The Effects of Paired Associative Stimulation with Transcutaneous Spinal Cord Stimulation on Corticospinal Excitability in Multiple Lower-limb Muscles

Paired associative stimulation (PAS) is a non-invasive method to modulate the excitability of the primary motor cortex (M1). PAS involves the combination of peripheral nerve stimulation and transcranial magnetic stimulation (TMS) over the primary motor cortex. However, for lower-limb muscles, PAS has only been applied to the few muscles innervated by peripheral nerves that can easily be stimulated. This study used transcutaneous spinal cord stimulation (tSCS) to the posterior root, stimulating the sensory nerves of multiple lower-limb muscles, and aimed to investigate the effect of PAS consisting of tSCS and TMS on corticospinal excitability. Twelve non-disabled men received 120 paired stimuli on two separate days in (1) an individual-ISI condition, using inter-stimulus intervals (ISIs) of paired stimuli individually calculated to send two signals to M1 with individually-adjusted ISI, and (2) a constant-ISI condition, using a constant ISI of 100 ms. Before and after PAS, corticospinal excitability was assessed in the lower-limb muscles. Facilitation of corticospinal excitability in the lower-leg and hamstring muscles was observed up to 30 min after PAS only in the individual-ISI condition (p < 0.05), although there was no significant difference between the individual-ISI and constant-ISI conditions. Additionally, our results revealed a difference in PAS-induced facilitation among lower-limb muscles, suggesting a spatial gradient of PAS-induced facilitation of corticospinal excitability, such that knee flexor muscles have a higher potential for plastic change than knee extensor muscles. These findings will foster a better understanding of the neural mechanisms underlying PAS-induced neuroplasticity, leading to better neurorehabilitation and motor learning strategies.