A Closed Loop Neural Activity Triggered Stroke Rehabilitation Device

Study Overview
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Brief Summary
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The purpose of this research is to determine if two non-invasive brain stimulation techniques, muscle stimulation of the arm and neuro-stimulation through the tongue, can increase the extent of stroke recovery.

Detailed Description
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The aim of this study is to determine if functional muscle stimulation, in addition to non-invasive neurostimulation through the tongue (TDU), directed by electroencephalogram (EEG) output, can increase the extent of stroke recovery on behavioral measures and induce brain plasticity as measured by functional magnetic resonance imaging (fMRI). Adult stroke patients with upper extremity motor impairments (henceforth experimental group), healthy controls, and participants with risk factors for stroke, without upper extremity impairment (allowing them to serve as controls for patients with upper extremity impairments (henceforth control group)), will be recruited in this study. Half of the participants in the experimental group will be randomly assigned to the EEG-BCI (brain-computer interface) training (closed-loop) group and will receive training on the BCI task along with muscle and tongue stimulation. The other half of the participants in the experimental group receiving traditional rehab will not receive any kind of FES or tongue stimulation for the first 8-10 weeks of study period and then will start receiving BCI-FES-tongue stimulation rehab therapy. All participants without UE impairment in Control group 1 will receive 4-6 (minimum 4, up to a maximum of 6) sessions of training on the BCI system and pre- and post MRI and 2 behavioral testing sessions. Addition of a Control group 2 is consistent with the AHA grants - Twenty four ischemic stroke patients with moderate upper extremity (dominant right hand affected) impairment (score of 1 or 2 on the motor sub-component of the NIH stroke scale (NIHSS) and ARAT score 20-45); no upper extremity injury or conditions that limited use prior to the stroke; and pre-stroke independence with a Modified Rankin Score of 0 or 1), will be recruited in this arm. All participants in this group will receive MR sessions and behavioral testing similar to the Experimental group. Addition of an Experimental group receiving EEG-BCI-bilateral FES intervention using the recoveriX system: recoveriX is a brain driven rehabilitation system for stroke patients that pairs mental activities with motor functions. Through the EEG-based recoveriX BCI system, the brain receives visual and tactile feedback in real-time, making rehabilitation more effective. A stroke patient imagines a hand movement while receiving visual feedback through a virtual avatar, and tactile feedback through electrical muscle stimulation paired to the patient's imagined movement, with the aim that these patients might regain the volitional ability to grasp following therapy. Unlike the current EEG-BCI-FES intervention that involves stimulation of only the impaired arm, with recoveriX, both arms are simultaneously stimulated during the course of the intervention. Specific Aims To determine if functional muscle stimulation of the arms, in addition to non-invasive neurostimulation through the tongue (TDU), directed by electroencephalogram (EEG) output, can increase the extent of stroke recovery as measured by behavioral measures and induce brain plasticity as measured by functional magnetic resonance imaging (fMRI). Primary objective To examine the effect of EEG guided functional muscle stimulation on improvement in upper extremity function Secondary objective To examine plasticity changes as measured by EEG/fMRI measures before and after EEG guided functional muscle stimulation.

Official Title
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A Closed Loop Neural Activity Triggered Stroke Rehabilitation Device

Conditions
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Stroke

Intervention / Treatment
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* Device: Functional Electric Stimulation (FES)
* Behavioral: Behavioral Assessments
* Other: Magnetic Resonance Imaging
* Other: EEG
* Other: RecoveriX
* Other: Delay
* Device: BCI-FES


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Experimental Group): Stroke patients with persistent upper extremity (UE) deficits Inclusion Criteria (Control Group 1) Stroke patients without UE impairments Participants with risk factors for stroke healthy controls No known neurologic, psychiatric or developmental disability Inclusion Criteria (Control Group 2) Stroke patients with persistent upper extremity (UE) deficits Moderate upper extremity (dominant right hand affected) impairment (score of 1 or 2 on the motor sub-component of the NIH stroke scale (NIHSS) and ARAT score 20-45) No upper extremity injury or conditions that limited use prior to the stroke Pre-stroke independence with a Modified Rankin Score of 0 or 1, for the standard FES only intervention. Exclusion Criteria (for all participants): Allergic to electrode gel, surgical tape and metals Participants under treatment for infectious diseases or having apparent oral lesions or inflammation will be excluded from the study Women who are pregnant or may become pregnant during the course of the study will be excluded Participants with contraindications for MRI will be offered the opportunity to participate in the interventions study only (e.g. EEG-BCI-FES and behavioral testing) Exclusion Criteria (for healthy controls) Contraindications for MRI Allergic to electrode gel, surgical tape, and metals.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group - Immediate BCI Therapy<br>EEG - BCI training (closed loop) | Behavioral: Behavioral Assessments<br>* These assessments will include measures of upper extremity motor assessments, standard stroke scales, and measures of activities of daily living.<br>Other: Magnetic Resonance Imaging<br>* A functional magnetic resonance image will be collected.<br>Other: EEG<br>* EEG electrodes will be attached to the participant's scalp using a standard, commercially available electrode cap. Proper electrode placement is made according to the international 10-20 system, ensuring complete electrode coverage over sensorimotor cortex.<br>* Other names: Electroencephalography;Device: BCI-FES<br> <br> |
| Experimental: Experimental Group - Delayed BCI Therapy<br>Scanned and tested 4 times over a 10-week period before EEG-BCI training | Behavioral: Behavioral Assessments<br>* These assessments will include measures of upper extremity motor assessments, standard stroke scales, and measures of activities of daily living.<br>Other: Magnetic Resonance Imaging<br>* A functional magnetic resonance image will be collected.<br>Other: EEG<br>* EEG electrodes will be attached to the participant's scalp using a standard, commercially available electrode cap. Proper electrode placement is made according to the international 10-20 system, ensuring complete electrode coverage over sensorimotor cortex.<br>* Other names: Electroencephalography;Other: Delay<br>* 10 week delay before intervention<br>Device: BCI-FES<br> <br> |
| Experimental: Experimental Group - RecoveriX<br>Recruited from participants who have completed the study intervention | Other: RecoveriX<br>* RecoveriX is a brain driven rehabilitation system for stroke patients that pairs mental activities with motor functions.<br>|
| Active Comparator: Control Group 1<br>48 stroke patients, 48 participants with risk factors for stroke, 48 healthy controls receiving 4-6 training sessions on the EEG-BCI, pre- and post- behavioral testing, and MRI | Behavioral: Behavioral Assessments<br>* These assessments will include measures of upper extremity motor assessments, standard stroke scales, and measures of activities of daily living.<br>Other: Magnetic Resonance Imaging<br>* A functional magnetic resonance image will be collected.<br>Other: EEG<br>* EEG electrodes will be attached to the participant's scalp using a standard, commercially available electrode cap. Proper electrode placement is made according to the international 10-20 system, ensuring complete electrode coverage over sensorimotor cortex.<br>* Other names: Electroencephalography;Device: BCI-FES<br> <br> |
| Active Comparator: Control Group 2<br>24 Stroke Patients with UE impairment receiving standard FES only therapy | Device: Functional Electric Stimulation (FES)<br>* FES uses low energy electrical pulses to artificially generate body movements in individuals with muscle paralysis. FES can be used to generate muscle contraction in otherwise paralyzed limbs to restore function.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Action Research Arm Test Scores | The Action Research Arm Test (ARAT) is designed for evaluation of upper extremity function. This test consists of sections for Grasp, Grip, Pinch and Gross Movements and comprise a total of 19 tests. Each test is scored 0-3 where 0 is 'no movement' and 3 is 'the movement is performed normally'. Each section is scored separately and the scores added for a total possible range of scores from 0-57 where the higher the score, the complete and efficient the movement. ARAT will be assessed at baseline and end of study (approximately 4 months) | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Electroencephalogram (EEG) Response Strength | The change in the strength of the EEG response before and after functional stimulation during left arm imagery with respect to right arm imagery. | 4 months | 
| Signal change in functional MRI | To compare the percent signal change in the functional MRI activations before and after functional stimulation. | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aneurysm, transient ischemic attack