Multi-scale structural rich-club organization of the brain in full-term newborns: a combined DWI and fMRI study

Objective. Our understanding of early brain development is limited due to rapid changes in white matter pathways after birth. In this study, we introduced a multi-scale cross-modal approach to investigate the rich club (RC) organization and topology of the structural brain networks in 40 healthy neonates using diffusion-weighted imaging and resting-state fMRI data. Approach. A group independent component analysis was first performed to identify eight resting state networks (RSNs) used as functional modules. A groupwise whole-brain functional parcellation was also performed at five scales comprising 100-900 parcels. The distribution of RC nodes was then investigated within and between the RSNs. We further assessed the distribution of short and long-range RC, feeder and local connections across different parcellation scales. Main results. Sharing the scale-free characteristic of small-worldness, the neonatal structural brain networks exhibited an RC organization at different nodal scales (NSs). The subcortical, sensory-motor and default mode networks were found to be strongly involved in the RC organization of the structural brain networks, especially in the zones where the RSNs overlapped, with an average cross-scale proportion of 45.9%, 28.5% and 10.5%, respectively. A large proportion of the connector hubs were found to be RC members for the coarsest (73%) to finest (92%) NSs. Our results revealed a prominent involvement of cortico-subcortical and cortico-cerebellar white matter pathways in the RC organization of the neonatal brain. Regardless of the NS, the majority (more than 65.2%) of the inter-RSN connections were long distance RC or feeder with an average physical connection of 105.5 and 97.4 mm, respectively. Several key RC regions were identified, including the insula and cingulate gyri, middle and superior temporal gyri, hippocampus and parahippocampus, fusiform gyrus, precuneus, superior frontal and precentral gyri, calcarine fissure and lingual gyrus. Significance. Our results emphasize the importance of the multi-scale connectivity analysis in assessing the cross-scale reproducibility of the connectivity results concerning the global and local topological properties of the brain networks. Our findings may improve our understanding of the early brain development.

Automated summary

This study introduced a multi-scale cross-modal approach to investigate the rich club (RC) organization and topology of the structural brain networks in healthy neonates. The results showed the involvement of subcortical, sensory-motor, and default mode networks in the RC organization of the structural brain networks, highlighting the importance of cortico-subcortical and cortico-cerebellar white matter pathways in neonatal brain development.