Wallace D. Wattles, a 19th-century American writer, asserted that "thinking is the hardest and most exhausting of all labors."

Although it may sound exaggerated, recent research suggests that prolonged and intense thinking can actually drain cognitive stamina, much like how physical exercise tires out our physical strength.

While physical labor manifests through visible signs like beads of sweat or trembling muscles, mental fatigue remains less apparent. When someone reports feeling mentally exhausted, it’s an experience that should be accepted at face value. Researchers are still working to understand why intense thinking induces cognitive fatigue. This is not simply a feeling of sleepiness, but a growing difficulty in maintaining focus. Some scientists now hypothesize that glutamate, the brain’s most abundant excitatory neurotransmitter, plays a significant role in mental endurance.

Glutamate, an excitatory amino acid found in more than 90 percent of human brain neurons, has surprised researchers with its diverse functions. Neurons regulate their signal strength by controlling glutamate release, and excess glutamate can cause neurons to self-destruct, potentially leading to issues such as heartburn. In an experiment, 24 participants engaged in intensive computer-based categorization for over six hours, which led to elevated glutamate levels in the lateral prefrontal cortex—a region associated with higher cognitive functions. In contrast, participants with less challenging tasks showed no glutamate buildup, suggesting a link between increased extracellular glutamate and mental fatigue.

The brain’s significant glucose consumption during mental exertion has also been recognized, though the biochemical reason behind how glucose depletion impairs cognitive function remains unclear. Some theories suggest that a sharp drop in glucose may lead to a loss of dopamine, making it easier to lose interest in cognitive tasks. Mathias Pessiglione, a clinical psychologist, posits that fatigue may not merely be an illusion designed to encourage more pleasurable activities but rather a signal to preserve the brain’s functional integrity. He also suggests that the removal of glutamate from synapses during sleep could contribute to the refreshing sensation experienced after a good night’s rest.

As scientists continue to explore the complexities of mental fatigue, they are uncovering how neurotransmitters like glutamate and the brain’s glucose consumption affect cognitive endurance. This emerging knowledge not only deepens our understanding of mental exertion but also highlights the essential role of restorative sleep in revitalizing cognitive functions.

The intricate relationship between mental exertion and cognitive fatigue continues to captivate researchers, revealing the crucial role of neurotransmitters like glutamate. Beyond its well-known function in neuron communication, glutamate’s involvement in cognitive endurance offers new insights into the biochemical underpinnings of mental fatigue. As the brain engages in demanding tasks, the lateral prefrontal cortex, which is responsible for higher cognitive functions, experiences a buildup of extracellular glutamate.

At the same time, the brain’s significant demand for glucose during mental exertion adds another layer of complexity. While the precise mechanisms connecting glucose depletion to cognitive difficulties remain unclear, the potential loss of dopamine, which may reduce interest in cognitive tasks, presents a plausible explanation. The groundbreaking experiment, where participants engaged in intensive cognitive tasks, further supports these findings, demonstrating a clear link between glutamate accumulation and mental fatigue. Mathias Pessiglione’s insights into the elimination of glutamate during sleep provide a compelling explanation for the restorative effects of a full night’s rest on cognitive functions.