Why Do You Tire of Thinking Too Much? An Experiment Looks for the Answer in Glutamate

    Research shows that performing complex cognitive tasks is accompanied by an accumulation of this substance, which, in excess, is neurotoxic

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    On September 10th, 1984, one of the most exciting world chess championships in history began. The 21-year-old Gari Kasparov and Anatoli Karpov, 12 years older and champion for a decade, faced each other. After an overwhelming start of four wins for the second and five boards (the championship was the best of six), the first forced 17 new boards in a row. After another victory by Karpov and four more draws, the challenger won his first game in game 32. After another series of draws, the challenger took victory in games 47 and 48.

    On February 9th, 1985, five months after the start of the championship and with a result of five to three 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 thinking a lot tires so much?

    A radical theory

    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 eye tracking 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 developed performance tests and questionnaires on the subjective level of exhaustion.

    The results of all these tests, published in the scientific journal Current Biology, 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 first 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).

    The business-minded person is always thinking of uncommon opportunities.
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    Higher levels of glutamate

    But the most definitive element for them is what they saw happening inside the head. Members of this first 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. He states: “Glutamate is the main excitatory neurotransmitter [activation of synapses] in 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”.

    Glutamate molecules (nothing to do with the food additive) 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, then, “brain activity in this region is regulated to the low to prevent further accumulation of glutamate, it is the moment when the brain says that it is tired”.

    Activation of the prefrontal cortex

    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?

    The brain´s alert system

    For other psychologists and neuroscientists, the brain’s fatigue would be an illusion generated by this organ as an alert 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.”: preserving the integrity of brain function”.

    The head of the neurology service at the University Hospital of Albacete, Tomás Segura, is studying those affected by persistent covid who report fog 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, who adds: “Glutamate, which is one of the 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 so-called neurological fatigue”.

    Just an hypothesis

    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 think tires, 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 hyperconnected with other areas of the brain.

    Why does glutamate accumulate in some areas and not in others?

    Karpov started winning 5-0 and was obsessed with making it 6-0 to cause Kasparov psychological trauma from which he would 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, 12 years younger and much stronger physically, realized that his only chance was to win byKarpov exhaustion.

    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 showed 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″, this way Campomanes prevented knowing if Kasparov, and mental fatigue, would have defeated Karpov.

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