Clinical trial NCT04658745: Effects of Theta Burst Stimulation on Modulation of Mirror Illusion-induced Rhythm Suppression in Stroke
Official title: Effects of Theta Burst Stimulation on Modulation of Mirror Illusion-induced Rhythm Suppression in Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stroke
Hemiplegia
Keywords: Stroke
upper extremity
intermittent theta burst stimulation
mirror visual feedback
event-related desynchronization
Lead sponsor: The Hong Kong Polytechnic University
Sponsor class: OTHER
Collaborators: name: Queen Mary Hospital, Hong Kong
First posted: 2020-12-08
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study aims to test the hypothesis that rTMS in the form of theta burst stimulation (TBS) over the ipsilateral and contralateral motor cortices can modulate mirror illusion-induced rhythm suppression while observing unilateral arm movement in stroke individuals. The investigators further hypothesize that this intervention will lead to the revision of interhemispheric asymmetry. Finally, this study will also explore the longitudinal relationship between rhythm suppression and motor recovery as indicated by motor excitability in the form of MEP. The results of this study will provide significant new information regarding neurophysiological motor relearning mechanisms which could inform the development and evaluation of innovative treatments for individuals with stroke

Detailed description: Stroke is the leading cause of physical disability. Facilitating the process of motor relearning would greatly accelerate the rehabilitation of motor functions and elicit positive neuroplasticity of the damaged brain area. Previous research has already explored the feasibility of motor priming techniques embedded in stroke rehabilitation programs using strategies such as non-invasive brain stimulation (NIBS) and mirror therapy (MT). These treatments are usually implemented along with the standardized rehabilitation, sequentially or simultaneously, and have been demonstrated to be more effective than the standardized rehabilitation programs alone.

Mirror neuron, as indicated traditionally by the decrease in the amplitude of Mu rhythm, i.e. a suppression over central electrodes of electroencephalography (EEG), reflects the "seeing" of movement after "perception". Such oscillations are based on neural substrates that are discharged during the observation and execution of a motor act, which is also associated with other human functions, such as imitation, language, etc. The core mirror neuron system (MNS) is thought to be located in the premotor and the primary sensorimotor cortices, indicating that motor learning could be enhanced during action observation and overt movement.

Preliminary research has shown that repetitive Transcranial Magnetic Stimulation (rTMS) can enhance the corticomotor excitability in mirror neurons during both observation of movement (by others) or imagined movement in healthy subjects; in particular, as measured by enhanced motor evoked potentials (MEP). Increases in MEP has also been induced by short-term action observation and mirror visual feedback in stroke survivors. However, it is not yet known if MNS can be activated by TMS in MT following a stroke, and the relationship between mirror neuron activation and clinical improvements in stroke remains unclear.

The investigators have already published preliminary findings in patients with hemiplegic upper extremity, rTMS, and MT. Here, the investigators propose to test the hypothesis that rTMS in the form of theta-burst stimulation (TBS) over the ipsilateral and contralateral motor cortices can modulate mirror illusion-induced rhythm suppression while observing unilateral arm movement in stroke individuals. The investigators further hypothesize that this intervention will lead to the revision of interhemispheric asymmetry. Finally, this study will also explore the longitudinal relationship between rhythm suppression and motor recovery as indicated by motor excitability in the form of MEP. The results of this study will provide significant new information regarding neurophysiological motor relearning mechanisms which could inform the development and evaluation of innovative treatments for individuals with stroke

Eligibility criteria: Inclusion Criteria:

1. type and location of stroke - ischemic or hemorrhagic, cortical or subcortical, confirmed by medical diagnoses compatible with a unilateral lesion involvement;
2. Acute stroke patients: stroke with onset of neurological condition ≤3 months, recruited from a local hospital; Chronic stroke patients: stroke with onset of neurological condition from 6 months to 3 years, recruited from self-help organization in the community. The randomization will be pre-stratified into 2 - subacute and chronic stages, and recruit from 2 centers - acute hospital and self-help organizations in the community.
3. normal or corrected-to-normal visual acuity better than 20/60 (6/18) in the better eye;
4. right-handed, verified by the Edinburgh Handedness Inventory;
5. mild to moderately impaired hemiplegic upper extremity functions, with functional levels 5-7 as rated by the Functional Test for the Hemiplegic Upper Extremity - Hong Kong version (FTHUE-HK);
6. the ability to understand and follow simple verbal instructions;
7. the ability to participate in a therapy session lasting at least 60 minutes; and
8. consent to participate in the study.

Exclusion Criteria:

1. prior neurological or psychiatric disorders;
2. severe spasticity (Modified Ashworth Scale \>3) over hemiplegic upper extremity;
3. a history of recent Botox injections or acupuncture to the hemiplegic upper extremity within the past three months;
4. use of central nervous system-active medicine;
5. any contraindication to TMS, according to the guideline of the Safety of TMS Consensus group, such as the risk of epilepsy, metal implants, and pregnancy;
6. the presence of unilateral neglect as screened by the Behavioural Inattention Test (CBIT-HK); and
7. participation in another clinical study elsewhere during recruitment. Informed written consent will be obtained from all patients prior to data collection.

Primary outcomes:
measure: Fugl-Meyer assessment (FMA)
timeFrame: Baseline
measure: Fugl-Meyer assessment (FMA)
timeFrame: 1 day
measure: Fugl-Meyer assessment (FMA)
timeFrame: 2 weeks
measure: Fugl-Meyer assessment (FMA)
timeFrame: 1-month after the completion of the intervention
measure: Action Research Arm Test (ARAT)
timeFrame: Baseline (immediately before the first session)
measure: Action Research Arm Test (ARAT)
timeFrame: 1 day
measure: Action Research Arm Test (ARAT)
timeFrame: 2 weeks
measure: Action Research Arm Test (ARAT)
timeFrame: 1-month after the completion of the intervention
Secondary outcomes:
measure: EEG rhythm power
timeFrame: Baseline (immediately before the first session)
measure: EEG rhythm power
timeFrame: 1 day
measure: EEG rhythm power
timeFrame: 2 weeks
measure: EEG rhythm power
timeFrame: 1-month after the completion of the intervention
measure: Motor-evoked Potential (MEP)
timeFrame: Baseline (immediately before the first session)
measure: Motor-evoked Potential (MEP)
timeFrame: 1 day
measure: Motor-evoked Potential (MEP)
timeFrame: 2 weeks
measure: Motor-evoked Potential (MEP)
timeFrame: 1-month after the completion of the intervention
measure: Cortical silent period
timeFrame: Baseline (immediately before the first session)
measure: Cortical silent period
timeFrame: 1 day
measure: Cortical silent period
timeFrame: 2 weeks
measure: Cortical silent period
timeFrame: 1-month after the completion of the intervention
measure: Ipsilateral silent period
timeFrame: Baseline (immediately before the first session)
measure: Ipsilateral silent period
timeFrame: 1 day
measure: Ipsilateral silent period
timeFrame: 2 weeks
measure: Ipsilateral silent period
timeFrame: 1-month after the completion of the intervention
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Kenneth FONG
Study officials:
affiliation: The Hong Kong Polytechnic University
name: Kenneth Nai Kuen FONG, PHD
role: PRINCIPAL_INVESTIGATOR
References: