Thinking hard for several hours can leave us feeling mentally tired – and now we may know why. Prolonged concentration leads to the build-up of a compound called glutamate in regions at the front of the brain.

This may provide an explanation as to why we avoid difficult tasks when mentally fatigued: glutamate overload makes further mental work difficult.

Too much glutamate is potentially harmful, says Antonius Wiehler at the Paris Brain Institute in France, who led the research. “The brain wants to avoid this, so it is trying to reduce activity.”

To learn more, Wiehler and his team used a technique called magnetic resonance spectroscopy (MRS), which measures levels of various chemicals in living tissue harmlessly.

They focused on a region towards the front and sides of the brain called the lateral prefrontal cortex, which much previous work has shown is involved in difficult mental tasks.

Levels of eight different brain chemicals were measured, including glutamate, which is the main signaling chemical between neurons. At the junctions between neurons, called synapses, electrical signals can’t leap the gap. Instead, tiny particles of compounds such as glutamate are released, which transmit the signal.

After completing the memory tasks for 6 hours, those doing the harder version had raised levels of glutamate in their lateral prefrontal cortex compared with the start of the experiment. In those doing the easier task, levels stayed about the same. Across all participants, there was no rise in the other seven brain chemicals that were measured.

Among the participants doing the harder tasks, their glutamate level rise tallied with dilation of the pupils in their eyes, another broad measure of fatigue. Those doing the simpler task reported feeling tired but had no glutamate rise or pupil dilation.

The researchers also investigated if mental fatigue affected decision-making. They did this by interspersing the memory task with different exercises, such as one where people chose between getting a sum of money straight away or a different one later.

As the participants doing the harder task felt more tired and had an accumulation of glutamate, they shifted to options that gave a small reward immediately. This could be an example of us avoiding difficult mental tasks, such as calculating which choice to make, to prevent the accumulation of potentially harmful glutamate levels.