Corticomotor responses to triple-pulse transcranial magnetic stimulation: effects of interstimulus interval and stimulus intensity

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(2.0)(1.5), and T(3.0)(1.5), 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(3.0)(1.5) 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. (C) 2009 Elsevier Inc. All rights reserved.