The development of the human brain remains one of the few unsolved mysteries of science. Recent advancements in developmental biology, neuroscience, behavior science, and medical imaging have brought us closer than ever to understand the mechanisms of brain development in health and disease. However, the precise role of mechanics throughout this process remains underappreciated and poorly understood. Here we show that mechanical stretch plays a crucial role in brain development. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we model the human brain as a living system with a morphogenetically growing outer surface and a stretch-driven growing inner core. This approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. We calibrate our model using magnetic resonance images from very preterm neonates. Our model predicts that deviations in cortical growth and thickness induce morphological abnormalities. Using the gyrification index, the ratio between the total and exposed surface area, we demonstrate that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. Understanding the mechanisms of cortical folding during brain development might have direct implications in the diagnostics and treatment of neurological disorders, including severe retardation, epilepsy, schizophrenia, and autism.

The development of the human brain remains one of the few unsolved mysteries of science. Recent advancements in developmental biology, neuroscience, behavior science, and medical imaging have brought us closer than ever to understand the mechanisms of brain development in health and disease. However, the precise role of mechanics throughout this process remains underappreciated and poorly understood. Here we show that mechanical stretch plays a crucial role in brain development. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we model the human brain as a living system with a morphogenetically growing outer surface and a stretch-driven growing inner core. This approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. We calibrate our model using magnetic resonance images from very preterm neonates. Our model predicts that deviations in cortical growth and thickness induce morphological abnormalities. Using the gyrification index, the ratio between the total and exposed surface area, we demonstrate that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. Understanding the mechanisms of cortical folding during brain development might have direct implications in the diagnostics and treatment of neurological disorders, including severe retardation, epilepsy, schizophrenia, and autism.