Understanding the Effects of Non-Invasive Transauricular Vagus Nerve Stimulation on EEG and HRV
January 19th, 2024
This protocol provides information on how to apply transcutaneous auricular vagus nerve stimulation (taVNS) in a clinical trial, including potential biomarkers such as EEG metrics and heart rate variability (HRV) to measure the effect of this treatment on the autonomic nervous system.
Transauricular Vagus Nerve Stimulation, taVNS for short, is a safe non-invasive stimulation technique that targets the auricular branch of the vagus nerve. Placing the electrodes at the concha of the ear, as an alternative to invasive stimulation, taVNS can affect several brain functions by stimulating the vagal afrins fibers. Several studies have demonstrated promising results of taVNS.
However, there is a lack of mechanistic studies to investigate its effect on neural network and autonomic nervous system. So in this clinical trial, we are assessing taVNS in health subjects, looking for potential biomarkers such as EEG metrics and heart rate variability. With this protocol, we are proposing a bilateral stimulation that does not significantly increase the likelihood of cardiovascular events, but enhances the effect of vagus stimulation.
taVNS holds significant promise for addressing mood disorders and chronic pain conditions among others. This study will provide insights into the safety, feasibility and general effects of the taVNS on psychological processes. Therefore, establishing a baseline understanding of how taVNS influences neuro-physiological mechanisms, fostering confidence in the technique's potential therapeutic value.
Understanding the variables associated with response to taVNS can help design future clinical trials to maximize the effects of this intervention. Based on that, our studies will be focused on how taVNS can be optimized to target specific neural pathways and treat different conditions. To begin, open an envelope containing the concealed randomization and prepare the correct active or sham device.
Hand the device over to the blinded investigator. Use the electronic format capture system or REDCap, to collect the data for this study with the subject. To start the QST Assessment, apply a Peltier Thermode to the right forearm of the subject to deliver short heat stimuli.
Instruct the subject to rate the pain intensity from zero to 100. Next, apply the test stimulus for 30 seconds at the test temperature. Ask the subject to rate the pain intensity at 10 second intervals from 10 to 30 seconds, after the thermode reaches the pain 60 temperature.
Five minutes after delivering the test stimulus, immerse the left hand of the subject in a water bath set between 10 to 12 degrees Celsius for 30 seconds. Then apply the same pain 60 temperature on the subject's right forearm, before asking him to rate the pain intensity. Now, ask the subjects to place a Heart Rate Variability or HRV monitor on their person.
Submerge the EEG cap in one liter of water with 11 grams of potassium chloride and five milliliters of baby shampoo for 10 to 15 minutes. Next, position the subject comfortably on the chair. Then cover the subject's shoulders with large towels.
To locate the vertex, place a mark at the halfway distance between nasion and inion. Mark the halfway distance between both preauricular points. Then mark the intersection of both marks.
Place the EEG cap carefully on the subject's head. Connect the EEG to a computer system and start the resting assessments. Simultaneously, assess the baseline HRV for five minutes on a tablet connected to the monitor via Bluetooth, before assessing the EEG.
Next, to perform the task related to the EEG assessment, clean the skin of the subject's ear with a 70%alcohol pad. Apply saline to the ear tips, then place the electrodes on the ear and check the current quality. Start the stimulation using the TAVNS.
After 60 minutes of stimulation, measure the subject for EEG, HRV, and pain. Then perform conditioned pain modulation as before. A topographic distribution of scalp plots was created in resting state EEG for Theta, Alpha, and Beta bands, in the Baseline, During and Post procedure.
An Asymmetric Alpha Pattern was noticed in the frontal region.
Overview
This study examines the application of transcutaneous auricular vagus nerve stimulation (taVNS) as a non-invasive method to engage the vagus nerve through the ear. It investigates the effect of taVNS on the autonomic nervous system using potential biomarkers like EEG metrics and heart rate variability (HRV) to provide insights into its therapeutic potential for mood disorders and chronic pain conditions.
Key Study Components
Area of Science
- Neuroscience
- Clinical Trials
- Autonomic Nervous System
Background
- taVNS targets the auricular branch of the vagus nerve.
- It is being explored as a safe, non-invasive alternative to traditional stimulation methods.
- Previous studies show promising results, yet mechanistic investigations are lacking.
- The study focuses on healthy subjects to establish baseline influences on neuro-physiological mechanisms.
Purpose of Study
- To assess the effects of taVNS on psychological processes.
- To evaluate potential biomarkers such as EEG and HRV.
- To optimize the application of taVNS for targeted therapeutic interventions.
Methods Used
- The study features a clinical trial setup with real-time data collection.
- Participants underwent various assessments including pain intensity ratings and HRV monitoring.
- The protocol includes precise application methods for EEG and taVNS stimulation.
- Randomization and control measures were carefully implemented to ensure validity.
- Post-stimulation measurements included EEG and HRV to analyze responses.
Main Results
- Initial findings suggest that taVNS is safe and did not significantly increase cardiovascular risks.
- EEG measurements indicated changes in brain activity during and after stimulation.
- HRV data may reveal the modulatory effects of taVNS on the autonomic nervous system.
- The study provides a framework for future mechanistic research and possible clinical applications.
Conclusions
- taVNS shows promise as a therapeutic intervention for various conditions, warranting further investigation.
- The study underscores the need for understanding individual variability in response to taVNS.
- Implications for future clinical trials have been identified to maximize therapeutic effects.
Frequently Asked Questions
Executive Industry Relevance
Transauricular vagus nerve stimulation (taVNS) offers a non-invasive modality to interrogate neural and autonomic pathways, supporting early-stage mechanistic de-risking in neurotherapeutic discovery. Quantitative EEG and HRV outputs provide objective biomarkers for target engagement and physiological modulation, informing translational continuity from preclinical models to human studies. This approach enables portfolio teams to assess intervention feasibility and optimize trial design for future therapeutic indications.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Enables interrogation of vagal pathway modulation through quantifiable EEG and HRV biomarkers.
- Supports mechanistic de-risking by isolating neural and autonomic effects in healthy subjects.
- Facilitates predictive confidence in target engagement for neuromodulation strategies.
Screening & Assay Development
- Establishes validated physiological readouts for downstream screening of neuromodulatory interventions.
- Standardizes EEG and HRV measurement protocols for reproducibility across studies.
- Provides quantitative endpoints to benchmark intervention effects in controlled settings.
Translational & Preclinical Research
- Aligns physiological biomarkers with translational endpoints relevant to mood and pain pathways.
- Enables continuity from mechanistic discovery to preclinical and early clinical validation.
- Supports risk-adjusted advancement decisions based on objective neurophysiological data.
Pipeline & Workflow Integration
taVNS with EEG and HRV monitoring integrates into the discovery-to-preclinical continuum, bridging mechanistic studies and translational biomarker development.
- Discovery Biology: Provides a platform for hypothesis testing of vagal modulation effects on neural and autonomic systems.
- Screening: Delivers reproducible, quantitative EEG and HRV outputs for intervention benchmarking.
- Analytics: Enables statistical comparison of active versus sham stimulation across multiple physiological domains.
- Translational Research: Aligns mechanistic biomarkers with endpoints relevant to future clinical trials.
- Enterprise Reuse: Establishes a reusable protocol for neuromodulation studies across therapeutic areas.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence and reduces mechanistic ambiguity in neuromodulation research.
- Operational Value: Standardizes physiological data collection and enhances reproducibility.
- Strategic Value: Informs go/no-go decisions and optimizes resource allocation for early-stage programs.
- Portfolio Impact: Supports risk-adjusted prioritization of neuromodulatory assets based on objective biomarker data.
Implementation Considerations
- Requires expertise in EEG and HRV acquisition and analysis.
- Demands access to validated instrumentation and data capture infrastructure.
- Necessitates protocol standardization for cross-study comparability.
- Adaptation may be needed for different subject populations or disease models.
- Interpretation of biomarker changes must consider baseline variability and sham controls.
