Targeting Plasticity for Rehabilitation with Activity-Dependent Electrical Stimulation of the Spinal Cord
Abstract
Rationale: The goal of the project is to evaluate the potential of a new rehabilitation therapy designed to improve the ability of individuals with spinal cord injury (SCI) to control voluntary movement of their limbs. The therapy is based on fundamental principles of the neurobiology of learning and current understanding of effective strategies for rehabilitation. Underlying behavioral learning of new skills are processes in the nervous system that modify the connectivity of nerve cells and shape the flow of information in neural circuits. These processes can be harnessed and guided by pharmacological and physiological interventions, including the delivery of electrical current to the nervous system. Electrical stimulation can be used to control the timing of activity in nerve cells, and, when delivered in conjunction with intrinsic signals from the brain, can change the wiring of neural circuits and strengthen their function. This approach is related to the principles of activity-based physical therapy, which is well-established as a means to improve movement control after SCI and other disorders of the nervous system. In our preliminary studies on spinal cord injured rodents, we synchronized electrical stimulation of the spinal cord with the animals’ conscious intention to move and produced marked improvement in their ability to perform forelimb behaviors. The objectives of the proposed research are to continue development of the intervention and extend its capability for restoring movement control after chronic cervical SCI. We believe the therapy can be readily translated to use in people with spinal injuries. Initial human trials will weigh the benefits conferred by the therapy with the risks of a treatment that requires an invasive surgical procedure and implantation of devices that interface with the nervous system. We believe the therapy can be of benefit to many individuals with SCI and will yield recovery outcomes that are substantially better than what is achieved with current rehabilitation methods. Although the proposed research investigates recovery of voluntary movements, we believe the therapy can be used to reorganize any neural circuit and may therefore be effective when applied to other neural systems that are affected by SCI. Future studies may examine the use of the therapy for alleviating chronic pain and restoring bowel, bladder, or sexual function. The new treatment will ultimately be applicable to rehabilitation of impairments in individuals with a wide range of injuries of the spinal cord at any level. Since it relies on neural circuits that are spared by the injury, it will probably not be effective for the most severe cases. However, we envision electrical stimulation as an important complementary treatment for future replacement and regeneration therapies that are being developed, such as stem cell transplants and cellular reprogramming. Interim Outcomes: Success of the project will lead to a translational study in non-human primates that will test the ability of the therapy to improve arm and hand function after chronic cervical SCI in an animal model with physiology and anatomy much more similar to humans. We hope to progress to a first-stage clinical trial in human subjects in the near future. Likely Contributions: The project will increase our basic understanding of how electrical stimulation can be used to treat damage to the nervous system and will continue the development of a specific, novel therapy to restore movement abilities in people with SCI. Thus, the study will contribute to both fundamental and translational knowledge in the SCI field. We believe the therapy has the potential to be a substantial advance in the treatment of many symptoms of SCI and will significantly improve the quality of life of people living with SCI. In the long term, we believe this form of electrical stimulation will facilitate the effectiveness of stem cell and regeneration ther
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710585
Entities
People
- Steve Perlmutter
Organizations
- United States Army
- University of Washington