Transspinal stimulation preceding step training reorganizes spinal locomotor circuits in human spinal cord injury: a randomized sham-controlled clinical trial

Introduction – Activity-based rehabilitation, such as locomotor training, is commonly used to induce positive systemic physiological adaptations and restore locomotion in individuals with chronic spinal cord injury (SCI). Restoration of locomotion with activity-based rehabilitation alone is not optimal and may require augmentation with neuromodulation strategies. Materials and methods – We characterized the excitability of spinal locomotor circuits during stepping in humans with SCI who underwent transspinal stimulation before locomotor training, within the same session. A total of 14 participants with chronic SCI received an average of 40 sessions of 30Hz transspinal stimulation delivered for 30min during standing (active or sham) or in the supine (active) position, followed by 30min of robotic-assisted step training. Before and after the completion of all training sessions, we assessed the soleus H-reflex phase-dependent amplitude modulation and reciprocal Ia and presynaptic inhibition in response to a conditioning stimulus delivered to the common peroneal nerve. Results – Transspinal stimulation administered before locomotor training promoted soleus H-reflex depression during the swing phase in the active standing group (n=5; F1, 309=4.52, p=0.034), stabilized soleus H-reflex excitability during the stance phase in the active supine group (n=5; F1, 327=18.44, p<0.001), and promoted reduced ankle co-contraction during assisted stepping in all groups. Reciprocal inhibition between ankle flexors and extensors after treatment was reduced at mid-stance and during the swing-to-stance transition phase in the active standing group (n=4; F1, 81=7.4, p=0.008), while it was markedly potentiated through the swing phase in the sham standing group (n=3; F1, 108=22.46, p<0.001). Finally, generalized soleus H-reflex depression after the intervention in the active (n=4; F1, 150=42.32, p<0.001) and sham (n=3; F1, 64=13.19, p<0.001) standing groups supported potentiation for presynaptic inhibition. Conclusion – This study demonstrated that transspinal stimulation preceding locomotor training was associated with modulation of the spinal reflex pathways. These neurophysiological adaptations suggest increased responsiveness of spinal circuits, although further studies are needed to determine whether these changes translate into functional improvements in people with chronic SCI.