Functional reorganization of spinal neural networks facilitating stepping in humans and rats after spinal cord injury

After a complete spinal cord injury, when supraspinal control of spinal cord neural circuits is impaired and voluntary control of the lower limb movement is lost, spinal motor pools may still be activated by peripheral and segmental input. However, whether the motor activity elicited in post-lesional spinal circuits may be regulated to support walking after complete spinal cord injury in humans is not clearly understood. In this dissertation, I describe a series of studies conducted by myself and others investigating the capability of the post-lesional spinal cord to use stepping-related sensory feedback to coordinate the activation of motor pools and spinal reflexes in a manner conducive to supporting walking.;We first examined the critical role of supraspinal input on the coordination of lower limb locomotor activity patterns during stepping. Leg muscle electromyographic (EMG) activity was evaluated in humans with functionally complete and incomplete spinal cord injury (SCI) as they stepped on a treadmill with body-weight support and manual assistance. Although none of the individuals studied had previously participated in a stepping regimen, coordinated muscle stepping patterns, including alternating activation of antagonistic muscles, could be observed in both clinically complete and incomplete SCI groups. This provided evidence in humans that although coordination of patterns may be altered after SCI, the ability for spinal networks to produce appropriate activity patterns in response to stepping-specific sensory feedback is not strictly related to the level of voluntary motor ability after SCI.;Next, the capability of the spinal cord to modulate the gain of spinal reflexes in the absence of supraspinal control was investigated. The amplitudes of monosynaptic reflexes evoked by percutaneous spinal cord electrical stimulation were assessed in multiple leg muscles as a function of the step cycle in clinically complete SCI and non-injured individuals. Evoked responses in both groups displayed step-phase dependent modulation. However, the patterns of modulation in the SCI group were inconsistent across subjects and different from those evoked in non-injured subjects. These findings demonstrate that transmission in monosynaptic reflex circuits can be regulated in the absence of clinically detectable supraspinal control. Inconsistency in the appearance and pattern of modulation of these monosynaptic reflexes suggest deficits in any of several areas where the amplitude of the monosynaptic reflex are influenced, such as, in the processing of sensory information, the regulation of synaptic transmission in the monosynaptic circuit, and the activation of spinal motoneurons.;In the final component of this dissertation, methods were explored to increase the likelihood for appropriate patterns of stepping EMG and reflex modulation to be consistently generated and maintained by modifying the physiological state of the spinal cord in spinal animal models. These studies were conducted in adult spinalized rats in which techniques that had been effective in facilitating stepping behavior were tested for their effect on the modulation of monosynaptic reflexes. These techniques include, step training, pharmacological administration of a serotonin receptor agonist, and application of continuous high-frequency epidural stimulation to the lumbar spinal cord. Step-phase dependent modulation of evoked monosynaptic responses was observed in spinal rats that had been trained to step on a treadmill and the application of high frequency stimulation resulted in improved modulation in the step cycle. These findings provide evidence of a phase-dependent regulation of transmission in the monosynaptic reflex circuit that can be achieved in the anatomically complete absence of supraspinal control through step training and transiently enhanced by external stimulation.