Enhancing the Autism Brain Imaging Data Exchange to Define the Autism Connectome

描述（由申请人提供）：2012年8月，自闭症脑成像数据交换（ABIDE）存储库的发布标志着自闭症谱系障碍（ASD）神经成像的一个里程碑。这一草根倡议通过汇总和公开共享静息状态功能磁共振成像（R-fMRI）、结构磁共振成像（structural MRI）以及先前从17个国际地点收集的1100多名个体（539名ASD患者和573名性别和年龄匹配的典型对照（TC））的表型数据，产生了前所未有的ASD神经成像数据样本。由该公司进行的可行性分析表明，该公司有能力成功地利用这样一个综合数据集进行勘探。然而，由于功能连接体的复杂性和ASD的实质性异质性，更大和更好表征的样本对于有效和变革性的发现至关重要。在这里，我们的目标是通过增加其规模（至少是原始存储库中数据集数量的两倍）和共享表型数据的广度来增强遵约资源的效用，以及它可以解决的问题的创新性和重要性。首先，扩展的存储库将允许在两个仔细匹配的分裂样本中进行全脑功能连接组比较（ASD与TC）的前所未有的性能。我们期望在两个样本中出现的组差异（即探索性和发现性分裂样本）将有力地代表ASD的核心神经生理相关因素。其次，扩大研究范围将增加患有自闭症谱系障碍的女性样本，而在样本量较小的研究中，女性的代表性通常大大不足。拟议的分析将揭示ASD女性大脑内在功能结构的特性，这些特性迄今为止仍是完全未知的。了解自闭症谱系障碍神经基质的性别差异将有助于了解其基础，从而了解可能的保护因素。最后，增强的数据集将有助于探索大脑-行为关系，例如与ASD精神共病的神经元相关的关系。具体来说，主要分析将集中在ADHD症状评分上。同时，该开放共享存储库提供的表型数据扩展中包含的其他精神病理学测量将使用户能够进行进一步的探索。这种高风险，高回报的策略有可能作为临床和大脑表型之间的关键联系，并最终扩展到遗传和表观遗传应用。因此，这种新颖的探索性项目影响相对较小

DESCRIPTION (provided by applicant): The release of the Autism Brain Imaging Data Exchange (ABIDE) repository in August 2012 marked a milestone for the neuroimaging of autism spectrum disorders (ASD). This grass-roots initiative has generated an unprecedented, open sample of ASD neuroimaging data by aggregating and openly sharing resting state fMRI (R-fMRI), structural MRI, as well as phenotypic data previously collected from over 1100 individuals (539 with ASD and 573 sex- and age-matched typical controls (TC)) from 17 international sites. Feasibility analyses performed by the ABIDE consortium demonstrated the ability to successfully carry out exploration with such an aggregate dataset. Nevertheless, due to the complexity of the functional connectome and the substantial heterogeneity of ASD, larger and better-characterized samples are critical for effective and transformative discovery. Here, we aim to enhance the utility of the ABIDE resource and the innovation and significance of the questions it can address by increasing both its size (to at least twice as many datasets as in the original repository) and the breadth of the phenotypic data shared. First, an expanded repository will allow for the unprecedented performance of whole-brain functional connectivity group comparisons (ASD vs. TC) in two carefully matched split samples. We expect that the group differences emerging in both samples (i.e., the exploratory and discovery split-samples) will robustly represent the core neurophysiological correlates of ASD. Second, the expansion will increase the sample of females with ASD, who are usually drastically underrepresented in studies with smaller sample sizes. Proposed analyses will reveal properties of the intrinsic functional architecture of the ASD female brain, which, to date, remain completely unknown. Understanding sex differences in the neural substrates of ASD will provide insights into their underpinnings and consequently, into possible protective factors. Finally, the enhanced dataset will facilitate explorations of brain-behavior relationships, such as those relevant to the neurona correlates of psychiatric comorbidity in ASD. Specifically, primary analyses will focus on ADHD symptom ratings. At the same time, other measures of psychopathology included in the expansion of phenotypic data provided by this open sharing repository, will enable users to conduct further explorations. This high-risk, high-reward strategy has the potential to serve as a crucial linkage between clinical and brain phenotypes, and eventually extend to genetic and epigenetic applications. Thus, this novel exploratory project is high impact for a relatively minor investment. As with genetic discovery, where the strategy of data aggregation and open sharing has proven to be fruitful, this project will offer, within a short time frame, a unique and unprecedented resource: the results of analyses will form the basis for future targeted investigations into the complex neurobiological mechanisms underlying ASD.