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We Finally Know Why Thinking Too Hard Makes You Tired

Our new favorite excuse for not doing our homework: it was poisoning our brain.


Dr. Katie Spalding

Katie has a PhD in maths, specializing in the intersection of dynamical systems and number theory.

Freelance Writer

A woman face down on a pile of books.
We've all been there. Image Credit: Inara Prusakova/Shutterstock

Have you ever been tired out by an exam? Not a physical one – we all know how exhausted a long day studying can make us, even if we don’t move an inch. A new study, published today in the journal Current Biology, shows the phenomenon isn’t all in your head. Well, it is, but – oh, you know what we mean.

“Even professional chess players start making mistakes, typically after 4–5 [hours] in the game, which they would not make when well rested,” explains the paper.


“However, the reason why exerting cognitive control is exhausting remains unclear.”

To investigate, researchers used magnetic resonance spectroscopy (MRS) to monitor brain metabolites over the course of just over six hours – roughly a workday – for two groups of people: those given mentally taxing tasks to complete, and those given easier versions.

As you may expect, the first group started showing classic signs of fatigue: pupil dilation, loss of self-regulation, saying things like “I’m totally exhausted,” that kind of thing. However, the MRS showed another symptom too: higher levels of the amino acid glutamate in the prefrontal cortex.

Now, seeing glutamate in the brain is very normal – it’s the most abundant amino acid in there, and it’s involved in a wide range of chemical interactions. However, it’s also toxic to nerve cells, and the researchers think this may be what causes the tiring effect of thinking too hard.


“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, a neuroscientist and co-author of the study, 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.”

In other words, the reason flexing our brain muscles makes us so tired may be because our prefrontal cortexes are literally getting overwhelmed with toxic byproducts of all that mental effort. The more we cogitate, the more glutamate our brains need to recycle – and the more costly each complex thought becomes.

So, now we know what causes the problem, can we find some way to beat that fatigue? 


“Not really, I'm afraid,” said Pessiglione – though the researchers do recommend adjusting work schedules to avoid burnout, and avoiding making important decisions or driving while mentally drained. 

With the results from their new study, they say, this may be easier, with glutamate levels acting as a proxy for fatigue. However, the team has yet to figure out exactly why the prefrontal cortex is so susceptible to glutamate build-up, or what the link may be to certain health conditions known to cause fatigue, such as depression or cancer – those are questions for future research projects.

Other than that, for those hoping to avoid brain fatigue, “I would employ good old recipes: rest and sleep!” added Peggiglione. “There is good evidence that glutamate is eliminated from synapses during sleep.”


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