Repetitive paired-pulse TMS increases motor cortex excitability and visuomotor skill acquisition in young and older adults

Transcranial magnetic stimulation (TMS) over primary motor cortex (M1) recruits indirect (I) waves that can be modulated by repetitive paired-pulse TMS (rppTMS). The purpose of this study was to examine the effect of rppTMS on M1 excitability and visuomotor skill acquisition in young and older adults. A total of 37 healthy adults (22 young, 18–32 yr; 15 older, 60–79 yr) participated in a study that involved rppTMS at early (1.4 ms) and late (4.5 ms) interstimulus intervals (ISIs), followed by the performance of a visuomotor training task. M1 excitability was examined with motor-evoked potential (MEP) amplitudes and short-interval intracortical facilitation (SICF) using posterior–anterior (PA) and anterior–posterior (AP) TMS current directions. We found that rppTMS increased M1 excitability in young and old adults, with the greatest effects for PA TMS at the late ISI (4.5 ms). Motor skill acquisition was improved by rppTMS at an early (1.4 ms) but not late (4.5 ms) ISI in young and older adults. An additional study using a non-I-wave interval (3.5 ms) also showed increased M1 excitability and visuomotor skill acquisition. These findings show that rppTMS at both I-wave and non-I-wave intervals can alter M1 excitability and improve visuomotor skill acquisition in young and older adults.