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Asymmetric alterations of white matter integrity in patients with insomnia disorder

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Abstract

Despite the adverse consequences of insomnia disorder for both individuals and society, the underlying neurobiological processes are poorly understood. The purpose was to further understand the alterations of white matter tracts in patients with insomnia and their association with sleep variables and also to determine if diffusion tensor imaging measures would be a useful disease marker. Twenty-six patients with insomnia and 26 age-matched healthy volunteers underwent diffusion tensor imaging. We employed an automated probabilistic tractography analysis approach using TRActs Constrained by UnderLying Anatomy (TRACULA) to quantify diffusion measures in major white matter tracts. We found significantly increased fractional anisotropy in the right cingulum-angular bundle and uncinate fasciculus in patients group compared to controls. Moreover, the mean diffusivity and radial diffusivity were reduced in the right cingulum-angular bundle in patients group in comparison with controls. We also found significantly increased fractional anisotropy along the bilateral cingulum-angular bundle and right uncinate fasciculus in patients. Also, mean and radial diffusivity were reduced along the right cingulum-angular bundle in patients group compared to controls. There is a significant positive correlation between fractional anisotropy and Epworth Sleepiness Scale scores. Moreover, there are negative correlations between mean, radial and axial diffusivity and total sleep time and sleep efficiency and also positive correlations between mean, radial and axial diffusivity and duration of disease and Pittsburgh Sleep Quality Index scores. This study showed the importance of examining whole-tract and waypoint white matter integrity in insomnia disorder. We found asymmetric widespread white matter integrity changes in patients with insomnia.

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Data availability

The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

References

  • 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.

    PubMed  Google Scholar 

  • Andrews-Hanna, J. R., Reidler, J. S., Sepulcre, J., Poulin, R., & Buckner, R. L. (2010). Functional-anatomic fractionation of the brain’s default network. Neuron, 65(4), 550–562.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Averill, C. L., Averill, L. A., Wrocklage, K. M., Scott, J. C., Akiki, T. J., Schweinsburg, B., Southwick, S. M., Krystal, J. H., & Abdallah, C. G. (2018). Altered white matter diffusivity of the cingulum angular bundle in posttraumatic stress disorder. Molecular Neuropsychiatry, 4, 75–82.

    PubMed  PubMed Central  Google Scholar 

  • Ballesio, A., Aquino, M. R. J. V., Kyle, S. D., Ferlazzo, F., & Lombardo, C. (2019). Executive functions in insomnia disorder: A systematic review and exploratory meta-analysis. Frontiers in Psychology, 10, 101.

    PubMed  PubMed Central  Google Scholar 

  • Benedetti, F., Melloni, E. M., Dallaspezia, S., Bollettini, I., Locatelli, C., Poletti, S., & Colombo, C. (2017). Night sleep influences white matter microstructure in bipolar depression. Journal of Affective Disorders, 218, 380–387.

    PubMed  Google Scholar 

  • Benjamini, Y., & Hochberg, Y. (1995). Controlling the false discovery rate: A practical and powerful approach to multiple testing. Journal of the Royal Statistical Society: Series B (methodological), 57(1), 289–300.

    Google Scholar 

  • Bonnet, M. H., & Arand, D. L. (2006). Consequences of insomnia. Sleep Medicine Clinics, 1(3), 351–358.

    Google Scholar 

  • Bubb, E. J., Metzler-Baddeley, C., & Aggleton, J. P. (2018). The cingulum bundle: Anatomy, function, and dysfunction. Neuroscience & Biobehavioral Reviews, 92, 104–127.

    Google Scholar 

  • Cai, W., Zhao, M., Liu, J., Liu, B., Yu, D., & Yuan, K. (2019). Right arcuate fasciculus and superior longitudinal fasciculus abnormalities in primary insomnia. Brain Imaging and Behavior, 13(6), 1746–1755.

    PubMed  Google Scholar 

  • Casagrande, M. (2010). 11 Laterality and Sleep. The Two Halves of the Brain, 313. MIT Press.

    Google Scholar 

  • Cheng, W., Rolls, E. T., 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.

    PubMed  PubMed Central  Google Scholar 

  • Ebeling, U., & Cramon, D. V. (1992). Topography of the uncinate fascicle and adjacent temporal fiber tracts. Acta Neurochirurgica, 115(3–4), 143–148.

    CAS  PubMed  Google Scholar 

  • Emamian, F., Mahdipour, M., Noori, K., Rostampour, M., Mousavi, S. B., Khazaie, H., Khodaie-Ardakani, M., Tahmasian, M., & Zarei, M. (2021). Alterations of subcortical brain structures in paradoxical and psychophysiological insomnia disorder. Frontiers in Psychiatry, 12, 611.

    Google Scholar 

  • Graham, M. S., Drobnjak, I., & Zhang, H. (2016). Realistic simulation of artefacts in diffusion MRI for validating post-processing correction techniques. NeuroImage, 125, 1079–1094.

    PubMed  Google Scholar 

  • Hwang, Y., & Kim, S. J. (2020). Brain activation changes in insomnia: A review of functional magnetic resonance imaging studies. Chronobiology in Medicine, 2(3), 103–108.

    Google Scholar 

  • Jespersen, K. V., Stevner, A., Fernandes, H., Sørensen, S. D., Van Someren, E., Kringelbach, M., & Vuust, P. (2020). Reduced structural connectivity in insomnia disorder. Journal of Sleep Research, 29(1), e12901.

    PubMed  Google Scholar 

  • Johns, M. W. (1991). A new method for measuring daytime sleepiness: The Epworth sleepiness scale. Sleep, 14(6), 540–545.

    CAS  PubMed  Google Scholar 

  • Joo, E. Y., Noh, H. J., Kim, J.-S., Koo, D. L., Kim, D., Hwang, K. J., Kim, J. Y., Kim, S. T., Kim, M. R., & Hong, S. B. (2013). Brain gray matter deficits in patients with chronic primary insomnia. Sleep, 36(7), 999–1007.

    PubMed  PubMed Central  Google Scholar 

  • Kamali, A., Flanders, A. E., Brody, J., Hunter, J. V., & Hasan, K. M. (2014). Tracing superior longitudinal fasciculus connectivity in the human brain using high resolution diffusion tensor tractography. Brain Structure and Function, 219(1), 269–281.

    PubMed  Google Scholar 

  • Kang, J. M., Joo, S. W., Son, Y.-D., Kim, H., Ko, K.-P., Lee, J. S., & Kang, S.-G. (2018). Low white-matter integrity between the left thalamus and inferior frontal gyrus in patients with insomnia disorder. Journal of Psychiatry & Neuroscience: JPN, 43(6), 366.

    CAS  Google Scholar 

  • Khazaie, H., Veronese, M., Noori, K., Emamian, F., Zarei, M., Ashkan, K., Leschziner, G. D., Eickhoff, C. R., Eickhoff, S. B., Morrell, M. J., & Osorio, R. S. (2017). Functional reorganization in obstructive sleep apnoea and insomnia: A systematic review of the resting-state fMRI. Neuroscience & Biobehavioral Reviews, 77, 219–231.

    Google Scholar 

  • Leerssen, J., Wassing, R., Ramautar, J. R., Stoffers, D., Lakbila-Kamal, O., Perrier, J., Bruijel, J., Foster-Dingley, J. C., Aghajani, M., & van Someren, E. J. (2019). Increased hippocampal-prefrontal functional connectivity in insomnia. Neurobiology of Learning and Memory, 160, 144–150.

    PubMed  Google Scholar 

  • Levenson, J. C., Kay, D. B., & Buysse, D. J. (2015). The pathophysiology of insomnia. Chest, 147(4), 1179–1192.

    PubMed  PubMed Central  Google Scholar 

  • Li, S., Tian, J., Bauer, A., Huang, R., Wen, H., Li, M., Wang, T., Xia, L., & Jiang, G. (2016). Reduced integrity of right lateralized white matter in patients with primary insomnia: A diffusion-tensor imaging study. Radiology, 280(2), 520–528.

    PubMed  Google Scholar 

  • Li, Y., Wang, E., Zhang, H., Dou, S., Liu, L., Tong, L., Lei, Y., Wang, M., Xu, J., Shi, D., & Zhang, Q. (2014). Functional connectivity changes between parietal and prefrontal cortices in primary insomnia patients: Evidence from resting-state fMRI. European Journal of Medical Research, 19(1), 32.

    PubMed  PubMed Central  Google Scholar 

  • Lu, F.-M., Dai, J., Couto, T. A., Liu, C.-H., Chen, H., Lu, S.-L., Tang, L. R., Tie, C. L., Chen, H. F., He, M. X., & Xiang, Y. T. (2017). Diffusion tensor imaging tractography reveals disrupted white matter structural connectivity network in healthy adults with insomnia symptoms. Frontiers in Human Neuroscience, 11, 583.

    PubMed  PubMed Central  Google Scholar 

  • Mole, J. P., Subramanian, L., Bracht, T., Morris, H., Metzler-Baddeley, C., & Linden, D. E. (2016). Increased fractional anisotropy in the motor tracts of Parkinson’s disease suggests compensatory neuroplasticity or selective neurodegeneration. European Radiology, 26(10), 3327–3335.

    PubMed  PubMed Central  Google Scholar 

  • Morin, C. M., Drake, C. L., Harvey, A. G., Krystal, A. D., Manber, R., Riemann, D., & Spiegelhalder, K. (2015). Insomnia disorder. Nature Reviews Disease Primers, 1(1), 1–18.

    Google Scholar 

  • Mulder, T. A., Kocevska, D., Muetzel, R. L., Koopman-Verhoeff, M. E., Hillegers, M. H., White, T., & Tiemeier, H. (2019). Childhood sleep disturbances and white matter microstructure in preadolescence. Journal of Child Psychology and Psychiatry, 60(11), 1242–1250.

    PubMed  Google Scholar 

  • Nofzinger, E. A., Buysse, D. J., Germain, A., Price, J. C., Miewald, J. M., & Kupfer, D. J. (2004). Functional neuroimaging evidence for hyperarousal in insomnia. American Journal of Psychiatry, 161(11), 2126–2128.

    PubMed  Google Scholar 

  • Passingham, R. E., Stephan, K. E., & Kötter, R. (2002). The anatomical basis of functional localization in the cortex. Nature Reviews Neuroscience, 3(8), 606–616.

    CAS  PubMed  Google Scholar 

  • Rimol, L. M., Botellero, V. L., Bjuland, K. J., Løhaugen, G. C., Lydersen, S., Evensen, K. A. I., Brubakk, A. M., Eikenes, L., Indredavik, M. S., & Martinussen, M. (2019). Reduced white matter fractional anisotropy mediates cortical thickening in adults born preterm with very low birthweight. NeuroImage, 188, 217–227.

    PubMed  Google Scholar 

  • Rostampour, M., Hashemi, H., Najibi, S. M., & Oghabian, M. A. (2018). Detection of structural abnormalities of cortical and subcortical gray matter in patients with MRI-negative refractory epilepsy using neurite orientation dispersion and density imaging. Physica Medica, 48, 47–54.

    PubMed  Google Scholar 

  • Sampaio-Baptista, C., & Johansen-Berg, H. (2017). White matter plasticity in the adult brain. Neuron, 96(6), 1239–1251.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Santarnecchi, E., Del Bianco, C., Sicilia, I., Momi, D., Di Lorenzo, G., Ferrone, S., Sprugnoli, G., Rossi, S., & Rossi, A. (2018). Age of insomnia onset correlates with a reversal of default mode network and supplementary motor cortex connectivity. Neural Plasticity. https://doi.org/10.1155/2018/3678534

    Article  PubMed  PubMed Central  Google Scholar 

  • Sateia, M. J. (2014). International classification of sleep disorders. Chest, 146(5), 1387–1394.

    PubMed  Google Scholar 

  • Sexton, C. E., Zsoldos, E., Filippini, N., Griffanti, L., Winkler, A., Mahmood, A., Allan, C. L., Topiwala, A., Kyle, S. D., & Spiegelhalder, K. (2017). Associations between self-reported sleep quality and white matter in community-dwelling older adults: A prospective cohort study. Human Brain Mapping, 38(11), 5465–5473.

    PubMed  PubMed Central  Google Scholar 

  • Spiegelhalder, K., Regen, W., Prem, M., Baglioni, C., Nissen, C., Feige, B., Schnell, S., Kiselev, V. G., Hennig, J., & Riemann, D. (2014). Reduced anterior internal capsule white matter integrity in primary insomnia. Human Brain Mapping, 35(7), 3431–3438.

    PubMed  Google Scholar 

  • Tahmasian, M., Aleman, A., Andreassen, O. A., Arab, Z., Baillet, M., Benedetti, F., Bresser, T., Bright, J., Chee, M. W., Chylinski, D., & Cheng, W. (2021). ENIGMA-sleep: Challenges, opportunities, and the road map. Journal of Sleep Research, e13347.

  • Tahmasian, M., Noori, K., Samea, F., Zarei, M., Spiegelhalder, K., Eickhoff, S. B., Van Someren, E., Khazaie, H., & Eickhoff, C. R. (2018). A lack of consistent brain alterations in insomnia disorder: An activation likelihood estimation meta-analysis. Sleep Medicine Reviews, 42, 111–118.

    PubMed  PubMed Central  Google Scholar 

  • Taylor, D. J., Lichstein, K. L., & Durrence, H. H. (2003). Insomnia as a health risk factor. Behavioral Sleep Medicine, 1(4), 227–247.

    PubMed  Google Scholar 

  • Telzer, E. H., Goldenberg, D., Fuligni, A. J., Lieberman, M. D., & Gálvan, A. (2015). Sleep variability in adolescence is associated with altered brain development. Developmental Cognitive Neuroscience, 14, 16–22.

    PubMed  PubMed Central  Google Scholar 

  • Wei, Y., Bresser, T., Wassing, R., Stoffers, D., Van Someren, E. J., & Foster-Dingley, J. C. (2019). Brain structural connectivity network alterations in insomnia disorder reveal a central role of the right angular gyrus. NeuroImage: Clinical, 24, 102019.

    Google Scholar 

  • Winkelman, J. W., Benson, K. L., Buxton, O. M., Lyoo, I. K., Yoon, S., O’Connor, S., & Renshaw, P. F. (2010). Lack of hippocampal volume differences in primary insomnia and good sleeper controls: An MRI volumetric study at 3 Tesla. Sleep Medicine, 11(6), 576–582.

    PubMed  Google Scholar 

  • Wu, J., Zhou, Q., Li, J., Chen, Y., Shao, S., & Xiao, Y. (2021). Decreased resting-state alpha-band activation and functional connectivity after sleep deprivation. Scientific Reports, 11(1), 1–10.

    Google Scholar 

  • Wu, Y., Liu, M., Zeng, S., Ma, X., Yan, J., Lin, C., Xu, G., Li, G., Yin, Y., Fu, S., & Hua, K. (2018). Abnormal topology of the structural connectome in the limbic cortico-basal-ganglia circuit and default-mode network among primary insomnia patients. Frontiers in Neuroscience, 12, 860.

    PubMed  PubMed Central  Google Scholar 

  • Yendiki, A., Panneck, P., Srinivasan, P., Stevens, A., Zöllei, L., Augustinack, J., Wang, R., Salat, D., Ehrlich, S., Behrens, T., & Jbabdi, S. (2011). Automated probabilistic reconstruction of white-matter pathways in health and disease using an atlas of the underlying anatomy. Frontiers in Neuroinformatics, 5, 23.

    PubMed  PubMed Central  Google Scholar 

  • Yu, S., Shen, Z., Lai, R., Feng, F., Guo, B., Wang, Z., Yang, J., Hu, Y., & Gong, L. (2018). The orbitofrontal cortex gray matter is associated with the interaction between insomnia and depression. Frontiers in Psychiatry, 9, 651.

    PubMed  PubMed Central  Google Scholar 

  • Zhang, H., Schneider, T., Wheeler-Kingshott, C. A., & Alexander, D. C. (2012). NODDI: Practical in vivo neurite orientation dispersion and density imaging of the human brain. NeuroImage, 61(4), 1000–1016.

    PubMed  Google Scholar 

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Acknowledgements

The authors gratefully appreciate Kermanshah University of Medical Sciences and the volunteers for participating in this study.

Funding

This work was supported by the Kermanshah University of Medical Sciences [Grant Numbers 981014].

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Author notes

  1. Masoumeh Rostampour and Zeinab Gharaylou have contributed equally to this work.

Authors and Affiliations

  1. Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Masoumeh Rostampour, Khadijeh Noori, Reza Fadaei & Habibolah Khazaie

  2. Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

    Zeinab Gharaylou

  3. Department of Medical Physics, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Nima Rostampour & Donya Kaveh

  4. Institute of Medical Science and Technology, Shahid Beheshti University, Tehran, Iran

    Masoud Tahmasian & Mojtaba Zarei

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  1. Masoumeh Rostampour
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  2. Zeinab Gharaylou
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  3. Nima Rostampour
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Contributions

MT, HK and MZ designed the study. NR and DK collected the data. MR and ZG processed the data and wrote the manuscript. KN and RF helped with statistical analysis and revised the manuscript. All authors reviewed the paper and approved the final version to be published.

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Correspondence to Habibolah Khazaie.

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The study was approved by Kermanshah University of Medical Science Ethics Committee.

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Rostampour, M., Gharaylou, Z., Rostampour, N. et al. Asymmetric alterations of white matter integrity in patients with insomnia disorder. Brain Imaging and Behavior 16, 389–396 (2022). https://doi.org/10.1007/s11682-021-00512-w

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