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.

Keywords: Neural plasticity; Neuromodulation; Painless transcutaneous electrical enabling motor control (pcEmc); Recovery; Spinal-cord injury.

Conflict of interest statement

of interest V. Reggie Edgerton and Yury Gerasimenko are shareholders in NeuroRecovery Technologies, the company providing the electric stimulator for this study. V. Reggie Edgerton is also the president and chair of the board for the company. V. Reggie Edgerton and Yury Gerasimenko hold certain inventorship rights on intellectual property licensed by The Regents of the University of California to NeuroRecovery Technologies and its subsidiaries. Ruslan Gorodnichev, Tatiana Moshonkina, Dimitry Sayenko, and Parag Gad declare that they have no conflicts of interest concerning this article.

Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Figures

Fig. 1

Angular excursions of the right (R) and left (L) knee joints and electromyography (EMG) activity in the right and left biceps femoris (BF) and right and left medial gastrocnemius (MG) muscles with painless transcutaneous electrical enabling motor control (pcEmc) (5 Hz) at T11 alone (A) and at C5+T11+L1 simultaneously (B). Angle-angle trajectory plots of multiple cycles (50-ms time bins) showing the left (horizontal)-right (vertical) kinematics coupling of the angular movements at the knee with pcEmc at T11 (C) and at C5+T11+L1 (D) as shown in (A) and (B), respectively. Color scheme in (C) and (D) reflects the density of the data points, with red the highest density. E-photo of the subject placed in the gravity-neutral device. Adapted from Gerasimenko et al. 2015.

Fig. 2

EMG patterns induced by spinal-cord stimulation with electrode configuration 1ABC (A) and 1ABC+3ABC (B). The mean rectified EMG of the rectus femoris (RF; black), BF (red), and knee displacement for a normalized step cycle during 1ABC (C) and 1ABC+3ABC (D) stimulation. E. Photo of surface array electrodes.

Fig. 3

A. Reconstruction of the approximate location of transcutaneous electrical spinal-cord stimulation over the lumbosacral enlargement, and (B) the location of the motor pools based on the segmental charts provided by Kendall et al. (1993) and Sharrard (1964). C. Evoked potentials in one subject with transcutaneous electrical spinal stimulation delivered between the spinous processes of the T10 and T11, T11 and T12, and T12 and L1 vertebrae. Shows the mean of 3 non-rectified responses in right muscles at each stimulation intensity from 2 to 100 mA. Shows the time window between 10 and 55 ms after the stimulus. D. Recruitment curves of right muscles at each location of spinal stimulation. Orange dotted lines on VL and SOL muscles indicate the initial increase of the recruitment curves. VL: vastus lateralis; RF: rectus femoris; MH: medial hamstrings; TA: tibialis anterior; SOL: soleus; MG: medial gastrocnemius muscles. Adapted from Sayenko et al., 2015.

Fig. 4

Possible pathways and structures that may be activated during electrical spinal-cord stimulation. Presents Ia, Ib, II afferents and α-motor neurons (MN).

Fig. 5

Initiation of involuntary stepping movements induced by pcEmc at T11 (30 Hz) and Co1 (5 Hz) and their combination in a motor-complete subject with spinal-cord injury (photo) placed in the gravity-neutral device. Shows angular movements of the knee joint and EMG activity in hamstring (HM), tibialis anterior (TA) and medial gastrocnemius (MG) muscles.

Fig. 6

Mean EMG activity (30 consecutive steps) from the rectus femoris (RF) and soleus muscles during a normalized step cycle with and without stimulation at T11 and T11+Co1 during active (with voluntary effort) and passive (without voluntary effort) mode.