The cortical thickness is a characteristic biomarker for a wide variety of neurological disorders. While the structural organization of the cerebral cortex is tightly regulated and evolutionarily preserved, its thickness varies widely between 1.5 and 4.5 mm across the healthy adult human brain. It remains unclear whether these thickness variations are a cause or consequence of cortical development. Recent studies suggest that cortical thickness variations are primarily a result of genetic effects. Previous studies showed that a simple homogeneous bilayered system with a growing layer on an elastic substrate undergoes a unique symmetry breaking into a spatially heterogeneous system with discrete gyri and sulci. Here, we expand on that work to explore the evolution of cortical thickness variations over time to support our finding that cortical pattern formation and thickness variations can be explained – at least in part – by the physical forces that emerge during cortical folding. Strikingly, as growth progresses, the developing gyri universally thicken and the sulci thin, even in the complete absence of regional information. Using magnetic resonance images, we demonstrate that these naturally emerging thickness variations agree with the cortical folding pattern in n = 9 healthy adult human brains, in n = 564 healthy human brains ages 7–64, and in n = 73 infant brains scanned at birth, and at ages one and two. Additionally, we show that cortical organoids develop similar patterns throughout their growth. Our results suggest that genetic, geometric, and physical events during brain development are closely interrelated. Understanding regional and temporal variations in cortical thickness can provide insight into the evolution and causative factors of neurological disorders, inform the diagnosis of neurological conditions, and assess the efficacy of treatment options.

皮质厚度是多种神经系统疾病的特征性生物标志物。虽然大脑皮层的结构组织受到严格调控并在进化上得以保留，但健康成人大脑的厚度在 1.5 至 4.5 毫米之间变化很大。目前尚不清楚这些厚度变化是皮质发育的原因还是结果。最近的研究表明，皮质厚度的变化主要是遗传效应的结果。先前的研究表明，在弹性基底上具有生长层的简单均匀双层系统会经历独特的对称性，从而打破具有离散回旋和脑沟的空间异质系统。这里，我们扩展了这项工作，以探索皮质厚度随时间变化的演变，以支持我们的发现，即皮质模式形成和厚度变化可以（至少部分）由皮质折叠过程中出现的物理力来解释。引人注目的是，随着生长的进行，发育中的脑回普遍变厚而脑沟变薄，即使在完全没有区域信息的情况下也是如此。使用磁共振图像，我们证明这些自然出现的厚度变化与皮层折叠模式一致n = 9 个健康成人大脑，n = 564 个年龄在 7-64 岁之间的健康人类大脑，以及n = 73 个在出生时、1 岁和 2 岁时扫描的婴儿大脑。此外，我们表明皮质类器官在整个生长过程中会形成相似的模式。我们的研究结果表明，大脑发育过程中的遗传、几何和物理事件密切相关。了解皮质厚度的区域和时间变化可以深入了解神经系统疾病的演变和致病因素，为神经系统疾病的诊断提供信息，并评估治疗方案的疗效。