Andy
Senior Member (Voting rights)
Significance
Mental fatigue is an ubiquitous experience that limits individual and societal productivity, especially in knowledge-based economies where cognitive performance drives growth. The origins of mental fatigue are controversially debated: While psychological theories explain fatigue via computational constraints, neurobiological models posit that neurometabolic changes contribute to fatigue after mental effort. Here, we provide evidence for the latter accounts: Combining noninvasive brain stimulation with magnetic resonance spectroscopy, we demonstrate that stronger prefrontal engagement during mental work comes at the cost of enhanced posteffort fatigue, instantiated by prefrontal glutamatergic accumulation. These findings establish a causal chain linking prefrontal activation, glutamate dynamics, and motivational fatigue, advancing our mechanistic understanding of why mental work feels costly and informing clinical models of pathological fatigue.Abstract
Successful goal-directed behavior often requires the exertion of effortful cognitive control processes, but it remains unclear why engaging in cognitive control is experienced as effortful and induces fatigue. Here, we tested the hypothesis that sustained activation in the dorsolateral prefrontal cortex (DLPFC)—a neural substrate of cognitive control—causally induces motivational fatigue via the accumulation of prefrontal glutamate metabolites. For this purpose, we combined brain stimulation with spectroscopy imaging to assess how increasing DLPFC excitability during an effortful mental task changes the motivation for mental effort and glutamate concentrations. We found that stimulating the DLPFC during mental effort exertion improved mental performance at the cost of increased posteffort motivational fatigue, suggesting a causal role of DLPFC activation for inducing fatigue. On the neural level, DLPFC activation during effortful cognition also increased prefrontal concentrations of glutamate, which statistically explained the fatigue-induced lower motivation for mental effort. A corresponding analysis of combined glutamate–glutamine (Glx) concentrations revealed converging effects. Together, these findings provide causal evidence that enhanced DLPFC activation contributes to fatigue via neurochemical changes, supporting neuro-metabolic accounts of fatigue and offering new insights into why demanding cognitive tasks are perceived as effortful.Paywall