Effects of Exercise and Sleep on Motor Learning and Functional Abilities in Multiple Sclerosis (ExSiMS)

Effects of Aerobic Exercise and Daytime Sleep on Neurorehabilitation and Functional Abilities in Multiple Sclerosis: Evidence of Training the Brain in Neurorehabilitation

The ExSiMS study is a randomized, controlled crossover study including 20 individuals (18-70 years) diagnosed with relapsing remitting Multiple Sclerosis (MS) This project investigates, through behavioral and neurophysiological measurements, how aerobic exercise on an ergometer bike and sleep in the form of a nap and overnight sleep may enhance cortical motor skill learning evaluated by a complex hand motor skill test and thereby improve functional capacity in individuals with MS. Beyond the effect on motor skill learning, the project investigate the effect on electroencephalography (EEG) - electromyography (EMG) coherence.

The study hypothesizes that individuals with neurological conditions, such as multiple sclerosis (MS), may experience beneficial effects on specific motor rehabilitation through systematically planned cardiovascular exercise and sleep scheduling, due to positive impacts on memory consolidation.

Aims:

• Investigate the brain's neurophysiological responses and memory effects following a training intervention and, separately, sleep, in the form of a power nap, in individuals with MS.
• Examine whether these effects persist beyond the few days previously observed in healthy individuals by implementing a longer-term intervention.
• Explore whether the training effect is influenced by disease activity in the brain, such as during relapses and during immunosuppressive treatment.
• Assess whether the presence of abnormally reduced cognitive endurance (fatigue) affects the impact of the intervention involving exercise and sleep.

The study is based on documented positive effects of physical activity and sleep in both young and older adults, as well as in individuals recovering from stroke. The research thus offers promising perspectives for broader applications within neurorehabilitation, and particularly for MS, as the disease is associated with functional impairments. At the same time, both physical exercise and sleep represent meaningful interventions that should be thoughtfully integrated into rehabilitation strategies.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis; Sleep; Exercise; Motor Learning; Memory
• Intervention / Treatment: Other: Aerobic Exercise; Behavioral: Daytime Sleep - Nap

Detailed Description

The ExSiMS-project consists of both a proof-of-concept study and a longitudinal study.

In both studies, participants will perform a visuomotor accuracy tracking task (VATT) with their dominant hand on the main experimental days. The participants will wear EEG and EMG electrodes during the VATT. This will make it possible to investigate cortical activity during skill acquisition and later analyse the corticomuscular coherence. After the VATT, the participants will be randomized to either 20 min aerobic exercise on an ergometer bike, a short 30-minute nap or control (sitting rest). The interventions will run over a longer period of time in the longitudinal study.

The participants will be asked to do a retention test of the visuomotor accuracy tracking task 24 hours later.

The studies will run over more experiment days divided into two experiment blocks of at least two experiment days separated by between two weeks to three months.

Methods:

• Electroencephalography (EEG) and Electromyography (EMG)
• Actigraphy/Accelerometry
• Visuomotor Accuracy Tracking Task (VATT)
• Training on an Ergometerbike: Graded Exercise Test (GXT), High Intensity Interval Training (HIIT)
• Polysomnography (PSG)

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Caroline Sadolin Muushardt, MSc; Phone Number: +45 46323200; Email: cmuu@regionsjaelland.dk
• Study Contact Backup: Name: Martin Ballegaard, MD MPG PhD; Email: mbag@regionsjaelland.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2200
    • Not yet recruiting
    • Section of Movement and Neuroscience, Department of Nutrition, Exercise, and Sports, University of Copenhagen
    • Contact: Jesper Lundbye-Jensen, PhD; Phone Number: +45 35 32 73 30; Email: jlundbye@nexs.ku.dk
    • Contact: Caroline Sadolin Muushardt, MSc; Email: cmuu@regionsjaelland.dk
  • Roskilde, Denmark, 4000
    • Recruiting
    • Zealand University Hospital Roskilde
    • Contact: Caroline Sadolin Muushardt, MSc; Email: cmuu@regionsjaelland.dk
    • Contact: Martin Ballegaard, MD MPG PhD; Phone Number: +45 46323200; Email: mbag@regionsjaelland.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Competent individuals (aged 18-70) diagnosed with early relapsing-remitting MS
• Expanded Disability Status Score, 1 < EDSS < 4.5
• MRC muscle strength ≥ 4+ in the dominant hand

Exclusion Criteria:

• Implanted devices, such as pacemakers or stimulators
• Epilepsy or neuromuscular diseases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aerobic Exercise - GXT; The aerobic exercise will consist of about 20 minutes of Graded Exercise Training (GXT) on an ergometer bike. The experimenter will instruct and motivate the participant through the aerobic exercise.	Other: Aerobic Exercise; The Aerobic Exercise Intervention consists of 20 minutes of Graded Exercise Test (GXT) on an ergometer bike. The participants start with 5 minutes of warm-up. The wattload will then be increased until exhaustion.
No Intervention: Control - Rest; The participant will rest in a sitting position in a quiet room for 20 minutes. The participant is allowed to read or engage in similar quiet and sitting activities.
Experimental: Daytime Sleep - Nap; The participants will be asked to try and take a 30-minute nap. The participant will be provided with a bed in a dark and quiet room.	Behavioral: Daytime Sleep - Nap; The Daytime sleep consists of a 30-minute nap after the acquisition of the visuomotor accuracy tracking task. The participants will be asked to rest in a supine position in a bed in a dark and quiet room.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motor/Skill Learning	Visuomotor accuracy tracking task. Online and offline effects. Unit: Range from 0 (lowest) to 100 (highest) percent.	Assessed on experiment days 1, 2, 3 and 4.
Neurophysiological Measurement I - Cortical Activity	Cortical activity will be measured with electroencephalography (EEG) during skill acquisition. Unit: EEG Power in several frequency bands.	Assessed on experiment day 1, 2, 3 and 4.
Neurophysiological Measurement II - Muscular Activity	Muscle activity will be measured with electromyography (EMG) during skill acquisition. Unit: EMG amplitude.	Assessed on experiment day 1, 2, 3 and 4.
Neurophysiological Measurement III - Corticocortical Functional Connectivity	Corticocortical functional connectivity will me measured as functional coupling in EEG during skill acquisition. Unit: functional coupling in EEG (scale 0-1).	Assessed on experiment day 1, 2, 3 and 4.
Neurophysiological Measurement IV - Corticomuscular Functional Connectivity	Corticomuscular functional connectivity during skill acquisition will be measured with functional coupling between EEG and EMG. Unit: functional coupling in EEG-EMG.	Assessed on experiment day 1, 2, 3 and 4.
Neurophysiological Measurement V - Muscular Functional Connectivity	Muscular functional connectivity during skill acquisition will be assessed using EMG-EMG coherence between M. Abductor Pollicis Brevis and First Dorsal Interosseus. Unit: EMG-EMG coherence (0-1)	Assessed on experiment day 1, 2, 3 and 4.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Actigraphy	Measurement of sedentary, moderate, and vigorous activity during the experiment period. Unit = hours:min.	Assessment from day 0 to experiment day 4.
Sleep quality - self reported sleep latency.	Self-reported sleep latency will be measured by the National Sleep Foundation Sleep Diary translated to Danish. Unit: Hour:minutes.	Assessed at the days leading up to experiment days 1,2,3, and 4.
Sleep quality - Self reported sleep duration	Self-reported sleep duration will be measured by the National Sleep Foundation Sleep Diary translated to Danish. Unit: Hour:min.	Assessed at the days leading up to experiment days 1,2,3, and 4.
Physical fitness level - work load	Graded exercise test (GXT) on an ergometer bike - maximum work load. Unit: watt	Assessed on either experiment day 1 or 3.
Physical fitness level - heart rate	Graded exercise test (GXT) on an ergometer bike - heart rate measured with a chest strap. Unit: beats per minute (BPM).	Assessed on either experiment day 1 or 3
Physical fitness level - rating of perceived exertion	Graded exercise test (GXT) on an ergometer bike - rating of perceived exertion with the Borg scale. Unit: Borg scale 6-20 (6 = rest, 20 = maximal exhaustion).	Assessed on either experiment day 1 or 3.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wakefulness	Wakefulness will be measured by the Stanford Sleepiness Scale: From 1 to 7. 1= "Feeling active and vital; alert; wide awake". 7= "Almost in reverie; sleep onset soon; lost struggle to remain awake. X = Asleep".	Assessed on experiment days 1, 2, 3 and 4.
Handedness	Handedness questionnaire to determine the participant's dominant hand. Unit: Laterality index (-100.00 (lefthanded) to 100.00 (righthanded).	Assessed on day 0.
Reaction Time Task	A simple Reaction Time Task on a computer. Unit: ms.	Assessed on day 0.
The fatigue scale for motor and cognitive functions (FSMC)	Questionnaire measuring fatigue in individuals with Multiple Sclerosis. Unit: FSMC_total = Points from 20-100 (≥ 43 Mild Fatigue, ≥ 53 Moderate Fatigue, ≥ 63 Severe Fatigue).	Assessed on day 0.

Collaborators and Investigators

• Sponsor: Zealand University Hospital
• Collaborators: University of Copenhagen
• Investigators: Principal Investigator: Martin Ballegaard, Zealand University Hospital - Roskilde

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2025
• Primary Completion (Estimated): August 30, 2028
• Study Completion (Estimated): November 30, 2028

Study Registration Dates

• First Submitted: November 26, 2025
• First Submitted That Met QC Criteria: December 11, 2025
• First Posted (Estimated): December 26, 2025

Study Record Updates

• Last Update Posted (Actual): January 8, 2026
• Last Update Submitted That Met QC Criteria: January 5, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Sleep; Memory; Aerobic Exercise; Cognitive Function; Motor Learning; Neurorehabilitation; Learning Ability; Daytime Sleep
• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Behavior; Multiple Sclerosis; Motor Activity; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise
• Other Study ID Numbers: SJ-1040 (Other Identifier: De Videnskabelige Komitéer)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No