T119. Strength of peripheral nerve stimulation impacts on the magnitude of synaptic plasticity induced at spinal motoneurons

Introduction Paired-associative stimulation (PAS), repeated transcranial magnetic stimulation (TMS) pairing with electrical peripheral nerve stimulation (ES), is one method of synaptic plasticity induction. If these two stimuli are delivered at the timing that descending volleys overlap with peripheral inputs at the spinal motoneurons (SM), long-term potentiation (LTP) like plasticity is induced at the SM synapses (SM-PAS). Here we investigated influences of stimulus intensity of ES on the degree of plasticity. Methods Eight right-handed healthy volunteers participated in this study. Electromyograms were recorded from right first dorsal interosseous muscle (FDI). Peripheral ES was delivered on right ulnar nerve at the wrist. TMS was applied over the left primary motor cortex (M1) hand area, and stimulus intensity was set at 120% resting motor threshold of the right FDI. We measured motor-evoked potentials (MEP) and F-wave latencies in each subject. As for SM-PAS, TMS and ES were delivered at the timing that antidromic volley derived by ES arrives at the postsynaptic terminals 1 ms before an initial descending volley evoked by TMS reaches the presynaptic terminals. A stimulus pairing of TMS with ES was given every 5 s (0.2 Hz) for 15 min (total of 180 pairs). Three different ES intensities were delivered at supramaximal intensity, at three times the sensory threshold (with muscle twitch), and at two times the sensory threshold (without muscle twitch). For evaluating SM synaptic excitability, single-pulse TMS was delivered at cervicomedullary junction level during brief contraction of the right FDI, and cervicomedullary MEP (CMEP) was recorded before and 1 min and every 10 min from 10 to 60 min after the SM-PAS intervention. Results CMEP increased after SM-PAS at supramaximal ES and at three times the sensory threshold, while SM-PAS at two times the sensory threshold induced no CMEP changes. SM-PAS with supramaximal ES was most effective. Conclusion SM-PAS at three times the sensory threshold induces sensory-motor associative plasticity constituted of sensory afferent inputs with multiple corticospinal descending volleys. Supramaximal ES stimulates both sensory afferent fibers and motor neuron axons antidromically, and SM-PAS may induce both sensory afferent and motor antidromic input associative plasticity. Antidromic inputs driven by supramaximal ES may augment associative synaptic plasticity at spinal motoneurons.