Therapy-specific motoneuron activation with epidural and dorsal root ganglion stimulation in spinal cord injury

Over the past decade, there has been a remarkable increase in the number of clinical trials using electrical spinal cord stimulation to alleviate sensorimotor dysfunctions caused by traumatic spinal cord injury (SCI). Interestingly, despite using different stimulation modalities across studies, such as epidural stimulation (ES) or dorsal root ganglia stimulation (DRGS), similar motor outcomes have been achieved, and in turn, strengthened momentum to translate spinal stimulation as a robust clinical tool for SCI rehabilitation. To investigate how spinal stimulation affects motor outcomes, surface electromyography is used to assess muscle activity in response to specific stimulation parameters (e.g., frequency, amplitude) and contact configurations. We characterized lower extremity evoked responses produced by ES and DRGS in 19 clinical trial participants with traumatic SCI. Our results showed that at threshold intensity, ES demonstrated bias for activating distal muscles whereas DRGS preferentially activated proximal muscles ipsilateral to the stimulation electrode. Following paired stimulation pulses spaced 50 ms apart, suppression of the second pulse response was observed in both modalities for all participants, while more pronounced suppression was observed with ES compared with DRGS. DRGS-evoked electromyography (EMG) response latencies were shorter compared with ES-evoked EMG response across proximal leg muscles. Altogether, these results demonstrate that ES and DRGS activate motoneurons projecting to lower extremity muscles through distinct yet overlapping mechanisms. These electrophysiological signatures are unique to each stimulation modality and may guide individually tailored therapies to improve task-specific lower extremity motor function. NEW & NOTEWORTHY Epidural and dorsal root stimulation have emerged as promising therapies to restore function after spinal cord injury. However, how each modality uniquely or jointly engages spinal circuits remains unclear. To address this, we analyzed leg electromyography (EMG) responses to epidural stimulation (ES) and dorsal root ganglia stimulation (DRGS) delivered to the lumbosacral cord in the same individuals.