Overthinking can increase levels of toxic substances

Science is still far from being able to say that “working hard mentally causes a toxic build-up of glutamate in the brain. (Photo: Reproduction)

You have probably found yourself in this situation. Left on the sofa, after a long and tiring day at work, during which he had to “think too much”. You don’t want to focus on anything else, you’re dating the delivery app or aimlessly browsing social media. But why? In a study published in the scientific journal Current Biology, French researchers suggest that this is linked to “the need to recycle potentially toxic substances accumulated during the exercise of cognitive control”. The substance in question is glutamate, the main excitatory neurotransmitter in the brain, which plays an important role in learning and memory.

According to research, the substance accumulates under “stressful conditions” or “with increasing task demands”. “The problem with very high concentrations of extracellular (outside the cell) glutamate is not only the disruption of the excitation/inhibition balance, but also the induction of activation bursts, which can alter the transmission of information and cause excitotoxicity (which can lead to death or nerve damage) in the most severe cases,” they write.

The study’s lead author, Antonius Weihler, a psychiatrist at GHU Paris Psychiatry and Neurosciences, told Science magazine that science is still far from being able to say that “working hard mentally causes a toxic buildup of glutamate in the brain.” In another scientific publication, Nature, he explained that he wanted to use the results to learn how to recover from mental exhaustion. “Does sleep help? How long do breaks need to last to have a positive effect? »


To test this metabolic hypothesis of cognitive fatigue, the scientists analyzed 40 people divided into two groups, performing cognitive tasks for about six hours. Some performed more complex activities and others performed tasks that were considered simpler.

After blocks of activity, participants had to make four economic choices, associated with monetary rewards. They were used for fatigue analysis. Indeed, the highest values ​​were associated with high effort demands – thinking or doing physical exercise, for example – and a longer time to receive it – delaying its reception.

While making these choices, the scientists analyzed glutamate levels in the lateral prefrontal cortex using MRI. The region of the brain is involved in decision making and emotional regulation – it is one of the last regions of the brain to develop and has significant maturation in adolescence. They also performed eye tracking to observe pupil dilation, which they say “has already been validated as an index of cognitive effort.”

The researchers found that the group that performed more complex tasks had “high levels” of glutamate in the lateral prefrontal cortex and reduced pupil dilation when making economic choices. Unlike those who did simpler activities, who preferred immediate reward options that required less effort, even if in the long run they represented less payoff. According to them, the results reproduce and extend research which has shown that exercising “intense cognitive control”, in intellectual work or endurance sport, induces a form of cognitive fatigue which “is manifested by a greater preference for immediate options”.


But the study has limitations. “Our results are only correlational and cannot be taken as evidence that what limits cognitive control effort is the need to prevent glutamate accumulation,” they warn. In addition, there are technical limitations: the scanners used do not allow the presence of other substances to be quantified.