Neural Plasticity
of the Human Spinal Cord
Occurs with Locomotor Training

Janell A. Beres¹, Roscelle Joaquin¹, Rita U. Lukacs², Rubia van den Brand¹, Wieteke Schouten¹, Keith E. Gordon¹, and Susan J. Harkema^1,2
1Department of Neuology, ²Brian Research Institute, University of California at Los Angeles, Los Angeles, CA, 90095

 

Table of Contents ::Home ::Abstract ::Introduction ::Methods ::Results ::References ::Conclusions ::Acknowledgments

::Abstract If neural circuits in the human lumbosacral spinal cord can adapt with step training, then significant locomotor recovery in severely injured spinal cord injury (SCI) patients may result. We studied four clinically complete and two clinically incomplete SCI subjects during locomotor training using body weight support on a treadmill (BWST) with manual assistance as needed. We recorded electromyography (EMG) from sixteen lower limb muscles, hip, knee and ankle angles, and individual limb loads before and after approximately 80 training sessions. Following training EMG burst activity during stepping had higher amplitudes and more discrete burst patterns associated with the stance and swing phases of the step cycle. Several muscles developed EMG activity after training that were inactive prior to training; others developed more complex burst patterns such as double bursting. Locomotor-like EMG patterns emerged after several weeks of training in two clinically complete SCI subjects, in which EMG activity was absent or minimal prior to training. Locomotor training also modulated EMG responses to changing limb loading and stepping velocity. SCI subjects could bear a greater amount of body weight load during stepping, and stepped more independently following training. These findings provide evidence that spinal networks can process proprioceptive inputs derived from stepping and remaining descending inputs to produce functional motor patterns and adapt to repetitive step training.   ::Introduction Recovery of human locomotion has been considered unattainable following a clinincally complete or severe incomplete spinal cord injury even after conventional therapy. It has been generally assumed that the processing of sensory information, plasticity, and learning after spinal cord injury must be attributed largely to supraspinal structures rather than to the spinal cord. However, spinally transected animals can relearn to independently hindlimb step by training that provides complex temporal patterns of sensory information related to locomotion, which is interpreted by the spinal cord (2, 4). The question remains as to the degree that spinal interneurons of humans can integrate and interpret complex sensory signals to produce functional efferent output and adapt to repetitive training like other mammals. Several recent studies have indicated that individuals with very limited supraspinal input after locomotor training using BWST and manual assistance can achieve significant levels of recovery of locomotion not predicted by their capacity to voluntarily move their lower limbs (1, 3, 5, 6, 7, 8, 10, 12, 14, 15, 16, 17). Clear evidence of independent stepping has not been shown in clinically complete SCI subjects; however, studies do suggest that extensive processing of sensory information at the level of the spinal cord occurs, which can facilitate locomotor patterns. We have previously demonstrated that the amplitudes of EMG activity can be modulated by level of lower limb loading (11) and velocity of stepping (13). We examined whether the human spinal cord can adapt to repetitive locomotor training using BWST and manual assistance. We studied the locomotor patterns of clinically complete and incomplete SCI subjects before and after several weeks/months of locomotor training.   ::Methods Subjects with both clinically complete and incomplete SCI were studied prior to and after several weeks of locomotor training using BWST and manual assistance. Each subject wore a harness connected to an overhead lift that allowed adjustment of lower limb loading (fig 1). During stepping using BWST trainers provided manual assistance at the lower limbs as needed. Hand placement distal to the patella facilitated extension during the stance phase, and hand placement proximal to the ankle facilitated foot clearance during the swing phase. Bungee cords and/or another trainer positioned behind the subject aided in hip stabilization and weight shifting during stepping as needed. Each training session consisted of a minimum of 60 minutes of weight bearing, including standing and at least 30 minutes of weight bearing stepping. Subjects were trained 3-7 times per week, depending on subject availability. The ranges of limb loading and treadmill speeds increased as training progressed. During experimental testing, body weight load (BWL) on the lower limbs ranged from 0% to the maximum loading level at which knee flexion during stance could be avoided, and treadmill speeds for each subject ranged from 0.29 m/s to 1.79 m/s. The number of training sessions for each subject arepresented in Table 1. We studied four subjects with clinically complete SCI and two subjects with clinically incomplete SCI, as graded by the American Spinal Injury Association (ASIA) Impairment Scale (9). (ASIA A: no voluntarily initiated muscle activity below the injury level and absent lower extremity sensory evoked potential; ASIA C and D: some voluntarily initiated EMG in some muscles below the injury level (C), or active movement against gravity with a full range of motion in at least half the muscles (D), and present lower extremity sensory evoked potentials). Joint kinematics, vertical ground reaction forces and the EMG activity from the lower limbs of subjects were assessed during manually assisted step training using BWST (11, 16, 17). Subject characteristics are summarized in Table 1.   ::Results click thumbnails for actual size FIGURE 2 shows that following locomotor training, subjects with SCI can bear a greater percentage of their body weight during stepping. Maximum mean body weight load attainable during stepping using BWST before and after locomotor training is plotted for SCI-A11, A12, A13, and A14 with manual assistance and for SCI-C4 and SCI-D5 during independent stepping*. FIGURE 3 shows that subject SCI-A13 developed EMG activity during stepping in both ankle and knee muscles, which was absent prior to locomotor training. EMG and joint angles are plotted over two steps during stepping using BWST at 27% BWL and 1.5 m/s before and after locomotor training. FIGURE 4 shows the modulation of the EMG response to load before and after several weeks of locomotor training in subject SCI-A12. Following training, there was a general increase in EMG amplitude in several lower limb muscles at both lower and higher loading levels. Additionally the MH EMG bursting pattern became more discretely timed with the step cycle, especially at the higher limb loads. FIGURE 5 shows that subject SCI-D5 developed more prominent EMG activity during stepping in both ankle and knee muscles, as well as a double bursting pattern in the MH following locomotor training. EMG and joint angles are plotted over two steps during stepping using BWST at 40% BWL and 1.34 m/s before and after locomotor training. FIGURE 6 shows the integrated EMG response to mean body weight load in SCI-A12 (left), and step cycle duration in subjects SCI-A11 (middle) and SCI-D5 (right) before and after locomotor training. Locomotor training resulted in increased integrated EMG, which was independent of changes in limb loading and stepping velocity, as well as less variability in the EMG amplitudes and burst durations following training across both load and speed conditions.   ::References 1. Barbeau, H. and Blunt, R. A novel interactive locomotor approach using body weight support to retrain gait in spastic paretic subjects. In Wernig, A. ed. Plasticity of Motorneuronal Connections. Elsevier Science Publishers. 1991, 461-474. 2. Barbeau, H. and Rossignol, S. Recovery of locomotion after chronic spinalization in the adult cat. Brain Res 412: 84-95, 1987. 3. Behrman, A. and Harkema, S. Locomotor training after human spinal cord injury: A series of case studies. Phys Ther 80: 688-700, 2000. 4. de Leon, R. D., Hodgson, J. A., Roy, R. R., and Edgerton, V. R. Locomotor capacity attributable to step training versus spontaneous recovery after spinalization in adult cats. J.Neurophysiology 79: 1329-1340, 1998. 5. Dietz, V., Colombo, G., and Jensen, L. Locomotor activity in spinal man. The Lancet 344: 1260-1263, 1994. 6. Dietz, V., Colombo, G., Jensen, L., and Baumgartner, L. Locomotor capacity of spinal cord in paraplegic patients. Ann Neurol 37: 574-582, 1995. 7. Dietz, V., Curt, A., and Colombo, G. Locomotor pattern in paraplegic patients: training effects and recovery of spinal cord function. Spinal Cord 36: 380-390, 1998a. 8. Dietz, V., Wirz, M., Colombo, G., and Curt, A. Locomotor capacity and recovery of spinal cord function in paraplegic patients: a clinical and electrophysiological evaluation. Electroencephalogr.Clin.Neurophysiol. 19: 140-153, 1998b. 9. Ditunno, J. F., Young, W., Donovan, W. H., and Creasey, G. The international standards booklet for neurological and functional classification of spinal cord injury. Paraplegia 32: 70-80, 1994. 10. Fung, J., Stewart, J. E., and Barbeau, H. The Combined Effects of Clonidine and Cyproheptadine with Interactive Training on the Modulation of Locomotion in Spinal Cord Injured Subjects. J Neurol Sci 100: 85-93, 1990. 11. Harkema, S. J., Hurley, S. L., Patel, U. K., Requejo, P., Dobkin, B. H., and Edgerton, V. R. Human lumbosacral spinal cord interprets loading during stepping. J Neurophysiol 77: 797-811, 1997. 12. Maegele, M., Müller, S., Wernig, A., Edgerton, V Reggie, and Harkema, S. J. Differential recruitment of spinal motor pools during voluntary attempts at lower limb movements versus load bearing stepping following human spinal cord injury. J.Neurotrauma . 2001. Ref Type: Unpublished Work 13. Patel, Uday Kirit, Dobkin, B. H., Edgerton, V Reggie, and Harkema, S. J. The response of neural locomotor circuits to changes in gait velocity. Society For Neuroscience 24, 2104-2104. 1998. Ref Type: Abstract 14. Stewart, J. E., Barbeau, H., and Gauthter, L. Modulation of locomotor patterns and spasticity with clonidine in spinal cord injured patients. Can J Neurol Sci 18: 321-332, 1991. 15. Wernig, A. and Müller, S. Improvement of walking in spinal cord injured persons after treadmill training. In Wernig, A. ed. Amsterdam, Elsevier Science Publishers BV. 1991, 475-485. 16. Wernig, A., Müller, S., Nanassy, A., and Cagol, E. Laufband locomotion with body weight support improved walking in persons with severe spinal cord injuries. Paraplegia 30: 229-238, 1992. 17. Wernig, A., Müller, S., Nanassy, A., and Cagol, E. Laufband therapy based on “rules of spinal locomotion” is effective in spinal cord injured persons. Eur J Neurosci 7: 823-829, 1995.   ::Conclusion 1. Locomotor training can facilitate the emergence of lower limb EMG activity associated with stepping in subjects with clinically complete and incomplete SCI. 2. Locomotor training can modulate an already established bursting pattern, inducing more complex bursting patterns timed to the stance and swing phases of the step cycle in subjects with clinically complete and incomplete SCI. 3. Following locomotor training, clinically complete and incomplete SCI subjects can bear a greater amount of their body weight during stepping using BWST. 4. Integrated EMG activity is consistently higher in lower limb flexor and extensors after locomotor training independent of the level of loading and the velocity of stepping in clinically complete and incomplete SCI subjects. 5. Following locomotor training, clinically complete SCI subjects can independently generate stance and swing phases of gait during stepping and can maintain the independence over several steps. 6. Following locomotor training, clinically incomplete SCI subjects stepped independently on a treadmill using BWST. These findings provide evidence that spinal networks can process proprioceptive inputs derived from stepping and remaining descending inputs to produce functional motor patterns and adapt to repetitive step training.   :: Acknowledgements We would like to thank Carlos Dominguez for his invaluable contributions to this poster. This work was supported by NIH grants NS-16333, NS-36584, and MO1-RR-00865-19.