Neural Reogranization of the Functionally Isolated Human Spinal Cord Occurs after Stand Training

C.K. Ferreira²; S.J. Harkema^1,2; J. Beres-Jones¹.
¹Department of Neurology - Assistant Professor, ²Brain Research Institute, University of California, Los Angeles, CA 90095

 

Table of Contents ::Home ::Introduction ::Methods ::Results ::Conclusions ::References ::Acknowledgements

::Introduction After clinically complete spinal cord injury (SCI), most individuals do not regain their ability to stand or step. Recovery of standing for individuals after SCI, even for short periods of time would greatly increase independence during daily tasks and influence the general health of the individual. It has been shown that spinally transected animals can relearn to stand and step when trained (1,3,4,8,13). Further, the task that is learned is specific to the practiced task, e.g. animals trained to stand learn to stand, but can’t step. Weight bearing on both legs provides afferent signals that activate the muscles and entrain standing. Providing the afferent input from repetitive stepping, e.g. alternating loading/unloading and flexion/extension of the legs entrain different patterns of efferent output than if the legs are continually loaded and extended as in standing. These results support that the afferent signaling during stepping and standing is interpreted by the spinal cord as unique patterns of sensory input for a given phase of the particular motor task which can be relearned even in the absence of supraspinal input. We, (8,11,12) and others (2,5-7,9,10,14) have demonstrated that the human spinal cord can generate locomotor-like EMG patterns from studies of clinically complete SCI subjects when stepping with manual assistance using body weight support on a treadmill (BWST). Further, with repetitive step training improvements in EMG patterns, higher levels of weight bearing by the legs, and independence from manual assistance during stepping and standing can occur. In this study, our aim was to determine whether the repetitive presentation of limb loading could induce reorganization of the functionally isolated human spinal cord. We assessed whether specific afferent cues related to the regimen of specific repetitive limb load patterns would alter the efferent response to the same kinematic and kinetic cues before and after training. Six functionally complete spinal cord injured subjects were randomly assigned to a training intervention consisting of 80 sessions of either bilateral or unilateral limb loading. Data were measured before and after each training intervention. Standing and stepping EMG patterns were modulated by the pattern of repetitive limb loading. Subjects were able to bear greater loads post-training. When the same kinematics and kinetics were presented the amplitude of the lower limb EMG were altered. There was an increase in EMG amplitude of extensors during standing in the limb(s) trained to bear weight, and an increase in the EMG amplitude of the flexors in the limbs that were flexed and unloaded during training. These results indicate that relearning a specific motor task may be highly dependent on the specific repetitive afferent stimuli provided when supraspinal input is limited.   ::Methods We studied 6 clinically complete SCI subjects that underwent bilateral stand training (n=3) or unilateral stand training (n=3) for 80 sessions (Table 1). Clinically complete subjects were characterized as having an absent sensory evoked potential (SEP) and no sensory or voluntary motor function below the level of their lesion (American Spinal Injury Association Impairment Scale, Score A). We recorded EMG (Konigsberg, Pasadena, CA) from the soleus (SOL), medial gastrocnemius (MG), tibialis anterior (TA), medial hamstrings (MH), vastus lateralis (VL) and rectus femoris (RF) muscles using bipolar surface electrodes, joint kinematics using electromagnetic sensors (SKILL technologies, Phoenix, AZ), and individual limb vertical ground reaction forces using insole pressure sensors (PEDAR, St. Paul, MN or FSCAN, Boston, MA) during stepping and during attempts at voluntary oscillatory joint movements. Subjects participated in approximately 80 sessions of weight bearing stand training (60 minutes/session, 3-7 sessions/week), during which the subjects were placed on the treadmill in an upright position and suspended by an overhead pulley (Vigor, Stevensville, MI) in a harness (Robertson, Hendersen, NV) at the maximum load at which knee-buckling and trunk collapse could be avoided (Figure 1). A trainer positioned behind the subject aided in pelvic and trunk stabilization, by anterior forces at the pelvis and/or posterior forces at the shoulders, ensuring that the trunk and pelvis were not flexed or hyperextended. Trainers also assisted in maintaining dynamic knee extension by applying posteriorly directed gentle pressure at the tibial tuberosity and stimulation of the patellar tendon to facilitate extensor activity of weight bearing limbs. All trainers were careful to provide assistance only when needed, thereby promoting a greater level of independence. During bilateral standing the load was distributed between both limbs, while during unilateral standing the extended ipsilateral limb assumes full loading and the contralateral limb is maintained in a flexed position, similar to mid-swing. Extensor activation was facilitated in the weight bearing legs by manually stimulating the patellar and Achilles tendons and flexor muscle activation was facilitated in the unloaded leg when needed by stimulating the hamstrings and tibialis anterior tendons. Body weight support was continuously reduced over the course of the 80 sessions as the individual increased their ability to bear weight on the legs. Stand training was gradually translated into an overground environment using a walker, in which the subjects were able to weight bear with minimal assistance.   ::Results Standing SOL, TA, MH, and VL EMG amplitude increased in the limbs trained to bear weight after bilateral and unilateral stand training. In the bilateral stand trained individual, there was an increase in the amplitude of all muscles. In the unilaterally stand trained individual (right-limb loaded), a dramatic increase in amplitude occurred in the right limb while no EMG amplitude change occurred in the left limb. Figure 2. EMG activity (microvolts; ?V) from the soleus (SOL), tibialis anterior (TA), medial hamstring (MH), and vastus lateralis (VL) of the left (top) and right (bottom) limbs from spinal cord injured subjects trained unilaterally and bilaterally on a treadmill using body weight support and manual assistance. Higher EMG occurred in the entrained limb post-training in the unilateral trained individual. Both limbs of the bilaterally trained individual produced higher EMG post training. Subjects were able to bear more load in late training, and were able to translate this to overground standing using a walker. Figure 3. (top) Percent of body weight support (%BWS) used during stand training vs number of training sessions. (bottom, left) Bilateral overground stand training. (bottom, right) Unilateral overground stand training. Subjects’ stand training were gradually translated to over ground concurrently with BWST stand training as subjects were able to bear greater limb loads. Trainers are positioned at the legs and trunk for safety and walker stabilization. Stepping Following locomotor training, the EMG amplitude and stepping pattern changed dramatically in both limbs. For example, discrete bursts emerged from a more tonic output as exemplified by the MH and clonicity was reduced in the SOL and MG. There was an increase in TA EMG activity, which also occurred during the appropriate phase of the step cycle, along with the MH. Further, knee extensor activity became less co-activated between the uni- and bi-articular knee extensors. Following unilateral stand training (left limb loaded), the overall stepping pattern was not significantly changed, but rather there was an increase in EMG amplitude all left limb muscles. Further, flexor activity emerged in the right TA and MH after training. Following bilateral stand training, the knee extensor muscles had a double-bursting pattern, whereas they were bimodal prior to the stand training. Figure 4. EMG activity (microvolts; uV) from the SOL, medial gastrocnemius (MG), TA, MH, and VL of the left (top) and right (bottom) limbs from a SCI step trained individual. A step-like pattern with higher EMG occurred following training. Figure 5. EMG activity (microvolts; uV) from the SOL, MG, TA, MH, and VL of the left (top) and right (bottom) limbs from a SCI trained to stand unilaterally on the left limb. Higher EMG resulted in the entrained left limb during stepping, however the overall stepping pattern remained minimally changed as compared to a step-trained SCI individual. Figure 6. EMG activity (microvolts; uV) from the SOL, MG, TA, MH, and VL of the left (top) and right (bottom) limbs from a SCI trained to stand bilaterally. EMG amplitude and the overall stepping pattern remained relatively unchanged.   ::Conclusion 1. Stand training results in higher EMG activity in the trained limb during stepping, but does not result in an overall improved locomotor pattern as compared to a step trained individual. 2. Subjects are able to bear more limb load after stand training, producing a higher EMG output. 3. Some subjects were able to stand independently as stand training was effectively translated to the over ground environment.   ::References 1. Barbeau H, Rossignol S. Recovery of locomotion after chronic spinalization in the adult cat. Brain Res, 1987; 412: 84-95. 2. Behrman AL, Harkema SJ. Locomotor training after human spinal cord injury: A series of case studies. Phys Ther, 2000; 80: 688-700. 3. de Leon RD, Hodgson JA, Roy RR, Edgerton VR. Full weight-bearing hindlimb standing following stand training in the adult spinal cat. J Neurophysiol, 1998; 80: 83-91. 4. de Leon RD, Hodgson JA, Roy RR, Edgerton VR. 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Modulation of locomotor patterns and spasticity with clonidine in spinal cord injured patients. Can J Neurol Sci, 1991; 18: 321-332.   ::Acknowledgements Top Row: Amy Budovitch, Janell Beres-Jones, Christie Ferreira, Michelle Adams Middle Row: Bruce Chorney, Patrick Hu, Sonia Newman, Jacquelyn Leong, Luis Alvarado Bottom Row: Jennifer Cobanov, Edward Lan, Jeanine Yip, Mary Tran We would like to thank the research volunteers for their dedication and their valuable contribution to this study. This work was supported by ChristopherReeve Foundation and Roman Reed Spinal Cord Injury Researh Fund of California