Axonal Tension as a Driver of Cortical Fold Placement and Compact Wiring

This project investigates how physical forces, specifically axonal tension or the pulling forces exerted by nerve fibers, shape the complex folded structure of the human brain. Understanding the mechanisms behind cortical folding is crucial because brain structure and function are closely related in neurological health and diseases. The primary hypothesis is that axonal tension helps determine the placement of cortical folds and ensures that the axonal connections of the brain are as efficient as possible. By developing advanced computational models, the research aims to test these hypotheses and understand better how axonal tension contributes to brain development. This study will advance our understanding of brain morphology, offering insights into conditions such as Autism Spectrum Disorder (ASD) that are associated with abnormal brain connectivity and folding. Additionally, the project will result in valuable computational tools and data for research into other complex biological tissues that contain fibers, and will provide training opportunities in interdisciplinary research at the intersection of mechanics, biology, neuroscience, and computation. The project aims to rigorously evaluate the axonal tension hypothesis by first developing a novel computational model of white matter, incorporating realistic axon orientations and densities (Aim 1). This model will then be used to analyze the impact of varying levels of axonal tension on the consistent placement of cortical folds (Aim 2) and on the global efficiency of white matter connectivity (Aim 3). The research will employ advanced finite element simulations to compare axonal tension with other known factors influencing cortical folding, such as thickness, stiffness, and growth. The expected outcomes include a quantitative understanding of how different perturbations affect fold placement and connectivity, contributing significantly to the field of brain development. This work could validate the axonal tension hypothesis and its role in cortical folding, offering new perspectives on neurological disorders associated with altered connectivity. 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.