Pairing tVNS with motor skill training in older adults

Summary Motor function is often compromised by neurological injury, such as stroke and even healthy aging. Decline in motor skills reduces the quality of life and independence in aging adults. In animal studies, applying brief vagus nerve stimulation (VNS) during motor training dramatically improved motor recovery and learning (180-260%), including strength and motor skills in stroke, spinal cord injury, and nondisabled rodents, young and old. Because VNS upregulates central neurotransmitters linked with motor learning (e.g., norepinephrine, acetylcholine), which decrease with age, this intervention is a hopeful candidate to help improve motor function in aging humans. This project will explore the crucial unresolved issues in translating the animal-based VNS intervention to human applications. One is the need to apply stimulation only after a successful trial to induce positive efficacy (post- success VNS), according to systematic studies in animal research. The second issue is the invasive procedure of implanting a VNS electrode and device in the neck and chest of humans, which would not be readily acceptable for study or rehabilitation purposes. The efficacy of adopting a noninvasive alternative, transcutaneous VNS (tVNS) via surface electrodes on the tragus of the outer ear, will need to be explored. To explore these critical issues, we have published a paper confirming that applying tVNS during training alters motor adaptation in young adults and have developed a closed-loop, automated, post-success tVNS system in which an individual’s motor performance is assessed in real time, and tVNS is automatically applied after a successful trial based on predetermined criteria. In this project, our primary aim is to examine the effect of post- success tVNS during motor training on motor learning in healthy older adults. We will also explore whether the amount of expected motor learning facilitation is associated with acute neuromodulation responsiveness to tVNS at rest. We will randomly assign healthy older adults to the tVNS or control group. Participants will undergo motor skill training sessions with post-success tVNS or sham stimulation, respectively. We will compare the time course of improvements and transfer of motor skills between the groups. We will also investigate the correlation between the improvements and a biomarker of acute neuromodulation response to tVNS (i.e., pupil size). This study will furnish vital information on the efficacy of post-success tVNS in enhancing motor learning for healthy older adults, and it has the potential applicability to other tasks, including whole-body control and strength, making it clinically significant. Future clinical studies can determine if this intervention is beneficial in treating individuals with movement disorders that suffer from spasticity (e.g., stroke, spinal cord injury), dyskinesia (Parkinson’s Disease), tremor (e.g., Essential Tremor), and discoordination (e.g., Spinocerebellar ataxia).