Control of isometric hindlimb ground reaction forces with acute epidural spinal cord and cauda equina stimulation in the rat

James Michael Goodman Jr.

doi:10.17918/etd-4237

Spinal cord injury (SCI) results in loss of motor function below the site of injury. So far, epidural spinal cord stimulation (ESCS) aimed at restoring motor function have focused heavily on using intact limbs and spinal circuits below the site of SCI to restore rhythmic locomotor activity. This study seeks to develop a stimulus device to control non-rhythmic movements with ESCS in rats and to understand the effects of stimulation on hindlimb movements. This study has four aims. The first is to design a system that can administer ESCS and record isometric ground reaction forces evoked by the rat hindlimb during ESCS. The second is to map tonic hindlimb response types, such as flexion or extension, to ESCS locations in the rat spinal cord that do not overlap with the most common stimulus site for eliciting locomotion. The third is to determine the sensitivity of hindlimb response parameters to stimulus parameters. The fourth is to identify the effects of spinal status (transected or healthy) and spinal cord hydration (mineral oil or physiologic saline) on responses to ESCS. For the first aim, the objectives of the design were to ensure isometric forces were generated by ESCS, to record ground reaction forces under the targeted hindlimb within a particular tolerance, to permit sufficient precision of ESCS electrode position along the length of the cord, and to coordinate stimulation, force measurement, and saving data with a software interface. For the second and third aims, transected and normal rats were anesthetized and electrodes were lowered onto the dural surface of the spinal cord, which was exposed from vertebral L1 to L6. Isometric force measurements in response to ESCS were recorded from the affected hindlimb. Stimulation sites encompassed both the spinal cord and cauda equina to observe both extensor and flexor forces in response to stimulation. The results of this study showed that we were able to record isometric forces from a novel Spinal Cord Stimulator System. In addition, stimulation of the cord underlying vertebral L2 and L3 results in extension-like hindlimb forces, and that stimulation at vertebral L4 and L5 results in flexion-like hindlimb forces. Furthermore, force magnitude was significantly correlated with stimulus current amplitude, and hindlimb response duration was well correlated with stimulus train duration, confirming the hypothesized correlation of ESCS parameters to limb force magnitude and duration. There were no differences in thresholds or correlations among groups, although the ratio of gross flexor or extensor force responses with respect to total stimulus trials was different among groups. The group with the most reliable rate of vertical hindlimb force responses was the transect-saline group, which is the group that corresponds most closely to a SCI condition. This study demonstrates a map of gross extensor and flexor force responses along the spinal cord and cauda equina of the rat, and also demonstrates that the response magnitude and duration are sensitive enough to control from stimulation parameters. The ultimate goal of this research is to identify a stimulus map to permit a means of limb actuation in a brain-machine interface for restoring movements after spinal injury. However, in the immediate future, further research will need to target the applicability of this map in animals chronically implanted with stimulus electrodes.

Control of isometric hindlimb ground reaction forces with acute epidural spinal cord and cauda equina stimulation in the rat

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Control of isometric hindlimb ground reaction forces with acute epidural spinal cord and cauda equina stimulation in the rat

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