Emergence of long- and short-range functional connectivity shapes neonatal brain gradients

The emergence of macroscale brain organisation during the perinatal period represents a critical but poorly understood process. Using resting-state fMRI in 325 term-born neonates within the first month of postnatal life, we characterised the early emergence of macroscale brain organisation with functional gradients. Neonatal functional gradients showed a distinct pattern compared with the canonical adult gradients: the principal gradient in neonates, separating the primary sensorimotor and visual networks, corresponded to the secondary gradient in adults (sensorimotor-visual axis), whereas the secondary gradient in neonates, spanning from primary visual to association networks, aligned with the principal gradient in adults (sensorimotor-association axis). We identified distance-dependent functional connectivity as a key mechanism shaping perinatal functional gradients and potentially underlying the protracted development of the sensorimotor-association hierarchy in neonates. Regions with a higher proportion of short-range functional connectivity contributed more to the sensorimotor-visual gradient in neonates, while regions with a greater proportion of middle-to long-range functional connectivity drive the sensorimotor-association hierarchy. Together, these findings highlight the critical role of short- and long-range functional connectivity in shaping neonatal macroscale functional hierarchy. Disruptions to this process during the perinatal period may alter macroscale brain organisation and contribute to the early origins of neurodevelopmental conditions. Significance statementMacroscale brain organisation, characterised by functional gradients, is a fundamental feature of the adult brain and is closely linked to neurodevelopmental conditions. Characterising its emergence in early life and the underlying mechanisms is therefore critical for understanding typical and atypical brain development. Here, we showed that macroscale brain organisation is present at birth, with neonatal functional gradients showing a reversed pattern compared to adults, highlighting the early maturation of primary visual and sensorimotor networks. We further demonstrated that the perinatal development of long- and short-range functional connectivity shapes neonatal functional gradients, identifying a potential mechanism through which early disruptions in functional connectivity may contribute to later neurodevelopmental outcomes.