Neural Mechanisms of Sensory OverResponsivity

项目摘要 感觉过度反应(SOR)，是对典型的非伤害性刺激的不寻常的负面反应，代表 许多神经发育疾病的显著特征，包括自闭症谱系障碍(ASD)， 焦虑、注意力缺陷/多动和发育协调障碍。SOR严重扰乱了所有 儿童发展的方方面面，包括学习和参与社会的能力。尽管越来越多的人认识到 SOR作为神经发育疾病的核心特征，其神经机制尚不清楚。 由于这种差距，SOR历来被认为是“行为上的”，或由于“不良的父母教育”或 “自闭症”的后果。来自我们实验室的数据和其他数据表明，这种看法受到了挑战 感觉加工障碍儿童脑白质微结构和功能成像的差异 (SPD)和ASD/SOR儿童。描述了隶属于SOR的底层神经网络，两者都 听觉和触觉，不仅将指导我们对这一状况的理解，而且还将转变概念化 一种可治疗的神经疾病的分类。获得SOR的神经特征将有助于 通过认知训练范式寻找神经重塑的生物标记物，类似于我们在 认知控制领域。我们利用实验室中对听觉SOR的直接评估的工作将测试 排序由高阶排序网络断开所产生的科学前提：后验 放射状的副花冠，上位的纵束和扣带状的束。我们将进一步确定 这种假定的SOR网络是否反映了后脑室周围区域的普遍脆弱性， 富含高度连接的白质束，或者是听觉SOR特有的。此外，如果这是 微结构断开是SOR特有的，那么它是多域SOR网络还是每个感官 域(例如，听觉和触觉)依赖于一组独特的连接--如不重叠的 受影响儿童的感觉域表型？一种多方面的表型和神经成像方法是 需要回答这些问题。这项建议的目的是推进我们对 感觉相关行为和应用新的结构神经成像方法来阐明神经结构 使用RDoC方法的SOR。为了实现这一目标，我们将使用 感觉处理：三维评估(SP-3D：A)配合创新的结构成像， 轴突定向弥散和密度成像，用于详细的微观结构评估，以及边缘 密度成像，用于先进的连接体评估，在170名8-12岁的儿童中， 神经发育方面的问题。所有表型和神经成像数据将于#年向现场提供。 以便在这一独特的数据集中支持对感觉处理的持续理解。

Project Summary Sensory over-responsivity (SOR), the unusual negative response to typically non-noxious stimuli, represents a prominent feature of many neurodevelopmental conditions, including Autism Spectrum Disorder (ASD), Anxiety, Attention Deficit/Hyperactivity, and Developmental Coordination Disorders. SOR severely disrupts all aspects of a child's development, including the ability to learn and socially engage. Despite growing recognition of SOR as a core feature in neurodevelopmental conditions, the neural mechanisms of SOR remain unclear. As a result of this gap, SOR has historically been thought to be “behavioral” or due to “bad parenting” or a consequence of “having autism”. This percept has been challenged by data from our lab and others showing white matter microstructural and functional imaging differences in children with sensory processing dysfunction (SPD) and in children with ASD/SOR. Delineating the underlying neural networks that subserve SOR, both auditory and tactile, will not only guide our understanding of this condition, but also shift the conceptualization of SOR to that of a treatable neurologic condition. Obtaining the neural signature of SOR will contribute to finding a biomarker for neural remodeling with cognitive training paradigms similar to what we have piloted in the domain of cognitive control. Our work utilizing in-lab direct assessment of auditory SOR will test the scientific premise that SOR results from the disconnection of a higher-order SOR network: the Posterior Corona Radiata, Superior Longitudinal Fasciculus, and the Cingulate Bundle. We will further determine whether this putative SOR network reflects a general vulnerability in the posterior periventricular regions, which are rich in highly connecting white matter tracts, or is specific to auditory SOR. Furthermore, if this microstructural disconnection is SOR specific, then is it a multi-domain SOR network or does each sensory domain (e.g. auditory and tactile) rely on a unique set of connections-- as is suggested by the non-overlapping sensory domain phenotypes in affected children? A multifaceted phenotype and neuroimaging approach is required to answer these questions. The objective of this proposal is to advance our direct assessment of sensory related behavior and apply novel structural neuroimaging methods to elucidate the neural architecture of SOR using an RDoC approach. To achieve this goal, we will assess auditory and tactile SOR using the Sensory Processing: Three Dimensions Assessment (SP-3D:A) paired with innovative structural imaging, Neurite Orientation Dispersion and Density Imaging, for detailed microstructural assessment, and Edge Density Imaging, for advance connectome assessment, in 170 children, ages 8-12 years, with neurodevelopmental concerns. All phenotype and neuroimaging data will be made available to the field in order to support ongoing understanding of sensory processing in this unique data set.