Several anatomical attributes of the human corpus callosum (CC) including the midsagittal cross-sectional area, thickness, and volume, have been used to assess CC integrity. We extended our previous lifespan quantitative diffusion tensor imaging (DTI) study of the regional CC midsagittal areas to include the CC volumes obtained from DTI fiber tracking. In addition to the entire CC tracked subvolumes we normalized volume with respect to each subject’s intracranial volume (ICV) and the corresponding DTI metrics of the different specialized fiber pathways of the CC on a cohort of 99 right-handed children and adults aged 7–59 years. Results indicated that the CC absolute volume, the normalized volume fraction, and the fractional anisotropy followed inverted U-shaped curves, while the radial diffusivities followed a U-shaped curve reflecting white matter progressive and regressive myelination dynamics that continue into young adulthood. Our study provides for the first time normative baseline macro- and microstructural age trajectories of the human CC subvolumes across the lifespan that can be helpful for normative behavioral and clinical studies.

The human brain uncinate fasciculus (UF) is an important cortico-cortical white matter pathway that directly connects the frontal and temporal lobes, although there is a lack of conclusive support for its exact functional role. Using diffusion tensor tractography, we extracted the UF, calculated its volume and normalized it with respect to each subject's intracranial volume (ICV) and analyzed its corresponding DTI metrics bilaterally on a cohort of 108 right-handed children and adults aged 7-68 years. Results showed inverted U-shaped curves for fractional anisotropy (FA) with advancing age and U-shaped curves for radial and axial diffusivities reflecting white matter progressive and regressive myelination and coherence dynamics that continue into young adulthood. The mean FA values of the UF were significantly larger on the left side in children (p=0.05), adults (p=0.0012) and the entire sample (p=0.0002). The FA leftward asymmetry (Left > Right) is shown to be due to increased leftward asymmetry in the axial diffusivity (p<0.0001) and a lack of asymmetry (p>0.23) for the radial diffusivity. This is the first study to provide baseline normative macro and microstructural age trajectories of the human UF across the lifespan. Results of this study may lend themselves to better understanding of UF role in future behavioral and clinical studies.

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Deficits in working memory (WM) are a common consequence of pediatric traumatic brain injury (TBI) and are believed to contribute to difficulties in a range of cognitive and academic domains. Reduced integrity of the corpus callosum (CC) after TBI may disrupt the connectivity between bilateral frontoparietal neural networks underlying WM. In the present investigation, diffusion tensor imaging (DTI) tractography of eight callosal subregions (CC1-CC8) was examined in relation to measures of verbal and visuospatial WM in 74 children sustaining TBI and 49 typically developing comparison children. Relative to the comparison group, children with TBI demonstrated poorer visuospatial WM, but comparable verbal WM. Microstructure of the CC was significantly compromised in brain-injured children, with lower fractional anisotropy (FA) and higher axial and radial diffusivity metrics in all callosal subregions. In both groups of children, lower FA and/or higher radial diffusivity in callosal subregions connecting anterior and posterior parietal cortical regions predicted poorer verbal WM, whereas higher radial diffusivity in callosal subregions connecting anterior and posterior parietal, as well as temporal, cortical regions predicted poorer visuospatial WM. DTI metrics, especially radial diffusivity, in predictive callosal subregions accounted for significant variance in WM over and above remaining callosal subregions. Reduced microstructural integrity of the CC, particularly in subregions connecting parietal and temporal cortices, may act as a neuropathological mechanism contributing to long-term WM deficits. The future clinical use of neuroanatomical biomarkers may allow for the early identification of children at highest risk for WM deficits and earlier provision of interventions for these children.