Noninvasive Cervical Vagal Nerve Stimulation Alters Brain Activity During Traumatic Stress in Individuals With Posttraumatic Stress Disorder
Matthew T Wittbrodt, Nil Z Gurel, Jonathon A Nye, Md Mobashir H Shandhi, Asim H Gazi, Amit J Shah, Bradley D Pearce, Nancy Murrah, Yi-An Ko, Lucy H Shallenberger, Viola Vaccarino, Omer T Inan, J Douglas Bremner, Matthew T Wittbrodt, Nil Z Gurel, Jonathon A Nye, Md Mobashir H Shandhi, Asim H Gazi, Amit J Shah, Bradley D Pearce, Nancy Murrah, Yi-An Ko, Lucy H Shallenberger, Viola Vaccarino, Omer T Inan, J Douglas Bremner
Abstract
Objective: Posttraumatic stress disorder (PTSD) is a disabling condition affecting a large segment of the population; however, current treatment options have limitations. New interventions that target the neurobiological alterations underlying symptoms of PTSD could be highly beneficial. Transcutaneous cervical (neck) vagal nerve stimulation (tcVNS) has the potential to represent such an intervention. The goal of this study was to determine the effects of tcVNS on neural responses to reminders of traumatic stress in PTSD.
Methods: Twenty-two participants were randomized to receive either sham (n = 11) or active (n = 11) tcVNS stimulation in conjunction with exposure to neutral and personalized traumatic stress scripts with high-resolution positron emission tomography scanning with radiolabeled water for brain blood flow measurements.
Results: Compared with sham, tcVNS increased brain activations during trauma scripts (p < .005) within the bilateral frontal and temporal lobes, left hippocampus, posterior cingulate, and anterior cingulate (dorsal and pregenual), and right postcentral gyrus. Greater deactivations (p < .005) with tcVNS were observed within the bilateral frontal and parietal lobes and left thalamus. Compared with tcVNS, sham elicited greater activations (p < .005) in the bilateral frontal lobe, left precentral gyrus, precuneus, and thalamus, and right temporal and parietal lobes, hippocampus, insula, and posterior cingulate. Greater (p < .005) deactivations were observed with sham in the right temporal lobe, posterior cingulate, hippocampus, left anterior cingulate, and bilateral cerebellum.
Conclusions: tcVNS increased anterior cingulate and hippocampus activation during trauma scripts, potentially indicating a reversal of neurobiological changes with PTSD consistent with improved autonomic control.Trial Registration: No. NCT02992899.
Conflict of interest statement
DECLARATION OF INTERESTS: Dr. Bremner reported having funding support from ElectroCore LLC. No other authors report potential conflicts of interests.
Copyright © 2021 by the American Psychosomatic Society.
Figures
Protocol timeline for the current study depicting timing of script delivery and non-invasive cervical vagal nerve (tcVNS)/sham stimulation. All scripts were delivered via headphones with stimulation initiated immediately following. Total session duration was five hours including a prolonged (90 min) rest period.
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Publication types
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- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
MeSH terms
- Brain / diagnostic imaging
- Gyrus Cinguli / diagnostic imaging
- Hippocampus / diagnostic imaging
- Humans
- Magnetic Resonance Imaging
- Stress Disorders, Post-Traumatic* / diagnostic imaging
- Stress Disorders, Post-Traumatic* / therapy
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Associated data
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Related information
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Sagittal slices presenting greater (p Figure 4:
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Sagittal slices presenting greater (p…
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- Cognitive function and brain activation before and after transcutaneous cervical vagus nerve stimulation in healthy adults: A concurrent tcVNS-fMRI study.Zhang H, Guo Z, Qu Y, Zhao Y, Yang Y, Du J, Yang C. Zhang H, et al. Front Psychol. 2022 Nov 11;13:1003411. doi: 10.3389/fpsyg.2022.1003411. eCollection 2022. Front Psychol. 2022. PMID: 36438376 Free PMC article.
- Transcutaneous cervical vagus nerve stimulation reduces behavioral and physiological manifestations of withdrawal in patients with opioid use disorder: A double-blind, randomized, sham-controlled pilot study.Gazi AH, Harrison AB, Lambert TP, Obideen M, Alavi P, Murrah N, Shallenberger L, Driggers EG, Ortega RA, Washington BP, Walton KM, Welsh JW, Vaccarino V, Shah AJ, Tang YL, Gupta R, Back SE, Inan OT, Bremner JD. Gazi AH, et al. Brain Stimul. 2022 Sep-Oct;15(5):1206-1214. doi: 10.1016/j.brs.2022.08.017. Epub 2022 Aug 27. Brain Stimul. 2022. PMID: 36041704 Free PMC article. Clinical Trial.
- Involvement of the brain-heart axis in the link between PTSD and cardiovascular disease.Seligowski AV, Webber TK, Marvar PJ, Ressler KJ, Philip NS. Seligowski AV, et al. Depress Anxiety. 2022 Oct;39(10-11):663-674. doi: 10.1002/da.23271. Epub 2022 Jun 16. Depress Anxiety. 2022. PMID: 35708302 Review.
- Robust Estimation of Respiratory Variability Uncovers Correlates of Limbic Brain Activity and Transcutaneous Cervical Vagus Nerve Stimulation in the Context of Traumatic Stress.Gazi AH, Wittbrodt MT, Harrison AB, Sundararaj S, Gurel NZ, Nye JA, Shah AJ, Vaccarino V, Bremner JD, Inan OT. Gazi AH, et al. IEEE Trans Biomed Eng. 2022 Feb;69(2):849-859. doi: 10.1109/TBME.2021.3108135. Epub 2022 Jan 20. IEEE Trans Biomed Eng. 2022. PMID: 34449355 Free PMC article. Clinical Trial.
Publication types
- Randomized Controlled Trial
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
MeSH terms
- Brain / diagnostic imaging
- Gyrus Cinguli / diagnostic imaging
- Hippocampus / diagnostic imaging
- Humans
- Magnetic Resonance Imaging
- Stress Disorders, Post-Traumatic* / diagnostic imaging
- Stress Disorders, Post-Traumatic* / therapy
- Vagus Nerve Stimulation* / methods
Associated data
- ClinicalTrials.gov/NCT02992899
Related information
Grant support
LinkOut - more resources
- Full Text Sources
- Medical
Full text links [x]
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM
Send To [x]
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
Follow NCBI
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
Sagittal slices presenting greater (p Figure 5:
Figure 5:
Sagittal slices presenting greater (p…
Figure 5:
Sagittal slices presenting greater (p
Sagittal slices presenting greater (p
Similar articles
- Non-invasive vagal nerve stimulation decreases brain activity during trauma scripts.Wittbrodt MT, Gurel NZ, Nye JA, Ladd S, Shandhi MMH, Huang M, Shah AJ, Pearce BD, Alam ZS, Rapaport MH, Murrah N, Ko YA, Haffer AA, Shallenberger LH, Vaccarino V, Inan OT, Bremner JD. Wittbrodt MT, et al. Brain Stimul. 2020 Sep-Oct;13(5):1333-1348. doi: 10.1016/j.brs.2020.07.002. Epub 2020 Jul 10. Brain Stimul. 2020. PMID: 32659483 Free PMC article. Clinical Trial.
- 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 JD, Wittbrodt MT, Gurel NZ, Shandhi MH, Gazi AH, Jiao Y, Levantsevych OM, Huang M, Beckwith J, Herring I, Murrah N, Driggers EG, Ko YA, Alkhalaf ML, Soudan M, Shallenberger L, Hankus AN, Nye JA, Park J, Woodbury A, Mehta PK, Rapaport MH, Vaccarino V, Shah AJ, Pearce BD, Inan OT. Bremner JD, et al. J Affect Disord Rep. 2021 Dec;6:100190. doi: 10.1016/j.jadr.2021.100190. Epub 2021 Jul 10. J Affect Disord Rep. 2021. PMID: 34778863 Free PMC article.
- Transcutaneous cervical vagal nerve stimulation reduces sympathetic responses to stress in posttraumatic stress disorder: A double-blind, randomized, sham controlled trial.Gurel NZ, Wittbrodt MT, Jung H, Shandhi MMH, Driggers EG, Ladd SL, Huang M, Ko YA, Shallenberger L, Beckwith J, Nye JA, Pearce BD, Vaccarino V, Shah AJ, Inan OT, Bremner JD. Gurel NZ, et al. Neurobiol Stress. 2020 Oct 20;13:100264. doi: 10.1016/j.ynstr.2020.100264. eCollection 2020 Nov. Neurobiol Stress. 2020. PMID: 33344717 Free PMC article.
- Transcutaneous vagal nerve stimulation blocks stress-induced activation of Interleukin-6 and interferon-γ in posttraumatic stress disorder: A double-blind, randomized, sham-controlled trial.Bremner JD, Gurel NZ, Jiao Y, Wittbrodt MT, Levantsevych OM, Huang M, Jung H, Shandhi MH, Beckwith J, Herring I, Rapaport MH, Murrah N, Driggers E, Ko YA, Alkhalaf ML, Soudan M, Song J, Ku BS, Shallenberger L, Hankus AN, Nye JA, Park J, Vaccarino V, Shah AJ, Inan OT, Pearce BD. Bremner JD, et al. Brain Behav Immun Health. 2020 Sep 11;9:100138. doi: 10.1016/j.bbih.2020.100138. eCollection 2020 Dec. Brain Behav Immun Health. 2020. PMID: 34589887 Free PMC article.
- Magnetic resonance imaging predictors of psychotherapy treatment response in post-traumatic stress disorder: A role for the salience network.Szeszko PR, Yehuda R. Szeszko PR, et al. Psychiatry Res. 2019 Jul;277:52-57. doi: 10.1016/j.psychres.2019.02.005. Epub 2019 Feb 2. Psychiatry Res. 2019. PMID: 30755338 Review.
Cited by
- A Prospect to Ameliorate Affective Symptoms and to Enhance Cognition in Long COVID Using Auricular Transcutaneous Vagus Nerve Stimulation.Colzato LS, Elmers J, Beste C, Hommel B. Colzato LS, et al. J Clin Med. 2023 Feb 2;12(3):1198. doi: 10.3390/jcm12031198. J Clin Med. 2023. PMID: 36769845 Free PMC article.
- Cognitive function and brain activation before and after transcutaneous cervical vagus nerve stimulation in healthy adults: A concurrent tcVNS-fMRI study.Zhang H, Guo Z, Qu Y, Zhao Y, Yang Y, Du J, Yang C. Zhang H, et al. Front Psychol. 2022 Nov 11;13:1003411. doi: 10.3389/fpsyg.2022.1003411. eCollection 2022. Front Psychol. 2022. PMID: 36438376 Free PMC article.
- Transcutaneous cervical vagus nerve stimulation reduces behavioral and physiological manifestations of withdrawal in patients with opioid use disorder: A double-blind, randomized, sham-controlled pilot study.Gazi AH, Harrison AB, Lambert TP, Obideen M, Alavi P, Murrah N, Shallenberger L, Driggers EG, Ortega RA, Washington BP, Walton KM, Welsh JW, Vaccarino V, Shah AJ, Tang YL, Gupta R, Back SE, Inan OT, Bremner JD. Gazi AH, et al. Brain Stimul. 2022 Sep-Oct;15(5):1206-1214. doi: 10.1016/j.brs.2022.08.017. Epub 2022 Aug 27. Brain Stimul. 2022. PMID: 36041704 Free PMC article. Clinical Trial.
- Involvement of the brain-heart axis in the link between PTSD and cardiovascular disease.Seligowski AV, Webber TK, Marvar PJ, Ressler KJ, Philip NS. Seligowski AV, et al. Depress Anxiety. 2022 Oct;39(10-11):663-674. doi: 10.1002/da.23271. Epub 2022 Jun 16. Depress Anxiety. 2022. PMID: 35708302 Review.
- Robust Estimation of Respiratory Variability Uncovers Correlates of Limbic Brain Activity and Transcutaneous Cervical Vagus Nerve Stimulation in the Context of Traumatic Stress.Gazi AH, Wittbrodt MT, Harrison AB, Sundararaj S, Gurel NZ, Nye JA, Shah AJ, Vaccarino V, Bremner JD, Inan OT. Gazi AH, et al. IEEE Trans Biomed Eng. 2022 Feb;69(2):849-859. doi: 10.1109/TBME.2021.3108135. Epub 2022 Jan 20. IEEE Trans Biomed Eng. 2022. PMID: 34449355 Free PMC article. Clinical Trial.
Publication types
- Randomized Controlled Trial
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
MeSH terms
- Brain / diagnostic imaging
- Gyrus Cinguli / diagnostic imaging
- Hippocampus / diagnostic imaging
- Humans
- Magnetic Resonance Imaging
- Stress Disorders, Post-Traumatic* / diagnostic imaging
- Stress Disorders, Post-Traumatic* / therapy
- Vagus Nerve Stimulation* / methods
Associated data
- ClinicalTrials.gov/NCT02992899
Related information
Grant support
LinkOut - more resources
- Full Text Sources
- Medical
Full text links [x]
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM
Send To [x]
Sagittal slices presenting greater (p
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