Detailed characterization of typical human neurodevelopment is key if we are to understand the nature of mental and neurological pathology. While research on the cellular processes of neurodevelopment has made great advances, in vivo human imaging is crucial to understand our uniquely human capabilities, as well as the pathologies that affect them. Using magnetoencephalography data in the largest normative sample currently available (324 participants aged 6–45 years), we assess the developmental trajectory of resting-state oscillatory power and functional connectivity from childhood to middle age. The maturational course of power, indicative of local processing, was found to both increase and decrease in a spectrally dependent fashion. Using the strength of phase-synchrony between parcellated regions, we found significant linear and nonlinear (quadratic and logarithmic) trajectories to be characterized in a spatially heterogeneous frequency-specific manner, such as a superior frontal region with linear and nonlinear trajectories in theta and gamma band respectively. Assessment of global efficiency revealed similar significant nonlinear trajectories across all frequency bands. Our results link with the development of human cognitive abilities; they also highlight the complexity of neurodevelopment and provide quantitative parameters for replication and a robust footing from which clinical research may map pathological deviations from these typical trajectories.

IntroductionThe underlying microstructural properties of white matter differences in children born very preterm (<32 weeks gestational age) can be investigated in depth using multi-shell diffusion imaging. The present study compared white matter across the whole brain using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) metrics in children born very preterm and full-term children at six years of age. We also investigated associations between white matter microstructure with early brain injury and developmental outcomes.MethodMulti-shell diffusion imaging, T1-weighted anatomical MR images and developmental assessments were acquired in 23 children born very preterm (16 males; mean scan age: 6.57 ± 0.34 years) and 24 full-term controls (10 males, mean scan age: 6.62 ± 0.37 years). DTI metrics were obtained and neurite orientation dispersion index (ODI) and density index (NDI) were estimated using the NODDI diffusion model. FSL's tract-based spatial statistics were performed on traditional DTI metrics and NODDI metrics. Voxel-wise comparisons were performed to test between-group differences and within-group associations with developmental outcomes (intelligence and visual motor abilities) as well as early white matter injury and germinal matrix/intraventricular haemorrhage (GMH/IVH).ResultsIn comparison to term-born children, the children born very preterm exhibited lower fractional anisotropy (FA) across many white matter regions as well as higher mean diffusivity (MD), radial diffusivity (RD), and ODI. Within-group analyses of the children born very preterm revealed associations between higher FA and NDI with higher IQ and VMI. Lower ODI was found within the corona radiata in those with a history of white matter injury. Within the full-term group, associations were found between higher NDI and ODI with lower IQ.ConclusionChildren born very preterm exhibit lower FA and higher ODI than full-term children. NODDI metrics provide more biologically specific information beyond DTI metrics as well as additional information of the impact of prematurity and white matter microstructure on cognitive outcomes at six years of age.

Children born very preterm (VPT; <32 weeks gestational age [GA]) are at greater risk for a range of cognitive deficits that typically manifest at school age. Here we examine the hypothesis that these children have altered myelin maturational that can be detected by myelin sensitive MRI measures prior to school age. We included 33 four-year old children born VPT (mean GA; 28.7 weeks) and 23 four-year old full term (FT) children and completed magnetization transfer (MT), T1-weighted (T1-w) and T2-weighted (T1-w) magnetic resonance imaging as well as developmental assessments. Both MT ratio (MTR) and T1-w/T2-w ratio images were calculated, and group differences were probed using tract-based spatial statistics (TBSS) in white matter, and region of interest (ROI) analysis in white, subcortical gray and cortical gray matter. The relations between MTR and T1-w/T2-w ratio, as well as with developmental assessments, were investigated in all three brain divisions. In children born VPT, TBSS and ROI analysis revealed that both MTR and T1-w/T2-w ratio were significantly reduced in white matter compared to children born FT. ROI analysis showed reductions in T1-w/T2-w ratio in VPT children compared to FT children in the thalamus, putamen and amygdala, as well as in the occipital and temporal lobes. Across the VPT and FT children, T1-w/T2-w ratio and MTR were highly correlated across white, subcortical gray and cortical gray matter. Both measures correlated positively with developmental assessments in individual white matter tracts and cortical and subcortical ROIs, suggesting that higher MTR and T1-w/T2-w ratio is related to better cognitive performance. Together these findings are consistent with delayed myelination in VPT born children.