Here's why thinking hard exhausts you

In a recent Current Biology journal study, researchers elucidate the neuro-metabolic mechanisms responsible for cognitive fatigue that occurs following extended and intense working hours. 

Study: A neuro-metabolic account of why daylong cognitive work alters the control of economic decisions. Image Credit: Ilya Lukichev / Study: A neuro-metabolic account of why daylong cognitive work alters the control of economic decisions. Image Credit: Ilya Lukichev /


Cognitive function describes the ability to perform objective tasks that require conscious mental effort. When these cognitive tasks are performed for an extended period, they may result in mental or cognitive fatigue.

Tiredness or fatigue after a day of engaging in mentally taxing or cognitively demanding activities are commonly reported. To date, there is no physiological explanation as to why exerting cognitive control can be exhausting. 

It is important to investigate the reasons behind mental fatigue, as it impacts economic decisions, clinical treatments, workplace management, and education. Furthermore, cognitive fatigue may impair an individual's ability to retain cognitive control, thereby increasing their inclination to engage in emotionally reactive behaviors that provide instant gratification.

Previously, researchers discovered that the lateral prefrontal cortex (LPFC) is associated with cognitive fatigue. More specifically, an increase in cognitive fatigue led to reduced LPFC activity. However, the cause of this fatigue after engaging in tasks requiring long-span cognitive effort remains obscure.

The present study found that cognitive fatigue may be caused by the depletion or accumulation of specific brain metabolites. These metabolic changes in the brain caused by cognitive fatigue may cause cognitive control to be more taxing or difficult, thus instigating behaviors that require less cognitive control or provide short-term rewards. 

The potentially toxic accumulation of certain metabolites like glutamate could be induced by prolonged cognitive control exertion.

About the study

The present study utilized in vivo proton magnetic resonance spectroscopy (1H-MRS) to quantify metabolites in neural tissues, whereas diffusion-weighted 1H MRS was used to measure the diffusion of glutamate-related substances. Behavioral tests and measurements were also used to define the relationship between cognitive fatigue and the cost of cognitive control.

The current study included 40 participants who completed cognitive tasks over five sessions totaling 6.25 hours. The test group consisted of 24 participants who completed the difficult version of a specified task, whereas the control group of 16 participants completed a simplified version of the same task. 

During the study, each participant selected a cash benefit that corresponded to either a greater or lesser level of cognitive effort. This protocol, which was chosen due to the subjective nature of the economic decision, was aimed at making it challenging for participants to observe and compensate for changes in their behavior while mentally fatigued.

Study findings

Behavioral measures of cognitive fatigue

Cognitive fatigue indicated a shift in preference toward options with low control costs. Fatigue also altered the way people make decisions, as it caused participants to favor algorithm choices that did not necessitate thoughtful consideration.

Test participants were also more likely to choose a small-reward option over a big-reward option post-cognitive fatigue, as the task linked to the smaller reward was more straightforward to assess.

Pupillary measures of cognitive fatigue

Pupil dilation has been substantiated as a measure of cognitive effort. Furthermore, pupil dilation has been linked to the activation of noradrenaline neurons in the locus coeruleus and the anterior cingulate cortex. Using eye-tracking during scanning sessions, cognitive fatigue was associated with reduced pupil dilation during the decision-making process. 

This observation can be interpreted as evidence of less cognitive effort invested in the economic choice, which reflects reduced LPFC activity that has been previously reported in functional magnetic resonance imaging (fMRI) studies. Furthermore, reduced pupil dilation indicates that the decrease in cognitive control during the economic choice is facilitated by the anterior cingulate cortex downregulating activity in the LPFC.

Neuro-metabolic measures of cognitive fatigue

There were significant differences in glutamate concentration and glutamate/glutamine diffusion in the LPFC between the high-demand and low-demand groups, with only a minimal difference observed in the visual cortex. Therefore, tasks that demanded higher cognitive control demand are associated with higher glutamate release, which subsequently leads to greater glutamate accumulation throughout a workday. 

During the high-demand conditions, the glutamate diffusion pattern increased, whereas, during the low-demand conditions, the diffusion pattern remained unchanged. Therefore, it may be possible to refine the interpretation since changes in glutamate/glutamine diffusion may indicate an accumulation in the extracellular space.


Reduced pupil dilation during decision-making was observed only in the high-demand group. Furthermore, task preferences in this group shifted to the short-delay and low-effort options, which indicated a low-cost bias that was captured by computational modeling. 

High-demand cognitive work increased glutamate concentrations and glutamate/glutamine diffusion in the LPFC as compared to low-demand cognitive work.

The current study findings suggest that glutamate accumulation triggers a regulatory mechanism that makes the activation of the LPFC more energy intensive. These results provide a greater mechanistic understanding as to why cognitive control is more difficult to exercise after a strenuous workday.

Journal reference:
  • Wiehler, A., Branzoli, F., Adanyeguh, I., et al. (2022). A neuro-metabolic account of why daylong cognitive work alters the control of economic decisions. Current Biology. doi:10.1016/j.cub.2022.07.010.
Nidhi Saha

Written by

Nidhi Saha

I am a medical content writer and editor. My interests lie in public health awareness and medical communication. I have worked as a clinical dentist and as a consultant research writer in an Indian medical publishing house. It is my constant endeavor is to update knowledge on newer treatment modalities relating to various medical fields. I have also aided in proofreading and publication of manuscripts in accredited medical journals. I like to sketch, read and listen to music in my leisure time.


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