The Immediate Effects of Intermittent Theta Burst Stimulation on Intracortical Excitability of the Primary Motor Cortex in Patients With Chronic Stroke

The Immediate Effects of Intermittent Theta Burst Stimulation on Intracortical Excitability of the Primary Motor Cortex in Patients With Chronic Stroke: A Concurrent TMS-EEG Sham-controlled Crossover Study

This study is to investigate the immediate effects of intermittent theta burst stimulation (iTBS) on intracortical excitatory and inhibitory circuits, neural connectivity, and network properties in patients with chronic stroke, using transcranial magnetic stimulation and electroencephalogram (TMS-EEG) and TMS-electromyography (EMG) and approaches.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Device: Intermittent theta burst stimulation (iTBS); Device: Sham intermittent theta burst stimulation (iTBS)

Detailed Description

The neurophysiological effect of intermittent theta burst stimulation (iTBS) has been examined with TMS-electromyography (EMG)-based outcomes in healthy people; however, its effects in intracortical excitability and inhibition are largely unknown in patients with stroke. Concurrent transcranial magnetic stimulation and electroencephalogram (TMS-EEG) recording can be used to investigate both intracortical excitatory and inhibitory circuits of the primary motor cortex (M1) and the property of brain networks.

This study is to investigate the immediate effects of iTBS on intracortical excitatory and inhibitory circuits, neural connectivity, and network properties in patients with chronic stroke, using TMS-EEG and TMS-EMG approaches.

In this randomized, sham-controlled, crossover study, 21 patients with chronic stroke receive two separate stimulation conditions: a single-session iTBS or sham stimulation applied to the ipsilesional M1, in two separate visits, with a washout period of five to seven days between the two visits after crossover. A battery of TMS-EMG and TMS-EEG measurements are taken before and immediately after stimulation during the visit.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong, 000000
    • Kenneth FONG

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. suffered from first-ever, ischemic or hemorrhagic, unilateral stroke, verified by neuroimaging examinations such as CT or MRI.
2. detectable motor evoked potentials from the affected first dorsal interosseous muscle;
3. provided written informed consent.

Exclusion Criteria:

1. had any contraindication to transcranial magnetic stimulation;
2. had a known neurological disease excluding stroke, or psychiatric disease;
3. were using a psychostimulant, sedative, antidepressant, or antiepileptic medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: A single-session intermittent theta burst stimulation (iTBS); The classical 600-pulse iTBS protocol is delivered to the motor hotspot over the ipsilesional hemisphere.	Device: Intermittent theta burst stimulation (iTBS); A single-session standard 600-pulse intermittent theta burst stimulation (iTBS) is applied to the ipsilesional primary motor cortex.
SHAM_COMPARATOR: A single-session sham intermittent theta burst stimulation (iTBS); The sham stimulation is the same as that of iTBS, but the coil is placed five centimeters away from the scalp.	Device: Sham intermittent theta burst stimulation (iTBS); The sham stimulation is the same as that of iTBS, but the coil is placed five centimeters away from the scalp. Electrical field simulation shows that the setups for sham stimulation would not induce any valid cortical activation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transcranial magnetic stimulation-evoked potential	Single pulses evoked an initial response in electroencephalogram, followed by a series of time- and phase-locked positive and negative deflections which could spread to the connected brain areas. The evoked potential is called transcranial magnetic stimulation-evoked potential.	Baseline (before iTBS stimulation)
Transcranial magnetic stimulation-evoked potential	Single pulses evoked an initial response in electroencephalogram, followed by a series of time- and phase-locked positive and negative deflections which could spread to the connected brain areas. The evoked potential is called transcranial magnetic stimulation-evoked potential.	10 minutes after a single-session iTBS stimulation
Motor evoked potential (MEP)	Single TMS pulses with suprathreshold intensity (120% of resting motor threshold of the stimulated cortex) applied to the primary motor cortex (M1) can produce recordable MEPs in contralateral muscles; additionally, the peak-to-peak amplitude of MEPs can be used to represent the corticospinal excitability	Baseline (before iTBS stimulation)
Motor evoked potential (MEP)	Single TMS pulses with suprathreshold intensity (120% of resting motor threshold of the stimulated cortex) applied to the primary motor cortex (M1) can produce recordable MEPs in contralateral muscles; additionally, the peak-to-peak amplitude of MEPs can be used to represent the corticospinal excitability	10 minutes after a single-session iTBS stimulation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cortical silent period	The cortical silent period (cSP) is a protocol measuring the intracortical inhibition, in which suprathreshold test pulses (120% of resting motor threshold of the stimulated cortex) are applied to the contralateral M1, while participants sustain 30% maximum voluntary contraction. Specifically, cSP refers to the interruption of background electromyographic (EMG) activity after the TMS pulse.	Baseline (before iTBS stimulation)
Cortical silent period	The cortical silent period (cSP) is a protocol measuring the intracortical inhibition, in which suprathreshold test pulses (120% of resting motor threshold of the stimulated cortex) are applied to the contralateral M1, while participants sustain 30% maximum voluntary contraction. Specifically, cSP refers to the interruption of background electromyographic (EMG) activity after the TMS pulse.	10 minutes after a single-session iTBS stimulation
Short-interval intracortical inhibition	Short-interval intracortical inhibition (SICI) is a form of paired-pulse protocol, in which a subthreshold conditioning pulse is delivered 2 ms before a suprathreshold test pulse. Theoretically, the amplitude of motor-evoked potentials (MEPs) evoked by a test pulse at a given intensity is suppressed compared with that evoked by a single pulse at the same intensity. Eight trials are recorded, with inter-trial intervals ranging from 4 s to 5 s. The intensity of test pulses is fixed at 120% of the resting motor threshold, and the intensity of the conditioning pulse is set at 80% of the resting motor threshold. The result of SICI is expressed as the ratio of a paired-pulse MEP amplitude to a single-pulse MEP amplitude.	Baseline (before iTBS stimulation)
Short-interval intracortical inhibition	Short-interval intracortical inhibition (SICI) is a form of paired-pulse protocol, in which a subthreshold conditioning pulse is delivered 2 ms before a suprathreshold test pulse. Theoretically, the amplitude of motor-evoked potentials (MEPs) evoked by a test pulse at a given intensity is suppressed compared with that evoked by a single pulse at the same intensity. Eight trials are recorded, with inter-trial intervals ranging from 4 s to 5 s. The intensity of test pulses is fixed at 120% of the resting motor threshold, and the intensity of the conditioning pulse is set at 80% of the resting motor threshold. The result of SICI is expressed as the ratio of a paired-pulse MEP amplitude to a single-pulse MEP amplitude.	10 minutes after a single-session iTBS stimulation
Intracortical facilitation	The setups for the intensity of intracortical facilitation (ICF) are almost the same as those for SICI; however, the interstimulus interval is longer, 10 ms. Eight trials are recorded, with inter-trial intervals ranging from 4 s to 5 s. The intensity of test pulses is fixed at 120% of the resting motor threshold, and the intensity of the conditioning pulse is set at 80% of the resting motor threshold. The result of ICF is expressed as the ratio of a paired-pulse MEP amplitude to a single-pulse MEP amplitude.	Baseline (before iTBS stimulation)
Intracortical facilitation	The setups for the intensity of intracortical facilitation (ICF) are almost the same as those for SICI; however, the interstimulus interval is longer, 10 ms. Eight trials are recorded, with inter-trial intervals ranging from 4 s to 5 s. The intensity of test pulses is fixed at 120% of the resting motor threshold, and the intensity of the conditioning pulse is set at 80% of the resting motor threshold. The result of ICF is expressed as the ratio of a paired-pulse MEP amplitude to a single-pulse MEP amplitude.	10 minutes after a single-session iTBS stimulation

Collaborators and Investigators

• Sponsor: The Hong Kong Polytechnic University
• Investigators: Principal Investigator: Kenneth Fong, PhD, Hong Kong Polytechnic University, QT517, Hung Hom

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 15, 2020
• Primary Completion (ACTUAL): July 30, 2021
• Study Completion (ACTUAL): May 15, 2022

Study Registration Dates

• First Submitted: August 18, 2022
• First Submitted That Met QC Criteria: August 18, 2022
• First Posted (ACTUAL): August 22, 2022

Study Record Updates

• Last Update Posted (ACTUAL): August 22, 2022
• Last Update Submitted That Met QC Criteria: August 18, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: stroke; cortical excitability; intracortical inhibition; theta burst stimulation; transcranial magnetic stimulation-evoked potentials
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: HSEARS20200621001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The data will be shared for research purpose upon reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No