Modulation of I-Wave Generating Pathways With Repetitive Paired-Pulse Transcranial Magnetic Stimulation: A Transcranial Magnetic Stimulation-Electroencephalography Study

Abstract

Objectives: Repetitive paired-pulse transcranial magnetic stimulation (iTMS) at indirect (I) wave intervals increases motor-evoked potentials (MEPs) produced by transcranial magnetic stimulation (TMS) to primary motor cortex (M1). However, the effects of iTMS at early and late intervals on the plasticity of specific I-wave circuits remain unclear. This study therefore aimed to assess how the timing of iTMS influences intracortical excitability within early and late I-wave circuits. To investigate the cortical effects of iTMS more directly, changes due to the intervention were also assessed using combined TMS-electroencephalography (EEG).

Material and methods: Eighteen young adults (aged 24.6 ± 4.2 years) participated in four sessions in which iTMS targeting early (1.5-millisecond interval; iTMS_1.5) or late (4.0-millisecond interval; iTMS_4.0) I-waves was applied over M1. Neuroplasticity was assessed using both posterior-to-anterior (PA) and anterior-to-posterior (AP) stimulus directions to record MEPs and TMS-evoked EEG potentials (TEPs) before and after iTMS. Short-interval intracortical facilitation (SICF) at interstimulus intervals of 1.5 and 4.0 milliseconds was also used to index I-wave activity.

Results: MEP amplitude was increased after iTMS (p < 0.01), and this was greater for PA responses (p < 0.01) but not different between iTMS intervals (p = 0.9). Irrespective of iTMS interval and coil current, SICF was facilitated after the intervention (p < 0.01). Although the N45 produced by AP stimulation was decreased by iTMS_1.5 (p = 0.04), no other changes in TEP amplitude were observed.

Conclusions: The timing of iTMS failed to influence which I-wave circuits were potentiated by the intervention. In contrast, decreases in the N45 suggest that the neuroplastic effects of iTMS may include disinhibition of intracortical inhibitory processes.

Keywords: I-wave periodicity repetitive transcranial magnetic stimulation; motor-evoked potential; primary motor cortex; transcranial magnetic stimulation–electroencephalography; transcranial magnetic stimulation–evoked potential.