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.

配对联想刺激 (PAS) 是一种调节初级运动皮层 (M1) 兴奋性的非侵入性方法。PAS 涉及在初级运动皮层上结合周围神经刺激和经颅磁刺激 (TMS)。然而，对于下肢肌肉，PAS 只应用于少数容易受到刺激的周围神经支配的肌肉。本研究使用经皮脊髓刺激 (tSCS) 对后根，刺激多处下肢肌肉的感觉神经，旨在研究由 tSCS 和 TMS 组成的 PAS 对皮质脊髓兴奋性的影响。在 (1)个人 ISI中，12 名非残疾男性在两个不同的日子里接受了 120 对刺激条件，使用单独计算的成对刺激的刺激间隔 (ISI) 以单独调整的 ISI 将两个信号发送到 M1，以及 (2)恒定 ISI条件，使用 100 ms 的恒定 ISI。在 PAS 之前和之后，评估下肢肌肉的皮质脊髓兴奋性。仅在个体 ISI条件下，在 PAS 后 30 分钟内观察到小腿和腘绳肌皮质脊髓兴奋性的促进( p < 0.05)，尽管个体 ISI和恒定 ISI 之间没有显着差异条件。此外，我们的研究结果揭示了 PAS 诱导的下肢肌肉促进的差异，表明 PAS 诱导的皮质脊髓兴奋性促进存在空间梯度，因此膝关节屈肌比膝伸肌具有更高的塑性变化潜力。这些发现将有助于更好地理解 PAS 诱导的神经可塑性背后的神经机制，从而产生更好的神经康复和运动学习策略。