CAREER: Unfolding the Cortex: Biomechanics-informed Analysis of Cortical Thickness

该奖项全部或部分由《2021年美国救援计划法案》（公法117-2）资助。这项教师早期职业发展（Career）资助将改变我们对力学在人类大脑的形式和功能中的作用的理解。我们大脑的外层，即皮层，其厚度在皱纹和褶皱中有所不同。这部分是由皮质折叠过程中产生的力决定的。由于这种折叠对皮质厚度的影响，很难对不同折叠模式的厚度进行比较。例如，子宫内发育或不同物种之间的差异。在这个项目中，PI将研究一种新的度量，消除折叠对皮质厚度的影响，称为修正皮质厚度。这项研究将促进更精确和有意义的皮质厚度的比较。这对于确定脑形态的进化、发育和病理变化是有用的。这种以力学为基础的分析将补充其他关于大脑发育和退行性疾病和紊乱的研究。因此，它有可能为早期诊断和有效治疗提供新的途径。此外，PI将开发野外生物力学项目，以培养本科生的科学素养和科学交流。与公众分享关于生物力学的激动人心的故事，促进学生对生物力学领域的兴趣将是关键的成果。为了在机械环境下分析局部皮质厚度，研究人员将开发一种确定改良皮质厚度的方法。图卷积网络将通过先进的大脑发育有限元模拟来校准，以预测大脑形态三维重建后的皮质厚度。然后，该方法将用于研究在哺乳动物进化（超过50种）和人类发育（从子宫到2年）过程中修改厚度的变化。这项工作需要对每个受试者的头部和白色表面进行三维重建，这些重建将与其他研究人员公开分享，为进一步的形态学、系统发育和发育研究开辟新的途径。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2).This Faculty Early Career Development (CAREER) grant will transform our understanding of the role of mechanics in the form and function of the human brain. The outer layer of our brains, the cortex, varies in thickness throughout its wrinkles and folds. This is partly determined by the forces generated during the process of cortical folding. Because of this effect of folding on cortical thickness, it is difficult to make comparisons of thickness across different folding patterns. For example, differences during development in the womb or between different species. In this project, the PI will investigate a new metric that removes the effect of folding on cortical thickness, called modified cortical thickness. This research will facilitate more precise and meaningful comparisons of cortical thickness. This is useful for the purposes of identifying evolutionary, developmental, and pathological changes in brain morphology. This mechanics-informed analysis will complement other research on developmental and degenerative diseases and disorders of the brain. Thus, it has the potential to lead to new pathways for early diagnosis and effective treatment. In addition, the PI will develop the Biomechanics in the Wild project to foster science literacy and science communication in undergraduate students. Sharing exciting stories about biomechanics with the public and promoting student interest in the field of biomechanics will be key outcomes.To analyze local cortical thickness in the context of the mechanical environment, the researchers will develop a method to determine the modified cortical thickness. A Graph Convolutional Network will be calibrated by advanced finite element simulations of brain development to predict modified cortical thickness from 3D reconstructions of brain morphology. Then, this method will be used to investigate how modified thickness varies throughout mammalian evolution (in over 50 species) and human development (in utero through 2 years). This work necessitates the development of 3D reconstructions of the pial and white surfaces for each subject, which will be shared publicly with other researchers, opening new avenues for further morphological, phylogenetic, and developmental studies.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.