Lateralization of sensorimotor behavior and cortical-cerebellar networks in autism

项目总结 自闭症谱系障碍(Asd)是一种大脑机制尚不健全的神经发育障碍。 明白了。ASD的静息状态功能磁共振成像(FMRI)研究表明 精选大脑网络的功能专门化减少，但感觉运动的功能专门化 ASD中的网络还没有被很好地理解。解决这一知识鸿沟很重要，因为感觉运动 自闭症患者的行为持续受到影响，受到离散的、映射良好的皮质-小脑的支持 与ASD有关的网络，并支持发展更高层次的认知和适应技能 患有自闭症。ASD感觉运动网络功能特化的研究进展 可能提供关于潜在大脑过程的重要信息，同时也指导治疗策略。这个 拟议的研究将检验ASD患者的中心假设，即ASD患者的侧化程度降低 感觉运动行为和相关皮质-小脑网络的功能和结构。在目标1下， 患有自闭症和典型发展中(TD)对照的参与者将在以下方面进行比较 主导型和非主导型手感觉运动控制。据预测，ASD患者的患病率将下降 显性期间的侧向优势--与非显性表现相比。在目标2下，参与者将 在基于任务的功能磁共振成像过程中完成类似的精确感觉运动测试。在优势手行为过程中， ASD患者有望表现出：(1)同侧激活和功能连接增强 初级运动皮质(M1)和对侧小脑，以及(2)激活和功能连接减少 对侧M1和同侧小脑。在两只手中，ASD患者预计会表现出 右后顶叶皮质(PPC)的激活和连接性降低。根据目标3，参与者将 完成一个结构核磁共振，它将提供有关皮质-小脑体积的信息。形态计量分析 将进行双侧M1、运动前皮质、PPC和小脑的检查。患有ASD的个人预计会 大脑皮质和小脑体积不对称程度减轻。拟议的研究与一个 训练计划旨在为研究员提供感觉运动行为和生理学方面的专门训练， 发展认知神经科学方法(包括测量功能连通性和结构性 形态计量学)，以及表征纵向发展的统计方法。这次培训将是 由在ASD的感觉运动生理学方面有专长的赞助者和一组贡献者支持 在感觉运动发育、ASD的功能脑机制、结构性疾病方面的专业知识互补 ASD的大脑发育，以及表征发育的先进统计分析方法。这个 应聘者的培训计划将支持应聘者朝着其发展的长期目标前进 研究神经发育障碍中感觉和运动问题的大脑机制。

PROJECT SUMMARY Autism spectrum disorder (ASD) is a neurodevelopmental disorder for which brain mechanisms are not yet well understood. Resting state functional magnetic resonance imaging (fMRI) studies of ASD have implicated reduced functional specialization of select brain networks, but functional specialization of sensorimotor networks in ASD is not well understood. Addressing this knowledge gap is important because sensorimotor behaviors are consistently impacted in ASD, are supported by discrete, well mapped, cortical-cerebellar networks implicated in ASD, and support the development of higher-order cognitive and adaptive skills that are compromised in ASD. Advancing knowledge of the functional specialization of sensorimotor networks in ASD may provide important information on underlying brain processes while also guiding therapeutic strategies. The proposed research will test the central hypothesis that individuals with ASD show reduced lateralization of sensorimotor behavior and the function and structure of associated cortical-cerebellar networks. Under Aim 1, participants with ASD and typically developing (TD) controls will be compared on precision measures of dominant and non-dominant hand sensorimotor control. Individuals with ASD are predicted to show reduced lateralized advantage during dominant- compared to non-dominant performance. Under Aim 2, participants will complete similar precision sensorimotor tests during task-based fMRI. During dominant hand behavior, individuals with ASD are expected to show (1) increased activation and functional connectivity of ipsilateral primary motor cortex (M1) and contralateral cerebellum, and (2) reduced activation and functional connectivity of contralateral M1 and ipsilateral cerebellum. Across both hands, individuals with ASD are expected to show reduced activation and connectivity of right posterior parietal cortex (PPC). Under Aim 3, participants will complete a structural MRI which will provide information on cortical-cerebellar volume. Morphometric analyses of bilateral M1, premotor cortex, PPC, and cerebellum will be conducted. Individuals with ASD are expected to show reduced cortical and cerebellar volumetric asymmetry. The proposed studies are integrated with a training plan designed to provide the fellow with specialized training in sensorimotor behavior and physiology, developmental cognitive neuroscience methods (including measures of functional connectivity and structural morphometry), and statistical methods for characterizing longitudinal development. This training will be supported by the Sponsor whose expertise is in sensorimotor physiology in ASD, and a team of Contributors with complementary expertise in sensorimotor development, functional brain mechanisms of ASD, structural brain development in ASD, and advanced statistical analysis methods for characterizing development. The candidate's Training Plan will support the candidate's advancement towards his long-term goal of developing a research program examining brain mechanisms of sensory and motor issues in neurodevelopmental disorders.