Transcutaneous Vagus Nerve Stimulation (tVNS) and Robotic Training to Improve Arm Function After Stroke

Promising new animal research suggests that vagus nerve stimulation paired with motor
intervention induces movement-specific plasticity in the motor cortex and improves limb
function after stroke. These results were recently extended to the first clinical trial, in
which patients with stroke demonstrated significant improvements in upper limb function
following rehabilitation paired with implanted VNS. Currently, vagus nerve stimulation is
being used clinically to treat a number of human diseases including migraine headaches,
epilepsy, and depression, and these investigations are expanding to deliver stimulation via a
transcutaneous route to potentially improve intervention efficacy and decrease side effects.
This pilot study will combine non-invasive transcutaneous stimulation of the vagus nerve with
upper limb robotic therapy to investigate the potential of tVNS to augment improvements
gained with robotic therapy in patients with chronic hemiparesis after stroke.

Inclusion Criteria:

- Individuals between 18 and 85 years of age

- First single focal unilateral supratentorial ischemic stroke with diagnosis verified
by brain imaging (MRI or CT scans) that occurred at least 6 months prior

- Cognitive function sufficient to understand the experiments and follow instructions
(per interview with Speech Pathologist or PI)

- Fugl-Meyer assessment 12 to 44 out of 66 (neither hemiplegic nor fully recovered motor
function in the muscles of the shoulder, elbow, and wrist).

Exclusion Criteria:

- Hemorrhagic stroke

- Botox treatment within 3 months of enrollment

- Fixed contraction deformity in the affected limb

- Complete and total flaccid paralysis of all shoulder and elbow motor performance

- Prior injury to the vagus nerve

- Severe dysphagia

- Introduction of any new rehabilitation interventions during study

- Individuals with scar tissue, broken skin, or irremovable metal piercings that may
interfere with the stimulation or the stimulation device

- Highly conductive metal in any part of the body, including metal injury to the eye;
this will be reviewed on a case by case basis for PI to make a determination

- Pregnant or plan on becoming pregnant or breastfeeding during the study period

- Specific medications that may interfere with acetylcholine and norepinephrine release
including muscarinic antagonists, benzodiazepines, selective serotonin reuptake
inhibitors, nicotinic antagonists, tricyclic antidepressants, anti-psychotic
medications, anti-epileptic medications, and γ-amino butyric acid agonists (enrollment
to be determined by PI review)

- Significant arrhythmias, including but not limited to, atrial fibrillation, atrial
flutter, sick sinus syndrome, and A-V blocks (enrollment to be determined by PI
review)

- Presence of an electrically, magnetically or mechanically activated implant (including
cardiac pacemaker), an intracerebral vascular clip, or any other electrically
sensitive support system; Loop recorders will be reviewed on a case by case basis by
PI and the treating Cardiologist to make a determination