Skip to main content
SpringerLink
Log in
Book cover

Vagus Nerve Stimulation pp 157–184Cite as

Transcutaneous Vagal Nerve Stimulation in Trauma Spectrum Psychiatric Disorders

  • 219 Accesses

Part of the Neuromethods book series (NM,volume 205)

Abstract

Post-traumatic stress disorder (PTSD) and related trauma spectrum psychiatric disorders, including major depression, borderline personality disorder, and the dissociative disorders, are associated with considerable morbidity and loss of function. Treatment of these disorders, which include medications and psychotherapy, have limitations. New neuromodulation approaches targeting the underlying neurobiology of these disorders—including elevated inflammation, impaired autonomic nervous system activity, and alterations in brain areas that mediate emotion and the stress response—could improve the treatment and management of these patients. Vagal nerve stimulation (VNS) blocks sympathetic and inflammatory responses, and modulates brain areas involved in stress. Implantable VNS devices are approved for treatment refractory depression. New generation transcutaneous VNS devices that stimulate branches of the vagus nerve via the neck (cervical) or ear (auricular) are potentially applicable to trauma spectrum psychiatric disorders. This chapter reviews the effects of VNS on neurobiology and applications to patients with these psychiatric disorders.

Key words

  • Neuromodulation
  • Stress disorders
  • Post-traumatic stress disorder (PTSD)
  • Depression
  • Vagus nerve
  • Vagus nerve stimulation
  • Depressive disorder

This is a preview of subscription content, access via your institution.

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Bremner JD (ed) (2016) Posttraumatic stress disorder: from neurobiology to treatment, 1st edn. Wiley, Hoboken

    Google Scholar 

  2. Bremner JD (2002) Does stress damage the brain? Understanding trauma-related disorders from a mind-body perspective. W.W. Norton, New York

    Google Scholar 

  3. Bremner JD, Wittbrodt MT (2020) Stress, the brain, and trauma spectrum disorders. Int Rev Neurobiol 152:1–22. https://doi.org/10.1016/bs.irn.2020.01.004

    CrossRef  PubMed  PubMed Central  Google Scholar 

  4. Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB (1995) Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry 52(12):1048–1060

    CrossRef  CAS  PubMed  Google Scholar 

  5. Ballenger JC, Davidson JR, Lecrubier Y, Nutt DJ, Foa EB, Kessler RC et al (2000) Consensus statement on posttraumatic stress disorder from the International Consensus Group on Depression and Anxiety. J Clin Psychiatry 61:60–66

    PubMed  Google Scholar 

  6. Foa EB, Davidson JRT, Frances A, Culpepper L, Ross R, Ross D (1999) The expert consensus guideline series: treatment of posttraumatic stress disorder. J Clin Psychiatry 60:4–76

    Google Scholar 

  7. Lancaster CL, Teeters JB, Gros DF, Back SE (2016) Posttraumatic stress disorder: overview of evidence-based assessment and treatment. J Clin Med 5(11):105. https://doi.org/10.3390/jcm5110105

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hembree EA, Foa EB, Dorfan NM, Street GP, Kowalski J, Tu X (2003) Do patients drop out prematurely from exposure therapy for PTSD? J Trauma Stress 16(6):555–562

    CrossRef  PubMed  Google Scholar 

  9. Foa EB, Hembree E, Rothbaum BO (2007) Prolonged exposure therapy for PTSD: emotional processing of traumatic experiences, therapist guide. Oxford University Press, New York

    CrossRef  Google Scholar 

  10. Foa EB, Rothbaum BO (1998) Treating the trauma of rape: cognitive-behavioral therapy for PTSD. The Guilford Press, New York

    Google Scholar 

  11. Schnurr PP, Friedman MJ, Engel CC, Foa EB, Shea T, Chow BK et al (2007) Cognitive behavioral therapy for posttraumatic stress disorder in women. J Am Med Assoc 297:820–830

    CrossRef  CAS  Google Scholar 

  12. Schottenbauer MA, Glass CR, Arnkoff DB, Tendick V, Gray SH (2008) Nonresponse and dropout rates in outcome studies on PTSD: review and methodological considerations. Psychiatry 71(2):134–168

    CrossRef  PubMed  Google Scholar 

  13. Ballenger JC, Davidson JR, Lecrubier Y, Nutt DJ, Marshall RD, Nemeroff CB et al (2004) Consensus statement update on posttraumatic stress disorder from the international consensus group on depression and anxiety. J Clin Psychiatry 65(Suppl 1):55–62

    PubMed  Google Scholar 

  14. Davis L, Hamner M, Bremner JD (2016) Pharmacotherapy for PTSD: effects on PTSD symptoms and the brain. In: Bremner JD (ed) Posttraumatic stress disorder: from neurobiology to treatment. Wiley Blackwell, Hoboken, pp 389–412

    Google Scholar 

  15. Institute of Medicine of the National Academies (2014) Treatment for posttraumatic stress disorder in military and veteran populations: final assessment. National Academies of Science, Engineering and Medicine: Health and Medicine Division, Washington, D.C.

    Google Scholar 

  16. Bremner JD, Krystal JH, Southwick SM, Charney DS (1995) Functional neuroanatomical correlates of the effects of stress on memory. J Trauma Stress 8:527–554

    CrossRef  CAS  PubMed  Google Scholar 

  17. Bremner JD (2003) Functional neuroanatomical correlates of traumatic stress revisited 7 years later, this time with data. Psychopharmacol Bull 37(2):6–25

    PubMed  Google Scholar 

  18. Reinertsen E, Nemati S, Vest AN, Vaccarino V, Lampert R, Shah AJ et al (2017) Heart rate-based window segmentation improves accuracy of classifying posttraumatic stress disorder using heart rate variability measures. Physiol Meas 38(6):1061–1076. https://doi.org/10.1088/1361-6579/aa6e9c

    CrossRef  PubMed  PubMed Central  Google Scholar 

  19. Shah A, Vaccarino V (2015) Heart rate variability in the prediction of risk for posttraumatic stress disorder. JAMA Psychiatry 72(10):964–965. https://doi.org/10.1001/jamapsychiatry.2015.1394

    CrossRef  PubMed  PubMed Central  Google Scholar 

  20. Shah AJ, Lampert R, Goldberg J, Veledar E, Bremner JD, Vaccarino V (2013) Posttraumatic stress disorder and impaired autonomic modulation in male twins. Biol Psychiatry 73(11):1103–1110. https://doi.org/10.1016/j.biopsych.2013.01.019

    CrossRef  PubMed  PubMed Central  Google Scholar 

  21. Agorastos A, Hauger RL, Barkauskas DA, Lerman IR, Moeller-Bertram T, Snijders C et al (2019) Relations of combat stress and posttraumatic stress disorder to 24-h plasma and cerebrospinal fluid interleukin-6 levels and circadian rhythmicity. Psychoneuroendocrinology 100:237–245. https://doi.org/10.1016/j.psyneuen.2018.09.009

    CrossRef  CAS  PubMed  Google Scholar 

  22. Baker DG, Ekhator NN, Kasckow JW, Hill KK, Zoumakis E, Dashevsky BA et al (2001) Plasma and cerebrospinal fluid interleukin-6 concentrations in posttraumatic stress disorder. Neuroimmunomodulation 9:209–217

    CrossRef  CAS  PubMed  Google Scholar 

  23. Li X, Wilder-Smith CH, Kan ME, Lu J, Cao Y, Wong RK (2014) Combat-training stress in soldiers increases S100B, a marker of increased blood-brain-barrier permeability, and induces immune activation. Neuro Endocrinol Lett 35(1):58–63

    Google Scholar 

  24. Lindqvist D, Dhabhar FS, Mellon SH, Yehuda R, Grenon M, Flory JD et al (2017) Increased pro-inflammatory milieu in combat related PTSD – a new cohort replication study. Brain Behav Immun 59:260–264

    CrossRef  CAS  PubMed  Google Scholar 

  25. Passos CI, Vasconcelos-Moreno MP, Costa LG, Kunz M, Brietzke E, Quevedo J et al (2015) Inflammatory markers in post-traumatic stress disorder: a systematic review, meta-analysis, and meta-regression. Lancet Psychiatry 2(11):1002–1012. https://doi.org/10.1016/S2215-0366(15)00309-0

    CrossRef  PubMed  Google Scholar 

  26. von Kanel R, Begre S, Abbas CC, Saner H, Gander ML, Schmid JP (2010) Inflammatory biomarkers in patients with posttraumatic stress disorder caused by myocardial infarction and the role of depressive symptoms. Neuroimmunomodulation 17:39–46

    CrossRef  Google Scholar 

  27. Tucker P, Jeon-Slaughter H, Pfefferbaum B, Khan Q, Davis NJ (2010) Emotional and biological stress measures in Katrina survivors relocated to Oklahoma. Am J Disaster Med 5(2):113–125

    CrossRef  PubMed  Google Scholar 

  28. Vidovic A, Gotovac K, Vilibic M, Sabioncello A, Jovanovic T, Rabatic S et al (2011) Repeated assessments of endocrine- and immune-related changes in posttraumatic stress disorder. Neuroimmunomodulation 18:199–211

    CrossRef  CAS  PubMed  Google Scholar 

  29. Miller RJ, Sutherland AG, Hutchison JD, Alexander DA (2001) C-reactive protein and interleukin 6 receptor in post-traumatic stress disorder: a pilot study. Cytokine 13(4):253–255. https://doi.org/10.1006/cyto.2000.0825

    CrossRef  CAS  PubMed  Google Scholar 

  30. Guo M, Tao Liu J-CG, Jiang X-L, Chen F, Gao Y-S (2012) Study on serum cytokine levels in posttraumatic stress disorder patients. Asian Pac J Trop Med 5(4):323–325

    Google Scholar 

  31. Gill J, Vythilingam M, Page GG (2008) Low cortisol, high DHEA, and high levels of stimulated TNF-alpha, and IL-6 in women with PTSD. J Trauma Stress 21(6):530–539. https://doi.org/10.1002/jts.20372

    CrossRef  PubMed  PubMed Central  Google Scholar 

  32. Gill J, Luckenbaugh D, Charney D, Vythilingam M (2010) Sustained elevation of serum interleukin-6 and relative insensitivity to hydrocortisone differentiates posttraumatic stress disorder with and without depression. Biol Psychiatry 68(11):999–1006. https://doi.org/10.1016/j.biopsych.2010.07.033

    CrossRef  CAS  PubMed  Google Scholar 

  33. Sutherland AG, Alexander DA, Hutchison JD (2003) Disturbance of pro-inflammatory cytokines in post-traumatic psychopathology. Cytokine 24(5):219–225

    CrossRef  CAS  PubMed  Google Scholar 

  34. von Känel R, Hepp U, Kraemer B, Traber R, Keel M, Mica L et al (2007) Evidence for low-grade systemic proinflammatory activity in patients with posttraumatic stress disorder. J Psychiatr Res 41(9):744–752

    CrossRef  Google Scholar 

  35. Lindqvist D, Wolkowitz OM, Mellon S, Yehuda R, Flory JD, Henn-Haase C et al (2014) Proinflammatory milieu in combat-related PTSD is independent of depression and early life stress. Brain Behav Immun 42:81–88. https://doi.org/10.1016/j.bbi.2014.06.003

    CrossRef  PubMed  Google Scholar 

  36. Plantinga L, Bremner JD, Miller AA, Jones DP, Veledar E, Goldberg J et al (2013) Association between posttraumatic stress disorder and inflammation: a twin study. Brain Behav Immun 30:125–132. https://doi.org/10.1016/j.bbi.2013.01.081

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  37. von Kanel R, Abbas CC, Begre S, Saner H, Gander ML, Schmid JP (2010) Posttraumatic stress disorder and soluble cellular adhesion molecules at rest and in response to a trauma-specific interview in patients after myocardial infarction. Psychiatry Res 179:312–317

    CrossRef  Google Scholar 

  38. Heath NM, Chesney SA, Gerhart JI, Goldsmith RE, Luborsky JL, Stevens NR et al (2013) Interpersonal violence, PTSD, and inflammation: potential psychogenic pathways to higher C-reactive protein levels. Cytokine 63(2):172–178. https://doi.org/10.1016/j.cyto.2013.04.030

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  39. Eraly SA, Nievergelt CM, Maihofer AX, Barkauskas DA, Biswas N, Agorastos A et al (2014) Assessment of plasma C-reactive protein as a biomarker of posttraumatic stress disorder risk. JAMA Psychiatry 71(4):423–431

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  40. Eswarappa M, Neylan TC, Whooley MA, Metzler TJ, Cohen BE (2019) Inflammation as a predictor of disease course in posttraumatic stress disorder and depression: a prospective analysis from the Mind Your Heart Study. Brain Behav Immun 75:220–227

    CrossRef  PubMed  Google Scholar 

  41. Lima BB, Hammadah M, Wilmot K, Pearce BD, Shah A, Levantsevych O et al (2019) Posttraumatic Stress Disorder is associated with enhanced interleukin-6 response to mental stress in subjects with a recent myocardial infarction. Brain Behav Immun 75:26–33. https://doi.org/10.1016/j.bbi.2018.08.015

    CrossRef  CAS  PubMed  Google Scholar 

  42. Bikson M, Grossman P, Thomas C, Zannou AL, Jiang J, Adnan T et al (2016) Safety of transcranial direct current stimulation: evidence based update 2016. Brain Stimul 9(5):641–661. https://doi.org/10.1016/j.brs.2016.06.004

    CrossRef  PubMed  PubMed Central  Google Scholar 

  43. Bikson M, Unal G, Brunoni A, Loo C (2017) What psychiatrists need to know about transcranial direct current stimulation. Psychiatric Times 1–3. October 24, 2017

    Google Scholar 

  44. Tortella G, Casati R, Aparicio LVM, Mantovani A, Senço N, D’Urso G et al (2015) Transcranial direct current stimulation in psychiatric disorders. World J Psychiatr 5(1):88–102

    CrossRef  PubMed  PubMed Central  Google Scholar 

  45. Woods AJ, Antal A, Bikson M, Boggio PS, Brunoni AR, Celnik P et al (2016) A technical guide to tDCS, and related non-invasive brain stimulation tools. Clin Neurophysiol 127:1031–1048. https://doi.org/10.1016/j.clinph.2015.11.012

    CrossRef  CAS  PubMed  Google Scholar 

  46. Schachter SC, Saper CB (1998) Vagus nerve stimulation. Epilepsia 39:677–686

    CrossRef  CAS  PubMed  Google Scholar 

  47. Merrill DR, Bikson M, Jefferys JG (2005) Electrical stimulation of excitable tissue: design of efficacious and safe protocols. J Neurosci Methods 141(2):171–198. https://doi.org/10.1016/j.jneumeth.2004.10.020

    CrossRef  PubMed  Google Scholar 

  48. Deng ZD, McClintock SM, Oey NE, Luber B, Lisanby SH (2015) Neuromodulation for mood and memory: from the engineering bench to the patient bedside. Curr Opin Neurobiol 30:38–43. https://doi.org/10.1016/j.conb.2014.08.015

    CrossRef  CAS  PubMed  Google Scholar 

  49. Kenney-Jung DL, Blacker CJ, Camsari DD, Lee JC, Lewis CP (2019) Transcranial direct current stimulation: mechanisms and psychiatric applications. Child Adolesc Psychiatr Clin N Am 28(1):53–60. https://doi.org/10.1016/j.chc.2018.07.008

    CrossRef  PubMed  Google Scholar 

  50. Krames E, Peckham PH, Rezai A, editors. (2018) Neuromodulation: comprehensive textbook of principles, technologies, and therapies, 2nd edn. Academic Press (an imprint of Elsevier), London

    Google Scholar 

  51. Peterchev AV, Wagner TA, Miranda PC, Nitsche MA, Paulus W, Lisanby SH et al (2012) Fundamentals of transcranial electric and magnetic stimulation dose: definition, selection, and reporting practices. Brain Stimul 5(4):435–453

    CrossRef  PubMed  Google Scholar 

  52. Bikson M, Brunoni AR, Charvet LE, Clark VP, Cohen LG, Deng ZD et al (2018) Rigor and reproducibility in research with transcranial electrical stimulation: An NIMH-sponsored workshop. Brain Stimul 11(3):465–480. https://doi.org/10.1016/j.brs.2017.12.008

    CrossRef  PubMed  Google Scholar 

  53. Truong DQ, Bikson M (2018) Physics of transcranial Direct Current Stimulation devices and their history. J ECT 34(3):137–143. https://doi.org/10.1097/yct.0000000000000531

    CrossRef  PubMed  Google Scholar 

  54. McGirr A, Berlim MT (2018) Clinical usefulness of therapeutic neuromodulation for major depression: a systematic meta-review of recent meta-analyses. Psychiatr Clin North Am 41(3):485–503. https://doi.org/10.1016/j.psc.2018.04.009

    CrossRef  PubMed  Google Scholar 

  55. Ben-Menachem E, Hellström K, Waldton C, Augustinsson LE (1999) Evaluation of refractory epilepsy treated with vagus nerve stimulation for up to 5 years. Neurology 52:1265–1267

    CrossRef  CAS  PubMed  Google Scholar 

  56. Ben-Menachem E, Mañon-Espaillat R, Ristanovic R, Wilder BJ, Stefan H, Mirza W et al (1994) Vagus nerve stimulation for treatment of partial seizures: 1. A controlled study of effect on seizures. Epilepsia 35(3):616–626

    CrossRef  CAS  PubMed  Google Scholar 

  57. George R, Salinsky M, Kuzniecky R, Rosenfeld W, Bergen D, Tarver WB et al (1994) Vagus nerve stimulation for treatment of partial seizures: 3. Long-term follow-up on the first 67 patients exiting a controlled study. Epilepsia 35(3):637–643

    CrossRef  CAS  PubMed  Google Scholar 

  58. Handforth A, DeGiorgio CM, Schachter SC, Uthman BM, Naritoku DK, Tecoma ES et al (1998) Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial. Neurology 51(1):48–55

    CrossRef  CAS  PubMed  Google Scholar 

  59. Salinsky MC, Uthman BM, Ristanovic RK, Wernicke JF, Tarver WB (1999) Vagus nerve stimulation for the treatment of medically intractable seizures. Results of a 1-year open-extension trial. The Vagus Nerve Stimulation Study Group. Arch Neurol 53(11):1176–1180

    CrossRef  Google Scholar 

  60. The Vagus Nerve Stimulation Study Group (1995) A randomized controlled trial of chronic vagus nerve stimulation for treatment of medically intractable seizures. Neurology 45(2):224–230

    CrossRef  Google Scholar 

  61. Berry SM, Broglio K, Bunker M, Jayewardene A, Olin B, Rush AJ (2013) A patient-level meta-analysis of studies evaluating vagus nerve stimulation therapy for treatment-resistant depression. Med Devices (Auckl) 6:17–35

    PubMed  Google Scholar 

  62. Brunoni AR, Moffa AH, Fregni F, Palm U, Padberg F, Blumberger DM et al (2016) Transcranial direct current stimulation for acute major depressive episodes: meta-analysis of individual patient data. Br J Psychiatry 208(6):522–531

    CrossRef  PubMed  PubMed Central  Google Scholar 

  63. Brunoni AR, Moffa AH, Sampaio-Junior B, Borrione L, Moreno ML, Fernandes RA et al (2017) Trial of electrical Direct-Current Therapy versus escitalopram for depression. N Engl J Med 376(26):2523–2533

    CrossRef  CAS  PubMed  Google Scholar 

  64. Brunoni AR, Valiengo L, Baccaro A, Zanão TA, de Oliveira JF, Goulart A et al (2013) The sertraline versus electrical current therapy for treating depression clinical study: results from a factorial, randomized, controlled trial. JAMA Psychiatry 70(4):383–390

    CrossRef  CAS  PubMed  Google Scholar 

  65. Dell-Osso B, Oldani L, Palazzo MC, Balossi I, Ciabatti M, Altamura AC (2013) Vagus nerve stimulation in treatment-resistant depression: acute and follow-up results of an Italian case series. J ECT 29(1):41–44

    CrossRef  PubMed  Google Scholar 

  66. George MS, Rush AJ, Marangell LB, Sackeim HA, Brannan SK, Davis SM et al (2005) A one-year comparison of Vagus Nerve Stimulation with treatment as usual for treatment-resistant depression. Biol Psychiatry 58:364–373

    CrossRef  PubMed  Google Scholar 

  67. George MS, Rush AJ, Sackeim HA, Marangell L (2003) Vagus Nerve Stimulation (VNS): utility in neuropsychiatric disorders. Int J Neuropsychopharmacol 6:73–83

    CrossRef  PubMed  Google Scholar 

  68. Marangell LB, Rush AJ, George MS, Sackeim HA, Johnson CR, Husain MM et al (2002) Vagus Nerve Stimulation (VNS) for major depressive episodes: longer-term outcome. Biol Psychiatry 51(4):280–287

    CrossRef  PubMed  Google Scholar 

  69. Rush AJ, George MS, Sackeim HA, Marangell LB, Husain M, Giller C et al (2000) Vagus Nerve Stimulation (VNS) for treatment-resistant depression: a multicenter study. Biol Psychiatry 47(4):276–286

    CrossRef  CAS  PubMed  Google Scholar 

  70. Rush AJ, Marangell LB, Sackeim HA, George MS, Brannan SK, Davis SM et al (2005) Vagus Nerve Stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Biol Psychiatry 58:347–354

    CrossRef  PubMed  Google Scholar 

  71. Rush AJ, Sackheim HA, Marangell LB, George MS, Brannan SK, Davis SM et al (2005) Effects of 12 months of Vagus Nerve Stimulation in treatment-resistant depression: a naturalistic study. Biol Psychiatry 58(5):355–363

    CrossRef  PubMed  Google Scholar 

  72. Sackeim HA, Brannan SK, Rush AJ, George MS, Marangell LB, Allen J (2007) Durability of antidepressant response to vagus nerve stimulation (VNS). Int J Neuropsychopharmacol 10:817–826

    CrossRef  CAS  PubMed  Google Scholar 

  73. Sackeim HA, Keilp JG, Rush AJ, George MS, Marangell LB, Dormer JS et al (2001) The effects of vagus nerve stimulation on cognitive performance in patients with treatment-resistant depression. Neuropsychiatry Neuropsychol Behav Neurol 14(1):53–62

    CAS  PubMed  Google Scholar 

  74. Sackeim HA, Rush AJ, George MS, Marangell LB, Husain MM, Nahas Z et al (2001) Vagus nerve stimulation (VNS) for treatment-resistant depression: efficacy, side effects, and predictors of outcome. Neuropsychopharmacology 25(5):713–728

    CrossRef  CAS  PubMed  Google Scholar 

  75. Aaronson ST, Sears P, Ruvuna F, Bunker M, Conway CR, Dougherty DD et al (2017) A five-year observational study of patients with treatment-resistant depression treated with VNS therapy or treatment-as-usual: comparison of response, remission, and suicidality. Am J Psychiatry 174(7):640–648. https://doi.org/10.1176/appi.ajp.2017.16010034

    CrossRef  PubMed  Google Scholar 

  76. George MS, Sackeim HA, Rush AJ, Marangell LB, Nahas Z, Husain MM et al (2000) Vagus nerve stimulation: a new tool for brain research and therapy. Biol Psychiatry 47:287–295

    CrossRef  CAS  PubMed  Google Scholar 

  77. Guiraud D, Andreu D, Bonnet S, Carrault G, Couderc P, Hagège A et al (2016) Vagus nerve stimulation: state of the art of stimulation and recording strategies to address autonomic function neuromodulation. J Neural Eng 13(4):041002. https://doi.org/10.1088/1741-2560/13/4/041002

    CrossRef  PubMed  Google Scholar 

  78. Schomer AC, Nearing BD, Schachter SC, Verrier RL (2014) Vagus nerve stimulation reduces cardiac electrical instability assessed by quantitative T-wave alternans analysis in patients with drug-resistant focal epilepsy. Epilepsia 55(12):1996–2002. https://doi.org/10.1111/epi.12855

    CrossRef  PubMed  Google Scholar 

  79. Agorastos A, Boel JA, Heppner PS, Hager T, Moeller-Bertram T, Haji U et al (2013) Diminished vagal activity and blunted diurnal variation of heart rate dynamics in posttraumatic stress disorder. Stress 16(3):300–310

    CrossRef  PubMed  Google Scholar 

  80. Bansal V, Ryu SY, Lopez N, Allexan S, Krzyzaniak M, Eliceiri B et al (2012) Vagal stimulation modulates inflammation through a ghrelin mediated mechanism in traumatic brain injury. Inflammation 35(1):214–220

    CrossRef  CAS  PubMed  Google Scholar 

  81. Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR et al (2000) Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405(6785):458–462. https://doi.org/10.1038/35013070

    CrossRef  CAS  PubMed  Google Scholar 

  82. Merrill CA, Jonsson MA, Minthon L, Ejnell H, C-son Silander H, Blennow K et al (2006) Vagus nerve stimulation in patients with Alzheimer’s disease: additional follow-up results of a pilot study through 1 year. J Clin Psychiatry 67(8):1171–1178

    CrossRef  CAS  PubMed  Google Scholar 

  83. Sjögren MJ, Hellstrom PT, Jonsson MA, Runnerstam M, Silander HC, Ben-Menachem E (2002) Cognition-enhancing effect of vagus nerve stimulation in patients with Alzheimer’s disease: a pilot study. J Clin Psychiatry 63(11):972–980

    CrossRef  PubMed  Google Scholar 

  84. Vonck K, Raedt R, Naulaerts J, De Vogelaere F, Thiery E, Van Roost D et al (2014) Vagus nerve stimulation. 25 years later! What do we know about the effects on cognition? Neurosci Biobehav Rev 45:63–71

    CrossRef  PubMed  Google Scholar 

  85. Bremner JD, Rapaport MH (2017) Vagus nerve stimulation: back to the future. Am J Psychiatry 174(7):609–610. https://doi.org/10.1176/appi.ajp.2017.17040422

    CrossRef  PubMed  PubMed Central  Google Scholar 

  86. Feldman RL, Dunner DL, Muller JS, Stone DA (2013) Medicare patient experience with vagus nerve stimulation for treatment-resistant depression. J Med Econ 16(1):63–74. https://doi.org/10.3111/13696998.2012.724745

    CrossRef  Google Scholar 

  87. Milev RV, Giacobbe P, Kennedy SH, Blumberger DM, Daskalakis ZJ, Downar J et al (2016) Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 4. Neurostimulation treatments. Can J Psychiatr 61(9):561–575

    CrossRef  Google Scholar 

  88. Rubenstein Engel E, Blake J, Liebler E (2015) Non-invasive vagus nerve stimulator (gammaCore®) was not associated with meaningful cardiovascular adverse effects (P1.292). Neurology 84(14 Supplement):P1.292

    Google Scholar 

  89. Yoo PB, Lubock NB, Hincapie JG, Ruble SB, Hamann JJ, Grill WM (2013) High-resolution measurement of electrically-evoked vagus nerve activity in the anesthetized dog. J Neural Eng 10(2):026003. https://doi.org/10.1088/1741-2560/10/2/026003

    CrossRef  PubMed  Google Scholar 

  90. Polak T, Markulin F, Ehlis A-C, Langer JBM, Ringel TM, Fallgatter AJ (2009) Far field potentials from brain stem after transcutaneous vagus nerve stimulation: optimization of stimulation and recording parameters. J Neural Transm 116(10):1237–1242. https://doi.org/10.1007/s00702-009-0282-1

    CrossRef  PubMed  Google Scholar 

  91. Gaul C, Magis D, Liebler EJ, Straube A (2017) Effects of non-invasive vagus nerve stimulation on attack frequency over time and expanded response rates in patients with chronic cluster headache: a post hoc analysis of the randomized, controlled PREVA study. J Headache Pain 18(22):1–7

    Google Scholar 

  92. Gaul C, Diener HC, Silver N, Magis D, Reuter U, Andersson A et al (2016) Non-invasive vagus nerve stimulation for PREVention and Acute treatment of chronic cluster headache (PREVA): a randomised controlled study. Cephalalgia 36(6):534–546. https://doi.org/10.1177/0333102415607070

    CrossRef  PubMed  Google Scholar 

  93. Gurel NZ, Mobashir HS, Bremner JD, Vaccarino V, Ladd SL, Shah A, et al. (2018) Toward closed-loop transcutaneous vagus nerve stimulation using peripheral cardiovascular physiological biomarkers: a proof-of-concept study. IEEE: Body Sensor Networks (BSN) 78–81. https://doi.org/10.1109/BSN.2018.8329663

  94. Gurel NZ, Huang M, Wittbrodt MT, Jung H, Ladd SL, Shandhi MH et al (2020) Quantifying acute physiological biomarkers of transcutaneous cervical vagal nerve stimulation in the context of psychological stress. Brain Stimul 13(1):47–59. https://doi.org/10.1016/j.brs.2019.08.002

    CrossRef  PubMed  Google Scholar 

  95. Bremner JD, Gurel N, Wittbrodt M, Nye J, Alam Z, Herring I et al (2019) Non-invasive vagal nerve stimulation paired with stress exposure in posttraumatic stress disorder (PTSD). Brain Stimul 12(2):438

    CrossRef  Google Scholar 

  96. Wittbrodt MT, Gurel NZ, Nye JA, Ladd S, Shandhi MMH, Huang M et al (2020) Non-invasive vagal nerve stimulation decreases brain activity during trauma scripts. Brain Stimul 13:1333. https://doi.org/10.1016/j.brs.2020.07.002

    CrossRef  PubMed  PubMed Central  Google Scholar 

  97. Gurel NZ, Gazi AH, Scott KL, Wittbrodt MT, Shah AJ, Vaccarino V et al (2020) Timing considerations for noninvasive Vagal Nerve Stimulation in clinical studies. AMIA Ann Symp Proc 2019:1061–1070. https://doi.org/10.1016/j.jpsychores.2020.110110

    CrossRef  Google Scholar 

  98. Gurel NZ, Wittbrodt WT, Jung H, Ladd SL, Shah AJ, Vaccarino V et al (2020) Automatic detection of target engagement in transcutaneous cervical Vagal Nerve Stimulation for traumatic stress triggers. IEEE J Biomed Health Inform 24(7):1917–1925. https://doi.org/10.1109/JBHI.2020.2981116

    CrossRef  PubMed  PubMed Central  Google Scholar 

  99. Li W, Olshansky B (2011) Inflammatory cytokines and nitric oxide in heart failure and potential modulation by vagus nerve stimulation. Heart Fail Rev 16(2):137–145

    CrossRef  CAS  PubMed  Google Scholar 

  100. Das UN (2011) Can vagus nerve stimulation halt or ameliorate rheumatoid arthritis and lupus? Lipids Health Dis 10:19

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  101. Brock C, Brock B, Aziz Q, Møller HJ, Pfeiffer Jensen M, Drewes AM et al (2017) Transcutaneous cervical vagal nerve stimulation modulates cardiac vagal tone and tumor necrosis factor-alpha. Neurogastroenterol Motil 29(5):1–4. https://doi.org/10.1111/nmo.12999

    CrossRef  CAS  Google Scholar 

  102. LeDoux JL (1993) In search of systems and synapses. Ann N Y Acad Sci 702:149–157

    CrossRef  CAS  PubMed  Google Scholar 

  103. Rosen JB, Davis M (1988) Enhancement of acoustic startle by electrical stimulation of the amygdala. Behav Neurosci 102:195–202

    CrossRef  CAS  PubMed  Google Scholar 

  104. Morgan CA, LeDoux JE (1995) Differential contribution of dorsal and ventral medial prefrontal cortex to the acquisition and extinction of conditioned fear in rats. Behav Neurosci 109(4):681–688

    CrossRef  CAS  PubMed  Google Scholar 

  105. Morgan CA, Romanski LM, LeDoux JE (1993) Extinction of emotional learning: contribution of medial prefrontal cortex. Neurosci Lett 163:109–113

    CrossRef  CAS  PubMed  Google Scholar 

  106. Quirk GJ, Garcia R, Gonzalez-Lima F (2006) Prefrontal mechanisms in extinction of conditioned fear. Biol Psychiatry 60(4):337–343

    CrossRef  PubMed  Google Scholar 

  107. Phillips RG, LeDoux JE (1992) Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav Neurosci 106:274–285

    CrossRef  CAS  PubMed  Google Scholar 

  108. Hardy SG (1995) Medullary projections to the vagus nerve and posterolateral hypothalamus. Anat Rec 242(2):251–258. https://doi.org/10.1002/ar.1092420215

    CrossRef  CAS  PubMed  Google Scholar 

  109. Nagai M, Hoshide S, Kario K (2010) The insular cortex and cardiovascular system: a new insight into the brain-heart axis. J Am Soc Hypertens 4(4):174–182. https://doi.org/10.1016/j.jash.2010.05.001

    CrossRef  PubMed  Google Scholar 

  110. Palminteri S, Justo D, Jauffret C, Pavlicek B, Dauta A, Delmaire C et al (2012) Critical roles for anterior insula and dorsal striatum in punishment-based avoidance learning. Neuron 76(5):998–1009. S0896-6273(12)00937-3 [pii]. https://doi.org/10.1016/j.neuron.2012.10.017

    CrossRef  CAS  PubMed  Google Scholar 

  111. Nagai M, Kishi K, Kato S (2007) Insular cortex and neuropsychiatric disorders: a review of recent literature. Eur Psychiatry 22(6):387–394

    CrossRef  CAS  PubMed  Google Scholar 

  112. Wen J, Desai NS, Jeffery D, Aygun N, Blitz A (2018) High-resolution isotropic three-dimensional MR imaging of the extraforaminal segments of the cranial nerves. Magn Reson Imaging Clin N Am 26:101–119. https://doi.org/10.1016/j.mric.2017.08.007

    CrossRef  PubMed  Google Scholar 

  113. Manta S, Dong J, Debonnel G, Blier P (2009) Enhancement of the function of rat serotonin and norepinephrine neurons by sustained vagus nerve stimulation. J Psychiatr Neurosci 34:272–280

    Google Scholar 

  114. Hassert DL, Miyashita T, Williams CL (2004) The effects of peripheral vagal nerve stimulation at a memory-modulating intensity on norepinephrine output in the basolateral amygdala. Behav Neurosci 118(1):79–88. https://doi.org/10.1037/0735-7044.118.1.79

    CrossRef  CAS  PubMed  Google Scholar 

  115. Roosevelt RW, Smith DC, Clough RW, Jensen RA, Browning RA (2006) Increased extracellular concentrations of norepinephrine in cortex and hippocampus following vagus nerve stimulation in the rat. Brain 1119(1):124–132

    CAS  Google Scholar 

  116. Hulsey DR, Riley JR, Loerwald KW, Rennaker RL, Kilgard MP, Hays SA (2017) Parametric characterization of neural activity in the locus coeruleus in response to vagus nerve stimulation. Neurology 289:21–30. https://doi.org/10.1016/j.expneurol.2016.12.005

    CrossRef  Google Scholar 

  117. Manta S, Dong J, Debonnel G, Blier P (2009) Optimization of vagus nerve stimulation parameters using the firing activity of serotonin neurons in the rat dorsal raphe. Eur Neuropsychopharmacol 19:250–255

    CrossRef  CAS  PubMed  Google Scholar 

  118. Manta S, El Mansari M, Debonnel G, Blier P (2013) Electrophysiological and neurochemical effects of long-term vagus nerve stimulation on the rat monoaminergic systems. Int J Neuropsychopharmacol 16:459–470. https://doi.org/10.1017/S1461145712000387

    CrossRef  CAS  PubMed  Google Scholar 

  119. McGaugh JL (1985) Peripheral and central adrenergic influences on brain systems involved in the modulation of memory storage. Ann N Y Acad Sci 444:150–161

    CrossRef  CAS  PubMed  Google Scholar 

  120. Dorr AE, Debonnel G (2006) Effect of vagus nerve stimulation on serotonergic and noradrenergic transmission. J Pharmacol Exp Ther 318(2):89–898. https://doi.org/10.1124/jpet.106.104166

    CrossRef  CAS  Google Scholar 

  121. Nichols JA, Nichols AR, Smirnakis SM, Engineer ND, Kilgard MP, Atzoni M (2011) Vagus nerve stimulation modulates cortical synchrony and excitability through the activation of muscarinic receptors. Neuroscience 189:207–214. https://doi.org/10.1016/j.neuroscience.2011.05.024

    CrossRef  CAS  PubMed  Google Scholar 

  122. Perez SM, Carreno FR, Frazer A, Lodge DJ (2014) Vagal nerve stimulation reverses aberrant dopamine system function in the methylazoxymethanol acetate rodent model of schizophrenia. J Neurosci 34(2):9261–9267

    CrossRef  PubMed  PubMed Central  Google Scholar 

  123. Hammond EJ, Uthman BM, Wilder BJ, Ben-Menachem E, Hamberger A, Hedner T et al (1992) Neurochemical effects of vagus nerve stimulation in humans. Brain Res 583(1–2):300–303

    CrossRef  CAS  PubMed  Google Scholar 

  124. Clancy JA, Mary DA, Witte KK, Greenwood JP, Deuchars SA, Deuchars J (2014) Non-invasive vagus nerve stimulation in healthy humans reduces sympathetic nerve activity. Brain Stimul 7:871–877. https://doi.org/10.1016/j.brs.2014.07.031

    CrossRef  PubMed  Google Scholar 

  125. Thayer JF, Lane RD (2007) The role of vagal function in the risk for cardiovascular disease and mortality. Biol Psychiatry 74:224–242

    CrossRef  Google Scholar 

  126. Weber CS, Thayer JF, Rudat M, Wirtz PH, Zimmermann-Viehoff F, Thomas A et al (2010) Low vagal tone is associated with impaired post stress recovery of cardiovascular, endocrine, and immune markers. Eur J Appl Physiol 109(2):201–211. https://doi.org/10.1007/s00421-009-1341-x

    CrossRef  PubMed  Google Scholar 

  127. Pagani M, Lombardi F, Guzzetti S, Rimoldi O, Furlan R, Pizzinelli P et al (1986) Power spectral analysis of heart rate and arterial pressure variability as a marker of sympatho-vagal interaction in man and conscious dog. Circ Res 59:178–193

    CrossRef  CAS  PubMed  Google Scholar 

  128. Bremner JD, Krystal JH, Southwick SM, Charney DS (1996) Noradrenergic mechanisms in stress and anxiety: I. preclinical studies. Synapse 23:28–38

    CrossRef  CAS  PubMed  Google Scholar 

  129. Bremner JD, Krystal JH, Southwick SM, Charney DS (1996) Noradrenergic mechanisms in stress and anxiety: II. Clinical studies. Synapse 23:39–51

    CrossRef  CAS  PubMed  Google Scholar 

  130. Southwick SM, Krystal JH, Bremner JD, Morgan CA, Nicolaou A, Nagy LM et al (1997) Noradrenergic and serotonergic function in posttraumatic stress disorder. Arch Gen Psychiatry 54:749–758

    CrossRef  CAS  PubMed  Google Scholar 

  131. Bremner JD, Pearce B (2016) Neurotransmitter, neurohormonal, and neuropeptidal function in stress and PTSD. In: Bremner JD (ed) Posttraumatic stress disorder: from neurobiology to treatment. Wiley-Blackwell, Hoboken, pp 181–232

    CrossRef  Google Scholar 

  132. Corsi-Zuelli FMG, Brognara F, Quirino GFS, Hiroki CH, Sobrano Fais R, Del-Ben CM et al (2017) Neuroimmune interactions in schizophrenia: focus on vagus nerve stimulation and activation of the alpha-7 nicotinic acetylcholine receptor. Front Immunol 8. https://doi.org/10.3389/fimmu.2017.00618

  133. Cunningham JT, Mifflin SW, Gould GG, Frazer A (2008) Induction of c-Fos and delta-FosB immunoreactivity in rat brain by vagal nerve stimulation. Neuropsychopharmacology 33:1884–1895

    CrossRef  CAS  PubMed  Google Scholar 

  134. De Herdt V, Bogaert S, Bracke KR, Raedt R, De Vos M, Vonck K et al (2009) Effects of vagus nerve stimulation on pro- and anti-inflammatory cytokine induction in patients with refractory epilepsy. J Neuroimmunol 214(1–2):104–108

    CrossRef  PubMed  Google Scholar 

  135. Lerman I, Hauger R, Sorkin L, Proudfoot J, Davis B, Huang A et al (2016) Noninvasive transcutaneous vagus nerve stimulation decreases whole blood culture-derived cytokines and chemokines: a randomized, blinded, healthy control pilot trial. Neuromodulation 19(3):283–290. https://doi.org/10.1111/ner.12398

    CrossRef  PubMed  Google Scholar 

  136. Majoie HJM, Rijkers K, Berfelo MW, Hulsman JARJ, Myint A, Schwarz M et al (2011) Vagus nerve stimulation in refractory epilepsy: effects on pro-and anti-inflammatory cytokines in peripheral blood. Neuroimmunomodulation 18(1):52–56

    CrossRef  CAS  PubMed  Google Scholar 

  137. Marsland AL, Walsh C, Lockwood K, John-Henderson NA (2017) The effects of acute psychological stress on circulating and stimulated inflammatory markers: a systematic review and meta-analysis. Brain Behav Immun 64:208–219

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  138. Steptoe A, Hamer M, Chida Y (2007) The effects of acute psychological stress on circulating inflammatory factors in humans: a review and meta-analysis. Brain Behav Immun 21:901–912

    CrossRef  CAS  PubMed  Google Scholar 

  139. Sugama S, Conti B (2008) Interleukin-18 and stress. Brain Res Rev 58(1):85–95

    CrossRef  CAS  PubMed  Google Scholar 

  140. Huston JM, Gallowitsch-Puerta M, Ochani M, Ochani K, Yuan R, Rosas-Ballina M et al (2007) Transcutaneous vagus nerve stimulation reduces serum high mobility group box 1 levels and improves survival in murine sepsis. Crit Care Med 35(12):2762–2768

    PubMed  Google Scholar 

  141. Wang X-W, Karki A, Du D-Y, Zhao X-J, Xiang X-Y, Lu Z-Q (2015) Plasma levels of high mobility group box 1 increase in patients with posttraumatic stress disorder after severe blunt chest trauma: a prospective cohort study. J Surg Res 193(1):308–315

    CrossRef  CAS  PubMed  Google Scholar 

  142. Nizri E, Brenner T (2013) Modulation of inflammatory pathways by the immune cholinergic system. Amino Acids 45(1):73–85

    CrossRef  CAS  PubMed  Google Scholar 

  143. Griffin GD, Charron D, Al-Daccak R (2014) Post-traumatic stress disorder: revisiting adrenergics, glucocorticoids, immune system effects and homeostasis. Clin Transl Immunol 3(11):e27

    CrossRef  Google Scholar 

  144. Zhou J, Nagarkatti P, Zhong Y, Ginsberg JP, Singh NP, Zhang J et al (2014) Dysregulation in microRNA expression is associated with alterations in immune functions in combat veterans with post-traumatic stress disorder. PLoS One 9(4):e94075

    Google Scholar 

  145. Pearce BD (2001) Neuroendocrine-immune interactions during viral infections. Adv Virus Res 56:465–509. https://doi.org/10.1002/9781118356142.ch9

    CrossRef  Google Scholar 

  146. Olofsson PS, Levine YA, Caravaca A, Chavan SS, Pavlov VA, Faltys M et al (2015) Single-pulse and unidirectional electrical activation of the cervical vagus nerve reduces tumor necrosis factor in endotoxemia. Bioelectron Med 2:37–42

    CrossRef  Google Scholar 

  147. Bremner JD, Vermetten E (2012) The hippocampus and post-traumatic stress disorders. In: Bartsch T (ed) The clinical neurobiology of the hippocampus: an integrative view. Oxford University Press, pp 262–272

    CrossRef  Google Scholar 

  148. Das S, Basu A (2008) Inflammation: a new candidate in modulating adult neurogenesis. J Neurosci Res 86(6):1199–1208. https://doi.org/10.1002/jnr.21585

    CrossRef  CAS  PubMed  Google Scholar 

  149. Myint AM (2012) Kynurenines: from the perspective of major psychiatric disorders. FEBS J 279(8):1375–1385

    CrossRef  CAS  PubMed  Google Scholar 

  150. Klinkenberg S, van den Borne C, Aalbers M, Verschuure P, Kessels A, Leenen L et al (2014) The effects of vagus nerve stimulation on tryptophan metabolites in children with intractable epilepsy. Epilepsy Behav 37:133–138

    CrossRef  CAS  PubMed  Google Scholar 

  151. Yehuda R (2002) Post-traumatic stress disorder. N Engl J Med 346:108–114

    CrossRef  CAS  PubMed  Google Scholar 

  152. Vermetten E (2008) Epilogue: neuroendocrinology of PTSD. Prog Brain Res 167:311–313. https://doi.org/10.1016/s0079-6123(07)67030-7

    CrossRef  PubMed  Google Scholar 

  153. de Kloet CS, Vermetten E, Geuze E, Kavelaars A, Heijnen CJ, Westenberg HG (2006) Assessment of HPA-axis function in posttraumatic stress disorder: pharmacological and non-pharmacological challenge tests, a review. J Psychiatr Res 40(6):550–567. https://doi.org/10.1016/j.jpsychires.2005.08.002

    CrossRef  PubMed  Google Scholar 

  154. van Zuiden M, Kavelaars A, Geuze E, Olff M, Heijnen CJ (2013) Predicting PTSD: pre-existing vulnerabilities in glucocorticoid-signaling and implications for preventive interventions. Brain Behav Immun 30:12–21

    CrossRef  PubMed  Google Scholar 

  155. Hosoi T, Okuma Y, Nomura Y (2000) Electrical stimulation of afferent vagus nerve induces IL-1β expression in the brain and activates HPA axis. Am J Physiol Regul Integr Comp Physiol 279(1):R141–R1R7

    CrossRef  CAS  PubMed  Google Scholar 

  156. Watkins LR, Maier SF, Goehler LE (1995) Cytokine-to-brain communication: a review and analysis of alternative mechanisms. Life Sci 57:1011–1026

    CrossRef  CAS  PubMed  Google Scholar 

  157. Thrivikraman KV, Zejnelovic F, Bonsall RW, Owens MJ (2013) Neuroendocrine homeostasis after vagus nerve stimulation in rats. Psychoneuroendocrinology 38(7):1067–1077. https://doi.org/10.1016/j.psyneuen.2012.10.015

    CrossRef  CAS  PubMed  Google Scholar 

  158. Zoladz PR, Diamond DM (2013) Current status on behavioral and biological markers of PTSD: a search for clarity in a conflicting literature. Neurosci Biobehav Rev 37(5):860–895

    CrossRef  PubMed  Google Scholar 

  159. Groves DA, Brown VJ (2005) Vagal nerve stimulation: a review of its applications and potential mechanisms that mediate its clinical effects. Neurosci Biobehav Rev 29:493–500

    CrossRef  PubMed  Google Scholar 

  160. Hays SA, Rennaker RL, Kilgard MP (2013) Targeting plasticity with vagus nerve stimulation to treat neurological disease. Prog Brain Res 207:275–299

    CrossRef  PubMed  PubMed Central  Google Scholar 

  161. Player MJ, Taylor JL, Weickert CS, Alonzo A, Sachdev PS, Martin D et al (2014) Increase in PAS-induced neuroplasticity after a treatment course of transcranial direct current stimulation for depression. J Affect Disord 167:140–147

    CrossRef  PubMed  Google Scholar 

  162. Marin MF, Camprodon JA, Dougherty DD, Milad MR (2014) Device-based brain stimulation to augment fear extinction: implications for PTSD treatment and beyond. Depress Anxiety 31(4):269–278

    CrossRef  PubMed  Google Scholar 

  163. McLaughlin KA, Alves S, Sheridan MA (2014) Vagal regulation and internalizing psychopathology among adolescents exposed to childhood adversity. Dev Psychobiol 56(5):1036–1051

    CrossRef  PubMed  Google Scholar 

  164. Noble IJ, Gonzalez IJ, Meruva VB, Callahan KA, Belfort BD, Ramanathan KR et al (2017) Effects of vagus nerve stimulation on extinction of conditioned fear and post-traumatic stress disorder symptoms in rats. Transl Psychiatry 7(e1217):1–8

    Google Scholar 

  165. Pena DF, Childs JE, Willett S, Vital A, McIntyre CK, Kroener S (2014) Vagus nerve stimulation enhances extinction of conditioned fear and modulates plasticity in the pathway from the ventromedial prefrontal cortex to the amygdala. Front Behav Neurosci 8(327):1–8. https://doi.org/10.3389/fnbeh.2014.00327

    CrossRef  Google Scholar 

  166. Peña DF, Engineer ND, McIntyre CK (2013) Rapid remission of conditioned fear expression with extinction training paired with vagus nerve stimulation. Biol Psychiatry 73(11):1071–1077. https://doi.org/10.1016/j.biopsych.2012.10.021

    CrossRef  PubMed  Google Scholar 

  167. Noble LJ, Meruva VB, Hays SA, Rennaker RL, Kilgard MP, McIntyre CK (2018) Vagus nerve stimulation promotes generalization of conditioned fear extinction and reduces anxiety in rats. Brain Stimul 12(1):9–18. https://doi.org/10.1016/j.brs.2018.09.013

    CrossRef  PubMed  PubMed Central  Google Scholar 

  168. Engineer CT, Engineer ND, Riley JR, Seale JD, Kilgard MP (2015) Pairing speech sounds with vagus nerve stimulation drives stimulus-specific cortical plasticity. Brain Stimul 8(3):637–644

    CrossRef  PubMed  PubMed Central  Google Scholar 

  169. Engineer ND, Riley JR, Seale JD, Vrana WA, Shetake JA, Sudanagunta SP et al (2011) Reversing pathological neural activity using targeted plasticity. Nature 470(7332):101–104

    CrossRef  PubMed  PubMed Central  Google Scholar 

  170. Kim HJ, Shim H-J, Kwak MY, An Y-H, Kim DH, Kim YJ et al (2015) Feasibility and safety of transcutaneous vagus nerve stimulation paired with notched music therapy for the treatment of chronic tinnitus. J Audiol Otol 18(3):159–167

    Google Scholar 

  171. Li T-T, Wang Z-J, Yang S-B, Zhu J-H, Zhang S-Z, Cai S-J et al (2015) Transcutaneous electrical stimulation at auricular acupoints innervated by auricular branch of vagus nerve pairing tone for tinnitus: study protocol for a randomized controlled clinical trial. Trials 16(101):1–9

    Google Scholar 

  172. Liu A, Zhao F-B, Wang J, Lu YF, Tian J, Zhao Y et al (2016) Effects of vagus nerve stimulation on cognitive functioning in rats with cerebral ischemia reperfusion. J Transl Med 14(101):1–12. https://doi.org/10.1186/s12967-016-0858-0

    CrossRef  CAS  Google Scholar 

  173. Clark KB, Naritoku DK, Smith DC, Browning RA, Jensen RA (1999) Enhanced recognition memory following vagus nerve stimulation in human subjects. Nat Neurosci 2(1):94–98

    CrossRef  CAS  PubMed  Google Scholar 

  174. Suthana N, Fried I (2014) Deep brain stimulation for enhancement of learning and memory. Neuroimage 85:996–1002

    CrossRef  PubMed  Google Scholar 

  175. Chen S-P, Ayd I, Lopes de Moraisa A, Qina T, Zhenga Y, Sadeghiana H et al (2015) Vagus nerve stimulation inhibits cortical spreading depression. Cephalagia 35(6S):219–221

    Google Scholar 

  176. Ben-Menachem E, Hamberger A, Hedner T, Hammond EJ, Uthman BM, Slater J et al (1995) Effects of vagus nerve stimulation on amino acids and other metabolites in the CSF of patients with partial seizures. Epilepsy Res 20:3

    CrossRef  Google Scholar 

  177. Oshinsky ML, Murphy AL, Hekierski H, Cooper M, Simon BJ (2014) Noninvasive vagus nerve stimulation as treatment for trigeminal allodynia. Pain 155:2037–1042

    CrossRef  Google Scholar 

  178. Nestler EJ, Lüscher C (2019) The molecular basis of drug addiction: linking epigenetic to synaptic and circuit mechanisms. Neuron 102(1):48–59. https://doi.org/10.1016/j.neuron.2019.01.016

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  179. Cahill L, McGaugh JL (1998) Mechanisms of emotional arousal and lasting declarative memory. Trends Neurosci 21:294–299

    CrossRef  CAS  PubMed  Google Scholar 

  180. McGaugh JL (2000) Memory – a century of consolidation. Science 287:248–251

    CrossRef  CAS  PubMed  Google Scholar 

  181. Bremner JD, Vythilingam M, Vermetten E, Newcomer JW, Charney DS (2004) Effects of dexamethasone on declarative memory function in posttraumatic stress disorder (PTSD). Psychiatry Res 129(1):1–10

    CrossRef  CAS  PubMed  Google Scholar 

  182. Bremner JD, Vythilingam M, Vermetten E, Newcomer JW, Charney DS (2004) Effects of glucocorticoids on declarative memory function in major depression. Biol Psychiatry 55(8):811–815

    CrossRef  CAS  PubMed  Google Scholar 

  183. Cahill L, Prins B, Weber M, McGaugh JL (1994) Beta-adrenergic activation and memory for emotional events. Nature 371:702–704

    CrossRef  CAS  PubMed  Google Scholar 

  184. Southwick SM, Horner B, Morgan CA, Bremner JD, Davis M, Cahill L et al (2002) Relationship of enhanced norepinephrine activity during memory consolidation to enhanced long-term memory in humans. Am J Psychiatry 159:1420–1422

    CrossRef  PubMed  Google Scholar 

  185. Flood JF, Smith GE, Morley JE (1987) Modulation of memory processing by cholecystokinin: dependence on the vagus nerve. Science 236(4803):832–834

    CrossRef  CAS  PubMed  Google Scholar 

  186. Williams CL, Jensen RA (1993) Effects of vagotomy on leuenkephalin-induced impairments in memory storage. Physiol Behav 54(4):659–663

    CrossRef  CAS  PubMed  Google Scholar 

  187. de Quervain DJ-F, Roozendaal B, Nitsch RM, McGaugh JL, Hock C (2000) Acute cortisone administration impairs retrieval of long-term declarative memory in humans. Nat Neurosci 3(4):313–314

    CrossRef  PubMed  Google Scholar 

  188. Liang KC, Juler RG, McGaugh JL (1986) Modulating effects of post-training epinephrine on memory: involvement of the amygdala noradrenergic system. Brain Res 368:125–133

    CrossRef  CAS  PubMed  Google Scholar 

  189. Elzinga BM, Bakker A, Bremner JD (2005) Stress-induced cortisol elevations are associated with impaired delayed, but not immediate recall. Psychiatry Res 134(3):211–223

    CrossRef  CAS  PubMed  Google Scholar 

  190. Elzinga BM, Bremner JD (2002) Are the neural substrates of memory the final common pathway in posttraumatic stress disorder (PTSD)? J Affect Disord 70(1):1–17. https://doi.org/10.1016/S0165-0327(01)00351-2

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  191. Tollenaar MS, Elzinga BM, Spinhoven P, Everaerd W (2009) Immediate and prolonged effects of cortisol, but not propranolol, on memory retrieval in healthy young men. Neurobiol Learn Mem 91(1):23–31. https://doi.org/10.1016/j.nlm.2008.08.002

    CrossRef  CAS  PubMed  Google Scholar 

  192. Revesz D, Tjernstrom M, Ben-Menachem E, Thorlin T (2008) Effects of vagus nerve stimulation on rat hippocampal progenitor proliferation. Exp Neurol 214:259–265. https://doi.org/10.1016/j.expneurol.2008.08.012

    CrossRef  PubMed  Google Scholar 

  193. Zuo Y, Smith DC, Jensen RA (2007) Vagus nerve stimulation potentiates hippocampal LTP in freely-moving rats. Physiol Behav 90(4):583–589

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  194. Ura H, Sugaya Y, Ohata H, Takumi I, Sadamoto K, Shibasaki T et al (2013) Vagus nerve stimulation induced long-lasting enhancement of synaptic transmission and decreased granule cell discharge in the hippocampal dentate gyrus of urethane-anesthetized rats. Brain Res 1492:63–71. https://doi.org/10.1016/j.brainres.2012.11.024

    CrossRef  CAS  PubMed  Google Scholar 

  195. Clark KB, Krahl SE, Smith DC, Jensen RA (1995) Post-training unilateral vagal stimulation enhances retention performance in the rat. Neurobiol Learn Mem 63(3):213–216

    CrossRef  CAS  PubMed  Google Scholar 

  196. Clark KB, Smith DC, Hassert DL, Browning RA, Naritoku DK, Jensen RA (1998) Posttraining electrical stimulation of vagal afferents with concomitant vagal efferent inactivation enhances memory storage processes in the rat. Neurobiol Learn Mem 70(3):364–373

    CrossRef  CAS  PubMed  Google Scholar 

  197. Smith DC, Modglin AA, Roosevelt RW, Neese SL, Jensen RA, Browning RA et al (2005) Electrical stimulation of the vagus nerve enhances cognitive and motor recovery following moderate fluid percussion injury in the rat. J Neurotrauma 22(12):1485–1502

    CrossRef  PubMed  Google Scholar 

  198. Smith DC, Tan AA, Duke A, Neese SL, Clough RW, Browning RA et al (2006) Recovery of function after vagus nerve stimulation initiated 24h after fluid percussion brain injury. J Neurotrauma 23(10):1549–1560

    CrossRef  PubMed  Google Scholar 

  199. Shen H, Fuchino Y, Miyamoto D, Nomura H, Matsuki N (2012) Vagus nerve stimulation enhances perforant path-CA3 synaptic transmission via the activation of beta-adrenergic receptors and the locus coeruleus. Int J Neuropsychopharmacol 4:523–530. https://doi.org/10.1017/s1461145711000708

    CrossRef  Google Scholar 

  200. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S et al (2003) Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 301(5634):805–809

    CrossRef  CAS  PubMed  Google Scholar 

  201. Duman RS (2004) Depression: a case of neuronal life and death? Biol Psychiatry 56:140–145

    CrossRef  PubMed  Google Scholar 

  202. Duman RS, Heninger GR, Nestler EJ (1997) A molecular and cellular theory of depression. Arch Gen Psychiatry 54:597–606

    CrossRef  CAS  PubMed  Google Scholar 

  203. Diamond DM, Branch BJ, Fleshner M, Rose GM (1995) Effects of dehydroepiandosterone and stress on hippocampal electrophysiological plasticity. Ann N Y Acad Sci 774:304–307

    CrossRef  CAS  PubMed  Google Scholar 

  204. Duman RS, Malberg JE, Nakagawa S (2001) Regulation of adult neurogenesis by psychotropic drugs and stress. J Pharmacol Exp Ther 299:401–407

    CAS  PubMed  Google Scholar 

  205. Souza RR, Robertson NM, Pruitt DT, Gonzales PA, Hays SA, Rennaker RL et al (2019) Vagus nerve stimulation reverses the extinction impairments in a model of PTSD with prolonged and repeated trauma. Stress 22:509. https://doi.org/10.1080/10253890.2019.1602604

    CrossRef  PubMed  Google Scholar 

  206. Childs JE, DeLeon J, Nickel E, Kroener S (2016) Vagus nerve stimulation reduces cocaine seeking and alters plasticity in the extinction network. Learn Memory 24(1):35–42

    CrossRef  Google Scholar 

  207. Hays SA (2016) Enhancing rehabilitative therapies with vagus nerve stimulation. Neurotherapeutics 13(2):382–394

    CrossRef  PubMed  Google Scholar 

  208. Hays SA, Ruiz A, Bethea T, Khodaparast N, Carmel JB, Rennaker RL et al (2016) Vagus nerve stimulation during rehabilitative training enhances recovery of forelimb function after ischemic stroke in aged rats. Neurobiol Aging 43:111–118

    CrossRef  PubMed  PubMed Central  Google Scholar 

  209. Khodaparast N, Kilgard MP, Casavant R, Ruiz A, Qureshi I, Ganzer PD et al (2015) Vagus nerve stimulation during rehabilitative training improves forelimb recovery after chronic ischemic stroke in rats. Neurorehabil Neural Repair 30(7):676–684

    CrossRef  PubMed  PubMed Central  Google Scholar 

  210. Pruitt DT, Schmid AN, Kim LL, Abe CM, Trieu JL, Choua C (2016) Vagus nerve stimulation delivered with motor training enhances recovery of function after traumatic brain injury. J Neurotrauma 33:871–879

    CrossRef  PubMed  PubMed Central  Google Scholar 

  211. Li M, Zheng C, Sato T, Kawada T, Sugimachi M, Sunagawa K (2004) Vagal nerve stimulation markedly improves long-term survival after chronic heart failure in rats. Circulation 109(1):120–124

    CrossRef  PubMed  Google Scholar 

  212. Meyers R, Pearlman A, Hyman R (1974) Beneficial effects of vagal stimulation and bradycardia during experimental acute myocardial ischemia. Circulation 49:943–947

    CrossRef  Google Scholar 

  213. Kent KM, Smith ER, Redwood DR, Epstein SE (1973) Electrical stability of acutely ischemic myocardium: influences to heart rate and vagal stimulation. Circulation 47:291–298

    CrossRef  CAS  PubMed  Google Scholar 

  214. Dawson J, Pierce D, Dixit A, Kimberley TJ, Robertson M, Tarver B et al (2016) Safety, feasibility, and efficacy of vagus nerve stimulation paired with upper-limb rehabilitation after ischemic stroke. Stroke 47:143–150. https://doi.org/10.1161/STROKEAHA.115.010477

    CrossRef  PubMed  Google Scholar 

  215. Shim HJ, Kwak MY, An Y-H, Kim DH, Kim YJ, Kim HJ (2015) Feasibility and safety of transcutaneous Vagus Nerve Stimulation paired with notched music therapy for the treatment of chronic tinnitus. J Audiol Otol 19(3):159–167

    CrossRef  PubMed  PubMed Central  Google Scholar 

  216. Jacobs HIL, Riphagen JM, Razat CM, Wiese S, Sack AT (2015) Transcutaneous vagus nerve stimulation boosts associative memory in older individuals. Neurobiol Aging 36(5):1860–1867. https://doi.org/10.1016/j.neurobiolaging.2015.02.023

    CrossRef  PubMed  Google Scholar 

  217. Barbanti P, Grazzi L, Egeo G, Padovan A, Liebler E, Bussone G (2015) Non-invasive vagus nerve stimulation for acute treatment of high-frequency and chronic migraine: an open-label study. J Headache Pain 16(1):1–5. https://doi.org/10.1186/s10194-015-0542-4

    CrossRef  Google Scholar 

  218. Nesbitt AD, Marin JCA, Tomkins E, Ruttledge MH, Goadsby PJ (2013) Non-invasive vagus nerve stimulation for the treatment of cluster headache: a case series. J Headache Pain 14(1):1–. https://doi.org/10.1186/1129-2377-14-S1-P231

  219. Ben-Menachem E, Revesz D, Simon BJ, Silberstein S (2015) Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Eur J Neurol 22(9):1260–1268. https://doi.org/10.1111/ene.12629

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  220. Hays SA, Khodaparast N, Hulsey DR, Ruiz A, Sloan AM, Rennaker RL et al (2014) Vagus nerve stimulation during rehabilitative training improves functional recovery after intracerebral hemorrhage. Stroke 45(10):3097–3100

    CrossRef  PubMed  PubMed Central  Google Scholar 

  221. Rong P, Liu J, Wang L, Liu R, Fang J, Zhao J et al (2016) Effect of transcutaneous auricular vagus nerve stimulation on major depressive disorder: a nonrandomized controlled pilot study. J Affect Disord 195:172–179. https://doi.org/10.1016/j.jad.2016.02.031

    CrossRef  PubMed  PubMed Central  Google Scholar 

  222. Lamb DG, Porges EC, Lewis GF, Williamson JB (2017) Non-invasive Vagal Nerve Stimulation effects on hyperarousal and autonomic state in patients with posttraumatic stress disorder and history of mild traumatic brain injury: preliminary evidence. Front Med 4:124. https://doi.org/10.3389/fmed.2017.00124

    CrossRef  Google Scholar 

  223. Bohning DE, Lomarev MP, Denslow S, Nahas Z, Shastri A, George MS (2001) Vagus Nerve Stimulation (VNS) synchronized BOLD-fMRI. Radiology 36:470–479

    CAS  Google Scholar 

  224. Chae JH, Nahas Z, Lomarev M, Denslow S, Lorberbaum JP, Bohning DE et al (2003) A review of functional neuroimaging studies of Vagus Nerve Stimulation (VNS). J Psychiatr Res 37(6):443–455

    CrossRef  PubMed  Google Scholar 

  225. Yakunina N, Kim SS, Nam E-C (2017) Optimization of transcutaneous vagus nerve stimulation using functional MRI. Neuromodulation 20(3):290–300. https://doi.org/10.1111/ner.12541

    CrossRef  PubMed  Google Scholar 

  226. Campanella C, Bremner JD (2016) Neuroimaging of PTSD. In: Bremner JD (ed) Posttraumatic stress disorder: from neurobiology to treatment. Wiley-Blackwell, Hoboken, pp 291–320

    CrossRef  Google Scholar 

  227. Schmahl CG, McGlashan T, Bremner JD (2002) Neurobiological correlates of borderline personality disorder. Psychopharmacol Bull 36:69–87

    PubMed  Google Scholar 

  228. Vermetten E, Schmahl C, Lindner S, Loewenstein RJ, Bremner JD (2006) Hippocampal and amygdalar volumes in Dissociative Identity Disorder. Am J Psychiatry 163:1–8

    CrossRef  Google Scholar 

  229. Smith MA, Makino S, Kvetnansky R, Post RM (1995) Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNA in the hippocampus. J Neurosci 15:1768–1777

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  230. Diamond DM, Fleshner M, Ingersoll N, Rose GM (1996) Psychological stress impairs spatial working memory: relevance to electrophysiological studies of hippocampal function. Behav Neurosci 110(4):661–672

    CrossRef  CAS  PubMed  Google Scholar 

  231. Sapolsky RM, Krey L, McEwen B (1985) Prolonged glucocorticoid exposure reduces hippocampal neuron number: implications for aging. J Neurosci 5:1221–1226

    CrossRef  Google Scholar 

  232. Woolley CS, Gould E, McEwen BS (1990) Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons. Brain Res 531:225–231

    CrossRef  CAS  PubMed  Google Scholar 

  233. Nibuya M, Morinobu S, Duman RS (1995) Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci 15(11):7539–7547

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  234. Vermetten E, Vythilingam M, Southwick SM, Charney DS, Bremner JD (2003) Long-term treatment with paroxetine increases verbal declarative memory and hippocampal volume in posttraumatic stress disorder. Biol Psychiatry 54(7):693–702

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  235. LeDoux JE (1996) The emotional brain: the mysterious underpinnings of emotional life. Simon & Schuster, New York, N.Y

    Google Scholar 

  236. Quirk GJ (2002) Memory for extinction of conditioned fear is long-lasting and persists following spontaneous recovery. Learn Memory 9:402–407

    CrossRef  Google Scholar 

  237. Stein MB, Simmons AN, Feinstein JS, Paulus MP (2007) Increased amygdala and insula activation during emotion processing in anxiety-prone subjects. Am J Psychiatry 164(2):318–327

    CrossRef  PubMed  Google Scholar 

  238. Bremner JD, Randall P, Scott TM, Bronen RA, Seibyl JP, Southwick SM et al (1995) MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry 152(7):973–981

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  239. Bremner JD, Randall PR, Vermetten E, Staib L, Bronen RA, Mazure CM et al (1997) Magnetic resonance imaging-based measurement of hippocampal volume in posttraumatic stress disorder related to childhood physical and sexual abuse: a preliminary report. Biol Psychiatry 41:23–32

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  240. Gurvits TG, Shenton MR, Hokama H, Ohta H, Lasko NB, Gilbertson MB et al (1996) Magnetic resonance imaging study of hippocampal volume in chronic combat-related posttraumatic stress disorder. Biol Psychiatry 40(11):1091–1099

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  241. Stein MB, Koverola C, Hanna C, Torchia MG, McClarty B (1997) Hippocampal volume in women victimized by childhood sexual abuse. Psychol Med 27(4):951–959

    CrossRef  CAS  PubMed  Google Scholar 

  242. Bremner JD, Randall PR, Capelli S, Scott TM, McCarthy G, Charney DS (1995) Deficits in short-term memory in adult survivors of childhood abuse. Psychiatry Res 59:97–107

    CrossRef  CAS  PubMed  Google Scholar 

  243. Bremner JD, Scott TM, Delaney RC, Southwick SM, Mason JW, Johnson DR et al (1993) Deficits in short-term memory in post-traumatic stress disorder. Am J Psychiatry 150:1015–1019

    CrossRef  CAS  PubMed  Google Scholar 

  244. Shin LM, Shin PS, Heckers S, Krangel TS, Macklin ML, Orr SP et al (2004) Hippocampal function in posttraumatic stress disorder. Hippocampus 14(3):292–300

    CrossRef  PubMed  Google Scholar 

  245. Bremner JD, Vythilingam M, Vermetten E, Southwick SM, McGlashan T, Staib LH et al (2003) Neural correlates of declarative memory for emotionally valenced words in women with posttraumatic stress disorder related to early childhood sexual abuse. Biol Psychiatry 53(10):879–889. S0006322302018917 [pii]

    CrossRef  PubMed  Google Scholar 

  246. Astur RS, St Germain SA, Tolin D, Ford J, Russell D, Stevens M (2006) Hippocampus function predicts severity of post-traumatic stress disorder. Cyberpsychol Behav 9(2):234–240

    CrossRef  PubMed  Google Scholar 

  247. Bremner JD, Vythilingam M, Vermetten E, Southwick SM, McGlashan T, Nazeer A et al (2003) MRI and PET study of deficits in hippocampal structure and function in women with childhood sexual abuse and posttraumatic stress disorder (PTSD). Am J Psychiatry 160(5):924–932

    CrossRef  PubMed  Google Scholar 

  248. Schmahl CG, Vermetten E, Elzinga BM, Bremner JD (2003) Magnetic resonance imaging of hippocampal and amygdala volume in women with childhood abuse and borderline personality disorder. Psychiatry Res Neuroimaging 122:193–198

    CrossRef  Google Scholar 

  249. Bremner JD (2002) Structural changes in the brain in depression and relationship to symptom recurrence. CNS Spectr 7:129–139

    CrossRef  PubMed  Google Scholar 

  250. Teicher MH, Anderson CM, Ohashi K, Polcari A (2014) Childhood maltreatment: altered network centrality of cingulate, precuneus, temporal pole and insula. Biol Psychiatry 76(4):297–305

    CrossRef  PubMed  Google Scholar 

  251. Kasai K, Yamasue H, Gilbertson MW, Shenton ME, Rauch SL, Pitman RK (2008) Evidence for acquired pregenual anterior cingulate gray matter loss from a twin study of combat-related posttraumatic stress disorder. Biol Psychiatry 63(6):550–556. https://doi.org/10.1016/j.biopsych.2007.06.022

    CrossRef  PubMed  Google Scholar 

  252. Kitayama N, Quinn S, Bremner JD (2006) Smaller volume of anterior cingulate cortex in abuse-related posttraumatic stress disorder. J Affect Disord 90(2–3):171–174

    CrossRef  PubMed  PubMed Central  Google Scholar 

  253. Schuff N, Neylan TC, Fox-Bosetti S, Lenoci M, Samuelson KW, Studholme C et al (2008) Abnormal N-acetylaspartate in hippocampus and anterior cingulate in posttraumatic stress disorder. Psychiatry Res 162(2):147–157. S0925-4927(07)00099-6 [pii]. https://doi.org/10.1016/j.pscychresns.2007.04.011

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  254. Yamasue H, Kasai K, Iwanami A, Ohtani T, Yamada H, Abe O et al (2003) Voxel-based analysis of MRI reveals anterior cingulate gray-matter volume reduction in posttraumatic stress disorder due to terrorism. Proc Natl Acad Sci U S A 100(15):9039–9043

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  255. Chen S, Xia W, Li L, Liu J, He Z, Zhang Z et al (2006) Gray matter density reduction in the insula in fire survivors with posttraumatic stress disorder: a voxel-based morphometric study. Psychiatry Res 146(1):65–72

    CrossRef  PubMed  Google Scholar 

  256. Chen S, Li L, Xu B, Liu J (2009) Insular cortex involvement in declarative memory deficits in patients with post-traumatic stress disorder. BMC Psychiatry 9:39. https://doi.org/10.1186/1471-244x-9-39

    CrossRef  PubMed  PubMed Central  Google Scholar 

  257. Bremner JD, Staib L, Kaloupek D, Southwick SM, Soufer R, Charney DS (1999) Neural correlates of exposure to traumatic pictures and sound in Vietnam combat veterans with and without posttraumatic stress disorder: a positron emission tomography study. Biol Psychiatry 45:806–816

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  258. Britton JC, Phan KL, Taylor SF, Fig LM, Liberzon I (2005) Corticolimbic blood flow in posttraumatic stress disorder during script-driven imagery. Biol Psychiatry 57(8):832–840

    CrossRef  PubMed  Google Scholar 

  259. Shin LM, McNally RJ, Kosslyn SM, Thompson WL, Rauch SL, Alpert NM et al (1999) Regional cerebral blood flow during script-driven imagery in childhood sexual abuse-related PTSD: a PET investigation. Am J Psychiatry 156:575–584

    CrossRef  CAS  PubMed  Google Scholar 

  260. Shin LM, Kosslyn SM, McNally RJ, Alpert NM, Thompson WL, Rauch SL et al (1997) Visual imagery and perception in posttraumatic stress disorder: a positron emission tomographic investigation. Arch Gen Psychiatry 54:233–237

    CrossRef  CAS  PubMed  Google Scholar 

  261. Shin LM, Orr SP, Carson MA, Rauch SL, Macklin ML, Lasko NB et al (2004) Regional cerebral blood flow in the amygdala and medial prefrontal cortex during traumatic imagery in male and female Vietnam veterans with PTSD. Arch Gen Psychiatry 61(2):168–176

    CrossRef  PubMed  Google Scholar 

  262. Fonzo GA, Simmons AN, Thorp SR, Norman SB, Paulus MP, Stein MB (2010) Blood oxygenation level-dependent response to threat-related emotional faces in women with intimate-partner violence posttraumatic stress disorder. Biol Psychiatry 68:433–441

    CrossRef  PubMed  PubMed Central  Google Scholar 

  263. Phan KL, Britton JC, Taylor SF, Fig LM, Liberzon I (2006) Corticolimbic blood flow during nontraumatic emotional processing in posttraumatic stress disorder. Arch Gen Psychiatry 63(2):184–192

    CrossRef  PubMed  Google Scholar 

  264. Yang P, Wu MT, Hsu CC, Ker JH (2004) Evidence of early neurobiological alternations in adolescents with posttraumatic stress disorder: a functional MRI study. Neurosci Lett 370(1):13–18

    CrossRef  CAS  PubMed  Google Scholar 

  265. Shin LM, Whalen PJ, Pitman RK, Bush G, Macklin ML, Lasko NB et al (2001) An fMRI study of anterior cingulate function in posttraumatic stress disorder. Biol Psychiatry 50:932–942

    CrossRef  CAS  PubMed  Google Scholar 

  266. Hopper JW, Frewen PA, van der Kolk BA, Lanius RA (2007) Neural correlates of reexperiencing, avoidance, and dissociation in PTSD: symptom dimensions and emotion dysregulation in responses to script-driven trauma imagery. J Trauma Stress 20(5):713–725. https://doi.org/10.1002/jts.20284

    CrossRef  PubMed  Google Scholar 

  267. Hou C, Liu J, Wang K, Li L, Liang M, He Z et al (2007) Brain responses to symptom provocation and trauma-related short-term memory recall in coal mining accident survivors with acute severe PTSD. Brain Res 1144:165–174. https://doi.org/10.1016/j.brainres.2007.01.089

    CrossRef  CAS  PubMed  Google Scholar 

  268. Lanius RA, Williamson PC, Hopper J, Densmore M, Boksman K, Gupta MA et al (2003) Recall of emotional states in posttraumatic stress disorder: an fMRI investigation. Biol Psychiatry 53(3):204–210

    CrossRef  PubMed  Google Scholar 

  269. Lanius RA, Williamson PC, Densmore M, Boksman K, Gupta MA, Neufeld RW et al (2001) Neural correlates of traumatic memories in posttraumatic stress disorder: a functional MRI investigation. Am J Psychiatry 158:1920–1922

    CrossRef  CAS  PubMed  Google Scholar 

  270. Liberzon I, Taylor SF, Amdur R, Jung TD, Chamberlain KR, Minoshima S et al (1999) Brain activation in PTSD in response to trauma-related stimuli. Biol Psychiatry 45:817–826

    CrossRef  CAS  PubMed  Google Scholar 

  271. Liberzon I, Britton JC, Phan KL (2003) Neural correlates of traumatic recall in posttraumatic stress disorder. Stress 6(3):151–156

    CrossRef  PubMed  Google Scholar 

  272. Shin LM, Wright CI, Cannistraro PA, Wedig MM, McMullin K, Martis B et al (2005) A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder. Arch Gen Psychiatry 62(3):273–281

    CrossRef  PubMed  Google Scholar 

  273. Bremner JD, Narayan M, Staib LH, Southwick SM, McGlashan T, Charney DS (1999) Neural correlates of memories of childhood sexual abuse in women with and without posttraumatic stress disorder. Am J Psychiatry 156:1787–1795

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  274. Rauch SL, van der Kolk BA, Fisler RE, Alpert NM, Orr SP, Savage CR et al (1996) A symptom provocation study of posttraumatic stress disorder using positron emission tomography and script-driven imagery. Arch Gen Psychiatry 53(5):380–387

    CrossRef  CAS  PubMed  Google Scholar 

  275. Sakamoto H, Fukuda R, Okuaki T, Rogers M, Kasai K, Machida T et al (2005) Parahippocampal activation evoked by masked traumatic images in posttraumatic stress disorder: a functional MRI study. Neuroimage 26(3):813–821

    CrossRef  PubMed  Google Scholar 

  276. Simmons AN, Paulus MP, Thorp SR, Matthews SC, Norman SB, Stein MB (2008) Functional activation and neural networks in women with posttraumatic stress disorder related to intimate partner violence. Biol Psychiatry 64(8):681–690. https://doi.org/10.1016/j.biopsych.2008.05.027

    CrossRef  PubMed  PubMed Central  Google Scholar 

  277. Bruce SE, Buchholz KR, Brown WJ, Yan L, Durbin A, Sheline YL (2013) Altered emotional interference processing in the amygdala and insula in women with post-traumatic stress disorder. Neuroimage Clin 2:43–49

    CrossRef  Google Scholar 

  278. Nicholson AA, Sapru I, Densmore M, Frewen PA, Neufeld RWJ, Théberge J et al (2016) Unique insula subregion resting-state functional connectivity with amygdala complexes in posttraumatic stress disorder and its dissociative subtype. Psychiatry Res Neuroimaging 250:61–72

    CrossRef  PubMed  Google Scholar 

  279. Osuch EA, Benson B, Geraci M, Podell D, Herscovitch P, McCann UD et al (2001) Regional cerebral blood flow correlated with flashback intensity in patients with posttraumatic stress disorder. Biol Psychiatry 50(4):246–253

    CrossRef  CAS  PubMed  Google Scholar 

  280. Admon R, Lubin G, Stern O, Rosenberg K, Sela L, Ben-Ami H et al (2009) Human vulnerability to stress depends on amygdala's predisposition and hippocampal plasticity. Proc Natl Acad Sci U S A 106(33):14120–14125

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  281. Bremner JD, Vermetten E, Schmahl C, Vaccarino V, Vythilingam M, Afzal N et al (2005) Positron emission tomographic imaging of neural correlates of a fear acquisition and extinction paradigm in women with childhood sexual abuse-related posttraumatic stress disorder. Psychol Med 35(6):791–806

    CrossRef  PubMed  PubMed Central  Google Scholar 

  282. Rauch SL, Shin LM, Wright CI (2003) Neuroimaging studies of amygdala function in anxiety disorders. Ann N Y Acad Sci 985:389–410

    CrossRef  PubMed  Google Scholar 

  283. Protopopescu X, Pan H, Tuescher O, Cloitre M, Goldstein M, Engelien W et al (2005) Differential time courses and specificity of amygdala activity in posttraumatic stress disorder subjects and normal control subjects. Biol Psychiatry 57(5):464–473

    CrossRef  PubMed  Google Scholar 

  284. Chung YA, Kim SH, Chung SK, Chae JH, Yang DW, Sohn HS et al (2006) Alterations in cerebral perfusion in posttraumatic stress disorder patients without re-exposure to accident-related stimuli. Clin Neurophysiol 117(3):637–642

    CrossRef  PubMed  Google Scholar 

  285. Felmingham KL, Williams LM, Kemp AH, Rennie C, Gordon E, Bryant RA (2009) Anterior cingulate activity to salient stimuli is modulated by autonomic arousal in posttraumatic stress disorder. Psychiatry Res 173(1):59–62. https://doi.org/10.1016/j.pscychresns.2008.12.005

    CrossRef  PubMed  Google Scholar 

  286. Semple WE, Goyer P, McCormick R, Donovan B, Muzic RF, Rugle L et al (2000) Higher brain blood flow at amygdala and lower frontal cortex blood flow in PTSD patients with comorbid cocaine and alcohol abuse compared to controls. Psychiatry 63:65–74

    CrossRef  CAS  PubMed  Google Scholar 

  287. Bryant RA, Felmingham KL, Kemp AH, Barton M, Peduto AS, Rennie C et al (2005) Neural networks of information processing in posttraumatic stress disorder: a functional magnetic resonance imaging study. Biol Psychiatry 58(2):111–118

    CrossRef  PubMed  Google Scholar 

  288. Armony JL, Corbo V, Clement MH, Brunet A (2005) Amygdala response in patients with acute PTSD to masked and unmasked emotional facial expressions. Am J Psychiatry 162(10):1961–1963

    CrossRef  PubMed  Google Scholar 

  289. Bryant RA, Kemp AH, Felmingham KL, Liddell B, Olivieri G, Peduto A et al (2008) Enhanced amygdala and medial prefrontal activation during nonconscious processing of fear in posttraumatic stress disorder: an fMRI study. Hum Brain Mapp 29(5):517–523. https://doi.org/10.1002/hbm.20415

    CrossRef  PubMed  Google Scholar 

  290. Kemp AH, Felmingham K, Das P, Hughes G, Peduto AS, Bryant RA et al (2007) Influence of comorbid depression on fear in posttraumatic stress disorder: an fMRI study. Psychiatry Res 155(3):265–269. https://doi.org/10.1016/j.pscychresns.2007.01.010

    CrossRef  PubMed  Google Scholar 

  291. Kemp AH, Felmingham KL, Falconer E, Liddell BJ, Bryant RA, Williams LM (2009) Heterogeneity of non-conscious fear perception in posttraumatic stress disorder as a function of physiological arousal: an fMRI study. Psychiatry Res 174(2):158–161. https://doi.org/10.1016/j.pscychresns.2009.04.012

    CrossRef  PubMed  Google Scholar 

  292. Rauch SL, Whalen PJ, Shin LM, McInerney SC, Macklin ML, Lasko NB et al (2000) Exaggerated amygdala response to masked facial stimuli in posttraumatic stress disorder: a functional MRI study. Biol Psychiatry 47(9):769–776

    CrossRef  CAS  PubMed  Google Scholar 

  293. Brohawn KH, Offringa R, Pfaff DL, Hughes KC, Shin LM (2010) The neural correlates of emotional memory in posttraumatic stress disorder. Biol Psychiatry 68(11):1023–1030. https://doi.org/10.1016/j.biopsych.2010.07.018

    CrossRef  PubMed  Google Scholar 

  294. Brunetti M, Sepede G, Mingoia G, Catani C, Ferretti A, Merla A et al (2010) Elevated response of human amygdala to neutral stimuli in mild post traumatic stress disorder: neural correlates of generalized emotional response. Neuroscience 168(3):670–679. https://doi.org/10.1016/j.neuroscience.2010.04.024

    CrossRef  CAS  PubMed  Google Scholar 

  295. Pissiota A, Frans O, Fernandez M, Von Knorring L, Fischer H, Fredrikson M (2002) Neurofunctional correlates of posttraumatic stress disorder: a PET symptom provocation study. Eur Arch Psychiatry Clin Neurosci 252:68–75

    CrossRef  PubMed  Google Scholar 

  296. Milad MR, Pitman RK, Ellis CB, Gold AL, Shin LM, Lasko NB et al (2009) Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder. Biol Psychiatry 66(12):1075–1082. https://doi.org/10.1016/j.biopsych.2009.06.026

    CrossRef  PubMed  PubMed Central  Google Scholar 

  297. Bremner JD, Vermetten E, Nafzal N, Vythilingam M (2004) Deficits in verbal declarative memory function in women with childhood sexual abuse-related posttraumatic stress disorder (PTSD). J Nerv Ment Dis 192(10):643–649

    CrossRef  PubMed  Google Scholar 

  298. Bremner JD, Campanella C (2016) Effects of psychotherapy for psychological trauma on PTSD symptoms and the brain. In: Bremner JD (ed) Posttraumatic stress disorder: from neurobiology to treatment. Wiley-Blackwell, Hoboken, pp 413–420

    CrossRef  Google Scholar 

  299. Letizia B, Andrea F, Paolo C (2007) Neuroanatomical changes after eye movement desensitization and reprocessing (EMDR) treatment in posttraumatic stress disorder. J Neuropsychiatry Clin Neurosci 19(4):475–476. https://doi.org/10.1176/appi.neuropsych.19.4.475

    CrossRef  PubMed  Google Scholar 

  300. Bremner JD, Mletzko T, Welter S, Quinn S, Williams C, Brummer M et al (2005) Effects of phenytoin on memory, cognition and brain structure in posttraumatic stress disorder: a pilot study. J Psychopharmacol 19(2):159–165

    CrossRef  CAS  PubMed  Google Scholar 

  301. Fani N, Kitayama N, Ashraf A, Reed L, Afzal N, Jawed F et al (2009) Neuropsychological functioning in patients with posttraumatic stress disorder following short-term paroxetine treatment. Psychopharmacol Bull 42(1):53–68

    PubMed  Google Scholar 

  302. Fani N, Ashraf A, Afzal N, Jawed F, Kitayama N, Reed L et al (2011) Increased neural response to trauma scripts in posttraumatic stress disorder following paroxetine treatment: a pilot study. Neurosci Lett 491(3):196–201. https://doi.org/10.1016/j.neulet.2011.01.037

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  303. Bohning DE, Shastri A, Lomarev MP, Lorberbaum JP, Nahas Z, George MS (2003) BOLD-fMRI response vs. transcranial magnetic stimulation (TMS) pulse-train length: testing for linearity. J Magn Reson Imaging 17(3):279–290

    CrossRef  PubMed  Google Scholar 

  304. Lomarev M, Denslow S, Nahas Z, Chae J-H, George MS, Bohning DE (2002) Vagus nerve stimulation (VNS): synchronized BOLD fMRI suggests that VNS in depressed adults has frequency and/or dose dependent effects at rest and during a simple task. J Psychiatr Res 36:219–227

    CrossRef  PubMed  Google Scholar 

  305. Henry TR (2002) Therapeutic mechanisms of vagus nerve stimulation. Neurology 59(Suppl 4):S3–S14

    CrossRef  PubMed  Google Scholar 

  306. Henry TR, Bakay RA, Votaw JR, Pennell PB, Epstein CM, Faber TL et al (1998) Brain blood flow alterations induced by therapeutic vagus nerve stimulation in partial epilepsy: I. Acute effects at high and low levels of stimulation. Epilepsia 39(9):983–990

    CrossRef  CAS  PubMed  Google Scholar 

  307. Henry TR, Sutherling WW, Engel J (1991) Interictal cerebral metabolism in partial epilepsies of neocortical origin. Epilepsy Res 10:174–182

    CrossRef  CAS  PubMed  Google Scholar 

  308. Henry TR, Votaw JR, Pennell PB, Epstein CM, Bakay RA, Faber TL et al (1999) Acute blood flow changes and efficacy of vagus nerve stimulation in partial epilepsy. Neurology 52(6):1166–1173

    CrossRef  CAS  PubMed  Google Scholar 

  309. Conway CR, Sheline YI, Chibnall JT, Bucholz RD, Price JL, Gangwani S et al (2012) Brain blood-flow change with acute vagus nerve stimulation in treatment-refractory major depressive disorder. Brain Stimul 5(2):163–171. https://doi.org/10.1016/j.brs.2011.03.001

    CrossRef  PubMed  Google Scholar 

  310. Van Laere K, Vonck K, Boon P, Versijpt J, Dierckx R (2002) Perfusion SPECT changes after acute and chronic vagus nerve stimulation in relation to prestimulus condition and long-term efficacy. J Nucl Med 43(6):733–744

    PubMed  Google Scholar 

  311. Sperling W, Reulbach U, Bleich S, Padberg F, Kornhuber J, Mueck-Weymann M (2010) Cardiac effects of vagus nerve stimulation in patients with major depression. Pharmacopsychiatry 43:7–11

    CrossRef  CAS  PubMed  Google Scholar 

  312. Stavrakis S, Humphrey MB, Scherlag B, Iftikhar O, Parwani P, Abbas M et al (2017) Low-level vagus nerve stimulation suppresses post-operative atrial fibrillation and inflammation: a randomized study. JACC Clin Electrophysiol 3(9):929–938

    CrossRef  PubMed  Google Scholar 

  313. Frangos E, Ellrich E, Komisaruk BR (2015) Non-invasive access to the vagus nerve central projections via electrical stimulation of the external ear: fMRI evidence in humans. Brain Stimul 8(3):624–636. https://doi.org/10.1016/j.brs.2014.11.018

    CrossRef  PubMed  Google Scholar 

  314. Badran BW, Dowdle LT, Mithoefer OJ, LaBate NT, Coatsworth J, Brown JC et al (2018) Neurophysiologic effects of transcutaneous auricular vagus nerve stimulation (taVNS) via electrical stimulation of the tragus: a concurrent taVNS/fMRI study and review. Brain Stimul 11(3):492–500. https://doi.org/10.1016/j.brs.2017.12.009

    CrossRef  PubMed  Google Scholar 

  315. Yakunina N, Kim SS, Nam EC (2018) BOLD fMRI effects of transcutaneous vagus nerve stimulation in patients with chronic tinnitus. PLoS One 13(11):e0207281. https://doi.org/10.1371/journal.pone.0207281

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  316. Fang J, Egorova N, Rong P, Liu J, Hong Y, Fan Y et al (2017) Early cortical biomarkers of longitudinal transcutaneous vagus nerve stimulation treatment success in depression. Neuroimage Clin 14:105–111. https://doi.org/10.1016/j.nicl.2016.12.016

    CrossRef  PubMed  Google Scholar 

  317. Fang J, Rong P, Hong Y, Fan Y, Liu J, Wang H et al (2016) Transcutaneous vagus nerve stimulation modulates default mode network in major depressive disorder. Biol Psychiatry 15(79):266–273. https://doi.org/10.1016/j.biopsych.2015.03.025

    CrossRef  Google Scholar 

  318. Liu J, Fang J, Wang Z, Rong P, Hong Y, Fan Y et al (2016) Transcutaneous vagus nerve stimulation modulates amygdala functional connectivity in patients with depression. J Affect Disord 205:319–326

    CrossRef  PubMed  Google Scholar 

  319. Tu Y, Fang J, Cao J, Wang Z, Park J, Jorgenson K et al (2018) A distinct biomarker of continuous transcutaneous vagus nerve stimulation treatment in major depressive disorder. Brain Stimul 11(3):501–508. https://doi.org/10.1016/j.brs.2018.01.006

    CrossRef  PubMed  PubMed Central  Google Scholar 

  320. Wang Z, Fang J, Liu J, Rong P, Jorgenson K, Park J et al (2018) Frequency-dependent functional connectivity of the nucleus accumbens during continuous transcutaneous vagus nerve stimulation in major depressive disorder. J Psychiatr Res 102(123–131):123–131. https://doi.org/10.1016/j.jpsychires.2017.12.018

    CrossRef  PubMed  Google Scholar 

  321. Frangos E, Komisaruk BR (2017) Access to vagal projections via cutaneous electrical stimulation of the neck: fMRI evidence in healthy humans. Brain Stimul 10(1):19–27. https://doi.org/10.1016/j.brs.2016.10.008

    CrossRef  PubMed  Google Scholar 

  322. Lerman I, Davis B, Huang M, Huang C, Sorkin L, Proudfoot J et al (2019) Noninvasive vagus nerve stimulation alters neural response and physiological autonomic tone to noxious thermal challenge. PLoS One 14(2):e0201212. https://doi.org/10.1371/journal.pone.0201212

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA

    J. Douglas Bremner & Matthew T. Wittbrodt

  2. Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA

    J. Douglas Bremner

  3. Atlanta VAMC, Decatur, GA, USA

    J. Douglas Bremner & Jeanie Park

  4. School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA

    Nil Z. Gurel, Md Mobashir H. Shandhi, Asim H. Gazi & Omer T. Inan

  5. Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA

    Jeanie Park

  6. Walter H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA

    Omer T. Inan

Authors
  1. J. Douglas Bremner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthew T. Wittbrodt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nil Z. Gurel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Md Mobashir H. Shandhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Asim H. Gazi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jeanie Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Omer T. Inan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Douglas Bremner .

Editor information

Editors and Affiliations

  1. Department of Obstetrics and Gynecology and Institute on Human Development and Disability, University of Washington, Seattle, WA, USA

    Martin G. Frasch

  2. Department of Clinical and Health Psychology and The Center For Cognitive Aging And Memory, University of Florida, Gainsville, Gainesville, FL, USA

    Eric C. Porges

Rights and permissions

Reprints and Permissions

Copyright information

© 2024 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Bremner, J.D. et al. (2024). Transcutaneous Vagal Nerve Stimulation in Trauma Spectrum Psychiatric Disorders. In: Frasch, M.G., Porges, E.C. (eds) Vagus Nerve Stimulation . Neuromethods, vol 205. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3465-3_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-3465-3_8

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3464-6

  • Online ISBN: 978-1-0716-3465-3

  • eBook Packages: Springer Protocols

search

Navigation