Fatigue - a feeling of exhaustion arising from exertion - is a significant barrier to successful behaviour and one of the most prominent symptoms in primary care. During extended behaviours, fatigue increases over time, leading to decrements in performance in both cognitively and physically demanding tasks. However, to date, theoretical accounts of fatigue have not fully characterised the neuroanatomical basis of cognitive and physical fatigue nor placed results within broader discussions of the functional properties of the systems implicated. Here, we review recent neurophysiological and neuroimaging research that has begun to identify the neural mechanisms underlying changes in behaviour occurring due to fatigue. Strikingly, this research has implicated systems in the brain, including the dorsal anterior cingulate cortex (dACC), anterior insula, and lateral prefrontal cortex, that in separate lines of research have been linked to motivating the exertion of effort, to persisting towards goals and to processing one's internal states. We put forward a neurocognitive framework for fatigue and its impact on motivation. Levels of fatigue arising from effortful behaviours impact on processing in systems that weigh up the costs and benefits of exerting effort. As a result, as levels of fatigue rise, the value of exerting effort into a task declines, leading to reductions in performance. This account provides a new framework for understanding the effects of fatigue during cognitively and physically demanding tasks as well as for understanding motivational impairments in health and disease.

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From a gym workout, to deciding whether to persevere at work, many activities require us to persist in deciding that rewards are ‘worth the effort’ even as we become fatigued. However, studies examining effort-based decisions typically assume that the willingness to work is static. Here, we use computational modelling on two effort-based tasks, one behavioural and one during fMRI. We show that two hidden states of fatigue fluctuate on a moment-to-moment basis on different timescales but both reduce the willingness to exert effort for reward. The value of one state increases after effort but is ‘recoverable’ by rests, whereas a second ‘unrecoverable’ state gradually increases with work. The BOLD response in separate medial and lateral frontal sub-regions covaried with these states when making effort-based decisions, while a distinct fronto-striatal system integrated fatigue with value. These results provide a computational framework for understanding the brain mechanisms of persistence and momentary fatigue.