The 19th-century American writer Wallace D. Wattles once claimed, "Thinking is the hardest and most exhausting of all labor."

On the surface, that might sound like a contentious comparison, but a new study suggests thinking too hard and too long really can drain your brain, much like exercise can wear out the body.

Hard physical labor is obviously tiresome, but the sweat on a person's brow or the quivering of their muscles says nothing of how hard they might be thinking.

When someone says they feel mentally exhausted, we just have to take their word for it.

As a result, scientists still don't really understand why intense thought causes cognitive fatigue. It isn't exactly a feeling of sleepiness; rather, it's a sensation that tasks are getting harder to complete or focus on.

Some researchers now suspect the most abundant excitatory neurotransmitter in the brain is to blame for this lack of mental endurance.

Glutamate is an excitatory amino acid that was only properly described in the 1950s, despite the fact that it is present in over 90 percent of neuron-to-neuron communications in the human brain.

Over the decades, this underestimated chemical has continued to surprise scientists. Neurons, for instance, have been found to control the strength of their signals in the brain by regulating the amount of glutamate they release to other neurons.

Glutamate can even excite neurons to death, with as many as 8,000 glutamate molecules encapsulated in a single pouch of a synapse, the junction where two neurons meet.

The overabundance of glutamate is clearly a problem, and that's part of why it has been linked to brain drain.

When monitoring the brain chemistry of 24 participants tasked with completing strenuous computer-based sorting tasks for over six hours, researchers found an increase in glutamate in the lateral prefrontal cortex. This is the part of the brain associated with higher-order cognitive powers, like short-term memory and decision-making.

In comparison, 16 other participants who were assigned easier tasks for the day didn't show signs of glutamate accumulation in this part of their brain.

As such, the researchers think a rise in extracellular glutamate may be at least one of the limiting factors to human mental endurance.

Obviously, the brain gobbles up a lot of glucose when it's working, too. Other theories suggest this energy source is probably another limiting factor, but it's still not clear how a loss of glucose makes thinking harder, biochemically speaking.

Some researchers have proposed that a plummet in glucose triggers a loss of dopamine in the brain, which makes a person lose interest in certain cognitive tasks more easily.

"Influential theories suggested that fatigue is a sort of illusion cooked up by the brain to make us stop whatever we are doing and turn to a more gratifying activity," explains clinical psychologist Mathias Pessiglione from the Pitié-Salpêtrière University in Paris, France.

"But our findings show that cognitive work results in a true functional alteration – accumulation of noxious substances – so fatigue would indeed be a signal that makes us stop working but for a different purpose: to preserve the integrity of brain functioning."

Pessiglione also says there is good evidence that glutamate is eliminated from synapses during sleep.

That could be part of the reason why a night of rest can allow a person to feel mentally refreshed the next day.

A brain imaging study from 2016, which used a functional MRI (fMRI), also found the lateral prefrontal cortex (lPFC) was involved in intense cognitive effort that reduced its excitability over time.

To activate this region at the end of a long, hard day would require even more effort than at the start. Hence, the feeling of brain drain.

"Taken together with previous fMRI data, these results support a neuro-metabolic model in which glutamate accumulation triggers a regulation mechanism that makes lPFC activation more costly, explaining why cognitive control is harder to mobilize after a strenuous workday," Pessiglione and colleagues conclude.

Glutamate is an incredibly fast-acting neurotransmitter. It's part of what makes this amino acid so powerful. But it also makes the chemical difficult to measure.

Studies like the current one are making use of new technology to explore glutamate's rapid role in our brains in greater detail.

The authors now hope to investigate why glutamate accumulates so much in the prefrontal cortex compared to other parts of the brain.

The study was published in Current Biology.