The Evolving Cerebellar and Cerebello-cortical Functional Connectivity Architecture during Infancy.

Abstract

The conventional understanding of the cerebellum as a sole movement control center has become obsolete, given its role in various higher-order functions, including cognition, emotion, and social processing. As these functions emerge during infancy, it is logical to assume that the cerebellum's functional organization must evolve in tandem or preemptively to underpin these functions. However, the longitudinal development of the cerebellum's functional architecture during the crucial early years of infant life remains largely unexplored, highlighting a significant research gap. In this study, leveraging a large cohort of both male and female full-term (n=155) and preterm (n=67) infants, we aimed to delineate the development of within-cerebellum and cerebello-cortical functional connections during the first two years of life. Our findings highlight comprehensive functional synchronization within the neonatal cerebellum with a striking cortical projection focus on primary sensorimotor and visual cortices. While the within-cerebellum synchronization demonstrated early emergence in neonates and developmental stability during the initial two years, the cerebello-cortical projection patterns evolved dramatically, marked by specialization, shifting, and higher-order cortex integration, providing exciting evidence of the cerebellum's involvement in higher-order functions from infancy. Furthermore, preterm infants exhibited decreased cerebello-cortical connectivity compared to their full-term counterparts, suggesting potential developmental alterations. These findings collectively illustrate a dynamic growth pattern of cerebellar functional organization marked by both within-cerebellum stability and cerebellar-cortical projection plasticity with significant implications for long-term cognitive and socioemotional development.Significance Statement The cerebellum is crucial for motor and higher-order cognitive and socioemotional processes. However, the role of early cerebellar development and its cortical projections in supporting these emerging functions during the first years of life remains poorly understood. Our study, based on a large cohort of full-term and preterm infants, reveals the early and stable functional organization of the cerebellar networks from birth to two years, alongside dynamic cerebello-cortical connectivity growth, reflecting both stability and developmental plasticity. We observed a dramatic shift in cerebello-cortical projections from sensorimotor to higher-order association cortices, highlighting its role in emerging higher-order functions. Moreover, diminished growth of these connections indicates possible developmental delays in preterm infants, emphasizing the cerebellum's importance in early brain and behavioral development.