Fatigability-related oscillatory brain activity changes in people with MS

Background: Fatigue, a multidimensional and challenging symptom associated with various underlying condi-tions, can manifest as a subjective feeling and a performance fatigability. The latter is often defined as an objectively measurable performance decline with time on task. Both syndromes are highly prevalent in people with multiple sclerosis (pwMS) and are often resistant to medical therapy. In the absence of valid and reliable objective parameters, the current cognitive fatigue diagnosis remains purely subjective. Assessing brain wave activity changes has repeatedly been a viable strategy for monitoring cognitive fatigue in healthy subjects. In this study, we aimed to investigate oscillatory brain activity changes and their associations with subjective fatigue in pwMS.Methods: We enrolled 21 pwMS and 21 healthy controls (HC) in this study. Subjects performed a sustained attention task divided into six blocks over the course of 30 minutes, and underwent resting state EEGs before and after the task. During the task, subjects were repeatedly asked to rate their subjective levels of mental fitness, mental exhaustion, and mind wandering. Using Linear Mixed Models, we explored fatigability-related changes by focusing on the time course of changes in reaction time variability, subjective ratings of fatigability, as well as frontomedial theta, and occipital alpha power. We further investigated initial and fatigability-induced differ-ences between pwMS and HC at rest. Finally, Pearson correlations were used to examine the relationship between subjective fatigue and objective fatigability parameters.Results: Our results revealed a systematically stronger fatigability development in pwMS that was objectively measurable. PwMS reported lower mental fitness levels and demonstrated greater variability in reaction times with time on task. Occipital alpha power significantly increased during the task. Especially for upper alpha power, this increase was significantly more prominent in pwMS compared to HC. However, the time-on-task -induced changes in our study were not associated with the subjective fatigue ratings.Conclusions: The results of this study expand the understanding of the neural mechanisms underlining cognitive fatigability and may complement the fatigue diagnosis and therapy monitoring with quantitative objective methods.

Automated summary

This study found that patients with multiple sclerosis (pwMS) show more measurable changes in cognitive fatigability compared to healthy controls. However, these changes in reaction time and brain activity were not associated with subjective fatigue ratings.