taVNS for Upper Limb Rehabilitation

Optimization of Closed-loop Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) as a Neurorehabilitation Tool

This study explores the use of a new form of neuromodulation known as transcutaneous auricular vagus nerve stimulation (taVNS) which stimulates the ear. This stimulation will be delivered concurrently with upper limb motor rehabilitation training (3 days/week for 4 weeks) in chronic stroke patients. Patients will undergo a series of baseline assessments (including a brain scan), a 4-week course of motor rehabilitation, and post-assessments (including a second brain scan)

This study aims to refine and develop closed loop taVNS, establish activity with key biomarkers, and show initial feasibility in a small clinical trial. For paired taVNS to succeed as a clinical treatment, it is critical to develop and refine a closed-loop taVNS platform that delivers stimulation concurrently during specific movements of the motor rehabilitation training.

Aim 1 develops this novel motion-gated closed-loop system that delivers taVNS in synchrony with specific upper limb motor activation (n=5) Aim 2 will combine the development of the closed-loop system with the investigator's mechanistic understanding to explore an open-label pilot trial (n=20) using closed-loop taVNS paired with task-specific training to determine the feasibility, safety, and potential effect size of this novel combination therapy.

Inclusion Criteria:

• 18-80 years old
• Ischemic or hemorrhagic stroke that occurred at least 6 months prior
• Completed conventional rehabilitation therapy at least one month prior
• Unilateral limb weakness with Fugl Meyer-Upper Extremity Scale score less than or equal to 58 (out of 66)

Exclusion Criteria:

• Primary intracerebral hematoma, or subarachnoid hemorrhage
• Bilateral upper extremity weakness
• Other concomitant neurological disorders affecting upper extremity motor function
• Documented history of dementia before or after stroke
• Documented history of uncontrolled depression or psychiatric disorder either before or after stroke which could affect their ability to participate in the experiment
• Uncontrolled hypertension despite treatment, specifically SBP (Systolic Blood Pressure) / DBP (Diastolic Blood Pressure) >=180/100mmHg at baseline
• Contraindicated for MRI scanning.