Neurofeedback for Stroke Rehabilitation

Study Overview
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Brief Summary
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Real-time neurofeedback aims to alter brain activation patterns through online feedback of ongoing brain activity using magnetic resonance imagining (MRI). Stroke survivors will be randomised to receive 3 sessions of real or sham neurofeedback. This study aims to investigate whether: 1) stroke survivors can maintain alterations in brain activity after the feedback is removed, 2) neurofeedback training leads to improvements in movement of the hand and arm, 3) neurofeedback training leads to changes in brain structure and function, 4) variability in response across people can be understood.

Detailed Description
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Many stroke survivors experience impairment in upper limb function, reducing independence in activities of daily living. These impairments are associated with atypical brain activity patterns. Real-time neurofeedback aims to alter brain activation patterns through online feedback of ongoing brain activity using magnetic resonance imagining (MRI). Patterns of brain activity are displayed to a participant while a task is being performed. The participant is instructed to try to alter the patterns in a particular way, promoting specific brain activity patterns. Previous studies have found that people with and without stroke are capable of utilising the feedback to alter their brain activity. This study aims to investigate whether: stroke survivors can maintain alterations in brain activity after the feedback is removed neurofeedback training leads to improvements in movement of the hand and arm neurofeedback training leads to changes in brain structure and function variability in response across people can be understood. 30 stroke survivors (> 6 months after stroke), with residual upper limb impairment, will be recruited between February 2018 and December 2020. Participants will be randomised to receive 3 sessions of real or sham neurofeedback over one week, taking place at the Wellcome Centre for Integrative Neuroimaging, University of Oxford. Changes in brain activity during affected hand movements will be assessed with and without feedback using functional MRI and after feedback sessions using electroencephalography (EEG). Brain connectivity and structure will also be assessed using MRI at baseline and at a follow-up one week later. Clinical measures of upper limb function and impairment will be performed at baseline and at follow up sessions one week and one month later (Action Research Arm Test, Fugl-Meyer upper limb assessment, Jebsen Taylor hand function test), and in each session following neurofeedback (Jebsen taylor test).

Official Title
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The Use of Real-Time fMRI and a Mobile EEG System to Provide Neurofeedback to Stroke Patients to Promote Neural Plasticity for Motor Rehabilitation.

Conditions
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Stroke

Intervention / Treatment
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* Other: Neurofeedback
* Other: Sham Neurofeedback


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stroke > 6 months previously Unilateral upper limb impairment, but physically able to complete the tasks required Exclusion Criteria: Contraindications to MRI, such as a pacemaker, metallic implants or aneurysm clips Inability to provide informed consent Inability to actively participate in the research procedures

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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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: Participants are randomly allocated (1:1 ratio) to either the intervention group (Real Neurofeedback) or the control group (Sham Neurofeedback). Randomisation is done after participants undergo baseline measurements using a computer-generated minimisation method that takes into account baseline upper limb function (Action Research Arm test score) and time since stroke.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Real Neurofeedback<br>3 sessions of Real Neurofeedback over 1 week | Other: Neurofeedback<br>* A visual representation of the participants brain activity during movement of their affected hand in the MRI scanner.<br>|
| Sham Comparator: Sham Neurofeedback<br>3 sessions of Sham Neurofeedback over 1 week | Other: Sham Neurofeedback<br>* A visual representation of brain activity pre-recorded from a previous participant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lateralisation of Brain Activity | Lateralisation of brain activity during movement of the affected hand, assessed using functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD) signal. The activation in the region of interest is calculated for each hemisphere and the laterality index calculated as: (ipsilesional hemisphere - contralesional hemisphere) / (ipsilesional hemisphere + contralesional hemisphere). As such, positive values are indicative of greater activation in the ipsilesional hemisphere. | Throughout the 3 intervention sessions, an average of 4 days | 
| Hand Function Assessed With the Jebsen Taylor Hand Function Test (Time, in Seconds) | Performance on the Jebsen Taylor hand function test (time, in seconds to complete specified activities reflecting daily living) | Throughout study completion, 5 assessment sessions spread over approximately 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Lateralisation of Brain Activity | Change in lateralisation of brain activity during movement of the affected hand, assessed using functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD) signal. | 1 week follow up | 
| Lateralisation of Brain Activity During Visuomotor Squeeze Task (MRI) | Lateralisation of brain activity during a visuomotor squeeze task, assessed using functional magnetic resonance imaging (BOLD signal). The activation in the region of interest is calculated for each hemisphere and the laterality index calculated as: (ipsilesional hemisphere - contralesional hemisphere) / (ipsilesional hemisphere + contralesional hemisphere). As such, positive values are indicative of greater activation in the ipsilesional hemisphere. | Baseline, 1 week follow up | 
| Lateralisation of Brain Activity During Visuomotor Squeeze Task (EEG) | Change in lateralisation of brain activity during a visuomotor squeeze task, assessed using EEG | Throughout study completion, an average of 3 weeks | 
| Upper Limb Function | Action research arm test score (ARAT; upper limb function). Range 0-57, higher numbers indicate better upper limb function | Baseline, 1 week follow up | 
| Change in Upper Limb Function | Change in action research arm test score (ARAT; upper limb function). Range 0-57, higher numbers indicate better upper limb function | 1 month follow up | 
| Upper Limb Impairment | Upper limb Fugl Meyer assessment score (upper limb impairment). Range 0-66, higher numbers indicate less upper limb impairment | Baseline, 1 week follow up | 
| Upper Limb Impairment | Upper limb Fugl Meyer assessment score (upper limb impairment). Range 0-66, higher numbers indicate less upper limb impairment | Baseline, 1 month follow up | 
| Change in Resting State Functional Connectivity | Change in resting state functional connectivity, assessed using fMRI Analysis still in progress | 1 week follow up | 
| Change in White Matter Tract Integrity | Change in integrity of the white matter tracts, assessed using diffusion tensor imaging Analysis nearly completed | 1 week follow up | 
| Change in Grey Matter Volume | Change in grey matter volume derived from structural (T1) MRI Analysis still in progress | Baseline, 1 week follow up | 
| Change in White Matter Microstructure | Change in white matter microstructure, specifically myelin content, assessed using MRI Multi-Parameter Mapping | 1 week follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Motor function, Brain activity