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

脑干对自闭症谱系障碍儿童感觉运动和核心症状的影响

• 批准号: 9789678
• 负责人: Brittany Gail Travers
• 金额: $ 43.19万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9789678
• 关键词: 9 year old; Address; Affect; Age; Anatomy; Area; Biological Markers; Biology; Brain; Brain Stem; Brain region; Cell Nucleus; Centers for Disease Control and Prevention (U.S.); Cerebrum; Child; Clinical Trials; Comorbidity; Complex; Data; Development; Developmental Disabilities; Diffusion Magnetic Resonance Imaging; Equilibrium; Face; Felis catus; Future; Goals; Hand Strength; Health Care Costs; Human; Image; Imaging Techniques; Individual; Individual Differences; Intervention; Investigation; Knowledge; Learning; Life; Longitudinal Studies; Maps; Measures; Medial lemniscus; Methodology; Mission; Modeling; Motor; National Institute of Child Health and Human Development; Neurobiology; Neurodevelopmental Disability; Neurologic; Outcome; Outcome Measure; Plant Roots; Play; Prevalence; Property; Protocols documentation; Public Health; Quality of life; Reporting; Research; Resources; Respiration; Reticular Formation; Role; Sensorimotor functions; Sensory; Severities; Sleep Wake Cycle; Social Behavior; Standardization; Structure; Symptoms; Techniques; Testing; United States National Institutes of Health; Work; associated symptom; autism spectrum disorder; autistic children; base; common symptom; communication behavior; disability; in vivo; individual variation; innovation; insight; motor symptom; potential biomarker; preclinical trial; prevent; raphe nuclei; repetitive behavior; skills; social communication; symptomatology; virtual; white matter

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.

项目摘要/摘要 脑干是一个复杂且早期发展的大脑区域，负责感觉，运动，自主神经， 和关键的生活功能。自闭症谱系障碍（ASD）的第一个基于生物学的假设建议 脑干的网状形成可能是ASD症状的根本原因。但是，技术 障碍阻止该领域能够可靠地表征体内脑干的子结构 在儿童中。令人兴奋的是，现在的新技术进步使我们能够检查 脑干的核和单个白质。该提议的总体科学前提是 脑干子结构可能对整体大脑发育和ASD的基础有关键的见解。 拟议工作的总体目的是确定特定的白质区和核 对合并症的感觉运动和核心症状挑战的脑干和核心症状挑战 脑干特性参考与ASD有关的其他大脑区域。鉴于脑干的功能 我们假设脑干子结构的微观结构特性与合并症有关 感觉运动症状和核心社会通讯和重复行为症状与ASD有关。 我们进一步假设，由于脑干的 在早期大脑发育中的作用。在强大的初步数据的指导下，这些假设将通过三个。 具体目的：1）确定脑干子结构的微观结构与 合并感官症状的个体差异； 2）确定哪个微观结构的程度 脑干子结构与核心社会通讯和重复的个体差异有关 行为症状； 3）确定脑干子结构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，该技术解决了脑干成像以前的挑战，以提供清晰的和清晰的 脑干及其子结构的解剖学精确图像。使用这种技术，我们将量化 80名ASD儿童（6-9岁）和 80岁的年龄匹配的儿童具有典型的发展。标准化评估将表征感觉运动 和核心症状特征。这项研究的成功完成将提供定量表征 与合并症的感觉运动特征和ASD中的核心症状有关的脑干子结构的 将提供与总体脑指标相关的ASD中脑干子结构的定量表征。 这些贡献将是重要的，因为它们将提高对神经生物学基础的理解 对于ASD，阐明合并症感觉运动挑战和核心症状的神经系统基础 在ASD中，并提供定量生物标志物，以作为临床试验的结果度量。