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The human brain is an amalgam of evolutionary growth and powerful wiring. It is also relatively little understood.

Scientists do know that highly folded brains are unique to humans (and some primates, dolphins, elephants and pigs); they know that human brains begin folding at the fetal stage, around the 20th week of gestation, and finishes around the time a child is about a year and a half old.

The basis for folded brains seems to be, from an evolutionary standpoint, twofold. First, a folded brain fits more into the space of a human head and second, folding makes the distance between two points shorter, thus quickening cognitive function.

But the way a brain folds has remained unknown.

However, researchers at Harvard John A. Paulson School of Engineering and Applied Sciences in collaboration withs scientists in Finland and France have proposed a theory that trumps other hypotheses until now.

The main reason a human brain folds is due to “simple mechanical instability associated with buckling.”

Scientists believe the discovery of how the brain folds will lead to better understanding of brain function and brain-related disorders, as function is a precursor to form.

“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,” said L. Mahadevan the Lola England de Valpine Professor of Applied Mathematics, Organismic and Evolutionary Biology, and Physics.

The research and a detailed report was published in Nature Physics.

The classification of Neuronal cells during brain growth, i.e. quantity, size, shape and position, directly affect the expansion of gray matter or cortex, in relation to white matter.

Gray matter contains neuronal cell bodies, dendrites and axon terminals—the place where synapses occur. White matter is comprised of axons that connect different parts of grey matter together.

The relationship of grey to white matter during growth puts the cortex under compression, leading to mechanical instability and causing the brain to crease.

“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,” added Mahadevan.

In conjunction with previous research into the growth difference between the brain’s outer cortex and the soft tissue underneath, Mahadevan alongside postdoctoral fellow Jun Young Chung, found that this explains variations in brain folding.

Adding onto this research, and collaborating with neuroanatomists and radiologists in France, the team tested the theory using data from human fetuses.

They developed a model that mimics the folding and shaping of human brains, using MRI images to create a three-dimensional model of a smooth fetal brain.

“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,” said Chung, remarking on the realness of the model. “It looks like a real brain.”

“The geometry of the brain is really important because it serves to orient the folds in certain directions,” said Chung. “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.”

“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.”

As far as the implications of such research on assisting those hundreds of thousands of babies already infected with the Zika virus, it is still unknown. Zika causes birth defects like microcephaly, a disorder that inhibits the fetal brain from folding, leaving babies permanently paralyzed.