Unraveling Active Ingredients of Neurorehabilitation: Investigating Cortical Activity During Task-oriented Exercises (INSIDE)

Investigate Neuro-rehabilitation Active Ingredients of Specific Task-oriented Training In People With Multiple Sclerosis With Different Challenging Conditions and Extrinsic Feedbacks

The driving idea of this project is to use new imaging techniques during 0functional movements to study relearning during a typical rehabilitation session.

The novelty of this project is to move from studies inquiring changes in brain activity patterns before and after rehabilitation toward a paradigm in which cortical activity is studied during the execution of the exercise. This would allow better understanding of cortical mechanisms underpinning functional improvements.

The project builds on preceding studies, partially funded by FISM, from the three research units involved in this project, aimed at assessing the impact of rehabilitation on mobility and balance and at assessing the effects of neurorehabilitation on brain plasticity. In this study, we will include 40 healthy subjects and a sample of 20 consecutive People with Multiple Sclerosis (PwMS), and we will investigate brain cortical activity during a typical session of task-oriented exercises. In specific, participants will undergo a treadmill training in which they will be required to keep their trunk and head stable in space using a biofeedback device. To study the effects of the session in improving dynamic stability, Head/trunk movements will be registered by inertial measurement units, while cortical activity will be concurrently assessed by functional near-infrared spectroscopy (fNIRS).

The first phase of the project will include healthy subjects and will be useful to understand the main cortical areas involved in the proposed motor tasks, in order to design the appropriate montage and protocol for fNIRS acquisition in PwMS. Finally, the analysis of the possible differences in cortical activation during different experimental conditions (e.g., biofeedback rehabilitation) in healthy subjects and PwMS will serve to develop a model for neurological rehabilitation.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis; Healthy Volunteer

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

Study Locations

• Italy
  • Genova, Italy, 16126
    • Recruiting
    • Università di Genova
    • Contact: Laura Bonzano, Associate Professor; Phone Number: +39 010 353 7040; Email: laura.bonzano@unige.it
    • Principal Investigator: Laura Bonzano, Associate Professor
  • Milan, Italy, 20148
    • Recruiting
    • IRCCS Santa Maria Nascente - Fondazione Don Carlo Gnocchi
    • Contact: Francesca Baglio, Medical Doctor - Neurologist; Phone Number: +39 0240308814; Email: fbaglio@dongnocchi.it
    • Principal Investigator: Francesca Baglio, Medical doctor - Neurologist
  • Milan, Italy, 20148
    • Active, not recruiting
    • Universita degli Studi di Milano

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

People with Multiple sclerosis people affiliated with the rehabilitation center of the IRCCS Santa Maria Nascente of the Don Gnocchi Foundation will be recruited. Participants should be able to maintain upright posture without any assistance for 30 seconds, and to walk without any assistance.

Description

Inclusion Criteria:

• subjects between 18 and 60 years of age,
• diagnosis of MS (McDonald criteria, Thompson et al, 2018), stable disease course without worsening more than 1 EDSS point over the last 3 months, EDSS between 3 and 4.5 points,
• healthy right-handed volunteers,
• able to release a written informed consent.

Exclusion Criteria:

• Unable to comprehend the aims of the study and to follow test instructions;
• Diagnosis of major depression (DSM-5);
• Severe joint and/or bone disorders interfering with balance and gait (based upon clinical judgment);
• Cardiovascular diseases;
• Severe visual impairments interfering with the execution of the protocol;
• epilepsy;
• intake of neuroleptic and antiepileptic drugs.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Multiple sclerosis; A sample of 20 consecutive PwMS will be recruited.
Healthy volunteers; We will recruit a group of healthy individuals to obtain normative reference data. These individuals will be matched for sex and age with the subjects having multiple sclerosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Head and trunk movements quantified with Inertial Measurement Units (IMU)	The following variables are calculated: (1) the angular displacements in the sagittal and frontal planes, calculated as 1 standard deviation (SD) from the angular displacement data; and the head and angular velocities, which are the root mean square of the first derivative of angular displacements in the sagittal and frontal planes.	Baseline
Cortical activation with Functional Infrared Spettroscopy (fNIRS)	fNIRS data analysis will identify the acquisition channels (and hence the cortical areas) significantly active in the different experimental conditions.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
10 Meters walking test	The 10-Meter Walking Test (10MWT) is a commonly used assessment to measure walking speed and functional mobility, especially in individuals with neurological conditions like multiple sclerosis	Baseline
Twelve-Item Multiple Sclerosis Walking Scale (MSWS_12)	to assess walking perceived ability of people with multiple sclerosis. The score ranges from 12 to 60, with higher scores indicating a higher degree of walking impairment.	Baseline
Modified Fatigue Impact Scale (MFIS)	To assess the perceived impact of fatigue in people with multiple sclerosis. The score ranges from 0 to 84, with higher scores indicating a higher degree of fatigue.	Baseline
Beck Depression Inventory (BDI-II)	To monitor anxiety and depression. The score ranges from 0 to 63, with higher scores indicating a higher degree of depression.	Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expanded Disability Status Scale (EDSS)	The EDSS is a widely used scale for measuring the level of disability in individuals with multiple sclerosis (MS). Developed by Kurtzke in 1955, it assesses both the severity of neurological impairment and the degree of disability in various functional systems. The score ranges from 0 to 10, with higher scores indicating a higher degree of disability.	Baseline

Collaborators and Investigators

• Sponsor: Fondazione Don Carlo Gnocchi Onlus
• Collaborators: University of Milan; Università degli Studi of Genova

Publications and helpful links

General Publications

• Prosperini L, Di Filippo M. Beyond clinical changes: Rehabilitation-induced neuroplasticity in MS. Mult Scler. 2019 Sep;25(10):1348-1362. doi: 10.1177/1352458519846096.
• Cattaneo D, Ferrarin M, Frasson W, Casiraghi A. Head control: volitional aspects of rehabilitation training in patients with multiple sclerosis compared with healthy subjects. Arch Phys Med Rehabil. 2005 Jul;86(7):1381-8. doi: 10.1016/j.apmr.2004.12.029.
• Bonilauri A, Sangiuliano Intra F, Pugnetti L, Baselli G, Baglio F. A Systematic Review of Cerebral Functional Near-Infrared Spectroscopy in Chronic Neurological Diseases-Actual Applications and Future Perspectives. Diagnostics (Basel). 2020 Aug 12;10(8):581. doi: 10.3390/diagnostics10080581.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Estimated): July 31, 2025
• Study Completion (Estimated): July 31, 2025

Study Registration Dates

• First Submitted: February 7, 2025
• First Submitted That Met QC Criteria: February 12, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 12, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: rehabilitation; multiple sclerosis; motor control; cortical plasticity
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: 2022/R-Multi/021

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