Novel Non-invasive Strategy for Spinal Neuromodulation to Control Human Locomotion

It is well-documented that neural control of stepping and standing can be generated in mammals within the spinal neuronal networks. Having a high level of automaticity, these locomotor-related neuronal circuits can produce a “stepping” movement pattern in the absence of input from the brain and/or peripheral afferent inputs. Recent observations have provided important insight into the properties of the spinal and supraspinal circuitry that are involved in movement control. We have shown that the spinal circuitry in mice, rats, cats, and humans can be neuromodulated to regain sensorimotor function after complete paralysis (Gerasimenko et al., 2008). We have also shown that with epidural spinal cord stimulation at the lumbar level, full weight-bearing standing, and voluntary movements of the lower limb can be recovered in humans with complete paralysis (Angeli et al., 2014). Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans. Recent breakthrough studies reported that chronically paralyzed individuals regained the over-ground walking with balance assistance through interleaved continous lumbosacral (L1-S1) epidural stimulation and task specific locomotor training (Angeli et al., 2018; Gill et al., 2018). We have developed a novel method of non-invasive transcutaneous spinal cord stimulation (scTS) which can modulate the excitability of spinal circuitry via electrodes placed on the skin overlying the cervical, lower thoracic, lumbosacral, and coccygeal vertebrae using a special form of electrical pulses delivered at a high frequency (Gerasimenko et al., 2015a). This methodology was able to neuromodulate the spinal locomotor networks such that involuntary stepping-like movements were induced in non-injured subjects when their legs were placed in a “gravity-neutral” apparatus (Gerasimenko et al., 2015b). In addition, our initial results with scTS show that this strategy can facilitate individuals having motor complete paralysis to generate rhythmic stepping patterns and non-repetitive voluntary movements (Gerasimenko Y. P. et al., 2015). The novel finding in this and ongoing studies is that specifically configured multisite stimulation can produce a more robust response when compared to the single site stimulation. Based on these findings, we developed a three-by-three multielectrode transcutaneous array that allows multiple sites to be modulated, thus, providing subject-specific options for controlling posture and locomotor behavior (Gerasimenko et al., 2015a). We observed that the effectiveness of inducing of involuntary stepping movements in a non-injured subject with legs placed in a “gravity-neutral” position during spinal cord stimulation at one level (T11) with 3 interconnected electrodes (A,B,C) located at midline (B) and laterally (A and C) to the spinal cord vs. stimulation at 2 levels (T11 + L1) with electrodes (T11-ABC) + (L1-ABC) was different. The amplitude of knee displacement and surface electromyographic (sEMG) activity of leg muscles were significantly higher with multi-site stimulation at 2 levels than at one level (Gerasimenko et al., 2015b). Our preliminary data reveal that use of the multielectrode surface array can fine-tune the control of the locomotor behavior. Here we introduce a new strategy of spinal neuromodulation using the continuous stimulation of locomotor circuitry and the rhythmic stimulation of motor pools.