Stroke
Conditions
Keywords
Motor function, Brain activity
Brief summary
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
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: 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. 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).
Interventions
OTHERNeurofeedback
A visual representation of the participants brain activity during movement of their affected hand in the MRI scanner.
OTHERSham Neurofeedback
A visual representation of brain activity pre-recorded from a previous participant
Sponsors
Wellcome Trust
University of Oxford
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hand Function Assessed With the Jebsen Taylor Hand Function Test (Time, in Seconds) | Throughout study completion, 5 assessment sessions spread over approximately 3 weeks | Performance on the Jebsen Taylor hand function test (time, in seconds to complete specified activities reflecting daily living) |
| Lateralisation of Brain Activity | Throughout the 3 intervention sessions, an average of 4 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lateralisation of Brain Activity During Visuomotor Squeeze Task (MRI) | Baseline, 1 week follow up | 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. |
| Lateralisation of Brain Activity During Visuomotor Squeeze Task (EEG) | Throughout study completion, an average of 3 weeks | Change in lateralisation of brain activity during a visuomotor squeeze task, assessed using EEG |
| Upper Limb Function | Baseline, 1 week follow up | Action research arm test score (ARAT; upper limb function). Range 0-57, higher numbers indicate better upper limb function |
| Change in Upper Limb Function | 1 month follow up | Change in action research arm test score (ARAT; upper limb function). Range 0-57, higher numbers indicate better upper limb function |
| Change in Resting State Functional Connectivity | 1 week follow up | Change in resting state functional connectivity, assessed using fMRI Analysis still in progress |
| Change in White Matter Tract Integrity | 1 week follow up | Change in integrity of the white matter tracts, assessed using diffusion tensor imaging Analysis nearly completed |
| Change in Grey Matter Volume | Baseline, 1 week follow up | Change in grey matter volume derived from structural (T1) MRI Analysis still in progress |
| Change in White Matter Microstructure | 1 week follow up | Change in white matter microstructure, specifically myelin content, assessed using MRI Multi-Parameter Mapping |
| Upper Limb Impairment | Baseline, 1 week follow up | Upper limb Fugl Meyer assessment score (upper limb impairment). Range 0-66, higher numbers indicate less upper limb impairment |
| Change in Lateralisation of Brain Activity | 1 week follow up | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Baseline Structure and Function as a Correlate of Response to Neurofeedback | Throughout study completion, an average of 3 weeks. | The correlation between baseline measures and change in lateralisation of brain activity during movement of the affected hand will be tested in order to identify markers to explain variability in response to real neurofeedback. Analysis still in progress |
Countries
United Kingdom
Participant flow
Recruitment details
Participants were recruited from the community, between February 2018 and March 2020
Pre-assignment details
3 participants were not randomised to a group. 1 was withdrawn because the location of their stroke lesion made it impossible to deliver the intervention. 1 withdrew because they did not like the MRI scan. 1 was unable to continue due to study suspension because of the coronavirus pandemic.
Participants by arm
| Arm | Count |
|---|---|
| Real Neurofeedback 3 sessions of Real Neurofeedback over 1 week
Neurofeedback: A visual representation of the participants brain activity during movement of their affected hand in the MRI scanner. | 12 |
| Sham Neurofeedback 3 sessions of Sham Neurofeedback over 1 week
Sham Neurofeedback: A visual representation of brain activity pre-recorded from a previous participant | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Total | Sham Neurofeedback | Real Neurofeedback |
|---|---|---|---|
| Affected Hand Left | 16 Participants | 6 Participants | 10 Participants |
| Affected Hand Right | 8 Participants | 6 Participants | 2 Participants |
| Age, Continuous | 62 years STANDARD_DEVIATION 12 | 59 years STANDARD_DEVIATION 13 | 64 years STANDARD_DEVIATION 11 |
| Race and Ethnicity Not Collected | 0 Participants | — | — |
| Region of Enrollment United Kingdom | 24 participants | 12 participants | 12 participants |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 19 Participants | 11 Participants | 8 Participants |
| Time since stroke | 76 months STANDARD_DEVIATION 65 | 72 months STANDARD_DEVIATION 63 | 79 months STANDARD_DEVIATION 70 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
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)
Time frame: Throughout study completion, 5 assessment sessions spread over approximately 3 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Real Neurofeedback | Hand Function Assessed With the Jebsen Taylor Hand Function Test (Time, in Seconds) | Day2 | 238 seconds | Standard Error 64 |
| Real Neurofeedback | Hand Function Assessed With the Jebsen Taylor Hand Function Test (Time, in Seconds) | Day4 | 220 seconds | Standard Error 61 |
| Real Neurofeedback | Hand Function Assessed With the Jebsen Taylor Hand Function Test (Time, in Seconds) | Day3 | 221 seconds | Standard Error 59 |
| Real Neurofeedback | Hand Function Assessed With the Jebsen Taylor Hand Function Test (Time, in Seconds) | Day5 | 214 seconds | Standard Error 61 |
| Real Neurofeedback | Hand Function Assessed With the Jebsen Taylor Hand Function Test (Time, in Seconds) | Day1 | 267 seconds | Standard Error 73 |
| Sham Neurofeedback | Hand Function Assessed With the Jebsen Taylor Hand Function Test (Time, in Seconds) | Day5 | 249 seconds | Standard Error 70 |
| Sham Neurofeedback | Hand Function Assessed With the Jebsen Taylor Hand Function Test (Time, in Seconds) | Day1 | 274 seconds | Standard Error 77 |
| Sham Neurofeedback | Hand Function Assessed With the Jebsen Taylor Hand Function Test (Time, in Seconds) | Day2 | 270 seconds | Standard Error 77 |
| Sham Neurofeedback | Hand Function Assessed With the Jebsen Taylor Hand Function Test (Time, in Seconds) | Day3 | 267 seconds | Standard Error 75 |
| Sham Neurofeedback | Hand Function Assessed With the Jebsen Taylor Hand Function Test (Time, in Seconds) | Day4 | 233 seconds | Standard Error 64 |
p-value: >0.05Mixed Models Analysis
Primary
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.
Time frame: Throughout the 3 intervention sessions, an average of 4 days
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Real Neurofeedback | Lateralisation of Brain Activity | Day 2 | 0.23 laterality index adjusted for baseline |
| Real Neurofeedback | Lateralisation of Brain Activity | Day 3 | 0.26 laterality index adjusted for baseline |
| Real Neurofeedback | Lateralisation of Brain Activity | Day 4 | 0.25 laterality index adjusted for baseline |
| Sham Neurofeedback | Lateralisation of Brain Activity | Day 2 | 0.30 laterality index adjusted for baseline |
| Sham Neurofeedback | Lateralisation of Brain Activity | Day 3 | 0.22 laterality index adjusted for baseline |
| Sham Neurofeedback | Lateralisation of Brain Activity | Day 4 | 0.25 laterality index adjusted for baseline |
p-value: >0.05Linear Mixed Model
Secondary
Change in Grey Matter Volume
Change in grey matter volume derived from structural (T1) MRI Analysis still in progress
Time frame: Baseline, 1 week follow up
Secondary
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.
Time frame: 1 week follow up
Secondary
Change in Resting State Functional Connectivity
Change in resting state functional connectivity, assessed using fMRI Analysis still in progress
Time frame: 1 week follow up
Secondary
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
Time frame: 1 month follow up
Population: Only participants who were able to attend the 1 month follow up are included
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Real Neurofeedback | Change in Upper Limb Function | Baseline | 31.7 score on a scale | Standard Error 5.5 |
| Real Neurofeedback | Change in Upper Limb Function | 1 month follow up | 34.7 score on a scale | Standard Error 5.7 |
| Sham Neurofeedback | Change in Upper Limb Function | Baseline | 38.3 score on a scale | Standard Error 3.9 |
| Sham Neurofeedback | Change in Upper Limb Function | 1 month follow up | 38.5 score on a scale | Standard Error 3.4 |
Secondary
Change in White Matter Microstructure
Change in white matter microstructure, specifically myelin content, assessed using MRI Multi-Parameter Mapping
Time frame: 1 week follow up
Secondary
Change in White Matter Tract Integrity
Change in integrity of the white matter tracts, assessed using diffusion tensor imaging Analysis nearly completed
Time frame: 1 week follow up
Secondary
Lateralisation of Brain Activity During Visuomotor Squeeze Task (EEG)
Change in lateralisation of brain activity during a visuomotor squeeze task, assessed using EEG
Time frame: Throughout study completion, an average of 3 weeks
Secondary
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.
Time frame: Baseline, 1 week follow up
Population: Outliers removed on the basis of head motion or laterality index greater than 2 standard deviations from the mean
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Real Neurofeedback | Lateralisation of Brain Activity During Visuomotor Squeeze Task (MRI) | Baseline | 0.31 laterality index | Standard Error 0.03 |
| Real Neurofeedback | Lateralisation of Brain Activity During Visuomotor Squeeze Task (MRI) | 1 week follow up | 0.29 laterality index | Standard Error 0.03 |
| Sham Neurofeedback | Lateralisation of Brain Activity During Visuomotor Squeeze Task (MRI) | Baseline | 0.21 laterality index | Standard Error 0.06 |
| Sham Neurofeedback | Lateralisation of Brain Activity During Visuomotor Squeeze Task (MRI) | 1 week follow up | 0.28 laterality index | Standard Error 0.05 |
Secondary
Upper Limb Function
Action research arm test score (ARAT; upper limb function). Range 0-57, higher numbers indicate better upper limb function
Time frame: Baseline, 1 week follow up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Real Neurofeedback | Upper Limb Function | Baseline | 31.9 score on a scale | Standard Error 3.5 |
| Real Neurofeedback | Upper Limb Function | 1 week follow up | 34.3 score on a scale | Standard Error 3.7 |
| Sham Neurofeedback | Upper Limb Function | Baseline | 35.3 score on a scale | Standard Error 3.9 |
| Sham Neurofeedback | Upper Limb Function | 1 week follow up | 35.8 score on a scale | Standard Error 3.7 |
Secondary
Upper Limb Impairment
Upper limb Fugl Meyer assessment score (upper limb impairment). Range 0-66, higher numbers indicate less upper limb impairment
Time frame: Baseline, 1 week follow up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Real Neurofeedback | Upper Limb Impairment | Baseline | 44.2 score on a scale | Standard Error 2.9 |
| Real Neurofeedback | Upper Limb Impairment | 1 week follow up | 45.8 score on a scale | Standard Error 2.2 |
| Sham Neurofeedback | Upper Limb Impairment | Baseline | 44.3 score on a scale | Standard Error 4 |
| Sham Neurofeedback | Upper Limb Impairment | 1 week follow up | 46.3 score on a scale | Standard Error 3.5 |
Secondary
Upper Limb Impairment
Upper limb Fugl Meyer assessment score (upper limb impairment). Range 0-66, higher numbers indicate less upper limb impairment
Time frame: Baseline, 1 month follow up
Population: Only participants who were able to attend the 1 month follow up are included
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Real Neurofeedback | Upper Limb Impairment | Baseline | 45.7 score on a scale | Standard Error 3.9 |
| Real Neurofeedback | Upper Limb Impairment | 1 month follow up | 46.6 score on a scale | Standard Error 3.9 |
| Sham Neurofeedback | Upper Limb Impairment | Baseline | 46.2 score on a scale | Standard Error 4.5 |
| Sham Neurofeedback | Upper Limb Impairment | 1 month follow up | 47.7 score on a scale | Standard Error 3.8 |
Other Pre-specified
Baseline Structure and Function as a Correlate of Response to Neurofeedback
The correlation between baseline measures and change in lateralisation of brain activity during movement of the affected hand will be tested in order to identify markers to explain variability in response to real neurofeedback. Analysis still in progress
Time frame: Throughout study completion, an average of 3 weeks.