Neuroimaging Biomarkers Toward a Personalized Upper Limb Action Observation Treatment in Chronic Stroke Patients

Study Overview
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Brief Summary
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Much recent interest was raised by the use of Action Observation Treatment (AOT) in stroke patients rehabilitation. AOT, well-grounded in neurophysiology, is an updated approach, based on mirror neuron system (MNS) used to rebuild motor function despite injuries by engaging the brain regions active during action execution in individuals with limited mobility. This project aims at identifying, for the first time in Italy, neurophysiological electroencephalographic (EEG) biomarkers able to predict rehabilitation outcomes and providing an innovative optimized AOT rehabilitation protocol for chronic Stroke outpatients. EEG will be recorded to identify the most effective stimuli, quantify changes/recovery, profile patients. Moreover, an innovative AOT home-based program will be implemented. The translational research results will ensure advances in the optimization and personalization of the rehabilitative process thus contributing to improve the quality of life of chronic stroke patients. Stroke is a leading cause of death and one of the greatest causes of long-term disability that interferes with a good quality of life. Nowadays the rehabilitation interventions are the major component of patient's care to achieve functional outcome. In the last few years, in order to improve Activity of Daily Living (ADL), new noninvasive strategies have emerged as rehabilitative treatments rather than traditional physical therapies. The Action Observation Treatment (AOT), supported by results collected through randomized controlled trials, is one of these. This new rehabilitation approach is based on the properties of the Mirror Neuron System (MNS; 11-13). The extensive research of the last 20 years on the human MNS (hMNS) showed its importance not only in action recognition but also in motor intentions and other social cognitive functions. Lastly, because recruited also in damage brain (18,19), the MNS is demonstrated to provide satisfactory rehabilitative outcomes. The AOT takes advantage of the opportunity to restore functions despite the patient's impairment and it seems to be a valid example of translational medicine from basic neuroscience to rehabilitation. To date, neurophysiological outcomes were never used for translational purposes aimed to the optimization of the therapy and no evidence, in Italy, related to the effectiveness of the home-based program were proposed.

Detailed Description
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This study protocol provides 3 experimental designs to satisfy 3 different specific aims as follows. Experimental design aim 1: To assess which kind of ADL visual stimuli will be most effective inducing motor excitability during action observation, EEG recording will be performed. 20 Stroke patients (10 with right lesion and 10 left one) will be recruited and video of feeding, self care and external actions showed. The EEG biomarkers will be identify. A comparison on EEG rhythm and biomarkers between the two groups and the ADL categories observed will be investigated. The most effective category will be subsequently selected for the Randomized Controlled Trial (RCT). Experimental design aim 2: This is an RCT study aimed to deeply investigate if EEG biomarkers are predictive of effectiveness of AOT on 40 Chronic Stroke outpatients in order to confirm the translational power of the optimized treatment. The subjects accurately enrolled for hospital program, will be randomly assigned to the Experimental Group (EG) or to the Control one (CG). The EG will observe and execute ADL actions, the CG will observe landscapes and perform the same actions observed by the others one but after verbal instructions. For each condition the patient will be presented with only 1 typology of motor task per day, starting from the easiest and ending with the most complex action throughout 15 sessions spread on 5 weeks (3 sessions/week). Tasks will be based on some relevant activities of daily living belonging to at least one between feeding, self-care or external actions category on the affected side. Each session will last about 15 minutes and will be repeated twice a day, at least 60 minutes apart. Before, after and in the middle of the treatment sessions all patients will be clinically, neurophysiologically (EEG and EMG) and behaviorally (Kinematics) assessed to verify neural plasticity and motor recovery. The follow-up at 2 months later will be carried out to assess retention of effects. Experimental design aim 3: The health policy to develop appropriate home-based rehabilitation programs for chronic stroke patients (24,25) could induce to explore whether AOT can meet the necessary translational requirements also for this type of care. A New group of 20 chronic stroke patients will be recruited and randomly assigned to the EG OR CG to follow the optimized AOT rehabilitation programs. After appropriate training of patients and caregivers, the use of tablets will let the home-based treatment. The investigators will define a low-cost highly accessible system based on tablet consumer technology for facilitating the AOT. In particular a tablet will be proposed with a web-based program that will be used to train the patients and receive a feedback of their progress. The whole treatment period will last 6 weeks. The focus of this evaluation will be on the feasibility of the home-based treatment and the usability of the platform as well as the subjects satisfaction with the services. A preliminary estimate of the recovery and overall improvement of functional performances of participants will also be provided with respect to clinical outcomes.

Official Title
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Neuroimaging Biomarkers Toward an Optimized and Personalized Action Observation Treatment in Chronic Stroke Patients: New Strategies to Maximize the Efficacy of Upper Limb Functional Rehabilitation.

Conditions
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Chronic Stroke

Intervention / Treatment
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* Other: Action Observation Treatrment
* Other: Observation of videos with Non Motor contents


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: chronic stroke (never experienced AOT); first-ever unilateral stroke due to ischemia provoking a clinically evident upper limb/hand deficit; diagnosis verified by brain imaging (MRI); cognitive function sufficient to understand the experimental instructions Chedoke-McMaster stroke Assessment Scale score greater than 1; informed written consent to participate in the study. Exclusion Criteria: bilateral impairment, severe sensory deficits in the paretic upper limb, cognitive impairment or behavioral dysfunction, refusal or inability to provide informed consent and other current severe medical problems.

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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group (EG)<br>The Experimental Group (EG) will observe and execute/repeat Activities of Daily Living (ADL) actions. | Other: Action Observation Treatrment<br>* Participants will be asked to carefully observe the videos showing different daily actions. Each action will consist of 3 to 4 constituent motor acts. Each motor act will be presented for 3 minutes, totally lasting 12 min/video. At the end of each motor act presentation, participants will be asked to execute with the affected hand the observed motor sequence for 2 minutes (20 minutes/session). 10 daily actions will be recorded. Each video will be presented to participants twice a day, in order to complexity as judged by the experimenter. Only 1 typology of motor task per day for each condition, starting from the easiest and ending with the most complex action throughout 15 sessions spread on 5 weeks (3 sessions/week). Tasks will be based on some relevant activities of daily living belonging to at least one between feeding, self-care or external actions category on the affected side. Each session will last about 15 minutes and will be repeated twice a day, at least 60 minutes apart.<br>* Other names: AOT;|
| Active Comparator: Control Group (CG)<br>The COntrol Group (CG) will observe landscapes and perform the same actions observed by their peers but after verbal instructions. | Other: Observation of videos with Non Motor contents<br>* Participants will be asked to observe video clips with no specific motor content. Videos will concern scientific, geographical and historical issues. As for cases, video clips will be divided into three to four parts. At the end of each part, controls will execute the same actions as cases, in the same order. In this way cases and controls will undergo the same amount of motor practice and receive the same amount of visual stimulation, the only difference being the content of visual stimuli.<br>* Other names: NMO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fugl-Meyer (FM) Test | The Fugl-Meyer Assessment (FMA) is a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, balance, sensation and joint functioning in patients with post-stroke hemiplegia. It is applied clinically and in research to determine disease severity, describe motor recovery, and to plan and assess treatment. The scale is comprised of five domains and there are 155 items in total: Motor functioning (the score ranges from 0 (hemiplegia) to 100 points (normal motor performance). Divided into 66 points for upper extremity and 34 points for the lower extremity. Sensory functioning (from 0 to 24 points) Balance (from 0 to 14) Joint range of motion (from 0 to 44) Joint pain (from 0 to 44 ) Scale items are scored on the basis of ability to complete the item using a 3-point ordinal scale where 0=cannot perform, 1=performs partially and 2=performs fully. The total possible scale score is 226. | At baseline-day 0 (T0), the middle of the treatment-day 15 (T1), at the end treatment-day 30 (T2), and at the follow up visit-day 90 (2 months both for the hospital-based and for the home based program) (T3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Frenchay Arm Test (FAT) | The Frenchay Arm Test (FAT) is a measure of upper extremity proximal motor control and dexterity during ADL performance in patients with impairments resulting from neurological conditions. The FAT is an upper extremity specific measure of activity limitation. | At baseline-day 0 (T0), the middle of the treatment-day 15 (T1), at the end treatment-day 30 (T2), and at the follow up visit-day 90 (2 months both for the hospital-based and for the home based program) (T3) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prevention and treatment of movement, Motor Function, Action Observation Therapy, Mirror Neuron System, Upper Limb Rehabilitation