Atypical Formation of Fiber Pathways and Cortical Folding in the Brain

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Abstract Emerging brain pathways and morphology are linked in typical and atypical brain development, and such changes can be 3-dimensionally imaged by MRI with our technique. The development of cortical convolutions, gyri and sulci, is a complex process that typically takes place during prenatal development. Despite numerous theories, neurogenic processes that cause the appearance of gyri/sulci and its relationships to underlying fiber pathways remain unknown. Lissencephaly (LIS), a rare neurological condition characterized by the lack of cortical convolutions, offers a great model to look into the biological processes that lead to the development of gyri and sulci. On the other hand, agenesis of the corpus callosum (AgCC) is another neurological disorder that is characterized by a partial or complete absence (agenesis) of the corpus callosum which connects the two cerebral hemispheres. These two developmental neurological disorders are great models to study spatiotemporal links between atypical formation of fibers and gyri/sulci, because LIS has obvious gyral malformations but their relationships to underlying fiber pathways are still elusive, while AgCC has obvious abnormal fiber pathways but their relationships to gyral structures are still elusive. Through our recent investigations, we observed that both LIS patients and AgCC patients had significantly smaller gyrification index (GI) compared to age/sex-matched controls. In addition, in patients with LIS, spatiotemporal distribution of projection pathways was preserved but short- to medium-length cortico-cortical association pathways were absent or few in number, while patients with AgCC had significantly smaller cortical surface area compared to controls. These observations are in line with suggested relationships between fiber pathways and cortical folding/surface morphology. However, more details of fiber/gyral development in these and other developmental disorders are still elusive. In this R01, built on a previous R03, we will utilize our technique to study detailed links of fiber pathways and gyral formation in LIS and AgCC ranging from newborn to young adult stages.