Development of neonatal brain functional centrality and alterations associated with preterm birth

Abstract

Formation of the functional connectome in early life underpins future learning and behaviour. However, our understanding of how the functional organisation of brain regions into interconnected hubs (centrality) matures in the early postnatal period is limited, especially in response to factors associated with adverse neurodevelopmental outcomes such as preterm birth. We characterised voxel-wise functional centrality (weighted degree) in 366 neonates from the Developing Human Connectome Project. We tested the hypothesis that functional centrality matures with age at scan in term-born babies and is disrupted by preterm birth. Finally, we asked whether neonatal functional centrality predicts general neurodevelopmental outcomes at 18 months. We report an age-related increase in functional centrality predominantly within visual regions and decrease within motor and auditory regions in term-born infants. Preterm-born infants scanned at term equivalent age had higher functional centrality predominantly within visual regions and lower measures in motor regions. Functional centrality was not related to outcome at 18 months old. Thus, preterm birth appears to affect functional centrality in regions undergoing substantial development during the perinatal period. Our work raises the question of whether these alterations are adaptive or disruptive, and whether they predict neurodevelopmental characteristics that are more subtle or emerge later in life.

Longitudinal neonatal brain development and socio-demographic correlates of infant outcomes following preterm birth

“…Research in term-born neonates using this metric has found the most connected ("hub") regions in infancy to be in motor and primary sensory cortices (Fransson et al, 2011). While strength and heterogeneity of functional connectivity increases with age in most networks during infancy (Cao et al, 2017), recent work in predominantly term-born neonates of the dHCP cohort has highlighted that sensorimotor cortex shows a decrease in relative degree centrality with increasing postmenstrual age (Fenn-Moltu et al, 2022). This may reflect a normative fine-tuning in the regional specificity of sensorimotor connectivity with increasing exposure to the surrounding environment, consistent with the emergence of functional specialisation of network connectivity in this period (Cao et al, 2017).…”

“…In order to derive voxelwise degree centrality maps (Fenn-Moltu et al, 2022), the timeseries from each voxel within the cortical grey matter mask (in template space) were extracted and a correlation matrix constructed from pairwise Pearson correlations between each pair of voxels. Correlations below 0.20 were excluded in order to avoid including spurious connections likely caused by noise.…”

Parsing brain-behavior heterogeneity in very preterm born children using integrated similarity networks

“…Resting-state functional MRI (rs-fMRI) data were pre-processed as in our previous work ( 50 ); for more details see Supplemental Information. Functional connectivity was evaluated using a measure of weighted degree centrality at the voxel-level (i.e., the sum of the correlations between the time-series of each voxel and all other voxels within a grey matter mask of the brain) ( 51,52 ). Edges with a correlation coefficient below a threshold of 0.2 were excluded and the degree centrality values for each voxel in the grey matter mask were z-scored and used in subsequent between-subgroup analyses.…”