Fatigue influences embodiment perception and motor performance in multiple sclerosis subjects: a cross-sectional immersive virtual reality study

Background: Multiple sclerosis (MS) represents a major cause of acquired disability in adults worldwide. Fatigue and upper limb (UL) impairments are common and disabling symptoms in people with MS (pwMS), even in the early stage of the disease. Rehabilitation proved to be effective in ameliorating Fatigue and UL function in pwMS. In particular, virtual reality (VR) represents a promising tool for delivering treatments in a highly engaging way, reproducing real-life gestures in a naturalistic manner. Immersive VR (IVR) tools can boost subjects’ immersion and presence, but very scarce evidence is currently available on IVR effects in this population. Aim: This study aims to test the feasibility of an IVR system for UL training in pwMS, analyzing clinical correlations of embodiment, fatigue, and UL motor performance. Methods: We conducted a cross-sectional study involving pwMS and age- and sex-matched healthy controls. pwMS under 65 years old reporting uni- or bilateral UL impairment were enrolled; no restrictions were applied regarding sex, MS phenotype, and disease severity (EDSS scores). All subjects underwent a single session of IVR UL training (Oculus Quest 2) using a previously developed and clinically tested IVR system. PwMS were assessed through the Modified Ashworth Scale (MAS), the Nine-Hole-Peg-Test (NHPT), and the Modified Fatigue Impact Scale (MFIS). Moreover, we collected measures of hand peak velocity during task execution and responses to a standardized questionnaire related to embodiment perception, (i.e. subjects’ feeling of being part of the virtual context) in terms of body ownership and motor agency, administered after the training session. Results: 25 pwMS were enrolled (Females: 56%, mean age: 53 ± 7 years) with EDSS scores ranging from 3.5 to 8 and with a mean score at the Modified Fatigue Impact Scale (MFIS) (0–84) of 35 ± 14. None of our subjects reported symptoms of cybersickness or any other adverse effects. All patients reported very high satisfaction rates (median score = 5 on a 5-point Likert scale, interquartile range (IQR) = 4–5); they also experienced strong subjective impression of both body ownership and motor agency (median score on a 9-points rated scale: body ownership = 9 (IQR = 8–9), motor agency = 9 (IQR = 8–9)). The median peak velocity of all patients exhibited a significant correlation with MFIS (ρ= – 0.57, p = 0.036). The MFIS score showed a significant correlation with embodiment and, specifically, a moderate correlation with agency (ρ= - 0.57, p = 0.036). Notably, low and high-fatigued pwMS showed significant differences in hand peak velocity achieved (p = 0.005) and in embodiment perception on the motor agency domain (p = 0.004) and body ownership one (p = 0.024), which means that higher MS-related fatigue seems associated with weaker embodiment perception, particularly affecting the experienced sense of motor interaction. No statistically significant differences in satisfaction, embodiment, and peak velocity rates were found when comparing pwMS and healthy controls. Conclusions: IVR use in pwMS seems feasible and well-tolerated. Additionally, MS-related fatigue showed a significant role in determining the rate of perceived embodiment, thus conditioning UL kinematics, in pwMS exposed to an IVR session.