Locomotor training improves reciprocal and nonreciprocal inhibitory control of soleus motoneurons in human spinal cord injury

Abstract

Pathologic reorganization of spinal networks and activity-dependent plasticity are common neuronal adaptations after spinal cord injury (SCI) in humans. In this work, we examined changes of reciprocal Ia and nonreciprocal Ib inhibition after locomotor training in 16 people with chronic SCI. The soleus H-reflex depression following common peroneal nerve (CPN) and medial gastrocnemius (MG) nerve stimulation at short conditioning-test (C-T) intervals was assessed before and after training in the seated position and during stepping. The conditioned H reflexes were normalized to the unconditioned H reflex recorded during seated. During stepping, both H reflexes were normalized to the maximal M wave evoked at each bin of the step cycle. In the seated position, locomotor training replaced reciprocal facilitation with reciprocal inhibition in all subjects, and Ib facilitation was replaced by Ib inhibition in 13 out of 14 subjects. During stepping, reciprocal inhibition was decreased at early stance and increased at midswing in American Spinal Injury Association Impairment Scale C (AIS C) and was decreased at midstance and midswing phases in AIS D after training. Ib inhibition was decreased at early swing and increased at late swing in AIS C and was decreased at early stance phase in AIS D after training. The results of this study support that locomotor training alters postsynaptic actions of Ia and Ib inhibitory interneurons on soleus motoneurons at rest and during stepping and that such changes occur in cases with limited or absent supraspinal inputs.

Keywords: Ib inhibition; locomotor training; neuromodulation; neuroplasticity; reciprocal inhibition; spinal cord injury.

Fig. 1.

Reciprocal inhibition before and after locomotor training during seated. A: nonrectified waveform averages (n = 20) of conditioned soleus H reflexes (black lines) by common peroneal nerve (CPN) stimulation at 2-, 3-, and 4-ms conditioning-test (C-T) intervals are shown superimposed on the associated unconditioned (grey lines) soleus H reflexes recorded before and after locomotor training. Reflexes are indicated for motor complete [American Spinal Injury Association Impairment Scale A (AIS A) R07] and motor incomplete (AIS C, R15; AIS D, R17) spinal cord injuries (SCIs). B–D: overall amplitude of the conditioned soleus H reflex as a percentage of the unconditioned H reflex recorded in AIS A, B, C, and D subjects at 2-, 3-, and 4-ms C-T intervals before and after training. *Statistically significant differences between the conditioned H reflexes recorded before and after training. Error bars denote the SE.

Fig. 2.

Reciprocal inhibition before and after locomotor training during stepping. Mean amplitudes of the conditioned and unconditioned soleus H reflexes recorded before and after locomotor training from AIS C (A and B) and AIS D (D and E) subjects during stepping as a percentage of the associated maximal M wave. *Decreased conditioned H reflexes compared with the unconditioned H reflexes. §Statistically significant differences between the conditioned H reflexes recorded before and after training. C and F: net modulation of reciprocal inhibition with positive values suggesting decreased reciprocal inhibition and negative values suggesting increased reciprocal inhibition. Bin 1 corresponds to heel contact. Bins 8, 9, and 16 correspond approximately to stance-to-swing transition, swing phase initiation, and swing-to-stance transition, respectively. Error bars in all graphs denote the SE.

Fig. 3.

Soleus M waves during stepping before and after training in SCI. Normalized M-wave amplitudes (as a percentage of the maximal M wave) recorded during stepping before and after locomotor training for the unconditioned soleus H reflex and following common peroneal nerve stimulation (reciprocal Ia inhibition) in AIS C (A and B) and in AIS D (C and D) subjects. For all cases, the M waves did not change across bins or time of testing.

Fig. 4.

Relationship between conditioned soleus H reflex and background EMG activity. A: normalized soleus background EMG activity (top) along with the mean normalized soleus EMG background activity plotted against the conditioned soleus (SOL) H reflex recorded at each bin of the step cycle (bottom) before and after locomotor training. B: normalized tibialis anterior (TA) background EMG activity (top) along with the mean normalized TA EMG background activity plotted against the conditioned soleus H reflex recorded at each bin of the step cycle (bottom) before and after locomotor training. For both graphs at the bottom, the 16 points correspond to the 16 bins of the step cycle.

Fig. 5.

Ib inhibition before and after locomotor training during seated. A: nonrectified waveform averages (n = 20) of conditioned soleus H reflexes (black lines) by medialis gastrocnemius (MG) nerve stimulation at 4-, 5-, and 6-ms C-T intervals are shown superimposed on the associated unconditioned (grey lines) soleus H reflexes recorded before and after locomotor training. Reflexes are indicated for motor complete (AIS A, R07) and motor incomplete (AIS C, R16; AIS D, R12) SCIs. B–D: overall amplitude of the conditioned soleus H reflex as a percentage of the unconditioned H reflex recorded in AIS A, B, C, and D subjects at 4-, 5-, and 6-ms C-T intervals before and after training. *Statistically significant differences between the conditioned H reflexes recorded before and after training. §Statistically significant differences between the conditioned and the unconditioned H reflexes recorded before training. Error bars denote the SE.

Fig. 6.

Ib inhibition before and after locomotor training during stepping. The mean amplitudes of the conditioned and unconditioned soleus H reflexes recorded before and after locomotor training from the right leg of AIS C (A and B) and AIS D (D and E) subjects during walking are shown as a percentage of the associated maximal M wave. *Decreased conditioned H reflexes compared with the unconditioned H reflexes. §Statistically significant differences between the conditioned H reflexes recorded before and after training. C and F: net modulation of Ib inhibition with positive values suggesting decreased Ib inhibition and negative values suggesting increased Ib inhibition. Bins 8, 9, and 16 correspond approximately to stance-to-swing transition, swing phase initiation, and swing-to-stance transition, respectively. Error bars in all graphs denote the SE.

Fig. 7.

Soleus M waves during stepping before and after training in SCI. Normalized M-wave amplitudes (as a percentage of the maximal M wave) recorded during stepping before and after locomotor training for the unconditioned soleus H reflex and following medial gastrocnemius nerve stimulation (nonreciprocal Ib inhibition) in AIS C (A and B) and in AIS D (C and D) subjects. For all cases, the M waves did not change across bins or time of testing.

Fig. 8.

Relationship between conditioned soleus H reflex and background EMG activity. A: normalized soleus background EMG activity (top) along with the mean normalized soleus background EMG activity plotted against the conditioned soleus H reflex for each bin of the step cycle (bottom) before and after locomotor training. B: normalized MG background EMG activity (top) along with the mean normalized MG background EMG activity plotted against the conditioned soleus H reflex for each bin of the step cycle (bottom) before and after locomotor training. For both graphs at the bottom, the 16 points correspond to the 16 bins of the step cycle.

Fig. 9.

Magnitude of spinal postsynaptic inhibition. A and B: percentage of change of the conditioned H reflex during seated from all subjects after training, reflecting the magnitude of reciprocal and nonreciprocal inhibition, is plotted against the number of locomotor training sessions attended. C and D: percentage of change of the conditioned H reflex during seated from all subjects after training, reflecting the magnitude of reciprocal and nonreciprocal inhibition, is plotted against the years postinjury.