Investigating Brain Connectivity in Autism at the Whole-Brain Level

摘要： 这一建议旨在阐明自闭症谱系障碍的整个大脑的功能组织 (以下称为自闭症)，一组神经发育障碍，大约每110人中就有1人受到影响 今天出生的人。我将测试最重要的假设，即不同地区之间的功能耦合 自闭症患者的大脑功能通常会降低。此外，我将探讨这样一种预测，即 连通性与异常行为相关。虽然解剖和功能证据的支持减少了 自闭症的大脑连通性，这从来没有在全脑水平上进行过测试。在这份申请中，我建议 获取静息状态和刺激诱发的血液氧合水平依赖(BOLD)活动 患有自闭症的高功能成年人和匹配的健康对照组参与者的整个大脑。一种衡量 通过检查功能耦合，功能连接性将从静止状态的粗体活动中派生出来 以成对的方式跨越大脑的所有区域。在4个具体目标中，我将测试以下各项 假设：(1)自闭症患者的大脑连接通常比正常少，但存在解剖学上的 这种减少的特异性，(2)可以检查整个大脑的功能响应性 同时在自闭症中使用复杂的自然主义刺激，并可以用来揭示哪些区域起作用 自闭症的异常，(3)异常的静息状态功能连接与诱发的减少有关 这些相同区域的活动，以及(4)广泛分布的大脑区域的功能特性包含 可以用来预测自闭症诊断的信息。培训期间将执行目标1和目标2 赠款的阶段(K99)，而目标3和4将在独立阶段(R00)完成。培训 组件将包括在加州理工大学脑成像中心学习最先进的功能成像方法 中心，以及用于模式分类的统计技术。总而言之，这些研究将提供 第一张关于自闭症大脑连接和大脑活动的全面图片，并为我的未来设定了方向 职业生涯。

ABSTRACT: 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.