Locomotor behavior is controlled by specific neural circuits called central pattern generators primarily located at the lumbosacral spinal cord. These locomotor-related neuronal circuits have a high level of automaticity; that is, they can produce a "stepping" movement pattern also seen on electromyography (EMG) in the absence of supraspinal and/or peripheral afferent inputs. These circuits can be modulated by epidural spinal-cord stimulation and/or pharmacological intervention. Such interventions have been used to neuromodulate the neuronal circuits in patients with motor-complete spinal-cord injury (SCI) to facilitate postural and locomotor adjustments and to regain voluntary motor control. Here, we describe a novel non-invasive stimulation strategy of painless transcutaneous electrical enabling motor control (pcEmc) to neuromodulate the physiological state of the spinal cord. The technique can facilitate a stepping performance in non-injured subjects with legs placed in a gravity-neutral position. The stepping movements were induced more effectively with multi-site than single-site spinal-cord stimulation. From these results, a multielectrode surface array technology was developed. Our preliminary data indicate that use of the multielectrode surface array can fine-tune the control of the locomotor behavior. As well, the pcEmc strategy combined with exoskeleton technology is effective for improving motor function in paralyzed patients with SCI. The potential impact of using pcEmc to neuromodulate the spinal circuitry has significant implications for furthering our understanding of the mechanisms controlling locomotion and for rehabilitating sensorimotor function even after severe SCI.

It was demonstrated previously that transcutaneous electrical stimulation of multiple sites over the spinal cord is more effective in inducing robust locomotor behavior as compared to the stimulation of single sites alone in both animal and human models. To explore the effects and mechanisms of interactions during multi-site spinal cord stimulation we delivered transcutaneous electrical stimulation to the single or dual locations over the spinal cord corresponding to approximately L2 and S1 segments. Spinally evoked motor potentials in the leg muscles were investigated using single and paired pulses of 1ms duration with conditioning-test intervals (CTIs) of 5 and 50ms. We observed considerable post-stimulation modulatory effects which depended on CTIs, as well as on whether the paired stimuli were delivered at a single or dual locations, the rostro-caudal relation between the conditioning and test stimuli, and on the muscle studied. At CTI-5, the paired stimulation delivered at single locations (L2 or S1) provided strong inhibitory effects, evidenced by the attenuation of the compound responses as compared with responses from either single site. In contrast, during L2-S1 paradigm, the compound responses were potentiated. At CTI-50, the magnitude of inhibition did not differ among paired stimulation paradigms. Our results suggest that electrical stimuli delivered to dual sites over the lumbosacral enlargement in rostral-to-caudal order, may recruit different populations of motor neurons initially through projecting sensory and intraspinal connections and then directly, resulting in potentiation of the compound spinally evoked motor potentials. The interactive and synergistic effects indicate multi-segmental convergence of descending and ascending influences on the neuronal circuitries during electrical spinal cord stimulation.

Neuronal control of stepping movement in healthy human is based on integration between brain, spinal neuronal networks, and sensory signals. It is generally recognized that there are continuously occurring adjustments in the physiological states of supraspinal centers during all routines movements. For example, visual as well as all other sources of information regarding the subject's environment. These multimodal inputs to the brain normally play an important role in providing a feedforward source of control. We propose that the brain routinely uses these continuously updated assessments of the environment to provide additional feedforward messages to the spinal networks, which provides a synergistic feedforwardness for the brain and spinal cord. We tested this hypothesis in 8 non-injured individuals placed in gravity neutral position with the lower limbs extended beyond the edge of the table, but supported vertically, to facilitate rhythmic stepping. The experiment was performed while visualizing on the monitor a stick figure mimicking bilateral stepping or being motionless. Non-invasive electrical stimulation was used to neuromodulate a wide range of excitabilities of the lumbosacral spinal segments that would trigger rhythmic stepping movements. We observed that at the same intensity level of transcutaneous electrical spinal cord stimulation (tSCS), the presence or absence of visualizing a stepping-like movement of a stick figure immediately initiated or terminated the tSCS-induced rhythmic stepping motion, respectively. We also demonstrated that during both voluntary and imagined stepping, the motor potentials in leg muscles were facilitated when evoked cortically, using transcranial magnetic stimulation (TMS), and inhibited when evoked spinally, using tSCS. These data suggest that the ongoing assessment of the environment within the supraspinal centers that play a role in planning a movement can routinely modulate the physiological state of spinal networks that further facilitates a synergistic neuromodulation of the brain and spinal cord in preparing for movements.