OBJECTIVE Three leading neurobiological hypotheses about autism spectrum disorder (ASD) propose underconnectivity between brain regions, atypical function of the amygdala, and generally higher variability between individuals with ASD than between neurotypical individuals. Past work has often failed to generalize, because of small sample sizes, unquantified data quality, and analytic flexibility. This study addressed these limitations while testing the above three hypotheses, applied to amygdala functional connectivity. METHODS In a comprehensive preregistered study, the three hypotheses were tested in a subset (N=488 after exclusions; N=212 with ASD) of the Autism Brain Imaging Data Exchange data sets. The authors analyzed resting-state functional connectivity (FC) from functional MRI data from two anatomically defined amygdala subdivisions, in three hypotheses with respect to magnitude, pattern similarity, and variability, across different anatomical scales ranging from whole brain to specific regions and networks. RESULTS A Bayesian approach to hypothesis evaluation produced inconsistent evidence in ASD for atypical amygdala FC magnitude, strong evidence that the multivariate pattern of FC was typical, and no consistent evidence of increased interindividual variability in FC. The results strongly depended on analytic choices, including preprocessing pipeline for the neuroimaging data, anatomical specificity, and subject exclusions. CONCLUSIONS A preregistered set of analyses found no reliable evidence for atypical functional connectivity of the amygdala in autism, contrary to leading hypotheses. Future studies should test an expanded set of hypotheses across multiple processing pipelines, collect deeper data per individual, and include a greater diversity of participants to ensure robust generalizability of findings on amygdala FC in ASD.

中文翻译：

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自闭症杏仁核的静息态功能连接：一项预先注册的大规模研究。


目的 关于自闭症谱系障碍 （ASD） 的三个主要神经生物学假说表明，大脑区域之间的连接不足、杏仁核的非典型功能以及 ASD 个体之间的变异性通常高于神经典型个体之间的变异性。由于样本量小、数据质量不明以及分析灵活性，过去的工作往往无法推广。本研究在测试适用于杏仁核功能连接的上述三个假设的同时解决了这些局限性。方法 在一项全面的预注册研究中，这三个假设在一个子集中进行了测试（排除后 N=488;N=212 与 ASD）的自闭症脑成像数据交换数据集。作者从来自两个解剖学定义的杏仁核细分的功能 MRI 数据中分析了静息态功能连接 （FC），在从整个大脑到特定区域和网络的不同解剖尺度上，以三种假设进行幅度、模式相似性和可变性。结果 贝叶斯假设评估方法在 ASD 中产生了非典型杏仁核 FC 幅度的不一致证据，有力证据表明 FC 的多变量模式是典型的，并且没有一致的证据表明 FC 的个体间变异性增加。结果在很大程度上取决于分析选择，包括神经影像学数据的预处理管道、解剖特异性和受试者排除。结论 与主要假设相反，一组预先注册的分析发现没有可靠的证据表明自闭症患者杏仁核的非典型功能连接。 未来的研究应该测试跨多个处理管道的一组扩展假设，收集每个人的更深层次的数据，并包括更多样化的参与者，以确保 ASD 中杏仁核 FC 研究结果的稳健泛化性。