Network Effects of Left M1 rTMS: A TMS-EEG Study (CORTEX-4)

Effects of Left Primary Motor Cortex rTMS on Cortical Connectivity Assessed With TMS-EEG Across Left M1, Right M1, Premotor, and Occipital Cortices

This study investigates the modification of connectivity patterns in response to one session of active repetitive transcranial magnetic stimulation (rTMS) applied to the primary motor cortex. Transcranial magnetic stimulation (TMS) will be applied to elicit electroencephalography (EEG) responses in healthy volunteers. TMS-evoked potentials (TEPs) will be recorded before and after the rTMS session and will serve as a reflection of cortical connectivity to TMS. Four cortical targets will be stimulated for TMS-EEG assessment: left primary motor cortex, right primary motor cortex, left premotor cortex, and right occipital cortex.

Study Overview

• Status: Recruiting
• Conditions: Cortical Plasticity
• Intervention / Treatment: Other: rTMS

Detailed Description

This study aims to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) applied to the left primary motor cortex (left M1) on cortical reactivity and brain connectivity in healthy volunteers using combined transcranial magnetic stimulation and electroencephalography (TMS-EEG).

Brain function depends on the dynamic interaction of distributed neuronal networks that allow efficient communication between cortical regions. Alterations in these connectivity patterns have been associated with several neurological and neuropsychiatric disorders, including chronic pain, depression, and motor dysfunction. Non-invasive neuromodulation techniques such as repetitive transcranial magnetic stimulation (rTMS) can influence cortical excitability and modulate activity within interconnected brain networks.

rTMS is a safe and non-invasive technique that uses rapidly changing magnetic fields to induce electrical currents in targeted cortical areas. Depending on the stimulation parameters, rTMS may facilitate or inhibit neuronal activity locally and across connected brain regions. Despite its increasing clinical use, the neurophysiological mechanisms through which rTMS modifies large-scale brain connectivity remain incompletely understood.

In this study, healthy volunteers will undergo TMS-EEG recordings before and after one session of active rTMS delivered over the left primary motor cortex. TMS pulses will be applied to four cortical targets - left primary motor cortex (M1), right primary motor cortex (M1), left premotor cortex, and right occipital cortex - in order to assess local cortical reactivity and the propagation of neural activity across distinct brain regions. TMS-evoked potentials (TEPs) recorded with EEG will serve as electrophysiological markers of cortical excitability and connectivity.

The study seeks to characterise how stimulation of the left M1 modulates both local and distributed cortical responses. Specifically, it is hypothesised that one session of active rTMS over the left M1 will induce measurable changes in TEPs and alter connectivity patterns across motor and non-motor cortical networks. These findings may contribute to a better understanding of the neurophysiological mechanisms underlying rTMS-induced plasticity and network modulation.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Enrico De Martino; Phone Number: +4591811183; Email: edm@hst.aau.dk

Study Locations

• Denmark
  • Gistrup, Denmark, 9260
    • Recruiting
    • Aalborg University
    • Contact: Enrico De Martino; Phone Number: 91811183; Email: edm@hst.aau.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy men and women
• Speak and understand English

Exclusion Criteria:

• Drug addiction defined as the use of cannabis, opioids or other drugs
• Previous neurologic, musculoskeletal or mental illnesses
• Lack of ability to cooperate
• History of chronic pain or current acute pain
• Contraindications to rTMS application (history of epilepsy, metal in the head or jaw etc.).
• Failure to pass the "TASS questionnaire" (TASS = Transcranial Magnetic Stimulation Adult Safety Screen)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Comparator : Classical rTMS to M1	Other: rTMS; Repetitive transcranial magnetic stimulation (rTMS) is applied to the primary motor cortex. The protocol consists of 15 minutes of 10Hz stimulation, 10 seconds on, 20 seconds off, at 90% RMT, for a total of 3000 pulses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cortical connectivity	Global and local mean field amplitude	Cortical connectivity changes will be investigated before and after rTMS (1 hour)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cortical connectivity	TMS-evoked potentials	Cortical excitability changes will be investigated before and after rTMS (1 hour)

Collaborators and Investigators

• Sponsor: Aalborg University

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: May 6, 2026
• First Submitted That Met QC Criteria: May 6, 2026
• First Posted (Actual): May 12, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: rTMS; TMS-EEG; Motor cortex; Premotor cortex; Visual cortex
• Other Study ID Numbers: r N-20210047-7

Drug and device information, study documents

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