Mental disorders; Monitor; Motivation; Myelin; Myelin Sheath; Neurites; Neurodevelopmental Disorder; Neurons; Pathogenesis; Pattern; Phase; Phenotype; Play; Policies; Prediction of Response to Therapy; Prefrontal Cortex; Prevention; Reporting; Research; Rest; Risk; Role; Signal Transduction; Solid; Statistical Data Interpretation; Structure; Structure-Activity Relationship; System; Therapeutic Intervention; Time; TimeLine; Tissues; Toddler; Water; autism spectrum disorder; blood oxygen level dependent; brain circuitry; connectome; density; flexibility; imaging biomarker; imaging study; improved; indexing; insight; myelination; nervous system disorder; neurobiological mechanism; neuroimaging; neuropathology; novel imaging technique; relating to nervous system; response; screening; tractography; white matter

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.

脑连通性与髓鞘在自闭症谱系障碍中的作用 摘要 髓鞘的成熟是人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(即大脑连通性)，并被认为是各种神经和精神疾病的基础 精神障碍，包括自闭症谱系障碍(ASD)。然而，目前对ASD中髓鞘的理解是 非常有限。因此，这项拟议的研究的目标是检查在 有髓白质微结构存在于个体ASD和典型发育之间，并 研究有髓白质及其发育对结构和发育的影响程度。 这两个组的功能连接性。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例自闭症患者的脑功能连接性特征 精神障碍和40个典型的发展中的对象。我们还将利用在以下领域的进展 定量核磁共振用于实施和获取髓鞘含水率的测量，这是一种替代测量 这些受试者的髓鞘含量。这些数据将使我们能够进行第一次关于 髓鞘在自闭症谱系障碍和允许我们检查髓鞘如何影响之间的关系 结构和功能的大脑连接。在下一阶段(R00)，我们测量和询问大脑 患自闭症风险较高的婴儿大脑发育早期的显微结构。我们会 按顺序检查大脑连通性和髓鞘含量的横断面神经发育轨迹 提供有关神经发育机制的知识和新见解 不断升级的混乱。我们期望这一详细的分析将产生关于 大脑的结构-功能关系，以及提供对关键作用的新理解 有髓白质具有调节大脑连接关系的作用。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及对最早的认识 这一损害障碍的表现。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对 制定更早、更有针对性的干预策略。