Connectome lateralization in autism across the first 14 years: heterogeneity related to developmental stage, hemisphere, and pathophysiology

Liu, Q.; Li, Q.; Li, X.; Wei, X.; Zhang, X.; Zhou, W.; Zhang, L.; Ren, T.; Huang, C.; Tan, H.; Huang, L.; Liu, K.; Chen, J.; Xu, W.; Zhang, Q.; Kendrick, K. M.; Zhao, W.; Li, F.

doi:10.64898/2026.03.02.708940

bioRxiv · 10.64898/2026.03.02.708940

Connectome lateralization in autism across the first 14 years: heterogeneity related to developmental stage, hemisphere, and pathophysiology

Liu, Q.·Li, Q.·Li, X.·Wei, X.·Zhang, X.·Zhou, W.·Zhang, L.·Ren, T.·Huang, C.·Tan, H.·Huang, L.·Liu, K.·Chen, J.·Xu, W.·Zhang, Q.·Kendrick, K. M.·Zhao, W.·Li, F.

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Abstract

Hemispheric lateralization is fundamental feature to neurodevelopment, yet its dynamic evolution in autism across childhood and underlying molecular mechanisms remain unknown. Thus, using a large-scale resting-state fMRI dataset (n = 1553, ages 1-14), we investigated developmental heterogeneity in connectome lateralization. At the group level, abnormalities in dynamic connectome lateralization strength (DCLS) progressed from focal patterns in early childhood ([≤] 6 years) to widespread distributions by late childhood ([≤] 14 years), independent of symptom severity. The late-stage patterns were validated using the ABIDE dataset (n=153). Late childhood also showed marked increases in inter-individual heterogeneity. These alterations were significantly associated with clinical phenotypes, transcriptomic profiles, and multiple neurotransmitter systems, with distinct patterns across childhood groups. Our findings reveal a developmentally dynamic trajectory of connectome lateralization in autism and highlight late childhood as a critical window for stage- and individual-specific interventions tailored to substantial individual heterogeneity.

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Liu, Q., Li, Q., Li, X., Wei, X., Zhang, X., Zhou, W., Zhang, L., Ren, T., Huang, C., Tan, H., Huang, L., Liu, K., Chen, J., Xu, W., Zhang, Q., Kendrick, K. M., Zhao, W., Li, F.. 2026-03-03. Connectome lateralization in autism across the first 14 years: heterogeneity related to developmental stage, hemisphere, and pathophysiology. https://doi.org/10.64898/2026.03.02.708940

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