• Posted August 12, 2022

Your Brain Gets Tired, and Scientists Now Know Why

Preparing your taxes is a purely mental activity, but one that leaves many exhausted by the end of the effort.

The same goes for reading a dense report, picking apart reams of spreadsheet data, or writing a fact-laden paper.

That feeling of exhaustion following a bout of intense thinking isn't all in your head, a new study argues.

Lab experiments show that work requiring a lot of thought can cause potentially toxic byproducts to build up in a part of the brain called the prefrontal cortex, French researchers reported Aug. 11 in the journal Current Biology.

This, in turn, alters your control over decisions, making you more apt to choose easier or quicker options as your brain grows weary, researchers argue. The prefrontal cortex is the part of the brain where people work out conflicting thoughts and perform high-level decision-making.

"Influential theories suggested that fatigue is a sort of illusion cooked up by the brain to make us stop whatever we are doing and turn to a more gratifying activity," senior researcher Mathias Pessiglione, of Pitié-Salpêtrière University in Paris, said in a written statement.

"But our findings show that cognitive work results in a true functional alteration -- accumulation of noxious substances -- so fatigue would indeed be a signal that makes us stop working but for a different purpose: to preserve the integrity of brain functioning," he added.

For this experiment, Pessiglione and his team recruited two sets of people and put both to work for a little more than six hours.

One group of 24 people was given a mentally strenuous task in which letters were displayed on a computer every 1.6 seconds, and they had to compare the letters to ones that had appeared before in various ways. Another group of 16 was asked to perform a similar but easier task.

While participants worked, researchers used scanning technology called magnetic resonance spectrometry to measure levels of glutamate that had built up in the prefrontal cortex of their brains.

Glutamate is a neurotransmitter that plays a major role in learning and memory, according to the Cleveland Clinic. It's needed in proper concentrations in the right places for your brain to function properly, but too much glutamate can cause neurons to become overexcited and lead to brain cell damage or death.

Researchers found that people given more difficult mental tasks did indeed have higher levels of glutamate build up in their prefrontal cortex. Those participants also showed other signs of fatigue, including reduced pupil dilation.

Both groups also were regularly given a financial choice, as a measure of whether their ongoing brain work had affected their decision-making ability. They could choose between a lesser but easier cash reward, or a larger cash reward that would require more effort or patience.

People in the group given more demanding brain activities started to shift their economic choices toward day's end, more often choosing the easier options proposing rewards at short delay with little effort.

This experiment has set up a reasonable alternative explanation for brain fatigue, said Dr. Donn Dexter, a fellow of the American Academy of Neurology and a neurologist at the Mayo Clinic in Eau Claire, Wis.

Most experts would tend to point to energy depletion as the reason for mental fatigue, he said.

"The brain demands glucose all the time, but there's a pretty good supply of it so that doesn't really make good sense on the face of it," Dexter said. "Building up toxic byproducts that interfere with performance could make sense."

If that were the case, it would explain why sleep -- even a short nap -- refreshes the brain, he said. There's evidence that our brains use sleep as a chance to flush away toxins that have built up during the day.

However, Dexter thought that the financial decisions weren't a very good marker of how weary a brain had become.

"I would be cautious about applying the findings more widely," Dexter said. "I'd like to see this replicated in another study."

Dr. Thomas Wisniewski, director of NYU Langone's Center for Cognitive Neurology in New York City, shared Dexter's concerns about the study's design.

Wisniewski said that both the MRS measure of glutamate levels and the measures of brain fatigue were "quite indirect."

"Certainly what they are saying is plausible, but it's a correlation. There's no causation evidence here," Wisniewski said. "Although what they're saying is possible, this is by no means proof that it is true."

More information

The Cleveland Clinic has more on glutamate.

SOURCES: Donn Dexter, MD, neurologist, Mayo Clinic, Eau Claire, Wis., and fellow, American Academy of Neurology, Minneapolis; Thomas Wisniewski, MD, director, NYU Langone Center for Cognitive Neurology, New York City; Current Biology, Aug. 11, 2022