Emergence of functional topography in the neonatal white matter

The functional architecture of the cerebral cortex is well characterized by a hierarchical organization. Recent studies suggest that white matter (WM) demonstrates intrinsic functional dynamics comparable to cortical regions. However, how these patterns of WM functional organization initially emerge during early human development remains poorly understood. Using multimodal MRI data from the Developing Human Connectome Project (dHCP) comprising 399 infants (348 term-born, 51 preterm-born), we investigate WM functional gradients in the neonatal brain and assess their prognostic relevance. We show that neonatal WM exhibits a sophisticated, gray matter-like functional topography, characterized by principal gradients along sensorimotor-to-visual and unimodal-to-transmodal axes. These gradients demonstrate rapid, tract-specific developmental changes during the perinatal period and show significant associations with underlying myelination, indexed by the T1w/T2w ratio. Preterm birth distinctly disrupts this nascent functional architecture, notably reducing gradient values in the right corticospinal tract and increasing gradient values in the bilateral cingulum cingulate and forceps major. Importantly, we demonstrate that neonatal WM gradient features significantly predict language outcomes at 18 months, specifically within the preterm-born cohort. These findings establish neonatal WM functional organization as a crucial aspect of early brain development and highlight its potential utility as a biomarker for identifying infants at heightened risk for adverse neurodevelopmental outcomes.