![]() To address these issues, we utilized spinal sensorimotor circuits that govern the contraction of the hindlimb flexor, i.e., the tibialis anterior (TA) muscle, as the focus of our study. These challenges have greatly limited the application of electrical neuromodulation techniques to treat SCI. In addition, the exact mechanism underlying the reconstruction of spinal cord neural circuits with electrical stimulation remains unknown. It remains unclear whether electrical stimulation can be used to precisely reassemble neural-circuit structures and restore function after SCI. Although a technological platform has been established to optimize neuromodulation in real time to achieve high-fidelity control of leg kinematics during locomotion in animals and patients 11, 12, the parameters of electrical stimulation to promote neural circuit remodeling and neural axon regeneration are poorly understood. When combined with overground locomotor training enabled by a weight-supporting device, epidural electrical stimulation (EES) promotes extensive reorganization of residual neural pathways that improves locomotion after the stimulation has stopped or stimulation therapy has ended 8, 9, 10. For example, lumbosacral epidural stimulation temporarily improves locomotor and autonomic function in both rodents and humans with SCI 7. Indeed, there is evidence that enhancing spinal excitability with either epidural or transcutaneous stimulation can restore some volitional motor output after spinal cord injury (SCI) 5, 6. Similar content being viewed by othersĮlectrical stimulation can augment or modify neuronal function and can have therapeutic benefits for certain neurological disorders 1, 2, 3, 4. Overall, the results provide insights into neural signal decoding during spinal sensorimotor circuit reconstruction, suggesting that the combination of epidural electrical and muscle stimulation is a promising method for the treatment of spinal cord injury. We demonstrate that a stimulus frequency of 10−20 Hz under dual stimulation conditions is required for structural and functional reconstruction of spinal sensorimotor circuits, which not only activates genes associated with axonal regeneration of motoneurons, but also improves the excitability of spinal neurons. Here, we develop a dual electrical stimulation system that combines epidural electrical and muscle stimulation to mimic feedforward and feedback electrical signals in spinal sensorimotor circuits. However, the characteristics of neural circuits reconstructed by electrical signals remain poorly understood, which greatly limits the application of such electrical neuromodulation techniques for the treatment of spinal cord injury. The neural signals produced by varying electrical stimulation parameters lead to characteristic neural circuit responses. ![]()
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