Clinical Validation of a Hybrid BCI-controlled FES for Upper Limb Rehabilitation After Stroke

Study Overview
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Brief Summary
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The RECOMMENCER project aims at developing and testing a novel hybrid Brain Computer Interface device based on cortico-muscular connectivity, that will be employed to activate Functional Electrical Stimulation (FES) of upper limb muscles. After the technical implementation of the device and its preliminary testing on healthy subject, the investigators will evaluate the effects of a 1 month training with the device (RECOM) on post-stroke patients undergoing standard rehabilitation (add-on). The proposed intervention will be compared with an active physiotherapy training including FES (CTRL) which will be focused on upper limb with similar intensity as the target intervention (also delivered in add-on).

Detailed Description
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Brain-Computer Interface (BCI) systems for upper limb rehabilitation have proven some efficacy in the context of several randomized controlled trials (RCT). Such systems rely on the possibility reinforce motor-related brain activity (derived eg from electroencephalography, EEG) harnessing neuroplasticity phenomena ultimately leading to favorable motor outcome. Up to now, no hybrid BCI (hBCI) has been tested successfully for this purpose in a clinical trial. Hybrid BCIs include signals from the periphery (most commonly muscles, via surface electromyography, EMG) and are usually employed to improve BCI performances. In a rehabilitative context, the investigators aim to employ EMG signals to characterize common post-stroke abnormalities (spasticity, co-contractions, motor overflow) and possibly include those in a novel hBCI paradigm to promote both volitional control (EEG) over upper limb movement and close to normal muscular activation (EMG). To do so, the investigators propose cortico-muscular coherence (CMC) as a hybrid feature for BCI control. CMC is a measure of EEG-EMG synchronization during movement and has been described extensively in post-stroke patients in relation to their residual motor ability. With respect to previous literature, the proposed approach foresees the estimation of CMC as a multimodal integrated EEG-EMG network, comprising multiple EEG electrodes over the scalp bilaterally and several upper limb muscles bilaterally, so as to capture the above mentioned motor abnormalities (eg abnormal recruitment of non-target muscles). The investigators have already tested such feature on healthy subjects and stroke patients offline and verified its capability to detect upper limb movements online (studies published and/or submitted, see references). An already available BCI prototype was adapted with the parameters derived from such offline studies (see references). The RECOM intervention will be validated within a RCT (single blinded, for evaluators) on stroke patients undergoing rehabilitation (add-on). Before and after the intervention, all patients will undergo an extensive clinical evaluation (see outcome measures) and neurophysiological assessment. The latter will consist in a high density EEG-EMG recording during simple/complex upper limb movements. The recording will include a cinematic analysis (inertial measurement units - IMUs). The investigators hypothesize a better functional motor outcome in the affected upper limb for the RECOM group, which will be described by means of common clinical/functional scales combined with EEG/EMG and cinematic evaluation. Furthermore, aspects related to acceptability and usability of the novel system will be evaluated. In detail mood, motivation and satisfaction will be evaluated before (mood motivation) and after (satisfaction) each training session by means of Visual Analogue Scales; workload will be evaluated at the end of second and last training session by means of the Nasa-Task Load Index.

Official Title
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RECOMmENceR: RE-establishing COrtico Muscular COMunication to ENhance Recovery. Clinical Validation of BCI-controlled Functional Electrical Stimulation for Upper Limb Rehabilitation After Stroke

Conditions
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Stroke Sequelae, Motor Disorders

Intervention / Treatment
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* Device: RECOM - hBCI training
* Other: CTRL - upper limb training with FES


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: unilateral stroke event at least 3 months before recruitment reduced strength in the upper limb Exclusion Criteria: concomitant diseases affecting upper limb function spasticity in the upper limb (4-5 of MAS) severe neuropsychological deficit preventing active participation to the study contraindication to FES or EEG/EMG recording

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Eligible patients admitted to Fondazione Santa Lucia will be randomized in equal proportions between target intervention (RECOM) and control (CTRL)
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RECOM - hBCI training<br>Patients in the RECOM group will receive treatment in add-on to standard rehabilitation as follows. The RECOM device is a h-BCI system that controls FES of upper limb muscles: the patient is asked to attempt simple upper limb movements (eg extension of fingers); the device recognizes (in correct trials) close-to-normal EEG-EMG activation and initiates FES of extensor muscles in the forearm. RECOM training consists in a set of trial repetition for a total duration per session of approximately 20-30 minutes (excluding set up time and calibration). FES parameters will be set specifically for each patients according to standard guidelines to achieve full movement and so as to avoid any kind of discomfort for the patients. The intervention regimen will be 2-3 times per week for 4 consecutive weeks. | Device: RECOM - hBCI training<br>* The RECOM device is a h-BCI system that controls FES of upper limb muscles: the patient is asked to attempt simple upper limb movements (eg extension of fingers); the device recognizes (in correct trials) close-to-normal EEG-EMG activation and initiates FES of extensor muscles in the forearm. RECOM training consists in a set of trial repetition for a total duration per session of approximately 20-30 minutes (excluding set up time and calibration). FES parameters will be set specifically for each patients according to standard guidelines to achieve full movement and so as to avoid any kind of discomfort for the patients. The intervention regimen will be 2-3 times per week for 4 consecutive weeks.<br>|
| Active Comparator: CTRL - upper limb training with FES<br>Patients in the CTRL group will receive treatment in add-on to standard rehabilitation as follows. An expert physiotherapist will define a set of active exercises focused on upper limb function; the exercises will be combined with FES of forearm muscles. FES parameters will be set specifically for each patients according to standard guidelines to achieve the full required movement and so as to avoid any kind of discomfort for the patients. Session duration will be approximately 20-30 minutes (excluding FES calibration time). The intervention regimen will be 2-3 times per week for 4 consecutive weeks. | Other: CTRL - upper limb training with FES<br>* An expert physiotherapist will define a set of active exercises focused on upper limb function; the exercises will be combined with FES of forearm muscles. FES parameters will be set specifically for each patients according to standard guidelines to achieve the full required movement and so as to avoid any kind of discomfort for the patients. Session duration will be approximately 20-30 minutes (excluding FES calibration time). The intervention regimen will be 2-3 times per week for 4 consecutive weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Fugl-Meyer Assessment (FMA) - upper limb section | Commonly employed functional scale for post-stroke motor function. The scale ranges from 0 (maximum possible impairment) to 66 (no impairment). | Pre-Randomization, Post Training (within 48 hours) | 
| Changes in Action Research Arm Test (ARAT) | Commonly employed functional scale for post-stroke upper limb function. Consists of 19 items with a four scale point. Total scores on the ARAT may range from 0-57 points, with a maximum score of 57 points indicating better performance. | Pre-Randomization, Post Training (within 48 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Modified Ashworth Scale for Spasticity (MAS) | Measure of arm spasticity (at shoulder + elbow + hand) as measured by means of MAS (score from 0 to 5 points, where 0 is equal to absence of spasticity, 5 is equal to high degree of spasticity) | Pre-Randomization, Post Training (within 48 hours) | 
| Changes Box and Block Test (BBT) | The BBT is composed of a wooden box divided in two compartments by a partition and 150 blocks. The BBT administration consists of asking the client to move, one by one, the maximum number of blocks from one compartment of a box to another of equal size, within 60 seconds. | Pre-Randomization, Post Training (within 48 hours) | 
| Changes Numeric Rating Scale for pain in the upper limb (NRS) | Measure of arm perceived pain by means of Numeric Rating Scale (score from 0 to 10 points where 0 is equal to NO PAIN and 10 is equal to UNSPEAKABLE PAIN) | Pre-Randomization, Post Training (within 48 hours) | 
| Changes in Manual Muscle Test (MMT) strength in upper limb segments | Evaluation of residual strength in upper limb muscles - shoulder abduction, elbow flexion and extension, wrist flexion and extension (each segment ranging from 0 - no muscular activation to 5 - full movement against resistance). | Pre-Randomization, Post Training (within 48 hours) | 
| Changes in NIH Stroke Scale | Measure of severity of stroke symptoms as for the National Institute of Health Stroke Scale-NIHSS (composed by 11 items with a total score ranging from 0 to a maximum depending on each item, where 0 is normal and maximum is pathological response) | Pre-Randomization, Post Training (within 48 hours) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stroke, eeg, emg, cortico-muscular coherence, brain computer interface