Large Brains Have Weaker Network Connections, May Explain Susceptibility to Mental Illness

In a study just published in the journal PLOS Biology, a research team compared the brains of primates with the smaller brains of mice. They found that larger brains have weaker neural connections, possibly explaining why mental illnesses are more common in animals with large brains.

In an earlier study, researchers from the United States, France, and Romania studied brain connections in macaque monkeys. Specifically, they studied the cortical network structure. The cerebral cortex is an important part of the brain responsible for many functions, including information processing and language. The researchers used their findings from connection trace studies and existing network theory to show that macaque brain networks follow a rule called the exponential distance rule. Also known as EDR, the exponential distance rule states that as the distance between connections increases, the strength of those connections will decrease. There are more short-range axons than long-range axons in the brain. If two cortical areas are close, there will be more connections between them and thus a stronger neural connection.

Researchers decided to compare the brain of the macaque to the brain of the mouse. Macaques have large cortexes while mice have a very small cortex. Using tracing data again, they found that the brain networks of the two species were organized in roughly the same way, even after accounting for the size difference. Both cortical networks followed the EDR. Since macaque brains are larger, they would have weaker neural connections due to distance.

Despite a significant size difference, mouse and macaque brains have the same type of cortical network structure. Both networks followed an EDR relationship, in which greater distance between neurons results in weaker connections. Since humans have brains five times as large as macaque monkeys, the researchers speculate that human brains have many weak long-range connections. This could explain why humans are so susceptible to mental illnesses such as schizophrenia and Alzheimer disease. Both illnesses are disconnection syndromes, caused when connection pathways become damaged or weakened. By studying the organization and functions of the cortical network, we can better understand these types of diseases.


Horvát S, Gamanut R, Ercsey-Ravasz M, Magrou L, Gamanut B, Van Essen DC, et al. Spatial Embedding and Wiring Cost Constrain the Functional Layout of the Cortical Network of Rodents and Primates. PLOS Biology (2016).

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