Functional Brain Asymmetry Reveals Heterogeneous Subtypes in Autism Spectrum Disorder

Abstract

Heterogeneity is a critical factor in understanding inter-individual brain and behavioral variability in autism spectrum disorder (ASD). Since individuals with ASD exhibit atypical communication and social interaction skills closely linked to brain lateralization, this study investigated ASD heterogeneity using an asymmetry index that captures interhemispheric differences in brain function. Degree centrality was computed from the functional connectivity matrix, and its asymmetry was quantified for each brain region. Using an unsupervised clustering algorithm, we identified three distinct subtypes within the ASD population that showed significant differences in brain asymmetry in the somatomotor, frontoparietal, and default mode networks. Comparisons of symptom severity indicated that subtype 2, which displayed atypical asymmetry patterns along the sensory–default mode axis, exhibited higher clinical severity. Functional connectivity analyses further revealed that subtype 1, characterized by rightward asymmetry, demonstrated hypoconnectivity across sensory and heteromodal association regions, whereas subtype 3, characterized by leftward asymmetry, exhibited hyperconnectivity. Cognitive decoding suggested distinct neurocognitive profiles for each subtype: subtype 1 was associated with increased engagement of self-referential and motivational processes (social-motivational subtype), subtype 2 with impaired regulatory and executive functions (cognitive control/impulsive subtype), and subtype 3 with enhanced involvement of mnemonic and language-related systems (memory-language subtype). Together, these findings advance our understanding of functional brain heterogeneity in ASD and demonstrate that subtype identification based on hemispheric asymmetry offers a promising framework for elucidating topological and behavioral variability within the ASD population.