Progressive resistance exercise training and changes in resting-state functional connectivity of the caudate in persons with multiple sclerosis and severe fatigue: A proof-of-concept study

Fatigue is one of the most disabling symptoms of multiple sclerosis (MS). While progressive resistance training (PRT) has been shown to reduce fatigue in persons with MS, it is not clear why these reductions occur. One hypothesis is that PRT may induce functional changes to the caudate, a region highly implicated in MS fatigue. The aim of the current study was to study the effects of PRT on overall fatigue impact and resting-state functional connectivity of the caudate in persons with MS reporting severe fatigue. Participants were semi-randomly assigned to either a 16-week home-based PRT (n = 5) or stretching control (n = 5) condition. Both groups demonstrated reductions in overall fatigue impact (main effect of time: F =.84, d =.65). Significant group × time interactions were found, with the PRT group demonstrating post-training increases in functional connectivity between the caudate and left inferior parietal (F = 66.0, p <.001), bilateral frontal (both p <.001), and right insula (F = 21.8, p =.002) regions compared to the stretching group. Furthermore, greater post-training increases in functional connectivity between the caudate and left inferior parietal region were associated with greater decreases in cognitive fatigue (r = −.52) specifically. This study provides initial evidence for the caudate as a potential neural substrate for the beneficial effects of PRT on fatigue in persons with MS.