Scientists have cracked how the human brain's walnut-like appearance develops with the use of 3D printing. The brain's wrinkled, interfolding look is nature's way of fitting a large, powerful processor inside a tiny space - the skull.

As the fetal brain grows, the weak spots in the cerebral cortex, which is the brain's outer layer, buckle and bend. This creates the "folded" parts that give the brain its signature look.

In the first 20 weeks, the fetal brain starts off smooth. Then it begins folding, which continues until the newborn is around 18 months old. More neurons are packed closely together, enabling the connections to become shorter and faster.

Harvard University's Lakshminarayanan Mahadevan said the folded cortex is about three times larger than a smooth brain.

"The number, size, shape and position of neuronal cells during brain growth all lead to the expansion of the gray matter, known as the cortex, relative to the underlying white matter," says Mahadevan who is the study's co-author.

The expansion compresses the cortex and leads to mechanical instability. This causes the expansive but thin cortex to crease or fold as it secures the weak spots. The result is a tightly packed cortex that can fit inside the skull. The process was likened to a thin sheet of flat paper that is crumpled tightly together in order to fit into a small space.

The group of researchers from Europe and the U.S. 3D printed an MRI scan of smooth fetal brains to create a gel model. The smooth top was coated with a layer of elastomer gel which represents the thin cortex.

The 3D gel model was immersed in a solvent that was absorbed by the cortex. This simulates the fetal brain growth as the cortex began to swell in specific deep areas. And then, the walnut-like appearance of a real human brain starts to take shape.

The team noted that other animals have brain folds including dolphins, elephants, chimpanzees and pigs. However, the human brain has the most wrinkles. The findings were published in the journal Nature Physics on Monday.

Ellen Kuhl from the Department of Bioengineering at Stanford University, said the findings could lead to breakthroughs in the diagnosis, treatment and prevention of many neurological disorders. For instance, over- or under-folding of the brain's cortex can lead to motor dysfunction, seizures, developmental delay or mental handicap. Kuhl was not involved in the Harvard study.

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