Functional connectome harmonics capture early brain organization and maturity in neonates

Abstract

The functional organization of the human brain is established early, yet the ontogeny of its large-scale functional gradients remains unclear. Using resting-state fMRI data from 714 neonates in the Developing Human Connectome Project, we mapped neonatal brain gradients via functional connectome harmonics (FCH). We identified adult-like sensory-to-multimodal and cognitive gradient patterns present at birth. Applying three FCH-derived metrics--entropy, power, and energy--we found that power and energy were higher in term-born compared to preterm neonates, while entropy was elevated in preterms. These metrics predicted up to ~30% of postmenstrual age, indicating their biological relevance. Our findings reveal that the neonatal brain possesses a robust gradient architecture underpinning early functional organization, offering novel biomarkers for assessing brain maturity and the impact of prematurity on neurodevelopment.