(Mahadevan Lab/Harvard SEAS)

Harvard scientists have 3-D printed a replica of a human brain — but it's not for any Frankenstein-esque experiments. The researchers wanted to help puzzle out the origins of the twisty, bendy folds found in a healthy brain. Most animals don't have these wrinkles, and while most scientists are pretty sure why it happens (more folding means more surface area means more brain cells in a tiny skull), the how is still an open question.

According to the new study published in Nature Physics, the brain may fold for a very simple reason: It could just be buckling under pressure as it grows bigger in fetuses and infants.

The team tested the process of brain folding by MRI scanning and then 3-D printing the scans of the smooth brain of a fetus — catching the organ before it started folding at the 20th week of gestation. They coated the surface of the "brain" with a thin layer of gel to mimic the cerebral cortex, which forms the outermost layer (or gray matter) of the brain. Then they put it into a liquid that caused it to slowly swell, mimicking expansion of the cortex. Soon, the brain was buckling and bending to form familiar shapes, with the outer layer's swell fighting against the limited surface area provided by the "white matter" it sat on.

Surprisingly, the big folds did a great job of matching up to those seen in real infant brains. Smaller folds were more varied — which is the case in real brains, too.

“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,” postdoctoral fellow and co-first-author Jun Young Chung said in a statement. “It looks like a real brain.”

Such a simple explanation seems fitting, said Zoltan Molnar, a neuroscientist at Oxford University who wasn't involved in the study, because many branches of the animal kingdom have some species with folded brains and some without. That suggests that brain folds may have evolved more than once. If folding is really that simple, it could have arisen by chance more easily.

Brain folding abnormalities are very serious, and babies born with totally smooth brains have extremely short life expectancies. Understanding how folds occur — and what might keep them from happening — could help neuroscientists better understand these ailments.

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