Convergence of Cortical, Thalamocortical, and Callosal Pathways during Human Fetal Development Revealed by Diffusion MRI Tractography

There has been evidence that during brain development, emerging thalamocortical (TC) and corticothalamic (CT) pathways converge in some brain regions and follow each other's trajectories to their final destinations. Corpus callosal (CC) pathways also emerge at a similar developmental stage, and are known to converge with TC pathways in specific cortical regions in mature brains. Given the functional relationships between TC and CC pathways, anatomical convergence of the two pathways are likely important for their functional integration. However, it is unknown (1) where TC and CT subcortically converge in the human brain, and (2) where TC and CC converge in the cortex of the human brain, due to the limitations of non-invasive methods. The goals of this study were to describe the spatio-temporal relationships in the development of the TC/CT and CC pathways in the human brain, using high-angular resolution diffusion MR imaging (HARDI) tractography. Emerging cortical, TC and CC pathways were identified in postmortem fetal brains ranging from 17 gestational weeks (GW) to 30 GW, as well as in vivo 34-40 GW newborns. Some pathways from the thalami were found to be converged with pathways from the cerebral cortex as early as 17 GW. Such convergence was observed mainly in anterior and middle regions of the brain until 21 GW. At 22 GW and onwards, posterior pathways from the thalami also converged with cortical pathways. Many CC pathways reached the full length up to the cortical surface as early as 17 GW, while pathways linked to thalami (not only TC axons but also including pathways linked to thalamic neuronal migration) reached the cortical surface at and after 20 GW. These results suggest that CC pathways developed earlier than the TC pathways. The two pathways were widespread at early stages, but by 40 GW they condensed and formed groups of pathways that projected to specific regions of the cortex and overlapped in some brain regions. These results suggest that HARDI tractography has the potential to identify developing TC/CT and CC pathways with the timing and location of their convergence in fetal stages persisting in postnatal development.