Advertisement

Abnormalities of thalamus volume and resting state functional connectivity in primary insomnia patients

  • Min Li
  • Ruonan Wang
  • Meng Zhao
  • Jinquan Zhai
  • Bo Liu
  • Dahua Yu
  • Kai Yuan
Original Research

Abstract

Primary insomnia (PI) is associated with deteriorating attention, memory, physical and mood complaints. Based on the extensive literature demonstrating the critical roles of the thalamus in sleep regulation, we hypothesized that insomnia would be associated with functional and structural changes of the thalamus. This information is needed to better understand the neural mechanisms of insomnia, and would be useful for informing future attempts to alleviate or treat insomnia symptoms. Twenty-seven PI patients and 39 matched healthy controls were included in the present study. Subcortical volume and resting state functional connectivity (RSFC) of thalamus were compared between groups, and the relationships between neuroimaging differences and clinical features, including the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index Scale (ISI), the Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS), also be explored. Compared with the control group, the PI group showed significantly reduced volume of thalamus. In addition, several brain regions showed reduced RSFC with thalamus in PI patients, such as anterior cingulate cortex (ACC), orbitofrontal cortex, hippocampus, caudate and putamen. Correlation analyses revealed that, several of these RSFC patterns were negatively correlated with PSQI score among PI patients, including thalamic connections with the putamen, caudate, hippocampus. Negative correlation was also observed between the RSFC strength of right thalamus–right ACC and SDS score in PI patients. This work demonstrates the structural and functional abnormalities of the thalamus in PI patients that were associated with key clinical features of insomnia. These data further highlight the important role of the thalamus in sleep and PI.

Keywords

Insomnia Thalamus Resting state functional connectivity Pittsburgh sleep quality index 

Notes

Acknowledgements

This work is supported by the National Natural Science Foundation of China under Grant Nos. 81571751, 81571753, 61771266, 81701780, the Fundamental Research Funds for the Central Universities under the Grant No. JB151204, the program for Young Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region NJYT-17-B11, the Natural Science Foundation of Inner Mongolia under Grant No. 2017MS(LH)0814, 2018LH08079, the program of Science and Technology in Universities of Inner Mongolia Autonomous Region NJZY17262, the Innovation Fund Project of Inner Mongolia University of Science and Technology No. 2015QNGG03, National Natural Science Foundation of Shaanxi Province under Grant No. 2017JM6051, 2018JM7075. The funding agencies played no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The authors report no biomedical financial interests or potential conflicts of interest.

Compliance with ethical standards

Ethical statements

Informed consent was obtained from all individual participants included in the study.

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflict of interest

The authors report no biomedical financial interests or potential conflicts of interest.

References

  1. Aggleton, J. P., O’Mara, S. M., Vann, S. D., Wright, N. F., Tsanov, M., & Erichsen, J. T. (2010). Hippocampal–anterior thalamic pathways for memory: Uncovering a network of direct and indirect actions. European Journal of Neuroscience, 31(12), 2292–2307.CrossRefPubMedGoogle Scholar
  2. Alexander, G. E., DeLong, M. R., & Strick, P. L. (1986). Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annual Review of Neuroscience, 9(1), 357–381.CrossRefPubMedGoogle Scholar
  3. Altena, E., Van Der Werf, Y. D., Strijers, R. L., & Van Someren, E. J. (2008). Sleep loss affects vigilance: Effects of chronic insomnia and sleep therapy. Journal of Sleep Research, 17(3), 335–343.CrossRefPubMedGoogle Scholar
  4. Altena, E., Vrenken, H., Van Der Werf, Y. D., van den Heuvel, O. A., & Van Someren, E. J. (2010). Reduced orbitofrontal and parietal gray matter in chronic insomnia: A voxel-based morphometric study. Biological Psychiatry, 67(2), 182–185.CrossRefPubMedGoogle Scholar
  5. Altena, E., Micoulaud-Franchi, J.-A., Geoffroy, P.-A., Sanz-Arigita, E., Bioulac, S., & Philip, P. (2016). The bidirectional relation between emotional reactivity and sleep: From disruption to recovery. Behavioral Neuroscience, 130(3), 336.CrossRefPubMedGoogle Scholar
  6. Ancoli-Israel, S., & Roth, T. (1999). Characteristics of insomnia in the United States: Results of the 1991 National Sleep Foundation survey. I. Sleep, 22, S347–S353.PubMedGoogle Scholar
  7. Backhaus, J., Junghanns, K., Born, J., Hohaus, K., Faasch, F., & Hohagen, F. (2006). Impaired declarative memory consolidation during sleep in patients with primary insomnia: Influence of sleep architecture and nocturnal cortisol release. Biological Psychiatry, 60(12), 1324–1330.CrossRefPubMedGoogle Scholar
  8. Baglioni, C., Spiegelhalder, K., Lombardo, C., & Riemann, D. (2010). Sleep and emotions: A focus on insomnia. Sleep Medicine Reviews, 14(4), 227–238.CrossRefPubMedGoogle Scholar
  9. Batterham, P. J., Glozier, N., & Christensen, H. (2012). Sleep disturbance, personality and the onset of depression and anxiety: Prospective cohort study. Australian & New Zealand Journal of Psychiatry, 46(11), 1089.CrossRefGoogle Scholar
  10. Bechara, A., Damasio, H., & Damasio, A. R. (2000). Emotion, decision making and the orbitofrontal cortex. Cerebral Cortex, 10(3), 295–307.CrossRefPubMedGoogle Scholar
  11. Berry, K. J., & Mielke Jr., P. W. (2000). A Monte Carlo investigation of the fisher Z transformation for normal and nonnormal distributions. Psychological Reports, 87(3_suppl), 1101–1114.CrossRefPubMedGoogle Scholar
  12. Boutin, A., Pinsard, B., Boré, A., Carrier, J., Fogel, S. M., & Doyon, J. (2017). Transient synchronization of hippocampo-striato-thalamo-cortical networks during sleep spindle oscillations induces motor memory consolidation. NeuroImage.Google Scholar
  13. Breslau, N., Roth, T., Rosenthal, L., & Andreski, P. (1996). Sleep disturbance and psychiatric disorders: A longitudinal epidemiologic study of young adults. Biological Psychiatry, 39(6), 411–418.CrossRefPubMedGoogle Scholar
  14. Bricolo, A. (1967). Insomnia after bilateral stereotactic thalamotomy in man. Journal of neurology, Neurosurgery, and Psychiatry, 30(2), 154.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Bruno, R. M., & Sakmann, B. (2006). Cortex is driven by weak but synchronously active thalamocortical synapses. Science, 312(5780), 1622–1627.CrossRefPubMedGoogle Scholar
  16. Bush, G., Luu, P., & Posner, M. I. (2000). Cognitive and emotional influences in anterior cingulate cortex. Trends in Cognitive Sciences, 4(6), 215–222.CrossRefPubMedGoogle Scholar
  17. Buysse, D. J., Reynolds, C. F., Monk, T. H., Berman, S. R., & Kupfer, D. J. (1989). The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Research, 28(2), 193–213.CrossRefPubMedGoogle Scholar
  18. Cai, C., Yuan, K., Yin, J., Feng, D., Bi, Y., Li, Y., et al. (2016). Striatum morphometry is associated with cognitive control deficits and symptom severity in internet gaming disorder. Brain Imaging and Behavior, 10(1), 12–20.CrossRefPubMedGoogle Scholar
  19. Coenen, V. A., Panksepp, J., Hurwitz, T. A., Urbach, H., & Mädler, B. (2012). Human medial forebrain bundle (MFB) and anterior thalamic radiation (ATR): Imaging of two major subcortical pathways and the dynamic balance of opposite affects in understanding depression. The Journal of Neuropsychiatry and Clinical Neurosciences, 24(2), 223–236.CrossRefPubMedGoogle Scholar
  20. Cooper, J. (2001). Diagnostic and statistical manual of mental disorders (4th edn, text revision)(DsM-IV-TR). RCP.Google Scholar
  21. Del Felice, A., Formaggio, E., Storti, S. F., Fiaschi, A., & Manganotti, P. (2012). The gating role of the thalamus to protect sleep: An f-MRI report. Sleep Medicine, 13(4), 447–449.CrossRefPubMedGoogle Scholar
  22. Dichter, G. S., Richey, J. A., Rittenberg, A. M., Sabatino, A., & Bodfish, J. W. (2012). Reward circuitry function in autism during face anticipation and outcomes. Journal of Autism and Developmental Disorders, 42(2), 147–160.CrossRefPubMedGoogle Scholar
  23. Drevets, W. C., Savitz, J., & Trimble, M. (2008). The subgenual anterior cingulate cortex in mood disorders. CNS Spectrums, 13(8), 663.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Eklund, A., Nichols, T. E., & Knutsson, H. (2016). Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates. Proceedings of the National Academy of Sciences, 113(28), 7900–7905.CrossRefGoogle Scholar
  25. Fernandez-Mendoza, J., Vgontzas, A. N., Bixler, E. O., Singareddy, R., Shaffer, M. L., Calhoun, S. L., et al. (2012). Clinical and polysomnographic predictors of the natural history of poor sleep in the general population. Sleep, 35(5), 689–697.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Ford, D. E., & Kamerow, D. B. (2016). Epidemiologic study of sleep disturbances and psychiatric disorders: An opportunity for prevention? Jama, 262(11), 1479–1484.CrossRefGoogle Scholar
  27. Fortier-Brochu, É., Beaulieu-Bonneau, S., Ivers, H., & Morin, C. M. (2012). Insomnia and daytime cognitive performance: A meta-analysis. Sleep Medicine Reviews, 16(1), 83–94.CrossRefPubMedGoogle Scholar
  28. Guzman-Marin, R., Suntsova, N., Methippara, M., Greiffenstein, R., Szymusiak, R., & McGinty, D. (2005). Sleep deprivation suppresses neurogenesis in the adult hippocampus of rats. European Journal of Neuroscience, 22(8), 2111–2116.CrossRefPubMedGoogle Scholar
  29. Hairston, I. S., Little, M. T., Scanlon, M. D., Barakat, M. T., Palmer, T. D., Sapolsky, R. M., et al. (2005). Sleep restriction suppresses neurogenesis induced by hippocampus-dependent learning. Journal of Neurophysiology, 94(6), 4224–4233.CrossRefPubMedGoogle Scholar
  30. Holtzheimer, P. E., & Mayberg, H. S. (2011). Deep brain stimulation for psychiatric disorders. Annual Review of Neuroscience, 34, 289–307.CrossRefPubMedPubMedCentralGoogle Scholar
  31. Koo, D. L., Shin, J.-H., Lim, J.-S., Seong, J.-K., & Joo, E. Y. (2017). Changes in subcortical shape and cognitive function in patients with chronic insomnia. Sleep Medicine, 35, 23–26.CrossRefPubMedGoogle Scholar
  32. Kopp, C., Longordo, F., Nicholson, J. R., & Lüthi, A. (2006). Insufficient sleep reversibly alters bidirectional synaptic plasticity and NMDA receptor function. Journal of Neuroscience, 26(48), 12456–12465.CrossRefPubMedGoogle Scholar
  33. Kyle, S. D., Espie, C. A., & Morgan, K. (2010a). “… not just a minor thing, it is something major, which stops you from functioning daily”: Quality of life and daytime functioning in insomnia. Behavioral Sleep Medicine, 8(3), 123–140.CrossRefPubMedGoogle Scholar
  34. Kyle, S. D., Morgan, K., & Espie, C. A. (2010b). Insomnia and health-related quality of life. Sleep Medicine Reviews, 14(1), 69–82.CrossRefPubMedGoogle Scholar
  35. Lazarus, M., Huang, Z.-L., Lu, J., Urade, Y., & Chen, J.-F. (2012). How do the basal ganglia regulate sleep–wake behavior? Trends in Neurosciences, 35(12), 723–732.CrossRefPubMedGoogle Scholar
  36. Li, Y., Yuan, K., Cai, C., Feng, D., Yin, J., Bi, Y., et al. (2015). Reduced frontal cortical thickness and increased caudate volume within fronto-striatal circuits in young adult smokers. Drug and Alcohol Dependence, 151, 211–219.CrossRefPubMedGoogle Scholar
  37. Lugaresi, E., Medori, R., Montagna, P., Baruzzi, A., Cortelli, P., Lugaresi, A., et al. (1986). Fatal familial insomnia and dysautonomia with selective degeneration of thalamic nuclei. New England Journal of Medicine, 315(16), 997–1003.CrossRefPubMedGoogle Scholar
  38. Ma, N., Dinges, D. F., Basner, M., & Rao, H. (2015). How acute total sleep loss affects the attending brain: A meta-analysis of neuroimaging studies. Sleep, 38(2), 233–240.CrossRefPubMedPubMedCentralGoogle Scholar
  39. Mirescu, C., Peters, J. D., Noiman, L., & Gould, E. (2006). Sleep deprivation inhibits adult neurogenesis in the hippocampus by elevating glucocorticoids. Proceedings of the National Academy of Sciences, 103(50), 19170–19175.CrossRefGoogle Scholar
  40. Morin, C. M., LeBlanc, M., Daley, M., Gregoire, J., & Merette, C. (2006). Epidemiology of insomnia: Prevalence, self-help treatments, consultations, and determinants of help-seeking behaviors. Sleep Medicine, 7(2), 123–130.CrossRefPubMedGoogle Scholar
  41. Neckelmann, D., Mykletun, A., & Dahl, A. A. (2002). Chronic sleep disturbances: A risk factor for developing anxiety and depression? A longitudinal epidemiological study. Acta Psychiatrica Scandinavica, 105, 46–46.Google Scholar
  42. Nissen, C., Kloepfer, C., Nofzinger, E. A., Feige, B., Voderholzer, U., & Riemann, D. (2006). Impaired sleep-related memory consolidation in primary insomnia—A pilot study. Sleep, 29(8), 1068–1073.CrossRefPubMedGoogle Scholar
  43. Ohayon, M. M. (2002). Epidemiology of insomnia: What we know and what we still need to learn. Sleep Medicine Reviews, 6(2), 97–111.CrossRefPubMedGoogle Scholar
  44. Oldfield, R. C. (1971). The assessment and analysis of handedness: The Edinburgh inventory. Neuropsychologia, 9(1), 97–113.CrossRefPubMedGoogle Scholar
  45. Pace-Schott, E. F., & Hobson, J. A. (2002). The neurobiology of sleep: Genetics, cellular physiology and subcortical networks. Nature Reviews Neuroscience, 3(8), 591.CrossRefPubMedGoogle Scholar
  46. Patel, A. X., Kundu, P., Rubinov, M., Jones, P. S., Vértes, P. E., Ersche, K. D., et al. (2014). A wavelet method for modeling and despiking motion artifacts from resting-state fMRI time series. Neuroimage, 95, 287–304.CrossRefPubMedPubMedCentralGoogle Scholar
  47. Perlis, M. L., Giles, D. E., Mendelson, W. B., Bootzin, R. R., & Wyatt, J. K. (1997). Psychophysiological insomnia: The behavioural model and a neurocognitive perspective. Journal of Sleep Research, 6(3), 179.CrossRefPubMedGoogle Scholar
  48. Power, J. D., Barnes, K. A., Snyder, A. Z., Schlaggar, B. L., & Petersen, S. E. (2012). Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. Neuroimage, 59(3), 2142–2154.CrossRefPubMedGoogle Scholar
  49. Qiu, M. H., Vetrivelan, R., Fuller, P. M., & Lu, J. (2010). Basal ganglia control of sleep–wake behavior and cortical activation. European Journal of Neuroscience, 31(3), 499–507.CrossRefPubMedGoogle Scholar
  50. Riemann, D., Voderholzer, U., Spiegelhalder, K., Hornyak, M., Buysse, D. J., Nissen, C., et al. (2007). Chronic insomnia and MRI-measured hippocampal volumes: A pilot study. Sleep, 30(8), 955–958.CrossRefPubMedPubMedCentralGoogle Scholar
  51. Roth, T., Coulouvrat, C., Hajak, G., Lakoma, M. D., Sampson, N. A., Shahly, V., et al. (2011). Prevalence and perceived health associated with insomnia based on DSM-IV-TR; international statistical classification of diseases and related health problems, tenth revision; and research diagnostic criteria/international classification of sleep disorders, criteria: Results from the America insomnia survey. Biological Psychiatry, 69(6), 592–600.CrossRefPubMedGoogle Scholar
  52. Saper, C. B., Scammell, T. E., & Lu, J. (2005). Hypothalamic regulation of sleep and circadian rhythms. Nature, 437(7063), 1257.CrossRefPubMedGoogle Scholar
  53. Schott, B., Michel, D., Mouret, J., Renaud, B., Quenin, P., & Tommasi, M. (1972). Monoamines et régulation de la vigilance. II. Syndromes lésionnels du système nerveux central. Revista de Neurologia, 127, 157–171.Google Scholar
  54. Sherman, S. M. (2016). Thalamus plays a central role in ongoing cortical functioning. Nature Neuroscience, 16(4), 533–541.CrossRefGoogle Scholar
  55. Sivertsen, B., Krokstad, S., Øverland, S., & Mykletun, A. (2009). The epidemiology of insomnia: Associations with physical and mental health.: The HUNT-2 study. Journal of Psychosomatic Research, 67(2), 109–116.CrossRefPubMedGoogle Scholar
  56. Steriade, M., Deschenes, M., Domich, L., & Mulle, C. (1985). Abolition of spindle oscillations in thalamic neurons disconnected from nucleus reticularis thalami. Journal of Neurophysiology, 54(6), 1473–1497.CrossRefPubMedGoogle Scholar
  57. Stickgold, R. (2005). Sleep-dependent memory consolidation. Nature, 437(7063), 1272.CrossRefPubMedGoogle Scholar
  58. Venkatraman, V., Chuah, Y. M., Huettel, S. A., & Chee, M. W. (2007). Sleep deprivation elevates expectation of gains and attenuates response to losses following risky decisions. Sleep, 30(5), 603–609.CrossRefPubMedGoogle Scholar
  59. Vetrivelan, R., Qiu, M.-H., Chang, C., & Lu, J. (2010). Role of basal ganglia in sleep–wake regulation: Neural circuitry and clinical significance. Frontiers in Neuroanatomy, 4.Google Scholar
  60. Wicklow, A., & Espie, C. (2000). Intrusive thoughts and their relationship to actigraphic measurement of sleep: Towards a cognitive model of insomnia. Behaviour Research and Therapy, 38(7), 679–693.CrossRefPubMedGoogle Scholar
  61. Winkelman, J. W., Plante, D. T., Schoerning, L., Benson, K., Buxton, O. M., O'Connor, S. P., et al. (2013). Increased rostral anterior cingulate cortex volume in chronic primary insomnia. Sleep, 36(7), 991–998.CrossRefPubMedPubMedCentralGoogle Scholar
  62. Yuan, K., Zhao, L., Cheng, P., Yu, D., Zhao, L., Dong, T., et al. (2013). Altered structure and resting-state functional connectivity of the basal ganglia in migraine patients without aura. The Journal of Pain, 14(8), 836–844.CrossRefPubMedGoogle Scholar
  63. Yuan, K., Yu, D., Bi, Y., Li, Y., Guan, Y., Liu, J., et al. (2016). The implication of frontostriatal circuits in young smokers: A resting-state study. Human Brain Mapping, 37(6), 2013–2026.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Life Science and TechnologyXidian UniversityXi’anPeople’s Republic of China
  2. 2.Engineering Research Center of Molecular and Neuro Imaging Ministry of EducationXi’anPeople’s Republic of China
  3. 3.Department of Medical Imaging, The First Affiliated Hospital of Baotou Medical CollegeInner Mongolia University of Science and TechnologyBaotouPeople’s Republic of China
  4. 4.Department of Neurology, The First Affiliated Hospital of Baotou Medical CollegeInner Mongolia University of Science and TechnologyBaotouPeople’s Republic of China
  5. 5.School of Information EngineeringInner Mongolia University of Science and TechnologyBaotouPeople’s Republic of China

Personalised recommendations