Why Thinking Makes You Tired
Mental exhaustion apparently leaves its mark on brain metabolism
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We’ve all been there: Your mind is cluttered, your concentration is waning, and your motivation to tackle complicated tasks is dwindling. After prolonged mental exertion, our brain signals that we need a break. But can this fatigue following mental exertion be explained solely in psychological terms—or do certain neurochemical or biological processes in the brain also change, causing us to run out of mental energy?
Until now, it has been a matter of debate whether there is a biological basis for fatigue following mental exertion. Psychological theories assume that we feel increasingly exhausted when further effort demands more from us than we expect to gain from it. Our willingness to continue working then declines, and we prefer to turn to easier or more pleasant tasks.
Motivation, the Prefrontal Cortex, and Glutamate
Neurobiological theories, on the other hand, suggest a link between brain activity, changes in certain neurotransmitters, and fatigue. For example, a study by the Paris Brain Institute provided evidence that prolonged mental exertion alters glutamate concentrations in the prefrontal cortex (Wiehler A. et al. 2022, Current Biology, DOI 10.1016/j.cub.2022.07.010).
Among other things, the prefrontal cortex is responsible for directing attention, storing information in working memory, and planning actions. It is particularly challenged during demanding mental tasks. Glutamate is one of the most important neurotransmitters in the brain. It enables neurons to transmit signals and plays a central role in attention, learning, and thinking. For signal transmission to function reliably, glutamate levels must be precisely regulated.
Brain Stimulation as an Experimental Approach
Prof. Dr. Alexander Soutschek, Professor of Neuroscience of Decision-Making at the Clinic and Polyclinic for Psychiatry, Psychosomatics, and Psychotherapy at the University Hospital of Würzburg (UKW), and his team wanted to get to the bottom of this and took a causal approach. Is activity in the prefrontal cortex actually the cause of mental fatigue, and can increased fatigue be explained by a rise in glutamate concentration?
To investigate this question, the researchers specifically intervened in the activity of the prefrontal cortex. As part of the study, 31 healthy participants were given a challenging, 20-minute memory task. While they were performing the task, some of them underwent stimulating transcranial brain stimulation over the dorsolateral prefrontal cortex (DLPFC), while the others received a sham treatment. Afterward, the participants were able to choose between challenging tasks with higher rewards and easier tasks with lower rewards. This allowed researchers to measure their motivational fatigue based on their behavior.
The results revealed a striking trade-off: Although the stimulated participants performed better during the mental task, they felt more exhausted afterward. Consequently, their motivation to invest further mental effort declined. “This means that improving our mental performance comes at a price. We are even more exhausted after the increased effort,” reports Hongmei Xia, a doctoral candidate in the Department of Psychology at Ludwig Maximilian University of Munich (LMU). There, Alexander Soutschek led an Emmy Noether Group for neurocognitive psychology until he moved to the UKW in March 2026. The study is the subject of Hongmei Xia’s doctoral dissertation.
Glutamate Changes and Motivational Fatigue
What about glutamate concentrations? Measurements using magnetic resonance spectroscopy (MRS) before and after the cognitive tasks showed that the stimulating intervention increased the concentration of glutamate and glutamatergic metabolites in the prefrontal cortex compared to the control group. Finally, statistical analyses suggested that the increase in glutamate concentration significantly contributed to the study participants feeling less willing to continue exerting themselves after the stimulation. An additional control experiment revealed that this effect occurred primarily during prolonged mental effort, but not during a task that required little concentration.
“Our study challenges purely psychological explanations for why sustained mental work is perceived as exhausting and shows that mental fatigue is related not only to motivational evaluations but also to neurobiological limitations. Glutamate, along with other metabolic byproducts, appears to play a role in this process. Fatigue is therefore not simply a matter of willpower,” says Alexander Soutschek, summarizing the findings. These findings have now been published in the journal *Proceedings of the National Academy of Sciences of the United States of America* (PNAS).
Implications for Future Research on Fatigue
Changes in glutamate metabolism could help us better understand in the future why mental effort leads to fatigue and which neurobiological processes play a role in this. This is not only of interest to people in demanding work environments. People with attention-deficit/hyperactivity disorder (ADHD) also frequently report that they become exhausted quickly after mental exertion. In addition, there are conditions such as depression, schizophrenia, or chronic fatigue syndrome (ME/CFS) that are associated with persistent fatigue. In the long term, a more precise understanding of the biological causes of pathological fatigue could contribute to the development of new treatment approaches.
Prof. Dr. Sebastian Walther, Director of the Department of Psychiatry, Psychosomatics, and Psychotherapy at UKW, summarizes: “This important study helps us understand how metabolic changes in the brain are related to mental exhaustion and exertion. The findings are groundbreaking for the treatment of many mental illnesses. Targeted brain stimulation techniques will likely be able to help those affected in the future.”
Note: This article has been translated using a computer system without human intervention. LUMITOS offers these automatic translations to present a wider range of current news. Since this article has been translated with automatic translation, it is possible that it contains errors in vocabulary, syntax or grammar. The original article in German can be found here.
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