Application of Noninvasive Vagal Nerve Stimulation to Stress-Related Psychiatric Disorders

Abstract

Background: Vagal Nerve Stimulation (VNS) has been shown to be efficacious for the treatment of depression, but to date, VNS devices have required surgical implantation, which has limited widespread implementation. Methods: New noninvasive VNS (nVNS) devices have been developed which allow external stimulation of the vagus nerve, and their effects on physiology in patients with stress-related psychiatric disorders can be measured with brain imaging, blood biomarkers, and wearable sensing devices. Advantages in terms of cost and convenience may lead to more widespread implementation in psychiatry, as well as facilitate research of the physiology of the vagus nerve in humans. nVNS has effects on autonomic tone, cardiovascular function, inflammatory responses, and central brain areas involved in modulation of emotion, all of which make it particularly applicable to patients with stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD) and depression, since dysregulation of these circuits and systems underlies the symptomatology of these disorders. Results: This paper reviewed the physiology of the vagus nerve and its relevance to modulating the stress response in the context of application of nVNS to stress-related psychiatric disorders. Conclusions: nVNS has a favorable effect on stress physiology that is measurable using brain imaging, blood biomarkers of inflammation, and wearable sensing devices, and shows promise in the prevention and treatment of stress-related psychiatric disorders.

Transcutaneous Cervical Vagal Nerve Stimulation in Patients with Posttraumatic Stress Disorder (PTSD): A Pilot Study of Effects on PTSD Symptoms and Interleukin-6 Response to Stress

“…Studies in both animals and humans showed that catecholamines released during stress act through the adrenergic receptor to activate the transcription factor, nuclear factor-κB (NF-κB), which leads to increases in cytokines, including IL-6 ( Bierhaus et al, 2003 ). Intervention at the level of IL-6 with VNS may be a useful intervention that reduces symptoms by targeting the underlying neurobiology of PTSD( Bremner et al, 2020b ; Noble et al, 2019 ; Souza et al, 2019 ).…”

“…Neuromodulation is a new approach that may be particularly useful in addressing the underlying psychobiology of stress-related psychiatric disorders ( Adair et al, 2020 ; Bikson et al, 2016 ; Bikson et al, 2017b ; Bremner et al, 2020b ; Krames et al, 2018 ; Schachter and Saper, 1998 ; Tortella et al, 2015 ; Woods et al, 2016 ). Vagal Nerve Stimulation (VNS) is a form of neuromodulation that has been shown to be efficacious in the treatment of epilepsy ( Ben-Menachem et al, 1999 ; Ben-Menachem et al, 1994 ; George et al, 1994 ; Handforth et al, 1998 ; Salinsky et al, 1999 ; The Vagus Nerve Stimulation Study Group, 1995 ) and treatment-refractory major depression ( Aaronson et al, 2017 ; Berry et al, 2013 ; Dell-Osso et al, 2013 ; George et al, 2005 ; George et al, 2003 ; George et al, 2000 ; Marangell et al, 2002 ; Rush et al, 2000 ; Rush et al, 2005a ; Rush et al, 2005b ; Sackeim et al, 2007 ; Sackeim et al, 2001a ; Sackeim et al, 2001b ).…”

“…A new generation of non-implantable VNS devices has the potential to be more widely implemented in psychiatry due to lower cost and greater convenience ( Bremner and Rapaport, 2017 ). VNS can be applied to branches of the vagus nerve in the ear (transcutaneous auricular VNS, or taVNS) or in the neck, where it travels through the carotid sheath (transcutaneous cervical VNS, or tcVNS) ( Adair et al, 2020 ; Badran et al, 2019 ; Bremner et al, 2020b ). PTSD is associated with an increase in the blood concentrations of the inflammatory marker interleukin (IL)-6 at baseline ( Gill et al, 2010 ; Gill et al, 2008 ; ( Guo et al, 2012 ); Li et al, 2014 ; Lindqvist et al, 2017 ; Miller et al, 2001 ; Passos et al, 2015 ; Sutherland et al, 2003 ; Tucker et al, 2010 ; Vidovic et al, 2011 ; von Kanel et al, 2010 ) and in response to mental stress such as public speaking ( Lima et al, 2019 ) or exposure to personalized traumatic scripts ( Bremner et al, 2020a ) as well as in diurnal cerebrospinal fluid (CSF) ( Baker et al, 2001 ).…”

Efficacy of Pranayama in Preventing COVID-19 in Exposed Healthcare Professionals: A Randomized Controlled Trial

“…Increasing duration of stress is expected to result in a shift from potentially adaptive changes to potentially detrimental changes, initially in cellular immunity and then in immune function more broadly 29 . Vagus Nerve Stimulation has been found to have a direct effect in managing stress and diseases born out of it 30 . Pranayama practices have been found to have a direct impact on Vagus Nerve stimulation 31 32 .…”

A method to quantify autonomic nervous system function in healthy, able-bodied individuals

“…Another possible application could be evaluation of targeted neuromodulation; specifically, there is clinical interest in stimulating the vagus nerve, which is involved with responses in cardiovascular, pulmonary, gastrointestinal, renal, hepatic, and endocrine systems (Chavan et al, 2017; Pavlov et al, 2018). Vagus nerve stimulation (VNS) has been used in previous studies for multiple conditions, including refractory epilepsy (Stefan et al, 2012; Rong et al, 2014), depression (Rong et al, 2016; Kong et al, 2018), PTSD (Bremner et al, 2020), pre-diabetes (Huang et al, 2014), tinnitus (Shim et al, 2015), stroke (Redgrave et al, 2018), and others, including oromotor dysfunction, rheumatoid arthritis, and obesity (Guiraud, et al, 2016). These studies have used a range of electrical stimulation settings and sites, and there is no optimal dose or set of parameters (Badran et al, 2018); the mechanism of VNS and responses are not well understood.…”