The brain chemistry underlying mental exhaustion.

Emily Underwood does a review of work by Wiehler et al. (open source) on the brain chemistry underlying mental fatigue, also describing several reservations expressed by other researchers. From her description:

The researchers divided 39 paid study participants into two groups, assigning one to a series of difficult cognitive tasks that were designed to induce mental exhaustion. In one, participants had to decide whether letters and numbers flashing on a computer screen in quick succession were green or red, uppercase or lowercase, and other variations. In another, volunteers had to remember whether a number matched one they’d seen three characters earlier...As the day dragged on, the researchers repeatedly measured cognitive fatigue by asking participants to make choices that required self-control—deciding to forgo cash that was immediately available so they could earn a larger amount later, for example. The group that had been assigned to more difficult tasks made about 10% more impulsive choices than the group with easier tasks, the researchers observed. At the same time, their glutamate levels rose by about 8% in the lateral prefrontal cortex—a pattern that did not show up in the other group...

Here is the Wiehler et al. abstract:  

Highlights

• Cognitive fatigue is explored with magnetic resonance spectroscopy during a workday 

• Hard cognitive work leads to glutamate accumulation in the lateral prefrontal cortex 

• The need for glutamate regulation reduces the control exerted over decision-making 

• Reduced control favors the choice of low-effort actions with short-term rewards

Summary

Behavioral activities that require control over automatic routines typically feel effortful and result in cognitive fatigue. Beyond subjective report, cognitive fatigue has been conceived as an inflated cost of cognitive control, objectified by more impulsive decisions. However, the origins of such control cost inflation with cognitive work are heavily debated. Here, we suggest a neuro-metabolic account: the cost would relate to the necessity of recycling potentially toxic substances accumulated during cognitive control exertion. We validated this account using magnetic resonance spectroscopy (MRS) to monitor brain metabolites throughout an approximate workday, during which two groups of participants performed either high-demand or low-demand cognitive control tasks, interleaved with economic decisions. Choice-related fatigue markers were only present in the high-demand group, with a reduction of pupil dilation during decision-making and a preference shift toward short-delay and little-effort options (a low-cost bias captured using computational modeling). At the end of the day, high-demand cognitive work resulted in higher glutamate concentration and glutamate/glutamine diffusion in a cognitive control brain region (lateral prefrontal cortex [lPFC]), relative to low-demand cognitive work and to a reference brain region (primary visual cortex [V1]). 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.