Background: Paired-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.
Methods: TMS 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 (D(1.5); IPI = 1.5 milliseconds), and triplets comprising D(1.5) with the addition of a third pulse at 1.5, 2.0, or 3.0 milliseconds (T(1.5)(1.5), T(1.5)(2.0), and T(1.5)(3.0), 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 D(1.5)) replacing the first 2 pulses in each triplet.
Results: At AMT, MEP responses were significantly larger for T(1.5)(1.5) and T(1.5)(3.0) compared with D(1.5). 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 D(1.5).
Conclusions: The 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.