Asian businesswoman online working at the night. Busy and exhausted of work overtime at home.

Mental strain can lead to changes in brain physiology that cause feelings of tiredness.Credit: Getty

It’s not just in your head: a desire to curl up on the couch after a day spent toiling at the computer could be a physiological response to mentally demanding work, according to a study that links mental fatigue to changes in brain metabolism.

The study, published on 11 August in Current Biology1, found that participants who spent more than six hours working on a tedious and mentally taxing assignment had higher levels of glutamate — an important signalling molecule in the brain. Too much glutamate can disrupt brain function, and a rest period could allow the brain to restore proper regulation of the molecule, the authors note. At the end of their work day, these study participants were also more likely than those who had performed easier tasks to opt for short-term, easily won financial rewards of lesser value than larger rewards that come after a longer wait or involve more effort.

The study is important in its effort to link cognitive fatigue with neurometabolism, says behavioural neuroscientist Carmen Sandi at the Swiss Federal Institute of Technology in Lausanne. But more research — potentially in non-human animals — will be needed to establish a causal link between feelings of exhaustion and metabolic changes in the brain, she adds. “It’s very good to start looking into this aspect,” says Sandi. “But for now this is an observation, which is a correlation.”

Tired brain

Previous research has demonstrated effects of mental strain on physiological parameters such as heart-rate variability and blood flow, but these tend to be subtle, says Martin Hagger, a health psychologist at the University of California, Merced. “It’s not like when you’re exercising skeletal muscle,” he says. “But it is perceptible.”

Cognitive neuroscientist Antonius Wiehler at the Paris Brain Institute and his colleagues thought that the effects of cognitive fatigue could be due to metabolic changes in the brain. The team enrolled 40 participants and assigned 24 of them to perform a challenging task: for example, watching letters appear on a computer screen every 1.6 seconds and documenting when one matched a letter that had appeared three letters ago. The other 16 participants were asked to perform a similar, but easier task. Both teams worked for just over six hours, with two ten-minute breaks.

While the study participants focused on their work, Wiehler and his team used a technique called magnetic resonance spectroscopy to measure levels of glutamate in a region of the brain called the lateral prefrontal cortex.

The prefrontal cortex is the home of cognitive control — the part of the brain that allows people to suppress their impulses. “If you get stung by an insect, you want to scratch,” says Wiehler. “If you’re stopping this reflex, that would be cognitive control.” It’s also the system that humans rely on to choose tempting short-term rewards, such as an unhealthy snack, over long-term gains.

The researchers found that participants who laboured on the more difficult task had accumulated more glutamate in this region of the brain by the end of the day than had those who worked on the easier task. And, given a choice between an immediate cash reward and a larger reward that would come months later, they were more likely to choose the smaller, short-term reward than they were at the start of the day.

Wiehler now hopes to use this system to learn more about how to recover from mental exhaustion. “It would be great to find out more about how glutamate levels are restored,” he says. “Is sleep helpful? How long do breaks need to be to have a positive effect?” Studies of cognitive fatigue could also be key to understanding how workers react to — and recover from — high-stakes mental work such as air-traffic control, in which even a brief loss of focus can cost lives.

And now that a system has been established to measure metabolic changes in response to mental fatigue, Hagger hopes that other researchers will try the approach. “Means to detect this have hitherto not been sensitive enough, so this research paves the way for future researchers to explore cognitive fatigue,” he says.

That research — and particularly animal studies, in which glutamate levels can be experimentally altered — could unpick the molecular mechanisms that cause the molecule to accumulate during difficult mental work and how that affects brain activity, says Sandi. “This is the tricky part.”