| Fatigue is an often occurring and disabling symptom in Multiple Sclerosis (MS). Despite its impact, the underlying pathophysiology of MS-related fatigue is still largely unknown. Furthermore, even less is known about secondary effects of motor fatigue (e.g. on cognitive performance). Although fatigue is considered to be difficult to define and quantify, motor fatigue is an important aspect of fatigue that can be examined. Motor fatigue can be caused by changes on a peripheral (peripheral nervous system and muscle) or central level (central nervous system, CNS). Recently, we developed a setup to measure several aspects of motor fatigue using functional magnetic resonance imaging (fMRI). Twitch-superimposition, EMG and force measurements are used to quantify the central drive to the muscles and fMRI provides vital information about the activation of involved brain areas. Hence, the combination of these techniques provides a unique tool to simultaneously study both central and peripheral factors of motor fatigue. We will use these techniques to address the question whether central fatigue contributes to the sense of fatigue in MS patients and whether the amount of central fatigue relates to changes in brain activation. In addition we hope to investigate if the integrity of the corticospinal tract is related to brain activation during a fatiguing task and whether the effects are similar for male and female patients. Changes in disease severity and the effect on brain activity will be studied in a longitudinal study. The experiments are important from both a fundamental and a clinical perspective. Knowledge about the underlying cause of fatigue, factors mediating fatigue and secondary effects of fatigue will increase the awareness of the problems associated with fatigue and will provide caregivers with insight into possible therapeutic interventions of fatigue-related problems. |
