Corticospinal reorganization after locomotor training in a person with motor incomplete paraplegia

Abstract

Activity-dependent plasticity as a result of reorganization of neural circuits is a fundamental characteristic of the central nervous system that occurs simultaneously in multiple sites. In this study, we established the effects of subthreshold transcranial magnetic stimulation (TMS) over the primary motor cortex region on the tibialis anterior (TA) long-latency flexion reflex. Neurophysiological tests were conducted before and after robotic gait training in one person with a motor incomplete spinal cord injury (SCI) while at rest and during robotic-assisted stepping. The TA flexion reflex was evoked following nonnociceptive sural nerve stimulation and was conditioned by TMS at 0.9 TA motor evoked potential resting threshold at conditioning-test intervals that ranged from 70 to 130 ms. Subthreshold TMS induced a significant facilitation on the TA flexion reflex before training, which was reversed to depression after training with the subject seated at rest. During stepping, corticospinal facilitation of the flexion reflex at early and midstance phases before training was replaced with depression at early and midswing followed by facilitation at late swing after training. These results constitute the first neurophysiologic evidence that locomotor training reorganizes the cortical control of spinal interneuronal circuits that generate patterned motor activity, modifying spinal reflex function, in the chronic lesioned human spinal cord.

Figure 1

EMG activity during robotic-assisted stepping before and after training. (a)–(f) EMG activity of the right side muscles during robotic-assisted stepping at 50% BWS and at 1.8 Km/h before and after training as a function of the step cycle. (g) Mean EMG amplitude for stepping before (black squares) and after (red squares) 35 sessions of robotic gait training. EMG: electromyography; SOL: soleus; MG: medial gastrocnemius; TA: tibialis anterior; PL: peroneus longus; MH: medial hamstrings; GRC: gracilis.

Figure 2

Effects of subthreshold TMS on the TA flexion reflex while seated before and after BWS robotic gait training. (a) Full-wave rectified waveform averages (n = 10) of the control tibialis anterior (TA) flexion reflex (grey line) and the conditioned flexion reflex following single pulse transcranial magnetic stimulation (TMS) of the right primary motor cortex at 0.9 TA motor evoked potentials (MEPs) resting threshold. (b) Mean amplitude of the conditioned TA flexion reflexes recorded before and after BWS robotic gait training with the seated subject. The conditioning-test interval is denoted on the abscissa. Asterisks indicate statistically significant differences between the conditioned TA flexion reflexes recorded before and after training. Error bars denote the SEM.

Figure 3

Changes in cortical control of the flexion reflex after 30 sessions of BWS robotic gait training during robotic-assisted stepping. The mean normalized long-latency tibialis anterior (TA) flexion reflex following single pulse transcranial magnetic stimulation (TMS) of the right primary motor cortex at 0.9 × TA motor evoked potentials (MEPs) at the conditioning-test interval of 70 (a) and 110 (b) ms is indicated as a function of the step cycle. Asterisks indicate suppressive and/or facilitatory conditioned flexion reflexes after locomotor training compared to those observed before training based on the P value computed from pairwise multiple comparisons (two-way ANOVA along with Holm-Sidak tests). Grey squares denote the stance phase. Error bars denote the SEM.