Brainstem Contributions to Sensorimotor and Core Symptoms in Children with Autism Spectrum Disorder

项目摘要/摘要 脑干是一个复杂的早期发育的大脑区域，负责感觉、运动、自主神经、 以及对生命至关重要的功能。第一个基于生物学的自闭症谱系障碍(ASD)假说提出 脑干的网状结构可能是ASD症状的根本原因。然而，技术上 障碍阻碍了这个领域能够可靠地描述活体脑干的亚结构。 在孩子们身上。令人兴奋的是，新的技术进步现在使我们能够检查 脑干的核和个别的白质束。这项提议的总体科学前提是 脑干亚结构可能包含对整个大脑发育和自闭症基础的关键见解。 拟议工作的总体目标是识别特定的白质束和核团。 脑干，帮助ASD的感觉运动和核心症状的共同挑战，并将其与上下文联系起来 参照ASD涉及的其他脑区的脑干特性。鉴于脑干的功能， 我们假设脑干亚结构的微结构特征与并存有关。 感觉运动症状和核心社交和重复行为症状与ASD有关。 我们进一步假设脑干与ASD的其他脑区明显相关，这是由于脑干的 在早期大脑发育中的作用。在强劲的初步数据的指导下，这些假设将通过三个阶段进行检验 具体目标：1)确定脑干亚结构的微结构与 共病感觉运动症状的个体差异；2)决定微结构的程度 脑干亚结构与核心社交沟通和重复性的个体差异有关。 行为症状；以及3)确定脑干亚结构和行为症状之间的明显对应关系 周围的大脑。一个关键的创新是，我们将通过应用扩散加权来实现这些目标 成像(DWI)技术，解决了以前脑干成像的挑战，提供了清晰和 脑干及其子结构的精确解剖图像。使用这项技术，我们将量化 80例自闭症儿童(6~9岁)脑干亚结构(及周围脑)的显微结构 80名发育典型的同龄儿童。标准化评估将成为感觉运动的特征 和核心症状特征。这项研究的成功完成将提供一个量化的表征 脑干亚结构与ASD合并感觉运动特征和核心症状的关系 将提供ASD中脑干亚结构与整体大脑指标的关系的定量表征。 这些贡献将是重要的，因为它们将促进对神经生物学基础的理解 对于ASD，阐明共病的感觉运动挑战和核心症状的神经学基础 在ASD中，并提供定量生物标记物作为临床试验的结果衡量标准。

PROJECT SUMMARY/ABSTRACT The brainstem is a complex and early-developing brain region that is responsible for sensory, motor, autonomic, and critical-for-life functions. The first biology-based hypothesis of autism spectrum disorder (ASD) suggested that the reticular formation of the brainstem may be a root cause of ASD symptoms. However, technological barriers have prevented the field from being able to reliably characterize substructures of the brainstem in vivo in children. Excitingly, new technological advances now allow us to examine the microstructural properties of the brainstem's nuclei and individual white matter tracts. The overall scientific premise of this proposal is that brainstem substructures may hold key insights into overall brain development and into the underpinnings of ASD. The overall objective of the proposed work is to identify specific white matter tracts and nuclei within the brainstem that subserve the comorbid sensorimotor and core symptom challenges of ASD and to contextualize brainstem properties in reference to other brain regions implicated in ASD. Given the functions of the brainstem, we hypothesize that the microstructural properties of the brainstem substructures are associated with comorbid sensorimotor symptoms and core social-communication and repetitive-behavior symptoms implicated in ASD. We further hypothesize that the brainstem relates distinctly to other brain regions in ASD, due to the brainstem's role in early brain development. Guided by strong preliminary data, these hypotheses will be tested through three specific aims: 1) Determine extent to which the microstructure of brainstem substructures is associated with individual differences in comorbid sensorimotor symptoms; 2) Determine extent to which microstructure of brainstem substructures is associated with individual differences in core social-communication and repetitive- behavior symptoms; and 3) Identify the distinct correspondence among brainstem substructures and the surrounding brain. A key innovation is that we will accomplish these aims by applying a diffusion-weighted imaging (DWI) technique that addresses the previous challenges of brainstem imaging to provide a clear and anatomically precise image of the brainstem and its substructures. With this technique, we will quantify the microstructure of brainstem substructures (and surrounding brain) in 80 children with ASD (6-9 years old) and 80 age-matched children with typical development. Standardized assessments will characterize sensorimotor and core symptom profiles. The successful completion of this research will provide a quantitative characterization of brainstem substructures in relation to the comorbid sensorimotor features and core symptoms in ASD, and it will provide a quantitative characterization of brainstem substructures in ASD in relation to overall brain metrics. These contributions will be significant because they will advance the understanding of the neurobiological basis for ASD, elucidate the neurological underpinnings of the comorbid sensorimotor challenges and core symptoms in ASD, and provide quantitative biomarkers to be used as outcome measures in clinical trials.