Psychology: Scientists say too much glutamate is the reason hard thinking makes you tired | Science & Technology

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A children’s chess tournament.Hans Nelemann (Getty Images)

On September 10, 1984, one of the most exciting World Chess Championships in history began. The competition faced 21-year-old challenger Garry Kasparov and Anatoly Karpov, 12 years older and world champion for the last ten years. After four wins for Karpov and five draws, Kasparov bounced back and forced 17 straight draws. Karpov won another match and needed just one more to win the championship, but Kasparov forced another four draws and finally beat Karpov in game 32 for his first win. After another series of draws, the challenger won games 47 and 48. Five months later, the President of the International Chess Federation, Florencio Campomanes, ended the tournament without a winner when the score remained 5-3. It was a controversial decision, which Campomanes justified by citing the mental exhaustion and physical deterioration of the players. This marked the beginning of a 20-year rivalry between the two players that went beyond the game of chess. But the question remained – why does hard thinking make you tired?

A team of French researchers think they have found the answer – tasks that require high levels of mental effort produce extra amounts of molecules that are essential for good brain function but can be neurotoxic in high concentrations. Our brain helps us avoid this by creating a feeling of exhaustion that makes us stop what we are doing. This intriguing hypothesis has not yet been confirmed by other neuroscientists and research.

To investigate why mental training can be just as tiring as physical training, the French scientists had 50 people perform a series of tasks for 6.5 hours (the average working day in France). One group was asked to perform more complex tasks than the other while the researchers examined their brains.

An eye movement tracking system was used to record pupil dilation. Other studies have found that when the brain is performing a calculation or in the final stages of decision-making, the eyes stop moving and the pupils dilate. In addition, they used a brain imaging technique (magnetic resonance spectroscopy) to measure activity in the prefrontal cortex, where executive brain functions take place, and to identify the residuals generated by this activity. They also developed performance tests and questionnaires to subjectively measure burnout levels.

“Glutamate is the main excitatory neurotransmitter in the brain; it is found in many parts of the brain and is necessary for normal brain function. We have found that it increases while performing demanding mental tasks.”

Antonius Wiehler, ICM Paris Brain Institute (France)

The study, recently published in Current Biology, found marked differences between the two groups (high-demand cognitive control tasks versus low-demand tasks). Only in the high-demand group did they observe signs of fatigue, including less dilation of the pupils. Over time, the high-demand group began to demand more immediate rewards for completing tasks. But the most compelling evidence was what they saw in the subjects’ brains. Those in the high-demand group had higher levels of a molecule — glutamate — in the synapses (the electrochemical connection between nerve endings) in the lateral prefrontal cortex, the brain region responsible for cognitive control.

Antonius Wiehler, a researcher at the ICM Paris Brain Institute and co-author of the study, told EL PAÍS: “Glutamate is the main pathogen [synapse activation] neurotransmitters in the brain; it is found in many parts of the brain and is necessary for normal brain function. We found that it increases while performing demanding mental tasks.” Glutamate molecules, not to be confused with monosodium glutamate (a food additive), are released in the synaptic cleft (the short space between the end of one neuron and the beginning of another), where the exchange of information takes place. Then, says Wiehler, “…brain activity in that region is downregulated to avoid further accumulation of glutamate.” That’s when the brain says it’s tired.

The study results suggest that the observed physical changes and the increased levels of glutamate make each additional activation of the prefrontal cortex more expensive, making cognitive control more difficult after a hard day of mental work.

The conclusions of these French scientists differ from the prevailing theories of mental exhaustion, especially the exhaustion theories. Using the analogy of energy expenditure during physical activity, they claim that cognitive control (what, how, when to do or not do something) requires energy expenditure and mental fatigue sets in when energy resources are depleted. But their study does not identify the specific energy resources depleted by cognitive control, although blood glucose has been suggested. Questions abound – why isn’t playing chess and seeing or hearing, which also require conscious brain work, tiring?

“Our results show that cognitive work leads to the accumulation of pollutants.”

Mathias Pessiglione, Pitié-Salpêtrière University Hospital in Paris (France)

Some psychologists and neuroscientists believe that mental fatigue is an illusion created by the brain that acts as a warning system, just as the feeling of burning skin is an illusion that warns of the danger of a fire. Mathias Pessiglione, a neuroscientist at the Pitié-Salpêtrière University Hospital in Paris (France) and co-author of the study, disagrees, saying: “Some influential theories have suggested that fatigue is a kind of illusion created by the brain to trick us into thinking that to stop what we’re doing and move on to a more rewarding activity…but our findings show that cognitive work leads to a real functional change—the accumulation of harmful substances. Fatigue is indeed a signal that makes us stop working, but it has another purpose – to maintain the integrity of brain function.”

Tomás Segura is Head of Neurology at Albacete University Hospital (Eastern Spain) and examines patients with post-Covid conditions such as mental fog and fatigue. “In general, fatigue, as a medical term, refers to the feeling of shortness of breath associated with exercise or heart failure,” Segura said. “As a result, many patients are diagnosed with non-respiratory, non-cardiac fatigue. In this sense we can call it neurological, cognitive or mental exhaustion.” A similar mental exhaustion as caused by intense cognitive tasks has been observed in a number of patients suffering from post-Covid illnesses.

“Let’s say you have to buy bread and just thinking about moving your body for it makes you tired. Shortness of breath doesn’t cause that feeling,” says Segura. “This has a lot to do with the brain regions where action is planned and the need for glutamatergic transmission to work well for the action to take place. When there is insufficient glutamate, one of the causes of brain damage in stroke victims, it can lead to certain neurodegenerative diseases and also produce what is known as neurological fatigue.”

Javier De Felipe, who heads the Cajal Cortical Circuits Laboratory at the Polytechnic University of Madrid (Spain), finds the French study very interesting and timely, but believes its conclusions went too far. “Why hard thinking causes fatigue is an excellent question, but its conclusion is only a hypothesis,” De Felipe said. He believes the study failed to establish a causal link between glutamate levels and mental fatigue. “Cognitive control is centered in the prefrontal cortex, but this area is over-connected to other regions of the brain. Why does glutamate accumulate in some areas and not others?” he asks.

Leontxo García has been the chess specialist of EL PAÍS since 1985, the year in which the longest series of chess games in history ended, and was present at the second round of this epic championship. García recalls that “In the 1984 championship, Karpov immediately won five games in a row and became obsessed with winning the championship 6-0 so that Kasparov was crushed by a psychological trauma from which he never recovered. Instead of making risky moves to win, Karpov started playing very conservatively, waiting for Kasparov to make mistakes. But the younger and physically stronger Kasparov realized he had to wear Karpov down.” Both players had sponsorships at the highest levels in the former Soviet Union. “The sponsors were both afraid that their man would lose because Karpov was showing signs of exhaustion and Kasparov was one game away from defeat. So Campomanes decided to sit out the championship and resumed it eight months later with the score set back to 0-0.” This is how Campomanes prevented us at the 1984 World Chess Championship from finding out whether Kasparov and his mental exhaustion could have finally defeated Karpov .

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