Three autism subtypes based on single-subject gray matter network revealed by semi-supervised machine learning

Autism spectrum disorder (ASD) is a heterogeneous, early-onset neurodevelopmental condition characterized by persistent impairments in social interaction and communication. This study aims to delineate ASD subtypes based on individual gray matter brain networks and provide new insights from a graph theory perspective. In this study, we extracted and normalized single-subject gray matter networks and calculated each network's topological properties. The heterogeneity through discriminative analysis (HYDRA) method was utilized to subtype all patients based on network properties. Next, we explored the differences among ASD subtypes in terms of network properties and clinical measures. Our investigation identified three distinct ASD subtypes. In the case–control study, these subtypes exhibited significant differences, particularly in the precentral gyrus, lingual gyrus, and middle frontal gyrus. In the case analysis, significant differences in global and nodal properties were observed between any two subtypes. Clinically, subtype 1 showed lower VIQ and PIQ compared to subtype 3, but exhibited higher scores in ADOS-Communication and ADOS-Total compared to subtype 2. The results highlight the distinct brain network properties and behaviors among different subtypes of male patients with ASD, providing valuable insights into the neural mechanisms underlying ASD heterogeneity.