Therapeutic efficacy and mechanisms of spinal cord stimulation in motor function restoration

Neurological injuries and disorders such as spinal cord injury, stroke, and cerebral palsy often result in persistent motor function deficits, severely impairing patients' independence, mobility, and overall quality of life. Over the past few years, spinal cord stimulation (SCS), including epidural spinal cord stimulation (eSCS) and transcutaneous spinal cord stimulation (tSCS), has emerged as a promising therapeutic approach to restore motor functions, demonstrating outcomes once considered unattainable. By carefully optimized stimulation parameters, both techniques have enabled patients to regain standing and walking abilities, perform voluntary movements, improve grasping functions, and undertake other essential motor tasks, even in individuals who have been paralyzed for many years. Epidural spinal cord stimulation was initially introduced for chronic pain relief. Subsequent research revealed that eSCS can re-engage spinal motor networks and central pattern generators, enabling not only rhythmic locomotor-like activity but also gradual improvements in voluntary control. Advanced protocols employing multi-electrode arrays and brain-spine interfaces can target specific spinal segments and muscle groups with high precision. These advancements allow patients with complete or incomplete spinal cord injuries to partially recover motor functions-even when stimulation is not applied-suggesting that eSCS fosters long-lasting neuroplastic changes. Moreover, eSCS has shown encouraging therapeutic potential for other neurological conditions, such as stroke and Parkinson's disease, by delivering targeted stimulation that enhances limb coordination, gait stability, and fine motor skills. Transcutaneous spinal cord stimulation offers a noninvasive, safe, and cost-effective alternative to eSCS. Although tSCS currently lacks spatial specificity and multi-target flexibility for eSCS, it has produced remarkable improvements in upper and lower limb function for patients with spinal cord injuries. Additionally, it has shown initial promise in aiding recovery for conditions like stroke and cerebral palsy. By leveraging high-frequency, modulated waveforms that reduce discomfort and improve current penetration, tSCS can diffusely enhance spinal circuitry excitability and responsiveness to residual descending inputs, promoting functional gains in standing, walking, and upper limb dexterity. Furthermore, emerging noninvasive techniques, such as temporal interference (TI) stimulation, offer the potential to overcome current limitations in precision and targeting depth. For future research, it is important to refine stimulation parameters and to develop personalized therapeutic protocols that account for individual differences in injury level, muscle activation patterns, and patient tolerance. Integrating advanced biomaterials, wearable electrode systems, and closed-loop feedback mechanisms with artificial intelligence-driven parameter optimization may further enhance treatment efficacy. Additionally, elucidating the underlying central and peripheral neural mechanisms, as well as expanding clinical evidence across a broader range of disorders, will help establish SCS as a more robust, accessible, and transformative therapeutic modality for both motor rehabilitation and pain relief. Ultimately, as our understanding of SCS deepens, it holds the promise of substantially improving motor function restoration and enriching the lives of countless patients worldwide.