Neuromodulation by repetitive paired-pulse TMS at late I-wave intervals in older adults

The efficacy of indirect (I) wave periodicity repetitive transcranial magnetic stimulation (iTMS) on the excitability of primary motor cortex (M1) in young adults can be modified by changing the late I-wave interval. Given that late I-wave activity is altered in older adults, this could contribute to age-related changes in M1 plasticity. To assess this possibility, the present study investigated the effects of iTMS using three late I-wave intervals (4.0, 4.5, and 5.0 ms) on M1 excitability in 17 older adults (69.6 ± 5.7 years; 10 females), which was compared to findings obtained previously in 17 young adults (27.2 ± 6.4 years, 12 females). Changes in M1 excitability were assessed using motor evoked potentials (MEPs) recorded from the right first dorsal interosseus to index single-pulse MEP_1.0mV and paired-pulse short-interval intracortical facilitation (SICF). To increase sensitivity to different intracortical circuits, both measures were also recorded using posterior-anterior (PA) and anterior-posterior (AP) TMS currents. Within older adults, PA MEP_1.0mV and SICF were facilitated following iTMS (both P < 0.0001) and these were not different between iTMS ISIs (both P > 0.077). In contrast, AP MEP_1.0mV and SICF were potentiated by iTMS_4.0 and iTMS_5.0 (both P < 0.023). iTMS_5.0 potentiation of AP circuits was also increased in older adults compared to young adults (both P < 0.004). These results suggest complex, timing-dependent effects of advancing age on the plasticity of the late I-wave circuits.