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

The sensorimotor (SM) network is crucial for optimal neurodevelopment. However, undergoing rapid maturation during the perinatal period, it is particularly vulnerable to preterm birth. Our work explores the prematurity impact on the microstructure and maturation of primary SM white matter (WM) tracts at term-equivalent age (TEA) and evaluates the relationships between these alterations and neurodevelopmental outcome. We analyzed diffusion MRI data from the developing Human Connectome Project (dHCP) database: 59 preterm (PT) low-risk infants scanned near TEA, compared to a control group of full-term (FT) neonates paired for age at MRI and sex. We dissected pairwise connections between primary SM cortices and subcortical structures using probabilistic tractography and evaluated their microstructure with diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) models. In addition to tract- specific univariate analyses of diffusion metrics, we computed a maturational distance related to prematurity based on a multi-parametric Mahalanobis distance of each PT infant relative to the FT group. Finally, we evaluated the relationships between this distance and Bayley Scales of Infant and Toddler Development (BSID-III) scaled scores at 18 months corrected age. Our results confirm important microstructural differences in SM tracts between PT and FT infants, with effects increasing with lower gestational age at birth. Additionally, comparisons of maturational distances highlight that prematurity has a differential effect on SM tracts which follows the established WM caudo-rostral developmental pattern. Our results suggest a particular vulnerability of projections involving the primary sensorimotor cortices (S1) and of the most rostral tracts, with cortico-cortical and S1-Lenticular tracts presenting the highest alterations at TEA. Finally, NODDI-derived maturational distances of specific tracts seem related to fine motor and cognitive scores. This study expands the understanding of the impact of early WM alterations in the emerging SM network on long-term neurodevelopment. In the future, related approaches have potential to lead to the development of neuroimaging markers for neurodevelopmental disorders, with special interest for subtle neuromotor impairments frequently observed in preterm-born children. ### Competing Interest Statement The authors have declared no competing interest. * AD : Axial diffusivity BG : basal ganglia BSID-III : Bayley Scales of Infant and toddler Development, 3rd edition Bstem : brainstem Caud : caudate nucleus CLD : chronic lung disease CSF : cerebrospinal fluid CST : corticospinal tract cUS : cranial ultrasonography dHCP : Developing Human Connectome Project dMRI : Diffusion-weighted MRI DTI : Diffusion tensor imaging FA : Fractional anisotropy FDR : False Discovery Rate FT : full-term born infants [ FT EVCt : ‘ extreme to very preterms’ matched FT controls, FT MLCt : ‘ moderate to late preterms’ matched FT controls] GA : gestational age GM : gray matter IMD : Index of multiple deprivation IUGR : intrauterine growth restriction Lenti : lentiform nucleus M1 : lateral portion of the primary motor cortex (precentral region) mCA : months of corrected age MD : Mean diffusivity MRI : magnetic resonance imaging NDI : Neurite Density Index NEC : Necrotizing enterocolitis NICU : neonatal intensive care unit NODDI : Neurite Orientation Dispersion and Density Imaging ODI : Orientation Dispersion Index ParaC : medial portions of the primary sensori-motor cortices (paracentral region) PMA : post-menstrual age PT : preterm infants [ PT EV : extreme to very preterms, PT ML : moderate to late preterms] RD : Radial diffusivity ROIs : regions of interest ROP : Retinopathy of prematurity S1 : lateral portion of the primary somatosensory cortex (postcentral region) SES : Socio-Economic Status Thal : thalamus TEA : term- equivalent age wGA : weeks of GA WM : white matter