Repetitive paired-pulse TMS at I-wave periodicity markedly increases corticospinal excitability: A new technique for modulating synaptic plasticity

Objective We hypothesised that facilitatory I-wave interaction set up by paired-pulse transcranial magnetic stimulation delivered with I-wave periodicity (iTMS) may reinforce trans-synaptic events and provide a means for modulating synaptic plasticity and cortical excitability. Our objective was to determine whether prolonged iTMS can increase corticospinal excitability, and whether this form of stimulation can have lasting aftereffects. Methods Paired stimuli of equal strength with a 1.5 ms inter-stimulus interval were delivered for 30 min at a rate of 0.2 Hz. Motor threshold and motor evoked potential (MEP) amplitude to single-pulse TMS was compared before and after intervention. Results Paired-pulse MEP amplitude increased linearly throughout the period of iTMS, and had increased five-fold by the end of the stimulation period. Single-pulse MEP amplitude was increased a mean of four-fold for 10 min after stimulation. Motor threshold was unaffected. Conclusions iTMS is an effective method for increasing excitability of the human motor cortex, and probably acts by increasing synaptic efficacy. Significance Reinforcement of trans-synaptic events by iTMS may provide a means to investigate and modulate synaptic plasticity in the brain.