Researchers prove that thinking hard does make you tired

It's not just in your head.
Deena Theresa
  • Mental exhaustion is real.
  • Researchers found that cognitive work results in the accumulation of toxic substances.
  • Sleep can help to a small extent.

Imagine this: After a whole day of 'thinking', you're exhausted, and your productivity is hampered. But you have trouble convincing others that you're tired of thinking. Doesn't sound like a real problem, they tell you.

Guess what.

Sitting around thinking hard for hours does make one feel worn out, and researchers have new evidence to explain this.

Their studies, reported in Current Biology on August 11, reveal that when intense cognitive work is prolonged for several hours, toxic byproducts can build up in the prefrontal cortex. This alters your control over decisions, making you shift toward low-cost actions that require zero effort or waiting as cognitive fatigue sets in.

"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," Mathias Pessiglione of Pitié-Salpêtrière University in Paris, France, said in a 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."

Recycling toxic substances from neural activity

Machines can compute continuously but the brain can't.

This led Pessiglione and colleagues, including the first author of the study, Antonius Wiehler, to delve into the intricacies of mental fatigue and understand what it really is. They suspected the reason had to do with the need to recycle potentially toxic substances that arise from neural activity.

They needed evidence to prove their suspicions. For this, they used magnetic resonance spectroscopy to monitor brain chemistry throughout a workday. They looked at two groups of people for the experiment: those who needed to think hard and those who had relatively easier cognitive tasks.

Signs of fatigue, including reduced pupil dilation, were only seen in the group doing hard work. Those in that group also showed in their choices a shift toward options that proposed rewards at short delay with little effort. Critically, they also had higher levels of glutamate in synapses of the brain’s prefrontal cortex. Along with earlier evidence, the authors said it supported the notion that glutamate accumulation makes further activation of the prefrontal cortex more costly, resulting in tougher cognitive control after a mentally taxing day.

Sleep is imperative

Is there some way around this?

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

There could be practical implications. Monitoring of prefrontal metabolites could help to detect severe mental fatigue. This may help adjust work agendas to avoid burnout. He also advises people to avoid making important decisions when they’re tired.

The researchers hope to learn why the prefrontal cortex is especially susceptible to glutamate accumulation and fatigue. In future studies, they also intend to learn whether the same markers of fatigue in the brain may predict recovery from health conditions, such as depression or cancer.


Behavioral activities that require control over automatic routines typically feel effortful and result in cognitive fatigue. Beyond subjective report, cognitive fatigue has been conceived as an inflated cost of cognitive control, objectified by more impulsive decisions. However, the origins of such control cost inflation with cognitive work are heavily debated. Here, we suggest a neuro-metabolic account: the cost would relate to the necessity of recycling potentially toxic substances accumulated during cognitive control exertion. We validated this account using magnetic resonance spectroscopy (MRS) to monitor brain metabolites throughout an approximate workday, during which two groups of participants performed either high-demand or low-demand cognitive control tasks, interleaved with economic decisions. Choice-related fatigue markers were only present in the high-demand group, with a reduction of pupil dilation during decision-making and a preference shift toward short-delay and little-effort options (a low-cost bias captured using computational modeling). At the end of the day, high-demand cognitive work resulted in higher glutamate concentration and glutamate/glutamine diffusion in a cognitive control brain region (lateral prefrontal cortex [lPFC]), relative to low-demand cognitive work and to a reference brain region (primary visual cortex [V1]). Taken together with previous fMRI data, these results support a neuro-metabolic model in which glutamate accumulation triggers a regulation mechanism that makes lPFC activation more costly, explaining why cognitive control is harder to mobilize after a strenuous workday.

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