V. Reggie Edgerton

Recovery of supraspinal control of stepping via indirect propriospinal relay connections after spinal cord injury

Spinal cord injuries (SCIs) in humans and experimental animals are often associated with varying degrees of spontaneous functional recovery during the first months after injury. Such recovery is widely attributed to axons spared from injury that descend from the brain and bypass incomplete lesions, but its mechanisms are uncertain. To investigate the neural basis of spontaneous recovery, we used kinematic, physiological and anatomical analyses to evaluate mice with various combinations of spatially and temporally separated lateral hemisections with or without the excitotoxic ablation of intrinsic spinal cord neurons. We show that propriospinal relay connections that bypass one or more injury sites are able to mediate spontaneous functional recovery and supraspinal control of stepping, even when there has been essentially total and irreversible interruption of long descending supraspinal pathways in mice. Our findings show that pronounced functional recovery can occur after severe SCI without the maintenance or regeneration of direct projections from the brain past the lesion and can be mediated by the reorganization of descending and propriospinal connections. Targeting interventions toward augmenting the remodeling of relay connections may provide new therapeutic strategies to bypass lesions and restore function after SCI and in other conditions such as stroke and multiple sclerosis.

Extensive spontaneous plasticity of corticospinal projections after primate spinal cord injury.

Although axonal regeneration after CNS injury is limited, partial injury is frequently accompanied by extensive functional recovery. To investigate mechanisms underlying spontaneous recovery after incomplete spinal cord injury, we administered C7 spinal cord hemisections to adult rhesus monkeys and analyzed behavioral, electrophysiological and anatomical adaptations. We found marked spontaneous plasticity of corticospinal projections, with reconstitution of fully 60% of pre-lesion axon density arising from sprouting of spinal cord midline-crossing axons. This extensive anatomical recovery was associated with improvement in coordinated muscle recruitment, hand function and locomotion. These findings identify what may be the most extensive natural recovery of mammalian axonal projections after nervous system injury observed to date, highlighting an important role for primate models in translational disease research.

Using robotics to teach the spinal cord to walk.

We have developed a robotic device (e.g. the rat stepper) that can be used to impose programmed forces on the hindlimbs of rats during stepping. In the present paper we describe initial experiments using this robotic device to determine the feasibility of robotically assisted locomotor training in complete spinally transected adult rats. The present results show that using the robots to increase the amount of load during stance by applying a downward force on the ankle improved lift during swing. The trajectory pattern during swing was also improved when the robot arms were programmed to move the ankle in a path that approximated the normal swing trajectory. These results suggest that critical elements for successful training of hindlimb stepping in spinal cord injured rats can be implemented rigorously and evaluated using the rat stepper.

Coexistent Hoffmann reflexes in human leg muscles are commonly due to volume conduction

The existence of concomitant (coexistent) electromyographic reflex responses in soleus and tibialis anterior muscles, produced by posterior tibial nerve stimulation, has been cited as evidence for reciprocal excitation between these antagonistic muscles normally reflexly linked by reciprocal inhibition. Using the Hoffmann reflex procedure and posterior tibial nerve stimulation, the existence of true reciprocal excitation was tested in six subjects with no neuromuscular impairment. Coexistent EMG responses were observed in all subjects. In no instance, however, could the tibialis anterior EMG volley to posterior tibial nerve stimulation of the soleus muscle be antidromically blocked by common peroneal nerve stimulation applied at 10 to 20 ms offset latencies. A second stimulation pulse applied to the common peroneal nerve at similar offset latencies did antidromically block a tibialis anterior reflex response to common peroneal nerve stimulation. Therefore, volume conduction of reflex activity from the posterior tibial compartment to the anterior tibial compartment was a common observance. We suggest that coexistent EMG reflex responses, presumed to reflect reciprocal excitation, should be tested by the procedure described to reject the possibility of EMG cross-talk as a confounding variable or as the actual variable under investigation.

Physiology of Motor Deficits and the Potential of Motor Recovery After a Spinal Cord Injury

The focus of this chapter is to highlight some fundamental concepts on the physiology of movement control after a spinal cord injury (SCI). We will discuss how these concepts are defined by the order of motor unit recruitment within a motor pool and how the relative recruitment across multiple motor pools defines the movements performed. We then will describe how these factors are affected by SCI. Understanding how these particular “neural decisions” might be modified by SCI will provide greater insight in assessing the etiology of the movement dysfunctions and thus in finding potential resolutions in a given individual at a given time post-injury (Fig. 2.1).