Background: The brains white matter undergoes profound changes during early childhood, which are believed to underlie the rapid development of cognitive and behavioral skills during this period. Neurite density, and complexity of axonal projections, have been shown to change across the life span, though changes during early childhood are poorly characterized. Here, we utilize neurite orientation dispersion and density imaging (NODDI) to investigate maturational changes in tract-wise neurite density index (NDI) and orientation dispersion index (ODI) during early childhood. Additionally, we assess hemispheric asymmetry of tract-wise NDI and ODI values, and longitudinal changes. Methods: Two sets of diffusion weighted images (DWI) with different diffusion-weighting were collected from 125 typically developing children scanned at baseline (N=125; age range=4.14-7.29; F/M=73/52), 6-month (N=8; F/M=8/0), and 12-month (N=52; F/M=39/13) timepoints. NODDI and template-based tractography using constrained spherical deconvolution were utilized to calculate NDI and ODI values for major white matter tracts. Mixed-effects models controlling for sex, handedness, and in-scanner head motion were utilized to assess developmental changes in tract-wise NDI and ODI. Paired t-tests were used to assess interhemispheric differences in tract-wise NDI and ODI values and longitudinal changes in cross-sectional and 12-month longitudinal analyses, respectively. Results: Maturational increases in NDI were seen in all major white matter tracts, though we did not observe the expected tract-wise pattern of maturational rates (e.g. fast commissural/projection and slow frontal/temporal tract change). ODI did not change significantly with age in any tract. We observed higher cross-sectional NDI and ODI values in the right as compared to the left hemisphere for most tracts, but no hemispheric asymmetry for longitudinal changes. Conclusions: These findings suggest that neurite density, but not orientation dispersion, increases with age during early childhood. In relation to NDI growth trends reported in infancy and late-childhood, our results suggest that early childhood may be a transitional period for neurite density maturation wherein commissural/projection fibers are approaching maturity, maturation in long range association fibers is increasing, and changes in limbic/frontal fibers remain modest. Rightward asymmetry in NDI and ODI values, but not longitudinal changes, suggests that rightward asymmetry of neurite density and orientation dispersion is established prior to age 4.

Maturation and interhemispheric asymmetry in neurite density and orientation dispersion in early childhood