Identification of Non-motor Brain Areas Involved in Upper Limb Motor Recovery After Stroke (NOMO-Stroke)

Why: Upper-limb recovery post-stroke is challenging. Rehabilitation, aiming to induce plasticity takes an important place in patients' treatment. The last years, non-invasive brain stimulation of the primary motor cortex has gained the communities' interest, allowing direct modification of neural excitability and thus impacting plasticity. Yet, research outcomes remain inconclusive to date. It's expected this to be related to patient heterogeneity including mild to severe motor deficits, and suboptimal site of stimulation. It might be questioned whether M1 stimulation is preferable over that of higher association areas like the parietal or premotor cortex.

What: The aim of the study is to identify alternative brain regions to stimulate, related to improved motor quality after a severe initial deficit. How: by following motor recovery over time, by co-recording movement kinematics and brain activity.

Because: Stimulation of the novel identified regions may improve motor recovery after stroke.

Study Overview

• Status: Terminated
• Conditions: Stroke; Upper Limb Ischemia
• Intervention / Treatment: Other: Magnetic Resonance Imaging

Detailed Description

Patients' brain activity and connectivity during an elbow flexion/extension task will be evaluated at 2 weeks (V0), 3 months (V1) and 6 months (V2) post-stroke. Between V0 and V1, patients will receive standard in-care rehabilitation at the physical and rehabilitation medicine department (PMR) of Montpellier's University Hospital: 120 minutes a day, for 5 days/week (orthopedic training, sitting/standing balance, walking, sensorimotor training - including 2 and 3 dimensional reach to grasp exercises with and without vision, functional electrical stimulation of the upper-limb, finger pinching exercises). On the day of imaging, a clinical evaluation will be performed to evaluate patients upper-limb function (Fugl-Meyer Upper Extremity scale) and capacity (WOLF motor function test & Box and Block test). The imaging protocol includes a 3DT1 for anatomical reference, a functional task-based MRI with block-design (30s rest alternated with 30s of activity) and diffusion tensor imaging (DTI) to quantify anatomical connectivity. During imaging, participants will lay on their back with their arm stretched along their body. A short auditory signal will inform patient when to start/stop moving. During movement, only the elbow will be rhythmically flexed and extended at a self-selected comfortable pace in the vertical plane. The motor task will be performed with both the paretic and ipsilesional upper-limb, in random order. Patients that are unable to move, will be asked to keep trying to move during the activity block.

Material: 3.0T whole-body magnet MRI (Prisma Siemens, Germany), MRI compatible 3D motion camera's (Qualisys, France).

Imaging data will be acquired by the I2FH research platform at the Montpellier University Hospital Data treatment: functional Imaging data will be preprocessed following standard procedures, including reorientation to the anterior commissure, slice-time correction, realignment, co-registering & normalization to 3DT1 anatomical template, smoothing. Subsequent group analyses using general linear models, will be corrected for multiple comparisons. Imaging data will be analyzed by the I2FH research platform. 3D-Movement time-series of upper-limb displacement will be analyzed by Euromov, using matlab the mathworks. The movement will be quantified by its shaping (e.g. Amplitude/Frequency) and structure (e.g. Fluency/Directness). Clinical testing will be performed as part of standard care evaluations at the physical rehabilitation medicine department of the hospital of Montpellier and Nimes.

Schedule visit:

Patients: V0: ~10 post-stroke, V1: ~3 months post-stroke, V2: ~6 months post stroke. Clinical testing will be performed on the day (+/- 1) of the MRI session.

Healthy subjects will be evaluated once

• Study Type: Observational
• Enrollment (Actual): 28

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34090
    • Montpellier University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

All patients admitted at the University hospital of Montpellier with an ischemic stroke that are meeting the inclusion criteria.

Description

Inclusion Criteria patients post-stroke:

• 18-85 yrs,
• First ever ischemic stroke of the middle cerebral artery,
• Initial severe motor deficit (fugl-Upper limb assessment score <30/66),
• Written consent.

Exclusion criteria patients post-stroke:

• The presence of secondary neurological or psychiatric deficits,
• Strong hemineglect (bell-test);
• Aphasie >3/5 on the Boston scale,
• Bilateral stroke,
• Hemorraghic stroke,
• MRI contra-indications,
• Pregnancy/breastfeading,
• Patient under curatele,
• Medical urgency.

Inclusion criteria healthy subjects:

• Age matching (+/- 5 yrs),
• Sexe matching,
• Written consent.

Exclusion criteria healthy subjets:

• Neurological or psychological deficits;
• MRI contra-indations;
• Pregnancy/breastfeeding,
• Personunder curatele.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Post-stroke; People with a first ever ischemic stroke of the middle cerebral artery presenting severe motor deficits of the upper-limb at onset. The patients	Other: Magnetic Resonance Imaging; IMR is a non-invasive imaging technology that produces three dimensional detailed anatomical images. It is often used for disease detection, diagnosis, and treatment monitoring. It is based on sophisticated technology that excites and detects the change in the direction of the rotational axis of protons found in the water that makes up living tissues.
Controls; Age and sexe matched healthy subjects without known neurological and or psychological deficits.	Other: Magnetic Resonance Imaging; IMR is a non-invasive imaging technology that produces three dimensional detailed anatomical images. It is often used for disease detection, diagnosis, and treatment monitoring. It is based on sophisticated technology that excites and detects the change in the direction of the rotational axis of protons found in the water that makes up living tissues.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of brain activity during motor task during post-stroke recovery	Functional MRI imaging with upper-limb elbow flexion in a blocked-design. Analysis with integrated movement kinematics that are registered simulateously.	~10days, 3 months and 6 months post-stroke.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fMRI task-based and resting state brain connectivity	Resting-state and functional MRI with upper-limb elbow flexion	at ~10days, 3 months and 6 months post-stroke.
Diffusion Tensor Imaging anatomical brain connectivity	DTI imaging	at ~10days, 3 months and 6 months post-stroke.

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Collaborators: Centre Hospitalier Universitaire de Nīmes; IMT Mines Alès; Euromov, Université Montpellier
• Investigators: Principal Investigator: Isabelle LAFFONT, PHD,MD, Montpellier University Hospital

Publications and helpful links

General Publications

• Belkacemi Z, Van Dokkum L, Deverdun J, Tchechmedjiev A, Rouges C, Troalen T, Laffont I, Mottet D, Le Bars E. How to integrate simultaneously recorded Kinematic into an individual fMRI Motor Task Analysis?. Annu Int Conf IEEE Eng Med Biol Soc. 2025 Jul;2025:1-7. doi: 10.1109/EMBC58623.2025.11253807.

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2022
• Primary Completion (Actual): June 13, 2025
• Study Completion (Actual): June 13, 2025

Study Registration Dates

• First Submitted: February 23, 2022
• First Submitted That Met QC Criteria: April 5, 2022
• First Posted (Actual): April 6, 2022

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: June 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Neuroplasticity; Motor recovery; Ischemic stroke; Functional MRI; Upper-limb
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Ischemic Stroke; Stroke; Investigative Techniques; Chemistry Techniques, Analytical; Spectrum Analysis; Magnetic Resonance Spectroscopy
• Other Study ID Numbers: RECHMPL20_0431

Drug and device information, study documents

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