Full Length ArticleMechanisms underlying muscle fatigue differ between multiple sclerosis patients and controls: A combined electrophysiological and neuroimaging study

Increased sense of fatigue is an important and conspicuous symptom in multiple sclerosis (MS). Muscle fatigue is associated with increased sense of fatigue in MS (Steens et al., 2011). The aim of this study was to investigate mechanisms that can explain muscle fatigue in MS patients and controls. We assessed changes in cortical activation (BOLD), voluntary activation (twitch interpolation) and muscle force during a sustained maximal voluntary contraction (MVC) in twenty MS patients and twenty healthy controls.In control participants, individual differences in force decline (mean 65% MVC, 8 SD) during the sustained maximal contraction could be accounted for by differences in maximal voluntary force (R2: 0.49, p = 0.001); stronger participants presented a larger force decline. The small decline in voluntary activation (mean 7.8%, 11.8 SD) did not contribute significantly to the force decline. During the sustained contraction, the force decline was accompanied by an increase in cortical activation in the main motor areas.In MS patients, the differences in the decline in force (mean 67% MVC, 9 SD) were significantly associated (R2: 0.51, p = 0.001) with a decline in voluntary activation (mean 20.1%, 20.6 SD) and not with maximal force or decline in rest twitch. The corresponding cortical activation in motor areas showed an increase in the first two intervals of the sustained contraction but declined during the last interval.Our data indicate that muscle fatigue during a sustained contraction in MS patients is associated with changes in the voluntary activation that are not sufficiently compensated by increased cortical activation. Control participants, however, show increased cortical activation to compensate for these fatigue-related changes in voluntary activation and the major cause of force decline is therefore to be found in the periphery (muscles).