Neurobiology of Disease (Jan 2023)
Cognitive fatigue-related sensory gating deficits in people with multiple sclerosis
Abstract
Background: Cognitive fatigue is highly prevalent in people with multiple sclerosis (pwMS) and significantly limits their quality of life. Fatigue can be subdivided into a subjective feeling of constant (trait) or current (state) exhaustion, as well as an objective performance decline, also known as fatigability. However, the current fatigue diagnosis in pwMS is purely subjective, leaving fatigability mostly unattended. Sensorimotor and sensory gating deficits have recently been described as possible objective markers for fatigability in healthy subjects. Thus, this study aimed to investigate the potential of prepulse inhibition (PPI) ratios and the P50 sensory gating suppression as surrogate markers for cognitive fatigue in pwMS. Methods: PPI and P50 sensory gating ratios were assessed before and after a 30-min fatigability-inducing AX- continuous performance task. Subjective trait fatigue was operationalized via self-report questionnaires, subjective state fatigue via visual analog scales (VAS), and fatigability via the change in both gating ratios. The data were analyzed using Linear Mixed Models and Pearson correlations. Results: We included 18 pwMS and 20 healthy controls (HC) in the final analyses. The task-induced fatigability was more pronounced in pwMS. While the initial PPI and P50 ratios were similar in both groups, P50 sensory gating was significantly disrupted after fatigability induction in pwMS. PPI, on the other hand, decreased in both groups. Moreover, initial P50 sensory gating ratios were negatively associated with subjective trait fatigue in pwMS, indicating that higher trait fatigue is associated with disrupted sensory gating. Finally, fatigability-related changes in P50 sensory gating were associated with the changes in VAS ratings, but only in HC. Conclusions: This study demonstrated that P50 sensory gating is a promising objective fatigue and fatigability parameter. Importantly, P50 sensory gating correlated with subjective trait and state fatigue ratings. Our results extend the subjective fatigue diagnosis and broaden the understanding of pathophysiological neuronal mechanisms in MS-related fatigue. This is the first study to present fatigue-related disruption of sensory gating in pwMS.
