International Neuromodulation Society Poster Submission, Abstract, References and Expanded Content

I am submitting my E poster for the International Neuromodulation Society today. It is an observational case study looking at the potential for using DFAα, a nonlinear HRV as a biomeasure to evaluate the addition of Transcutaneous Vagal Nerve Stimulation (TAVNS) to standard acupuncture treatment. Acupuncture improves autonomic tone (increases vagal-parasympathetic activity and decreases sympathetic activity) in part by stimulating the Neuroendocrine immune response. The hypothesis is that adding TAVNS to acupuncture treatment, we will see more of an improvement in autonomic tone. The other hypothesis is that by using DFAα, it will correlate with standard frequency measures LF/HF but might be more robust since it can be measured every minute, and is less prone to artifact. My study was partially successful, but there is still room for improvement. With better electrode placement and parameters, I think I’ll get there. pdf here INS Poster 2021 8.24.2021 version 2

Power point is here INS Poster 2021 8.24.2021

An expanded version of the poster follows the official abstract.

Official Title ”

EPV203; HEART RATE VARIABILITY MONITORING OF CLINICAL TRANSCUTANEOUS AURICULAR VAGAL NERVE STIMULATION

Introduction

Improved autonomic balance leads to reduction in inflammation as well as other health benefits. Inflammation is implicated in medical conditions from cardiovascular disease to depression, to cancer, to aging . Efforts to “hack” the autonomic nervous system with implanted vagal nerve stimulators have had some success. Transcutaneous Auricular Vagal Nerve Stimulation (TAVNS) has the promise of being a safe alternative since it relies on noninvasive afferent input to a peripheral branch of the vagus. Recent research has helped to define best parameters for TAVNS treatment, including frequency, intensity, electrode placement and timing. As with any treatment modality, however, individual patient variation can affect the efficacy of implanted vagal nerve stimulators and TAVNS. There are some exploratory investigations using heart rate variability (HRV) as feedback for implanted vagal nerve stimulation and for TAVNS also. Acupuncture has been shown to improve autonomic balance, so the hypothesis was that TAVNS added to acupuncture treatment would further improve HRV and autonomic balance.

Methods/Materials

Patients monitored (HRV) in supine position for 5 minute baseline and then for entire treatment including TAVNS application, needling and resting with needles in for additional 20 minutes. TAVNS applied using clip electrode on the cymba concha bilaterally, and in some instances unilaterally. Frequency of TAVNS varied between, 1 hz, 25Hz, or 100 hz. HRV analysis of 3 minute segments during treatment using several HRV parameters including time, frequency and nonlinear analysis. 1 minute segments for DFAα1 (a nonlinear parameter) were also charted.

Results

There was individual patient variation in HRV response with added TAVNS. HRV analysis is characterized by a significant noise/signal ratio. DFAα1 mitigated that problem. Patients who showed the most improvement were those who had low HRV to start, though other variables such as clinical condition and gender might play a role.

Discussion

The hypothesis that TAVNS would improve HRV did not hold up in all patients. Of the HRV parameters measured and recorded, DFAα1 over one minute segments had the strongest signal/noise ratio so was the most promising as a measure. Furthermore, HRV analysis might have the potential to determine best TAVNS parameters for treatment such as intensity, frequency, duration etc… Individual patients’ HRV data will be presented and discussed.

Conclusions

TAVNS did not improve HRV in all patients so HRV may help to better define which patients would benefit most from TAVNS. DFAα1 was found to be the most reliable HRV measure.

References

1 Eugenijus Kaniusas1*, Stefan Kampusch1,2 et al, Marc Tittgemeyer3,4 Current Directions in the Auricular Vagus Nerve Stimulation II – An Engineering Perspective Front Neurosci 13.772 July 24 2019

2 Romero-Ugalde HM^1,2, Le Rolle V^1,2, Bonnet JL³, et al A novel controller based on state-transition models for closed-loop vagus nerve stimulation: Application to heart rate regulation. PLoS One. 2017 Oct 27;12(10):17.

3 Liu HY^1,2, Yang Z¹, Meng FG^3,4, et al Preoperative Heart Rate Variability as Predictors of Vagus Nerve Stimulation Outcome in Patients with Drug-resistant Epilepsy. Sci Rep. 2018 Mar 1;8(1):3856.

4 Sclocco R¹, Garcia RG², Kettner NW³, et al The influence of respiration on brainstem and cardiovagal response to auricular vagus nerve stimulation: A multimodal ultrahigh-field (7T) fMRI study. Brain Stimul. 2019 Feb 10.

5 Ulloa L¹, Quiroz-Gonzalez S², Torres-Rosas R³. Nerve Stimulation: Immunomodulation and Control of Inflammation.Trends Mol Med. 2017 Dec;23(12):1103-1120.

#Transcutaneous Auricular Vagal Nerve Stimulation, TAVNS, Heart Rate Variability, HRV, Acupuncture

Objective:

Objective of this case study is to explore the use of Detrended Fluctuation Analysis (DFAα), a nonlinear measure, compared to standard frequency Fast Fourier Transform measurement- Low Frequency to High Frequency (LF/HF) Heart Rate Variability as feedback during application of Transcutaneous Vagal Nerve Stimulation in the clinic.

Hypothesis: This study is part of an ongoing project to devise a simple TAVNS system for home use by patients. The hypothesis is that adding TAVNS to clinical acupuncture treatment there will be a further improvement in autonomic tone, ie. increase parasympathetic (vagal) activity and decrease sympathetic activity.

Background.

Peripheral nerve stimulation in the form of acupuncture has been used for millenia for the treatment of pain, arthritis and other inflammatory conditions. Acupuncture has been shown with HRV to improve autonomic balance by decreasing sympathetic activity and increasing parasympathetic activity. Recent studies show that acupuncture needling activates the Neuroendocrineimmune response, a series of feedbacks which leads to a decrease in inflammation by downregulating inflammatory markers via the autonomic nervous system.

HRV is well suited for clinical study because it is noninvasive and give results over various time scales, minutes to hours or as a trend over time. Adding TAVNS to the acupuncture treatment might further improve autonomic balance because TAVNS connects to the nucleus tractus solitarius (NTS) and decreases sympathetic activity and increases vagal activity.

TAVNS. This poster presentation is part of a project to create a user friendly means to provide TAVNS to patients as an at home addition to their acupuncture treatment. For that reason, the TAVNS unit is a simple, inexpensive one, and the ear electrode simple clip.

Researchers

Materials and Methods.

A sampling of patients’ data is included for demonstration, and is purely observational study.

Patients’ HRV was monitored (HRV) (Nonin Pulse Oximeter, analysis Vivosense software) in supine position for 5 minute baseline and then for entire treatment including TAVNS application, needling and resting with needles in for additional 20 minutes. TAVNS applied using clip electrode on the cymba concha unilaterally on the left ear. Frequency of TAVNS was 1 hz. Analysis of 3 minute segments during treatment using several HRV parameters including time, frequency and nonlinear analysis. Q 1 minute data for DFAα was also collected. Only DFAα 1 minute data is shown.

Results:

Patient 1. 60+ y.o. Female with Peripheral Neuropathy successfully treated with acupuncture

DFAα1

Patient 2. 30 y.o. Female with daily migraines successfully treated with acupuncture

Patient 3. 70+ y.o. Female with intention tremor successfully treated with acupuncture

Results

The data show modest improvements in autonomic tone with TAVNS in some cases.
DFAα differences with the TAVNS are not pronounced, but do follow the trend of LF/HF in general.
The DFAα results appear to be less prone to artifact than LF/HF.

Discussion:

The most significant problem with this study is that TAVNS is added to acupuncture treatment and not tested on its own. Since acupuncture already improves autonomic tone, it is impossible to know the effect of TAVNS on its own.
Researchers believe that TAVNS decreases sympathetic activity more than increasing vagal activity

Electrode placement and contact, as well as stimulation parameters must be optimized.

The cymba concha region has the highest density of the auricular branch of the vagus nerve.
The stimulation should not be painful in order to stimulate the A__ fibers
Bilateral or unilateral stimulation can be applied, but unilateral is simpler for home use.
The grounding pad can be placed on the between the neck and the shoulder on the trapezius, or on the anterior surface of the arm near the wrist
Though higher frequencies 25 hz are thought to stimulate vagal activity and lower .5 to 2 hz inhibit sympathetic activity and were used for this study.
Though the ear clip is not an optimal electrode since it delivers over a larger and more diffuse area, it is easier for patients to use it and would be easier to transition into a home application.

Since this is an ongoing project to determine best

TAVNS may decrease sympathetic activity more than increase vagal activity according to some researchers.

In this study TAVNS was added to acupuncture which improves autono

When sympathetic activity and vagal activity were evaluated, as well as LF/HF, there were no substantial differences between treatment with acupuncture only versus the addition of TAVNS. (Data was not presented here.)

The hypothesis that using 1 minute segments for DFAα1 (a nonlinear parameter) may reveal more detailed HRV response and be a more accurate reflection of TAVNS effect on the acupuncture patients’ response was not born out. Though the response did reflect more subtlety in the response in detailed one minute segments, there was a modest difference.

To provide an in home solution to provide TAVNS to patients with more confidence, it would be optimal to document improved autonomic balance with the treatment protocol used.

Previous studies indicate that healthy people may not have as robust a response to TAVNS as do those with an underlying condition[i].

Caveats for TAVNs application.

The cymba concha region has the highest density of the auricular branch of the vagus nerve.
The stimulation should not be painful in anyway, to stimulate only the ____ fibers.
Bilateral or unilateral stimulation can be applied, but unilateral is simpler for home use.
The grounding pad can be placed on the between the neck and the shoulder on the trapezius, or on the anterior surface of the arm near the wrist
Though higher frequencies 25 hz are thought to stimulate vagal activity and lower .5 to 2 hz inhibit sympathetic activity, in the clinic lower frequencies were more consistently helpful in lowering DFAα.
Though the ear clip is not an optimal electrode since it delivers over a larger and more diffuse area, it is easier for patients to use it and would be easier to transition into a home application.

In this HRV analysis protocol, there was a 5 minute baseline and then needling and application of TAVNS with a 20 minute rest period.

A recent paper used the Higuchi Fractal Dimension, another nonlinear measure, and they did two sessions of TAVNS separated by 10 minutes of rest in between. This may be a promising protocol if patients are willing and clinic time allows.

. A novel way to make customized ear electrodes developed in mice, may help to better focus treatment.

To use proprietary software with noninvasive oximeter probe important to the project, so that it could be implemented in a clinical setting.

Healthy subjects may not have as much of an improvement in their autonomic tone as, say, diabetic or otherwise healty subjects. Likely elderly neither.

Not concerned with clinical outcomes in this presentation.

Not concerned with the overall TAVNS, trying to see individual differences between treatments, and perhaps individuals.s

Longer treatment times if possible

Conclusion: These anecdotal, observational data show a modest improvement in autonomic balance in some cases with the addition of TAVNS to standard acupuncture treatment. By using HRV as a feedback varying duration of stimulation, parameters of stimulation and improved ear electrodes improvements in the protocol for in home TAVNS application may be obtained.

Patient 1 70 year old female with Neuropathy

[i] Gomolka RS, Kampusch S, Kaniusas E, Thürk F, Széles JC, Klonowski W. Higuchi Fractal Dimension of Heart Rate Variability During Percutaneous Auricular Vagus Nerve Stimulation in Healthy and Diabetic Subjects. Front Physiol. 2018;9:1162. Published 2018 Aug 21. doi:10.3389/fphys.2018.01162