Sleep and Biological Rhythms

, Volume 15, Issue 2, pp 167–177 | Cite as

Unbalanced resting-state networks activity in psychophysiological insomnia

  • Daniel Ruivo Marques
  • Ana Allen Gomes
  • Vanda Clemente
  • José Moutinho dos Santos
  • Isabel Catarina Duarte
  • Gina Caetano
  • Miguel Castelo-Branco
Original Article


Psychophysiological insomnia (PI) is a clinical condition characterized by sleep-related disturbing cognitive activity and biased self-related information processing. This hypothetical cognitive arousal has been hypothesized to be associated with overactivation within different brain areas and networks, especially when individuals are at rest, e.g., in the absence of any attention-demanding task. In this study, we carried out a resting-state fMRI experiment aimed at investigating activity of the different resting-state networks in PI. Our pool of participants was compound of 5 PI patients and 5 sex- and age-matched healthy controls recruited from the community. Participants from both groups also completed a set of self-report measures, including the sleep diary, Insomnia Severity Index (ISI), dysfunctional beliefs and attitudes about sleep (DBAS-30), and the World Health Organization Quality of Life Measure (WHOQOL-Bref). Our results showed that insomnia patients presented altered activation in the default-mode network (DMN), visual and auditory networks, and bilateral fronto-parietal networks. In the DMN, the patients presented a pattern of both decreased (right superior frontal gyrus, left medial frontal gyrus, and right middle temporal gyrus) and increased activation (left superior frontal gyrus, left anterior and posterior cingulate, right precuneus, left cingulate gyrus, and left middle temporal gyrus). Our findings on unbalanced resting-state networks in PI, with special emphasis on the DMN, may lay grounds to better understanding of the cognitive arousal experienced by PI patients and might help to further improve the clinical management of insomnia.


Insomnia Resting-state networks Neural activation Default-mode network Neuroimaging fMRI 


  1. 1.
    van den Heuvel M, Pol H. Exploring the brain network: A review on resting-state fMRI functional connectivity. Eur Neuropsychopharmacol. 2010;20:519–34.CrossRefPubMedGoogle Scholar
  2. 2.
    Buckner R, Krienen F, Yeo T. Opportunities and limitations of intrinsic functional connectivity MRI. Nat Neurosci. 2013;16:832–37.CrossRefPubMedGoogle Scholar
  3. 3.
    Poldrack R, Mumford J, Nichols T. Handbook of functional MRI data analysis. New York: Cambridge University Press; 2011.CrossRefGoogle Scholar
  4. 4.
    Raichle M, MacLeod A, Snyder A, Powers W, Gusnard D, Schulman G. A default mode of brain function. Proc Natl Acad Sci USA. 2001;98:676–82.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Whitfield-Gabrieli S, Ford J. Default mode network activity and connectivity in psychopathology. Annu Rev Clin Psychol. 2012;8:49–76.CrossRefPubMedGoogle Scholar
  6. 6.
    Buckner R, Andrews-Hanna J, Schacter D. The brain’s default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci. 2008;1124:1–38.CrossRefPubMedGoogle Scholar
  7. 7.
    Buckner R. The serendipitous discovery of the brain’s default network. Neuroimage. 2012;62:1137–45.CrossRefPubMedGoogle Scholar
  8. 8.
    Anticevic A, Cole M, Murray J, et al. The role of default network deactivation in cognition and disease. Trends Cogn Sci. 2013;16:584–92.CrossRefGoogle Scholar
  9. 9.
    Broyd S, Demanuele C, Debener S, Helps S, James C, Sonuga-Barke E. Default-mode brain dysfunction in mental disorders: a systematic review. Neurosci Biobehav Rev. 2009;33:279–96.CrossRefPubMedGoogle Scholar
  10. 10.
    Greicius M, Krasnow B, Reiss A, Menon V. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci USA. 2003;100:253–58.CrossRefPubMedGoogle Scholar
  11. 11.
    AASM. International Classification of sleep disorders: Diagnostic and coding manual. 2nd ed. Westchester: American Academy of Sleep Medicine; 2005.Google Scholar
  12. 12.
    AASM. International Classification of sleep disorders: Diagnostic and coding manual. 3rd ed. Westchester: American Academy of Sleep Medicine; 2014.Google Scholar
  13. 13.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013.CrossRefGoogle Scholar
  14. 14.
    Riemann D, Spiegelhalder K, Feige B, Voderholzer U, Berger M, Perlis M, et al. The hyperarousal model of insomnia: a review of the concept and its evidence. Sleep Med Rev. 2010;14:19–31.CrossRefPubMedGoogle Scholar
  15. 15.
    Marques D, Gomes A, Clemente V, Santos J, Castelo-Branco M. Default-mode network activity and its role in comprehension and management of psychophysiological insomnia: a new perspective. New Ideas Psychol. 2015;36:30–7.CrossRefGoogle Scholar
  16. 16.
    Nofzinger E. Brain imaging in insomnia. In: Sateia M, Buysse D, eds. Insomnia: diagnosis and treatment, UK: Informa Health Care; 2010, p. 77–83.CrossRefGoogle Scholar
  17. 17.
    Nofzinger E Functional neuroimaging of primary insomnia. In: Nofzinger E, Maquet P, Thorpy M, eds. Neuroimaging of sleep and sleep disorders. Cambridge: Cambridge University Press; 2013, pp. 197–208.CrossRefGoogle Scholar
  18. 18.
    Nofzinger E, Buysse D, Germain A, Price J, Miewald J, Kupfer D. Functional neuroimaging evidence for hyperarousal in insomnia. Am J Psychiatry. 2004;161:2126–29.CrossRefPubMedGoogle Scholar
  19. 19.
    Koike T, Kan S, Misaki M, Miyauchi S. Connectivity pattern changes in default-mode network with deep non-REM and REM sleep. Neurosci Res. 2011;69:322–30.CrossRefPubMedGoogle Scholar
  20. 20.
    Sämann P, Wehrle L, Hoehn D, Spoormaker V, Peters H, Tully C, et al. Development of the brain´s default mode network from wakefulness to slow wave sleep. Cereb Cortex. 2011;21:2082–93.CrossRefPubMedGoogle Scholar
  21. 21.
    Wamsley E, Stickgold R. Memory, sleep and dreaming: experiencing consolidation. Sleep Med Clin. 2011;6:97–108.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Hasler B, James J, Franzen P, Nofzinger E, Germain A, Buysse D. Variation in default mode network connectivity across sleep-wake states differs between adults with primary insomnia and good sleepers. Sleep. 2013;36:e192.Google Scholar
  23. 23.
    Drummond S, Walker M, Almklov E, Campos M, Anderson D, Strauss L. Neural correlates of working memory performance in primary insomnia. Sleep. 2013;36:1307–16.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Huang Z, Liang P, Jia X, Zhan S, Li N, Ding Y, et al. Abnormal amygdala connectivity in patients with primary insomnia: evidence from resting state fMRI. Eur J Radiol. 2012;81:1288–95.CrossRefPubMedGoogle Scholar
  25. 25.
    Buysse D, Germain A, Hall M, Monk T, Nofzinger E. A neurobiological model of insomnia. Drug Discov Today Dis Models. 2011;8:129–37.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Coutinho J, Gonçalves O, Maia L, Fernandes Vasconcelos C, Perrone-McGovern K, Simon-Dack S, et al. Differential activation of the default mode network in jet lagged individuals. Chronobiol Int. 2014;32:143–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Killgore W, Schwab Z, Kipman M, DelDonno S, Weber M. Insomnia-related complaints correlate with functional connectivity between sensory–motor regions. NeuroReport. 2013;24:233–40.CrossRefPubMedGoogle Scholar
  28. 28.
    Clemente V. Dysfunctional beliefs and attitudes about sleep—DBAS-30, European Portuguese Version. Portugal: Coimbra University Hospital Centre, Sleep Medicine Centre; 2007, 2013.Google Scholar
  29. 29.
    Morin C. Insomnia: psychological assessment and management. New York: The Guilford Press; 1993.Google Scholar
  30. 30.
    Bastien C, Vallières A, Morin C. Validation of the Insomnia Severity Index as an outcome measure for insomnia research. Sleep Med. 2001;2:297–307.CrossRefPubMedGoogle Scholar
  31. 31.
    Clemente V. Insomnia Severity Index—ISI, European Portuguese Version. Coimbra University Hospital Centre, Sleep Medicine Centre, Portugal; 2007, 2013.Google Scholar
  32. 32.
    Clemente V. Sleep Diary, European Portuguese Version. Coimbra University Hospital Centre, Sleep Medicine Centre, Portugal; 2006.Google Scholar
  33. 33.
    Vaz-Serra A, Canavarro MC, Simões MR, Pereira M, Gameiro S, Quartilho M, et al. Estudos psicométricos do instrumento de avaliação da qualidade de vida da Organização Mundial de Saúde (WHOQOL-Bref) para Português de Portugal [Psychometric studies on the quality of life assessment instrument of World Health Organization (WHOQOL-Bref) for European Portuguese]. Psiquiatria Clín 2006;27:41–9.Google Scholar
  34. 34.
    Long X, Zuo X, Kiviniemi V, Yang W, Zou Q, Zhu C, et al. Default mode network as revealed with multiple methods for resting-state functional MRI analysis. J Neurosci Methods. 2008;171:349–55.CrossRefPubMedGoogle Scholar
  35. 35.
    Andrews-Hanna J, Reidler J, Sepulcre J, Poulin R, Buckner R. Functional-anatomic fractionation of the brain’s default network. Neuron. 2010;65:550–62.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Formisano E, Esposito F, Di Salle F, Goebel R. Cortex-based independent component analysis of fMRI time-series. Magn Reson Imaging. 2004;22:1493–504.CrossRefPubMedGoogle Scholar
  37. 37.
    De Martino F, Gentile F, Esposito F, Balsi M, Di Salle F, Goebel R, et al. Classification of fMRI independent components using IC-fingerprints and support vector machine classifiers. Neuroimage. 2007;34:177–94.CrossRefPubMedGoogle Scholar
  38. 38.
    Esposito R, Mosca A, Pieramico V, Cieri F, Cera N, Sensi L. Characterization of resting state activity in MCI individuals. PeerJ 2013:1:e.135.CrossRefGoogle Scholar
  39. 39.
    Esposito F, Scarabino T, Hyvarinen A, Himberg J, Formisano E, Comani S, et al. Independent component analysis of fMRI group studies by self-organizing clustering. Neuroimage. 2004;25:193–205.CrossRefGoogle Scholar
  40. 40.
    Goebel R, Esposito F, Formisano E. Analysis of functional image analysis contest (FIAC) data with Brainvoyager QX: From single-subject to cortically aligned group general linear model analysis and self-organizing group independent component analysis. Hum Brain Mapp. 2006;27:392–401.CrossRefPubMedGoogle Scholar
  41. 41.
    Kornelsen J, Sboto-Frankenstein U, McIver T, Gervai P, Wacnik P, Berrington N, et al. Default mode network functional connectivity altered in failed back surgery syndrome. J Pain. 2013;14:483–91.CrossRefPubMedGoogle Scholar
  42. 42.
    Jann K, Kottlow M, Dierks T, Boesch C, Koenig T. Topographic electrophysiological signatures of fMRI resting state networks. PloS One. 2010;5:e12945.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Franzen P, Siegle G, Jones N, Buysse D. Elevated amygdala activation during voluntary emotion regulation in primary insomnia. Sleep. 2013;36:e194.Google Scholar
  44. 44.
    Ansfield M, Wegner D, Bowser R. Ironic effects of sleep urgency. Behav Res Ther. 1996;34:523–31.CrossRefPubMedGoogle Scholar
  45. 45.
    Schacter D, Addis D. On the nature of medial temporal lobe contributions to the constructive simulation of future events. Philos Trans Roy Soc London. 2009;364:1245–53.CrossRefGoogle Scholar
  46. 46.
    Wang K, Jiang T, Yu C, Tian L, Liu Y, Zhou Y, et al. Spontaneous activity associated with primary visual cortex: a resting-state fMRI study. Cereb Cortex. 2008;18:697–704.CrossRefPubMedGoogle Scholar
  47. 47.
    Dai XJ, Peng DC, Gong HH, Wan A, Nie X, Li H, Wang Y. Altered intrinsic regional brain spontaneous activity and subjective sleep quality in patients with chronic primary insomnia: a resting-state fMRI study. Neuropsychiatr Dis Treat. 2014;10:2163–75.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Li C, Ma X, Dong M, Yin Y, Hua K, Li M, et al. Abnormal spontaneous regional brain activity in primary insomnia: a resting-state functional magnetic resonance imaging study. Neuropsychiatr Dis Treat. 2016;12:1371–8.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Liu, C. H., Liu, C. Z., Zhang, J., Yuan, Z., Tang, L. R., Tie, C. L. et al. (2016). Reduced spontaneous neuronal activity in the insular cortex and thalamus in healthy adults with insomnia symptoms. Brain Res 2016;1648:317–24.CrossRefPubMedGoogle Scholar

Copyright information

© Japanese Society of Sleep Research 2017

Authors and Affiliations

  • Daniel Ruivo Marques
    • 1
    • 2
  • Ana Allen Gomes
    • 3
    • 4
  • Vanda Clemente
    • 5
  • José Moutinho dos Santos
    • 5
  • Isabel Catarina Duarte
    • 6
  • Gina Caetano
    • 2
    • 6
    • 7
  • Miguel Castelo-Branco
    • 2
    • 6
  1. 1.Department of Education and PsychologyUniversity of AveiroAveiroPortugal
  2. 2.Institute for Biomedical Imaging and Life SciencesIBILICoimbraPortugal
  3. 3.Faculty of Psychology and Educational SciencesUniversity of CoimbraCoimbraPortugal
  4. 4.Centro de Investigação do Núcleo de Estudos e Intervenção Cognitivo-Comportamental/Research and Development Unit (FCT), Cognitive and Behavioral Center for Research and InterventionCINEICCCoimbraPortugal
  5. 5.Sleep Medicine CentreCoimbra University Hospital Centre (CHUC)CoimbraPortugal
  6. 6.Brain Imaging NetworkICNASCoimbraPortugal
  7. 7.ISR-Lisboa/LARSyS and Department of Bioengineering, Instituto Superior TécnicoUniversidade de LisboaLisbonPortugal

Personalised recommendations