The Neurobiology of Pathological Fatigue: New Models, New Questions

The last decade has seen the emergence of new theoretical frameworks to explain pathological fatigue, a much neglected, yet highly significant symptom across a wide range of diseases. While the new models of fatigue provide new hypotheses to test, they also raise a number of questions. The primary purpose of this essay is to examine the predictions of three recently proposed models of fatigue, the overlap and differences between them, and the evidence from diseases that may lend support to the models of fatigue. I also present expansions for the sensory attenuation model of fatigue. Further questions examined here are the following: What are the neural substrates of fatigue? How can sensory attenuation, which underpins agency also explain fatigue? Are fatigue and agency related?