Abstract The past decade has experienced renewed interest in the physical processes that fold the developing cerebral cortex. Biomechanical models and experiments suggest that growth of the cortex, outpacing growth of underlying subcortical tissue (prospective white matter), is sufficient to induce folding. However, current models do not explain the well-established links between white matter organization and fold morphology, nor do they consider subcortical remodeling that occurs during the period of folding. Here we propose a framework by which cortical folding may induce subcortical fiber growth and organization. Simulations incorporating stress-induced fiber elongation indicate that subcortical stresses resulting from folding are sufficient to induce stereotyped fiber organization beneath gyri and sulci. Model predictions are supported by high-resolution ex vivo diffusion tensor imaging of the developing rhesus macaque brain. Together, results provide support for the theory of cortical growth-induced folding and indicate that mechanical feedback plays a significant role in brain connectivity.
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Mechanical hierarchy in the formation and modulation of cortical folding patterns
The important mechanical parameters and their hierarchy in the growth and folding of the human brain have not been thoroughly understood. In this study, we developed a multiscale mechanical model to investigate how the interplay between initial geometrical undulations, differential tangential growth in the cortical plate, and axonal connectivity form and regulate the folding patterns of the human brain in a hierarchical order. To do so, different growth scenarios with bilayer spherical models that features initial undulations on the cortex and uniform or heterogeneous distribution of axonal fibers in the white matter were developed, statistically analyzed, and validated by the imaging observations. The results showed that the differential tangential growth is the inducer of cortical folding, and in a hierarchal order, high-amplitude initial undulations on the surface and axonal fibers in the substrate regulate the folding patterns and determine the location of gyri and sulci. The locations with dense axonal fibers after folding settle in gyri rather than sulci. The statistical results also indicated that there is a strong correlation between the location of positive (outward) and negative (inward) initial undulations and the locations of gyri and sulci after folding, respectively. In addition, the locations of 3-hinge gyral folds are strongly correlated with the initial positive undulations and locations of dense axonal fibers. As another finding, it was revealed that there is a correlation between the density of axonal fibers and local gyrification index, which has been observed in imaging studies but not yet fundamentally explained. This study is the first step in understanding the linkage between abnormal gyrification (surface morphology) and disruption in connectivity that has been observed in some brain disorders such as Autism Spectrum Disorder. Moreover, the findings of the study directly contribute to the concept of the regularity and variability of folding patterns in individual human brains.
more » « less- NSF-PAR ID:
- 10441077
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Scientific Reports
- Volume:
- 13
- Issue:
- 1
- ISSN:
- 2045-2322
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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