Repetitive suprathreshold paired-pulse transcranial magnetic stimulation alters corticospinal excitability

Background: Suprathreshold paired-pulse transcranial magnetic stimulation (TMS) at interstimulus intervals (ISIs) of 20-30 ms evokes cumulative online increases in corticospinal excitability. Whether these changes persist beyond stimulation remains unclear. This study investigated whether repetitive paired-pulse TMS targeting periods of net excitation or inhibition induces offline changes in corticospinal excitability. Methods: Nineteen healthy participants completed three sessions, separated by at least one week, involving 40 pairs of repetitive paired-pulse TMS delivered to the left primary motor cortex at an ISI of 20 ms (rPPS20) or 100 ms (rPPS100), or a single-pulse control condition (rSPS). Offline changes in corticospinal excitability were assessed using motor evoked potential (MEP) amplitudes recorded before and after stimulation. Results: During stimulation, MEP amplitudes decreased across trials in the rPPS100 condition, although online changes did not differ significantly between conditions. Following stimulation, MEP amplitudes were significantly reduced for up to 40 minutes after rPPS100 (p = 0.017) but were not changed following rPPS20 or rSPS (all p > 0.05). Conclusion: Contrary to our hypothesis, repetitive paired-pulse TMS targeting periods of net excitation did not induce offline changes in corticospinal excitability. In contrast, stimulation targeting long-interval intracortical inhibition (LICI) produced sustained reductions in corticospinal excitability, suggesting that repetitive LICI-inducing stimulation can induce lasting plasticity within the corticospinal system.