Stroke, Upper Limb Function
Conditions
Keywords
Non-Invasive Brain Stimulation, Stroke, Upper Limb, Electroencephalography, Transcranial Alternating Current Stimulation, Beta Oscillations
Brief summary
Non-invasive brain stimulation (NIBS) has the potential to boost rehabilitation after stroke by creating a 'pro-plastic' environment, where the brain is more adaptable in response to movement (motor) training. However, responses to classical NIBS protocols are highly variable. Movement-related changes in specific brain rhythms have previously been shown to be related to recovery of hand/arm function after a stroke. The investigators propose to use NIBS to target movement-related activity in the beta band (13-30Hz) within the motor cortical regions of the brain. The investigators will use a type of NIBS called transcranial alternating current stimulation (tACS), which uses a sinusoidally-varying electrical current where the stimulation frequency is determined to be relevant to the underlying brain rhythms of interest, and the stimulation timed to coincide with specific phases of the hand/arm movement. The primary aim is to investigate whether beta-tACS improves upper limb movement in stroke survivors.
Detailed description
Stroke is a leading cause of death and long-term disability worldwide. More than 70% of stroke survivors experience motor impairments, often resulting in difficulties in daily activities, such as walking, reaching and grasping objects. Regaining upper-limb motor function is key to quality of life and for reducing the high annual costs due to stroke. Research indicates that upper-limb motor function recovery depends on the plasticity of neural circuits controlling movement. Beta activity (β, \ 13-30 Hz) in the sensorimotor cortex has been associated with brain plasticity and has been proposed to play a pivotal role in human movement and movement disorders. This activity attenuates during movement execution, known as event-related desynchronization (β-ERD), and temporarily increases after the end of movement, known as event-related synchronization (β-ERS). β-ERD and β-ERS are reliably observed during active and passive movement, movement imagination and movement observation. Changes in movement-related β-ERD and β-ERS have been linked to motor learning, and motor dysfunction in neurological conditions, such as stroke. Studies have shown that stroke survivors with upper limb impairments exhibit significantly lower beta activity compared to healthy individuals, and recovery-related improvements in motor function are accompanied by increases in both sensorimotor β-ERD and β-ERS. Therefore, modulation of movement-related beta activity (i.e., β-ERD and β-ERS) holds great promise for promoting motor function after stroke. Non-invasive brain stimulation (NIBS) can be applied during movements to increase plasticity and enhance motor learning and function. However, prior studies have delivered NIBS using a relatively broad approach; modulating general cortical excitability rather than enhancing specific endogenous oscillations in the brain. Transcranial alternating current stimulation (tACS) is a safe and well-tolerated type of NIBS which provides an option for modulating specific frequencies of brain oscillations by delivering a low-intensity sinusoidal electrical current to the brain at a specific frequency. Therefore, this study will deliver beta-tACS to the ipsilesional motor cortex (M1) aiming to modulate sensorimotor beta activity during upper limb movement in stroke survivors. This study will investigate whether functionally timed beta-tACS has the potential to enhance motor recovery, by assessing whether stimulation delivered at the end of the movement improves upper limb movement (accuracy, smoothness and hand function) and increases the modulation of beta activity. Additionally, the investigators will evaluate whether the effectiveness of the stimulation relates to baseline neuroimaging and neurophysiological measures. Identifying correlates of intervention responsiveness will help future studies to target patients who are most likely to benefit.
Interventions
OTHERTranscranial Alternating Current Stimulation (beta-tACS)
The study intervention is transcranial alternating current stimulation (tACS). The electrode montage will include one electrode positioned on the scalp over the left or right motor cortex (either C3 or C4 using the international 10-20 EEG system), depending on the location of the stroke, and a second electrode over posterior area (Pz). A low intensity of stimulation (max. 4 mA peak to peak amplitude) will be used for up to 30 minutes in total (delivered in short bouts of up to 5 seconds based on the timing of movement of the upper limb).
OTHERTranscranial Alternating Current Stimulation (sham)
The comparator is sham stimulation. Stimulation is delivered for a very short duration or timed in such a way relative to movement to mimic the scalp sensations of the active stimulation without delivering stimulation that would be anticipated to impact relevant brain activity rhythms.
Sponsors
University of Oxford
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
There will be two experimenters: one delivering the stimulation, who will NOT be blinded and one who will be taking behavioural measures and communicating with the participant who WILL be blinded to stimulation condition.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant is willing and able to give informed consent for participation in the study. * Aged 18 years or above. * Clinical diagnosis of stroke affecting the upper limb, with sufficient ability to perform the upper limb reaching task. * At least 3 months post-stroke and discharged from inpatient care.
Exclusion criteria
* Inability to follow task instructions. * Other neurological condition affecting movement (e.g. Parkinson's Disease, Multiple Sclerosis). * Standard contraindications to non-invasive brain stimulation (TMS, tACS). including (but not limited to) the presence of intracranial metallic or magnetic hardware, seizures, pregnancy, and the presence of a pacemaker or other stimulators/implants. * Insufficient verbal and written English to comprehend the study and provide informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reaching Performance | From the first stimulation session to the completion of the third and final session, an average of 1 month | Performance on the reaching task, assessed using a motion sensor as the error (deviation from the ideal path) in cubic centimeters. Higher numbers indicate worse error/reaching performance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Movement-related Brain Rhythms | From the first stimulation session to the completion of the third and final session, an average of 1 month | Movement-related beta activity measured using electroencephalography (EEG), as power in decibels. Higher values indicate stronger (better) movement-related beta activity. |
| Hand Function | From the first stimulation session to the completion of the third and final session, an average of 1 month | Change in hand function measured with the Box and Blocks Test from pre-stimulation to post-stimulation. Box and blocks test performance is measured as the number of blocks moved with the affected hand in 1 minute, higher numbers indicate better hand function. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Brain Structure at baseline (grey matter volume) | baseline | Brain structure measured with magnetic resonance imaging at baseline as the volume of grey matter in the motor-related areas of the ipsilesional hemisphere of the brain. Higher numbers indicate greater grey matter (brain) volume. |
| Brain Function at Baseline (connectivity) | baseline | Brain function measured with resting state functional magnetic resonance imaging at baseline. Higher numbers indicate greater functional brain connectivity. |
| Brain Function (neurochemicals) at Baseline | baseline | Brain function measured with magnetic resonance spectroscopic imaging as the concentration of neurochemicals GABA and Glutamate in the sensorimotor regions of interest. Higher numbers indicate a greater neurochemical concentration. |
| Corticospinal tract integrity at Baseline | baseline | Corticospinal tract integrity measured as the presence or absence of a motor evoked potential in the affected upper limb using transcranial magnetic stimulation at baseline (binary yes=1, no-0). A score of 1(yes) indicates a (at least partially) intact corticospinal tract. |
| Smoothness of reaching movement (peaks) | From the first stimulation session to the completion of the third and final session, an average of 1 month | Smoothness of reaching movement assessed using a motion sensor as the number of peaks (number). Higher values indicate worse smoothness of reaching movement. |
| Motor Impairment at Baseline (Fugl Meyer Assessment) | baseline | Upper Limb Motor impairment assessed with the Fugl Meyer Assessment, score 0-66. Higher numbers indicate less upper limb motor impairment |
| Brain Structure at baseline (grey matter damage) | baseline | Brain structure measured with magnetic resonance imaging at baseline as the percentage (%) of regions (parcels) damaged by the lesion. Higher numbers indicate greater grey matter (brain) damage. |
| Brain Structure at baseline (white matter damage) | baseline | Brain structure measured with magnetic resonance imaging at baseline as the percentage (%) of regions (tracts) disconnected due to the lesion. Higher numbers indicate greater white matter (brain) damage. |
| Motor Ability at Baseline (Action Research Arm Test) | baseline | Motor ability assessed with the Action Research Arm Test, score 0-57. Higher numbers indicate better upper limb motor ability |
| Smoothness of reaching movement (arrest periods) | From the first stimulation session to the completion of the third and final session, an average of 1 month | Smoothness of reaching movement assessed using a motion sensor as the time of arrest periods (seconds). Higher numbers indicate worse smoothness of movement. |
| Smoothness of reaching movement (Jerk) | From the first stimulation session to the completion of the third and final session, an average of 1 month | Smoothness of reaching movement assessed using a motion sensor as the jerk metric (time rate of change in acceleration) in centimeters per second. Lower values indicate better smoothness of reaching movement. |
Countries
United Kingdom
Contacts
Primary ContactMelanie Fleming, PhD
Outcome results
None listed