The abundance of crevices and ridges in the outer layer of the human brain – commonly referred to as “folds” – make the organ instantly recognizable. Theory holds that the folding brain is a result of evolution, a way to condense the cerebral cortex and improve brain cell communication and functioning. Now, researchers have shed light on how folding occurs in the human brain and how it changes with age.

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Researchers find that the cerebral cortex loses tension as we age, and this change is even more pronounced in patients with Alzheimer’s disease.

The cerebral cortex is a critical part of the human brain. Composed of folded gray matter, the cerebral cortex is responsible for higher-level functions, such as consciousness, language, intelligence, and memory.

Only a handful of species – including humans, cats, dogs, and dolphins – have folds in the cerebral cortex.

Previous research has suggested that the way in which these folds arise follows a universal law across species, meaning that they all fold in the same way, irrespective of the shape and size of the cortex.

“However, it was yet to be determined whether this law also applies to the morphological diversity of different individuals in a single species, in particular with respect to factors, such as age, sex, and disease,” note the study authors, led by Dr. Yujiang Wang of Newcastle University in the United Kingdom.

To find out whether folding of the cerebral cortex is universal in humans, Dr. Wang and team used magnetic resonance imaging (MRI) to map the brain folds of more than 1,000 healthy adults.

The results – published in the Proceedings of the National Academy of Sciences – revealed that cortical brain folding in humans does follow a “simple universal law.”

However, the team found that as we age, cortical folding changes. Specifically, the researchers found that tension on the inside of the cerebral cortex reduces.

“It would be similar to the skin,” explains Dr. Wang. “As we age, the tension drops and the skin starts to slacken.”

The researchers also identified gender differences in cortical folding; among men and women of the same age, the cerebral cortex of women showed slightly less folding.

On assessing cortical folding in the brains of patients with Alzheimer’s disease, the team found that these patients showed more pronounced, earlier changes in cortical tension and folding than healthy adults.

Additionally, the mechanism by which cortical folding changes in patients with Alzheimer’s disease differed to that of healthy men and women.

“More work is needed in this area but it does suggest that the effect Alzheimer’s disease has on the folding of the brain is akin to premature aging of the cortex,” says Dr. Wang. “The next step will be to see if there is a way to use the changes in folding as an early indicator of disease.”

Overall, the researchers believe their study has provided some much-needed insight into the factors that influence cortical folding in the human brain.

“It has long been known that the size and thickness of the cortex changes with age but the existence of a general law for folding shows us how to combine these quantities into a single measure of folding that can then be compared between genders, age groups, and disease states.”

Dr. Yujiang Wang

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