Forty-hertz triple-pulse stimulation induces motor cortical facilitation in humans

A single pulse of transcranial magnetic stimulation (TMS) can reset the 15- to 30-Hz beta-band oscillations in the motor cortex. These oscillations are known to influence the amplitude of corticospinal activity evoked by TMS. To garner further evidence for this resetting, we tested how electromyographic responses to motor cortex TMS were modulated by a preceding series of TMS pulses. We used a triad of conditioning TMS pulses at various interstimulus intervals (ISIs) in an attempt to drive cortical activity at the corresponding frequency. We then analyzed how the amplitude of motor-evoked potentials (MEPs) to a test pulse varied at different intervals after the conditioning triad. When conditioning pulses were given at an ISI of 25 ms, responses to the fourth (test) pulse were facilitated 25 ms later. Neither a single conditioning pulse nor triad of conditioning pulses separated by other ISIs enhanced responses to the test pulse at the expected timings. Triads of pulses at an ISI of 25 ms did not enhance subsequent MEPs to brainstem stimulation. Based on the intensity of the conditioning stimuli necessary to produce this effect and on the effective interval, we conclude that the facilitation at 25 ms differs from intracortical facilitation at 7-10 ms seen in the paired-pulse experiment originally reported by Kujirai et al. These results suggest that a triad of TMS pulses can enhance an intrinsic oscillatory rhythm of the motor cortex (40 Hz) and facilitate cortical activity at an ISI corresponding to the frequency of that rhythm.