The aim of this study is to characterize perceptive abilities in PwMS compared to controls when performing prolonged functional tasks such as walking and repeated standing from a seated position.

This study proposes primary and secondary research questions which will be tested in the context of two different newly designed experimental tasks and will be performed in maximum three days.

The self-reported beliefs over perceptive abilities and the performance in the experimental perceptive tasks will be compared between persons with multiple sclerosis and an equally sized group of age and gender matched healthy controls. The results of this study may uncover specific deficits in the MS population and will help in defining subgroups of patients with weaker perceptive capacities to gauge their motor performance and therefore in need for tailored interventions additional to the standard practice.

For all work packages, the following information will be recorded from all participants in the first day: demographic data and PROMs of physical activity level [Godin Leisure-Time Exercise questionnaire], sleep quality [Pittsburgh Sleep Quality Index], self-efficacy [General and MS-specific Self-Efficacy scales], affectivity [Positive and Negative Affect Schedule], anxiety and depression [Hospital Anxiety and Depression Scale], habitual symptoms and fatigue [Checklist for Symptoms in Daily life, Brief Pain Inventory, Fatigue Scale for Motor and Cognitive Functions and Modified Fatigue Impact Scale], body and mobility perception [Multidimensional Assessment of Interoceptive Awareness (MAIA-2), Interoceptive Sensitivity and Attention Questionnaire (ISAQ), Postural Awareness Scale (PAS), Multiple Sclerosis Walking Scales, Falls Efficacy Scale] are recorded via secured digital surveys (CASTOR© Electronic Data Capture system). Symbol Digit Modalities Test (SDMT) for processing speed; Brief Visuospatial Memory Test (BVMT) for memory skills; Dual Joint Position Test (DJPT) for proprioception Timed 25-Foot Walk test (T25FW) for maximal walking speed; Test for the Sensory Interaction of Balance (for postural control; 6-Minutes Walking Test (6MWT, walking as far but safe during 6') and 30 seconds Chair Stand Test (30CST, completing as many STSs in 30 seconds) for specific walking and STS performance. IMUs are applied (APDM©, see below) and subjective state fatigue is measured before and after motor performance tasks using a Visual Analogue Scale (VAS, scoring from 0 to 10).

Work package 1a -Protocol: Participants will be familiarized with task-specific perceptual reporting methods. Standardized instructions are formulated in a neutral way to not bias participants' attention toward their symptoms. They will be instructed to report the time-points of perceived changes ("as soon as you perceive it"), either positive or negative, in quantitative or qualitative aspects of their motor performance: the speed or the smoothness of their self-motion. It is explained to the participants as 'a movement that happens in a continual fashion, without any interruptions'. To collect reports we designed a light portable haptic device fitting in the hand (shaped in a similar fashion as the Jamar hand-dynamometer®) and connected via Bluetooth® to a peak-detection Matlab© algorithm. Reports were given by a squeeze. To remove the signal noise produced by involuntary hand-grip forces, the threshold sensitivity of the sensor (i.e., minimum to save a report) will be set at 25% of the maximal hand-grip strength of the participant.

The first task involves a 6MWT at maximal walking speed in silence (eg. no information on time-on-test or verbal encouragements), while instructed to perceive fluctuations in either speed either smoothness (2 walking sessions, counterbalanced order) fluctuations and, as soon as they perceive a performance change, squeeze the sensor in the handheld device. The second task consists on repeated STS transitions: participants perform STSs at a fixed pace (one every ten seconds for six minutes), each one attempting to maximize speed, from a chair with normalized seat-height (lower leg length). Participants will use the handheld force sensor to indicate when variations are perceived during the task, comparing speed/smoothness (2 STS sessions, counterbalanced order) of consecutive STS transitions. Motor performance in the 2 tasks will be recorded with wearable sensors: 6 APDM© inertial motion units (2 over the dorsal part of the feet, 2 on the lower legs, 1 anterior to the sternum and 1 posterior to the fourth lumbar vertebra). The recordings allow for an objective comparison between reported and actual performance variations. Fatigue perception will be assessed before and after each session using the VAS. A brief interview will follow, asking participants to rate their confidence for having been accurate in detecting performance variations (on a scale from to 100) and to describe their own strategy: the sensory cues they relied on, for their reports.

-Work package 1b. "Imposed motor performance" WP1b assesses perceptive awareness for externally-imposed motor performance variations. After assessing perceptive sensitivity for performance variations in self-paced scenarios, we now focus on the quantification of subjects' perceptive accuracy using a real-time verbal reporting approach. Like in WP1a, we will use 2 tasks, walking and STS, with order counterbalanced at group level.

Protocol Walking task - Treadmill Participants will familiarize during a 10-minute supervised treadmill session with the moving belt, safety bars, and general usability. To determine a personalized speed range, participants will start walking at 50% of their maximal walking speed, calculated in their 6MWT overground performance as the highest 15-second moving average. They need to confirm if that is their comfortable treadmill walking speed. If not, adjustments will be made. Participants will see a vertical visual scale in front of them to indicate perceived variations: verbal descriptors will indicate walking speed, with 0% representing comfort and +100% representing maximal walking speed. Afterwards, they will be instructed to adapt their gait to continuous belt acceleration toward their maximal walking speed. This is as familiarization with their personalized range of speed: they will be informed about every 10th step on the VAS (0-100), experiencing how it feels to walk at those speed levels.

Participants will walk on a treadmill with the speed systematically increasing and decreasing within the predefined individual range. The task lasts 6 minutes, starting with 1 minute at the self-selected comfortable speed. Then, speed increases for all participants by 1.5 km/h in 15 steps (0.1 km/h each) over 150 seconds, never exceeding the participant's max walking speed. After a brief plateau, imposed speed is decreasing in the same manner over 150 seconds. Speed changes occur at randomly timed intervals of 5-15 seconds each while verbal reports are prompted and recorded every 10 seconds. The choice of a fixed range of imposed speed, with identical magnitude and timing of speed increments, was defined after piloting the experiment with PwMS and HC to ensure a standardized comparison of absolute speed changes between groups. In order to not alter the participants' gait pattern on the treadmill, we avoided the use of a safety harness, what was also not needed for PwMS with mild impairment. Also, to remove external cues as treadmill sound, we ask participants to wear noise cancelling headphones playing white noise.

Protocol STS task - Chair for Interoceptive Assessment n.0 (CIA0) To impose STS difficulty variations, we mounted a standard chair on a hydraulic system that allows real-time seat height adjustments while an infrared optical sensor continuously measures the distance from the ground, ensuring precise control. This setup enables dynamic and personalized STS assessments and training and we believe it may open new possibilities for rehabilitation and tele-rehabilitation. The baseline seat height will be individually normalized to each participant's lower leg length (measured as the distance from the ground to the inferior margin of the patella). To define a personalized range of imposed difficulty, the seat height will be adjusted between ±20% of this baseline, with the lowest height representing the most challenging condition. Participants will familiarize themselves with each STS level by performing transitions at different seat heights while being informed of their corresponding position on a vertical visual scale (every 10th step, ranging from 0% comfort to -100% minimal seat height).

Participants will perform STS transitions at a fixed pace and completing one repetition every 10 seconds, but always starting from a standing position, sitting down and immediately after shifting their weight on the chair stand up as quickly as possible. No specific instructions are given about the stand-to-sit phase, considered as part of the perceptive strategy. To ensure they rely solely on movement perception, they look straight ahead not receiving any feedback on seat height changes. During the stance phase in between STS repetitions, the seat height will be modified starting from the baseline (comfortable seat-height= lower leg length + its 20%) with fixed decrements (5% of lower leg length) but with randomized number of repetitions (0, 1 or 2) in between variations in seat height. The seat-height lowering will continue down to the personalized lowest seat-height (not having safety constraints in this case), stabilizing on that value before increasing toward the baseline height. After each repetition, participants will verbally report the number corresponding to their perceived difficulty level based on the pre-established scale.

Inclusion Criteria:

• age between 18 and 70 years old
• ability to walk for 6 minutes without rest and without the need of a walking aid
• ability to repeatedly perform the sit to stand transitions on a standard chair (43cm seat height) without hand support

For People with Multiple Sclerosis group

• a diagnosis of MS (2017 revisions of the McDonalds criteria)
• no disease relapses >1 month preceding the start of the study

Exclusion Criteria:

• cognitive impairment hindering understanding of study instructions
• ongoing or suspected pregnancy
• musculoskeletal disorders in the lower limbs
• cardiovascular red flags for exercise (screened with Physical Activity Readines Questionnaire)
• other diagnosis for neurological or metabolic disease limiting the full execution of the tests

44 PwMS and 44 healthy controls will be recruited from the Flemish MS rehabilitation centers in Melsbroek (NMSC) and Pelt (Noorderhart RMSC), and as well from the REVAL research center in UHasselt. No economical compensation will be provided. We will search age and sex-matching healthy controls, considering a 5-year range per subject. After giving informed consent, demographics of age and gender, height and weight, years of education, as well as MS-related information such as EDSS, type of MS, use of assistive device for walking in daily life, and year of diagnosis, will be collected and provided by the centers or via self-report. The participants will be instructed to keep their normal routine but to avoid extraneous physical activity at least 24 hours before the data collection session.