The human brain is immediately recognizable by its cortex (meaning bark in Latin), the prominent outer layer of tissue, with its characteristic pattern of ridges and furrows, which sits atop the deep structures. The cortex is just several millimetres thick, but has a surface area of about two-and-a-half square feet, and is therefore heavily convoluted so it can be packed into the skull.

This fleshy landscape begins to form during the second trimester of pregnancy, and continues into the first year of life. It is often assumed to be the result of genetics, like most other aspects of brain development. Forty years ago, however, Harvard researchers put forward the controversial idea that the brain folds up because of physical forces, and a new study now provides the first evidence this.

According to this old model, the brain’s folds form as a result of differential growth which causes the cortex to grow in size far more quickly than other brain structures, leading it to buckle and fold as its surface area increases, due to the constraints of the skull.



To test this, Tuomos Tallinen of the University of Jyväskylä in Finland and his colleagues used magnetic resonance images to create a 3D-printed cast of an unfolded 22-week-old human brain. This was made with a technique called layer-by-layer drop casting, and consisted of a soft polymer core coated with a thin sheet of an absorbent elastomer gel representing the cortex.

When immersed in a liquid, the surface of the outer layer tissue swells up, leading to small compression forces that make it crease, buckle up, and fold in on itself. The process begins with the emergence of short, isolated furrows which then elongate and branch to establish a basic pattern. This is later modified with the addition of new bends, leading to rounded ridges between sharply cusped furrows that form three-way junctions and S-shaped bends.

All of this occurs as a consequence of the mechanical instability produced by constrained expansion, leading to a pattern of convolutions that is remarkably similar in appearance to that seen in the adult human brain (see video above).

3D-printed brain tissue Read more

Tallinen and his colleagues also produced a mathematical model of how their 3D-printed brains grew, and compared it with what we know about how real human brains grow. Between 22 weeks of fetal development and adulthood, the volume of real brains increases some 20-fold, from approximately 60 to 2,000 millilitres, and this is accompanied by a 30-fold increase in the surface area of the cortex.

The 3D-printed brains do not increase their volume 20-fold as fetal brains do – they only seem to model the initial folding events within idealised structures, and this, the researchers say, is the biggest limiting factor in their experiments. Nor do the experiments take into account the potential role of the skull in the folding process. Nevertheless, the study offers a novel way of studying brain development, and of investigating lissencephaly (or “smooth brain”) and other neurological conditions that cause brain malformations.

References

Tallinen, T., et al. (2016). On the growth and form of cortical convolutions. Nat. Physics, DOI: 10.1038/nphys3632 [Abstract]

Richman, D. P., et al. (1975). Mechanical Model of Brain Convolutional Development. Science, 189: 18-21 [PDF]