DBS Orientation Selective Pathway Activation for Gait Ignition Following SCI
Abstract
Neuromodulation approaches are presently some of the most promising strategies for the treatment of spinal cord injury (SCI). By stimulating the nervous system, they can improve the function of the spinal cord after injury. As a potential neuromodulation strategy for improving walking in persons with partial SCI, deep brain stimulation (DBS) may be used to activate brain cells controlling spinal neurons involved in producing walking. DBS is an effective, relatively safe, reversible, and adjustable treatment for difficult-to-treat movement disorders. DBS has not been used to treat persons with SCI, even though a significant percentage of new and chronic injuries are motor incomplete (making up approximately 67% of all new injuries [National SCI Statistical Center, 2020]) and connections between the spinal cord and brain still persist. In our previously funded Department of Defense study, we explored the use of DBS to promote walking in a large animal model (the Yucatan micropig) of SCI. Our target was an area of the brain known as the mesencephalic locomotor region (MLR) that is responsible for controlling walking. We found that stimulating this area can initiate stepping early after injury when stepping was not possible before and later, improves walking by increasing muscle activation and stepping frequency, regularity, and coordination. Although we have found stimulation sites that can bring about walking, off-target stimulation can reduce the effectiveness of stimulation and produce unwanted side effects precluding the usefulness of the stimulation. Our most recent findings, however, indicate that the effectiveness of stimulation of even off-target sites can be optimized by slightly adjusting the way we stimulate this complex region of the brain. By adjusting the stimulation parameters, we can initiate well-coordinated walking while minimizing side effects, even from sites that were ineffective by themselves. These results suggest that complex programming can maximize the effectiveness of MLR DBS and further enhance the quality of stepping after SCI where damage to the connections between the brain and spinal cord is severe. The purpose of this study is to develop a “stimulation model” of this part of the brain, which will aid in target selection and activation and minimize any side effects produced by off-target placements. Recent advances in brain imaging and computer modeling of the effects of DBS will be used for this purpose. We propose to develop this model in a translational large animal model of SCI and use specialized imaging of the brain to help guide the stimulation programming required to maximize the activation of these neurons and minimize side effects produced by off-target placements. Understanding the general principles of stimulation programming within this area of the brain will help to decide the most effective stimulation sites and parameters for optimized motor control in persons with incomplete SCI. Paralysis is common in military personnel, and Veterans with incomplete SCI who could potentially benefit from this approach. Many people with SCI recover some motor function and can walk under specialized conditions such as with body weight support. However, their walking ability is limited in the community and thus, they continue to use wheelchairs, placing them at continued risk for associated secondary complications such as shoulder injuries, pressure ulcers, and loss of bone density. We hypothesize that persons with incomplete injuries (ASIA C or D), who cannot effectively walk overground would experience improved gait with this method. Activation of MLR may also reveal that clinically silent motor pathways are present and can be activated to achieve stepping. We expect this work to quickly lead to a phase 1 clinical study and further preclinical studies that involve DBS and locomotor training or a combination of several other neuromodulatory approaches, such as supplementary transmitter replacement o
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110791
Entities
People
- Brian Noga
Organizations
- United States Army
- University of Miami