Investigating the Effects of Transcranial Stimulation to Advance Stroke Rehabilitation (T-STAR)

University of Oxford

Status: Enrolling

Conditions: Stroke; Upper Limb Function

Treatments: Other: Transcranial Alternating Current Stimulation (beta-tACS); Other: Transcranial Alternating Current Stimulation (sham)

Study type: Interventional

Funder types: Other

Identifiers

NCT06842095

PID17878

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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60 participants in 2 patient groups

Active Stimulation (beta-tACS)

Experimental group

Description:

Participants will receive one session of active stimulation (beta-tACS) to the ipsilesional hemisphere. 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).

Treatment:

Other: Transcranial Alternating Current Stimulation (beta-tACS)

Sham Stimulation (tACS)

Sham Comparator group

Description:

Participants will receive one session of sham stimulation. The electrode placement will be the same as for the experimental condition, but duration or timing of stimulation will be insufficient to induce intended brain rhythm changes.

Treatment:

Other: Transcranial Alternating Current Stimulation (sham)