Chronic pathological fatigue is a highly debilitating symptom with a significant impact on quality of life of stroke survivors. Despite its high prevalence, research into the mechanisms that underlie post-stroke fatigue is lacking. This thesis outlines how changes in cortical neurophysiology results in alterations in sensorimotor processing associated with the perception of effort and how prolonged experience of high effort can subsequently result in chronic pathological fatigue. I show that the perception of effort for what are usually low effort activities is altered in non-depressed, chronic stroke survivors with minimal physical impairment. Low effort voluntary contractions are perceived as more effortful in stroke survivors with high fatigue compared to those with low fatigue. Sensory attenuation, the ability to attend away from predictable sensory input, is thought to underlie altered effort perception. If one is unable to attend away from predictable sensory input associated with a voluntary movement, this will give rise to the perception of higher effort afforded to the movement. I show that stroke survivors with high fatigue do not show reduced sensory attenuation of sensory input arising from mechanoreceptors as quantified using a force matching task and suggest that high effort afforded to simple voluntary movements may be a result of reduced sensory attenuation of information arising from within the body, namely proprioceptive afferent information from the contracting muscle. Using TMS, I show that cortical excitability both at rest and during movement preparation is altered in stroke survivors with high fatigue and propose that cortical excitability reflects the degree of sensory attenuation at the level of the sensorimotor cortex. Finally, I show that neuromodulatory techniques such as transcranial direct current stimulation, are potential tools that can be used to reduce fatigue severity by potentially resetting cortical neurophysiology and reducing perceived effort. Overall, the data provides some evidence in support of the sensory attenuation model of fatigue and provides a novel insight into the mechanisms implicated in post- stroke fatigue
