Investigating Brain Connectivity in Autism at the Whole-Brain Level

描述（由申请人提供）：本提案旨在阐明自闭症谱系障碍（以下简称自闭症）中整个大脑的功能组织，自闭症是一组神经发育障碍，大约每110个出生的人中就有1个受到影响。我将测试一个最重要的假设自闭症患者大脑不同区域之间的功能耦合通常会减少。此外，我将探讨这种连接减少与异常行为相关的预测。虽然解剖和功能证据支持自闭症患者大脑连通性降低，但这从未在全脑水平上进行过测试。在这个应用中，我建议在高功能自闭症成人和匹配的健康对照参与者中获得静息状态和刺激诱发的全脑血氧水平依赖（BOLD）活动。通过以成对的方式检查大脑所有区域的功能耦合，将从静息状态BOLD活动中得出功能连通性的测量。在4个具体目标中，我将测试以下假设：(1)自闭症大脑的连接通常比正常人少，但这种减少有解剖学上的特殊性；(2)在自闭症患者中，可以使用复杂的自然刺激同时检查整个大脑的功能反应，并可以用来揭示自闭症患者中哪些区域功能异常；(3)异常的静息状态功能连接与这些区域的诱发活动减少有关。(4)广泛分布的大脑区域的功能特性包含可用于预测自闭症诊断的信息。目标1和2将在拨款的培训阶段（K99）进行，而目标3和4将在独立阶段（R00）完成。培训部分将包括在加州理工学院脑成像中心学习最先进的功能成像方法，以及模式分类的统计技术。总之，这些研究将提供自闭症患者大脑连通性和大脑活动的第一张全面图片，并为我未来的职业生涯设定方向。

DESCRIPTION (provided by applicant): This proposal aims to elucidate the functional organization of the whole brain in Autism Spectrum Disorders (hereafter referred to as autism), a group of neurodevelopmental disorders that affect roughly 1 in 110 individuals born today. I will test the overarching hypothesis that functional coupling between different regions of the brain in autism is generally reduced. Moreover, I will explore the prediction that such reduced connectivity is associated with abnormal behavior. While anatomical and functional evidence support reduced brain connectivity in autism, this has never been tested at the whole-brain level. In this application, I propose to acquire resting-state and stimulus-evoked Blood Oxygenation Level Dependent (BOLD) activity across the entire brain in high-functioning adults with autism and matched healthy control participants. A measure of functional connectivity will be derived from the resting-state BOLD activity, by examining the functional coupling across all regions of the brain in a pairwise manner. In each of 4 specific aims, I will test the following hypotheses: (1) that the autistic brain is generally less connected than normal, but that there is anatomical specificity to this reduction, (2) that the functional responsivity of the entire brain can be examined simultaneously in autism using complex naturalistic stimuli, and can be used to reveal which regions function abnormally in autism, (3) that abnormal resting-state functional connectivity is associated with reduced evoked activity in those same regions, and (4) that the functional properties of broadly distributed brain regions contain information that can be used to predict a diagnosis of autism. Aims 1 & 2 will be carried out during the training phase (K99) of the grant, while Aims 3 & 4 will be completed during the independent phase (R00). The training component will consist of learning state-of-the-art functional imaging methods at the Caltech Brain Imaging Center, together with statistical techniques for pattern classification. Together, these studies will provide the first comprehensive picture of brain connectivity and brain activity in autism, and set the direction for my future career. PUBLIC HEALTH RELEVANCE: These studies will provide mentored training and research to help better understand brain connectivity in autism. This will be important information for guiding future diagnoses and intervention.