Skip to main content
SpringerLink
Log in

Anxiety Disorders and the Brain’s Resting State Networks: From Altered Spatiotemporal Synchronization to Psychopathological Symptoms

  • Chapter
  • First Online:
Anxiety Disorders

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1191))

Abstract

Anxiety disorders include a variety of different disorders including panic disorder (PD), social anxiety disorder (SAD), generalized anxiety disorder (GAD), and phobias. We here focus our review on GAD, SAD, and PD and put a specific emphasis on resting state networks and the coupling between the brain and the heart as all anxiety disorders exhibit abnormal perception of their own heartbeat in some way or the other. Resting state functional connectivity (rsFC) studies demonstrate abnormalities in default-mode network (DMN) in all anxiety disorders, e.g., mostly decreases in rsFC of DMN. In contrast, resting state fMRI shows increased rsFC in salience network (SN) (SAD, GAD) and/or somato-motor/sensory network (SMN) (PD). Since rsFC is coherence- or phase-based operating in the infraslow frequency domain (0.01–0.1 Hz), these data suggest spatiotemporal hypo- or hyper-synchronization in DMN and SMN/SN, respectively. These abnormalities in the neural network’s spatiotemporal synchronization may, in turn, impact phase-based temporal synchronization of neural and cardiac activities resulting in decreased (DMN) or increased (SMN/SN) neuro-cardiac coupling in anxiety disorders. That, in turn, may be related to the various psychopathological symptoms like unstable sense of self (as based on unstable DMN showing spatiotemporal hypo-synchronization), increased emotions and specifically anxiety (as related to increased SN showing spatiotemporal hyper-synchronization), and increased bodily awareness (mediated by increased SMN with spatiotemporal hyper-synchronization) in anxiety disorders. Taken together, we here suggest altered spatiotemporal synchronization of neural and cardiac activity within the brain’s resting state to underlie various psychopathological symptoms in anxiety disorders. Such spatiotemporal basis of psychopathological symptoms is well compatible with the recently suggested “Spatiotemporal Psychopathology.”

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
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

Institutional subscriptions

References

  1. Olesen KKW, Madsen M, Lip GYH, Egholm G, Thim T, Jensen LO, et al. Coronary artery disease and risk of adverse cardiac events and stroke. Eur J Clin Invest. 2017 Nov;47(11):819–28.

    Article  PubMed  Google Scholar 

  2. Kim EY, Lee MY, Kim SH, Ha K, Kim KP, Ahn YM. Diagnosis of major depressive disorder by combining multimodal information from heart rate dynamics and serum proteomics using machine-learning algorithm. Prog Neuropsychopharmacol Biol Psychiatry. 2017 Jun;76:65–71.

    Article  CAS  PubMed  Google Scholar 

  3. Kim Y-K, Yoon H-K. Common and distinct brain networks underlying panic and social anxiety disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jan;80(Pt B):115–22.

    Article  PubMed  Google Scholar 

  4. Chalmers JA, Quintana DS, Abbott MJ-A, Kemp AH. Anxiety disorders are associated with reduced heart rate variability: a meta-analysis. Front Psychiatry. 2014;5:80.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Wiebking C, de Greck M, Duncan NW, Heinzel A, Tempelmann C, Northoff G. Are emotions associated with activity during rest or interoception? An exploratory fMRI study in healthy subjects. Neurosci Lett. 2011 Mar;491(1):87–92.

    Article  CAS  PubMed  Google Scholar 

  6. Avery JA, Drevets WC, Moseman SE, Bodurka J, Barcalow JC, Simmons WK. Major depressive disorder is associated with abnormal interoceptive activity and functional connectivity in the insula. Biol Psychiatry. 2014 Aug;76(3):258–66.

    Article  PubMed  Google Scholar 

  7. Cui H, Zhang J, Liu Y, Li Q, Li H, Zhang L, et al. Differential alterations of resting-state functional connectivity in generalized anxiety disorder and panic disorder. Hum Brain Mapp. 2016 Apr;37(4):1459–73.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Cui S, Len J, Zhang J, Li C, Northoff G. Alterations in interceptive awareness and the brain’s resting state and task-evoked activity in generalized anxiety disorder. Biol Psychiatry Cogn Neurosci Neuroimaging. In review. 2019

    Google Scholar 

  9. Emdin CA, Odutayo A, Wong CX, Tran J, Hsiao AJ, Hunn BHM. Meta-analysis of anxiety as a risk factor for cardiovascular disease. Am J Cardiol. 2016 Aug;118(4):511–9.

    Article  PubMed  Google Scholar 

  10. Northoff G. Spatiotemporal psychopathology I: no rest for the brain’s resting state activity in depression? Spatiotemporal psychopathology of depressive symptoms. J Affect Disord. 2016 Jan;190:854–66.

    Article  PubMed  Google Scholar 

  11. Northoff G. Spatiotemporal psychopathology II: how does a psychopathology of the brain’s resting state look like? Spatiotemporal approach and the history of psychopathology. J Affect Disord. 2016 Jan;190:867–79.

    Article  PubMed  Google Scholar 

  12. Northoff G. “Paradox of slow frequencies” – are slow frequencies in upper cortical layers a neural predisposition of the level/state of consciousness (NPC)? Conscious Cogn. 2017 Sep;54:20–35.

    Article  PubMed  Google Scholar 

  13. Northoff G. The brain’s spontaneous activity and its psychopathological symptoms – “spatiotemporal binding and integration”. Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jan;80(Pt B):81–90.

    Article  PubMed  Google Scholar 

  14. Northoff G, Duncan NW. How do abnormalities in the brain’s spontaneous activity translate into symptoms in schizophrenia? From an overview of resting state activity findings to a proposed spatiotemporal psychopathology. Prog Neurobiol. 2016 Oct;145–146:26–45.

    Article  PubMed  Google Scholar 

  15. Northoff G, Stanghellini G. How to link brain and experience? Spatiotemporal psychopathology of the lived body. Front Hum Neurosci. 2016;10:76.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Fingelkurts AA, Fingelkurts AA. Brain space and time in mental disorders: paradigm shift in biological psychiatry. Int J Psychiatry Med. 2018 Aug;91217418791438

    Google Scholar 

  17. Chang C, Metzger CD, Glover GH, Duyn JH, Heinze H-J, Walter M. Association between heart rate variability and fluctuations in resting-state functional connectivity. Neuroimage. 2013 Mar;68:93–104.

    Article  PubMed  Google Scholar 

  18. Thome J, Densmore M, Frewen PA, McKinnon MC, Theberge J, Nicholson AA, et al. Desynchronization of autonomic response and central autonomic network connectivity in posttraumatic stress disorder. Hum Brain Mapp. 2017 Jan;38(1):27–40.

    Article  PubMed  Google Scholar 

  19. Rabellino D, D’Andrea W, Siegle G, Frewen PA, Minshew R, Densmore M, et al. Neural correlates of heart rate variability in PTSD during sub- and supraliminal processing of trauma-related cues. Hum Brain Mapp. 2017 Oct;38(10):4898–907.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Jennings JR, Sheu LK, Kuan DC-H, Manuck SB, Gianaros PJ. Resting state connectivity of the medial prefrontal cortex covaries with individual differences in high-frequency heart rate variability. Psychophysiology. 2016 Apr;53(4):444–54.

    Article  PubMed  Google Scholar 

  21. Park H-D, Correia S, Ducorps A, Tallon-Baudry C. Spontaneous fluctuations in neural responses to heartbeats predict visual detection. Nat Neurosci. 2014 Apr;17(4):612–8.

    Article  CAS  PubMed  Google Scholar 

  22. Park H-D, Tallon-Baudry C. The neural subjective frame: from bodily signals to perceptual consciousness. Philos Trans R Soc Lond B Biol Sci. 2014 May;369(1641):20130208.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Park H-D, Bernasconi F, Bello-Ruiz J, Pfeiffer C, Salomon R, Blanke O. Transient modulations of neural responses to heartbeats covary with bodily self-consciousness. J Neurosci. 2016 Aug;36(32):8453–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Park H-D, Bernasconi F, Salomon R, Tallon-Baudry C, Spinelli L, Seeck M, et al. Neural sources and underlying mechanisms of neural responses to heartbeats, and their role in bodily self-consciousness: an intracranial EEG study. Cereb Cortex. 2018 Jul;28(7):2351–64.

    Article  PubMed  Google Scholar 

  25. Babo-Rebelo M, Wolpert N, Adam C, Hasboun D, Tallon-Baudry C. Is the cardiac monitoring function related to the self in both the default network and right anterior insula? Philos Trans R Soc Lond B Biol Sci. 2016 Nov;371(1708)

    Article  Google Scholar 

  26. Babo-Rebelo M, Richter CG, Tallon-Baudry C. Neural responses to heartbeats in the default network encode the self in spontaneous thoughts. J Neurosci. 2016 Jul;36(30):7829–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Garfinkel SN, Seth AK, Barrett AB, Suzuki K, Critchley HD. Knowing your own heart: distinguishing interoceptive accuracy from interoceptive awareness. Biol Psychol. 2015 Jan;104:65–74.

    Article  PubMed  Google Scholar 

  28. Forkmann T, Scherer A, Meessen J, Michal M, Schachinger H, Vogele C, et al. Making sense of what you sense: disentangling interoceptive awareness, sensibility and accuracy. Int J Psychophysiol. 2016 Nov;109:71–80.

    Article  PubMed  Google Scholar 

  29. Critchley HD, Wiens S, Rotshtein P, Ohman A, Dolan RJ. Neural systems supporting interoceptive awareness. Nat Neurosci. 2004 Feb;7(2):189–95.

    Article  CAS  PubMed  Google Scholar 

  30. Kuehn E, Mueller K, Lohmann G, Schuetz-Bosbach S. Interoceptive awareness changes the posterior insula functional connectivity profile. Brain Struct Funct. 2016 Apr;221(3):1555–71.

    Article  PubMed  Google Scholar 

  31. Wiebking C, Duncan NW, Tiret B, Hayes DJ, Marjanska M, Doyon J, et al. GABA in the insula – a predictor of the neural response to interoceptive awareness. Neuroimage. 2014 Feb;86:10–8.

    Article  CAS  PubMed  Google Scholar 

  32. Wiebking C, Duncan NW, Qin P, Hayes DJ, Lyttelton O, Gravel P, et al. External awareness and GABA – a multimodal imaging study combining fMRI and [18F]flumazenil-PET. Hum Brain Mapp. 2014 Jan;35(1):173–84.

    Article  PubMed  Google Scholar 

  33. Menon V. Large-scale brain networks and psychopathology: a unifying triple network model. Trends Cogn Sci. 2011 Oct;15(10):483–506.

    Article  PubMed  Google Scholar 

  34. Seeley WW, Menon V, Schatzberg AF, Keller J, Glover GH, Kenna H, et al. Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci. 2007 Feb;27(9):2349–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL. A default mode of brain function. Proc Natl Acad Sci USA. 2001 Jan;98(2):676–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Greicius MD, Krasnow B, Reiss AL, Menon V. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci USA. 2003 Jan;100(1):253–8.

    Article  CAS  PubMed  Google Scholar 

  37. Tallon-Baudry C, Campana F, Park H-D, Babo-Rebelo M. The neural monitoring of visceral inputs, rather than attention, accounts for first-person perspective in conscious vision. Cortex. 2018 May;102:139–49.

    Article  PubMed  Google Scholar 

  38. Pollatos O, Herbert BM, Mai S, Kammer T. Changes in interoceptive processes following brain stimulation. Philos Trans R Soc Lond B Biol Sci. 2016 Nov;371(1708)

    Article  Google Scholar 

  39. Huang Z, Zhang J, Longtin A, Dumont G, Duncan NW, Pokorny J, et al. Is there a nonadditive interaction between spontaneous and evoked activity? Phase-dependence and its relation to the temporal structure of scale-free brain activity. Cereb Cortex. 2017 Feb;27(2):1037–59.

    PubMed  Google Scholar 

  40. He BJ. Spontaneous and task-evoked brain activity negatively interact. J Neurosci. 2013 Mar;33(11):4672–82.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Lakatos P, Schroeder CE, Leitman DI, Javitt DC. Predictive suppression of cortical excitability and its deficit in schizophrenia. J Neurosci. 2013 Jul;33(28):11692–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Northoff G, Huang Z. How do the brain’s time and space mediate consciousness and its different dimensions? Temporo-spatial theory of consciousness (TTC). Neurosci Biobehav Rev. 2017 Sep;80:630–45.

    Article  PubMed  Google Scholar 

  43. Northoff G, Heinzel A. First-Person Neuroscience: a new methodological approach for linking mental and neuronal states. Philos Ethics Humanit Med. 2006 Mar;1(1):E3.

    Article  PubMed  Google Scholar 

  44. Qin P, Northoff G. How is our self related to midline regions and the default-mode network? Neuroimage. 2011 Aug;57(3):1221–33.

    Article  PubMed  Google Scholar 

  45. Blanke O. Multisensory brain mechanisms of bodily self-consciousness. Nat Rev Neurosci. 2012 Jul;13(8):556–71.

    Article  CAS  PubMed  Google Scholar 

  46. Enzi B, de Greck M, Prosch U, Tempelmann C, Northoff G. Is our self nothing but reward? Neuronal overlap and distinction between reward and personal relevance and its relation to human personality. PLoS One. 2009 Dec;4(12):e8429.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Northoff G, Wiebking C, Feinberg T, Panksepp J. The “resting-state hypothesis” of major depressive disorder-a translational subcortical-cortical framework for a system disorder. Neurosci Biobehav Rev. 2011 Oct;35(9):1929–45.

    Article  PubMed  Google Scholar 

  48. Craig AD. The sentient self. Brain Struct Funct. 2010 Jun;214(5–6):563–77.

    Article  PubMed  Google Scholar 

  49. Peterson A, Thome J, Frewen P, Lanius RA. Resting-state neuroimaging studies: a new way of identifying differences and similarities among the anxiety disorders? Can J Psychiatry. 2014 Jun;59(6):294–300.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Fonzo GA, Etkin A. Affective neuroimaging in generalized anxiety disorder: an integrated review. Dialogues Clin Neurosci. 2017 Jun;19(2):169–79.

    PubMed  PubMed Central  Google Scholar 

  51. MacNamara A, DiGangi J, Phan KL. Aberrant spontaneous and task-dependent functional connections in the anxious brain. Biol psychiatry Cogn Neurosci neuroimaging. 2016 May;1(3):278–87.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Shin Y-W, Dzemidzic M, Jo HJ, Long Z, Medlock C, Dydak U, et al. Increased resting-state functional connectivity between the anterior cingulate cortex and the precuneus in panic disorder: resting-state connectivity in panic disorder. J Affect Disord. 2013 Sep;150(3):1091–5.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Lai C-H, Wu Y-T. The alterations in inter-hemispheric functional coordination of patients with panic disorder: the findings in the posterior sub-network of default mode network. J Affect Disord. 2014 Sep;166:279–84.

    Article  PubMed  Google Scholar 

  54. Pannekoek JN, van der Werff SJA, Stein DJ, van der Wee NJA. Advances in the neuroimaging of panic disorder. Hum Psychopharmacol. 2013 Nov;28(6):608–11.

    Article  PubMed  Google Scholar 

  55. Lai C-H, Wu Y-T. The changes in the low-frequency fluctuations of cingulate cortex and postcentral gyrus in the treatment of panic disorder: the MRI study. World J Biol Psychiatry. 2016;17(1):58–65.

    Article  PubMed  Google Scholar 

  56. Mochcovitch MD, da Rocha Freire RC, Garcia RF, Nardi AE. A systematic review of fMRI studies in generalized anxiety disorder: evaluating its neural and cognitive basis. J Affect Disord. 2014;167:336–42.

    Article  PubMed  Google Scholar 

  57. Makovac E, Meeten F, Watson DR, Herman A, Garfinkel SN, D Critchley H, et al. Alterations in amygdala-prefrontal functional connectivity account for excessive worry and autonomic dysregulation in generalized anxiety disorder. Biol Psychiatry. 2016 Nov;80(10):786–95.

    Article  PubMed  Google Scholar 

  58. Hilbert K, Lueken U, Beesdo-Baum K. Neural structures, functioning and connectivity in generalized anxiety disorder and interaction with neuroendocrine systems: a systematic review. J Affect Disord. 2014 Apr;158:114–26.

    Article  PubMed  Google Scholar 

  59. Makovac E, Watson DR, Meeten F, Garfinkel SN, Cercignani M, Critchley HD, et al. Amygdala functional connectivity as a longitudinal biomarker of symptom changes in generalized anxiety. Soc Cogn Affect Neurosci. 2016 Nov;11(11):1719–28.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Zhang Y, Zhu C, Chen H, Duan X, Lu F, Li M, et al. Frequency-dependent alterations in the amplitude of low-frequency fluctuations in social anxiety disorder. J Affect Disord. 2015 Mar;174:329–35.

    Article  PubMed  Google Scholar 

  61. Wang W, Hou J, Qian S, Liu K, Li B, Li M, et al. Aberrant regional neural fluctuations and functional connectivity in generalized anxiety disorder revealed by resting-state functional magnetic resonance imaging. Neurosci Lett. 2016 Jun;624:78–84.

    Article  CAS  PubMed  Google Scholar 

  62. Yuan C, Zhu H, Ren Z, Yuan M, Gao M, Zhang Y, et al. Precuneus-related regional and network functional deficits in social anxiety disorder: A resting-state functional MRI study. Compr Psychiatry. 2018 Apr;82:22–9.

    Article  PubMed  Google Scholar 

  63. Caseras X, Murphy K, Mataix-Cols D, Lopez-Sola M, Soriano-Mas C, Ortriz H, et al. Anatomical and functional overlap within the insula and anterior cingulate cortex during interoception and phobic symptom provocation. Hum Brain Mapp. 2013 May;34(5):1220–9.

    Article  PubMed  Google Scholar 

  64. Zhang J, Magioncalda P, Huang Z, Tan Z, Hu X, Hu Z, et al. Altered global signal topography and its different regional localization in motor cortex and hippocampus in mania and depression. Schizophr Bull. 2018 Oct;

    Google Scholar 

  65. Wen H, Liu Z. Broadband electrophysiological dynamics contribute to global resting-state fMRI signal. J Neurosci. 2016 Jun;36(22):6030–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. He BJ, Zempel JM, Snyder AZ, Raichle ME. The temporal structures and functional significance of scale-free brain activity. Neuron. 2010 May;66(3):353–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Ganzetti M, Mantini D. Functional connectivity and oscillatory neuronal activity in the resting human brain. Neuroscience. 2013 Jun;240:297–309.

    Article  CAS  PubMed  Google Scholar 

  68. Christoff K, Irving ZC, Fox KCR, Spreng RN, Andrews-Hanna JR. Mind-wandering as spontaneous thought: a dynamic framework. Nat Rev Neurosci. 2016 Nov;17(11):718–31.

    Article  CAS  PubMed  Google Scholar 

  69. Miloyan B, Bulley A, Suddendorf T. Episodic foresight and anxiety: proximate and ultimate perspectives. Br J Clin Psychol. 2016 Mar;55(1):4–22.

    Article  PubMed  Google Scholar 

  70. Miloyan B, Pachana NA, Suddendorf T. The future is here: a review of foresight systems in anxiety and depression. Cogn Emot. 2014;28(5):795–810.

    Article  PubMed  Google Scholar 

  71. Paulus MP, Stein MB, Craske MG, Bookheimer S, Taylor CT, Simmons AN, et al. Latent variable analysis of positive and negative valence processing focused on symptom and behavioral units of analysis in mood and anxiety disorders. J Affect Disord. 2017 Jul;216:17–29.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Makovac E, Meeten F, Watson DR, Garfinkel SN, Critchley HD, Ottaviani C. Neurostructural abnormalities associated with axes of emotion dysregulation in generalized anxiety. NeuroImage Clin. 2015;10:172–81.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Khalsa SS, Adolphs R, Cameron OG, Critchley HD, Davenport PW, Feinstein JS, et al. Interoception and mental health: a roadmap. Biol psychiatry Cogn Neurosci Neuroimaging. 2018 Jun;3(6):501–13.

    Article  PubMed  Google Scholar 

  74. Quadt L, Critchley HD, Garfinkel SN. The neurobiology of interoception in health and disease. Ann NY Acad Sci. 2018 Sep;1428(1):112–28.

    Article  PubMed  Google Scholar 

  75. Mallorqui-Bague N, Bulbena A, Pailhez G, Garfinkel SN, Critchley HD. Mind-body interactions in anxiety and somatic symptoms. Harv Rev Psychiatry. 2016;24(1):53–60. 71.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. EJLB-Michael Smith Chair for Neuroscience and Mental Health, Royal Ottawa Healthcare Group, University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada

    Georg Northoff

Authors
  1. Georg Northoff
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Georg Northoff .

Editor information

Editors and Affiliations

  1. College of Medicine, Korea University, Gyeonggido, Korea (Republic of)

    Yong-Ku Kim

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Northoff, G. (2020). Anxiety Disorders and the Brain’s Resting State Networks: From Altered Spatiotemporal Synchronization to Psychopathological Symptoms. In: Kim, YK. (eds) Anxiety Disorders. Advances in Experimental Medicine and Biology, vol 1191. Springer, Singapore. https://doi.org/10.1007/978-981-32-9705-0_5

Download citation

Publish with us

Policies and ethics

Search

Navigation