The potential impact of using multi-site spinal cord stimulation as a strategy to neuromodulate

21 The mammalian lumbar spinal cord has the capability to generate locomotor activity in the 22 absence of input from the brain. Previously, we reported that transcutaneous electrical 23 stimulation of the spinal cord at vertebral level T11 can activate the locomotor circuitry in non24 injured subjects when their legs are placed in a gravity neutral position (Gorodnichev et al., 25 2012). In the present study we hypothesized that stimulating multiple spinal sites and therefore 26 unique combinations of networks converging on postural and locomotor lumbosacral networks 27 would be more effective in inducing more robust locomotor behavior and more selective control 28 than stimulation of more restricted networks. We demonstrate that simultaneous stimulation at 29 the cervical, thoracic, and lumbar levels induced coordinated stepping movements with a greater 30 range of motion at multiple joints in five of six non-injured subjects. We show that the addition 31 of stimulation at L1 and/or at C5 to stimulation at T11 immediately resulted in enhancing the 32 kinematics and inter-limb coordination as well as the EMG patterns in proximal and distal leg 33 muscles. Sequential cessation of stimulation at C5 and then at L1 resulted in a progressive 34 degradation of the stepping pattern. The synergistic and interactive effects of transcutaneous 35 stimulation suggest a multi-segmental convergence of descending and ascending, and most likely 36 propriospinal, influences on the spinal neuronal circuitries associated with locomotor activity. 37 The potential impact of using multi-site spinal cord stimulation as a strategy to neuromodulate 38 the spinal circuitry has significant implications in furthering our understanding of the 39 mechanisms controlling posture and locomotion and for regaining significant sensorimotor 40 function even after a severe spinal cord injury. 41