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Review
. 2012:2012:254948.
doi: 10.1155/2012/254948. Epub 2012 Jun 4.

Plasticity of corticospinal neural control after locomotor training in human spinal cord injury

Affiliations
Review

Plasticity of corticospinal neural control after locomotor training in human spinal cord injury

Maria Knikou. Neural Plast. 2012.

Abstract

Spinal lesions substantially impair ambulation, occur generally in young and otherwise healthy individuals, and result in devastating effects on quality of life. Restoration of locomotion after damage to the spinal cord is challenging because axons of the damaged neurons do not regenerate spontaneously. Body-weight-supported treadmill training (BWSTT) is a therapeutic approach in which a person with a spinal cord injury (SCI) steps on a motorized treadmill while some body weight is removed through an upper body harness. BWSTT improves temporal gait parameters, muscle activation patterns, and clinical outcome measures in persons with SCI. These changes are likely the result of reorganization that occurs simultaneously in supraspinal and spinal cord neural circuits. This paper will focus on the cortical control of human locomotion and motor output, spinal reflex circuits, and spinal interneuronal circuits and how corticospinal control is reorganized after locomotor training in people with SCI. Based on neurophysiological studies, it is apparent that corticospinal plasticity is involved in restoration of locomotion after training. However, the neural mechanisms underlying restoration of lost voluntary motor function are not well understood and translational neuroscience research is needed so patient-orientated rehabilitation protocols to be developed.

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Figures

Figure 1
Figure 1
Schematic illustration of cortical control of spinal reflex circuits and spinal interneuronal circuits investigated after 60 sessions of locomotor training in the same SCI subject. The soleus H-reflex evoked by posterior tibial nerve stimulation, tibialis anterior (TA) muscle motor evoked potential (MEP), soleus H-reflex conditioned by subthreshold transcranial magnetic stimulation (TMS) delivered at an optimal site (“hot spot”) for evoking an MEP in the right soleus muscle, soleus H-reflex depression by common peroneal nerve stimulation that is mediated by Ia inhibitory interneurons (Ia INs; reciprocal inhibition), and the reciprocal inhibition conditioned by subthreshold TMS delivered at an optimal site (“hot spot”) for evoking an MEP in the right TA muscle were all investigated in the same patient at rest and/or during assisted stepping after locomotor training. Open triangles indicate excitatory synapses, while the filled circle indicates inhibitory synapses. The cortical control on these spinal circuits is indicated as a synapse that may increase (+) or decrease (−) actions of flexor-extensor α motor neurons and/or Ia inhibitory interneurons.
Figure 2
Figure 2
TA MEP modulation during stepping before and after locomotor training in SCI. The tibialis anterior (TA) motor evoked potential (MEP) amplitude before (dashed line) and after (solid line) 60 body weight-supported treadmill training (BWSTT) sessions is indicated as a function of the step cycle during body weight-supported (BWS) assisted stepping for one patient with American Spinal Injury Association (ASIA) Impairment Scale (AIS) D (49 yo female, 5 years after injury, T5–7). The TA MEP was evoked randomly every 3 to 4 steps at 1.3 times TA MEP threshold while stepping at 0.5 m/s with 50% BWS before training and at 0.89 m/s with 20% BWS after training. MEP threshold was established with subject standing at equivalent levels of BWS utilized during stepping. The step cycle was divided into 16 equal time windows or bins. Stance phase duration is identified by the grey region. Bin 1 corresponds to heel strike. Bins 8, 9, and 16 correspond approximately to stance-to-swing transition, swing phase initiation, and swing-to-stance transition, respectively.
Figure 3
Figure 3
Soleus H-reflex modulation during assisted stepping before and after locomotor training in SCI. The unconditioned soleus H-reflex modulation before (dashed lines) and after (solid lines) 60 sessions of body weight-supported treadmill training (BWSTT) (a) and the conditioned soleus H-reflex by subthreshold TMS at the conditioning-test interval of 1 ms (b) are indicated as a function of the step cycle. The mean amplitude of the unconditioned and conditioned soleus H-reflexes evoked at each bin is expressed as a percentage of the maximal M-wave evoked 80 ms after the test H-reflex. TMS was delivered at 0.95 times MEP threshold for the soleus muscle at a conditioning-test interval of 1-ms. Unconditioned and conditioned soleus H-reflexes were accepted when the associated M-waves ranged from 4 to 8% of the maximal M-wave evoked at each bin. H-reflex values are not indicated for some of the bins after BWSTT because they were not accepted based on the M-wave amplitude as a percentage of the maximal M-wave, which is different from not being evocable as was the case for before BWSTT. The step cycle was divided into 16 equal time windows or bins. Stance phase duration is identified by the grey region. Bin 1 corresponds to heel strike. Bins 8, 9, and 16 correspond approximately to stance-to-swing transition, swing phase initiation, and swing-to-stance transition, respectively.
Figure 4
Figure 4
Cortical control of spinal reflex circuits after locomotor training in SCI. Mean size (n = 20) of soleus H-reflex conditioned by common peroneal nerve stimulation at the conditioning-test interval of 3 ms, which reflects the amount of reciprocal Ia inhibition (RCI), soleus H-reflex conditioned by subthreshold TMS (TMS + H-reflex) at a C-T interval of 1 ms, and reciprocal inhibition conditioned with subthreshold TMS (TMS + RCI) at C-T intervals of 1 and 3 ms, respectively. Data are from the same patient. The size of the conditioned H-reflexes is expressed as a percentage of the mean amplitude of the control soleus H-reflex. Error bars indicate the SEM, and asterisks denote a statistically significant difference (paired t-test, P < 0.05) for conditioned H-reflexes recorded before and after 60 BWSTT sessions.
Figure 5
Figure 5
Changes in the cortical control of reciprocal Ia inhibition after locomotor training in SCI. Net effects of subthreshold transcranial magnetic stimulation (TMS) on reciprocal Ia inhibition during BWS assisted stepping before and after 60 body weight-supported treadmill training (BWSTT) sessions. The net effects of subthreshold TMS on reciprocal inhibition were estimated at each bin of the step cycle based on the equation (D-C)-(B-A) whereas A is the test H-reflex during stepping, B is the soleus H-reflex conditioned by subthreshold TMS during stepping at a conditioning-test (C-T) interval of 1 ms, C is the soleus H-reflex conditioned by common peroneal nerve stimulation (i.e., reciprocal inhibition) at a C-T interval of 3 ms during stepping, and D is the reciprocal inhibition conditioned by subthreshold TMS (3 and 1 ms C-T intervals). Positive values indicate potentiation of reciprocal inhibition and negative values indicate attenuation of reciprocal inhibition by cortical inputs.

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