Investigating the Effects of Transcranial Stimulation to Advance Stroke Rehabilitation

Official title

Investigating the Effects of Beta Transcranial Stimulation to Advance Stroke Rehabilitation

Overview

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

• Other Transcranial 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 o
• Other Transcranial 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.

Primary outcome measures

• Reaching Performance [Time frame: From the first stimulation session to the completion of the third and final session, an average of 1 month]

Secondary outcome measures (2)

• Movement-related Brain Rhythms [Time frame: From the first stimulation session to the completion of the third and final session, an average of 1 month]
• Hand Function [Time frame: From the first stimulation session to the completion of the third and final session, an average of 1 month]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Triple blind

Primary purpose

Treatment

Study locations

United Kingdom · 1 center

• Oxford Centre for Functional MRI of the Brain (FMRIB) — Oxford

Publications

• Wischnewski M, Schutter DJLG, Nitsche MA. Effects of beta-tACS on corticospinal excitability: A meta-analysis. Brain Stimul. 2019 Nov-Dec;12(6):1381-1389. doi: 10.1016/j.brs.2019.07.023. Epub 2019 Jul 28. PMID 31405789
• Toledo DR, Manzano GM, Barela JA, Kohn AF. Cortical correlates of response time slowing in older adults: ERP and ERD/ERS analyses during passive ankle movement. Clin Neurophysiol. 2016 Jan;127(1):655-663. doi: 10.1016/j.clinph.2015.05.003. Epub 2015 May 9. PMID 26024982
• Tang CW, Hsiao FJ, Lee PL, Tsai YA, Hsu YF, Chen WT, Lin YY, Stagg CJ, Lee IH. beta-Oscillations Reflect Recovery of the Paretic Upper Limb in Subacute Stroke. Neurorehabil Neural Repair. 2020 May;34(5):450-462. doi: 10.1177/1545968320913502. Epub 2020 Apr 23. PMID 32321366
• Stancak A Jr, Pfurtscheller G. Desynchronization and recovery of beta rhythms during brisk and slow self-paced finger movements in man. Neurosci Lett. 1995 Aug 18;196(1-2):21-4. doi: 10.1016/0304-3940(95)11827-j. PMID 7501247
• Stagg CJ, Bachtiar V, Johansen-Berg H. The role of GABA in human motor learning. Curr Biol. 2011 Mar 22;21(6):480-4. doi: 10.1016/j.cub.2011.01.069. Epub 2011 Mar 3. PMID 21376596
• Rossi S, Antal A, Bestmann S, Bikson M, Brewer C, Brockmoller J, Carpenter LL, Cincotta M, Chen R, Daskalakis JD, Di Lazzaro V, Fox MD, George MS, Gilbert D, Kimiskidis VK, Koch G, Ilmoniemi RJ, Lefaucheur JP, Leocani L, Lisanby SH, Miniussi C, Padberg F, Pascual-Leone A, Paulus W, Peterchev AV, Quartarone A, Rotenberg A, Rothwell J, Rossini PM, Santarnecchi E, Shafi MM, Siebner HR, Ugawa Y, Wasse PMID 33243615
• Pogosyan A, Gaynor LD, Eusebio A, Brown P. Boosting cortical activity at Beta-band frequencies slows movement in humans. Curr Biol. 2009 Oct 13;19(19):1637-41. doi: 10.1016/j.cub.2009.07.074. Epub 2009 Oct 1. PMID 19800236
• Pfurtscheller G, Neuper C, Brunner C, da Silva FL. Beta rebound after different types of motor imagery in man. Neurosci Lett. 2005 Apr 22;378(3):156-9. doi: 10.1016/j.neulet.2004.12.034. Epub 2005 Jan 8. PMID 15781150

Identifiers

NCT: NCT06842095 · PID17878

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗