TMS-EEG as a Tool to Study the Neuromodulatory Effects of Theta Burst Stimulation

Study Overview
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Brief Summary
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To assess the effect of continuous (cTBS) and intermittent theta burst stimulation (iTBS) stimulation on motor cortex excitability using TMS-EEG. Based on prior literature, the investigators hypothesized that N100 amplitude would be differently modulated by these two modalities.

Detailed Description
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Each participant underwent three experimental sessions, at least one week apart in a cross-over design, assessing the effects of a single TBS train over the motor cortex on TMS-evoked potentials measured at the same location and resting-state EEG, immediately before and after the intervention. At each session a different type of TBS was applied (cTBS, iTBS or sham) in a randomized sequence. Subjects were uninformed about the expected effects of each intervention. Sham stimulation was achieved by adding a plastic spacer (25mm thickness) between coil and scalp, preventing effective cortical stimulation.

Official Title
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TMS-EEG as a Tool to Study the Neuromodulatory Effects of Theta Burst Stimulation

Conditions
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Cortical Excitability

Intervention / Treatment
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* Device: theta burst stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65 years Male Right handed subjects IQ > 70 Healthy participants, as determined by history, clinical investigation and investigator's judgment No history of central nervous system condition No chronic intake of neurotropic drugs TMS Safety Screening questionnaire and informed consent signed Exclusion Criteria: Pregnancy, short-term birth wish or childbearing age without adequate birth control Intracranial metal hardware (excluding dental filling): surgical clips, shrapnell, electrodes under the stimulation area Presence of pacemaker, implantable cardioverter-defibrillator (ICD), permanent medication pumps, cochlear implants or deep brain stimulation (DBS)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: three experimental sessions at randomized order, at least one week apart, in a cross-over design
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: continuous theta burst stimulation<br>cTBS over the left motor hotspot, delivered at 80% of resting motor threshold (RMT), according to the Huang et al. protocol, consisting of bursts of stimuli that are presented every 200ms (5Hz), with bursts consisting of 3 stimuli at 50 Hz. A total of 600 pulses are delivered in a continuous train of 40s. | Device: theta burst stimulation<br>* TBS over the left motor hotspot, delivered at 80% of resting motor threshold (RMT), according to the Huang et al. protocol, consisting of bursts of stimuli that are presented every 200ms (5Hz), with bursts consisting of 3 stimuli at 50 Hz. A total of 600 pulses are delivered.<br>|
| Active Comparator: intermittent theta burst stimulation<br>iTBS over the left motor hotspot, delivered at 80% of resting motor threshold (RMT), according to the Huang et al. protocol, consisting of bursts of stimuli that are presented every 200ms (5Hz), with bursts consisting of 3 stimuli at 50 Hz. A total of 600 pulses are delivered in an intermittent train of 190s for iTBS, with repeated cycles of 2s stimulation and 8s pause. | Device: theta burst stimulation<br>* TBS over the left motor hotspot, delivered at 80% of resting motor threshold (RMT), according to the Huang et al. protocol, consisting of bursts of stimuli that are presented every 200ms (5Hz), with bursts consisting of 3 stimuli at 50 Hz. A total of 600 pulses are delivered.<br>|
| Sham Comparator: sham stimulation<br>Sham stimulation over the left motor hotspot, delivered at 80% of resting motor threshold (RMT), according to the Huang et al. protocol, consisting of bursts of stimuli that are presented every 200ms (5Hz), with bursts consisting of 3 stimuli at 50 Hz. A total of 600 pulses are delivered in a continuous train of 40s using a plastic spacer (25mm thickness) between coil and scalp, preventing effective cortical stimulation. | Device: theta burst stimulation<br>* TBS over the left motor hotspot, delivered at 80% of resting motor threshold (RMT), according to the Huang et al. protocol, consisting of bursts of stimuli that are presented every 200ms (5Hz), with bursts consisting of 3 stimuli at 50 Hz. A total of 600 pulses are delivered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TBS-induced modulation of single-pulse TMS-evoked EEG responses (TEPs) - peak latency/amplitude of TEP components at Cz |  | measurement takes place immediate before and after TBS stimulation train | 
| TBS-induced modulation of single-pulse TMS-evoked EEG responses (TEPs) - Local Mean Field Power (LMFP) across a region of interest (ROI) |  | measurement takes place immediate before and after TBS stimulation train | 
| TBS-induced modulation of single-pulse TMS-evoked EEG responses (TEPs) - divergence index (DI) across all EEG channels |  | measurement takes place immediate before and after TBS stimulation train | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TBS-induced modulation of paired-pulse TMS-evoked EEG responses (TEPs) |  | measurement takes place immediate before and after TBS stimulation train | 
| TBS-induced modulation of resting-state EEG |  | measurement takes place immediate before and after a single TBS stimulation train |