PhD Thesis Defense

Activity of Bifunctional Motoneurons during Fictive Locomotion: A Computational Modeling Study
Author: Khaldoun Hamade
Supervisor: Ilya Rybak, Ph.D.

Wednesday, August 11, 2010 at 10:00 AM
Bossone Research Enterprise Center, Room 709

More than 90 years ago, Graham Brown demonstrated that the cat spinal cord can generate a locomotor rhythm in the absence of input from higher brain centers and afferent feedback, and proposed a general schematic for the spinal central pattern generator (CPG) generating rhythmic alternating activity of flexor and extensor motoneurons during locomotion, the “half-center” model. Since that time, the half-center concept has been used as the basis in many CPG models. Despite many advantages, classical half-center models of the locomotor CPG have been so far unable to reproduce and explain the generation of more complex activity patterns expressed during locomotion by some bifunctional motoneurons actuating muscles controlling more than one joint, such as posterior biceps and semitendinosus (PBSt) and rectus femoris (RF), which were found to be active within a portion of one phase or generated activity during both phases.

During normal locomotion, the activity patterns of PBSt and RF are modulated by supra-spinal inputs and afferent feedback and vary with gate and locomotor conditions. However, even during fictive locomotion in the absence of afferent feedback and patterned supra-spinal inputs, PBSt and RF demonstrate a variety of complex activity patterns, similar to those observed in real locomotion under different conditions. This suggests that the complex patterns of bifunctionals are defined by the intrinsic spinal CPG organization. The non-trivial activity profiles expressed by bifunctional motoneurons have been considered as a strong argument against a bipartite half-center organization of the spinal locomotor CPG. The challenging task of this study was to find and propose the neural organization of the spinal locomotor CPG that is able to reproduce the full repertoire of PBSt and RF activities observed during fictive locomotion within the framework of the bipartite organization of the locomotor CPG, implement it in a computational model, and validate the model by reproducing the behavior of bifunctional motoneurons during various types of deletions occurring during fictive locomotion.

This study represents a significant step towards understanding the organization of the mammalian spinal locomotor CPG, shaping complex patterns of bifunctional motoneurons, and offers a mechanism for their control by afferent feedback.

PhD Thesis Defense

Identifying the Substrate for Successful Robot Rehabilitation in Adult Rats Spinalized as Neonates: The Role of the Trunk in Locomotor Recovery after Complete Low-Thoracic Transection
Author: Ubong Ime Udoekwere
Supervisor: Simon F. Giszter, Ph.D.

Friday, August 13, 2010
Bossone Research Enterprise Center, Room 709

Approximately 200,000 people live with spinal cord injury (SCI) worldwide, and more than 10,000 new cases are reported each year. Patients with SCI usually suffer devastating neurological deficits and severe loss of function below the level of injury, especially in cases where the cord is completely severed (paraplegia and quadriplegia). After SCI, secondary injury processes extend and worsen the damage, subsequently limiting the spinal cord’s endogenous response to spontaneously repair and regenerate axons. This limits recovery of function. As a result, additional therapeutic interventions are often required to improve recovery. Unfortunately, there are no fully restorative therapies for SCI, but a lot of promising therapeutic techniques are currently being explored in animal models in many research labs across the globe.

One promising animal model for studying SCI recovery is a low thoracic spinal cord transection or spinalization in neonatal rats. This injury completely inhibits functional hindlimb stepping and locomotion (paraplegia). SCI studies using this model have shown that some SCI neonates (~28%) manage to recover significant locomotor function and achieve autonomous hindlimb weight supported (WS) stepping as adults. Furthermore, intracortical microstimulation, cortical lesion, and locomotor kinematic findings from the Giszter lab have identified cortical reorganization of trunk representation and trunk control as being essential elements for the recovery seen in these animals.

The spinalized neonatal model is the only reported successful autonomous recovery model known. Unfortunately, the mechanisms for this recovery have not yet been sufficiently investigated and are presently poorly understood. Consequently, in this thesis we explored the influence of trunk sensorimotor mechanisms on locomotor recovery after SCI in the neonatal rat. We investigated this trunk influence in two ways. First, we investigated trunk-locomotor interactions in adult intact rats by studying the effect of trunk muscle afferents on locomotion. Results from this study indicate that trunk muscle afferents modulate hindlimb extensor output during locomotion, which suggests the possibility of neuronal pathway(s) between trunk afferents and the spinal locomotor generator circuits and hindlimb weight support mechanisms. In the rehabilitative tradition of using sensorimotor training to modify afferent transmissions in hindlimb reflex pathways after SCI, modifying trunk afferent reflexes in a similar context could also contribute to locomotor recovery after SCI. Secondly, we therefore studied the effect of trunk sensorimotor training on locomotor recovery in neonatally spinalized rats. To achieve this, we developed a robotic rehabilitation system that employs impedance training techniques that dynamically interact with the trunk at the level of the pelvis. The results from our trunk rehabilitation therapy suggest that trunk sensorimotor training significantly improves the likelihood and degree of autonomous weight supported locomotor recovery by ~20% in neonatally spinalized rats.

Journal Club Presentation References - Fall 2009

Journal Club Presentation References - 2008-2009