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