A variety of hypotheses on how the brain folds have been proposed but none have been directly used to make testable predictions. Now, a group of scientists led by Harvard University researcher L. Mahadevan has shown that while many molecular processes are important in determining cellular events, what ultimately causes the brain to fold is a mechanical instability associated with buckling.
Gel model of a fetal brain after being immersed in liquid solvent, the resulting compression led to the formation of folds similar in size and shape to real brains. Image credit: Tuomas Tallinen et al.
The rapid growth of the human cortex during development is accompanied by the folding of the brain into a highly convoluted structure.
Several previous studies have focused on “the genetic and cellular regulation of cortical growth, but understanding the formation of the gyral and sulcal convolutions also requires consideration of the geometry and physical shaping of the growing brain.”
To study this, Prof. Mahadevan and his colleagues from the United States, France, and Finland made a 3D gel model of a smooth fetal brain based on MRI images.
“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 fetal brains,” explained Prof. Mahadevan, senior author of a paper published Monday in the journal Nature Physics.
The surface of the team’s model was coated with a thin layer of elastomer gel, as an analog 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. The extent of the similarities surprised even the scientists.
“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. It looks like a real brain,” said co-author Dr. Jun Young Chung, also from Harvard University.
The key to those similarities lies in the unique shape of the human brain.
“The geometry of the brain is really important because it serves to orient the folds in certain directions. 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 fetal brains quite well,” Dr. Chung said.
The largest folds seen in the model gel brain are similar in shape, size and orientation to what is seen in the fetal 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,” Dr. Chung said.
“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 dysfunction in the brain.”
_____
Tuomas Tallinen et al. On the growth and form of cortical convolutions. Nature Physics, published online February 1, 2016; doi: 10.1038/nphys3632
