Neurology · Medical Literature
Transspinal stimulation preceding step training reorganizes spinal locomotor circuits in human spinal cord injury: a randomized sham-controlled clinical trial.
Abstract
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. 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 30 Hz transspinal stimulation delivered for 30 min during standing (active or sham) or in the supine (active) position, followed by 30 min 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. Transspinal stimulation administered before locomotor training promoted soleus H-reflex depression during the swing phase in the active standing group (n = 5; F 1, 309 = 4.52, p = 0.034), stabilized soleus H-reflex excitability during the stance phase in the active supine group (n = 5; F 1, 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; F 1, 81 = 7.4, p = 0.008), while it was markedly potentiated through the swing phase in the sham standing group (n = 3; F 1, 108 = 22.46, p < 0.001). Finally, generalized soleus H-reflex depression after the intervention in the active (n = 4; F 1, 150 = 42.32, p < 0.001) and sham (n = 3; F 1, 64 = 13.19, p < 0.001) standing groups supported potentiation for presynaptic inhibition. 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.
Clinical relevance
This randomized sham-controlled trial addresses a critical gap in neurorehabilitation for chronic spinal cord injury (SCI): activity-based locomotor training alone yields suboptimal restoration of ambulation, and adjunctive neuromodulation strategies are needed to augment spinal circuit plasticity. The study targets a highly refractory population—individuals with chronic, established SCI—where spontaneous neurological recovery is minimal and conventional rehabilitation plateaus are common. Clinicians managing SCI rehabilitation should attend to this work as it provides neurophysiological evidence that the timing and positioning of transspinal stimulation (TSS) relative to locomotor training meaningfully shapes spinal reflex circuit reorganization.
Key findings
1. Active TSS at 30 Hz delivered for 30 minutes during standing, preceding robotic-assisted step training, significantly promoted soleus H-reflex depression during the swing phase in the active standing group (n=5; F₁,₃₀₉=4.52, p=0.034), indicating improved phase-dependent reflex modulation critical for safe stepping. 2. Active TSS administered in the supine position before locomotor training stabilized soleus H-reflex excitability during the stance phase (n=5; F₁,₃₂₇=18.44, p<0.001), suggesting a posture-dependent modulatory effect on spinal motor circuit gain. 3. Reduced ankle co-contraction during robotic-assisted stepping was observed across all treatment groups following the intervention, implying a generalized beneficial effect on agonist-antagonist coordination regardless of stimulation condition. 4. Reciprocal Ia inhibition between ankle flexors and extensors was reduced at mid-stance and during the swing-to-stance transition in the active standing group after treatment (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), highlighting divergent reflex pathway remodeling between active and sham conditions. 5. Generalized soleus H-reflex depression supporting potentiation of presynaptic inhibition was demonstrated post-intervention in both the active standing group (n=4; F₁,₁₅₀=42.32, p<0.001) and the sham standing group (n=3; F₁,₆₄=13.19, p<0.001), suggesting that locomotor training itself contributes to presynaptic inhibitory upregulation. 6. The trial involved 14 participants with chronic SCI completing an average of 40 sessions, with group sizes of n=3–5 for neurophysiological subanalyses; while statistically significant effects were detected, the small per-group sample sizes limit generalizability and necessitate replication in larger cohorts.
Practice implications
Clinicians delivering neurorehabilitation to patients with chronic SCI should consider integrating 30 Hz transspinal stimulation for 30 minutes immediately before locomotor training sessions, as this sequencing—rather than concurrent application—appears to prime spinal locomotor circuits for activity-dependent plasticity, with the standing delivery position offering advantages for swing-phase reflex modulation. Patient selection should prioritize individuals with chronic SCI who have reached a rehabilitation plateau on locomotor training alone, and neurophysiological biomarkers such as soleus H-reflex phase-dependent modulation and reciprocal inhibition profiles may serve as objective outcome measures to track circuit-level responsiveness over the course of treatment. Larger randomized controlled trials are warranted before this protocol can be adopted as standard of care, and future study designs should incorporate functional gait outcomes (e.g., 10-meter walk test, WISCI-II) to determine whether the observed spinal neurophysiological adaptations translate into clinically meaningful improvements in ambulation.