Physics of brain wrinkles copied in a jar

Scientists have reproduced the wrinkled shape of a human brain using a simple gel model with two layers.

They made a solid replica of a foetal brain, still smooth and unfolded, and coated it with a second layer which expanded when dunked into a solvent.

That expansion produced a network of furrows that was remarkably similar to the pattern seen in a real human brain.

This suggests that brain folds are caused by physics: the outer part grows faster than the rest, and crumples.

Such straightforward, mechanical buckling is one of several proposed explanations for the distinctive twists and turns of the brain's outermost blanket of cells, called the "cortex".

Alternatively, researchers have suggested that biochemical signals might trigger expansion and contraction in particular parts of the sheet, or that the folds arise because of stronger connections between specific areas.

"There have been several hypotheses, but the challenge has been that they are difficult to test experimentally," said Tuomas Tallinen, a soft matter physicist at the University of Jyväskylä in Finland and a co-author of the study, which appears in Nature Physics.

"I think it's very significant... that we can actually recreate the folding process using this quite simple, physical model."

The gel model started out smooth, like the brain of a 22-week-old foetus, and ended up with a pattern of folds similar to that of a brain at 34 weeks

Humans are one of just a few animals - among them whales, pigs and some other primates - that possess these iconic undulations. In other creatures, and early in development, the cortex is smooth.

The replica in the study was based on an MRI brain scan from a 22-week-old foetus - the stage just before folds usually appear.

A 3D printout of that scan was used to make a mould, which in turn was filled with a silicon-based gel to make the "gel brain".

Finally, a 1mm-thick layer of slightly different gel was added to the surface - to play the role of the cortex.

Distinctive grooves

When placed in a glass jar full of an organic solvent for 20-30 minutes, this outer layer swelled up and contorted itself into a very familiar shape.

"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 co-author Jun Young Chung from Harvard University, US.

"It looks like a real brain."

Specifically, the shape and direction of the gel brain's major grooves were an excellent match to those found in a typical 34-week-old human brain.

Surprisingly like the real thing: The finished, folded "gel brain"

The team also created a computer simulation of the process.

Starting with the same shape as the replica foetus brain, split into its two simple layers, this mathematical model allowed them to follow the expansion process much further - until the simulated brain reached adulthood.

"In real brains there's something like a 20-fold increase in cortical area during development," Dr Tallinen told the BBC. "We can't create that in physical model - but in the numerical model we can. And we can also use more realistic parameters."

The experiments were a continuation of previous research by the same team, in which they stuck an expanding layer onto a simple spherical shape and calculated the stiffness and depth of "cortex" that produced wrinkles of a brain-appropriate size.

"In this paper we use real brain geometries, and we reproduce a developmental setting," Dr Tallinen explained. "We can study how brain geometry affects folding and creates the kind of arrangements of folds that we see in human brains."

Using a computer simulation, the team to extend the model into adulthood

As for whether these findings clinch the argument for brain folding being a purely mechanical process, Dr Tallinen was circumspect.

"The things that we saw in our model will inevitably happen in real brains as well, just as a consequence of this simple expansion. But there could be some other biological factors that modulate this process."

Abnormal folding

Zoltan Molnar, a neuroscientist at Oxford University who studies cortical development, said this was an impressive study that reconciled different ideas about how the brain folds, using a simple model.

"It's an excellent start - and it's almost alarming how similar it looks!" he told BBC News.

The simplicity of the mechanical mechanism is appealing, Prof Molnar explained, because it helps explain why "almost every branch" of the evolutionary tree has some species with brain folds, and some without.

"It has to be quite simple, because evolution is not going to keep inventing things twice. This way, you can see why it's so common."

The work also holds promise, he added, for studying diseases in which the brain fails to fold in the usual way.

"If they could recreate [a disorder] by changing some of the parameters... that would really help us to understand some of these folding abnormalities."

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