Quadro-pulse stimulation is more effective than paired-pulse stimulation for plasticity induction of the human motor cortex

Objective Repetitive paired-pulse transcranial magnetic stimulation (TMS) at I-wave periodicity has been shown to induce a motor-evoked potential (MEP) facilitation. We hypothesized that a greater enhancement of motor cortical excitability is provoked by increasing the number of pulses per train beyond those by paired-pulse stimulation (PPS). Methods We explored motor cortical excitability changes induced by repetitive application of trains of four monophasic magnetic pulses (quadro-pulse stimulation: QPS) at 1.5-ms intervals, repeated every 5 s over the motor cortex projecting to the hand muscles. The aftereffects of QPS were evaluated with MEPs to a single-pulse TMS, motor threshold (MT), and responses to brain-stem stimulation. These effects were compared to those after PPS. To evaluate the QPS safety, we also studied the spread of excitation and after discharge using surface electromyograms (EMGs) of hand and arm muscles. Results Sizes of MEPs from the hand muscle were enhanced for longer than 75 min after QPS; they reverted to the baseline at 90 min. Responses to brain-stem stimulation from the hand muscle and cortical MEPs from the forearm muscle were unchanged after QPS over the hand motor area. MT was unaffected by QPS. No spreads of excitation were detected after QPS. The appearance rate of after discharges during QPS was not different from that during sham stimulation. Conclusions Results show that QPS can safely induce long-lasting, topographically specific enhancement of motor cortical excitability. Significance QPS is more effective than PPS for inducing motor cortical plasticity.