Locomotor rhythm and pattern generating networks of the human lumbar spinal cord: an electrophysiological and computer modeling study

Abstract

The view on the neural control of human locomotion has undergone changes in the past decades. In spite of the encephalization and the erect, bipedal mode of walking characteristic for human beings, independent observations imply that unperturbed locomotor patterns can be generated by similar spinal neural circuits as in other vertebrates. However, little is known about the organization of these rhythm and pattern generating networks in humans. It has been shown that the human lumbar spinal cord isolated from supraspinal control due to traumatic spinal cord injury (SCI) can generate rhythmic, locomotor-like activity in response to sustained epidural spinal cord stimulation (SCS) of certain frequencies. The rhythmic activities consist of a series of stimulus time-related and rhythmically modulated posterior-root muscle (PRM) reflexes, each initiated in posterior root afferents and electromyographically recorded as compound muscle action potentials (CMAPs). The relation between individual stimuli and responses, as well as their electromyographic (EMG) characteristics, allow for the identification of mechanisms in addition to the information gained from the overall EMG patterns. This thesis aims at uncovering the locomotor capabilities and their underlying mechanisms intrinsic to the human lumbar spinal cord. In the first part, rhythmic EMG data in response to SCS were analyzed, both, regarding overall patterns and the constituent units. Based on the information gained, in the second part, computer models were formulated to test hypotheses, to learn about their implications to primary and secondary phenomena and to generate research questions. EMG activities of quadriceps, hamstrings, tibialis anterior and triceps surae, bilaterally in response to epidural stimulation at - 42 Hz were analyzed in 10 individuals with motor complete posttraumatic SCI. Thirty-nine segments (duration: 10 s) of rhythmic activities found in all four-muscle groups of one lower limb were identified in 7 subjects. Phases of bursting and suppressed activities were recognized. Latencies of PRM reflexes were calculated. A computational network model of neurons with Hodgkin-Huxleylike membrane dynamics was developed to test whether hypothesized rhythm and pattern generating networks would reproduce the recorded data. A core rhythm-generating network model was extended by adding conduction delays, presynaptic inhibition and disinhibition of parallel central pathways. Within a given 10-s s…