ABSTRACT Background Evidence shows functional electrical stimulation (FES) and intermittent theta‐burst stimulation (iTBS) improve motor function in spinal cord injury (SCI). It is unclear whether high‐definition cathodal transcranial direct current stimulation (HD C‐tDCS) preconditioning could enhance the neuromodulatory aftereffect of iTBS to produce greater improvements in walking function. Objective This study examined the synergistic effects of combining HD C‐tDCS preconditioning with iTBS and FES therapy on walking ability in individuals with SCI. Methods Sixty‐four participants with incomplete SCI were randomly assigned to either active or sham HD C‐tDCS preconditioning, both followed by identical iTBS and FES interventions. Interventions were delivered once daily, five times weekly for four weeks. Both brain stimulation techniques targeted the primary motor cortex (M1) leg area. The primary outcome was the Lower Extremity Motor Score (LEMS). Secondary outcomes included Fugl‐Meyer Assessment of Lower Extremity (FMA‐LE), Berg Balance Scale (BBS), Spinal Cord Independence Measure III (SCIM‐III), Walking Index for Spinal Cord Injury II (WISCI‐II), the root mean square (RMS) values of the rectus femoris and tibialis anterior, step height, knee and ankle range of motion (ROM), and brain functional connectivity via functional near‐infrared spectroscopy (fNIRS), evaluated before and after intervention. Results Statistically significant differences were observed in all indices between the two groups before and after intervention ( p < 0.001). Compared with the control group, the treatment group exhibited a markedly greater improvement in LEMS (MD = 2.12, p < 0.001). In addition, the treatment group demonstrated notably more pronounced enhancements than the control group in the FMA‐LE (MD = 1.32, p < 0.001), BBS (MD = 3.48, p < 0.001), SCIM‐III (MD = 3.27, p < 0.001), WISCI‐II (MD = 0.80, p < 0.001), RMS values of the rectus femoris (MD = 65.19, p < 0.001) and tibialis anterior (MD = 7.20, p < 0.001), step height (MD = 44.39, p < 0.001), as well as changes in knee (MD = 11.99, p < 0.001) and ankle (MD = 8.38, p < 0.001) ROM. Furthermore, fNIRS data revealed that the treatment group exhibited significantly stronger functional connectivity across multiple motor‐related cortical networks compared with the control group, including connectivity between the prefrontal cortex (PFC) and M1 (t = 2.92, p = 0.021), the right premotor cortex (rPMC) and M1 (t = 4.99, p < 0.001), and M1 and primary somatosensory cortex (S1) (t = 4.70, p < 0.001). Conclusions This study shows that HD C‐tDCS targeting M1 as a preconditioning intervention before iTBS, combined with FES‐assisted walking training, synergistically enhances walking performance and activities of daily living in individuals with SCI. By modulating cortical excitability and promoting motor network reorganization, this sequential multimodal approach enhances neural plasticity and training effects, providing novel mechanistic evidence for mechanistically driven targeted SCI rehabilitation.
Chen et al. (2026) studied this question.