Bimanual Motor Skill Learning in Acute Stroke (MLAS4)

Exploring the Neural Substrates of Proximal and Distal Bimanual Motor Skill Learning Through Robotics and Multimodal Brain Imaging

The subacute phase of stroke provides a window into how a lesion perturbs sensorimotor functions prior to reorganisation driven by plasticity and neurorehabilitation. The recovery from motor impairment has been extensively studied, but it is currently unknown whether motor skill learning (MSkL) is enhanced or impaired during acute stroke, especially bimanual motor skill learning (bim-MSkL), which likely requires more motor-attentional-cognitive resources than unimanual MSkL.

The goals of this project are: to determine the neural substrates critical to achieve proximal and distal bimanual motor skill learning (bim-MSkL) by specifying whether (sub)acute stroke to different brain areas (cortical and subcortical) induce specific deficits in bimanual and/or distal bim-MSkL, which behavioral components are involved in bim-MSkL, and whether damage to the motor, sensory and inter-hemispheric pathways specifically impairs proximal and/or distal bim-MSkL.

Study Overview

• Status: Recruiting
• Conditions: Stroke, Acute; Stroke, Subacute
• Intervention / Treatment: Device: REAplan®; Device: Dextrain Manipulandum®

Detailed Description

Over 3 consecutive days, the patients will be evaluated and will train on the rehabilitation robot REAplan® (http://www.axinesis.com/) to assess proximal bim-MSkL and on the manual dexterity tool Dextrain Manipulandum (https://www.dextrain.com/) to assess distal bim-MSkL.

For proximal bim-MSkL, patients will train over the 3 days on the serious game Circuit on the bimanual REAplan® and will be randomised to two different bimanual versions. By this means, the investigators will explore the components of bim-MSkL in acute stroke patients.

The motor skill learning setup (Circuit) that was developed and successfully used in healthy individuals and stroke patients has already been implemented in the REAplan® environment and will be used as innovative serious games based on a speed/accuracy trade-off (SAT), allowing a detailed analysis of motor skill learning components (speed, accuracy, SAT, movement smoothness, dynamics...). For the serious game Circuit, who based on motor skill learning, the subjects will have to practice a complex circuit and move a cursor as quickly and accurately as possible by controlling the handles of the robot with both arms.

For distal bim-MSkL, patients will train on a complex sequence of finger movements involving both hands. Each day, several successive repetitions of the sequence will be displayed, corresponding to one block. 3 to 6 blocks will be repeated, each separated by 30 sec of rest. After training on the third day, a new sequence will be repeated for 3 blocks to assess generalization.

To explore the role of different brain structures in bim-MskL, Voxel-based Lesion Symptom Mapping (VLSM) based on high-resolution brain magnetic resonance imaging (MRI) scans, will be used to analyse the relationship between tissue damage and proximal/distal bim-MskL scores on a voxel-by-voxel basis.

Diffusion Tensor Imaging (DTI) will quantify the integrity of several white matter tracts, allowing through correlation analyses to unveil the white matter tracts crucial to achieve proximal and/or distal bim-MskL.

In addition, several "classical" clinical scales and tests will be used to evaluate overall motor-sensory-cognitive functions.

In addition to the (sub)acute stroke patients, a group of healthy individuals who will not undergo MRI (n=60) will be enrolled as control group. Subjects in this group will also be randomized 1/1 in the two versions of the bimanual Circuit task on the REAplan® robot.

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yves Vandermeeren, MD, PhD; Phone Number: +32 81 42 33 21; Email: yves.vandermeeren@uclouvain.be
• Study Contact Backup: Name: Coralie van Ravestyn, MSc; Phone Number: +32 81 34 06; Email: coralie.vanravestyn@uclouvain.be

Study Locations

• Belgium
  • Yvoir, Belgium, 5530
    • Recruiting
    • University Hospital CHU Dinant Godinne UCL
    • Contact: Yves Vandermeeren, MD, PhD; Email: yves.vandermeeren@uclouvain.be
  • Namur
    • Yvoir, Namur, Belgium, 5530
      • Recruiting
      • Chu Ucl Namur
      • Contact: Coralie van Ravestyn; Phone Number: +3281423406; Email: coralie.vanravestyn@uclouvain.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

ACUTE STROKE PATIENTS:

Inclusion Criteria:

• acute stroke (< 21 days)
• aged 18-90 years
• with a demonstrated stroke (ischemic or hemorrhagic) lesion on brain imaging

Exclusion Criteria:

• " classical " contre-indication to MRI (non-MR-compatible pacemaker, pregnancy, non-MR-compatible implanted devices, claustrophobia, etc ...)
• difficulty in understanding or executing commands
• drug/alcohol abuse
• severe aphasia / cognitive deficits interfering with study
• inability to complete the tasks (i.e. full paralysis of the arm)
• multiple strokes / dementia / psychiatric condition

HEALTHY INDIVIDUALS:

Inclusion Criteria:

• 18-90 years

Exclusion Criteria:

• medical history with a previous stroke / relevant neurological deficit
• drug/alcohol abuse
• psychiatric condition/ dementia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bimanual Circuit version 1; Training on the REAplan® robot with a serious game based on proximal motor skill learning (bim-MSkL) with the bimanual version 1 of the Circuit task and training on the Dextrain Manipulandum with a serious game based on distal bim-MSkL	Device: REAplan®; motor skill learning with the REAplan® rehabilitation robot, to be performed with both arms; Device: Dextrain Manipulandum®; motor skill learning with the Dextrain Manipulandum® dexterity tool to be performed with both hands
Experimental: Bimanual Circuit version 2; Training on the REAplan® robot with a serious game based on motor skill learning (MSkL) with bimanual version 2 of the Circuit task and training on the Dextrain Manipulandum with a serious game based on distal bim-MSkL	Device: REAplan®; motor skill learning with the REAplan® rehabilitation robot, to be performed with both arms; Device: Dextrain Manipulandum®; motor skill learning with the Dextrain Manipulandum® dexterity tool to be performed with both hands

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
bimanual Speed/Accuracy Trade-off (bi-SAT), bimanual Speed/Accuracy Trade-off measured by the REAplan® robot	bimanual Speed/Accuracy Trade-off: mathematical computation of the relationship between speed and accuracy	change between baseline (Day 1) and after training (Day 3)
bimanual Coordination factor (bi-CO), bimanual Coordination factor measured by the REAplan® robot	bimanual Coordination factor, mathematical measure of the phase coherence between speeds of both arms	change between baseline (Day 1) and after training (Day 3)
bi-Force, bimanual force measured by the REAplan® robot	bimanual forces, forces exerted in the wrong direction by each arm (Newtons)	change between baseline (Day 1) and after training (Day 3)
Root Mean Square Error (RMSE), bimanual root mean square error measured by the Dextrain Manipulandum	Tracking error between the actual applied force and the target force	change between baseline (Day 1) and after training (Day 3)
Bimanual Dexterity Coordination Index measured by the Dextrain Manipulandum	bimanual Coordination factor, mathematical measure of the phase coherence between speeds of both thumb-index clamps	change between baseline (Day 1) and after training (Day 3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reaction time measured by the Dextrain Manipulandum	time between the target appearance and when the force applied exceeds threshold	change between baseline (Day 1) and after training (Day 3)
Rise time measured by the Dextrain Manipulandum	time between the reaction time and reaching the plateau	change between baseline (Day 1) and after training (Day 3)
Coactivation measured by the Dextrain Manipulandum	binary measure of unasked fingers activated above the force threshold	change between baseline (Day 1) and after training (Day 3)
Hold time measured by the Dextrain Manipulandum	time of plateau maintenance	change between baseline (Day 1) and after training (Day 3)
Voxel-based Lesion Symptom Mapping (VLSM)	Diffusion Weighted Imaging (DWI)	Baseline
Diffusion Tensor Imaging (DTI)	Fractional Anisotropy	Baseline
Fugl Meyer Upper Extremity Test (FMA-UE)	Tests impairments of the upper limb after stroke. Range: 0-66. A higher score means less impairment.	Day1
Arm Motor Ability (AMA) test	Measure disabilities of the upper limb after stroke. Range: 0-100. A higher score means less disabilities in activities of daily living.	Day 1
Montreal Cognitive Assessment (MoCA)	Tests the short-term memory, visuospatial skills, executive functions, attention, concentration, working memory, language and orientation in time and space. Range: 0-30, higher score means no cognitive impairment.	Day 1
Fatigue Visual Analog Scale (VAS)	Visual Analog Scale to evaluate fatigue = a psychometric response scale which can be used in questionnaires. It is a measurement instrument for subjective characteristics or attitudes that cannot be directly measured. When responding to a VAS item, respondents specify their level of agreement to a statement by indicating a position along a continuous line between two end-points. Range : 0- 10. A higher score means a higher level of fatigue.	Day 1
Shoulder Abduction Finger Extension (SAFE) test	A prognostic determinant of the function of the hemiparetic upper limb (UL) after a stroke. For each of the 2 subitems, the range is 0-5. A score of 5 means normal power. A score of 0 means no contraction possible.	Day 1
Modified Ashworth Scale (mAS)	clinical measure of spasticity. For each of the 8 subitems, the range is 0-4. A higher score means a higher level of spasticity	Day 1

Collaborators and Investigators

• Sponsor: University Hospital of Mont-Godinne
• Investigators: Principal Investigator: Yves Vandermeeren, MD, PhD, UCLouvain IONS

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2023
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: February 22, 2023
• First Submitted That Met QC Criteria: March 6, 2023
• First Posted (Actual): March 8, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Rehabilitation; Upper limb; Acute stroke; Subacute stroke; Motor Skill Learning
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke
• Other Study ID Numbers: Bim-MSkL acute

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data Management Plan REDCap
• IPD Sharing Time Frame: The data will become available during the beginning of the study and for 20 years.
• IPD Sharing Access Criteria: Login user of the Hospital of CHU UCL Namur -Site Godinne
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No