"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," said Mathias Pessiglione, the study's author from the Pitie-Salpetriere University Hospital in Paris.
"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."
Tiring work to see how people get tired
The researchers monitored brain chemistry over the course of a work day in 40 people, 24 of whom needed to use their brain a lot while the others did not.
In the group doing hard mental work, they saw signs of fatigue, including reduced pupil dilation as well as signs that they also made low-effort decisions, indicative of being tired.
Critically, the researchers said, they also had higher levels of a chemical called glutamate in the brain's prefrontal cortex, a chemical which accumulates in the synapses between neurons, interfering with how messages are passed throughout the brain.
This, the authors said, is proof that glutamate makes further activation of this part of the brain costly, such that cognitive control is more difficult after a mentally tough work day.
Sleep the only cure to fatigue
Dr Pessiglione warned, however, that there are no shortcuts to stop your brain making you tired, with a nap the only cure.
"I would employ good old recipes: rest and sleep," he said. "There is good evidence that glutamate is eliminated from synapses during sleep."
The volunteers were given tasks interspersed with choice trials, where they were asked to pick between cash rewards – either small values given instantly, or larger values they would have to wait for.
Those subjected to difficult tasks were more likely to choose the low-effort rewards that required less waiting time to receive.
These decisions could be because the brain is trying to protect itself from toxins built up during intense cognitive effort, the experts said.
Listen to your bodies
The volunteers were also asked to score their levels of fatigue.
Interestingly, the two groups rated themselves similarly, which the researchers think could suggest people are not good at listening to their bodies.
"This dissociation is common in everyday life; for instance, when people go on working or driving and start making errors because they failed to detect their true fatigue state," the researchers wrote in the study.
The findings were published in the journal Current Biology.
