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Participants attend two sessions, one week apart, as part of a randomized crossover study involving either an active or sham intervention. Both sessions follow identical procedures, except for the TMS intervention. Each session includes: three pain pressure threshold measurements, two TMS-EEG recordings, 30 minutes of moderate-intensity exercise on a stationary bike, and two resting-state EEG recordings. Repetitive TMS is administered as an active intervention in one session and as a sham in the other, and more.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Aerobic Exercise & rTMS | Experimental | Each session includes identical procedures, except for the type of repetitive transcranial magnetic stimulation (rTMS) administered. Participants receive active rTMS in one session and sham rTMS in the other, with the order randomized. The intervention arm includes the following procedures (not in order): Pain pressure threshold (PPT) assessments performed three times per session TMS-EEG data collection conducted at two time points per session 30 minutes of moderate-intensity cycling on a stationary bike Resting-state EEG recorded twice per session Repetitive TMS intervention: active stimulation in one session, sham stimulation in the other |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| repetitive Transcranial Magnetic Stimulation | Device | Repetitive transcranial magnetic stimulation (rTMS) is administered using a figure-of-eight coil from MagVenture positioned over the left primary motor cortex (M1) in an anteroposterior direction. High-frequency rTMS is delivered at 10 Hz, consisting of 100 trains of 10-second duration (3000 pulses), with 20-second inter-train intervals, at ~90% of resting motor threshold (RMT) depending on participant tolerance and TMS-EEG brain response. |
| Measure | Description | Time Frame |
|---|---|---|
| Cortical connectivity | Global and local mean field amplitude | Day 1 |
| Cortical connectivity | Global and local mean field amplitude | Day 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Pain Pressure Threshold | Pain Pressure Threshold in kPa will be measured 3 times per session using handheld algometer. | Day 1 |
| Pain Pressure Threshold | Pain Pressure Threshold in kPa will be measured 3 times per session using handheld algometer. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Enrico De Martino, MD, PhD | Aalborg University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aalborg University | Gistrup | 9260 | Denmark |
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Participants attend two laboratory sessions scheduled one week apart, as part of a randomized, crossover study. In this design, each participant receives both conditions - an active and a sham repetitive transcranial magnetic stimulation (rTMS) intervention - in a randomized order. This within-subject crossover approach allows each participant to serve as their own control, improving statistical power and reducing the influence of inter-individual variability.
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Randomization is applied only at the participant level: each participant is randomly assigned to start with either the active or sham condition, with the alternate condition administered in the second session. The study is single-blinded, meaning that participants are blinded to the intervention type (active vs. sham), while the investigators administering the sessions are aware of the allocation.
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| Sham repetitive Transcranial Magnetic Stimulation | Device | This intervention involves high-frequency repetitive transcranial magnetic stimulation (rTMS) applied over the primary motor cortex (M1), using a figure-of-eight coil. In the sham condition, the same coil is used, but it is oriented away from the scalp at an angle that prevents effective magnetic stimulation of the brain, while still producing similar auditory and tactile sensations. This allows participants to remain blinded to the intervention type, maintaining the single-blind nature of the study. The active stimulation is delivered at 10 Hz, comprising 30 trains of 10 seconds (9900 milliseconds)(3000 pulses in total), with 20-second inter-train intervals, at ~110% of the individual's resting motor threshold (rMT). Stimulation is delivered while the participant is seated at rest, and the full rTMS protocol takes approximately 15 minutes to complete. |
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| Day 2 |
| Cortical excitability | TMS-evoked potentials from the TMS-EEG. | Day 1 |
| Cortical excitability | TMS-evoked potentials from the TMS-EEG. | Day 2 |
| Borg-20 | Questionnaire for subjective fatique level on a scale from 6 to 20, where 6 is rest and 20 is maximal exertion. We will ask the rating at different timepoints during the 30 minutes exercise. | Day 1 |
| Borg-20 | Questionnaire for subjective fatique level on a scale from 6 to 20, where 6 is rest and 20 is maximal exertion. We will ask the rating at different timepoints during the 30 minutes exercise. | Day 2 |
| Pain Numerical Rating Scale (NRS) | The subject will be asked to rate their pain during exercise on an NRS ranging from 0 to 10 with 0 corresponding to no pain and 10 corresponding to worst imaginable pain. We will ask the rating at different timepoints during the 30 minutes exercise. | Day 1 |
| Pain Numerical Rating Scale (NRS) | The subject will be asked to rate their pain during exercise on an NRS ranging from 0 to 10 with 0 corresponding to no pain and 10 corresponding to worst imaginable pain. We will ask the rating at different timepoints during the 30 minutes exercise. | Day 2 |
| ID | Term |
|---|---|
| D050781 | Transcranial Magnetic Stimulation |
| ID | Term |
|---|---|
| D055909 | Magnetic Field Therapy |
| D013812 | Therapeutics |
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