Clinical trial NCT06842095: Investigating the Effects of Transcranial Stimulation to Advance Stroke Rehabilitation
Official title: Investigating the Effects of Beta Transcranial Stimulation to Advance Stroke Rehabilitation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Stroke
Upper Limb Function
Keywords: Non-Invasive Brain Stimulation
Stroke
Upper Limb
Electroencephalography
Transcranial Alternating Current Stimulation
Beta Oscillations
Lead sponsor: University of Oxford
Sponsor class: OTHER
First posted: 2025-02-24
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Reaching Performance
timeFrame: From the first stimulation session to the completion of the third and final session, an average of 1 month
Secondary outcomes:
measure: Movement-related Brain Rhythms
timeFrame: From the first stimulation session to the completion of the third and final session, an average of 1 month
measure: Hand Function
timeFrame: From the first stimulation session to the completion of the third and final session, an average of 1 month
Other outcomes:
measure: Smoothness of reaching movement (peaks)
timeFrame: From the first stimulation session to the completion of the third and final session, an average of 1 month
measure: Smoothness of reaching movement (arrest periods)
timeFrame: From the first stimulation session to the completion of the third and final session, an average of 1 month
measure: Smoothness of reaching movement (Jerk)
timeFrame: From the first stimulation session to the completion of the third and final session, an average of 1 month
measure: Brain Structure at baseline (grey matter volume)
timeFrame: baseline
measure: Brain Function at Baseline (connectivity)
timeFrame: baseline
measure: Brain Function (neurochemicals) at Baseline
timeFrame: baseline
measure: Corticospinal tract integrity at Baseline
timeFrame: baseline
measure: Motor Ability at Baseline (Action Research Arm Test)
timeFrame: baseline
measure: Motor Impairment at Baseline (Fugl Meyer Assessment)
timeFrame: baseline
measure: Brain Structure at baseline (grey matter damage)
timeFrame: baseline
measure: Brain Structure at baseline (white matter damage)
timeFrame: baseline
Locations:
city: Oxford
country: United Kingdom
facility: Oxford Centre for Functional MRI of the Brain (FMRIB)
Study officials:
affiliation: University of Oxford
name: Charlotte J Stagg, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Oxford
name: Catharina Zich, PhD
role: STUDY_DIRECTOR
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