| Summary: | <p>Fatigue, a feeling of tiredness or exhaustion, increases with effortful exertion and impacts motivation and performance. While healthy people typically recover during periods of rest, persistent forms of fatigue are a debilitating symptom in many medical conditions and in particular in Parkinson’s disease (PD). To date, the neural and computational mechanisms in the brain that underlie fatigue and its impact on the willingness to exert effort are still poorly understood. Using physical effort-based decision-making paradigms and trial-by-trial self-report ratings in combination with a novel computational model, functional Magnetic Resonance Imaging and pharmacological manipulation, this thesis addresses the following outstanding research questions: How are brain systems implicated in effort-based decision-making impacted by momentary levels of fatigue in healthy individuals (Chapter 2)? Do people prioritise effort or reward information before option selection and are these preferences associated with fatigue and motivation to exert effort (Chapter 3)? How does fatigue develop as a function of effort, rest and rewards (Chapter 4), and what are the specific effects of dopaminergic medication in PD patients (Chapter 5)? Finally, how closely linked are dynamic changes in fatigue ratings and in the motivation to exert effort (Chapter 6)?</p>
<p>Together, the findings suggest that levels of fatigue fluctuate on a moment-to-moment basis as a function of the recent history of effortful exertion and rest, with underlying recoverable and unrecoverable components, impacting people’s sensitivity to efforts and the subjective value of exerting effort to obtain rewards. Separate frontal sub-regions signalled recoverable and unrecoverable fatigue states, while current fatigue levels were integrated with value in the ventral striatum and the frontal pole. Dopaminergic medication affected self-reported fatigue, playing a differential role in recovery. In addition to these insights, the studies demonstrate that the paradigms and the computational model developed here may provide new approaches for the assessment and quantification of pathological forms of fatigue and associated deficits in motivation and might thereby help identify potential avenues for prevention and treatment.</p>
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