Phase-dependent modulation of percutaneously elicited multisegmental muscle responses after spinal cord injury

Abstract

Phase-dependent modulation of monosynaptic reflexes has been reported for several muscles of the lower limb of uninjured rats and humans. To assess whether this step-phase-dependent modulation can be mediated at the level of the human spinal cord, we compared the modulation of responses evoked simultaneously in multiple motor pools in clinically complete spinal cord injury (SCI) compared with noninjured (NI) individuals. We induced multisegmental responses of the soleus, medial gastrocnemius, tibialis anterior, medial hamstring, and vastus lateralis muscles in response to percutaneous spinal cord stimulation over the Th11-Th12 vertebrae during standing and stepping on a treadmill. Individuals with SCI stepped on a treadmill with partial body-weight support and manual assistance of leg movements. The NI group demonstrated phase-dependent modulation of evoked potentials in all recorded muscles with the modulation of the response amplitude corresponding with changes in EMG amplitude in the same muscle. The SCI group demonstrated more variation in the pattern of modulation across the step cycle and same individuals in the SCI group could display responses with a magnitude as great as that of modulation observed in the NI group. The relationship between modulation and EMG activity during the step cycle varied from noncorrelated to highly correlated patterns. These findings demonstrate that the human lumbosacral spinal cord can phase-dependently modulate motor neuron excitability in the absence of functional supraspinal influence, although with much less consistency than that in NI individuals.

Figures

Fig. 1.

A and B: overlay of 10 responses in the soleus muscle to double pulses of percutaneous spinal cord stimulation administered at 0 and 50 ms in a noninjured (NI) (A, N2) and a spinal cord injured (SCI) individual (B, A28) in the prone position. The time of the stimulus pulse is indicated by the up arrow and the time of the conditioned response is indicated in the area shaded gray. C–F: the mean response in the soleus muscle to percutaneous spinal cord stimulation in the absence (C and D) or the presence (E and F) of vibration of the Achilles tendon in NI (C and E) and SCI (D and F) individuals lying prone.

Fig. 2.

Ball and stick diagrams of right leg kinematics in the stance and swing phases of one exemplary step cycle in a NI individual (A) during stepping on a treadmill and in an SCI individual (B) during stepping on a treadmill with 47% bodyweight support and manual assistance. A 10 ms interval is between each stick trace. The arrow indicates the direction of stepping.

Fig. 3.

The average (dark trace) and SD (gray trace) of 12 multisegmental monosynaptic responses (MMRs) evoked during standing in the muscles of the right leg soleus (SOL), medial gastrocnemius (MG), tibialis anterior (TA), medial hamstrings (MH), and vastus lateralis (VL) muscles of exemplary (A) NI (N2) and (B) SCI (A29) individuals. Gray shading indicates expected time of MMRs. Arrows indicate stimulus artifact <0.5 ms after the stimulus pulse. C: group data of the average MMR in each muscle as a percentage of the average amplitude of the MMR in the soleus muscle during standing displayed as box and whisker plots showing the median (horizontal line in box), interquartile range (box height), and the range ≤1.5-fold the interquartile range (whiskers). Asterisk indicates significant differences between group median values at P < 0.05.

Fig. 4.

Exemplary data in NI (A, N2) and SCI (B, A29) individuals showing modulation of electromyographic (EMG) activity compared with MMR amplitude across the step cycle. Left column graphs: the linear correlation between the amplitude of average EMG and MMRs was assessed across the step cycle (alpha 0.05 at r = 0.5) with identification of MMRs occurring in stance (filled circles) and swing (open circles). In all, 16 points were used to model the correlation, although similar values resulted in overlapping data points. Right column graphs: comparison of the amplitude of MMRs evoked during standing (dotted line), MMRs during stepping (line connecting open circles), and step cycle EMG activity (line connecting filled circles) as a function of time in the step cycle. Gray bars indicate time the leg was in stance.

Fig. 5.

Mean amplitudes of soleus MMRs and EMG from an individual in the NI (A, N2) and SCI (B, A29) groups during standing and the midstance (bin 7) and midswing (bin 14) of the step cycle.

Fig. 6.

A: NI (N2) data juxtaposed with SCI data to demonstrate modulation of soleus and medial gastrocnemius MMRs across the step cycle that was similar (B, A30) and dissimilar (C, A27) to the NI group pattern. Modulation of MMRs during stepping in all muscles was determined by comparing the average amplitude (black line connecting open circles) of single MMRs (gray dots) with a 95% confidence interval (CI) formed from 5,000 estimates of the mean amplitude of MMRs randomly resampled into 16 bins and corrected for multiple comparisons (upper and lower boundaries demarcated by horizontal lines). MMRs were classified by the location of the mean response in a bin being above, below, or within the CI. Gray bars indicate time the leg was in stance.

Fig. 7.

Heat map showing when during the step cycle MMRs were significantly increased (orange), decreased (blue), or not modulated (gray). The average step cycle was characterized by modulation in 16 time bins with the end of stance indicated by a vertical bar in the (A) NI and (B) SCI groups. Medial hamstring and vastus lateralis muscles for N4 were omitted because of an inability to measure MMRs in those muscles.

Fig. 8.

Greater depth of MMR modulation during stepping was represented by a higher modulation index in NI and SCI individuals. Modulation indexes were calculated by the equation {[max (MMR) − min (MMR)]/max (MMR)} × 100. An additional temporally restricted SCI group modulation index (SCI-R) was calculated by selecting maximum and minimum MMRs values only during times when MMRs were increased or decreased, respectively, in the NI step cycle. Asterisks indicate significant differences in group means in each muscle at P < 0.05.

Fig. 9.

Amount of training experience (number of 60 min sessions) was compared with the restricted modulation index shown in Fig. 8 (SCI-R) in the SCI group. Individuals could have experienced step-training (black circles), stand-training (gray circles), or not have any training experience (open circles).