The Origami Of The Brain’s Enigmatic Fold

The Folded Landscape Of The Brain

The human brain comprises approximately eighty-six trillion nerve cells, along with a similar number of supporting cells. The neural tube forms during early fetal development, with preliminary structures emerging in the first weeks of pregnancy, which later develop into various parts of the mature brain and spinal cord. During later developmental stages, some of the stem cells differentiate into nerve cells, growing, sending out extensions, and even migrating. During this stage the brain assumes its typical heavily folded appearance. These folds optimize the surface-to-volume ratio, similar to other systems in the body like the colon, allowing for efficient cell compression in a small volume while maintaining access to oxygen and nutrients from the bloodstream.

Not all mammals exhibit a folded brain structure. For instance, mice, commonly used in research, have completely smooth brains, which does not seem to impair their brain function. However, the absence of expected folds in species that typically have many folds can lead to severe functional impairments. Smooth Brain Syndrome is a condition that occasionally occurs in humans, resulting in a brain that develops without folds. This syndrome is caused by mutations in genes responsible for nerve cell migration, among other functions. Infants with Smooth Brain Syndrome suffer from intellectual disabilities, epilepsy, significant developmental difficulties, and a shortened life span. Brain folds begin forming during fetal development, with initial folds forming early in fetal tissue formation, and most folds developing during the third trimester. While the folds in the brain's right and left hemispheres are usually symmetrical, the symmetry is not complete.  

The mature brain of most adults exhibits a consistent appearance with similar structures and folds. Researchers have mapped these brain folds and assigned them names, allowing neuroscientists to describe specific areas in individuals and enabling researchers worldwide to precisely identify and study these regions in other brains. Protruding ridges between folds are called Gyri (singular - Gyrus), while the depressions or gaps between two folds are called Sulci (singular - Sulcus).

Not Found In Everyone

Yet, not all brains share the exact same structure. One notable difference is a particular sulcus found in only thirty to sixty percent of the population. Known as the Paracingulate Sulcus, this fold is part of the anterior cingulate cortex. It develops in the later stages of development and can form asymmetrically, often found predominantly in the left hemisphere.   

While initially believed to be unique to humans, studies investigating its prevalence in other animals have shown that the Paracingulate Sulcus also exists in members of the great apes family, including chimpanzees, gorillas, and orangutans. Similar to humans, this fold is found only in a portion of these species' populations. Notably, the fold does not appear to exist in monkeys and other non-great ape animals.

Managerial Fold

In humans, the presence of this brain fold is believed to be linked to cognitive abilities. Research indicates that individuals with this fold in the left hemisphere performed better in tasks testing managerial functions, such as speech fluency, spatial perception, and working memory. The researchers hypothesize that this fold enables more effective connectivity between the anterior cingulate cortex and the prefrontal cortex - an area crucial for complex cognitive processes, such as planning, decision-making, and abstract thinking. However, the study was conducted on a small number of subjects and further research is required to confirm these findings.

Other studies have also found a connection between this fold and cognitive and emotional traits. For example, a study conducted in teenagers found a link between a symmetrical fold and feelings of interpersonal closeness. 

The Link Between The Fold And Dementia

In a recent study, researchers examined 186 patients who developed frontotemporal dementia without a known genetic background for the disease. They found that patients with a paracingulate sulcus in their right hemisphere were diagnosed with the disease, on average, two years later in life compared to those without this anatomical feature, indicating delayed symptom onset.

The researchers also analyzed additional factors such as the overall volume of brain tissue and years of education of the patients but found no other variables that correlated with the delayed diagnosis.

However, having such a fold in the right hemisphere may not necessarily be advantageous. The study revealed that while individuals with the fold experienced later symptom onset, their average age of death was nearly identical to that of those without the fold. This suggests that life expectancy following diagnosis was shorter for people with this fold in their right hemisphere. 

Is It The Fold, Or Adjacent Tissues?

The studies discussed suggest a correlation between this unique fold and various aspects of the human nervous system, including cognitive abilities, emotional traits, and the onset timing of certain types of dementia.  However, these studies still leave a crucial question unanswered: What is the underlying cause of this link? In other words, why does the presence or absence of the fold impact all of these qualities?

It's plausible that the fold itself may not be directly responsible, but rather the structural changes it induces in adjacent tissues by its presence. Areas near the Paracingulate sulcus, involved in emotional processing, decision-making, and inter-area communication within the brain, could potentially be influenced by structural differences in their vicinity due to the fold’s presence.

Further research is necessary to elucidate how the presence of the fold in either hemisphere affects the aforementioned qualities. A better understanding of this fold is not only intrinsically valuable,  but could also pave the way for insights into frontotemporal dementia and the development of more effective strategies to delay the disease.