Feeling burnt out? Scientists now know what's going on inside your brain when this happens

"Potentially toxic by-products of neural activity accumulate in the prefrontal cortex," one researcher says

By Matthew Rozsa

Staff Writer

Published August 17, 2022 5:55PM (EDT)

A young woman sits at her desk and takes notes. She has her head in her hand in concentration. (Getty Images/FatCamera)
A young woman sits at her desk and takes notes. She has her head in her hand in concentration. (Getty Images/FatCamera)

Feeling burned out, mentally exhausted, or brain-fried are all colloquial ways of talking about what neurologists formally refer to as "cognitive fatigue." It's a common feeling that nearly all of us suffer at some point, and can arise from such quotidian things as taking an all-day exam or just being overworked at a mentally taxing job

Now, a new study suggests that there is actually something physically happening inside the brain that leads to cognitive fatigue. Indeed, the scientists behind a new paper in the journal Current Biology have shed some light on what is actually going on inside our heads. And it doesn't sound pleasant: "potentially toxic by-products" can build up in one's brain when one is cognitively fatigued. 

"We find some evidence in the direction that when intense cognitive work is prolonged for several hours, some potentially toxic by-products of neural activity accumulate in the prefrontal cortex," Dr. Antonius Wiehler, a professor at the Paris Brain Institute and one of the paper's corresponding authors, told Salon by email. Wiehler noted that the study provides evidence for this, they haven't "definitively proven" what is happening just yet.

The prefrontal cortex constitutes lobes near the front of the brain. If you look at someone's eyes and gaze up, the prefrontal cortex would be the blood-rich gray matter right behind their forehead. It is responsible for a number of cognitive functions including prospective memory, focus and impulse inhibition. Many neurotransmitters are used in this section of the brain — including glutamate, which plays a significant role in memory and learning.

That build-up of glutamate can be a bad thing for your brain because, if it has to focus on regulating glutamate, the brain then has less control over decision-making.

Yet glutamate can build up in one's brain, for reasons ranging from traumatic stress to physical illness — and often for reasons that remain mysterious. That build-up of glutamate can be a bad thing for your brain because, if it has to focus on regulating glutamate, the brain then has less control over decision-making. Glutamate build-up is directly linked to preferring low-effort actions with short-term rewards.

"This alters the control over decisions, which are shifted towards low-cost actions (no effort, no wait), as cognitive fatigue emerges (note that we are talking mental exhaustion here, not drowsiness)," Wiehler explained.

If you have ever experienced cognitive fatigue, the symptoms are likely familiar. Depression feels inevitable. The mere thought of exertion is exhausting. You struggle to pay attention. Often your limbs feel heavy, as if they are being held down by weights. Your heart may feel like it's sinking inside your chest. Even the inside of your head can seem out of sorts, like the gears inside just aren't able to work properly.

The Current Biology paper is not the first one in recent years to examine cognitive fatigue from a physical as well as psychological perspective. In 2020, a systematic review study published in the journal Psychophysiology linked cognitive fatigue to elevated electroencephalographic (EEG) activity. Electroencephalographs are tests that measure electrical activity in your brain by attaching electrodes to your scalp.

Similarly, a systematic review of medical literature as of 2017 and published in the journal Sports Medicine found that people who are mentally exhausted have lower endurance. Moreover, the study emphasized that cognitive fatigue has a harsher effect on one's ability to work when the physical task is likewise more challenging.


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"The duration and intensity of the physical task appear to be important factors in the decrease in physical performance due to mental fatigue," the authors explained. "The most important factor responsible for the negative impact of mental fatigue on endurance performance is a higher perceived exertion."

The new Current Biology study, while revelatory, does not paint the whole picture of what happens inside the brain when we feel cognitive fatigue. For that answer, more research will be needed.

If your brain has to focus on regulating glutamate, you have less control over your decision-making.

"It's very good to start looking into this aspect," behavioral neuroscientist Carmen Sandi at the Swiss Federal Institute of Technology in Lausanne told Nature Magazine. "But for now this is an observation, which is a correlation."

Wiehler himself acknowledged to Nature that more research is needed.

"It would be great to find out more about how glutamate levels are restored," Wiehler explained. "Is sleep helpful? How long do breaks need to be to have a positive effect?"

Yet while it's easy to tell people to cool off when they're at risk of overexerting themselves physically, is there any advice that applies when their cognitive fatigue is solely due to cognitive work? Does the research in the latest paper lend itself to advice which the authors of the latest study would have for, say, a college student who is cramming for an exam?

"Not really, I'm afraid," Wiehler told Salon. "I would employ good old recipes: rest and sleep. There is good evidence that glutamate is eliminated from synapses during sleep."

Wiehler added this piece of advice: "Check that you're not too tired before making important decisions!"


By Matthew Rozsa

Matthew Rozsa is a staff writer at Salon. He received a Master's Degree in History from Rutgers-Newark in 2012 and was awarded a science journalism fellowship from the Metcalf Institute in 2022.

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