3D Printing Reveals the Hidden Physics Behind the Brain's Folds and Furrows

Michael Byrne

Understanding how the brain's outermost layer develops means new understandings of intelligence, neurological disorders.

The outermost layer of the brain, the cortex, is a confounding geography of furrows, folds, and wrinkles. One could even say that the defining physical feature of the brain is the presence of these folds, which serve to increase the surface area of the brain and thereby increase its population of cortical neurons. This has a direct link to intelligence: memory, attention, awareness, thought, etc. More cortical neurons, more intelligence.

How these folds came to be, however, has been an ongoing neuroscience mystery. Much research has been dedicated to studying the genetic and cellular mechanisms behind cortical growth, but increasing attention has been given to mathematical and physical models. One well-publicized study from last summer, for example, found that cortical development follows a simple mathematical function: "A power function derived from the product of cortical surface area and the square root of cortical thickness," according to Scientific American.

A study out this week in Nature Physics again investigates cortical development as a physical process—in other words, a process that can be explained by the rules of physics rather than biology. The researchers behind the work, an international team based at Harvard University and Finland's University of Jyväskylä, used 3D printed materials to simulate the brain in its formative stages, finding that as their simulated cortices grew, they experienced compression forces due to the differing rates of growth among layers of the brain.

Not only does this insight help settle an old argument about how the brain's folds—and the associated intelligence—come to be, but it could offer clues into the mechanisms behind neurological disorders.

The technical name for the cortical folding process is gyrification. All mammal brains begin smooth and it's usually during fetal development that gyri (the peaks of cortical folds) and sulci (the troughs) begin to form. For most mammals, the process continues into postnatal life.

"[Gyrification] has evolved as an efficient way of packing a large cortex into a relatively small skull with natural advantages for information processing," the study explains. "Thus, although the functional rationale for gyrification is clear, the physiological mechanism behind gyrification has been unclear." Proposed mechanisms include "biochemical prepatterning" of the cortex (where folding is the result of some chemistry built into the original smooth cortex) and a theorized process by which neurons in the white matter regions of the brain below the cortex add just the right amount of tension in the right places to induce folding as the brain develops.

Evidence supporting either of these hypotheses is scant, however.

"At present, the most likely hypothesis is also the simplest one: tangential expansion of the cortical layer relative to sublayers generates compressive stress, leading to the mechanical folding of the cortex," the authors note. "This mechanical folding model produces realistic sizes and shapes of gyral and sulcal patterns that are presumably modulated by brain geometry, but the hypothesis has not been tested before with real three-dimensional (3D) fetal brain geometries in a developmental setting."

This is where the 3D printing comes in. The physical model demonstrated by the group used various printed gels that expand at different rates when put in some liquid solution. This swelling acts as a simulation of real-world brain growth and so it became possible to watch the gyrification process unfold (heh) without needing to, you know, crack open the skulls of very young children.

"This swelling relative to the interior puts the outer layers of the gel into compression, yielding surface folding patterns qualitatively similar to sulci and gyri," the researchers write. The group's physical observations were further supported by a corresponding mathematical model.

It's hoped that new understandings of cortical development will help us to better understand neurodevelopment and neurodevelopmental disorders. Gyrification is implicated in schizophrenia, autism, and severe disorders of neuronal migration, to name a few. It's at least interesting to consider that the cause of some neurological diseases may have their roots in physics, rather than biology.