BackgroundPaired-pulse transcranial magnetic stimuli (TMS) applied to the motor cortex enhances motor-evoked potential (MEP) responses at specific interpulse intervals (IPIs), probably from summation of I-waves by the secondary TMS pulse. This study investigated the properties of I-wave periodicity by comparing double-pulse with triple-pulse TMS at varying IPIs and stimulus intensities.MethodsTMS was delivered to the optimal scalp position for the resting dominant first dorsal interosseous muscle at either active motor threshold (AMT) or AMT-5% stimulator output. In experiment 1, 4 conditions were tested, a double-pulse (D1.5; IPI = 1.5 milliseconds), and triplets comprising D1.5 with the addition of a third pulse at 1.5, 2.0, or 3.0 milliseconds (T1.51.5, T1.52.0, and T1.53.0, respectively). Each condition was tested at 2 stimulation intensities. In a second experiment, the same protocol was repeated with a single-pulse (giving an MEP equivalent to D1.5) replacing the first 2 pulses in each triplet.ResultsAt AMT, MEP responses were significantly larger for T1.51.5 and T1.53.0 compared with D1.5. Triple-pulse stimulation at AMT-5% resulted in no additional increase in MEP amplitude, or effect of IPI. Double-pulse TMS showed similar effects to the triplets when the first pulse was delivered at an intensity equivalent to D1.5.ConclusionsThe results are consistent with an intensity-dependent facilitation of MEPs produced by triple-pulse TMS, possibly through summation of cortical I-waves. Triple-pulse TMS at I-wave periodicity may have application in the investigation of the cortical circuitry involved in the generation of I-waves, or form a basis for the further development of neuromodulatory TMS interventions.