Effects of Stand and Step Training with Epidural Stimulation on Motor Function for Standing in Chronic Complete Paraplegics

Abstract

Individuals affected by motor complete spinal cord injury are unable to stand, walk, or move their lower limbs voluntarily; this diagnosis normally implies severe limitations for functional recovery. We have recently shown that the appropriate selection of epidural stimulation parameters was critical to promoting full-body, weight-bearing standing with independent knee extension in four individuals with chronic clinically complete paralysis. In the current study, we examined the effects of stand training and subsequent step training with epidural stimulation on motor function for standing in the same four individuals. After stand training, the ability to stand improved to different extents in the four participants. Step training performed afterwards substantially impaired standing ability in three of the four individuals. Improved standing ability generally coincided with continuous electromyography (EMG) patterns with constant levels of ground reaction forces. Conversely, poorer standing ability was associated with more variable EMG patterns that alternated EMG bursts and longer periods of negligible activity in most of the muscles. Stand and step training also differentially affected the evoked potentials amplitude modulation induced by sitting-to-standing transition. Finally, stand and step training with epidural stimulation were not sufficient to improve motor function for standing without stimulation. These findings show that the spinal circuitry of motor complete paraplegics can generate motor patterns effective for standing in response to task-specific training with optimized stimulation parameters. Conversely, step training can lead to neural adaptations resulting in impaired motor function for standing.

Keywords: epidural stimulation; spinal cord injury; spinal motor learning; standing; training.

Conflict of interest statement

No competing financial interests exist.

Figures

FIG. 1.

Experimental protocol timeline. (A) Weeks devoted to complete training and experimental sessions (related and unrelated to the present study) performed before any training (pre-training), after stand training (post-stand), and after step training (post-step). Total number of stand and step training sessions performed by each participant is also reported. (B) Assessments performed during different experimental sessions at pre-training, post-stand, and post-step.

FIG. 2.

Time course of full weight-bearing standing and resting time throughout stand training. (A) Total standing time, standing time without external assistance for knee extension, and resting (sitting) time are plotted as a function of the number of training sessions performed by the research participants. Vertical black dotted lines indicate that electrode configuration was modified to optimize standing. (B) Cumulative standing time without external assistance for knee extension throughout the 80 stand training sessions. (C) Longest standing bout without external assistance for knee extension performed during stand training.

FIG. 3.

Full weight-bearing standing time without external assistance for hip and knee extension. The ability to stand without external assistance for hip and knee extension was assessed during a 10 min session before training (pre), after stand training (post-stand), and after step training (post-step). At post-stand and post-step, stimulation parameters adjusted for standing throughout stand training were used. Standing time without external assistance (triangles), without assistance for hip extension (gray circles), and for knee extension (empty squares) is reported for each of the three time points. Stimulation frequency, electrode configuration (cathodes in black, anodes in gray, and inactive in white), and stimulation intensity range are reported for each participant. At post-stand and post-step, participant A53 was stimulated with four programs (P.1 to P.4) delivered sequentially at 10 Hz by the same electrode array, resulting in an ongoing 40 Hz stimulation frequency.

FIG. 4.

Electromyography (EMG) and ground reaction forces recorded during full weight-bearing standing before any activity-based training, after stand training, and after step training with epidural stimulation. (A) Time course of EMG and ground reaction forces recorded during representative full weight-bearing standing performed before stand training (pre), after stand training (post-stand), and after step training (post-step). The amount of external assistance is reported at the top of each panel. At post-stand and post-step, stimulation parameters adjusted for standing throughout stand training were used. Stimulation frequency, amplitude, and electrode configuration (cathodes in black, anodes in gray, and inactive in white) are reported for each participant. At post-stand and post-step, participant A53 was stimulated with four programs (P.1 to P.4) delivered sequentially at 10 Hz by the same electrode array, resulting in an ongoing 40 Hz stimulation frequency. EMG was recorded from the following muscles of the left lower limb: IL, iliopsoas; GL, gluteus maximus; MH, medial hamstring; VL, vastus lateralis; TA, tibialis anterior; SOL, soleus. (B) Coefficient of variation calculated for EMG activity (average value among the six investigated muscles) and ground reaction forces is reported in A.

FIG. 5.

Electromyography (EMG) and ground reaction forces recorded during full weight-bearing standing after stand training with initial stimulation parameters. (A) Time course of EMG and ground reaction forces recorded during representative full weight-bearing standing performed after stand training with stimulation parameters selected prior to stand training. Stimulation intensity was adjusted for A45 after training. Amount of external assistance is reported at the top of each panel. Stimulation frequency, intensity, and electrode configuration (cathodes in black, anodes in gray, and inactive in white) are reported for each participant. EMG was recorded from the following muscles of the left lower limb: IL, iliopsoas; GL, gluteus maximus; MH, medial hamstring; VL, vastus lateralis; TA, tibialis anterior; SOL, soleus. (B) Coefficient of variation calculated for EMG activity (average value among the six investigated muscles) and ground reaction forces are reported in A.

FIG. 6.

Sitting and assisted standing without epidural stimulation before training, after stand training, and after step training. (A) Time course of electromyography (EMG) and ground reaction forces recorded during sitting and assisted standing without epidural stimulation before training (pre), after stand training (post-stand), and after step training (post-step) in participant A53. (B) EMG amplitude calculated as the root mean square (RMS) over 10 sec of steady sitting and standing. Standing data were recorded during overground full weight-bearing standing (participants A53 and B07) or during standing with a body weight load of 60% (participants A45 and B13) with external assistance for knee and hip extension provided by trainers. EMG was recorded from the following muscles of the left lower limb: IL, iliopsoas; GL, gluteus maximus; MH, medial hamstring; VL, vastus lateralis; TA, tibialis anterior; SOL, soleus.

FIG. 7.

Effects of stand and step training on electromyography (EMG) amplitude modulation induced by the change in body position from sitting to standing. (A) Evoked potentials recorded from the right vastus lateralis (R VL) muscle of participant A45 during sitting and assisted standing before training (pre), after stand training (post-stand), and after step training (post-step). (B) Ratio between peak–peak EMG amplitude of evoked potentials (mean ± SD; n = 20) recorded during standing and sitting from R VL of participant A45 at the three investigated time points. (C) Stand–sit ratio of peak–peak EMG amplitude (n = 20 evoked potentials considered for each muscle) expressed as an average among primary extensor muscles (left and right soleus, medial gastrocnemius, vastus lateralis, rectus femoris; empty squares; n = 160), among primary flexor muscles (left and right tibialis anterior and medial hamstring; empty triangles; n = 80), and as an average among all investigated muscles (left and right soleus, medial gastrocnemius, vastus lateralis, rectus femoris, tibialis anterior and medial hamstring; black diamonds; n = 240). Values are mean ± SD. Differences were tested by Friedman test, and following multiple comparisons by Dunn's post-hoc test. *p ≤ 0.05; **p < 0.0001. Standing data were recorded during overground full weight-bearing standing (participant A53) or during standing with a body weight load of 60% (participants A45 and B13) with external assistance for knee and hip extension provided by trainers. Stimulation frequency, intensity, and electrode configuration (cathodes in black, anodes in gray, and inactive in white) are reported at the bottom of the figure.

FIG. 8.

Characteristics of evoked potentials recorded with the subject in the supine position. (A) Evoked potentials to epidural stimulation recorded from the right vastus lateralis (participant A45) and from the right soleus (participant B13) prior to any training (pre), after stand training (post-stand), and after step training (post-step). The colored traces are the average of five responses represented in gray, which were those with the largest peak to peak amplitude being induced by the stimulation intensity corresponding to the arrows shown in B (recruitment curves). Data are shown from the time window between the stimulation onset and 50 ms following the stimulation. (B) Representative recruitment curves recorded at pre (diamonds), post-stand (squares), and post-step (triangles) are shown for participants A45 (right vastus lateralis) and B13 (right soleus) at stimulation intensities ranging from 0.1 to 5 V. Each peak–peak electromyography (EMG) amplitude value is reported as mean ± SD of n = 5 evoked potentials. Arrows indicate the largest value at each time point. (C) Peak–peak EMG amplitude (n = 5 evoked potentials considered for each muscle) was expressed as percent of pre-training values, and was averaged among primary extensor muscles (left and right soleus, medial gastrocnemius, vastus lateralis, rectus femoris, gluteus maximus; empty squares; n = 50), among primary flexor muscles (left and right tibialis anterior and medial hamstring; empty triangles; n = 20), and as an average among all investigated muscles (left and right soleus, medial gastrocnemius, vastus lateralis, rectus femoris, gluteus maximus, tibialis anterior and medial hamstring; black diamonds; n = 70). Values are mean ± SD. Differences were tested by Friedman test, and following multiple comparisons by Dunn's post-hoc test. *p ≤ 0.05; **p < 0.001. (D) Muscle activation threshold. For each individual, the underlined muscle was that with the lowest activation threshold detected before training (reference muscle). At each time point (pre, diamonds; after stand training, post-stand, squares; after step training, post-step, triangles), the activation threshold of each muscle was expressed as a percent of that observed for the reference muscle. Stimulation intensity range is reported for each participant. L, left; R, right; GL, gluteus maximus; MH, medial hamstring; RF, rectus femoris; VL, vastus lateralis; MG, medial gastrocnemius; SOL, soleus; TA, tibialis anterior. Stimulation frequency and electrode configuration (cathodes in black, anodes in gray, and inactive in white) are reported at the bottom of the figure.