Background & Aims

High-frequency repetitive transcranial magnetic stimulation (rTMS) to the primary motor cortex (M1) shows promise as a non-pharmacological approach to pain relief (Attal et al. 2021). However, its mechanisms, particularly regarding analgesic effects, are not fully understood. Previous studies have combined TMS with functional MRI to observe significant changes in brain activity in connected non-motor areas, including the insular, prefrontal, and cingulate cortices (Jung et al. 2020; Bergmann et al. 2021). Although these changes might play an important role in the therapeutic effects of rTMS-induced neuromodulation, it remains unclear how 10 Hz rTMS on M1 influences enduring plastic changes in such areas. This study aims to explore whether 10 Hz rTMS applied to M1 alters cortical excitability and oscillatory activity (connectivity) in these non-motor cortical regions.

Methods

To assess non-motor cortical excitability TMS coupled with electroencephalography (TMS-EEG) were applied in 20 healthy participants, focusing on the left dorsolateral prefrontal cortex (DLFPC), anterior cingulate cortex (ACC), and left posterosuperior insula (PSI). Measurements were conducted before and immediately after administering 10 Hz active or sham rTMS to the left M1 for 15 minutes (30 trains of 10-seconds pulses at 10 Hz with 20-second inter train interval; totaling 3000 pulses). We evaluated local and global brain excitability (via local and global mean field power) and analyzed three frequency bands (?, lower-?, and higher-?) using event-related spectral perturbation (ERSP: cortical excitability at a given frequency range) and inter-trial coherence (ITC: effective connectivity).

Results

Analyses of local and global mean field power, alongside time-frequency assessments, showed no significant differences in cortical excitability. ERSP and ITC were not significantly different between active and sham 10 Hz rTMS sessions in the DLPFC, ACC and PSI (all p > 0.05).

Conclusions

Previous TMS-fMRI findings suggested activation in functionally connected regions. Our study found no evidence of neuroplastic changes in these areas following 10 Hz rTMS to M1. This might indicate that the effects are either transient or require multiple sessions to induce lasting neuroplasticity. These findings prompt further research into the optimal use of rTMS in pain therapy.

References

Attal N, Poindessous-Jazat F, De Chauvigny E, Quesada C, Mhalla A, Ayache SS, Fermanian C, Nizard J, Peyron R, Lefaucheur J, et al. 2021. Repetitive transcranial magnetic stimulation for neuropathic pain: a randomized multicentre sham-controlled trial. Brain.:3328–3339. doi:10.1093/brain/awab208.

Jung JY, Bungert A, Bowtell R, Jackson SR. 2020. Modulating Brain Networks With Transcranial Magnetic Stimulation Over the Primary Motor Cortex: A Concurrent TMS/fMRI Study. Front Hum Neurosci. 14. doi:10.3389/fnhum.2020.00031.

Bergmann TO, Varatheeswaran R, Hanlon CA, Madsen KH, Thielscher A, Siebner HR. 2021. Concurrent TMS-fMRI for causal network perturbation and proof of target engagement. Neuroimage. 237. doi:10.1016/j.neuroimage.2021.118093.

Presenting Author

Bruno Andry Nascimento Couto

Poster Authors

Bruno Andry Couto

Master

Aalborg University

Lead Author

E-mail

Enrico De Martino

Aalborg University

Lead Author

E-mail

Thomas Graven-Nielsen

Thomas Graven-Nielsen

Lead Author

E-mail

Adenauer Girardi Casali

Federal University of São Paulo

Lead Author

E-mail

Maryam Mahmoodi Omandani

Aalborg University

Lead Author

E-mail

Topics

  • Treatment/Management: Interventional Therapies – Neuromodulation