Accumulation of ‘toxins’ in brain is why thinking hard is tiring, study suggests

Scientists have unearthed new evidence to explain why long periods of thinking intensely can feel as exhausting as physical labour.

According to their theory, this fatigue is caused by an accumulation of potentially toxic substances in the brain.

This build-up – of a chemical called glutamate – in turn alters our control over decision-making, so that we shift toward actions that require no effort or waiting as cognitive fatigue sets in.

The fatigue potentially occurs as a way of telling the brain to shut down in order to save itself, according to the new study published in the Current Biology journal.

“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,” said co-author Mathias Pessiglione, of France’s Pitie-Salpetriere University.

“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.”

As part of their study, the Paris-based researchers used MRS scanning to monitor brain chemistry over the course of a workday, comparing two groups of people.

The first group comprised 24 individuals who needed to think hard, while the other involved 12 participants who had relatively easier cognitive tasks.

In the group doing hard work, the scientists observed signs of fatigue, including reduced pupil dilation.

The two groups were also asked to make various economic decisions throughout the day – choosing between expending either a low amount of effort to win a variable reward, or to expand a variable amount of effort for a reward of 50 euros.

People in the group carrying out more intense cognitive tasks were found to be more inclined to make choices which proposed rewards with little effort and less delay, such as receiving cash immediately versus a bank transfer up to one year later.

Critically, the researchers say, the participants in this group also had higher levels of glutamate in their brains’ prefrontal cortex.

Together with earlier evidence, the authors said their findings support the notion that glutamate accumulation makes further activation of this part of the brain costly – to the extent that cognitive control is more difficult after a mentally tough workday.

Fortunately, Dr Pessiglione said that “there is good evidence that glutamate is eliminated from synapses during sleep”, and advised people to avoid making important decisions when they are tired.

There may be other practical implications, however. For example, the researchers suggest that monitoring of prefrontal metabolites could help to detect severe mental fatigue – which in turn could help adjust work agendas to avoid burnout.

In future studies, the scientists hope to learn why the prefrontal cortex seems especially susceptible to glutamate accumulation and fatigue.

They are also curious to understand whether the same markers of fatigue in the brain could predict recovery from health conditions, such as depression or cancer.