Abstract
Previous neuroimaging studies have reported brain morphological alterations and the occurrence of mental disorders in primary insomnia (PI) patients. However, studies of the effect of disrupted sleep on brain structure have showed inconsistent results. In this study, DARTEL-VBM was used to evaluate the changes in gray matter volume from 60 PI patients and 53 controls. Voxel-wise statistics was performed in two ways. One is a more liberal statistical analysis using an uncorrected P < 0. 001 with 25 voxels, and the other one is a more conservative approach using a threshold of P < 0.05, corrected for multiple comparisons using the Gaussian random field (GRF) method. Partial correlation was used to analyze the relationship between abnormal volume and clinical features. PI patients had reduced gray matter volume primarily in the right middle cingulate cortex with correction (P < 0.05). Correlation analysis showed gray matter changes in the left middle cingulate cortex were negatively associated with self-ratings for anxiety and depression. This study showed that gray matter deficits in cingulate cortex in patients with insomnia, and the decreased gray matter volume may be associated with the difficulties in emotional management due to insomnia. Functional roles of the affected regions in emotion and regulation of sleep might provide supplementary evidence and guide further research that may facilitate understanding the mechanisms underlying insomnia.
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References
Allman, J. M., Hakeem, A., Erwin, J. M., Nimchinsky, E., & Hof, P. (2001). The anterior cingulate cortex. The evolution of an interface between emotion and cognition. Annals of the New York Academy of Sciences, 935, 107–117.
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. https://doi.org/10.1111/j.1365-2869.2008.00671.x.
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. https://doi.org/10.1016/j.biopsych.2009.08.003.
Ashburner, J. (2007). A fast diffeomorphic image registration algorithm. Neuroimage, 38(1), 95–113. https://doi.org/10.1016/j.neuroimage.2007.07.007.
Ashburner, J., & Friston, K. J. (2000). Voxel-based morphometry–the methods. Neuroimage, 11(6 Pt 1), 805–821. https://doi.org/10.1006/nimg.2000.0582.
Ashburner, J., & Friston, K. J. (2005). Unified segmentation. Neuroimage, 26(3), 839–851. https://doi.org/10.1016/j.neuroimage.2005.02.018.
Baglioni, C., Battagliese, G., Feige, B., Spiegelhalder, K., Nissen, C., Voderholzer, U.,.. . Riemann, D. (2011). Insomnia as a predictor of depression: a meta-analytic evaluation of longitudinal epidemiological studies. Journal of Affective Disorders, 135(1–3), 10–19. https://doi.org/10.1016/j.jad.2011.01.011.
Baglioni, C., Spiegelhalder, K., Lombardo, C., & Riemann, D. (2010). Sleep and emotions: a focus on insomnia. Sleep Medicine Reviews, 14(4), 227–238. https://doi.org/10.1016/j.smrv.2009.10.007.
Bastien, C. H., Vallieres, A., & Morin, C. M. (2001). Validation of the insomnia severity index as an outcome measure for insomnia research. Sleep Medicine, 2(4), 297–307.
Buysse, D. J., Reynolds, C. F., 3rd, 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.
Cardoso, E. F., Maia, F. M., Fregni, F., Myczkowski, M. L., Melo, L. M., Sato, J. R.,.. . Amaro, E. Jr. (2009). Depression in Parkinson’s disease: convergence from voxel-based morphometry and functional magnetic resonance imaging in the limbic thalamus. Neuroimage, 47(2), 467–472. https://doi.org/10.1016/j.neuroimage.2009.04.059.
Chee, M. W., Tan, J. C., Zheng, H., Parimal, S., Weissman, D. H., Zagorodnov, V., & Dinges, D. F. (2008). Lapsing during sleep deprivation is associated with distributed changes in brain activation. Journal Neuroscience, 28(21), 5519–5528. https://doi.org/10.1523/JNEUROSCI.0733-08.2008.
Davidson, R. J., Abercrombie, H., Nitschke, J. B., & Putnam, K. (1999). Regional brain function, emotion and disorders of emotion. Current Opinion in Neurobiology, 9(2), 228–234.
Davidson, R. J., Irwin, W., Anderle, M. J., & Kalin, N. H. (2003). The neural substrates of affective processing in depressed patients treated with venlafaxine. The American Journal of Psychiatry, 160(1), 64–75. https://doi.org/10.1176/appi.ajp.160.1.64.
Finos, L., & Salmaso, L. (2007). FDR-and FWE-controlling methods using data-driven weights. Journal of Statistical Planning and Inference, 137(12), 3859–3870.
Glascher, J., Adolphs, R., Damasio, H., Bechara, A., Rudrauf, D., Calamia, M.,.. . Tranel, D. (2012). Lesion mapping of cognitive control and value-based decision making in the prefrontal cortex. Proceeding National Academy of Science of the United States of America, 109(36), 14681–14686. https://doi.org/10.1073/pnas.1206608109.
Joo, E. Y., Kim, H., Suh, S., & Hong, S. B. (2014). Hippocampal substructural vulnerability to sleep disturbance and cognitive impairment in patients with chronic primary insomnia: magnetic resonance imaging morphometry. Sleep, 37(7), 1189–1198. https://doi.org/10.5665/sleep.3836.
Joo, E. Y., Noh, H. J., Kim, J. S., Koo, D. L., Kim, D., Hwang, K. J.,.. . Hong, S. B. (2013). Brain gray matter deficits in patients with chronic primary insomnia. Sleep, 36(7), 999–1007. https://doi.org/10.5665/sleep.2796.
Kempton, M. J., Salvador, Z., Munafo, M. R., Geddes, J. R., Simmons, A., Frangou, S., & Williams, S. C. (2011). Structural neuroimaging studies in major depressive disorder. Meta-analysis and comparison with bipolar disorder. Archives of General Psychiatry, 68(7), 675–690. https://doi.org/10.1001/archgenpsychiatry.2011.60.
Krausz, Y., Freedman, N., Lester, H., Barkai, G., Levin, T., Bocher, M.,.. . Bonne, O. (2007). Brain SPECT study of common ground between hypothyroidism and depression. International Journal Neuropsychopharmacol, 10(1), 99–106. https://doi.org/10.1017/S1461145706006481.
Kripke, D. F., Garfinkel, L., Wingard, D. L., Klauber, M. R., & Marler, M. R. (2002). Mortality associated with sleep duration and insomnia. Archives of General Psychiatry, 59(2), 131–136.
Kyle, S. D., Morgan, K., & Espie, C. A. (2010). Insomnia and health-related quality of life. Sleep Medicine Reviews, 14(1), 69–82. https://doi.org/10.1016/j.smrv.2009.07.004.
Leuner, B., & Shors, T. J. (2013). Stress, anxiety, and dendritic spines: what are the connections? Neuroscience, 251, 108–119. https://doi.org/10.1016/j.neuroscience.2012.04.021.
Li, S., Tian, J., Bauer, A., Huang, R., Wen, H., Li, M.,.. . 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. https://doi.org/10.1148/radiol.2016152038.
McNamee, D., Rangel, A., & O’Doherty, J. P. (2013). Category-dependent and category-independent goal-value codes in human ventromedial prefrontal cortex. Nature Neuroscience, 16(4), 479–485. https://doi.org/10.1038/nn.3337.
Morin, C. M., & Benca, R. (2012). Chronic insomnia. Lancet, 379(9821), 1129–1141. https://doi.org/10.1016/S0140-6736(11)60750-2.
Murphy, M., Riedner, B. A., Huber, R., Massimini, M., Ferrarelli, F., & Tononi, G. (2009). Source modeling sleep slow waves. Proceeding of the National Academy of Sciences of the United States of America, 106(5), 1608–1613. https://doi.org/10.1073/pnas.0807933106.
National Institutes of Health (2005). National institutes of health state of the science conference statement on manifestations and management of chronic insomnia in adults. Sleep, 28(9), 13–15. 1049–1057.
Neylan, T. C., Mueller, S. G., Wang, Z., Metzler, T. J., Lenoci, M., Truran, D.,.. . Schuff, N. (2010). Insomnia severity is associated with a decreased volume of the CA3/dentate gyrus hippocampal subfield. Biological Psychiatry, 68(5), 494–496. https://doi.org/10.1016/j.biopsych.2010.04.035.
Noh, H. J., Joo, E. Y., Kim, S. T., Yoon, S. M., Koo, D. L., Kim, D.,.. . Hong, S. B. (2012). The relationship between hippocampal volume and cognition in patients with chronic primary insomnia. Journal of Clinical Neurology, 8(2), 130–138. https://doi.org/10.3988/jcn.2012.8.2.130.
Ohayon, M. M. (2002). Epidemiology of insomnia: what we know and what we still need to learn. Sleep Med Rev, 6(2), 97–111.
Oldfield, R. C. (1971). The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia, 9(1), 97–113.
Phillips, M. L., Drevets, W. C., Rauch, S. L., & Lane, R. (2003). Neurobiology of emotion perception I: the neural basis of normal emotion perception. Biological Psychiatry, 54(5), 504–514.
Piantoni, G., Poil, S. S., Linkenkaer-Hansen, K., Verweij, I. M., Ramautar, J. R., Van Someren, E. J., & Van Der Werf, Y. D. (2013). Individual differences in white matter diffusion affect sleep oscillations. Journal of Neurosciences, 33(1), 227–233. https://doi.org/10.1523/JNEUROSCI.2030-12.2013.
Poline, J. B., Worsley, K. J., Evans, A. C., & Friston, K. J. (1997). Combining spatial extent and peak intensity to test for activations in functional imaging. Neuroimage, 5(2), 83–96. https://doi.org/10.1006/nimg.1996.0248.
Riemann, D., & Voderholzer, U. (2003). Primary insomnia: a risk factor to develop depression? Journal of Affective Disorders, 76(1–3), 255–259.
Riemann, D., Voderholzer, U., Spiegelhalder, K., Hornyak, M., Buysse, D. J., Nissen, C.,.. . Feige, B. (2007). Chronic insomnia and MRI-measured hippocampal volumes: a pilot study. Sleep, 30(8), 955–958.
Sadaghiani, S., Scheeringa, R., Lehongre, K., Morillon, B., Giraud, A. L., & Kleinschmidt, A. (2010). Intrinsic connectivity networks, alpha oscillations, and tonic alertness: a simultaneous electroencephalography/functional magnetic resonance imaging study. Journal of Neuroscience, 30(30), 10243–10250. https://doi.org/10.1523/JNEUROSCI.1004-10.2010.
Shackman, A. J., Salomons, T. V., Slagter, H. A., Fox, A. S., Winter, J. J., & Davidson, R. J. (2011). The integration of negative affect, pain and cognitive control in the cingulate cortex. Natural Reviews Neuroscience, 12(3), 154–167. https://doi.org/10.1038/nrn2994.
Spiegelhalder, K., Regen, W., Baglioni, C., Kloppel, S., Abdulkadir, A., Hennig, J.,.. . Feige, B. (2013). Insomnia does not appear to be associated with substantial structural brain changes. Sleep, 36(5), 731–737. https://doi.org/10.5665/sleep.2638.
Squire, R. F., Noudoost, B., Schafer, R. J., & Moore, T. (2013). Prefrontal contributions to visual selective attention. Annual Review of Neuroscience, 36, 451–466. https://doi.org/10.1146/annurev-neuro-062111-150439.
Stoffers, D., Moens, S., Benjamins, J., van Tol, M. J., Penninx, B. W., Veltman, D. J.,.. . Van Someren, E. J. (2012). Orbitofrontal gray matter relates to early morning awakening: a neural correlate of insomnia complaints? Front Neurology, 3, 105. https://doi.org/10.3389/fneur.2012.00105.
Szily, E., & Keri, S. (2008). Emotion-related brain regions. Ideggyogy Sz, 61(3–4), 77–86.
Taylor, D. J., Lichstein, K. L., Durrence, H. H., Reidel, B. W., & Bush, A. J. (2005). Epidemiology of insomnia, depression, and anxiety. Sleep, 28(11), 1457–1464.
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.
Wang, T., Li, S., Jiang, G., Lin, C., Li, M., Ma, X.,.. . Tian, J. (2016). Regional homogeneity changes in patients with primary insomnia. European Radiology, 26(5), 1292–1300. https://doi.org/10.1007/s00330-015-3960-4.
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 T. Sleep Medicine, 11(6), 576–582. https://doi.org/10.1016/j.sleep.2010.03.009.
Yassa, M. A., & Stark, C. E. (2009). A quantitative evaluation of cross-participant registration techniques for MRI studies of the medial temporal lobe. Neuroimage, 44(2), 319–327. https://doi.org/10.1016/j.neuroimage.2008.09.016.
Zhang, H., Nichols, T. E., & Johnson, T. D. (2009). Cluster mass inference via random field theory. Neuroimage, 44(1), 51–61. https://doi.org/10.1016/j.neuroimage.2008.08.017.
Funding
This study was funded by the National Natural Science Foundation of China (Grant number: 81471639, 81771807, and 81701111), the Science and Technology Planning Project of Guangdong Province, China (Grant number: 2016A020215125, and 2017A020215077), the Natural Science Foundation of Guangdong Province, China (Grant number: 2015A030313723), and the Science and Technology Planning Project of Guangzhou, Guangdong, China (Grant number: 201607010056).
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Author Meng Li declare that they have no conflict of interest. Author Jianhao Yan declare that they have no conflict of interest. Author Shumei Li declare that they have no conflict of interest. Author Tianyue Wang declare that they have no conflict of interest. Author Hua Wen declare that they have no conflict of interest. Author Yi Yin declare that they have no conflict of interest. Author Shishun Fu declare that they have no conflict of interest. Author Luxian Zeng declare that they have no conflict of interest. Author Junzhang Tian declare that they have no conflict of interest. Guihua Jiang declare that they have no conflict of interest.
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Li, M., Yan, J., Li, S. et al. Altered gray matter volume in primary insomnia patients: a DARTEL-VBM study. Brain Imaging and Behavior 12, 1759–1767 (2018). https://doi.org/10.1007/s11682-018-9844-x
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DOI: https://doi.org/10.1007/s11682-018-9844-x