Mechanical Engineering and Materials Science, Washington University in Saint Louis, Saint Louis, MO, USA.
Engineering, University of Southern Indiana, Evansville, IN, USA.
Philos Trans R Soc Lond B Biol Sci. 2018 Sep 24;373(1759):20170321. doi: 10.1098/rstb.2017.0321.
Cortical folding, or gyrification, coincides with several important developmental processes. The folded shape of the human brain allows the cerebral cortex, the thin outer layer of neurons and their associated projections, to attain a large surface area relative to brain volume. Abnormal cortical folding has been associated with severe neurological, cognitive and behavioural disorders, such as epilepsy, autism and schizophrenia. However, despite decades of study, the mechanical forces that lead to cortical folding remain incompletely understood. Leading hypotheses have focused on the roles of (i) tangential growth of the outer cortex, (ii) spatio-temporal patterns in the birth and migration of neurons, and (iii) internal tension in axons. Recent experimental studies have illuminated not only the fundamental cellular and molecular processes underlying cortical development, but also the stress state, mechanical properties and spatio-temporal patterns of growth in the developing brain. The combination of mathematical modelling and physical measurements has allowed researchers to evaluate hypothesized mechanisms of folding, to determine whether each is consistent with physical laws. This review summarizes what physical scientists have learned from models and recent experimental observations, in the context of recent neurobiological discoveries regarding cortical development. Here, we highlight evidence of a combined mechanism, in which spatio-temporal patterns bias the locations of primary folds (i), but tangential growth of the cortical plate induces mechanical instability (ii) to propagate primary and higher-order folds.This article is part of the Theo Murphy meeting issue 'Mechanics of development'.
皮质折叠，又称脑回形成，与几个重要的发育过程同时发生。人脑的折叠形状使大脑皮层（神经元及其相关突起的薄层）相对于脑容量达到了较大的表面积。皮质折叠异常与严重的神经、认知和行为障碍有关，如癫痫、自闭症和精神分裂症。然而，尽管已经进行了几十年的研究，导致皮质折叠的机械力仍然不完全清楚。主要假说集中在以下几个方面：（i）大脑外层的切线生长；（ii）神经元的出生和迁移的时空模式；（iii）轴突内的张力。最近的实验研究不仅阐明了皮质发育的基本细胞和分子过程，还阐明了发育中大脑的应力状态、力学性质和时空生长模式。数学建模和物理测量的结合使研究人员能够评估折叠的假设机制，以确定每个机制是否符合物理定律。这篇综述总结了物理科学家从模型和最近的实验观察中了解到的情况，这些观察结果涉及到最近关于皮质发育的神经生物学发现。在这里，我们强调了一种综合机制的证据，即时空模式偏置初级褶皱的位置（i），但大脑皮层的切线生长诱导机械不稳定性（ii）来传播初级褶皱和更高阶褶皱。本文是 Theo Murphy 会议“发育力学”专题的一部分。
