Extensor muscles of the hind limbs are actively involved in weight support and walking activities. These muscles are extensively linked by inhibitory, force dependent pathways which 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. Weightings of these linkages vary across control, decerebrate animals when quiescent, but obey a proximal to distal gradient during stepping on a treadmill. This finding indicates the strength and distribution of these reflex pathways are subject to modulation in a task-dependent manner. Our preliminary data in animals suggest that spinal cord hemisection 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 mediated by receptors other than Golgi tendon organs and that results from bilateral injury to the dorsal half of the spinal cord. Changes 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 problems seen in humans with spinal cord injuries (SCIs). These findings provide new insight into potential mechanisms contributing to disruption of motor function following injury. Our guiding hypothesis is: SCI- induced force-feedback dysregulation results in strong inhibition directed toward proximal muscles and contributes to inadequate limb stiffness during weight support phases of movement. The current application has evolved from collaborative work across two established laboratories, bringing together expertise in SCI, plasticity, force feedback and motor control. The proposed studies are designed to understand and map changes in force feedback control following SCI, characterize associated changes in gait subphases where inhibitory force feedback is thought to be most active across diverse locomotor tasks, and determine which white matter tracts may modulate spinal circuitry responsible for force feedback. Data generated in the proposed projects will be compared with an existing laboratory database containing force feedback findings from control decerebrate preparations. Overall, findings from these studies will explicate the impact of disrupting this intralimb control system on performance, provide critical mechanistic insight likely to be essential for design of the most effective rehabilitation programs for those with SCIs and other neurological disorders, and lay groundwork for development of a new method for testing force feedback in humans

Public Health Relevance

Coordination of muscles in each leg and appropriate limb stiffness are critical for weight support and walking. Even though it is not directly damaged, the basic system responsible, which lies partially in the muscle, becomes dysfunctional following spinal cord injury. This study will assess this change and why it occurs, with the long term goal of enhancing recovery for those with spinal cord injuries.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS097781-04
Application #
9894867
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Bambrick, Linda Louise
Project Start
2017-04-01
Project End
2022-03-31
Budget Start
2020-04-01
Budget End
2021-03-31
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Louisville
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
057588857
City
Louisville
State
KY
Country
United States
Zip Code
40292