Multisite Transcranial Direct Current Stimulation to Promote Hand Function Recovery After Stroke

Study Overview
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Brief Summary
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A novel multisite high definition tDCS (HD-tDCS) in healthy people showed that such network-targeted stimulation could enhance motor excitability beyond traditional stimulation which targeting only one region. It showed that the excitability following multisite HD-tDCS was more than double the increase following conventional tDCS. To consider the various lesion site of different stroke survivors. The electrode placements based on personalized lesion profiles and anatomical features can be determined using finite element modeling, with lesion profiles generated from fMRI and advanced algorithms calculating the current density to maximize the modulation effect. Combining motor network interaction and the new multisite electrode montage may further provide a potential to facilitate stroke recovery.

Official Title
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Multisite Transcranial Direct Current Stimulation Targeting Motor Network by Mapping Electric Fields With Task-based fMRI to Promote Hand Function Recovery After Stroke

Conditions
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Stroke

Intervention / Treatment
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* Device: multisite HD-tDCS
* Device: Conventional tDCS
* Device: multisite HD-tDCS EMG-driven robot hand
* Device: Sham HD-tDCS EMG-driven robot hand


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: first-ever stroke, the duration after stroke exceeds 12 months; mild to moderate upper extremity motor function deficit, determined by the Fugl-meyer assessment of upper extremity (FMAUE) scores between 15 and 53; detectable voluntary muscle sEMG signal from flexor digitorum (FD) and extensor digitorum (ED); scored below 3 in the Modified Ashworh Score (MAS) of FD and ED; sufficient cognitive function to follow the assessment and training instructions, determined by Mini Mental State Examination score of more than 21. Exclusion Criteria: history of epilepsy, or any other contradictions of brain stimulation; severe joint contracture of elbow or shoulder, or pain induced by any other neurological, neuromuscular, and orthopedic diseases.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multisite HD-tDCS group<br>Constant current will be applied for 20min and the electrodes will be placed over the target area | Device: multisite HD-tDCS<br>* 5-8 sintered Ag/AgCl ring electrodes will be placed based on the neuroimaging and computation modelling. The electrodes will be placed inside plastic electrode holders which will be filled with gel to have good contact with the scalp.<br>|
| Active Comparator: Conventional tDCS Group<br>Constant current (1mA) will be applied for 20min and the anode will be placed over the standard C3/C4 position | Device: Conventional tDCS<br>* A pair of 25 cm2 rubber electrodes enclosed in saline-soaked sponges and affixed to the head with rubber bands.<br>|
| Sham Comparator: Sham HD-tDCS group<br>The stimulator will be applied for 20 minutes with only 30s ramp-up and ramp-down stimulation delivered. | Device: Conventional tDCS<br>* A pair of 25 cm2 rubber electrodes enclosed in saline-soaked sponges and affixed to the head with rubber bands.<br>|
| Experimental: multisite HD-tDCS with EMG-driven robot hand group<br>The stimulation electrodes are fixed on the ipsilesional sensorimotor cortex according to the brain activation map detected by task based fMRI. | Device: multisite HD-tDCS EMG-driven robot hand<br>* Multisite HD-tDCS will individual stimulation montages with robot hand training will be applied on chronic stroke survivors. In the multisite HD-tDCS group, 5-8 sintered Ag/AgCl ring electrodes will be placed based on the neuroimaging and computation modelling. The location of the electrodes will be identified by the individual brain activity in the primary motor cortex derived from tasked-based fMRI. The Finite Element Model (FEM) will be used to simulate the electric field distribution on individual brain. Optimization of stimulation montages will be based on the derived activation pattern of the brain. After 20-minute multisite HD-tDCS, EMG-driven robot hand training will be conducted.<br>|
| Sham Comparator: Sham HD-tDCS EMG-driven robot hand group<br>The stimulator will be applied for 20 minutes with only 30s ramp-up and ramp-down stimulation delivered. | Device: Sham HD-tDCS EMG-driven robot hand<br>* Sham stimulation with robot hand training will be applied on chronic stroke survivors. A pair of 25 cm2 rubber electrodes enclosed in saline-soaked sponges and affixed to the head with rubber bands. After the sham stimulation, EMG-driven robot hand training will be conducted.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Action Research Arm Test | The ARAT is a 19-item measure divided into 4 sub-tests (grasp, grip, pinch, and gross arm movement) to assess upper limb functioning | 6-month after intervention | 
| Fugl-Meyer Assessment Upper Extremity | It is used to evaluate and measure upper-limb recovery in post-stroke hemiplegic patients, and items are scored on a 3-point ordinal scale | 6-month after intervention | 
| Electroencephalography (EEG) and Electromyography (EMG) | It is used to investigate the changes in corticomuscular coherence for studying connectivity between the brainwave using EEG and the affected hand muscles using EMG. In addition, EMG will be used to detect muscle activation change and muscle co-contraction pattern alteration. | 6-month after intervention | 
| Magnetic Resonance Imaging (MRI) | It is used to identify neural correlates of stimulation-induced behavioral gains for investigating tDCS-induced changes in brain activations | 6-month after intervention |