3D model replicates how human brain folds

Scientists, including one of Indian-origin, have created a 3D gel model of the human brain that replicates how the distinctive folds of the organ form in the foetus.

Understanding how the brain folds could help unlock the inner workings of the brain and unravel brain-related disorders, as function often follows form, researchers said.

In humans, folding begins in foetal brains around the 20th week of gestation and is completed only when the child is about a year and a half.

Folded brains likely evolved to fit a large cortex into a small volume with the benefit of reducing neuronal wiring length and improving cognitive function.

How the brain folds is less understood. Several hypotheses have been proposed but none have been directly used to make testable predictions.

Researchers at the Harvard University in US collaborating with scientists in Finland and France have shown that while many molecular processes are important in determining cellular events, what ultimately causes the brain to fold is a simple mechanical instability associated with buckling.

They made a 3D gel model of a smooth foetal brain based on magnetic resonance imaging (MRI) images. The model's surface was coated with a thin layer of elastomer gel, as an analogue of the cortex.

To mimic cortical expansion, the gel brain was immersed in a solvent that is absorbed by the outer layer causing it to swell relative to the deeper regions.

Within minutes of being immersed in liquid solvent, the resulting compression led to the formation of folds similar in size and shape to real brains.

"Our model, which has the same large scale geometry and curvature as a human brain, leads to the formation of folds that matches those seen in real foetal brains quite well," said Jun Young Chung, a post doctoral fellow at Harvard.

"We found that we could mimic cortical folding using a very simple physical principle and get results qualitatively similar to what we see in real foetal brains," said L Mahadevan, professor at Harvard University.

The number, size, shape and position of neuronal cells during brain growth all lead to the expansion of the grey matter, known as the cortex, relative to the underlying white matter.

This puts the cortex under compression, leading to a mechanical instability that causes it to crease locally.

The largest folds seen in the model gel brain are similar in shape, size and orientation to what is seen in the foetal brain, and can be replicated in multiple gel experiments.

The smallest folds are not conserved, mirroring similar variations across human brains.
"Brains are not exactly the same from one human to another, but we should all have the same major folds in order to be healthy," said Chung.

The research was published in the journal Nature Physics.