Friday, November 22, 2024
11/22/2024
PROJECT SUMMARY Fatigue, a feeling of tiredness and exhaustion, occurs throughout life and significantly impacts our decisions to engage in effortful daily activities. A wide range of neuropsychiatric and neurological disorders report fatigue as either a symptom or comorbidity and are associated with disruptions in effort-based decision-making. Despite the prevalence of fatigue in health and disease, there is a limited understanding of how fatigue evolves over time and ultimately impacts effort-based decision-making. The goal of this proposal is to understand the mechanisms that subserve the evolution of physical and cognitive fatigue through repeated exertion, and how fatigue influences decision-making in healthy humans. Furthermore, we aim to understand how these mechanisms are disrupted in individuals with major depressive disorders (MDD), of which fatigue is a cardinal symptom. To this end, we will use a combination of experiments in human participants, computational modeling of behavior, and functional magnetic resonance imaging (fMRI). Aim 1 we will investigate how the evolution of fatigue influences the dynamics of effort-based decision-making. We will poll participants' momentary subjective fatigue as they perform bouts of fatiguing exertion and make effort-based decisions. We will use computational modeling to characterize participants' fatigue and test how this fatigue influences decisions to exert. We will use model-based fMRI to examine how the brain integrates information about fatigue to drive choice. In Aim 2, we will investigate how motivational state modulates feelings of fatigue and effort-based decision-making. In this Aim we will pair fatiguing exertions with different levels of monetary incentive to modulate participants' motivational state. This manipulation will allow us to study how motivation influences feelings of fatigue and decisions to exert and the underlying neural mechanisms. In Aim 3, we will identify how fatigue influences effort-based decision-making in individuals with MDD. Participants with MDD will undergo fatiguing exertions, rate their feelings of fatigue, and make effort-based choices. We will examine how feelings of fatigue and effort-based choice are related to MDD symptomology. In sum, our proposed studies will have a broad impact on the field of decision-making by dissecting the behavioral and neural mechanisms responsible for the influence of feelings of fatigue on physical and cognitive effort valuation. In the long term, these studies may reveal novel behavioral and neural markers to aid in the study, classification, and treatment of fatigue.
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