Background High-frequency (10 Hz) repetitive transcranial magnetic stimulation (rTMS) to the primary motor cortex (M1) is used to treat several neuropsychiatric disorders, but its main mechanism of action remains unclear.

Objective To probe four cortical hubs used for rTMS (M1; dorsolateral-prefrontal cortex, DLPFC; anterior cingulate cortex, ACC; posterosuperior insula, PSI) with TMS coupled with high-density electroencephalography (TMS-EEG) and measure cortical excitability and oscillatory dynamics before and after active and sham rTMS to M1.

Methods Before and immediately after active or sham M1-rTMS (15 min, 3,000 pulses at 10 Hz), single-pulse TMS evoked EEG were recorded at the four targets in 20 healthy individuals. Measures of cortical excitability and oscillatory dynamics were extracted at the main frequency bands (α [8-13 Hz], low-β [14-24 Hz], high-β [25-35 Hz]).

Results Comparing active and sham M1 rTMS, M1 TMS-EEG demonstrated an increase in high-β synchronization in electrodes around M1 stimulation area and remotely in the contralateral hemisphere (p=0.026). The increase in high-β synchronization (48-83 ms after TMS-EEG stimulation) was succeeded by an enhancement in low-β power (86-144 ms after TMS-EEG stimulation) both locally and in the contralateral hemisphere (p=0.006). No significant differences were observed in TMS-EEG responses probing DLPFC, ACC, or PSI.

Conclusion M1-rTMS engaged a sequence of enhanced phase synchronization, followed by an increase in power occurring within M1, that spread to remote areas and was measurable after the end of the stimulation session. These results are relevant to understanding the M1 neuroplastic effects of rTMS and associated changes in cortical activity dynamics.

The authors have declared no competing interest.

NCT05714020

The Center for Neuroplasticity and Pain (CNAP) is supported by the Danish National Research Foundation (DNRF121). The current study is supported by a Novo Nordisk (Grant NNF21OC0072828) and ERC Horizon Europe Consolidator grant (PersoNINpain 101087925).

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The local ethics committee approved the study (N-20220018). Den Videnskabsetiske Komite for Region Nordjylland Niels Bohrs Vej 30, 9220 Aalborg ost

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