Weijin Liu

Brain development in preterm infants shows marked heterogeneity, often obscured by group‐level analyses. Between the group‐level and the individual difference, subgroup can model the heterogeneity of early developmental trajectories. To characterize this, we analyzed longitudinal functional connectome data from 90 preterm infants (scanned at birth and term‐equivalent age) and 521 full‐term controls from the developing Human Connectome Project. A machine learning model predicted individual brain‐age gap (BAG), quantifying maturational deviation. Clustering of longitudinal BAG trajectories revealed two distinct preterm subgroups with divergent developmental pathways. These subgroups exhibited significantly different functional network architectures and, at 19‐month follow‐up, distinct behavioral outcomes in cognitive, language, and motor domains. Our findings establish that early preterm brain maturation follows identifiable, heterogeneous trajectories, providing a data‐driven framework for early risk stratification.

The mechanisms linking structural maturation to the emergence of functional networks in the perinatal brain remain unresolved. While prevailing models attribute functional connectivity to white matter myelination, neonates paradoxically exhibit adult-like resting-state networks despite profoundly immature white matter tracts. Here, we proposed gray matter myelination covariance as a critical basis of early functional connectivity emergence. We introduced a dual-axis myelination covariance framework and derived a myelination-function coupling (MFC) index specific to the newborn brain. Results revealed that the MFC exhibited distinct spatial patterns dominated by primary sensory and motor cortices, increased with age, and showed a distance-dependent strength. Crucially, neonatal MFC patterns showed a strong spatial correlation with gene expression profiles implicated in neurovascular coupling and specifically predicted later behaviors. These findings suggest that during infancy, the integration of brain function is not initially dominated by only the white matter connections but is also shaped by the synchrony of intracortical microstructure that reflects shared developmental trajectories, which offers a framework for understanding the formation of the developmental connectome.