Transcutaneous electrical spinal-cord stimulation in humans

Abstract

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.

Supraspinal Control Predicts Locomotor Function and Forecasts Responsiveness to Training after Spinal Cord Injury

“…Multi-site transcutaneous spinal cord stimulation with a customized stimulator elicits involuntary steplike behavior in non-disabled subjects when positioned in sidelying with the legs suspended to counteract the effects of gravity. 110 Involuntary stepping similar to that described for multi-site transcutaneous spinal cord stimulation has also been observed with vibration to the muscles of the thigh in non-disabled subjects, 111,112 as well as in subjects with motor-incomplete and with motor-complete SCI. 112 These responses are thought to be attributed to activation of the spinal pattern generating circuits.…”

Enhancing Nervous System Recovery through Neurobiologics, Neural Interface Training, and Neurorehabilitation

“…Several avenues for therapy have been explored, including various physical rehabilitation paradigms (Wernig and Müller, 1992; Protas et al, 2001; Taub and Morris, 2001; Taub et al, 2002; Duncan et al, 2011; Harkema et al, 2012; Mackay-Lyons et al, 2013) and electrical stimulation modalities (Shik and Orlovsky, 1976; Dimitrijevic et al, 1998; Rattay et al, 2000; Carhart et al, 2004; Minassian et al, 2004, 2007; Levy et al, 2008; DeFina et al, 2010; Dy et al, 2010; Troyk et al, 2012; Gad et al, 2013a,b; Angeli et al, 2014; Gerasimenko et al, 2015a,b; Prochazka, 2016). Individually each of these areas has yielded only modest results; however, by combining and improving techniques, significant progress has been made (Carhart et al, 2004; reviewed in Breceda and Dromerick, 2013).…”

“…Spinal stimulation to enhance motor performance in human patients with upper motor neuron disease (e.g., multiple sclerosis) was demonstrated as early as 1973 (Cook and Weinstein, 1973; Illis et al, 1976; Dooley and Sharkey, 1977–1978; Dimitrijevic et al, 1980, 2015), followed later by evidence that central pattern generators exist within the mammalian lumbosacral spinal cord that could be stimulated to produce locomotion (Grillner, 1985; Iwahara et al, 1992; Dimitrijevic et al, 1998; Minassian et al, 2007). Using electrical techniques to generate stepping in combination with extensive goal-directed physical therapy, patients with chronic and complete SCI have now shown the ability to develop positive functional plasticity and regain some voluntary control of lower extremity movement (Gad et al, 2015; Gerasimenko et al, 2015a,b). Other subjects with complete SCIs have regained the ability to selectively move their hips, knees, and ankles, as well as regain some coordination of flexor and extensor muscles (Sayenko et al, 2014; Dimitrijevic et al, 2015).…”

“…Furthermore, some of these patients learned how to stand independently and activate lower limb musculature during partial weight-bearing stepping (Sayenko et al, 2014). In addition to attaining better lower extremity control, improvements in cardiovascular, temperature, bladder, and bowel control have been noted, as well as enhanced sexual function in some (Harkema et al, 2011; Angeli et al, 2014; Gad et al, 2015; Gerasimenko et al, 2015a,b). In other subjects, subthreshold epidural stimulation between L2 and S1, or direct stimulation of the pudendal nerve, has been shown to initiate micturition (Gad et al, 2014; McGee and Grill, 2014; McGee et al, 2015).…”

An Epidermal Stimulation and Sensing Platform for Sensorimotor Prosthetic Control, Management of Lower Back Exertion, and Electrical Muscle Activation

“…[21] This previous work focused, however, on materials and circuit design aspects without any demonstrated application. Combining these functions in a single, simple device platform designed for operation on the trunk or limbs of the body is attractive for neuromuscular electrical stimulation, [22] neuromodulation rehabilitation therapy, [23] pain mitigation and prevention, [24] human–machine interfaces, [5] and sensorimotor control in prosthetic and orthotic devices, [25] where electromyography (EMG) and electrostimulation can serve as sensing and actuating platforms. Here, we present systems of this type, where multiple transcutaneous electrical stimulation electrodes cointegrate on a common substrate with sensors for electromyography, temperature, and mechanical strain.…”