Abstract
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.
Highlights
Thalamocortical/corticothalamic (TC/CT) and corpus callosal (CC) pathways are major white matter tracts in the brain which are conserved across species throughout evolution, and partake in fundamental brain functions
Throughout development, TC pathways grew toward the cortex and cortical pathways descended toward the center of the brain
A majority of the pathways linked to the thalami were terminated around the lower edge of the cortical pathways located within the cortical plate (CP) until 22 gestational weeks (GW), with only a few pathways penetrating into the CP, while such long penetrating pathways were found more in number at and after 30 GW, and by term, these pathways were found at the upper edge of the cerebral cortex
Summary
Thalamocortical/corticothalamic (TC/CT) and corpus callosal (CC) pathways are major white matter tracts in the brain which are conserved across species throughout evolution, and partake in fundamental brain functions. The TC axons go through a number of steps in order to reach their final destinations (Rakic, 1975, 1988), following a distinct pathway stemming from the thalamus and reaching into the cerebral cortex (LópezBendito and Molnar, 2003; Garel and Rubenstein, 2004). Around the second and third gestational weeks (GW) in humans, the neocortex and thalamus start to link with each other through specific and reciprocal connections (Leyva-Díaz and López-Bendito, 2013), and continue increasing the number of connections between them. It is still under debate how human TC pathways find a way to go through brain regions to project to the cortex
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