Foetal brains begin to fold around the midpoint of the third trimester, but little is known about the actual process. A new model, in which a hunk of gel was made to swell in a liquid bath, shows how it happens in surprisingly accurate detail.
Very few animals have brains that feature these troughs and crests, a select group that includes humans, some primates, dolphins, elephants and pigs. In humans, the process starts around the 20th week of gestation and typically ends when an infant is about a year and a half.
The reason for the folding is that our big bulbous brains likely had to evolve this capacity in order to fit inside our skulls, while also reducing wiring length and boosting cognitive function. Neuroscientists have some basic ideas about how the brain folds, but none have actually lived up to empirical scrutiny. A new study published in Nature Physics by researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences corrects this limitation.
The final gel model of a foetal brain after being immersed in solvent. Via Mahadevan Lab/Harvard SEAS
To get a better handle on cortical convolutions, as they’re called, a team led by biophysicists Julien Lefèvre and Lakshminarayanan Mahadevan used brain scans to build a 3D-printed layered gel model of the developing, smooth, foetal brain. To mimic the cortex, a thin layer of elastomer gel was coated on the model. By immersing it in a solvent, the researchers were able to replicate cortical growth and the tell-tale “constrained expansion”. In just a matter of minutes, the experiment yielded a brain that looked remarkably human-like.
“When I put the model into the solvent, I knew there should be folding but I never expected that kind of close pattern compared to human brain,” noted study co-author Jun Young Chung in a Harvard news release. “It looks like a real brain.”
The researchers also created a computer simulation of the folding brain, and it pretty much worked the same way.
A similar process likely happens in the foetal brain. As the cortex grows, it comes under increasing pressure. The resulting compression leads to a mechanical instability that causes the iconic creases. “This simple evolutionary innovation, with iterations and variations, allows for the thin but expansive cortex to be packed into a small volume, and is the dominant cause behind brain folding, known as gyrification,” said Mahadevan.
In addition to shedding new light on foetal brain development, this line of research could explain the causes of certain brain disorders.
“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. “Our research shows that if a part of the brain does not grow properly, or if the global geometry is disrupted, we may not have the major folds in the right place, which may cause potential dysfunction.”
Top image: Mahadevan Lab/Harvard SEAS