Neuromodulation by paired-pulse TMS at an I-wave interval facilitates multiple I-waves

Corticospinal excitability can be increased by a transcranial magnetic stimulation (TMS) intervention that delivers repeated paired TMS pulses at an I (indirect)-wave interval of 1.5 ms. This is thought to target excitatory synaptic events by reinforcing facilitatory I-wave interaction, however, it remains to be determined what effect this intervention has on the various I-wave components. In the present study we compared I-wave facilitation curves over a range of inter-pulse intervals (IPIs) encompassing the first three I-waves, before and after 15 min of a paired-pulse TMS intervention with an IPI of 1.5 ms. The three peaks in the I-wave facilitation curves occurred at the same IPIs pre- and post-intervention (1.3, 2.5 and 4.3 ms). The facilitation curves were increased in amplitude for all three I-wave peaks post-intervention (mean increase 33%), and the mean increase across all IPIs correlated with the post-intervention increase in single-pulse MEP amplitude (r = 0.77). Modelling showed that the changes in the post-intervention curves were consistent with an increase in amplitude and broadening of the individual I-wave peaks. We conclude that an iTMS intervention with an IPI of 1.5 ms is able to target multiple I-waves. The findings are consistent with existing models of I-wave generation and suggest that the intervention increases the efficacy of synaptic events associated with the generation of descending I-wave volleys