Self-Assisted Standing Enabled by Non-Invasive Spinal Stimulation after Spinal Cord Injury

Abstract

Neuromodulation of spinal networks can improve motor control after spinal cord injury (SCI). The objectives of this study were to (1) determine whether individuals with chronic paralysis can stand with the aid of non-invasive electrical spinal stimulation with their knees and hips extended without trainer assistance, and (2) investigate whether postural control can be further improved following repeated sessions of stand training. Using a double-blind, balanced, within-subject cross-over, and sham-controlled study design, 15 individuals with SCI of various severity received transcutaneous electrical spinal stimulation to regain self-assisted standing. The primary outcomes included qualitative comparison of need of external assistance for knee and hip extension provided by trainers during standing without and in the presence of stimulation in the same participants, as well as quantitative measures, such as the level of knee assistance and amount of time spent standing without trainer assistance. None of the participants could stand unassisted without stimulation or in the presence of sham stimulation. With stimulation all participants could maintain upright standing with minimum and some (n = 7) without external assistance applied to the knees or hips, using their hands for upper body balance as needed. Quality of balance control was practice-dependent, and improved with subsequent training. During self-initiated body-weight displacements in standing enabled by spinal stimulation, high levels of leg muscle activity emerged, and depended on the amount of muscle loading. Our findings indicate that the lumbosacral spinal networks can be modulated transcutaneously using electrical spinal stimulation to facilitate self-assisted standing after chronic motor and sensory complete paralysis.

Keywords: balance control; neuromodulation; neuroplasticity; paralysis; transcutaneous electrical spinal cord stimulation.

Conflict of interest statement

V.R.E., Y.P.G., and J.W.B., researchers on the study team, hold shareholder interest in NeuroRecovery Technologies. They hold certain inventorship rights on intellectual property licensed by the regents of the University of California to NeuroRecovery Technologies and its subsidiaries.

Figures

FIG. 1.

Schematics presenting the experimental design and interventions. (A) Fifteen individuals were tested in a single experimental session without and in the presence of tSCS. Eleven participants received sham stimulation by using intentionally ineffective for standing pulse configuration or location of delivery. (B) Six participants underwent 12 training sessions, where trials without and with spinal stimulation were randomly assigned within each session. Shown is an example of protocol during a single training session. (C) Decision tree exemplifying the adjustment of the stimulation parameters during “ostural adjustments” in each experimental session (see description in the text).”+” and “−” indicate an increase or decrease of spinal stimulation intensity, respectively. tSCS, transcutaneous electrical spinal cord stimulation.

FIG. 2.

Individual reactions during tSCS. (A) EMG activity of the left leg muscles during tSCS delivered with a frequency of 15 Hz at incremental intensities over T11 and L1 during sitting and standing, recorded in a representative participant (P3). Right panels indicate spinally evoked motor potentials recorded during the indicated stimulation intensities. (B) Transition from sitting to standing, recorded in a representative participant (P2). Note minimum EMG activity and low amount of body-weight bearing on the force plate during the upright position without spinal stimulation, and modulated EMG activity and a high amount of the body-weight on the support surface during stimulation. Also note “oscillating” versus “smooth” patterns of the hip displacement during the transition without and with spinal stimulation, respectively (shown by dotted traces). EMG, electromyogram; tSCS, transcutaneous electrical spinal cord stimulation.

FIG. 3.

Characteristics of spinal stimulation to induce self-assisted standing. (A) EMG activity in the leg muscles during standing without (black traces), in the presence of sham (olive traces and font, show intensities from 40 to 110 mA) and effective (red traces and font, show intensities from 10 to 80 mA) tSCS delivered over the L1 at 15 Hz, recorded in a representative participant (P2). “L Knee” and “R Knee,” readings from the pressure sensors placed above the participant's knees quantifying assistance provided by the trainer. “Self-assisted” label indicates both knees and hips extension independent of trainer assistance. (B) Pooled effects of the amount of assistance applied to the participants' knees during standing without stimulation (n = 15, black font), during sham stimulation (n = 11, olive font), and during standing enabled by tSCS (n = 15, red font). Without and during sham stimulation, all participants required trainers' assistance applied to the knees and hips, whereas in the presence of tSCS, the incidence and required force of knee assistance were reduced; hip assistance was not required in eight participants (also see Table 1). “LKs” and “RKs” indicate the left and right knee being supported, respectively; “LKi” and “RKi” indicate the left and right knee being independent, respectively; “NS” indicates standing with no stimulation (gray and black); “sham” indicates sham stimulation (light and dark yellow); “stim” indicates standing during tSCS (pink and red). (C) The mean muscle EMG amplitude during standing with no stimulation (n = 15), in the presence of sham stimulation (n = 11), and sitting and standing (n = 15) in the presence of tSCS of the same intensity during the first experimental session. (D) Recruitment curves of motor evoked potentials in the left leg muscles obtained at different frequencies of spinal stimulation delivered over the L1 during standing in a representative participant (P3). Vertical dashed lines indicate the stimulation intensity sufficient to generate self-assisted standing at indicated frequency. Note the decrease in the evoked potentials' magnitude at higher stimulation frequencies. Lower panels present the center of pressure (COP) oscillations in the anteroposterior (AP) direction, as well as the frequency spectrum corresponding to the AP COP. With tSCS frequency of 5 Hz, the dominant frequency of the COP oscillations corresponds to that of the stimulation (e.g., 5 Hz). During tSCS of higher frequencies, the COP oscillations are independent from the stimulation frequency. (E) Pooled effects (n = 6) of tSCS delivered over the T11 and L1 at 5, 15, and 25 Hz on EMG responses in leg muscles. The magnitude of responses was normalized to the maximum amplitude of each muscle during stimulation delivered at 0.2 Hz. EMG, electromyogram; tSCS, transcutaneous electrical spinal cord stimulation.

FIG. 4.

Self-initiated body-weight displacements. (A) Modulation of EMG activity in the left leg muscles and the COP signal during self-initiated body-weight displacements in the mediolateral or anteroposterior directions before (blue traces) and after (red traces) stand training in a representative participant (P2) without and in the presence of tSCS delivered over the L1 with frequency of 15 Hz. The directions of the body-weight displacements are indicated on the top. Lower panel presents individual spinally evoked motor potentials in the initial (center) position and during the body-weight displacements in a particular direction. Note VL activity (arrows) occurred independently of the stimulation during the body-weight displacements following stand training. (B) Pooled data (n = 6) demonstrating modulatory effects of the body-weight displacements in the mediolateral or anteroposterior directions on the magnitude of spinally evoked motor potentials in the left and right leg muscles during standing enabled by tSCS following training. The magnitude of spinally evoked motor potentials was normalized to the peak-to-peak amplitude of each muscle at the initial position, that is prior to movement in either direction (shown by red dashed line). COP, center of pressure; EMG, electromyogram; tSCS, transcutaneous electrical spinal cord stimulation; VL, vastus lateralis.

FIG. 5.

Effects of stand training intervention on electrophysiological characteristics (n = 6). (A) Types and duration of activities practiced during the training period. “Postural adjustments” included the participant's positioning in the stand frame and on the force plate, optimization of stimulation parameters, and self-initiated body-weight displacements without and in presence of spinal stimulation; “game-based exercises” included “Circle” and “Basketball” tasks practice. (B) Stimulation intensity required to induce self-assisted or minimally assisted standing, leg muscle activity during standing without and in the presence of spinal stimulation, and during sit-to-stand transitions through the training period. Filled and outlined by dashed line symbols correspond to intensities during which the micturition reflexes occurred in participants P2 and P3 during sessions 6 and 10, respectively. (C) Stimulation intensity required to evoke motor threshold response in the leg muscles in the sitting and standing positions during the training period. Horizontal bars indicate significant differences between training sessions, stimulated versus unstimulated trials, and muscles.

FIG. 6.

Effects of stand training intervention on functional features. (A) The COP trajectory during the “Circle” game-based exercise without (blue traces) and in presence of spinal stimulation (red traces) in a representative participant (P4). (B) The COP trajectory during the “Basketball” exercise during spinal stimulation in a representative participant (P6). Note the increased score after the stand training. Gradient colors at the horizontal bars present time series synchronized with the cumulative COP trajectories displayed above. (C) Pooled data (n = 6) of the performance during the first and last training sessions of the stand training. The average score was calculated from three trials of each exercise. Examples of the game-based exercises are presented in the top left corner of each graph. (D) Progressive decrease of the level of assistance provided by trainer to the left and right knees during standing in the presence of tSCS (pink and red) as percent of the values during standing without stimulation (NS, gray and black) recorded using the FSR sensors within each session. Zero value indicates that the knee is independently extended (no assistance needed). Participants P2 and P3 (not displayed) did not require any knee assistance during standing in the presence of tSCS starting from training session 1. Hip assistance was not needed during standing in the presence of tSCS for participants P1 and P2 starting from training session 1, and for participant P3—starting from training session 4. Participants P4–P6 required hip assistance during standing in the presence of tSCS throughout the training period. (E) The COP area during self-initiated body-weight displacements performed without and in the presence of spinal stimulation during the training period (n = 6). Horizontal bars indicate significant differences of the COP area between training sessions. COP, center of pressure; FSR, force-sensing resistor; tSCS, transcutaneous electrical spinal cord stimulation.

FIG. 7.

Effects of multi-site spinal stimulation. (A) Changes in the EMG activity pattern during one-site stimulation delivered over the L1 at frequency of 15 Hz, and combined stimulation over the T11 (30 Hz) and L1 (15 Hz) in participant P1. Note changes of the tonic pattern of the muscle activity during L1 stimulation to the rhythmic, “bursting” pattern, resembling “stepping” during the combined stimulation. (B) Goniograms of the right hip and knee and EMG activity of the leg muscles during unilateral stepping motion in participant P15, performed by the right foot, without (left panel), during spinal stimulation applied over the T11 at 30 Hz (middle panel), and over the T11 at 30 Hz and L1 at 15 Hz levels (right panel). Note increased angular displacement in the ipsilateral hip and knee joints, as well as larger activity in the contralateral SOL, during combined T11+L1 stimulation. The thin gray traces indicate individual responses (n = 3), whereas the bold black traces indicate the average of three responses. EMG, electromyogram; SOL, soleus.