Reardon Alexandra M, Li Kaiming, Langley Jason, Hu Xiaoping P
Department of Bioengineering, University of California, Riverside, California, USA.
Center for Advanced Neuroimaging, University of California, Riverside, California, USA.
Brain Connect. 2022 Mar;12(2):193-205. doi: 10.1089/brain.2020.0997. Epub 2021 Sep 28.
Autism spectrum disorder (ASD) is a highly heterogeneous developmental disorder with diverse clinical manifestations. Neuroimaging studies have explored functional connectivity (FC) of ASD through resting-state functional magnetic resonance imaging studies; however, the findings have remained inconsistent, thus reflecting the possibility of multiple subtypes. Identification of the relationship between clinical symptoms and FC measures may help clarify the inconsistencies in earlier findings and advance our understanding of ASD subtypes. Canonical correlation analysis was performed on 210 ASD subjects from the Autism Brain Imaging Data Exchange to identify significant linear combinations of resting-state connectomic and clinical profiles of ASD. Then, hierarchical clustering defined ASD subtypes based on distinct brain-behavior relationships. Finally, a support vector machine (SVM) classifier was used to verify that subtypes comprised subjects with distinct clinical and connectivity features. Three ASD subtypes were identified. Subtype 1 exhibited increased intra-network FC, increased Intelligence Quotient (IQ) scores, and restricted and repetitive behaviors. Subtype 2 was characterized by decreased whole-brain FC and more severe Autism Diagnostic Interview-Revised and Social Responsiveness Scale symptoms. Subtype 3 demonstrated mixed FC, low IQ scores, as well as social motivation and verbal deficits. To verify subtype assignment, a multi-class SVM using connectomic and clinical profiles yielded an average accuracy of 71.3% and 65.2% respectively for subtype classification, which is significantly higher than chance (33.3%). The present study demonstrates that combining connectomic and behavioral measures is a powerful approach for disease subtyping and suggests that there are ASD subtypes with distinct connectomic and clinical profiles.
自闭症谱系障碍(ASD)是一种高度异质性的发育障碍,临床表现多样。神经影像学研究通过静息态功能磁共振成像研究探索了ASD的功能连接性(FC);然而,研究结果仍不一致,这反映了多种亚型存在的可能性。确定临床症状与FC测量之间的关系可能有助于澄清早期研究结果中的不一致之处,并加深我们对ASD亚型的理解。对来自自闭症脑成像数据交换库的210名ASD受试者进行了典型相关分析,以确定ASD静息态连接组学和临床特征的显著线性组合。然后,基于不同的脑-行为关系进行层次聚类来定义ASD亚型。最后,使用支持向量机(SVM)分类器来验证这些亚型包含具有不同临床和连接特征的受试者。确定了三种ASD亚型。亚型1表现为网络内FC增加、智商(IQ)分数升高以及存在局限和重复行为。亚型2的特征是全脑FC降低以及自闭症诊断访谈修订版和社会反应量表症状更严重。亚型3表现出混合的FC、低智商分数以及社交动机和语言缺陷。为了验证亚型分类,使用连接组学和临床特征的多类SVM对亚型分类的平均准确率分别为71.3%和65.2%,显著高于随机概率(33.3%)。本研究表明,结合连接组学和行为测量是疾病亚型分类的有效方法,并表明存在具有不同连接组学和临床特征的ASD亚型。