Motor Fatigue in Multiple Sclerosis: Role of Central Mechanisms

ABSTRACT

Background: The main objective of this proposal is to investigate the role of central mechanisms in motor fatigue and to unmask the alterations in the neural connectivity patterns underpinning central fatigue in PwMS. Specifically, we aim to 1) determine the role of central mechanisms in motor fatigue in PwMS, and 2) to determine the neural correlates of central fatigue in PwMS. Methods: Aim 1 Fatigue Assessment PwMS and healthy controls are currently being recruited to participate in a fatiguing motor task involving a sustained contraction of plantarflexor (PF) muscles for 60 seconds. We are using the interpolated twitch technique to determine voluntary activation (VA) of the PF muscles. The decline in VA during motor task represents the inability of the central nervous system to maximally drive muscles for a sustained period and provides an index of central fatigue. We further relate this objective index of central fatigue to decline in the balance control during standing (pre- and post fatigue test) and the fast six-minute walk test. We hypothesize that 1a PwMS will exhibit significantly higher central fatigue during the performance of the fatiguing motor task, and 1b Central fatigue will be related to the decline in balance control during standing and walking performance. Aim 2 Neuroimaging Resting-state functional MRI (RS-fMRI) is being collected in the participants from Aim 1 to investigate neural mechanisms underlying motor fatigue in PwMS. We hypothesize that 2) The severity of central fatigue in PwMS will be associated with increased functional connectivity among the cortico-striatal structures in the motor circuit of the basal ganglia. Status We have screened a total of 109 subjects for participation in this study. Of those screened, a total of 43 subjects (20 healthy controls and 23 PwMS) have completed data collection for Aim 1 and Aim 2.