“A Neuro-Metabolic Account of Why Daylong Cognitive Work Alters the Control of Economic Decisions”, 2022-08-11 ():
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
[media] 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.
[Keywords: fatigue, cognitive control, decision-making, reward, delay, effort, prefrontal cortex, glutamate, spectroscopy, computational modeling]
…Obviously, our results are only correlational and cannot be taken as proof that what limits cognitive control exertion is the need to prevent glutamate accumulation. Causal manipulations would be required to validate this assumption. In addition, the metabolic spectrum was narrow and constrained by technical limitations, as there are metabolites that cannot be quantified with in-vivo MRS methods or at least in a 3T MRI scanner, using a semi-LASER sequence, with the echo-time optimized for glutamate. For instance, GABA would also have been a possible candidate but could not be reliably quantified with our MRS data acquisition sequence. In any case, it should be noted that the target substance requiring regulation may not be glutamate itself but any substance whose concentration is linked to glutamate accumulation. Nevertheless, glutamate regulation has been pointed out as an essential component in the brain energy budget and discussed as a potential source of cognitive fatigue.48–50 Indeed, there are good reasons for which glutamate accumulation may need to be regulated
…Even if our model provides proof of concept that a metabolic account of cognitive fatigue can be combined with a cost-benefit mechanistic framework, several aspects remain speculative at this stage. Notably, how glutamate levels would be monitored to estimate the costs of cognitive control is unclear. It remains possible that the brain may not monitor glutamate itself but any phenomenon linked to glutamate accumulation (eg. GABA synthesis). Also, an explanation is still missing for why cognitive control regions would accumulate glutamate more than other regions like the visual cortex. On a different note, research is needed to explore the recovery of glutamate levels at rest or during sleep. Interestingly, the cognitive control network is deactivated in rest conditions that activate the default mode network,10,61 which could favor the clearance of extracellular glutamate. Moreover, it has been shown that glutamate concentrations decrease during sleep, in relation to EEG slow-wave activity.62 Glutamate could therefore belong to the potentially toxic substances that are eliminated during sleep, which could mediate recovery from cognitive fatigue.63 Finally, how cognitive fatigue due to excessive use of cognitive control relates to other forms of fatigue remains to be specified. As it was also observed in a mild form of burnout syndrome25 and patients with low-grade glioma,23 we tend to believe that an elevated cost of cognitive control is key to several clinical manifestations of fatigue,64,65 but this speculation still requires empirical confirmation. It would also require a theoretical articulation between the objective fatigue of the cognitive control brain system documented here with choice-related markers and the subjective fatigue sensation that might represent the main complaint of patients in the clinics.