Early structural connectivity within the sensorimotor network: Deviations related to prematurity and association to neurodevelopmental outcome

Abstract

Consisting of distributed and interconnected structures that interact through cortico-cortical connections and cortico-subcortical loops, the sensorimotor (SM) network undergoes rapid maturation during the perinatal period and is thus particularly vulnerable to preterm birth. However, the impact of prematurity on the development and integrity of the emerging SM connections and their relationship to later motor and global impairments are still poorly understood. In this study we aimed to explore to which extent the early microstructural maturation of SM white matter (WM) connections at term-equivalent age (TEA) is modulated by prematurity and related with neurodevelopmental outcome at 18 months corrected age. We analyzed 118 diffusion MRI datasets from the developing Human Connectome Project (dHCP) database: 59 preterm (PT) low-risk infants scanned near TEA and a control group of full-term (FT) neonates paired for age at MRI and sex. We delineated WM connections between the primary SM cortices (S1, M1 and paracentral region) and subcortical structures using probabilistic tractography, and evaluated their microstructure with diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) models. To go beyond tract-specific univariate analyses, we computed a maturational distance related to prematurity based on the multi-parametric Mahalanobis distance of each PT infant relative to the FT group. Our results confirmed the presence of microstructural differences in SM tracts between PT and FT infants, with effects increasing with lower gestational age at birth. Maturational distance analyses highlighted that prematurity has a differential effect on SM tracts with higher distances and thus impact on (i) cortico-cortical than cortico-subcortical connections; (ii) projections involving S1 than M1 and paracentral region; and (iii) the most rostral cortico-subcortical tracts, involving the lenticular nucleus. These different alterations at TEA suggested that vulnerability follows a specific pattern coherent with the established WM caudo-rostral progression of maturation. Finally, we highlighted some relationships between NODDI-derived maturational distances of specific tracts and fine motor and cognitive outcomes at 18 months. As a whole, our results expand understanding of the significant impact of premature birth and early alterations on the emerging SM network even in low-risk infants, with possible relationship with neurodevelopmental outcomes. This encourages further exploration of these potential neuroimaging markers for prediction of neurodevelopmental disorders, with special interest for subtle neuromotor impairments frequently observed in preterm-born children.

Keywords: Diffusion Tensor Imaging (DTI); NODDI (neurite orientation dispersion and density imaging); brain development; diffusion MRI (dMRI); multivariate Mahalanobis distance; preterm at term-equivalent age; tractography; white matter microstructure maturation.