Tragus based Vagus Nerve Stimulation for Stress Reduction

Surej Mouli

1 a

, Ramaswamy Palaniappan

1 b

, Jane Ollis

, Ian McLoughlin

3 c

Rahul Kanegaonkar

4,5

and Sunil Arora

Data Science Research Group, School of Computing, University of Kent, U.K.

MindSpire Ltd., U.K.

ICT Cluster, Singapore Institute of Technology, Singapore

Canterbury Christ Church University, U.K.

Kent Surrey Clinical Research Network, U.K.

Frimley Park Hospital, Camberley, U.K.

Keywords:

Electrocardiogram, Stress Reduction, Tragus, Vagus Nerve Stimulation.

Abstract:

Non-invasive vagus nerve stimulation is fast becoming a popular alternative treatment method for various

health disorders. The authors investigated the effects of auricular vagus nerve stimulation at tragus for acti-

vating the parasympathetic nervous system to reduce stress, in light of mixed results from other studies. Stim-

ulation frequency of 25 Hz with a pulse-width of 200 µs was administered at tragus with ECG data recorded

during pre- and post-stimulation trials to investigate changes in the low-frequency (LF) and high-frequency

(HF) parameters of heart rate variability (HRV). The results from ﬁve subjects demonstrate an increase in

the HF component and a decrease in LF when comparing pre- and post- stimulation values, denoting that

VNS stimulated more of the parasympathetic activity. The LF/HF ratio was reduced for all participants after

stimulation, with an average reduction of 64.5% observed. Overall, this study has indicated the feasibility of

using tragus as a stimulation site to stimulate the vagus nerve; tragus being easier to administrate than many

alternative sites while still being effective for stress reduction.

1 INTRODUCTION

Constant demands in routine daily life are a catalyst

for increased stress and anxiety issues leading to var-

ious mental disorders (Hidaka, 2012; Bandelow and

Michaelis, 2015; Kessler et al., 2009). Stress is the

leading contributory factor and major cause to the de-

velopment of diseases such as cardiovascular, chronic

skin conditions, chronic cluster headaches and vari-

ous other psychiatric illnesses (Blixen et al., 2016).

For clinicians, treating patients with stress-related ill-

ness through drug administered approaches is not a

good solution as the average efﬁcacy rate of most

drugs does not exceed 50%, and moreover can cause

intolerable adverse side effects (Ambrosini and Cop-

pola, 2020). To address these issues and to minimise

the adverse side effects of drugs, alternate treatments

https://orcid.org/0000-0002-2876-3961

https://orcid.org/0000-0001-5296-8396

https://orcid.org/0000-0001-7111-2008

have been sought in recent years, notably methods

based on nerve stimulation are being explored widely.

Such methods are sometimes referred as neuromodu-

lation, due to their ability to modulate the nervous sys-

tem. Amongst various neuromodulation techniques,

vagus nerve stimulation (VNS) has been widely in-

vestigated since 1990 using implanted or invasive

VNS devices (Akerman and Romero-Reyes, 2020).

The vagus nerve is the tenth cranial nerve that

consists of approximately 80% afferent ﬁbres project-

ing into the brain and 20% efferent ﬁbres that project

to the rest of the body. It is considered to be the

major parasympathetic innervation of the autonomic

nervous system (Akerman and Romero-Reyes, 2020;

Johnson and Wilson, 2018; Kaniusas et al., 2019b;

McClintock et al., 2009). Since the ﬁrst human im-

plant of VNS devices in 1989, over 50, 000 patients

have been treated with VNS worldwide and the vagus

nerve is often considered protective, defensive and re-

laxing (Vonck et al., 2009). VNS has been recently

approved by the FDA in the US for therapeutic use in

164

Mouli, S., Palaniappan, R., Ollis, J., McLoughlin, I., Kanegaonkar, R. and Arora, S.

Tragus based Vagus Nerve Stimulation for Stress Reduction.

DOI: 10.5220/0010222201640168

In Proceedings of the 14th International Joint Conference on Biomedical Engineering Systems and Technologies (BIOSTEC 2021) - Volume 4: BIOSIGNALS, pages 164-168

ISBN: 978-989-758-490-9

patients aged over 12, as well as those presenting with

drug resistant epilepsy and depression (Johnson and

Wilson, 2018). However, there have been confound-

ing results in the literature where one study (Borges

et al., 2019) has indicated no difference between sham

stimulation and VNS. Hence, in this study, we have

investigated the effects of VNS at the tragus site,

and investigated its stress reduction effect. For this

analysis, we used Heart Rate Variability (HRV), as a

promising marker (Malik et al., 1996) of stress. HRV

is the ﬂuctuation in the time intervals between adja-

cent heartbeats (Shaffer and Ginsberg, 2017). It is

sensitive to changes in sympathetic and parasympa-

thetic nervous systems from which stress levels can

be inferred. Various studies report that when stress is

induced, the HRV variable HF decreases, and LF in-

creases, to lower the parasympathetic activity (Thayer

et al., 2012; Kim et al., 2018).

Figure 1: Stimulation protocol.

More recent studies have focused on non-invasive

methods of VNS, which can circumvent complex

implantation procedures and reduce associated risks

such as infection. To address this, electrical stimula-

tion of the auricular vagus nerve has been appropri-

ately investigated using bioelectronics with the main

focus being on the therapeutic effects (Kaniusas et al.,

2019a). Stimulating the auricular branch of the vagus

nerve (ABVN) also known as Alderman’s nerve or

Arnold’s nerve has proven to be effective in the treat-

ment of depression (Hein et al., 2013; Bermejo et al.,

2017; Trevizol et al., 2015; Fang et al., 2016; Rong

et al., 2016).

To apply electrical stimulation on the auricular

branch, the location could either be the cymba con-

chae or tragus as these have most of the vagus ﬁbres.

Even though the conchae consists of 100% vagus ﬁ-

bres, the tragus is easier to apply electrical stimulation

to both walls of the ear with a suitable stimulation clip

(Badran et al., 2018) despite having fewer vagus ﬁ-

bres. Electrical stimulation frequency and pulse width

are crucial parameters that need to be chosen carefully

to activate any parasympathetic response. The stim-

ulation pattern determines the activation of parasym-

pathetic and sympathetic responses. Higher stimula-

tion frequencies of 20–25 Hz are required to stimulate

the parasympathetic system, while lower frequencies

0.5–10 Hz usually stimulate the sympathetic response

(Dietrich et al., 2008). One complicating factor is the

frequency selectivity of the skin barrier between elec-

trodes and nerve cells.

A stimulation frequency of 25 Hz is commonly

used in experimental studies related to auricular VNS

(Badran et al., 2018; Sclocco et al., 2017; Badran

et al., 2019), and a pulse width of 200 µs is considered

to be effective and safe for long periods of stimulation

(Bikson et al., 2018).

2 METHODOLOGY

To administer VNS on the left tragus, a stimulation

protocol as shown in Figure 1 was followed. The

stimulation frequency was ﬁxed at 25 Hz with a pulse

width of 200 µs. Data collection was performed in

three trials over two sessions, starting with a rest pe-

riod of ﬁve minutes for the baseline recording, stimu-

lation/placebo session for 15 minutes and a post stim-

ulation session of ﬁve minutes. Custom hardware

was developed for administering the stimulation as

explained in the Hardware Design section.

Figure 2: Functional block diagram of the equipment devel-

oped for the experiments.

2.1 Hardware Design

Functional blocks for the hardware are shown in Fig-

ure 2. To collect the ECG data, a Biosemi Active Two

system with standalone battery pack was used with

two electrodes attached using conductive gel to the

left and right wrists of each participant. CMS and

DRL electrodes were used as reference and ground.

For stimulation, the pulse was generated using an

ARM Cortex M4 microcontroller, which was pro-

grammed to generate PWM pulses for use in our pro-

tocol (Mouli and Palaniappan, 2017; Mouli and Pala-

niappan, 2020). Along with the hardware prototype,

code was developed to generate pulses at a rate of

25 Hz with a pulse-width of 200 µs. This was fed

Tragus based Vagus Nerve Stimulation for Stress Reduction

165

to a DC-DC controller to regulate the output current

(which did not exceed 2 mA as a safety precaution

(Bikson et al., 2018)), and provided pulse amplitudes

of 2.2 volts. The output timing was controlled by us-

ing another ARM Cortex M4 microcontroller to set

the stimulation time duration of 15 minutes as well

as controlling a dual pole, dual throw relay module to

switch the pulses ON/OFF when the stimulator was

activated. The output of the relay module was con-

nected to a small ear clip as shown in Figure 3 with

two circular electrodes that can comfortably attach to

both sides of the tragus wall.

Figure 3: Tragus clip.

The chosen pulse width and rate are based on

other VNS experimental studies (Kaniusas et al.,

2019b; Badran et al., 2019), although in this case we

stimulated the tragus site. The hardware prototype is a

standalone unit with pre-programmed stimulation fre-

quency and powered by 5 V DC battery pack, which

makes it safer to use and avoids any external power

surges and interferences.

2.2 Procedure

For this study, ﬁve healthy participants (three females,

two males, with age 38.6 ± 12.5 years) took part in

the data recording for two sessions, which comprised

stimulation and placebo on different days. Each par-

ticipant was seated comfortably with electrodes at-

tached using gel to both wrists for ECG collection.

The current stimulator ear clip was coated with con-

ductive paste and was connected to the left tragus with

the anode on the inner side of the tragus and the cath-

ode on the outer side of the tragus. Each session

involved taking three separate ECG recordings be-

ginning with a ﬁve-minute baseline (pre-stimulation)

followed by a 15 min session without stimulation

(placebo) and ending with a ﬁve-minute post ‘stimu-

lation’ session, as shown diagrammatically in Figure

1. The recordings were repeated for the same partici-

pant on a different day, once with placebo and once

with active current stimulation. The precise order

of stimulation/placebo was randomised between par-

ticipants who were not informed which session was

placebo and which involved active VNS. Ethics ap-

proval for the experiment was obtained from the Sci-

ences Research Ethics committee at the University of

Kent. The collected data were anonymised and anal-

ysed to study the effects of current stimulation.

2.3 Data Processing

Two sets of data were analysed separately for placebo

and VNS sessions in each participant. Data was con-

verted from the 128 Hz sample rate of the 24 − bit

Biosemi Data Format (BDF) recordings to European

Data Format (EDF) using the EEGLAB plug-in in

MATLAB. Data was ﬁltered from 1 to 35 Hz using

an IIR Elliptic ﬁlter and the ECG was extracted from

the channel corresponding to the left wrist with the

right wrist used as a re-reference channel. R-R peaks

were detected using a peak detection method in MAT-

LAB that involved a pre-deﬁned threshold that was

veriﬁed manually for each experiment to ensure that

artefact induced peaks were excluded. These R-R in-

tervals were fed into Kubios HRV 3.3.1 analysis soft-

ware (Tarvainen et al., 2014) to compute the values

for LF (0.04-0.15 Hz), HF (0.15-0.4 Hz) and the ratio

LF/HF.

3 RESULTS AND DISCUSSION

From HRV, the LF and HF components can be com-

puted to evaluate the inﬂuence of VNS. Computed

values from pre- and post- VNS sessions are shown in

Table 1 for all the ﬁve participants. Based on these re-

sults, it is evident that LF values were reduced and HF

values were increased with VNS, denoting a stronger

activation of the parasympathetic system compared

to the sympathetic system. The overall reduction in

the LF/HF ratio from the pre-VNS and post-VNS ses-

sions was also computed. Over all ﬁve participants,

an average reduction of 64.5% was observed between

pre- and post- VNS sessions. Meanwhile an aver-

age reduction of 6.8% was observed between pre- and

post- placebo sessions. Figure 4 also shows the reduc-

tion in electrocardiogram derived respiration (EDR).

A small reduction is to be expected when someone

is sitting down relaxed for short periods of time, how-

ever the increased reduction observed for the VNS

sessions may indicate the effectiveness of the stimula-

tion in reducing stress. Figure 4 shows an example of

the HRV frequency analysis from one participant for

both pre- and post- VNS sessions where the higher HF

increase over LF increase in post-VNS can be seen

showing an increase in the parasympathetic activity

as compared to sympathetic. Changes in the HRV pa-

rameters as a result of VNS has also been reported

BIOSIGNALS 2021 - 14th International Conference on Bio-inspired Systems and Signal Processing

166

Figure 4: Pre - and Post - VNS session from one participant.

Table 1: Pre- and Post - VNS results from all participants.

Session Participant P1 P2 P3 P4 P5

Pre- VNS

LF (n.u.) 88.40 67.50 46.50 57.70 93.13

HF (n.u.) 11.60 30.30 53.40 42.20 6.85

LF/HF (%) 7.62 2.23 0.87 1.37 13.60

Post- VNS

LF (n.u.) 71.20 40.00 26.20 35.70 81.8

HF (n.u.) 28.80 59.90 73.20 64.20 18.17

LF/HF (%) 2.47 0.67 0.36 0.56 4.50

% Reduction 67.56 70.02 58.90 59.33 66.89

in various studies using similar frequency (Constan-

tinescu et al., 2019; Kamath et al., 1992; De Couck

et al., 2017).

4 CONCLUSION

The study reported here explored the possibilities of

non-invasive auricle vagus nerve stimulation at the

tragus. The experiments stimulated the left tragus for

15 minutes to activate a parasympathetic response, in-

ducing a more relaxed (less stressful) state. A fre-

quency of 25 Hz using a pulse width of 200 µs was

generated using portable standalone hardware and

administered during stimulation. The vagus nerve

was easily stimulated at the tragus using a generic

ear clip for both anode and cathode, in contrast to

the cymba conchae location, which would require

custom-shaped attachments for each participant. A

reduction in LF/HF ratio after VNS was observed for

all participants even with a relatively stimulation short

period of 15−minutes, with LF components decreas-

ing and HF components increasing after the stimula-

tion to indicate a higher parasympathetic vs sympa-

thetic activation. For this study, the VNS period was

limited to 15 minutes to explore the inﬂuence of non-

invasive stimulation, but future studies could explore

longer periods of stimulation, or the effect of sessions

at regular intervals involving clinical patients. Cus-

tomised cymba conchae designs to stimulate the va-

gus nerve could also be explored, which may lead to

improved results, given that the density of vagus nerve

ﬁbres is higher at the conchae compared to the tragus.

ACKNOWLEDGEMENTS

The project was funded by Enabling Innovation: Re-

search to Application (EIRA, Research England’s

Connecting Capability Fund, CCF) grant RD005 -

MindSpire Proof of Concept.

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