Differential activation of brainstem neurons with transcutaneous auricular vagus nerve stimulation and its comparability to cervical vagus nerve stimulation

Authors' Affiliations

Misty Owens, Department of Biomedical Sciences, East Tennessee State University, Johnson City, TN Vincent Jacquemet, Department of Pharmacology and Physiology, Institute of Biomedical Engineering, University of Montreal, Quebec, Canada and Sacred Heart Hospital of Montreal, Research Center, Quebec, Canada Vitaly Napadow, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA Eric Beaumont, Department of Biomedical Sciences, East Tennessee State University, Johnson City, TN

Location

Culp Center Rm. 311

Start Date

4-25-2023 2:00 PM

End Date

4-25-2023 2:20 PM

Faculty Sponsor’s Department

Biomedical Sciences

Name of Project's Faculty Sponsor

Eric Beaumont

Additional Sponsors

Dr. Michelle Chandley Dr. Matthew Zahner Dr. Diego Rodriguez Gil Dr. Antonio Rusinol

Classification of First Author

Graduate Student-Doctoral

Competition Type

Competitive

Type

Oral Presentation

Project's Category

Neuroscience

Abstract or Artist's Statement

Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) is a neuromodulatory technique used to activate vagal afferent fibers located in the concha of the outer ear. Vagal afferents project to the nucleus of the solitary tract (NTS) where information is processed and propagated to higher brain regions. Widespread NTS connections provide a mechanism through which taVNS can be used to influence multiple systems and be a potential treatment for many disorders including heart failure, gastric motility disorders, and migraines. Recent studies are now investigating taVNS as an alternative treatment option to invasive cervical vagus nerve stimulation (cVNS) which is FDA approved to treat drug-resistant epilepsy and depression but has limited patient availability due to the invasiveness of the procedure. Migraine and epilepsy clinical studies have shown therapeutic taVNS benefits and human fMRI studies have demonstrated comparable brain activation between cVNS and taVNS. However, questions remain regarding optimal taVNS parameters, and no study has compared the direct mechanisms responsible for cVNS and taVNS effects. In this study, a high-impedance tungsten electrode was stereotaxically placed into NTS in 10 chloralose-anesthetized rats, and 40-70 neurons were interrogated using electrophysiological methods. Firing rate changes during stimulation on-times were compared to activity levels during stimulation off-times. Neurons were classified as positive responders if they displayed consistent firing rate increases during stimulation, negative responders if they displayed consistent decreases, and non-responders if there was no consistency using a mathematical cosine similarity score. Six taVNS stimulation parameters were investigated using three frequencies (20, 100, 250Hz) at two intensities (0.5, 1.0mA) to identify parameter-specific effects on NTS neurons. Additionally, neuronal activity was evaluated following cVNS at 20 and 250Hz at the bradycardic intensity (lowest intensity to generate a transient 5% decrease in heart rate, BI) and compared to taVNS effects at the corresponding frequencies. Our data shows that taVNS at 20Hz, 1.0mA yields the greatest number of positive responders and 100Hz, 1.0mA yields the greatest number of negative responders (p<0.05) suggesting different taVNS parameters can differentially influence NTS activity. Comparisons between the number of responders generated with cVNS and taVNS revealed significantly fewer negative responders with cVNS at 20Hz compared to taVNS at 20Hz regardless of intensity (p<0.01) but yielded comparable positive responders between cVNS at 20Hz, BI and taVNS at 20Hz, 1.0mA. No significant differences were observed between the number of cVNS and taVNS responders at 250Hz. Interestingly, individual neuronal responses were different between both methods of stimulation, suggesting that they could work through different neuronal pathways.

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Apr 25th, 2:00 PM Apr 25th, 2:20 PM

Differential activation of brainstem neurons with transcutaneous auricular vagus nerve stimulation and its comparability to cervical vagus nerve stimulation

Culp Center Rm. 311

Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) is a neuromodulatory technique used to activate vagal afferent fibers located in the concha of the outer ear. Vagal afferents project to the nucleus of the solitary tract (NTS) where information is processed and propagated to higher brain regions. Widespread NTS connections provide a mechanism through which taVNS can be used to influence multiple systems and be a potential treatment for many disorders including heart failure, gastric motility disorders, and migraines. Recent studies are now investigating taVNS as an alternative treatment option to invasive cervical vagus nerve stimulation (cVNS) which is FDA approved to treat drug-resistant epilepsy and depression but has limited patient availability due to the invasiveness of the procedure. Migraine and epilepsy clinical studies have shown therapeutic taVNS benefits and human fMRI studies have demonstrated comparable brain activation between cVNS and taVNS. However, questions remain regarding optimal taVNS parameters, and no study has compared the direct mechanisms responsible for cVNS and taVNS effects. In this study, a high-impedance tungsten electrode was stereotaxically placed into NTS in 10 chloralose-anesthetized rats, and 40-70 neurons were interrogated using electrophysiological methods. Firing rate changes during stimulation on-times were compared to activity levels during stimulation off-times. Neurons were classified as positive responders if they displayed consistent firing rate increases during stimulation, negative responders if they displayed consistent decreases, and non-responders if there was no consistency using a mathematical cosine similarity score. Six taVNS stimulation parameters were investigated using three frequencies (20, 100, 250Hz) at two intensities (0.5, 1.0mA) to identify parameter-specific effects on NTS neurons. Additionally, neuronal activity was evaluated following cVNS at 20 and 250Hz at the bradycardic intensity (lowest intensity to generate a transient 5% decrease in heart rate, BI) and compared to taVNS effects at the corresponding frequencies. Our data shows that taVNS at 20Hz, 1.0mA yields the greatest number of positive responders and 100Hz, 1.0mA yields the greatest number of negative responders (p<0.05) suggesting different taVNS parameters can differentially influence NTS activity. Comparisons between the number of responders generated with cVNS and taVNS revealed significantly fewer negative responders with cVNS at 20Hz compared to taVNS at 20Hz regardless of intensity (p<0.01) but yielded comparable positive responders between cVNS at 20Hz, BI and taVNS at 20Hz, 1.0mA. No significant differences were observed between the number of cVNS and taVNS responders at 250Hz. Interestingly, individual neuronal responses were different between both methods of stimulation, suggesting that they could work through different neuronal pathways.