Abstract
This study aimed to systematically investigate abnormal morphological connectivity in subregions of the thalamus and examine the clinical relevance of this connectivity in patients with chronic insomnia. One hundred and two patients with chronic insomnia (aged 45.50 [34.75 ~ 58.00] years; 24 men, 78 women) and one hundred and one healthy controls (aged 45.00 [34.00 ~ 55.00] years; 32 men, 69 women) were recruited. Intrathalamic and thalamocortical morphological connectivity in the thalamic subregions defined in the Human Brainnetome Atlas were computed and compared between the two groups. Spearman’s correlation was used to estimate the association between thalamic morphological connectivity alterations and clinical variables. Compared with the control group, the insomnia group exhibited higher intrathalamic mean morphological connectivity than the control group, though no alterations in thalamocortical morphological connectivity were observed. However, no correlation was found between altered intrathalamic morphological connectivity and behavioral scales. In addition, alterations in morphological connectivity among thalamic subregions were found mainly in the left medial premotor thalamus, left medial prefrontal thalamus, and left sensory thalamus; however, these results were no longer significant after correction. Our findings suggest increased intrathalamic morphological connectivity in patients with chronic insomnia, thus enriching the understanding of morphological connectivity at the individual level and providing new perspectives for clinical interventions and diagnostic imaging.
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The deidentified data are available from the corresponding author upon reasonable request.
References
Altena, E., Vrenken, H., Van Der Werf, Y. D., van den Heuvel, O. A., & Van Someren, E. J. W. (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. (2005). Unified segmentation. NeuroImage, 26(3), 839–851. https://doi.org/10.1016/j.neuroimage.2005.02.018
Bertisch, S. M., Pollock, B. D., Mittleman, M. A., Buysse, D. J., Bazzano, L. A., Gottlieb, D. J., & Redline, S. (2018). Insomnia with objective short sleep duration and risk of incident cardiovascular disease and all-cause mortality: Sleep Heart Health Study. Sleep, 41(6). https://doi.org/10.1093/sleep/zsy047
Bi, G., & Poo, M. (1999). Distributed synaptic modification in neural networks induced by patterned stimulation. Nature, 401(6755), 792–796. https://doi.org/10.1038/44573
Bowman, A. W., & Azzalini, A. (1997). Applied smoothing techniques for data analysis: The kernel approach with S-Plus illustrations, 18. New York: Oxford University Press.
Bullmore, E. T., Frangou, S., & Murray, R. M. (1997). The dysplastic net hypothesis: An integration of developmental and dysconnectivity theories of schizophrenia. Schizophrenia Research, 28(2–3), 143–156. https://doi.org/10.1016/S0920-9964(97)00114-X
Cassel, J., & Vasconcelos, A. P. (2021). Routes of the thalamus through the history of neuroanatomy. Neuroscience & Biobehavioral Reviews, 125, 442–465. https://doi.org/10.1016/j.neubiorev.2021.03.001
Cortelli, P., Perani, D., Montagna, P., Gallassi, R., Tinuper, P., Federica, P., Avoni, P., Ferrillo, F., Anchisi, D., Moresco, R. M., Fazio, F., Parchi, P., Baruzzi, A., Lugaresi, E., & Gambetti, P. (2006). Pre-symptomatic diagnosis in fatal familial insomnia: Serial neurophysiological and 18FDG-PET studies. Brain, 129(3), 668–675. https://doi.org/10.1093/brain/awl003
Essen, D. C. V. (1997). A tension-based theory of morphogenesis and compact wiring in the central nervous system. Nature, 385(6614), 313–318. https://doi.org/10.1038/385313a0
Fan, L., Li, H., Zhuo, J., Zhang, Y., Wang, J., Chen, L., Yang, Z., Chu, C., Xie, S., Laird, A. R., Fox, P. T., Eickhoff, S. B., Yu, C., & Jiang, T. (2016). The human brainnetome Atlas: A new brain Atlas based on connectional architecture. Cerebral Cortex, 26(8), 3508–3526. https://doi.org/10.1093/cercor/bhw157
Fasiello, E., Gorgoni, M., Scarpelli, S., Alfonsi, V., Strambi, F., & De Gennaro, L. (2022). Functional connectivity changes in insomnia disorder: A systematic review. Sleep Medicine Reviews, 61, 101569. https://doi.org/10.1016/j.smrv.2021.101569
Fernandez, L. M. J., & Lüthi, A. (2020). Sleep spindles: Mechanisms and functions. Physiological Reviews, 100(2), 805–868. https://doi.org/10.1152/physrev.00042.2018
Fortier-Brochu, E., Beaulieu-Bonneau, S., Ivers, H., & Morin, C. M. (2012). Insomnia and daytime cognitive performance: A meta-analysis. Sleep Medicine Reviews, 16(1), 83–94. https://doi.org/10.1016/j.smrv.2011.03.008
Fortier-Brochu, E., & Morin, C. M. (2014). Cognitive impairment in individuals with insomnia: Clinical significance and correlates. Sleep, 37(11), 1787–1798. https://doi.org/10.5665/sleep.4172
Fox, M. D. (2018). Mapping symptoms to brain networks with the human connectome. New England Journal of Medicine, 379(23), 2237–2245. https://doi.org/10.1056/NEJMra1706158
Gent, T. C., Bassetti, C. L., & Adamantidis, A. R. (2018). Sleep-wake control and the thalamus. Current Opinion in Neurobiology, 52, 188–197. https://doi.org/10.1016/j.conb.2018.08.002
Gong, G., He, Y., Chen, Z. J., & Evans, A. C. (2012). Convergence and divergence of thickness correlations with diffusion connections across the human cerebral cortex. NeuroImage, 59(2), 1239–1248. https://doi.org/10.1016/j.neuroimage.2011.08.017
Guo, H., Wei, M., & Ding, W. (2017). Changes in cognitive function in patients with primary insomnia. Shanghai Archives of Psychiatry, 29(3), 137. https://doi.org/10.11919/j.issn.1002-0829.216097
Guthery, F. S., Burnham, K. P., & Anderson, D. R. (2003). Model selection and multimodel inference: A practical information-theoretic approach. The Journal of Wildlife Management, 67(3), 655. https://doi.org/10.2307/3802723
Halassa, M. M., & Sherman, S. M. (2019). Thalamocortical circuit motifs: A general framework. Neuron, 103(5), 762–770. https://doi.org/10.1016/j.neuron.2019.06.005
Hertenstein, E., Feige, B., Gmeiner, T., Kienzler, C., Spiegelhalder, K., Johann, A., Jansson-Fröjmark, M., Palagini, L., Rücker, G., Riemann, D., & Baglioni, C. (2019). Insomnia as a predictor of mental disorders: A systematic review and meta-analysis. Sleep Medicine Reviews, 43, 96–105. https://doi.org/10.1016/j.smrv.2018.10.006
Honjoh, S., Sasai, S., Schiereck, S. S., Nagai, H., Tononi, G., & Cirelli, C. (2018). Regulation of cortical activity and arousal by the matrix cells of the ventromedial thalamic nucleus. Nature Communications, 9(1), 2100. https://doi.org/10.1038/s41467-018-04497-x
Horwitz, B. (2003). The elusive concept of brain connectivity. NeuroImage, 19(2), 466–470. https://doi.org/10.1016/S1053-8119(03)00112-5
Huang, Y., Kong, X., Zhen, Z., & Liu, J. (2013). The comparison of multiple testing corrections methods in Genome-wide Association Studies: The comparison of multiple testing corrections methods in Genome-wide Association Studies. Advances in Psychological Science, 21(10), 1874–1882. https://doi.org/10.3724/SP.J.1042.2013.01874
Humer, E., Pieh, C., & Brandmayr, G. (2020). Metabolomics in sleep, insomnia and sleep apnea. International Journal of Molecular Sciences, 21(19), 7244. https://doi.org/10.3390/ijms21197244
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 and Neuroscience, 43(6), 366–374. https://doi.org/10.1503/jpn.170195
Kong, X., Wang, X., Huang, L., Pu, Y., Yang, Z., Dang, X., Zhen, Z., & Liu, J. (2014). Measuring individual morphological relationship of cortical regions. Journal of Neuroscience Methods, 237, 103–107. https://doi.org/10.1016/j.jneumeth.2014.09.003
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. https://doi.org/10.1016/j.sleep.2017.04.002
Li, M., Wang, R., Zhao, M., Zhai, J., Liu, B., Yu, D., & Yuan, K. (2019). Abnormalities of thalamus volume and resting state functional connectivity in primary insomnia patients. Brain Imaging and Behavior, 13(5), 1193–1201. https://doi.org/10.1007/s11682-018-9932-y
Li, M., Yan, J., Li, S., Wang, T., Wen, H., Yin, Y., Fu, S., Zeng, L., Tian, J., & Jiang, G. (2018). Altered gray matter volume in primary insomnia patients: A DARTEL-VBM study. Brain Imaging and Behavior, 12(6), 1759–1767. https://doi.org/10.1007/s11682-018-9844-x
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. https://doi.org/10.1148/radiol.2016152038
Li, X., Guo, S., Wang, C., Wang, B., Sun, H., & Zhang, X. (2017). Increased interhemispheric resting-state functional connectivity in healthy participants with insomnia symptoms: A randomized clinical consort study. Medicine, 96(27), e7037. https://doi.org/10.1097/MD.0000000000007037
Li, Y., Wang, N., Wang, H., Lv, Y., Zou, Q., & Wang, J. (2021). Surface-based single-subject morphological brain networks: Effects of morphological index, brain parcellation and similarity measure, sample size-varying stability and test-retest reliability. NeuroImage, 235, 118018. https://doi.org/10.1016/j.neuroimage.2021.118018
Liu, C., Kong, X., Liu, X., Zhou, R., & Wu, B. (2014). Long-term total sleep deprivation reduces thalamic gray matter volume in healthy men. NeuroReport, 25(5), 320–323. https://doi.org/10.1097/WNR.0000000000000091
Ma, C., Zhong, P., Liu, D., & Barger, Z. K. (2019). Sleep regulation by neurotensinergic neurons in a thalamo-amygdala circuit. Neuron, 103(2), 323–334. https://doi.org/10.1016/j.neuron.2019.05.015
Ma, X., Fu, S., Xu, G., Liu, M., Xu, Y., Jiang, G., & Tian, J. (2022). Reduced left lateralized functional connectivity of the thalamic subregions between short-term and chronic insomnia disorder. Sleep and Biological Rhythms, 20(2), 229–237. https://doi.org/10.1007/s41105-021-00362-5
Mechelli, A., Friston, K. J., Frackowiak, R. S., & Price, C. J. (2005). Structural covariance in the human cortex. Journal of Neuroscience, 25(36), 8303–8310. https://doi.org/10.1523/JNEUROSCI.0357-05.2005
Nofzinger, E. A., Buysse, D. J., Miewald, J. M., Meltzer, C. C., Price, J. C., Sembrat, R. C., Ombao, H., Reynolds, C. F., Monk, T. H., Hall, M., Kupfer, D. J., & Moore, R. Y. (2002). Human regional cerebral glucose metabolism during non-rapid eye movement sleep in relation to waking. Brain, 125(5), 1105–1115. https://doi.org/10.1093/brain/awf103
Oldfield, R. C. (1971). The assessment and analysis of handedness: The Edinburgh inventory. Neuropsychologia, 9(1), 97–113. https://doi.org/10.1016/0028-3932(71)90067-4
O’Reilly, C., Iavarone, E., Yi, J., & Hill, S. L. (2021). Rodent somatosensory thalamocortical circuitry: Neurons, synapses, and connectivity. Neuroscience & Biobehavioral Reviews, 126, 213–235. https://doi.org/10.1016/j.neubiorev.2021.03.015
Pigeon, W. R., Bishop, T. M., & Krueger, K. M. (2017). Insomnia as a precipitating factor in new onset mental illness: A systematic review of recent findings. Current Psychiatry Reports, 19(8), 44. https://doi.org/10.1007/s11920-017-0802-x
Pinault, D. (2004). The thalamic reticular nucleus: Structure, function and concept. Brain Research Reviews, 46(1), 1–31. https://doi.org/10.1016/j.brainresrev.2004.04.008
Ren, S., Wang, Y., Yue, F., Cheng, X., Dang, R., Qiao, Q., Sun, X., Li, X., Jiang, Q., Yao, J., Qin, H., Wang, G., Liao, X., Gao, D., Xia, J., Zhang, J., Hu, B., Yan, J., Wang, Y., & Hu, Z. (2018). The paraventricular thalamus is a critical thalamic area for wakefulness. Science, 362(6413), 429–434. https://doi.org/10.1126/science.aat2512
Rosenblatt, M. (1956). Remarks on some nonparametric estimates of a density function. The annals of mathematical statistics, 27(3), 832–837. https://doi.org/10.1214/aoms/1177728190
Salgado, J. V., Malloy-Diniz, L. F., Abrantes, S. S. C., Moreira, L., Schlottfeldt, C. G., Guimarães, W., Freitas, D. M. U., Oliveira, J., & Fuentes, D. (2011). Applicability of the Rey Auditory-Verbal Learning Test to an adult sample in Brazil. Revista Brasileira de Psiquiatria, 33(3), 234–237. https://doi.org/10.1590/S1516-44462011005000007
Sateia, M. J. (2014). International classification of sleep disorders-third edition. Chest, 146(5), 1387–1394. https://doi.org/10.1378/chest.14-0970
Scott, D. W., & Sheather, S. J. (1985). Kernel density estimation with binned data. Communications in Statistics - Theory and Methods, 14(6), 1353–1359. https://doi.org/10.1080/03610928508828980
Swanson, L. W., Sporns, O., & Hahn, J. D. (2019). The network organization of rat intrathalamic macroconnections and a comparison with other forebrain divisions. Proceedings of the National Academy of Sciences, 116(27), 13661–13669. https://doi.org/10.1073/pnas.1905961116
Taber, K. H. (2004). The limbic thalamus. Journal of Neuropsychiatry, 16(2), 127–132. https://doi.org/10.1176/appi.neuropsych.16.2.127
Tijms, B. M., Series, P., Willshaw, D. J., & Lawrie, S. M. (2012). Similarity-based extraction of individual networks from gray matter MRI scans. Cerebral Cortex, 22(7), 1530–1541. https://doi.org/10.1093/cercor/bhr221
Tombaugh, T. N. (2004). Trail making test A and B: Normative data stratified by age and education. Archives of Clinical Neuropsychology, 19(2), 203–214. https://doi.org/10.1016/S0887-6177(03)00039-8
Valentine, T., Block, C., Eversole, K., Boxley, L., & Dawson, E. (2020). Wechsler adult intelligence scale‐IV (WAIS‐IV). The Wiley Encyclopedia of Personality and Individual Differences, Measurement and Assessment, 2 pp. 457–463. https://doi.org/10.1002/9781119547167.CH146
Wang, H., Jin, X., Zhang, Y., & Wang, J. (2016). Single-subject morphological brain networks: Connectivity mapping, topological characterization and test–retest reliability. Brain and Behavior, 6(4). https://doi.org/10.1002/brb3.448.
Wang, X., & Wei, H. (2006). MoCA-Test-Chinese_Beijing. http://www.mocatest.org/pdf_files/test/MoCA-Test-Chinese_Beijing.pdf
Wolff, M., & Vann, S. D. (2019). The cognitive thalamus as a gateway to mental representations. The Journal of Neuroscience, 39(1), 3–14. https://doi.org/10.1523/JNEUROSCI.0479-18.2018
Yan, C., Liu, C., Wang, X., Huo, J., Zhou, P., Shuai, Z., Qing-Nan, F., Jie, Z., Zhong-Yan, W., & Liu, Q.-Q. (2018). Abnormal functional connectivity of anterior cingulate cortex in patients with primary insomnia: A resting-state functional magnetic resonance imaging study. Frontiers in Aging Neuroscience, 10, 167. https://doi.org/10.3389/fnagi.2018.00167
Zhao, W., Van Someren, E. J. W., Li, C., Chen, X., Gui, W., Tian, Y., Liu, Y., & Lei, X. (2021). EEG spectral analysis in insomnia disorder: A systematic review and meta-analysis. Sleep Medicine Reviews, 59, 101457. https://doi.org/10.1016/j.smrv.2021.101457
Zhu, Y., Feng, Z., Xu, J., Fu, C., Sun, J., Yang, X., Shi, D., & Qin, W. (2016). Increased interhemispheric resting-state functional connectivity after sleep deprivation: A resting-state fMRI study. Brain Imaging and Behavior, 10(3), 911–919. https://doi.org/10.1007/s11682-015-9490-5
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This work was supported by the National Natural Science Foundation of China (Nos. 82001792) and the Science Foundation of Guangdong Second Provincial General Hospital (No. 3D-A2021009).
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X.Y., G.X. and Y.Y. performed the experiments and wrote the main manuscript text. Y.Y. and S. analyzed the data. X.W. prepared Figs. 1, 2 and 3. X.M. conceived and designed the experiments and revised the main manuscript text. All authors reviewed the manuscript.
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Ye, X., Yang, Y., Xu, G. et al. Enhanced intrathalamic morphological connectivity in patients with chronic insomnia. Brain Imaging and Behavior 17, 114–124 (2023). https://doi.org/10.1007/s11682-022-00747-1
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DOI: https://doi.org/10.1007/s11682-022-00747-1