Why do you tire of thinking too much? An experiment looks for the answer in glutamate

On September 10, 1984, one of the most exciting world chess championships in history began.

The 21-year-old Garry Kasparov and Anatoli Karpov, 10 years older and champion for a decade, faced each other.

After an overwhelming start of four wins for the latter and five draws (the championship was a best of six), the former forced 17 new draws in a row, winning his first game in game 32. After another series of draws, the challenger took the victory at 47 and 48. On February 9, 1985, five months after the start of the championship and with a result of 5 to 3 for Kárpov, the president of the International Chess Federation, Florencio Campomanes, ended the tournament without a winner. in a decision that generated much controversy at the time.

Campomanes argued the decision on the mental fatigue of the players and their physical deterioration.

Then began a two-decade rivalry between the two chess players that went beyond sports.

But a question remained in the air, why think a lot tires so much?

A group of researchers from French universities now proposes an answer: mental tasks that require greater effort would generate an accumulation and extra diffusion of molecules essential for proper brain function, but which, in excess, are neurotoxic.

To avoid it, the brain would order to stop, creating that feeling of exhaustion.

The idea is, although very suggestive, only a hypothesis yet to be proven by other neuroscientists.

What the French scientists did to study why mental exercise is as exhausting as physical exercise was to recruit fifty people to perform a series of tasks for 6.5 hours (the average working day in France).

But while one group performed more complex ones (essentially remembering a greater number and combinations of uppercase and lowercase letters and in different colors that appeared on the computer screen), the demand for the other group was much lower.

During the experiment they studied the outside and inside of the brain of the participants.

Thus, they performed an eye tracking (with an

system , as it is known in English) to record the greater or lesser dilation of the pupil.

Previous research has found that eye movement stops and dilates when performing a calculation or in the final stages of making a decision.

In addition, they used a brain imaging technique (magnetic resonance spectroscopy) to measure activity in the prefrontal cortex, the so-called executive brain, and the debris it left behind.

They also conducted performance tests and questionnaires on the subjective level of exhaustion.

“Glutamate is the main excitatory neurotransmitter in the brain, involved in many regions and in its regular functioning.

What we see is an increase with demanding tasks”

Antonius Wiehler, researcher at the Paris Brain Institute

The results of all these tests, published in the scientific journal

, show clear differences between the group that had to think less and those whose mental effort was greater.

Thus, they saw signs of fatigue, including a reduction in pupil dilation, only in the second group.

They also observed that, as the working hours passed, the participants with more complex tasks ended up asking for more immediate rewards (what they were given for completing them).

But the most definitive element for them is what they saw happening inside the head.

Members of this second group have higher levels of a molecule, glutamate, in the synapses (the electrochemical connection between nerve endings) in the lateral prefrontal cortex, which is responsible for cognitive control.

Antonius Wiehler is a researcher at the Paris Brain Institute, at the Pitié-Salpêtrière University Hospital, and co-author of this study.

Glutamate is the main

[activation of synapses] of the brain, involved in many regions and in their regular functioning.

What we observe is an increase with demanding tasks: continuous work on tasks that require a high level of cognitive control leads to an increase in diffusion (spontaneous movement of molecules)”, he explains in an email.

Glutamate molecules are released in the brief space between the end of one neuron and the beginning of another, the synaptic cleft, where the exchange of information takes place, being essential in the process.

Wiehler adds that "brain activity in this region is then downregulated to prevent further accumulation of glutamate."

It is the moment when the brain says that it is tired.

For the authors of the study, the greater presence of glutamate, together with the other changes observed, would support the idea that the accumulation of this molecule makes the additional activation of the prefrontal cortex more expensive, so that cognitive control is more difficult after a hard day of mental work.

The proposal of these scientists differs from the dominant ideas about mental exhaustion, in particular from the group of theories on resource depletion.

In a simile with physical exercise and its energy consumption, its proponents maintain that cognitive control (what to do, how and when or what not to do) incurs an energy expenditure and when resources are exhausted mental fatigue would appear.

But which energy is depleted has not been shown (blood glucose has been suggested, for example).

In addition, these proposals leave even more questions: Why is playing chess tiring and why does seeing or hearing, which also require conscious brain work for processing, not exhaust it?

“Our findings show that cognitive work results in the accumulation of harmful substances”

Mathias Pessiglione, neuroscientist at the Pitié-Salpêtrière University Hospital in Paris

For other psychologists and neuroscientists, brain fatigue would be an illusion generated by this organ as a warning system, like the burning of the skin from the danger of fire.

Mathias Pessiglione, Wiehler's colleague at the Parisian university hospital and co-author of the study, comments on these positions: "Some influential theories have proposed that fatigue is a kind of illusion invented by the brain so that we stop what we are doing and spend to a more rewarding activity.

However, he adds in a note, "our findings show that cognitive work results in a true functional alteration, the accumulation of harmful substances, so fatigue would be a signal that makes us stop working, but with a different purpose." :

The head of the neurology service at the University Hospital of Albacete, Tomás Segura, is studying those affected by persistent covid who report

and mental fatigue.

“In general, fatigue as a medical term refers to the feeling of shortness of breath linked to exercise or heart failure.

That is why we say that in post-coronavirus syndrome there are many patients who have non-respiratory or cardiac fatigue.

In that sense we can call it neurological, cognitive or mental fatigue”, explains Segura.

What they have observed in these long-term patients affected by the coronavirus is a fatigue similar to that caused by intensive cognitive tasks.

“Just thinking that you have to go downstairs to buy bread, and it's not that you're out of breath to do it, but just by considering the motor act, you feel tired.

This has a lot to do with those areas of the brain where actions are planned and with the need for all glutamatergic transmission to work well for them to be activated," says Segura, adding, "glutamate, which is one of the villains indicated in the generation of brain damage in stroke, is also implicated, in this case due to its lack, in certain neurodegenerative diseases and also in the explanation of the so-called neurological fatigue”.

Javier De Felipe, from the Cajal Laboratory of Cortical Circuits of the Polytechnic University of Madrid, considers the work of his French colleagues very suggestive and timely, but believes that they go too far.

"They pose the question very well, why do you tire of thinking, but their answer is only a hypothesis," he says.

For him, they do not demonstrate the causal relationship between glutamate accumulation and mental fatigue.

“Cognitive control is focused on the prefrontal cortex, but this area is

with other areas of the brain.

Why does glutamate accumulate in some areas and not in others? ”, He raises.

Leontxo García has been El País's chess specialist since 1985, the year in which the longest series of games in history came to an end and he was present at the start of the second chapter of that story.

“Karpov started winning 5-0 and was obsessed with making it 6-0 to cause Kasparov psychological trauma from which he could never recover.

So instead of risking to win a game, even if he lost a few along the way, he played very conservatively, waiting for an error from Kasparov.

But this one, twelve years younger and much stronger physically, realized that his only trump card was to win by exhaustion of Karpov ”, he recalls.

They both had godparents in the highest echelons of the former Soviet Union.

“The godfathers of both were afraid that their man would lose;

those of Karpov,

because he gave clear signs of exhaustion;

those of Kasparov, because a single defeat was enough.

So Campomanes decided to suspend the duel without a winner and resume it eight months later with the score 0-0″, García concludes.

Campomanes prevented knowing if Kasparov, and mental fatigue, would have defeated Karpov.

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