Transcutaneous cervical vagal nerve stimulation reduces sympathetic responses to stress in posttraumatic stress disorder: A double-blind, randomized, sham controlled trial

Gurel, Nil Z.; Wittbrodt, Matthew T.; Jung, Hewon; Shandhi, Md. Mobashir Hasan; Driggers, Emily; Ladd, Stacy L.; Huang, Minxuan; Ko, Yi‐An; Shallenberger, Lucy; Beckwith, Joy; Nye, Jonathon A.; Pearce, Bradley D.; Vaccarino, Viola; Shah, Amit; Inan, Omer T.; Bremner, J. Douglas

doi:10.1016/j.ynstr.2020.100264

Cited by 41 publications

(23 citation statements)

References 102 publications

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“…In turn, stimulation of viscerosensory pathways, directly via invasive and non-invasive vagus nerve stimulation (VNS) or indirectly via cardiorespiratory exercises such as heart rate variability (HRV) biofeedback, has been found to reduce mood and anxiety symptoms and attendant autonomic and neuroendocrine dysfunctions [29][30][31][32][33][34] . Hence, functional alterations in thalamocortical interoceptive pathways may be one systems-level mechanism by which taVNS may reduce symptom burdens in multiple disorders.…”

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confidence: 99%

Auricular transcutaneous vagus nerve stimulation modulates the heart-evoked potential

et al. 2022

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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confidence: 99%

Auricular transcutaneous vagus nerve stimulation modulates the heart-evoked potential

et al. 2022

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“…We showed that tcVNS blocks IL-6 and IFNγ response to traumatic script stress in PTSD ( Bremner et al, 2020a ) and blocks the rise in Pituitary Adenylate Cyclase Activating Peptide (PACAP) over three days of stressful tasks in traumatized subjects with and without PTSD ( Gurel et al, 2020c ). We also previously reported that tcVNS in traumatized healthy human subjects with and without PTSD blocked peripheral sympathetic and enhanced parasympathetic responses both at baseline and in response to both personalized traumatic scripts and mental stressors ( Gazi et al, 2020 ; Gurel et al, 2020a ; Gurel et al, 2020b ; Gurel et al, 2018 ; Gurel et al, 2020d ; Gurel et al, 2020e ) and modulated brain response to traumatic scripts ( Wittbrodt et al, 2020 ), and other studies reported that tcVNS blocked sympathetic function in healthy subjects ( Brock et al, 2017 ; Lerman et al, 2019 ) while taVNS blocked sympathetic function in healthy human subjects ( Badran et al, 2018b ; Bretherton et al, 2019 ; Clancy et al, 2014 ) and patients with co-morbid mild Traumatic Brain Injury (mTBI) and PTSD ( Lamb et al, 2017 ). This work replicated findings in healthy subjects using implanted VNS ( Schomer et al, 2014 ).…”

Section: Introductionmentioning

confidence: 68%

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

Bremner

Wittbrodt

Gurel

et al. 2021

Journal of Affective Disorders Reports

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Background: Posttraumatic stress disorder (PTSD) is a highly disabling condition associated with alterations in multiple neurobiological systems, including increases in inflammatory and sympathetic function, responsible for maintenance of symptoms. Treatment options including medications and psychotherapies have limitations. We previously showed that transcutaneous Vagus Nerve Stimulation (tcVNS) blocks inflammatory (interleukin (IL)-6) responses to stress in PTSD. The purpose of this study was to assess the effects of tcVNS on PTSD symptoms and inflammatory responses to stress. Methods: Twenty patients with PTSD were randomized to double blind active tcVNS (N=9) or sham (N=11) stimulation in conjunction with exposure to personalized traumatic scripts immediately followed by active or sham tcVNS and measurement of IL-6 and other biomarkers of inflammation. Patients then self administered active or sham tcVNS twice daily for three months. PTSD symptoms were measured with the PTSD Checklist (PCL) and the Clinician Administered PTSD Scale (CAPS), clinical improvement with the Clinical Global Index (CGI) and anxiety with the Hamilton Anxiety Scale (Ham-A) at baseline and one-month intervals followed by a repeat of measurement of biomarkers with traumatic scripts. After three months patients self treated with twice daily open label active tcVNS for another three months followed by assessment with the CGI. Results: Traumatic scripts increased IL-6 in PTSD patients, an effect that was blocked by tcVNS (p<.05). Active tcVNS treatment for three months resulted in a 31% greater reduction in PTSD symptoms compared to sham treatment as measured by the PCL (p=0.013) as well as hyperarousal symptoms and somatic anxiety measured with the Ham-A p<0.05). IL-6 increased from baseline in sham but not tcVNS. Open label tcVNS resulted in improvements measured with the CGI compared to the sham treatment period p<0.05). Conclusions: These preliminary results suggest that tcVNS reduces inflammatory responses to stress, which may in part underlie beneficial effects on PTSD symptoms.

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“…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. While there have been studies that report mixed or no reported significant effects of VNS on HRV, pupil diameter, and evoked potentials, the preliminary effects on clinical populations are clear (Burger et al, 2020 ; Gurel et al, 2020b ; Libbus et al, 2017 ). The taVNS protocol used in this study (pulse width of 300 μs at a continuous rate of 30 Hz for 5 min) did not produce any significant effects (Debnath et al, n.d. ), but short-term taVNS (3.4 s ON, 26–27 s OFF) elicited robust pupil dilation and alpha oscillations compared to sham stimulation, showing that significant pupillary and EEG markers can be observed (Sharon et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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Background The autonomic nervous system (ANS) maintains physiological homeostasis in various organ systems via parasympathetic and sympathetic branches. ANS function is altered in common diffuse and focal conditions and heralds the beginning of environmental and disease stresses. Reliable, sensitive, and quantitative biomarkers, first defined in healthy participants, could discriminate among clinically useful changes in ANS function. This framework combines controlled autonomic testing with feature extraction during physiological responses. Methods Twenty-one individuals were assessed in two morning and two afternoon sessions over two weeks. Each session included five standard clinical tests probing autonomic function: squat test, cold pressor test, diving reflex test, deep breathing, and Valsalva maneuver. Noninvasive sensors captured continuous electrocardiography, blood pressure, breathing, electrodermal activity, and pupil diameter. Heart rate, heart rate variability, mean arterial pressure, electrodermal activity, and pupil diameter responses to the perturbations were extracted, and averages across participants were computed. A template matching algorithm calculated scaling and stretching features that optimally fit the average to an individual response. These features were grouped based on test and modality to derive sympathetic and parasympathetic indices for this healthy population. Results A significant positive correlation (p = 0.000377) was found between sympathetic amplitude response and body mass index. Additionally, longer duration and larger amplitude sympathetic and longer duration parasympathetic responses occurred in afternoon testing sessions; larger amplitude parasympathetic responses occurred in morning sessions. Conclusions These results demonstrate the robustness and sensitivity of an algorithmic approach to extract multimodal responses from standard tests. This novel method of quantifying ANS function can be used for early diagnosis, measurement of disease progression, or treatment evaluation. Trial registration This study registered with Clinicaltrials.gov, identifier NCT04100486. Registered September 24, 2019, https://www.clinicaltrials.gov/ct2/show/NCT04100486.

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Transcutaneous cervical vagal nerve stimulation reduces sympathetic responses to stress in posttraumatic stress disorder: A double-blind, randomized, sham controlled trial

Cited by 41 publications

References 102 publications

Auricular transcutaneous vagus nerve stimulation modulates the heart-evoked potential

Auricular transcutaneous vagus nerve stimulation modulates the heart-evoked potential

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

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

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