Abstract— Non-invasive vagus nerve stimulation (n-VNS)
devices offer non-surgical alternatives to implantable VNS
therapy for possible treatment of autonomic nervous system
disorders. In this work, we investigate the patient outcomes for
n-VNS devices applied in tandem with traumatic stress. A total
of 25 human subjects participated in a double-blind study, half
undergoing active n-VNS and half undergoing sham stimulus.
The protocol included audible delivery of neutral recordings
(voice recordings about pleasant scenery) and traumatic stress
recordings (personalized voice recordings based on prior
traumatic experiences). Stimulation was administered
immediately after the traumatic stress recordings. Patient
outcomes were quantified with visual analog ratings of five
mood dimensions: nervousness, anxiety, fear, anger, highness
measured during baseline, after each neutral recording, and
after each traumatic stress recording followed by n-VNS. Our
results reveal that the sham group experienced significantly
increased anger responses after hearing traumatic stressors,
compared to baseline (p<0.05), whereas the active group did not
show a significant anger response (p=0.18). These findings
suggest that active n-VNS blocks adverse behavioral responses
to reminders of traumatic stress. N-VNS may a useful
intervention for stress-related psychiatric disorders.
Electrical stimulation of the vagus nerve, one of the major
components of the autonomic nervous system, has clinical
applications for a wide range of disorders . Traditional
stimulation approaches involve surgically implanted vagus
nerve stimulation (VNS) devices that are expensive and
potentially lead to complications from the surgery.
Non-invasive VNS (n-VNS) has the potential to reduce the
shortcomings of implantable VNS. In prior work, we
presented physiological biomarkers of n-VNS that could
quantify the real-time response to acute treatment [2, 3]. In
our current study, we investigate the patient outcomes based
on visual analog scales that represent the current mood state.
The data were obtained from a double-blind study held in
the Emory University School of Medicine with 25 human
subjects separated into active n-VNS (n = 12) and sham (n =
13) groups. The protocol included audible delivery of neutral
recordings (voice recordings about pleasant scenery to serve
as control) and traumatic stress recordings (personalized voice
recordings based on prior traumatic experiences). Traumatic
This work is based on material supported by the Defense Advanced
Research Projects Agency (DARPA), Arlington, VA, under Cooperative
N.Z. Gurel, O.T. Inan are with Inan Research Lab, School of Electrical
and Computer Engineering, Georgia Institute of Technology, Atlanta, GA,
30332 (corresponding author e-mail: email@example.com).
M.T. Wittbrodt, J.D. Bremner, A.J. Shah, V. Vaccarino are with Emory
School of Medicine and Rollins School of Public Health, Atlanta, GA,
stress recordings were immediately followed with stimulation
using noninvasive handheld devices with the same operation
and appearance (gammaCore). Sham or n-VNS was
administered to each subject six times throughout the session.
Visual analog ratings representing current mood in five
dimensions (nervousness, anxiety, fear, anger, highness) were
obtained during baseline, after each six neutral recordings, and
after each six traumatic stress recordings followed by
stimulation. Data were averaged across each interval and
dimension for each subject. For comparison of each dimension
between three intervals, analysis of variance methods
(Kruskal-Wallis) and post-hoc multiple comparisons (Tukey’s
Honestly Significant Difference) were conducted.
Anger responses were significantly increased in the sham
group following traumatic scripts compared to baseline
(p=0.01, Figure 1). Anger was not significantly increased
within the active n-VNS group (p=0.18). No differences in
other scales were found between groups. Active n-VNS
blocks anger responses to reminders of traumatic events.
Given the known role of autonomic function in stress-related
behavioral responses including anger, the current findings are
consistent with our prior findings of reduced sympathetic
activity in response to stress .
 D. Guiraud et al., "Vagus nerve stimulation: state of the art of
stimulation and recording strategies to address autonomic
function neuromodulation," J Neural Eng, vol. 13, no. 4, p.
041002, Aug 2016.
 N. Z. Gurel et al., "Abstract# 36: Toward Wearable Sensing
Enabled Closed-Loop Non-Invasive Vagus Nerve Stimulation: A
Study of Real-Time Physiological Biomarkers," Brain
Stimulation, vol. 12, no. 2, p. e13, August 2019.
 N. Z. Gurel et al., "Toward Closed-Loop Transcutaneous Vagus
Nerve Stimulation using Peripheral Cardiovascular Physiological
Biomarkers: A Proof-of-Concept Study," presented at the IEEE
15th International Conference on Wearable and Implantable
Body Sensor Networks (BSN), Las Vegas, NV, 2018.
Noninvasive Vagal Nerve Stimulation Effects on Anger Response
Nil Z. Gurel, Student Member, IEEE, Matthew T. Wittbrodt, Amit J. Shah, Viola Vaccarino, Omer T.
Inan, Senior Member, IEEE, and J. Douglas Bremner
Figure 1. Anger scores classified by device status. (Shades represent
68% confidence intervals, *p<0.05 from baseline to trauma)