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The altered functional modular organization in systemic lupus erythematosus: an independent component analysis study

Abstract

The aim of this study was to investigate the abnormities in functional connectivity (FC) within each modular network and between modular networks in patients with systemic lupus erythematosus (SLE). Twelve meaningful modular networks were identified via independent component analysis from 41 patients and 40 volunteers. Parametric tests were used to compare the intra- and intermodular FC between the groups. Partial correlation analysis was used to seek the relationships between abnormal FCs and the clinical data. Compared to the controls, SLE patients showed decreased intramodular FC in the anterior default mode network (aDMN), posterior default mode network (pDMN), ventral attention network (VAN), and sensorimotor network (SMN) and increased intramodular FC in the medial visual network (mVN) and left frontoparietal network. In addition, SLE patients showed decreased intermodular FC between the SMN and the lateral visual network (lVN), between the SMN and the VAN, and between the pDMN and the lVN and exhibited increased intermodular FC between the SMN and the salience network (SAN), between the pDMN and the SAN, and between the aDMN and the VAN. Moreover, we found several correlations among the abnormal FCs and the Mini-Mental State Examination in SLE patients. Mild cognitive impairment is compensated by the hyperconnectivity between the aDMN and the VAN, while severe cognitive impairment tends to be compensated by the hyperconnectivity between the SMN and the SAN. The FC value between the SMN and the SAN and between the aDMN and the VAN may serve as neuroimaging markers for monitoring cognitive progression in SLE patients.

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Abbreviations

aDMN:

Anterior default mode network

AN:

Auditory network

ECN:

Executive control network

DAN:

Dorsal attention network

FC:

Functional connectivity

FWE:

Family-wise error rate

ICA:

Independent component analysis

HC:

Healthy control

LFPN:

Left frontoparietal network

lVN:

Lateral visual network

MMSE:

Mini-mental state examination

mVN:

Medial visual network

pDMN:

Posterior default mode network

RFPN:

Right frontoparietal network

SAN:

Salience network

SLE:

Systemic lupus erythematosus

SMN:

Sensorimotor network

VAN:

Ventral attention network

References

  1. Barraclough, M., McKie, S., Parker, B., Jackson, A., Pemberton, P., Elliott, R., & Bruce, I. N. (2019). Altered cognitive function in systemic lupus erythematosus and associations with inflammation and functional and structural brain changes. Annals of the Rheumatic Diseases. https://doi.org/10.1136/annrheumdis-2018-214677

    Article  PubMed  Google Scholar 

  2. Bengtsson, S. L., Ehrsson, H. H., Forssberg, H., & Ullén, F. (2004). Dissociating brain regions controlling the temporal and ordinal structure of learned movement sequences. European Journal of Neuroscience, 19(9), 2591–2602. https://doi.org/10.1111/j.0953-816X.2004.03269.x

    Article  Google Scholar 

  3. Calhoun, V. D., Liu, J., & Adali, T. (2009). A review of group ICA for fMRI data and ICA for joint inference of imaging, genetic, and ERP data. NeuroImage, 45(1 Suppl), S163–S172. https://doi.org/10.1016/j.neuroimage.2008.10.057

    Article  PubMed  Google Scholar 

  4. Chen, Z., Hu, X., Chen, Q., & Feng, T. (2019). Altered structural and functional brain network overall organization predict human intertemporal decision-making. Human Brain Mapping, 40(1), 306–328. https://doi.org/10.1002/hbm.24374

    Article  PubMed  Google Scholar 

  5. Chiong, W., Wilson, S. M., D’Esposito, M., Kayser, A. S., Grossman, S. N., Poorzand, P., Seeley, W. W., Miller, B. L., & Rankin, K. P. (2013). The salience network causally influences default mode network activity during moral reasoning. Brain, 136(6), 1929–1941. https://doi.org/10.1093/brain/awt066

    Article  PubMed  PubMed Central  Google Scholar 

  6. Diano, M., D’Agata, F., Cauda, F., Costa, T., Geda, E., Sacco, K., & Geminiani, G. C. (2016). Cerebellar clustering and functional connectivity during pain processing. The Cerebellum, 15(3), 343–356. https://doi.org/10.1007/s12311-015-0706-4

    CAS  Article  PubMed  Google Scholar 

  7. Friederici, A. D., & Gierhan, S. M. (2013). The language network. Current Opinion in Neurobiology, 23(2), 250–254. https://doi.org/10.1016/j.conb.2012.10.002

    CAS  Article  PubMed  Google Scholar 

  8. Gitelman, D. R. (2003). Attention and its disorders. British Medical Bulletin, 65, 21–34.

    Article  Google Scholar 

  9. Gottwald, B., Wilde, B., Mihajlovic, Z., & Mehdorn, H. M. (2004). Evidence for distinct cognitive deficits after focal cerebellar lesions. Journal of Neurology, Neurosurgery and Psychiatry, 75(11), 1524–1531. https://doi.org/10.1136/jnnp.2003.018093

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. Habas, C. (2010). Functional imaging of the deep cerebellar nuclei: A review. Cerebellum, 9(1), 22–28. https://doi.org/10.1007/s12311-009-0119-3

    Article  PubMed  Google Scholar 

  11. Habas, C., Kamdar, N., Nguyen, D., Prater, K., Beckmann, C. F., Menon, V., & Greicius, M. D. (2009). Distinct cerebellar contributions to intrinsic connectivity networks. Journal of Neuroscience, 29(26), 8586–8594. https://doi.org/10.1523/JNEUROSCI.1868-09.2009

    CAS  Article  PubMed  Google Scholar 

  12. Jiang, L. W., Qian, R. B., Fu, X. M., Zhang, D., Peng, N., Niu, C. S., & Wang, Y. H. (2018). Altered attention networks and DMN in refractory epilepsy: A resting-state functional and causal connectivity study. Epilepsy and Behavior, 88, 81–86. https://doi.org/10.1016/j.yebeh.2018.06.045

    Article  PubMed  Google Scholar 

  13. Kirschen, M. P., Davis-Ratner, M. S., Milner, M. W., Chen, S. H., Schraedley-Desmond, P., Fisher, P. G., & Desmond, J. E. (2008). Verbal memory impairments in children after cerebellar tumor resection. Behavioural Neurology, 20(1–2), 39–53. https://doi.org/10.3233/BEN-2008-0216

    Article  PubMed  Google Scholar 

  14. Menon, V. (2011). Large-scale brain networks and psychopathology: A unifying triple network model. Trends in Cognitive Sciences, 15(10), 483–506. https://doi.org/10.1016/j.tics.2011.08.003

    Article  PubMed  Google Scholar 

  15. Mikdashi, J. A. (2016). Altered functional neuronal activity in neuropsychiatric lupus: A systematic review of the fMRI investigations. Seminars in Arthritis and Rheumatism, 45(4), 455–462. https://doi.org/10.1136/annrheumdis-2018-214677

    Article  PubMed  Google Scholar 

  16. Nystedt, J., Mannfolk, P., Jonsen, A., Bengtsson, A., Nilsson, P., Sundgren, P. C., & Strandberg, T. O. (2018). Functional connectivity changes in systemic lupus erythematosus: A resting-state study. Brain Connectivity, 8(4), 220–234. https://doi.org/10.1089/brain.2017.0557

    Article  PubMed  Google Scholar 

  17. Nystedt, J., Mannfolk, P., Jönsen, A., Nilsson, P., Strandberg, T. O., & Sundgren, P. C. (2019). Functional connectivity changes in core resting state networks are associated with cognitive performance in systemic lupus erythematosus. Journal of Comparative Neurology. https://doi.org/10.1002/cne.24656

    Article  Google Scholar 

  18. O’Neill, S., & Cervera, R. (2010). Systemic lupus erythematosus. Best Practice and Research Clinical Rheumatology, 24(6), 841–855. https://doi.org/10.1016/j.berh.2010.10.006

    Article  PubMed  Google Scholar 

  19. Ouyang, X., Chen, K., Yao, L., Wu, X., Zhang, J., Li, K., Jin, Z., & Guo, X. (2015). Independent component analysis-based identification of covariance patterns of microstructural white matter damage in Alzheimer’s disease. PLoS ONE, 10(3), e119714. https://doi.org/10.1371/journal.pone.0119714

    CAS  Article  Google Scholar 

  20. Rocca, M. A., Agosta, F., Mezzapesa, D. M., Ciboddo, G., Falini, A., Comi, G., & Filippi, M. (2006). An fMRI study of the motor system in patients with neuropsychiatric systemic lupus erythematosus. NeuroImage, 30(2), 478–484. https://doi.org/10.1016/j.neuroimage.2005.09.047

    Article  PubMed  Google Scholar 

  21. Sammler, D., Grosbras, M. H., Anwander, A., Bestelmeyer, P. E., & Belin, P. (2015). Dorsal and ventral pathways for prosody. Current Biology, 25(23), 3079–3085. https://doi.org/10.1016/j.cub.2015.10.009

    CAS  Article  PubMed  Google Scholar 

  22. Shapira-Lichter, I., Vakil, E., Litinsky, I., Oren, N., Glikmann-Johnston, Y., Caspi, D., Hendler, T., & Paran, D. (2013). Learning and memory-related brain activity dynamics are altered in systemic lupus erythematosus: A functional magnetic resonance imaging study. Lupus, 22(6), 562–573. https://doi.org/10.1177/0961203313480399

    Article  PubMed  Google Scholar 

  23. Shapira-Lichter, I., Weinstein, M., Lustgarten, N., Ash, E., Litinsky, I., Aloush, V., Anouk, M., Caspi, D., Hendler, T., & Paran, D. (2016). Impaired diffusion tensor imaging findings in the corpus callosum and cingulum may underlie impaired learning and memory abilities in systemic lupus erythematosus. Lupus, 25(11), 1200–1208. https://doi.org/10.1177/0961203316636471

    CAS  Article  PubMed  Google Scholar 

  24. Shine, J. M., O’Callaghan, C., Halliday, G. M., & Lewis, S. J. (2014). Tricks of the mind: Visual hallucinations as disorders of attention. Progress in Neurobiology, 116, 58–65. https://doi.org/10.1016/j.pneurobio.2014.01.004

    Article  PubMed  Google Scholar 

  25. Tomietto, P., Annese, V., D’Agostini, S., Venturini, P., La Torre, G., de Vita, S., & Ferraccioli, G. F. (2007). General and specific factors associated with severity of cognitive impairment in systemic lupus erythematosus. Arthritis and Rheumatism, 57(8), 1461–1472. https://doi.org/10.1002/art.23098

    CAS  Article  PubMed  Google Scholar 

  26. van de Ven, V. G., Formisano, E., Prvulovic, D., Roeder, C. H., & Linden, D. E. (2004). Functional connectivity as revealed by spatial independent component analysis of fMRI measurements during rest. Human Brain Mapping, 22(3), 165–178. https://doi.org/10.1002/hbm.20022

    Article  PubMed  PubMed Central  Google Scholar 

  27. Wei, L., Hu, X., Zhu, Y., Yuan, Y., Liu, W., & Chen, H. (2017). Aberrant intra-and internetwork functional connectivity in depressed Parkinson’s disease. Scientific Reports, 7(1), 2568. https://doi.org/10.1038/s41598-017-02127-y

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. Whitfield-Gabrieli, S., Moran, J. M., Nieto-Castañón, A., Triantafyllou, C., Saxe, R., & Gabrieli, J. D. (2011). Associations and dissociations between default and self-reference networks in the human brain. NeuroImage, 55(1), 225–232. https://doi.org/10.1016/j.neuroimage.2010.11.048

    Article  PubMed  Google Scholar 

  29. Wiseman, S. J., Bastin, M. E., Amft, E. N., Belch, J. F., Ralston, S. H., & Wardlaw, J. M. (2018). Cognitive function, disease burden and the structural connectome in systemic lupus erythematosus. Lupus, 27(8), 1329–1337. https://doi.org/10.1177/0961203318772666

    CAS  Article  PubMed  Google Scholar 

  30. Xu, M., Tan, X., Zhang, X., Guo, Y., Mei, Y., Feng, Q., Xu, Y., & Feng, Y. (2017). Alterations of white matter structural networks in patients with non-neuropsychiatric systemic lupus erythematosus identified by probabilistic tractography and connectivity-based analyses. NeuroImage: Clinical, 13, 349–360. https://doi.org/10.1016/j.nicl.2016.12.021

    Article  Google Scholar 

  31. Zhang, H., Zuo, X. N., Ma, S. Y., Zang, Y. F., Milham, M. P., & Zhu, C. Z. (2010). Subject order-independent group ICA (SOI-GICA) for functional MRI data analysis. NeuroImage, 51(4), 1414–1424. https://doi.org/10.1016/j.neuroimage.2010.03.039

    Article  PubMed  Google Scholar 

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Funding

This study has received funding by National Natural Science Foundation of China (NSFC81571652); Science and technology project of Yangzhou (YZ2018059); "333 Project" of Jiangsu Province (BRA2017154). Yangzhou City Science and Education Strengthening Key Talents Project (ZDRC201873).

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Correspondence to Jing-Tao Wu.

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Cao, ZY., Wang, N., Wei, H. et al. The altered functional modular organization in systemic lupus erythematosus: an independent component analysis study. Brain Imaging and Behavior (2021). https://doi.org/10.1007/s11682-021-00528-2

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Keywords

  • Cognitive impairment
  • Functional connectivity
  • Independent component analysis
  • Modular network
  • Systemic lupus erythematosus