Robust Autism Spectrum Disorder‐Related Spatial Covariance Gray Matter Pattern Revealed With a Large‐Scale Multi‐Center Dataset

ABSTRACT Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder and its underlying neuroanatomical mechanisms still remain unclear. The scaled subprofile model of principal component analysis (SSM‐PCA) is a data‐driven multivariate technique for capturing stable disease‐related spatial covariance pattern. Here, SSM‐PCA is innovatively applied to obtain robust ASD‐related gray matter volume pattern associated with clinical symptoms. We utilized T1‐weighted structural MRI images (sMRI) of 576 subjects (288 ASDs and 288 typically developing (TD) controls) aged 7–29 years from the Autism Brain Imaging Data Exchange II (ABIDE II) dataset. These images were analyzed with SSM‐PCA to identify the ASD‐related spatial covariance pattern. Subsequently, we investigated the relationship between the pattern and clinical symptoms and verified its robustness. Then, the applicability of the pattern under different age stages were further explored. The results revealed that the ASD‐related pattern primarily involves the thalamus, putamen, parahippocampus, orbitofrontal cortex, and cerebellum. The expression of this pattern correlated with Social Response Scale and Social Communication Questionnaire scores. Moreover, the ASD‐related pattern was robust for the ABIDE I dataset. Regarding the applicability of the pattern for different age stages, the effect sizes of its expression in ASD were medium in the children and adults, while small in adolescents. This study identified a robust ASD‐related pattern based on gray matter volume that is associated with social deficits. Our findings provide new insights into the neuroanatomical mechanisms of ASD and may facilitate its future intervention.