Mechanics of the Formation of Cortical Folding Patterns in the Developing Human Brain

这个项目旨在了解人类大脑在早期胎儿发育阶段的生长和折叠机制。这项工作将促进对大脑折叠、大脑连通性和大脑功能之间关系的基本理解。大脑折叠提供了有关人脑正常和异常发育的重要信息。目前，折叠的开发是基于简单的模拟模型，不能反映人脑的复杂结构。这项研究将使用先进的大脑成像和创新的计算模拟来阐明人类大脑在正常胎儿大脑早期发育期间是如何生长和折叠的。这项工作的结果将描述正常大脑发育过程中的折叠。未来的研究可能会揭示具有结构差异和连接中断的大脑疾病的起源，如自闭症和精神分裂症。这项研究成果将促进健康科学的进步，造福于国民健康。除了科学成果，这项研究还将被整合到一系列教育和推广计划中，旨在吸引代表不足的群体进入工程学，改善生物力学和机械生物学的本科生和研究生学习。这项研究的首要目标是发现不同的切线生长和神经连接在发育中的人脑的形态发生中的作用，以及它们对折叠图案的变异性和规律性的贡献。这项研究将有助于深入理解在发育中的人脑在全面的人脑尺度上形成第二和第三折叠模式的潜在机制。这项研究将使用一种创新的基于图像的多尺度建模方法来模拟大脑发育，将组织和器官水平上的力学与轴突纤维束在细胞水平上的影响联系起来。这项研究的结果有望从根本上推动脑折叠机制领域的发展，并为研究脑障碍患者的异常脑折叠过程奠定基础。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

This project aims to understand the mechanics of growth and folding of the human brain at the early fetal stages of development. This work will advance the fundamental understanding of the relationship between brain folding, brain connectivity, and brain function. Brain folding provides important information about both normal and abnormal development of the human brain. Currently, the development of folds is based on simple simulation models that do not reflect the complicated structure of the human brain. This research will use advanced brain imaging and innovative computational simulations to elucidate how the human brain grows and folds during the early development of a normal fetal brain. The results of this work will characterize folding in normal brain development. Future studies may reveal the origin of brain disorders that have structural discrepancies and connectivity disruptions such as autism and schizophrenia. The outcome of this research will promote the progress of health science and benefit national health. In addition to the scientific outcomes, this research will be integrated into a range of educational and outreach programs aimed at attracting underrepresented groups to engineering, improving undergraduate and graduate learning on biomechanics and mechanobiology. The overarching objective of this research is to discover the roles of differential tangential growth and neural wiring on the morphogenesis of the developing human brain, and their contributions to the variability and regularity of folding patterns. The research will contribute an in-depth understanding of the underlying mechanism that forms the secondary and tertiary folding patterns in the developing human brain on a comprehensive human brain scale. This research will use an innovative image-based multiscale modeling approach to the simulation of brain development, linking the mechanics at the tissue and organ level with the effect of axonal fiber bundles on the cellular level. The outcomes of this study are expected to fundamentally advance the field of brain folding mechanics and lay a foundation for investigating abnormal brain folding processes for brain disorders.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.