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Techniques & Tools Spectroscopy

Losing (Cognitive) Control

Mental fatigue has long puzzled scientists. Why do we feel it? What generates it? These questions nagged researchers from Pitié-Salpêtrière University in Paris, France, as they contemplated why machines can do cognitive tasks continuously without fatigue but the brain cannot. They hypothesized that fatigue arises from an increase in the cost of exerting cognitive control – which stems from glutamate accumulation in the brain (1).

To test this theory, two groups of participants executed either high- or low-demand cognitive tasks, interlaced with economic decisions, while researchers measured the levels of metabolites in their brains. The researchers found that, when intense cognitive work is prolonged for several hours, some potentially toxic byproducts of neural activity, such as glutamate, accumulate in the prefrontal cortex. “This alters the control over decisions, which are shifted towards low-cost actions (no effort, no wait) as cognitive fatigue emerges,” explains Antonius Wiehler, co-author of the paper. Other signs of fatigue in the group performing mentally challenging tasks included pupil dilation and increased levels of glutamate in the synapses of the inferior prefrontal cortex.

In previous studies, the researchers used fMRI – but this technique could not explain why the cost of cognitive control increases over time. Instead, the team used magnetic resonance spectroscopy (MRS), which meant that they could measure brain metabolites while human subjects carried out the tasks.

Although the study had minor limitations – such as the low spatial and temporal resolution of MRS – and the results were only correlational, they do offer an explanation as to why cognitive control is harder to mobilize after a strenuous workday. Wiehler hopes that, in the future, “prefrontal metabolites could be monitored using MRS to detect cases of severe fatigue/burnout in many different situations, such as employees after work, athletes during heavy training programs, or students during revisions before their exams.”

In further studies, the researchers hope to learn why the prefrontal cortex is more susceptible to fatigue and glutamate accumulation than other brain regions. Wiehler seeks to understand how metabolite buildup could be prevented or removed from the synapses. He adds, “Going forward, we may also be exploring whether markers of fatigue are predictive of clinical outcome across diseases such as cancer or depression.”

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  1. A Wiehler et al., Current Biology, 32, 1 (2022). DOI: 10.1016/j.cub.2022.07.010.
About the Author
Georgia Hulme

Georgia Hulme is Associate Editor at The Analytical Scientist

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