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Cortical thickness reductions associate with abnormal resting-state functional connectivity in non-neuropsychiatric systemic lupus erythematosus

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Abstract

To detect the abnormal cortical thickness and disrupted brain resting-state functional connectivity (RSFC) in patients with systemic lupus erythematosus (SLE) without neuropsychiatric symptoms (non-NPSLE). Using T1-weighted 3D brain structural data, we first determined the regions with abnormal cortical thickness in a cohort of 33 adult female non-NPSLE patients. By taking brain regions with significantly reduced cortical thickness as the seeds, we calculated their RSFC based on the resting-fMRI data and detected the relationship between the RSFC and cortical thickness in the non-NPSLE patients. Compared to the controls, the non-NPSLE patients showed significantly cortical thinning in the left fusiform gyrus (FUS.L), left lingual gyrus (LING.L), right lingual gyrus (LING.R) and left superior frontal cortex (SFC.L). As for the RSFC, statistical analyses indicated that the abnormal cortical thickness in LING.L is associated with increased RSFC in the left posterior cingulate cortex (PCC.L), and cortical thinning in SFC.L associated with decreased RSFC in left cerebellum 6 (CRBL 6.L) in non-NPSLE patients. In addition, in non-NPSLE patients, the decreased cortical thickness in LING.L was correlated to the increased RSFC in PCC.L, and decreased cortical thickness in SFC.L was correlated to the decreased RSFC in CRBL 6.L. Our findings suggest that the cortical abnormalities may affect brain intrinsic connectivity in non-NPSLE patients.

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Abbreviations

SLE:

Systemic lupus erythematosus

NPSLE:

Neuropsychiatric systemic lupus erythematosus

non-NPSLE:

Non-neuropsychiatric systemic lupus erythematosus

RSFC:

Resting-state functional connectivity

SBM:

Surface-based morphometry

ACR:

American College of Rheumatology

SLEDAI:

Systemic Lupus Erythematosus Disease Activity Index

SLICC/ACR:

Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index

GM/WM:

Gray matter/white matter

CSF:

Cerebrospinal fluid

R-fMRI:

Resting-state fMRI

T-fMRI:

Task-fMRI

References

  • Achard, S., & Bullmore, E. (2007). Efficiency and cost of economical brain functional networks. PLoS Comput Biol, 3(2), e17.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Appenzeller, S., Bonilha, L., Rio, P. A., Li, L. M., Costallat, L. T. L., & Cendes, F. (2007). Longitudinal analysis of gray and white matter loss in patients with systemic lupus erythematosus. NeuroImage, 34(2), 694–701.

    Article  PubMed  Google Scholar 

  • Bellebaum, C., & Daum, I. (2007). Cerebellar involvement in executive control. Cerebellum, 6(3), 184–192.

    Article  PubMed  Google Scholar 

  • Caspers, J., Zilles, K., Amunts, K., Laird, A. R., Fox, P. T., & Eickhoff, S. B. (2014). Functional characterization and differential coactivation patterns of two cytoarchitectonic visual areas on the human posterior fusiform gyrus. Hum Brain Mapp, 35(6), 2754–2767.

    Article  PubMed  Google Scholar 

  • Dale, A. M., Fischl, B., & Sereno, M. I. (1999). Cortical surface-based analysis: I. Segmentation and surface reconstruction. NeuroImage, 9(2), 179–194.

    Article  PubMed  CAS  Google Scholar 

  • Difrancesco, M. W., Holland, S. K., Ris, M. D., Adler, C. M., Nelson, S., Delbello, M. P., Altaye, M., & Brunner, H. I. (2007). Functional magnetic resonance imaging assessment of cognitive function in childhood-onset systemic lupus erythematosus: A pilot study. Arthritis Rheum, 56(12), 4151–4163.

    Article  PubMed  Google Scholar 

  • Difrancesco, M. W., Gitelman, D. R., Klein-Gitelman, M. S., Sagcal-Gironella, A. C. P., Zelko, F., Beebe, D., Parrish, T., Hummel, J., Ying, J., & Brunner, H. I. (2013). Functional neuronal network activity differs with cognitive dysfunction in childhood-onset systemic lupus erythematosus. Arthritis Research & Therapy, 15(2), R40. doi:10.1186/ar4197.

    Article  Google Scholar 

  • Du Boisgueheneuc, F., Levy, R., Volle, E., Seassau, M., Duffau, H., Kinkingnehun, S., Samson, Y., Zhang, S., & Dubois, B. (2006). Functions of the left superior frontal gyrus in humans: A lesion study. Brain, 129(12), 3315–3328.

    Article  PubMed  Google Scholar 

  • Ecker, C., Ginestet, C., Feng, Y., Johnston, P., Lombardo, M. V., Lai, M. C., Suckling, J., Palaniyappan, L., Daly, E., & Murphy, C. M. (2013). Brain surface anatomy in adults with autism: The relationship between surface area, cortical thickness, and autistic symptoms. JAMA Psychiatry, 70(1), 59–70.

    Article  PubMed  Google Scholar 

  • Fischl, B., & Dale, A. M. (2000). Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proc Natl Acad Sci U S A, 97(20), 11050–11055.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fischl, B., Van Der Kouwe, A., Destrieux, C., Halgren, E., Ségonne, F., Salat, D. H., Busa, E., Seidman, L. J., Goldstein, J., & Kennedy, D. (2004). Automatically parcellating the human cerebral cortex. Cereb Cortex, 14(1), 11–22.

    Article  PubMed  Google Scholar 

  • Fox, M. D., Zhang, D., Snyder, A. Z., & Raichle, M. E. (2009). The global signal and observed anticorrelated resting state brain networks. J Neurophysiol, 101(6), 3270–3283.

    Article  PubMed  PubMed Central  Google Scholar 

  • Fusar-Poli, P., Placentino, A., Carletti, F., Landi, P., & Abbamonte, M. (2009). Functional atlas of emotional faces processing: A voxel-based meta-analysis of 105 functional magnetic resonance imaging studies. J Psychiatry Neurosci, 34(6), 418–432.

    PubMed  PubMed Central  Google Scholar 

  • Gladman, D. D., Urowitz, M. B., Goldsmith, C. H., Fortin, P., Ginzler, E., Gordon, C., Hanly, J. G., Isenberg, D. A., Kalunian, K., & Nived, O. (1997). The reliability of the systemic lupus International Collaborating Clinics/American College of Rheumatology damage index in patients with systemic lupus erythematosus. Arthritis Rheum, 40(5), 809–813.

    Article  PubMed  CAS  Google Scholar 

  • Gladman, D. D., Urowitz, M. B., Kagal, A., & Hallett, D. (2000). Accurately describing changes in disease activity in systemic lupus erythematosus. J Rheumatol, 27(2), 377–379.

    PubMed  CAS  Google Scholar 

  • Greicius, M. D., Krasnow, B., Reiss, A. L., & Menon, V. (2003). Functional connectivity in the resting brain: A network analysis of the default mode hypothesis. Proc Natl Acad Sci U S A, 100(1), 253–258.

    Article  PubMed  CAS  Google Scholar 

  • Habas, C., Kamdar, N., Nguyen, D., Prater, K., Beckmann, C. F., Menon, V., & Greicius, M. D. (2009). Distinct cerebellar contributions to intrinsic connectivity networks. J Neurosci, 29(26), 8586–8594.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Herting, M. M., Fair, D., & Nagel, B. J. (2011). Altered fronto-cerebellar connectivity in alcohol-naive youth with a family history of alcoholism. NeuroImage, 54(4), 2582–2589.

    Article  PubMed  Google Scholar 

  • Hester, R., Nestor, L., & Garavan, H. (2009). Impaired error awareness and anterior cingulate cortex hypoactivity in chronic cannabis users. Neuropsychopharmacology, 34(11), 2450–2458.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hochberg, M. C. (1997). Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum, 40(9), 1725.

    Article  PubMed  CAS  Google Scholar 

  • Horn, D. I., Yu, C., Steiner, J., Buchmann, J., Kaufmann, J., Osoba, A., Eckert, U., Zierhut, K. C., Schiltz, K., & He, H. (2010). Glutamatergic and resting-state functional connectivity correlates of severity in major depression – The role of Pregenual anterior cingulate cortex and anterior insula. Front Syst Neurosci, 4(33). doi:10.3389/fnsys.2010.00033.

  • Hou, J., Lin, Y., Zhang, W., Song, L., Wu, W., Wang, J., Zhou, D., Zou, Q., Fang, Y., & He, M. (2013). Abnormalities of frontal-parietal resting-state functional connectivity are related to disease activity in patients with systemic lupus erythematosus. PLoS One, 8(9), e74530. doi:10.1371/journal.pone.0074530.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hutton, C., Draganski, B., Ashburner, J., & Weiskopf, N. (2009). A comparison between voxel-based cortical thickness and voxel-based morphometry in normal aging. NeuroImage, 48(2), 371–380.

    Article  PubMed  PubMed Central  Google Scholar 

  • Jung, R. E., Segall, J. M., Grazioplene, R. G., Qualls, C., Sibbitt Jr., W. L., & Roldan, C. A. (2010). Cortical thickness and subcortical gray matter reductions in neuropsychiatric systemic lupus erythematosus. PLoS One, 5(3), e9302.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kaul, A., Gordon, C., Crow, M. K., Touma, Z., Urowitz, M. B., Van Vollenhoven, R., Ruiz-Irastorza, G., & Hughes, G. (2016). Systemic lupus erythematosus. Nat Rev Dis Primers, 2, 16039. doi:10.1038/nrdp.2016.39.

    Article  PubMed  Google Scholar 

  • Kevin, M., Birn, R. M., Handwerker, D. A., Jones, T. B., & Bandettini, P. A. (2009). The impact of global signal regression on resting state correlations: Are anti-correlated networks introduced? NeuroImage, 44(3), 893–905.

    Article  Google Scholar 

  • Leech, R., & Sharp, D. J. (2014). The role of the posterior cingulate cortex in cognition and disease. Brain, 137(1), 12–32.

    Article  PubMed  Google Scholar 

  • Liang, M., Corzillius, M., Bae, S., Lew, R., Fortin, P., Gordon, C., Isenberg, D., Alarcon, G., Straaton, K., & Denburg, S. (1999). The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum, 42(4), 599–608.

    Article  Google Scholar 

  • Lin, Y., Zou, Q. H., Wang, J., Wang, Y., Zhou, D. Q., Zhang, R. H., Zhang, Y. W., Lii, H. T., & Fang, Y. F. (2011). Localization of cerebral functional deficits in patients with non-neuropsychiatric systemic lupus erythematosus. Hum Brain Mapp, 32(11), 1847–1855.

    Article  PubMed  Google Scholar 

  • Lüsebrink, F., Wollrab, A., & Speck, O. (2013). Cortical thickness determination of the human brain using high resolution 3T and 7T MRI data. NeuroImage, 70, 122–131.

    Article  PubMed  Google Scholar 

  • Ly, M., Motzkin, J. C., Philippi, C. L., Kirk, G. R., Newman, J. P., Kiehl, K. A., & Koenigs, M. (2012). Cortical thinning in psychopathy. Am J Psychiatry, 169(7), 743–749.

    Article  PubMed  Google Scholar 

  • Maddock, R. J., Garrett, A. S., & Buonocore, M. H. (2001). Remembering familiar people: The posterior cingulate cortex and autobiographical memory retrieval. Neuroscience, 104(3), 667–666.

    Article  PubMed  CAS  Google Scholar 

  • Mak, A., Ren, T., Fu, E. H., Cheak, A. A., & Ho, R. C. (2012). A prospective functional MRI study for executive function in patients with systemic lupus erythematosus without neuropsychiatric symptoms. Semin Arthritis Rheum, 41(6), 849–858.

    Article  PubMed  Google Scholar 

  • Mak, A., Ho, R. C.-M., Tng, H.-Y., Koh, H. L., Chong, J. S. X., & Zhou, J. (2016). Early cerebral volume reductions and their associations with reduced lupus disease activity in patients with newly-diagnosed systemic lupus erythematosus. Sci Report, 6(22231). doi:10.1038/srep22231.

  • Martina, L., Motzkin, J. C., Philippi, C. L., Kirk, G. R., Newman, J. P., Kiehl, K. A., & Michael, K. (2012). Cortical thinning in psychopathy. Am J Psychiatry, 169(7), 743–749.

    Article  Google Scholar 

  • Navari, S., & Dazzan, P. (2009). Do antipsychotic drugs affect brain structure? A systematic and critical review of MRI findings. Psychol Med, 39(11), 1763–1777.

    Article  PubMed  CAS  Google Scholar 

  • Ren, T., Ho, R. C. M., & Mak, A. (2012). Dysfunctional cortico–basal ganglia–thalamic circuit and altered hippocampal–amygdala activity on cognitive set-shifting in non-neuropsychiatric systemic lupus erythematosus. Arthritis Rheum, 64(12), 4048–4059.

    Article  PubMed  Google Scholar 

  • Rykhlevskaia, E., Gratton, G., & Fabiani, M. (2008). Combining structural and functional neuroimaging data for studying brain connectivity: A review. Psychophysiology, 45(2), 173–187.

    Article  PubMed  Google Scholar 

  • Ségonne, F., Dale, A., Busa, E., Glessner, M., Salat, D., Hahn, H., & Fischl, B. (2004). A hybrid approach to the skull stripping problem in MRI. NeuroImage, 22(3), 1060–1075.

    Article  PubMed  Google Scholar 

  • Ségonne, F., Pacheco, J., & Fischl, B. (2007). Geometrically accurate topology-correction of cortical surfaces using nonseparating loops. IEEE Trans Med Imaging, 26(4), 518–529.

    Article  PubMed  Google Scholar 

  • Sestieri, C., Corbetta, M., Romani, G. L., & Shulman, G. L. (2011). Episodic memory retrieval, parietal cortex, and the default mode network: Functional and topographic analyses. J Neurosci, 31(12), 4407–4420.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shapiralichter, I., Vakil, E., Litinsky, I., Oren, N., Glikmannjohnston, 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.

    Article  Google Scholar 

  • Sled, J. G., Zijdenbos, A. P., & Evans, A. C. (1998). A nonparametric method for automatic correction of intensity nonuniformity in MRI data. IEEE Trans Med Imaging, 17(1), 87–97.

    Article  PubMed  CAS  Google Scholar 

  • Späti, J., Hänggi, J., Doerig, N., Ernst, J., Sambataro, F., Brakowski, J., Jäncke, L., Grosse Holtforth, M., Seifritz, E., & Spinelli, S. (2015). Prefrontal thinning affects functional connectivity and regional homogeneity of the anterior cingulate cortex in depression. Neuropsychopharmacology, 40(7), 1640–1648.

    Article  PubMed  PubMed Central  Google Scholar 

  • Van Tol, M.-J., Li, M., Metzger, C., Hailla, N., Horn, D., Li, W., Heinze, H., Bogerts, B., Steiner, J., & He, H. (2014). Local cortical thinning links to resting-state disconnectivity in major depressive disorder. Psychol Med, 44(10), 2053–2065.

    Article  PubMed  Google Scholar 

  • Vannini, P., O'brien, J., O’keefe, K., Pihlajamäki, M., Laviolette, P., & Sperling, R. (2011). What goes down must come up: Role of the posteromedial cortices in encoding and retrieval. Cereb Cortex, 21(1), 22–34.

    Article  PubMed  CAS  Google Scholar 

  • Voets, N. L., Hough, M. G., Douaud, G., Matthews, P. M., James, A., Winmill, L., Webster, P., & Smith, S. (2008). Evidence for abnormalities of cortical development in adolescent-onset schizophrenia. NeuroImage, 43(4), 665–675.

    Article  PubMed  Google Scholar 

  • Wang, Y., Zhong, S., Jia, Y., Sun, Y., Wang, B., Liu, T., Pan, J., & Huang, L. (2016). Disrupted resting-state functional connectivity in Nonmedicated bipolar disorder. Radiology, 280(2), 529–536. doi:10.1148/radiol.2016151641.

    Article  PubMed  Google Scholar 

  • Xu, J., Cheng, Y., Lai, A., Lv, Z., Campbell, R. A., Yu, H., Luo, C., Shan, B., Xu, L., & Xu, X. (2015). Autoantibodies affect brain density reduction in Nonneuropsychiatric systemic lupus erythematosus patients. Journal of Immunology Research, 2015, 11. doi:10.1155/2015/920718.

    Article  CAS  Google Scholar 

  • Yan, C.-G., Cheung, B., Kelly, C., Colcombe, S., Craddock, R. C., Martino, A. D., Li, Q., Zuo, X.-N., Castellanos, F. X., & Milham, M. P. (2013). A comprehensive assessment of regional variation in the impact of head micromovements on functional connectomics. NeuroImage, 76, 183–201.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang, Z., Wang, Y., Shen, Z., Yang, Z., Li, L., Chen, D., Yan, G., Cheng, X., Shen, Y., & Tang, X. (2016). The neurochemical and microstructural changes in the brain of systemic lupus erythematosus patients: A multimodal MRI study. Sci Report, 6, 19026. doi:10.1038/srep19026.

    Article  CAS  Google Scholar 

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Acknowledgements

The authors thank the three anonymous reviewers for their constructive comments and their suggestions.

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Author notes

  1. Chen Niu and Xiangliang Tan contributed equally to this work.

Authors and Affiliations

  1. Center for the Study of Applied Psychology, School of Psychology, Key Laboratory of Mental Health and Cognitive Science of Guangdong Province, Institute for Brain Research and Rehabilitation (IBRR), South China Normal University, Guangzhou, 510631, People’s Republic of China

    Chen Niu, Xiaojin Liu, Meiqi Niu, Ling Zhao, Feng Deng, Xiaoyan Wu, Huiyuan Huang & Ruiwang Huang

  2. Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China

    Xiangliang Tan, Yuankui Wu & Yikai Xu

  3. Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China

    Kai Han

  4. Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China

    Jun Xu

  5. Department of Rheumatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China

    Qin Huang

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  1. Chen Niu
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  2. Xiangliang Tan
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  3. Xiaojin Liu
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  4. Kai Han
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  5. Meiqi Niu
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  6. Jun Xu
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  7. Ling Zhao
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  8. Yuankui Wu
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  10. Qin Huang
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  11. Xiaoyan Wu
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  12. Huiyuan Huang
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  13. Yikai Xu
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  14. Ruiwang Huang
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Corresponding authors

Correspondence to Yikai Xu or Ruiwang Huang.

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Funding

This work was partly supported by the Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, and was partly funded by the National Natural Science Foundation of China [Grant number: 81,271,548, 81,271,560, 81,371,535, 81,428,013, and 81,471,654].

Conflict of interests

The authors declare that they have no competing financial interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

Additional information

Highlights:

1. We found cortical thinning in FUS.L, LING.L, LING.R and SFC.L in non-NPSLE patients.

2. Observed lower frontal-cerebellar RSFC in non-NPSLE patients compared to healthy controls.

3. Decreased cortical thickness in LING.L positively correlated with the connectivity of LING.L-PCC.L in non-NPSLE.

4. Cortical thinning in SFC.L positively correlated with connectivity of SFC.L-CRBL 6.L in non-NPSLE.

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Niu, C., Tan, X., Liu, X. et al. Cortical thickness reductions associate with abnormal resting-state functional connectivity in non-neuropsychiatric systemic lupus erythematosus. Brain Imaging and Behavior 12, 674–684 (2018). https://doi.org/10.1007/s11682-017-9729-4

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