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bioRxiv · 10.1101/2025.02.19.638284

White-matter controllability at birth predicts social engagement and language outcomes in toddlerhood

Sun, H.·Vernetti, A.·Spann, M.·Chawarska, K.·Ment, L.·Scheinost, D.
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Abstract

Social engagement and language are connected through early development. Alterations in their development can have a prolonged impact on childrens lives. However, the role of white matter at birth in this ongoing connection is less well-known. Here, we investigate how white matter at birth jointly supports social engagement and language outcomes in 642 infants. We use edge-centric network control theory to quantify edge controllability, or the ability of white-matter connections to drive transitions between diverse brain states, at 1 month. Next, we used connectome-based predictive modeling (CPM) to predict the Quantitative Checklist for Autism in Toddlers (Q-CHAT) for social engagement risks and the Bayley Scales of Infant and Toddler Development (BSID-III) for language skills at 18 months from edge controllability. We created the social engagement network (SEN) to predict Q-CHAT scores and the language network (LAN) to predict BSID-III scores. The SEN and LAN were complex, spanning the whole brain. They also significantly overlapped in anatomy and generalized across measures. Controllability in the SEN at 1 month partially mediated associations between Q-CHAT and BSID-III language scores at 18 months. Further, controllability in the SEN significantly differed between term and preterm infants and predicted Q-CHAT scores in an external sample of preterm infants. Together, our results suggest that the intertwined nature of social engagement and language development is rooted in an infants white-matter controllability. Significance StatementDuring infancy and toddlerhood, social engagement and language emerge together. Delays are often observed in both simultaneously. These interactions persist into later childhood, potentially affecting life quality. We reveal that the interplay between social engagement and language milestones in toddlerhood is rooted in the infants structural connectivity, which may assist in early risk identification of developmental delays. Insights into the early brain foundations for emerging social engagement and language skills may open opportunities for individualized interventions to improve developmental outcomes.

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Sun, H., Vernetti, A., Spann, M., Chawarska, K., Ment, L., Scheinost, D.. 2025-02-19. White-matter controllability at birth predicts social engagement and language outcomes in toddlerhood. https://doi.org/10.1101/2025.02.19.638284

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