Microelectrode Recordings From the Vagus Nerve in Awake Humans

Study Overview
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Brief Summary
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This Anchillary project uses a refined technique of ultrasound-guided microneurography of the human cervical vagus nerve, an approach developed by Professor Vaughan Macefield and used safely to-date in 44 prior study participants. The overall goal of this project is to build upon prior data obtained using this approach by undertaking a detailed neurophysiological investigation of the human vagus nerve and to identify the nerve fibers activated during vagal nerve stimulation (VNS) in participants with implanted VNS devices in response to different stimulation parameters. In addition to providing data in unprecedented detail into the physiology of the human vagus nerve, this project will investigate different stimulus intensities, durations and frequencies that differentially excite myelinated and unmyelinated nerve fibers. These results will inform the CSP and guide future development of novel neural interfaces for VNS for various clinical applications.

Official Title
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Microelectrode Recordings From the Vagus Nerve in Awake Humans

Conditions
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Epilepsy

Intervention / Treatment
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* Other: VNS stimulation and intraneural recordings
* Other: Record multi-unit activity from intraneural sites


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant is greater than or equal to (≥)18 years and is less than or equal to (≤) 40 years of age English speaking Medicare covered or equivalent health insurance from a partner country Exclusion Criteria: Pregnant Smokes and is unwilling to abstain from smoking on the day of the experiment. Inability or unwillingness to provide written informed consent. Individuals with difficulty standing unassisted for 5 minutes during the tilt-table testing Individuals found to have a significant carotid artery plaque or intima-media thickness > 1 mm as assessed by ultrasonography during the ultrasound-screening steps of the study visit Vagus nerve not visible on ultrasound VNS electrodes are not in a suitable location to allow for microelectrode insertion Any other clinical reasons deemed by the investigators

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VNS<br>participants with surgically implanted VNS electrodes to treat drug-resistant epilepsy | Other: VNS stimulation and intraneural recordings<br>* A minimum of three stimulation frequencies (1, 10 and 30 Hz), each up to 60s in duration, will be delivered via the VNS device. Intraneural recordings proximal or distal to the VNS electrodes during delivery of VNS will be performed. Approximately two to five fascicles will be explored in each nerve.<br>|
| Experimental: non-VNS participants<br>participants without implanted VNS devices | Other: Record multi-unit activity from intraneural sites<br>* Perform a more detailed vagal nerve mapping study by recording from single nerve fibers, including those fibers supplying the heart, lungs, airways and other end-organs. The investigators shall perform functional mapping of the left and right vagus nerves, such as those with cardiac-related and/or respiratory-related neural activity. The research team will also record activity from other nearby fibers to map the differences in neurological behavior in fascicles that control the heart, lungs, airways and other systems.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| identify action potential morphology of specific fibers activated by vagal nerve stimulation (VNS) | assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module | 4 hours | 
| identify ratio of myelinated fibers in specific fibers activated by vagal nerve stimulation (VNS) | assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module. Whether a nerve fiber is (un)myelinated can be determined by visual inspection. Myelinated fibers typically produce a positive-going narrow spike profile. | 4 hours | 
| physiological identification of the specific fibers activated by vagal nerve stimulation (VNS) | assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module. use of tracing and nerve recordings analysis to identify the types of nerves | 4 hours | 
| identify firing rates of the specific fibers activated by vagal nerve stimulation (VNS) | assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module. in Hertz | 4 hours | 
| identify stimulus current required to activate specific fibers activated by vagal nerve stimulation (VNS) | assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module. in milli-amps | 4 hours | 
| differences in firing rates of cardiac parasympathetic vagal activity | compare any changes in parasympathetic vagal activity with participants who have not been implanted with a vagal nerve stimulator (Non-VNS Participants). Labchart; spike histogram module. Unit: Hz. | 4 hours | 
| Discharge variability of cardiac parasympathetic nerve fibers | Vagal nerve stimulator device. Coefficient of variation, % | 4 hours |