Extensor muscles of the leg are actively involved in weight support and walking activities. These muscles are extensively linked by inhibitory, bidirectional, force dependent pathways that contribute to the successful execution of a range of functional behaviors, including locomotion. These reflex pathways are thought to arise from Golgi tendon organs and are believed to regulate limb stiffness and promote inter-joint coordination during movements. The relative magnitudes of these linkages in the two directions between any two muscles vary across control decerebrate animals when quiescent, but obey a predominantly proximal to distal gradient during stepping on a treadmill. This finding indicates that the strength and distribution of these reflex pathways are subject to modulation in a task-dependent manner. Our preliminary data suggest that thoracic spinal cord lateral hemisection immediately and persistently alters the normal distribution and a dominant distal-to- proximal inhibitory gradient emerges. Animals with this lesion do not exhibit clasp-knife inhibition, a phenomenon known to be mediated by receptors other than Golgi tendon organs and that results from bilateral injury to the dorsal half of the spinal cord. The change in the strength and distribution of force feedback that we have observed is correlated with diminished limb stiffness and poor weight acceptance during locomotor tasks ? both of which are challenging problems seen in humans with spinal cord injuries. These findings provide new insight into potential mechanisms contributing to disruption of motor function following injury and identify a new, potential rehabilitation strategy. Our guiding hypothesis is that SCI-induced force-feedback dysregulation results in strong inhibition directed toward proximal muscles, contributes to inadequate limb stiffness during weight support phases of movement, and can be reversed using eccentric- focused training. The current application has evolved from collaborative work, using a large animal model, across two established laboratories, bringing together expertise in spinal cord injury, plasticity, force feedback and motor control. The proposed studies are divided into two sets of experiments. The first set will carefully characterize the impact of a low thoracic hemisection on gait kinematics during subphases where inhibitory force feedback is thought to be most active (Aim 1a). These phases typically are associated with coordinated eccentric activity and/or weight acceptance/support. Pre- and post-SCI data, across time, will be compared. In the same animals, a comprehensive picture of force-feedback organization following SCI will be developed during terminal decerebrate studies at two chronic time points (Aim 1b). Both standing and walking preparations, in combination with mechanographic approaches, will be used to test task-specificity of heterogenic force feedback responses in specific muscle combinations. In the second set of experiments, the basic experimental design is the same except that eccentric-focused training will be introduced at 2 wks post- SCI. This allows animals used in Aims 1a and 1b to serve as the controls for Aims 2a and 2b. Eccentric training will use different ?downslope? gait tasks to more strongly activate force feedback circuitry. Gait kinematics will be carefully assessed during select subphases to test for training effects during different flat and downslope tasks (Aim 2a) and decerebrate, mechanographic studies used to characterize training effects on force dependent organization at the level of specific muscle combinations. Histology will be completed in all animals to verify lesion characteristics. Data generated in the proposed work will be compared with an existing laboratory database containing force feedback findings from control decerebrate preparations, to reduce the number of animals used. Collectively, these studies will provide important information for evidence-based rehabilitation of motor skills by understanding the gait-associated impact of disrupting force feedback (Aim 1a), the extent of the disruption of this intralimb control system following SCI (Aim 1b), and the potential to alter this disruption at the voluntary gait (Aim 2a) and basic reflex levels (2b) using a physical training approach.
The mission of the Spinal Cord Injury & Disorders System of Care is to support, promote, and maintain the health, independence, quality of life, and productivity of veterans with SCI throughout their lives. The current research proposal addresses these needs through basic animal studies which assess the effects of SCI and a novel rehabilitation strategy. Coordination of muscles in each leg and appropriate limb stiffness are critical for weight support and walking. Even though not directly damaged, the basic system responsible, lying partially in the muscle, becomes dysfunctional post-SCI. This study will increase understanding of, and test a new rehabilitation strategy designed to reverse, these changes and improve weight support and walking. The long term goal is enhanced recovery for those with SCIs. Knowledge gained also may be relevant for other neurological disorders with loss of connections and walking difficulty.
