Spinal associative stimulation: a non-invasive stimulation paradigm to modulate spinal excitability.

OBJECTIVE Repetitive, paired peripheral and transcranial stimulation targeting the cerebral cortex can increase cortical excitability, outlasting the stimulation period. It is unknown whether paired stimulation specifically targeting the spinal cord can modulate spinal excitability. We tested whether the H-reflex facilitation from a sub-threshold conditioning TMS pulse could modulate spinal excitability if delivered repetitively. METHOD In 13 healthy subjects, we delivered single-pulse TMS (80% RMT) for the right soleus muscle, 20 ms prior to an electrical peripheral nerve stimulus delivered over the posterior tibial nerve on the same side at 0.1 Hz during 15 min. RESULTS PNS alone evoked an H-reflex of 0.25 mV ± 0.06 SEM, while pairing of TMS and PNS facilitated the H-reflex to 0.7 ± 0.11 mV. TMS-PNS pairs delivered at 0.1 Hz for 15 min progressively increased in the evoked response to ∼130% (r(2) = 0.97) of the starting amplitude (normalized to 1st min). Post-intervention, H-reflex threshold decreased (pre = 12.9 ± 1.7 mA; post =11.6 ± 1.6 mA; p = 0.04), as did the stimulus intensity at maximum H-reflex amplitude (pre = 23.5 ± 02.8 mA; post = 21.6 ± 2.6 mA; p = 0.03), and recruitment curve width (pre = 11.6 ± 1.5 mA; post = 10.93 ± 1.4 mA; p = 0.03). No such changes were observed with intervention of PNS or TMS alone. CONCLUSION Paired stimulation targeting spinal facilitatory interactions, when applied repetitively, can increase spinal excitability during and after the intervention. SIGNIFICANCE Spinal associative stimulation may have potential for neuromodulation in spinal cord injury patients.