Early development and co-evolution of microstructural and functional brain connectomes: A multi-modal MRI study in preterm and full-term infants

Abstract Introduction Functional networks characterised by coherent neural activity across distributed brain regions have been observed to emerge early in neurodevelopment. Synchronized maturation across regions that relate to functional connectivity (FC) could be partially reflected in the developmental changes in underlying microstructure. Nevertheless, covariation of regional microstructural properties, termed ‘microstructural connectivity’ (MC), and its relationship to the emergence of functional specialization during the early neurodevelopmental period remains poorly understood. Methods We investigated the evolution of MC and FC postnatally across a set of cortical and subcortical regions, focusing on 45 preterm infants scanned longitudinally, and compared to 45 matched full-term neonates as part of the developing Human Connectome Project (dHCP) using direct comparisons of grey-matter connectivity strengths as well as network-based analyses. Results Our findings revealed a global strengthening of both MC and FC with age, with connection-specific variability influenced by the connection maturational stage. Prematurity at term-equivalent age was associated to significant connectivity disruptions, particularly in FC. During the preterm period, direct comparisons of MC and FC strength showed positive linear relationship, which seemed to weaken with development. On the other hand, overlaps between MC-and FC-derived networks (estimated with Mutual Information) increased with age, suggesting a potential convergence towards a shared underlying network structure that may support the co-evolution of microstructural and functional systems. Conclusion Our study offers novel insights into the dynamic interplay between microstructural and functional brain development and highlights the potential of MC as a complementary descriptor for characterizing the brain network development and alterations due to perinatal insults such as premature birth. Keypoints Our study reveals a significant positive linear relationship between grey-matter functional connectivity and underlying microstructural connectivity during development, that decreases with age and varies across connection types. Despite progressive maturational decoupling of microstructural and functional connectivity, a shared network structure may underlie changes in both properties. Prematurity impacts the maturation of connectivity in both modalities, but with a higher reduction of functional than microstructural connectivity strengths.