Reactivating Residual Motor Circuits in Complete Spinal Cord Injury Through Mode- and Site-Specific Transcranial Magnetic Stimulation: A Pilot Randomized Controlled Trial

Background: Recovery after motor complete spinal cord injury (cSCI) remains limited, though spared fibers and latent neural circuits may support neuroplasticity. Transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS) induces LTP like plasticity, however their comparative efficacy in cSCI remains unclear. We compared rTMS/ iTBS; iTBS at various sites combined with rehabilitation on motor outcomes and their underlying mechanism following cSCI. Methods: In this double blind randomized controlled trial, 37 individuals with thoracolumbar AIS-A (<3 months post injury) were randomized to five groups: sham, motor cortex rTMS, motor cortex iTBS, spinal cord iTBS, and combined motor cortex and spinal cord iTBS. 30 participants who completed follow-up (n=6/group), received 2 TMS sessions/day X 5 days alongside standardized rehabilitation. Lower Extremity Motor Score (LEMS) was the primary outcome; secondary outcomes included functional, electrophysiological, biochemical, neurotransmitter, pain and quality-of-life measures, assessed at baseline, post-intervention, and two follow-ups. Results and Conclusion: Both iTBS (MC) and iTBS (MC+SC) groups showed an increase in LEMS and improved WISCI II scores (p < 0.05). LEMS strongly correlated with WISCI (R = 0.60, p = 0.0019), suggesting the regain of assisted ambulation by FU2. LEMS showed positive correlation with MEPamplitude (R = 0.49, p = 0.014), area under the curve (AUC; R = 0.43, p = 0.034) and negative correlation with pNF (R = 0.54, p = 0.0006), indicating enhanced recruitment of dormant pathways and reduced neuronal injury. Glutamate levels also negatively correlated with LEMS (R = -0.4, p = 0.05). Quality of life improved significantly (p< 0.05) in both rTMS and iTBS groups. Keywords: Spinal Cord Injury, Intermittent Theta Burst Stimulation, Neuromodulation, Spinal Cord Stimulation, Neuroplasticity, Sensori-motor Recovery, Biomarkers