Skip to main content

Advertisement

SpringerLink
Log in

The resting-state functional connectivity of amygdala subregions associated with post-traumatic stress symptom and sleep quality in trauma survivors

  • Original Paper
  • Published:
European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Abstract

Neuroimaging findings suggest that the amygdala plays a primary role in both the psychopathology of posttraumatic stress disorder (PTSD) and poor sleep quality, which are common in trauma survivors. However, the neural mechanisms of these two problems in trauma survivors associated with amygdala remain unclear. In the current study, we aimed to explore the role of functional connectivity of amygdala subregions in both PTSD symptoms and poor sleep quality. A total of 94 trauma-exposed subjects were scanned on a 3T MR system using resting-state functional magnetic resonance imaging. Both Pittsburgh Sleep Quality Index and Clinician-Administered PTSD Scale scores were negatively correlated with the resting-state functional connectivity between the left basolateral amygdala-left medial prefrontal cortex and the right basolateral amygdala-right medial prefrontal cortex. Our findings suggest a shared amygdala subregional neural circuitry underlying the neuropathological mechanisms of PTSD symptoms and poor sleep quality in trauma survivors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE (2005) Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 62(6):617–627

    Article  PubMed  PubMed Central  Google Scholar 

  2. 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

    Article  CAS  PubMed  Google Scholar 

  3. Shalev A, Liberzon I, Marmar C (2017) Post-traumatic stress disorder. N Engl J Med 376(25):2459–2469

    Article  PubMed  Google Scholar 

  4. Mysliwiec V, Brock MS, Creamer JL, O’Reilly BM, Germain A, Roth BJ (2018) Trauma associated sleep disorder: a parasomnia induced by trauma. Sleep Med Rev 37:94–104

    Article  PubMed  Google Scholar 

  5. Clum GA, Nishith P, Resick PA (2001) Trauma-related sleep disturbance and self-reported physical health symptoms in treatment-seeking female rape victims. J Nerv Ment Dis 189(9):618–622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. McEwen BS (2006) Protective and damaging effects of stress mediators: central role of the brain. Dialogues Clin Neurosci 8(4):367–381

    Article  PubMed  PubMed Central  Google Scholar 

  7. Rothbaum BO, Davis M (2003) Applying learning principles to the treatment of post-trauma reactions. Ann N Y Acad Sci 1008:112–121

    Article  PubMed  Google Scholar 

  8. van Wingen GA, Geuze E, Caan MW et al (2012) Persistent and reversible consequences of combat stress on the mesofrontal circuit and cognition. Proc Natl Acad Sci U S A 109(38):15508–15513

    Article  PubMed  PubMed Central  Google Scholar 

  9. Stark EA, Parsons CE, Van Hartevelt TJ et al (2015) Post-traumatic stress influences the brain even in the absence of symptoms: a systematic, quantitative meta-analysis of neuroimaging studies. Neurosci Biobehav Rev 56:207–221

    Article  CAS  PubMed  Google Scholar 

  10. Patel R, Spreng RN, Shin LM, Girard TA (2012) Neurocircuitry models of posttraumatic stress disorder and beyond: a meta-analysis of functional neuroimaging studies. Neurosci Biobehav Rev 36(9):2130–2142

    Article  PubMed  Google Scholar 

  11. Rabinak CA, Angstadt M, Welsh RC et al (2011) Altered amygdala resting-state functional connectivity in post-traumatic stress disorder. Front Psychiatry 2:62

    Article  PubMed  PubMed Central  Google Scholar 

  12. Sripada RK, King AP, Garfinkel SN et al (2012) Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder. J Psychiatry Neurosci 37(4):241–249

    Article  PubMed  PubMed Central  Google Scholar 

  13. Duvarci S, Pare D (2014) Amygdala microcircuits controlling learned fear. Neuron 82(5):966–980

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hayes JP, Hayes SM, Mikedis AM (2012) Quantitative meta-analysis of neural activity in posttraumatic stress disorder. Biol Mood Anxiety Disord 2:9

    Article  PubMed  PubMed Central  Google Scholar 

  15. Sartory G, Cwik J, Knuppertz H et al (2013) In search of the trauma memory: a meta-analysis of functional neuroimaging studies of symptom provocation in posttraumatic stress disorder (PTSD). PLoS ONE 8(3):e58150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Lanius RA, Bluhm RL, Coupland NJ et al (2010) Default mode network connectivity as a predictor of post-traumatic stress disorder symptom severity in acutely traumatized subjects. Acta Psychiatr Scand 121(1):33–40

    Article  CAS  PubMed  Google Scholar 

  17. Casement MD, Harrington KM, Miller MW, Resick PA (2012) Associations between Pittsburgh Sleep Quality Index factors and health outcomes in women with posttraumatic stress disorder. Sleep Med 13(6):752–758

    Article  PubMed  PubMed Central  Google Scholar 

  18. Lind MJ, Baylor A, Overstreet CM et al (2017) Relationships between potentially traumatic events, sleep disturbances, and symptoms of PTSD and alcohol use disorder in a young adult sample. Sleep Med 34:141–147

    Article  PubMed  PubMed Central  Google Scholar 

  19. Lind MJ, Brown E, Farrell-Carnahan L et al (2017) Sleep disturbances in OEF/OIF/OND veterans: associations with PTSD, personality, and coping. J Clin Sleep Med 13(2):291–299

    Article  PubMed  PubMed Central  Google Scholar 

  20. Plumb TR, Peachey JT, Zelman DC (2014) Sleep disturbance is common among servicemembers and veterans of operations enduring freedom and Iraqi freedom. Psychol Serv 11(2):209–219

    Article  PubMed  Google Scholar 

  21. Germain A, Buysse DJ, Nofzinger E (2008) Sleep-specific mechanisms underlying posttraumatic stress disorder: integrative review and neurobiological hypotheses. Sleep Med Rev 12(3):185–195

    Article  PubMed  Google Scholar 

  22. Motomura Y, Kitamura S, Oba K et al (2014) Sleepiness induced by sleep-debt enhanced amygdala activity for subliminal signals of fear. BMC Neurosci 15:97

    Article  PubMed  PubMed Central  Google Scholar 

  23. Amunts K, Kedo O, Kindler M et al (2005) Cytoarchitectonic mapping of the human amygdala, hippocampal region and entorhinal cortex: intersubject variability and probability maps. Anat Embryol (Berl) 210(5–6):343–352

    Article  CAS  Google Scholar 

  24. Phelps EA, Delgado MR, Nearing KI, LeDoux JE (2004) Extinction learning in humans: role of the amygdala and vmPFC. Neuron 43(6):897–905

    Article  CAS  PubMed  Google Scholar 

  25. Davis M, Whalen PJ (2001) The amygdala: vigilance and emotion. Mol Psychiatry 6(1):13–34

    Article  CAS  PubMed  Google Scholar 

  26. LeDoux JE (2000) Emotion circuits in the brain. Annu Rev Neurosci 23:155–184

    Article  CAS  PubMed  Google Scholar 

  27. LeDoux J (1998) Fear and the brain: where have we been, and where are we going. Biol Psychiatry 44(12):1229–1238

    Article  CAS  PubMed  Google Scholar 

  28. Nicholson AA, Ros T, Frewen PA et al (2016) Alpha oscillation neurofeedback modulates amygdala complex connectivity and arousal in posttraumatic stress disorder. Neuroimage Clin 12:506–516

    Article  PubMed  PubMed Central  Google Scholar 

  29. Nicholson AA, Densmore M, Frewen PA et al (2015) The dissociative subtype of posttraumatic stress disorder: unique resting-state functional connectivity of basolateral and centromedial amygdala complexes. Neuropsychopharmacology 40(10):2317–2326

    Article  PubMed  PubMed Central  Google Scholar 

  30. Nicholson AA, Sapru I, Densmore M 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

    Article  PubMed  Google Scholar 

  31. Langevin JP, Koek RJ, Schwartz HN et al (2016) Deep brain stimulation of the basolateral amygdala for treatment-refractory posttraumatic stress disorder. Biol Psychiatry 79(10):e82–e84

    Article  PubMed  Google Scholar 

  32. Lavano A, Guzzi G, Della Torre A, Lavano SM, Tiriolo R, Volpentesta G (2018) DBS in treatment of post-traumatic stress disorder. Brain Sci 8(1):18

    Article  PubMed Central  Google Scholar 

  33. Brown VM, LaBar KS, Haswell CC et al (2014) Altered resting-state functional connectivity of basolateral and centromedial amygdala complexes in posttraumatic stress disorder. Neuropsychopharmacology 39(2):351–359

    Article  PubMed  Google Scholar 

  34. First MB, Gibbon M, Spitzer RL, Williams JBW (2004) The structured clinical interview for DSM-IV axis I disorders (SCID-I) and the structured clinical interview for DSM-IV axis II disorders (SCID-II)

  35. Blake DD, Weathers FW, Nagy LM et al (1995) The development of a clinician-administered PTSD scale. J Trauma Stress 8(1):75–90

    Article  CAS  PubMed  Google Scholar 

  36. Mollayeva T, Thurairajah P, Burton K, Mollayeva S, Shapiro CM, Colantonio A (2016) The Pittsburgh sleep quality index as a screening tool for sleep dysfunction in clinical and non-clinical samples: a systematic review and meta-analysis. Sleep Med Rev 25:52–73

    Article  PubMed  Google Scholar 

  37. Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23(1):56–62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Thompson E (2015) Hamilton rating scale for anxiety (HAM-A). Occup Med (Lond) 65(7):601

    Article  Google Scholar 

  39. Yuan M, Qiu C, Meng Y et al (2018) Pre-treatment resting-state functional MR imaging predicts the long-term clinical outcome after short-term paroxtine treatment in post-traumatic stress disorder. Front Psychiatry 9:532

    Article  PubMed  PubMed Central  Google Scholar 

  40. Yan CG, Wang XD, Zuo XN, Zang YF (2016) DPABI: data processing and analysis for (resting-state) brain imaging. Neuroinformatics 14(3):339–351

    Article  PubMed  Google Scholar 

  41. Fox MD, Raichle ME (2007) Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci 8(9):700–711

    Article  CAS  PubMed  Google Scholar 

  42. Jenkinson M, Bannister P, Brady M, Smith S (2002) Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage 17(2):825–841

    Article  PubMed  Google Scholar 

  43. Desikan RS, Ségonne F, Fischl B et al (2006) An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage 31(3):968–980

    Article  PubMed  Google Scholar 

  44. David AS, Farrin L, Hull L, Unwin C, Wessely S, Wykes T (2002) Cognitive functioning and disturbances of mood in UK veterans of the Persian Gulf War: a comparative study. Psychol Med 32(8):1357–1370

    Article  CAS  PubMed  Google Scholar 

  45. Ambrosi E, Arciniegas DB, Madan A et al (2017) Insula and amygdala resting-state functional connectivity differentiate bipolar from unipolar depression. Acta Psychiatr Scand 136(1):129–139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Toazza R, Franco AR, Buchweitz A et al (2016) Amygdala-based intrinsic functional connectivity and anxiety disorders in adolescents and young adults. Psychiatry Res 257:11–16

    Article  Google Scholar 

  47. Baron RM, Kenny DA (1986) The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. J Pers Soc Psychol 51(6):1173–1182

    Article  CAS  PubMed  Google Scholar 

  48. Hayes AF (1986) Beyond Baron and Kenny: statistical mediation analysis in the new millennium. Commun Monogr 76(4):408–420

    Article  Google Scholar 

  49. Lei D, Li K, Li L et al (2015) Disrupted functional brain connectome in patients with posttraumatic stress disorder. Radiology 276(3):818–827

    Article  PubMed  Google Scholar 

  50. Buckner RL, Andrews-Hanna JR, Schacter DL (2008) The brain’s default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci 1124:1–38

    Article  PubMed  Google Scholar 

  51. Raichle ME, Gusnard DA (2005) Intrinsic brain activity sets the stage for expression of motivated behavior. J Comp Neurol. 493(1):167–176

    Article  PubMed  Google Scholar 

  52. Bluhm RL, Williamson PC, Osuch EA et al (2009) Alterations in default network connectivity in posttraumatic stress disorder related to early-life trauma. J Psychiatry Neurosci 34(3):187–194

    PubMed  PubMed Central  Google Scholar 

  53. Sripada RK, King AP, Welsh RC et al (2012) Neural dysregulation in posttraumatic stress disorder: evidence for disrupted equilibrium between salience and default mode brain networks. Psychosom Med 74(9):904–911

    Article  PubMed  PubMed Central  Google Scholar 

  54. Zhou Y, Wang Z, Qin LD et al (2012) Early altered resting-state functional connectivity predicts the severity of post-traumatic stress disorder symptoms in acutely traumatized subjects. PLoS ONE 7(10):e46833

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Malivoire BL, Girard TA, Patel R, Monson CM (2018) Functional connectivity of hippocampal subregions in PTSD: relations with symptoms. BMC Psychiatry 18(1):129

    Article  PubMed  PubMed Central  Google Scholar 

  56. O’Keefe J, Recce ML (1993) Phase relationship between hippocampal place units and the EEG theta rhythm. Hippocampus 3(3):317–330

    Article  PubMed  Google Scholar 

  57. Sumner JA, Hagan K, Grodstein F, Roberts AL, Harel B, Koenen KC (2017) Posttraumatic stress disorder symptoms and cognitive function in a large cohort of middle-aged women. Depress Anxiety 34(4):356–366

    Article  PubMed  PubMed Central  Google Scholar 

  58. Kyle SD, Espie CA, Morgan K (2010) ”…Not just a minor thing, it is something major, which stops you from functioning daily”: quality of life and daytime functioning in insomnia. Behav Sleep Med 8(3):123–140 8

    Article  PubMed  Google Scholar 

  59. de Voogd LD, Klumpers F, Fernández G, Hermans EJ (2017) Intrinsic functional connectivity between amygdala and hippocampus during rest predicts enhanced memory under stress. Psychoneuroendocrinology 75:192–202

    Article  PubMed  Google Scholar 

  60. Cheng W, Rolls ET, Ruan H, Feng J (2018) Functional connectivities in the brain that mediate the association between depressive problems and sleep quality. JAMA Psychiatry 75(10):1052–1061

    Article  PubMed  PubMed Central  Google Scholar 

  61. Nielsen T, Levin R (2007) Nightmares: a new neurocognitive model. Sleep Med Rev 11(4):295–310

    Article  PubMed  Google Scholar 

  62. Silvestri AJ (2005) REM sleep deprivation affects extinction of cued but not contextual fear conditioning. Physiol Behav 84(3):343–349

    Article  CAS  PubMed  Google Scholar 

  63. Yoo SS, Gujar N, Hu P, Jolesz FA, Walker MP (2007) The human emotional brain without sleep–a prefrontal amygdala disconnect. Curr Biol 17(20):R877–R878

    Article  CAS  PubMed  Google Scholar 

  64. Germain A, James J, Insana S et al (2013) A window into the invisible wound of war: functional neuroimaging of REM sleep in returning combat veterans with PTSD. Psychiatry Res 211(2):176–179

    Article  PubMed  Google Scholar 

  65. Yuan M, Pantazatos SP, Zhu H et al (2019) Altered amygdala subregion-related circuits in treatment-naïve post-traumatic stress disorder comorbid with major depressive disorder. Eur Neuropsychopharmacol 29:1092–1101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Zhang X, Zhang J, Wang L, Li R, Zhang W (2016) Altered resting-state functional connectivity of the amygdala in Chinese earthquake survivors. Prog Neuropsychopharmacol Biol Psychiatry 65:208–214

    Article  PubMed  Google Scholar 

  67. Zhang Y, Li Y, Zhu H et al (2017) Characteristics of objective daytime sleep among individuals with earthquake-related posttraumatic stress disorder: a pilot community-based polysomnographic and multiple sleep latency test study. Psychiatry Res 247:43–50

    Article  PubMed  Google Scholar 

  68. Zhang Q, Wang D, Qin W et al (2013) Altered resting-state brain activity in obstructive sleep apnea. Sleep 36(5):651–659B

    PubMed  Google Scholar 

  69. Apfel BA, Ross J, Hlavin J et al (2011) Hippocampal volume differences in Gulf War veterans with current versus lifetime posttraumatic stress disorder symptoms. Biol Psychiatry 69(6):541–548

    Article  PubMed  Google Scholar 

  70. Karl A, Schaefer M, Malta LS, Dörfel D, Rohleder N, Werner A (2006) A meta-analysis of structural brain abnormalities in PTSD. Neurosci Biobehav Rev 30(7):1004–1031

    Article  PubMed  Google Scholar 

  71. Togo H, Rokicki J, Yoshinaga K et al (2017) Effects of field-map distortion correction on resting state functional connectivity MRI. Front Neurosci 11:656

    Article  PubMed  PubMed Central  Google Scholar 

  72. Birn RM, Molloy EK, Patriat R et al (2013) The effect of scan length on the reliability of resting-state fMRI connectivity estimates. Neuroimage 83:550–558

    Article  PubMed  Google Scholar 

  73. Gonzalez-Castillo J, Handwerker DA, Robinson ME et al (2014) The spatial structure of resting state connectivity stability on the scale of minutes. Front Neurosci 8:138

    Article  PubMed  PubMed Central  Google Scholar 

  74. Li F, He N, Li Y et al (2014) Intrinsic brain abnormalities in attention deficit hyperactivity disorder: a resting-state functional MR imaging study. Radiology 272(2):514–523

    Article  PubMed  Google Scholar 

  75. Zhao L, Liu J, Dong X et al (2013) Alterations in regional homogeneity assessed by fMRI in patients with migraine without aura stratified by disease duration. J Headache Pain 14:85

    Article  PubMed  PubMed Central  Google Scholar 

  76. Zhu H, Qiu C, Meng Y et al (2015) Altered spontaneous neuronal activity in chronic posttraumatic stress disorder patients before and after a 12-week paroxetine treatment. J Affect Disord 174:257–264

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was funded by National Natural Science Foundation of China (Grant No. 81701328, 81871061, and 61973090); National Key Research & Development Program of China (Grant No. 2016YFC1307200); The Special Project on Natural Chronic Non-infectious Diseases (Grant No. 2016YFC1307201); Department of Science & Technology of Sichuan Province (Grant No. 2018 SZ0131); China Postdoctoral Science Foundation (Grant No. 2017M612972) and Postdoctoral Foundation of Sichuan University (Grant No. 2018SCU12042) to Dr. H.Z..

Author information

Author notes

  1. Zuxing Wang and Hongru Zhu have contributed equally to this work.

Authors and Affiliations

  1. Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China

    Zuxing Wang, Hongru Zhu, Minlan Yuan, Yuchen Li, Changjian Qiu, Zhengjia Ren, Cui Yuan & Wei Zhang

  2. Sichuan Provincial Center for Mental Healthy, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu, China

    Zuxing Wang

  3. Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, China

    Hongru Zhu

  4. Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Hongru Zhu

  5. Department of Clinical Psychology, Southwest Hospital, Army Medical University (The Third Military Medical University), Chongqing, China

    Zhengjia Ren

  6. Huaxi MR Research Center (HMRRC), Department of Radiology, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China

    Su Lui & Qiyong Gong

Authors
  1. Zuxing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hongru Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Minlan Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuchen Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Changjian Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhengjia Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Cui Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Su Lui
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Qiyong Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Wei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wei Zhang.

Ethics declarations

Conflict of interest

None.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 1374 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Z., Zhu, H., Yuan, M. et al. The resting-state functional connectivity of amygdala subregions associated with post-traumatic stress symptom and sleep quality in trauma survivors. Eur Arch Psychiatry Clin Neurosci 271, 1053–1064 (2021). https://doi.org/10.1007/s00406-020-01104-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00406-020-01104-3

Keywords

Search

Navigation