Disrupted brain functional network topology in unilateral acute brainstem ischemic stroke

Abstract

This study aimed to investigate the topological properties of brain functional connectome in unilateral acute brainstem ischemic stroke using graph theory. Fifty-three acute brainstem ischemic stroke patients, consisted of 27 left-sided and 26 right-sided brainstem stroke patients, and 20 age, gender, and education-matched healthy controls (HCs) were recruited to undergo a resting-state functional magnetic resonance imaging (rs-fMRI) scan in this study. Graph theory analyses were then used to examine the group-specific topological properties of the functional connectomes seperately. The unilateral acute brainstem stroke patients and HCs all exhibited “small-world” brain network topology. The functional connectome of the left brainstem stroke patients showed significant differences in all topological properties while the right brainstem stroke patients showed a significant increase in clustering coefficient Cp (p < 0.001) and local efficiency Elocal (p < 0.001), and a significantly decrease in normalized clustering coefficient γ (p < 0.001) and global efficiency Eglobal (p < 0.001), suggesting both a shift toward regular networks. At the nodal level, abnormal nodal centralities were mainly observed in the defaut mode network, subcortical network, frontal and occipital lobe. The findings of disrupted topological properties of functional brain networks may help better understanding the disease characterization and innovation in management for acute brainstem ischemic stroke patients.

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References

  1. Bernhardt, B. C., Chen, Z., He, Y., Evans, A. C., & Bernasconi, N. (2011). Graph-theoretical analysis reveals disrupted small-world organization of cortical thickness correlation networks in temporal lobe epilepsy. Cerebral Cortex, 21(9), 2147–2157. https://doi.org/10.1093/cercor/bhq291.

    Article  PubMed  Google Scholar 

  2. Burger, K. M., Tuhrim, S., & Naidich, T. P. (2005). Brainstem vascular stroke anatomy. Neuroimaging Clinics of North America, 15(2), 297–324. https://doi.org/10.1016/j.nic.2005.05.005.

    Article  PubMed  Google Scholar 

  3. Caliandro, P., Vecchio, F., Miraglia, F., Reale, G., Della Marca, G., La Torre, G., et al. (2017). Small-world characteristics of cortical connectivity changes in acute stroke. Neurorehabilitation and Neural Repair, 31(1), 81–94. https://doi.org/10.1177/1545968316662525.

    Article  PubMed  Google Scholar 

  4. Chen, H., Jiang, L., Zhang, H., Zhang, Y. D., Geng, W., Feng, Y., et al. (2018). Corticospinal tract changes in acute brainstem ischemic stroke patients: A diffusion kurtosis imaging study. Neurology India, 66(3), 726–732. https://doi.org/10.4103/0028-3886.232281.

    Article  PubMed  Google Scholar 

  5. Chen, H., Shi, M., Zhang, H., Zhang, Y.-D., Geng, W., Jiang, L., et al. (2019). Different patterns of functional connectivity alterations within the default-mode network and sensorimotor network in basal ganglia and pontine stroke. Medical Science Monitor, 25, 9585–9593.

    Article  Google Scholar 

  6. Forster, S., Vaitl, A., Teipel, S. J., Yakushev, I., Mustafa, M., la Fougere, C., et al. (2010). Functional representation of olfactory impairment in early Alzheimer’s disease. Journal of Alzheimer’s Disease, 22(2), 581–591. https://doi.org/10.3233/JAD-2010-091549.

    Article  PubMed  Google Scholar 

  7. Friedrich, B., Gawlitza, M., Fahnert, J., Quäschling, U., Kahn, T., Lobsien, D., et al. (2015). Interventional ischemic stroke treatment – A (R)evolution. RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 188(03), 259–267. https://doi.org/10.1055/s-0041-106899.

    Article  Google Scholar 

  8. Giralt-Steinhauer, E., Medrano, S., Soriano-Tarraga, C., Mola-Caminal, M., Rasal, R., Cuadrado-Godia, E., et al. (2018). Brainstem leukoaraiosis independently predicts poor outcome after ischemic stroke. European Journal of Neurology, 25(8), 1086–1092. https://doi.org/10.1111/ene.13659.

    CAS  Article  PubMed  Google Scholar 

  9. Jiang, L., Geng, W., Chen, H., Zhang, H., Bo, F., Mao, C. N., et al. (2018). Decreased functional connectivity within the default-mode network in acute brainstem ischemic stroke. European Journal of Radiology, 105, 221–226. https://doi.org/10.1016/j.ejrad.2018.06.018.

    Article  PubMed  Google Scholar 

  10. Kim, D. J., Kent, J. S., Bolbecker, A. R., Sporns, O., Cheng, H., Newman, S. D., et al. (2014). Disrupted modular architecture of cerebellum in schizophrenia: A graph theoretic analysis. Schizophrenia Bulletin, 40(6), 1216–1226. https://doi.org/10.1093/schbul/sbu059.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Link, T. W., Santillan, A., & Patsalides, A. (2020). Intra-arterial neuroprotective therapy as an adjunct to endovascular intervention in acute ischemic stroke: A review of the literature and future directions. Interventional Neuroradiology, 1591019920925677. https://doi.org/10.1177/1591019920925677.

  12. Long, Z., Duan, X., Xie, B., Du, H., Li, R., Xu, Q., et al. (2013). Altered brain structural connectivity in post-traumatic stress disorder: A diffusion tensor imaging tractography study. Journal of Affective Disorders, 150(3), 798–806. https://doi.org/10.1016/j.jad.2013.03.004.

    Article  PubMed  Google Scholar 

  13. Lynall, M. E., Bassett, D. S., Kerwin, R., McKenna, P. J., Kitzbichler, M., Muller, U., et al. (2010). Functional connectivity and brain networks in schizophrenia. The Journal of Neuroscience, 30(28), 9477–9487. https://doi.org/10.1523/JNEUROSCI.0333-10.2010.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. Miyake, A., & Friedman, N. P. (2012). The nature and organization of individual differences in executive functions: Four general conclusions. Current Directions in Psychological Science, 21(1), 8–14. https://doi.org/10.1177/0963721411429458.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ortiz de Mendivil, A., Alcala-Galiano, A., Ochoa, M., Salvador, E., & Millan, J. M. (2013). Brainstem stroke: Anatomy, clinical and radiological findings. Seminars in Ultrasound, CT, and MR, 34(2), 131–141. https://doi.org/10.1053/j.sult.2013.01.004.

    Article  PubMed  Google Scholar 

  16. Powers, W., Rabinstein, A., Ackerson, T., Adeoye, O., Bambakidis, N., Becker, K., et al. (2018). 2018 guidelines for the early management of patients with acute ischemic stroke. Stroke, 49(3), e46–e110.

    Article  Google Scholar 

  17. Renier, L. A., Anurova, I., De Volder, A. G., Carlson, S., VanMeter, J., & Rauschecker, J. P. (2010). Preserved functional specialization for spatial processing in the middle occipital gyrus of the early blind. Neuron, 68(1), 138–148. https://doi.org/10.1016/j.neuron.2010.09.021.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. Riascos, R. F., Kamali, A., Hakimelahi, R., Mwangi, B., Rabiei, P., Seidler, R. D., et al. (2019). Longitudinal analysis of quantitative brain MRI in astronauts following microgravity exposure. Journal of Neuroimaging, 29(3), 323–330. https://doi.org/10.1111/jon.12609.

    Article  PubMed  Google Scholar 

  19. Roa, J. A., Maud, A., Jabbour, P., Dabus, G., Pazour, A., Dandapat, S., et al. (2020). Transcirculation approach for mechanical thrombectomy in acute ischemic stroke: A multicenter study and review of the literature. Frontiers in Neurology, 11, 347. https://doi.org/10.3389/fneur.2020.00347.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Salgado, J. V., Costa-Silva, M., Malloy-Diniz, L. F., Siqueira, J. M., & Teixeira, A. L. (2007). Prefrontal cognitive dysfunction following brainstem lesion. Clinical Neurology and Neurosurgery, 109(4), 379–382. https://doi.org/10.1016/j.clineuro.2007.01.002.

    Article  PubMed  Google Scholar 

  21. Sanz-Arigita, E. J., Schoonheim, M. M., Damoiseaux, J. S., Rombouts, S. A., Maris, E., Barkhof, F., et al. (2010). Loss of ‘small-world’ networks in Alzheimer’s disease: graph analysis of FMRI resting-state functional connectivity. PLoS One, 5(11), e13788. https://doi.org/10.1371/journal.pone.0013788.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. Satpute, A. B., & Lindquist, K. A. (2019). The default mode network’s role in discrete emotion. Trends in Cognitive Sciences, 23(10), 851–864. https://doi.org/10.1016/j.tics.2019.07.003.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Seeley, W. W., Menon, V., Schatzberg, A. F., Keller, J., Glover, G. H., Kenna, H., et al. (2007). Dissociable intrinsic connectivity networks for salience processing and executive control. The Journal of Neuroscience, 27(9), 2349–2356. https://doi.org/10.1523/JNEUROSCI.5587-06.2007.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. Suo, X., Lei, D., Li, K., Chen, F., Li, F., Li, L., et al. (2015). Disrupted brain network topology in pediatric posttraumatic stress disorder: A resting-state fMRI study. Human Brain Mapping, 36(9), 3677–3686. https://doi.org/10.1002/hbm.22871.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Tang, W. K., Hermann, D. M., Chen, Y. K., Liang, H. J., Liu, X. X., Chu, W. C., et al. (2014). Brainstem infarcts predict REM sleep behavior disorder in acute ischemic stroke. BMC Neurology, 14, 88. https://doi.org/10.1186/1471-2377-14-88.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Tao, J., Jiang, X., Wang, X., Liu, H., Qian, A., Yang, C., et al. (2017). Disrupted control-related functional brain networks in drug-naive children with attention-deficit/hyperactivity disorder. Frontiers in Psychiatry, 8, 246–258. https://doi.org/10.3389/fpsyt.2017.00246.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Tippett, D. C., Godin, B. R., Oishi, K., Oishi, K., Davis, C., Gomez, Y., et al. (2018). Impaired recognition of emotional faces after stroke involving right amygdala or insula. Seminars in Speech and Language, 39(1), 87–100. https://doi.org/10.1055/s-0037-1608859.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Uddin, L. Q. (2015). Salience processing and insular cortical function and dysfunction. Nature Reviews. Neuroscience, 16(1), 55–61. https://doi.org/10.1038/nrn3857.

    CAS  Article  PubMed  Google Scholar 

  29. Vecchio, F., Caliandro, P., Reale, G., Miraglia, F., Piludu, F., Masi, G., et al. (2019). Acute cerebellar stroke and middle cerebral artery stroke exert distinctive modifications on functional cortical connectivity: A comparative study via EEG graph theory. Clinical Neurophysiology, 130(6), 997–1007. https://doi.org/10.1016/j.clinph.2019.03.017.

    Article  PubMed  Google Scholar 

  30. Xiao, F., Lei, D., An, D., Li, L., Chen, S., Chen, F., et al. (2015). Functional brain connectome and sensorimotor networks in rolandic epilepsy. Epilepsy Research, 113, 113–125. https://doi.org/10.1016/j.eplepsyres.2015.03.015.

    Article  PubMed  Google Scholar 

  31. Xu, J., Chen, F., Lei, D., Zhan, W., Sun, X., Suo, X., et al. (2018). Disrupted functional network topology in children and adolescents with post-traumatic stress disorder. Frontiers in Neuroscience, 12, 709. https://doi.org/10.3389/fnins.2018.00709.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Zhang, J., Wang, J., Wu, Q., Kuang, W., Huang, X., He, Y., et al. (2011). Disrupted brain connectivity networks in drug-naive, first-episode major depressive disorder. Biological Psychiatry, 70(4), 334–342. https://doi.org/10.1016/j.biopsych.2011.05.018.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Zhi, D., Calhoun, V. D., Lv, L., Ma, X., Ke, Q., Fu, Z., et al. (2018). Aberrant dynamic functional network connectivity and graph properties in major depressive disorder. Frontiers in Psychiatry, 9, 339–350. https://doi.org/10.3389/fpsyt.2018.00339.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Zhu, Y., Bai, L., Liang, P., Kang, S., Gao, H., & Yang, H. (2017). Disrupted brain connectivity networks in acute ischemic stroke patients. Brain Imaging and Behavior, 11(2), 444–453. https://doi.org/10.1007/s11682-016-9525-6.

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was funded by Jiangsu Provincial Special Program of Medical Science (BE2017614).

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Correspondence to Yu-Chen Chen or Liping Wang.

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Shi, M., Liu, S., Chen, H. et al. Disrupted brain functional network topology in unilateral acute brainstem ischemic stroke. Brain Imaging and Behavior 15, 444–452 (2021). https://doi.org/10.1007/s11682-020-00353-z

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Keywords

  • Brainstem ischemic stroke
  • rs-fMRI
  • Graph theory
  • Functional connectome
  • Small-worldness