Background Responses to plasticity-inducing brain stimulation protocols are highly variable. However, no data are available concerning the variability of responses to quadripulse stimulation (QPS). Objective We assessed the QPS parameters of motor cortical plasticity induction in a systematic manner, and later investigated the variability of QPS using optimal parameters. Methods First, two different interburst intervals (IBI) with the same total number of pulses were compared. Next we investigated three different IBIs with a different total number of pulses but with same duration of intervention. We also compared the after-effects of monophasic and biphasic QPS. Finally, variability of QPS was tested in 35 healthy subjects. Twenty motor evoked potentials (MEPs) were measured every 5–10 min for up to one hour after intervention. Results QPS at an IBI of 5 s produced MEPs changes that are dependent on the interstimulus interval of the four magnetic pulses, consistent with previous reports. Unexpectedly, QPS at an IBI of 2.5 s did not induce any plasticity, even with the same total number of pulses, that is, 1440. QPS at an IBI of 7.5 s produced a variable response but was likely to be comparable to conventional QPS. Biphasic QPS had shorter lasting after-effects compared with monophasic QPS. Finally, the after-effects of QPS were relatively consistent across subjects: more than 80% of subjects responded as expected in the excitatory QPS at an IBI of 5 s. Conclusions The IBI, total duration of the procedure and pulse waveform strongly affected the magnitude or duration of the plasticity induced by QPS. In this cohort, 80% of subjects responded to excitatory QPS as expected.
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