application of transcutaneous auricular vagus nerve stimulation to measure its effect on eeg metrics and heart rate variability

Measurement of Neuromodulation by Transcutaneous Auricular Vagus Nerve  Stimulation

Transauricular vagus nerve stimulation (taVNS) is a recent neuromodulation technique that does not require surgery and utilizes a non-invasive stimulation device placed at the concha or tragus of the ear. Consequently, it is more accessible and safer for patients1. In recent years, the taVNS field has rapidly expanded, primarily focusing on clinical trials demonstrating potential therapeutic advantages for various pathological conditions, including epilepsy, depression, tinnitus, Parkinson's disease, impaired glucose tolerance, schizophrenia, and atrial fibrillation2. There is much to discuss about taVNS and its effects on biological processes in the central and peripheral systems. Ideally, a biological marker might demonstrate that the auricular branch of the vagus was stimulated, affecting intracranial structures and allowing researchers to analyze how taVNS affects physiological function. Nevertheless, without a trustworthy biomarker, it is not easy to understand what the taVNS data mean and how to interpret them effectively.
Electroencephalography (EEG) is an encouraging imaging tool to provide biomarkers for taVNS. It is a non-invasive, reliable, inexpensive approach to measure and quantify cortical activity3,4. Following this process, our group performed a systematic review, demonstrating elementary details that taVNS could influence cortical activity, mainly increasing EEG power spectrum activity in lower frequencies (delta and theta). However, diverse results in higher frequencies (alpha) and changes in early ERP components related to inhibitory tasks were also detected. High heterogeneity between the studies was found; therefore, more homogeneous, more significant, and well-planned studies are essential to make more robust conclusions about the effects of taVNS on brain activity measured by EEG3. Assessing EEG during taVNS could advance future research on integrating the two techniques for a mobile, closed-loop, monitoring, and non-invasive stimulation tool to affect brain oscillatory activity4.
Alpha asymmetry, which assesses the relative alpha band activity between the brain hemispheres, particularly at frontal electrodes, is a frequently researched EEG biomarker. Previous literature has used this biomarker to analyze the approach-withdraw hypothesis5,6, which holds that the right frontal side of the brain is associated with withdrawal behaviors. In contrast, the left frontal side is associated with approach behaviors. Since alpha is associated with low brain activity, an increase in alpha on the left side of the brain suggests lower activity and may show a lack of approach behavior. This concept helps to explain some results in the alpha band at the left side hemisphere in depressed patients7. Additionally, EEG electrodes record the activity of neuronal populations, examining Functional Connectivity (FC) or changes in large-scale brain networks, such as the default mode network (DMN)7,8.
Based on that, quantitative electroencephalography can be employed to assess the effects of taVNS on brain activity; however, more studies are required to systematically demonstrate the specific metrics and effects that would highlight the non-invasive stimulation through the auricular branch of the vagus nerve.
Peripherally, the vagus nerve and sympathetic nervous system mediate the heart's contractile and electrical function9. This regulation promotes the heart's pacemaker ability and controls it through physiological manifestations of the body, known as sinus depolarizations. Heart rate variability (HRV) records the changes per beat of sinus depolarization, thus non-invasively describing vagal influences on the sinus node10. Given this function, HRV has been seen and studied as a prominent neurocardiac function biomarker associated with an individual's well-being and the likelihood of morbidity, mortality, and stress11,12.
In the context of taVNS, HRV has been recorded in many trials, and stimulation has been thought to modulate HRV9,11,12. Considering that decreased HRV has been related to the morbidity and mortality of different diseases through mechanisms such as over-activity of the sympathetic nervous system, inflammatory response, and oxidative stress, the vagal nerve modulation of taVNS is thought to directly impact HRV and its sinus regulation13,14. In fact, some trials have already indicated that taVNS can increase HRV in healthy subjects, thus supporting this hypothesis15,16. However, there is still a need to understand better whether different taVNS parameters can affect HRV differently.
Currently, no mechanistic studies have investigated the taVNS neural network and autonomic nervous system effects of this technique together. Therefore, this protocol aims to assess how taVNS can affect EEG metrics and HRV and evaluate its safety. Additionally, this also aims to identify predictors that can influence the response to taVNS. Understanding the variables associated with the response to taVNS can help design future clinical trials to maximize the effects of this intervention.

Author Spotlight: Exploring the Effects of Transauricular Vagus Nerve Stimulation

Understanding the Effects of Non&#45;Invasive Transauricular Vagus Nerve Stimulation on EEG and HRV

Transauricular Vagus Nerve Stimulation, taVNS for short, is a safe, noninvasive 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 afferent 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 taVNS on psychological processes, therefore establishing a baseline understanding of how taVNS influences neurophysiological mechanisms, fostering confidence in the techniques 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.

Application of Transcutaneous Auricular Vagus Nerve Stimulation to Measure its Effect on EEG Metrics and Heart Rate Variability

Research

JoVE Journal

Neuroscience

Several studies have demonstrated promising results of transcutaneous auricular vagus nerve stimulation (taVNS) in treating various disorders; however, no ...