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date: 06 July 2022

Abstract and Keywords

Commonly used repetitive transcranial magnetic stimulation (rTMS) protocols, including regular rTMS, intermittent and continuous theta-burst stimulation (TBS) and quadripulse stimulation (QPS) are presented with respect to their induced neuromodulatory after-effects and the underlying cellular and synaptic neurophysiological mechanisms. The anatomical target is typically primary motor cortex since motor evoked potentials (MEPs) before and after the intervention can be used to assess effects of the respective rTMS protocol. High-frequency regular rTMS and intermittent TBS protocols tend to increase corticospinal excitability as indexed by MEP amplitude, whereas low-frequency regular rTMS and continuous TBS protocols tend to reduce corticospinal excitability. These effects are primarily due to LTP-like and LTD-like synaptic changes mediated by GABA and NMDA receptors. Changes in the balance between excitatory and inhibitory cortical microcircuits play a secondary role, with inconsistent effects as determined by paired-pulse TMS protocols. Finally, the challenge of large inter-subject response variability, and current directions of research to optimize rTMS effects through EEG-dependent personalized TMS are discussed.

Keywords: transcranial magnetic stimulation, repetitive transcranial magnetic stimulation, theta-burst stimulation, quadripulse stimulation, neuromodulation, plasticity, corticospinal excitability, Introduction and historical perspective

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