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

Измерение нейромодуляции с помощью чрескожной стимуляции ушного блуждающего нерва

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.

В центре внимания автора: Изучение эффектов стимуляции трансаурикулярного блуждающего нерва

Понимание влияния неинвазивной трансаурикулярной стимуляции блуждающего нерва на ЭЭГ и ВСР

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.

Применение чрескожной стимуляции ушного блуждающего нерва для измерения ее влияния на показатели ЭЭГ и вариабельность сердечного ритма

Для начала откройте конверт со скрытой рандомизацией. И подготовьте правильное активное или бутафорское устройство. Передайте устройство ослепленному следователю.Используйте систему захвата в электронном формате, или REDCap, для сбора данных для этого исследования с субъектом. Чтобы начать оценку QST, нанесите термод Пельтье на правое предплечье субъекта, чтобы доставить короткие тепловые стимулы. Попросите испытуемого оценить интенсивность боли от нуля до 100.Далее примените тестовый стимул в течение 30 секунд при температуре теста. Попросите испытуемого оценить интенсивность боли с интервалом в 10 секунд от 10 до 30 секунд после того, как термод достигнет температуры боли 60. Через пять минут после подачи тестового стимула погрузите левую руку испытуемого в водяную баню, установленную при температуре от 10 до 12 градусов Цельсия, на 30 секунд.Затем приложите ту же боль температурой 60 градусов к правому предплечью испытуемого, прежде чем попросить его оценить интенсивность боли. Теперь попросите испытуемых установить на себя монитор вариабельности сердечного ритма, или монитор ВСР. Погрузите колпачок ЭЭГ в один литр воды с 11 граммами хлорида калия и пятью миллилитрами детского шампуня на 10-15 минут.Затем удобно расположите объект на стуле. Затем накройте плечи объекта съемки большими полотенцами. Чтобы определить местоположение вершины, поставьте отметку на полпути между насионом и инионом.Отметьте расстояние на полпути между обеими преаурикулярными точками. Затем отметьте пересечение обеих отметок. Осторожно наденьте ЭЭГ-шапочку на голову субъекта.Подключите ЭЭГ к компьютерной системе и начните оценку состояния покоя. Одновременно оценивайте исходный уровень ВСР в течение пяти минут на планшете, подключенном к монитору через Bluetooth, прежде чем оценивать ЭЭГ. Далее, для выполнения задания, связанного с оценкой ЭЭГ, очистите кожу уха испытуемого 70% спиртовой салфеткой.Нанесите физиологический раствор на подушечки ушей, затем поместите электроды на ухо и проверьте качество тока. Начните стимуляцию с помощью ТАВНС. После 60 минут стимуляции измерьте предмет на ЭЭГ, ВСР и боль.Затем выполните условную модуляцию боли, как и раньше. Было создано топографическое распределение графиков скальпа в состоянии покоя для тета-, альфа- и бета-полос на исходном уровне, во время и после процедуры. В лобной области был замечен асимметричный альфа-рисунок.

Research

JoVE Journal

Neuroscience

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

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

Author Spotlight: Exploring the Effects of Transauricular Vagus Nerve Stimulation

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