Aberrant resting-state functional connectivity of salience network in first-episode schizophrenia
- 45 Downloads
The disruption of salience network (SN) has been consistently found in patients with schizophrenia and thought to give rise to specific symptoms. However, the functional dysconnectivity pattern of SN remains unclear in first-episode schizophrenia (FES). Sixty-five patients with FES and sixty-six health controls (HC) were enrolled in this study and underwent resting-state functional magnetic resonance imaging (rs-fMRI). The eleven regions of interest (ROIs) within SN were derived from the peaks of the group independent component analysis (gICA). Seed-based whole-brain functional connectivity (FC) analyses were performed with all SN ROIs as the seeds. Both hyper- and hypo-connectivity of SN were found in the FES. Specifically, the increased FC mainly existed between the SN and cortico-cerebellar sub-circuit and prefrontal cortex, while the reduced FC mainly existed within cortico-striatal-thalamic-cortical (CSTC) sub-circuit. Our findings suggest that FES is associated with pronounced dysregulation of SN, characterized prominently by hyperconnectivity of SN-prefrontal cortex and cerebellum, as well as hypoconnectivity of CSTC sub-circuit of the SN.
KeywordsFirst-episode schizophrenia Resting-state functional magnetic resonance imaging Salience network Functional connectivity
DG and JW designed the current study. HH drafted the manuscript. HH, BZ, YT, TZ, LX, JW, JL, ZQ, JX, CL, and JW performed the experiments. HH, BZ, YJ, YT, TZ, LX, HW, CL, JX, and JW analyzed the data. HH, YJ, HW, JX, and JW revised the the manuscript. All of the authors read and approved the final manuscript.
This work was supported by grants from Ministry of Science and Technology of China (2016YFC1306803), National Natural Science Foundation of China (81671329, 81671332), Program of Shanghai Academic/Technology Research Leader (16XD1402400), Shanghai Science and Technology Committee (16JC1420200, 17ZR1424700), National Key Clinical Disciplines at Shanghai Mental Health Center (OMA-MH, 2011–873), Shanghai Key Laboratory of Psychotic Disorders (13dz2260500), Shanghai Jiao Tong University Foundation (14JCRY04, YG2014MS40), SHSMU- ION Research Center for Brain Disorders (2015NKX001, 15ZH2015, W35XT), Medicine Engineering Intersection Program of Shanghai Jiaotong University (YG2015ZD12) and Shanghai Hospital Development Center (16CR2015A, 16CR3017A). Projects of medical and health development in Shandong province (2017WS115), Projects of medical and health development in Qingdao city (2016WJZD068), Doctoral Innovation Fund from Shanghai Jiaotong University School of Medicine (BXJ201639).
Compliance with ethical standards
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The Ethics Committee of SMHC approved the study protocol(2012-45C1).
The written, informed consent of all subjects was obtained after receiving a complete description of the study.
- Allman, J. M., Tetreault, N. A., Hakeem, A. Y., Manaye, K. F., Semendeferi, K., Erwin, J. M., Park, S., Goubert, V., & Hof, P. R. (2010). The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans. Brain Structure & Function, 214(5–6), 495–517. https://doi.org/10.1007/s00429-010-0254-0.CrossRefGoogle Scholar
- Chen, Y. L., Tu, P. C., Lee, Y. C., Chen, Y. S., Li, C. T., & Su, T. P. (2013). Resting-state fMRI mapping of cerebellar functional dysconnections involving multiple large-scale networks in patients with schizophrenia. Schizophrenia Research, 149(1–3), 26–34. https://doi.org/10.1016/j.schres.2013.05.029.CrossRefGoogle Scholar
- Damoiseaux, J. S., Rombouts, S. A., Barkhof, F., Scheltens, P., Stam, C. J., Smith, S. M., et al. (2006). Consistent resting-state networks across healthy subjects. Proceedings of the National Academy of Sciences of the United States of America, 103(37), 13848–13853. https://doi.org/10.1073/pnas.0601417103.CrossRefGoogle Scholar
- Dong, D., Wang, Y., Chang, X., Luo, C., & Yao, D. (2017). Dysfunction of large-scale brain networks in schizophrenia: A meta-analysis of resting-state functional connectivity. Schizophr Bull. https://doi.org/10.1093/schbul/sbx034.
- Dosenbach, N. U., Fair, D. A., Miezin, F. M., Cohen, A. L., Wenger, K. K., Dosenbach, R. A., et al. (2007). Distinct brain networks for adaptive and stable task control in humans. Proceedings of the National Academy of Sciences of the United States of America, 104(26), 11073–11078. https://doi.org/10.1073/pnas.0704320104.CrossRefGoogle Scholar
- Fornito, A., Harrison, B. J., Goodby, E., Dean, A., Ooi, C., Nathan, P. J., Lennox, B. R., Jones, P. B., Suckling, J., & Bullmore, E. T. (2013). Functional dysconnectivity of corticostriatal circuitry as a risk phenotype for psychosis. JAMA Psychiatry, 70(11), 1143–1151. https://doi.org/10.1001/jamapsychiatry.2013.1976.CrossRefGoogle Scholar
- Fox, M. D., Snyder, A. Z., Vincent, J. L., Corbetta, M., Van Essen, D. C., & Raichle, M. E. (2005). The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A, 102(27), 9673–9678. https://doi.org/10.1073/pnas.0504136102. CrossRefGoogle Scholar
- Glahn, D. C., Laird, A. R., Ellison-Wright, I., Thelen, S. M., Robinson, J. L., Lancaster, J. L., Bullmore, E., & Fox, P. T. (2008). Meta-analysis of gray matter anomalies in schizophrenia: Application of anatomic likelihood estimation and network analysis. Biological Psychiatry, 64(9), 774–781. https://doi.org/10.1016/j.biopsych.2008.03.031.CrossRefGoogle Scholar
- Guo, W., Liu, F., Chen, J., Wu, R., Zhang, Z., Yu, M., Xiao, C., & Zhao, J. (2015a). Resting-state cerebellar-cerebral networks are differently affected in first-episode, drug-naive schizophrenia patients and unaffected siblings. Scientific Reports, 5, 17275. https://doi.org/10.1038/srep17275.CrossRefGoogle Scholar
- Han, S. W., Eaton, H. P., & Marois, R. (2018). Functional fractionation of the Cingulo-opercular network: Alerting insula and updating cingulate. Cereb Cortex. https://doi.org/10.1093/cercor/bhy130.
- Jiang, Y., Duan, M., Chen, X., Chang, X., He, H., Li, Y., Luo, C., & Yao, D. (2017). Common and distinct dysfunctional patterns contribute to triple network model in schizophrenia and depression: A preliminary study. Prog Neuropsychopharmacol Biol Psychiatry, 79(Pt B), 302–310. https://doi.org/10.1016/j.pnpbp.2017.07.007.CrossRefGoogle Scholar
- Leucht, S., Samara, M., Heres, S., Patel, M. X., Furukawa, T., Cipriani, A., Geddes, J., & Davis, J. M. (2015). Dose equivalents for second-generation antipsychotic drugs: The classical mean dose method. Schizophrenia Bulletin, 41(6), 1397–1402. https://doi.org/10.1093/schbul/sbv037.CrossRefGoogle Scholar
- Liu, H., Fan, G., Xu, K., & Wang, F. (2011). Changes in cerebellar functional connectivity and anatomical connectivity in schizophrenia: A combined resting-state functional MRI and diffusion tensor imaging study. Journal of Magnetic Resonance Imaging, 34(6), 1430–1438. https://doi.org/10.1002/jmri.22784.CrossRefGoogle Scholar
- Manoliu, A., Riedl, V., Zherdin, A., Muhlau, M., Schwerthoffer, D., Scherr, M., et al. (2014). Aberrant dependence of default mode/central executive network interactions on anterior insular salience network activity in schizophrenia. Schizophrenia Bulletin, 40(2), 428–437. https://doi.org/10.1093/schbul/sbt037.CrossRefGoogle Scholar
- Menon, V. (2015). Salience network. Brain Mapping: An Encyclopedic Reference, 2, 597–611. https://doi.org/10.1016/b978-0-12-397025-1.00052-x.
- Mikolas, P., Melicher, T., Skoch, A., Matejka, M., Slovakova, A., Bakstein, E., Hajek, T., & Spaniel, F. (2016). Connectivity of the anterior insula differentiates participants with first-episode schizophrenia spectrum disorders from controls: A machine-learning study. Psychological Medicine, 46(13), 2695–2704. https://doi.org/10.1017/S0033291716000878.CrossRefGoogle Scholar
- Seeley, W. W., Menon, V., Schatzberg, A. F., Keller, J., Glover, G. H., Kenna, H., Reiss, A. L., & Greicius, M. D. (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.CrossRefGoogle Scholar
- Sridharan, D., Levitin, D. J., & Menon, V. (2008). A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks. Proceedings of the National Academy of Sciences of the United States of America, 105(34), 12569–12574. https://doi.org/10.1073/pnas.0800005105.CrossRefGoogle Scholar
- Tu, P. C., Hsieh, J. C., Li, C. T., Bai, Y. M., & Su, T. P. (2012). Cortico-striatal disconnection within the cingulo-opercular network in schizophrenia revealed by intrinsic functional connectivity analysis: A resting fMRI study. Neuroimage, 59(1), 238–247. https://doi.org/10.1016/j.neuroimage.2011.07.086.CrossRefGoogle Scholar
- Tu, P. C., Lee, Y. C., Chen, Y. S., Hsu, J. W., Li, C. T., & Su, T. P. (2015). Network-specific cortico-thalamic dysconnection in schizophrenia revealed by intrinsic functional connectivity analyses. Schizophrenia Research, 166(1–3), 137–143. https://doi.org/10.1016/j.schres.2015.05.023.CrossRefGoogle Scholar
- Uddin, L. Q., Supekar, K., Amin, H., Rykhlevskaia, E., Nguyen, D. A., Greicius, M. D., & Menon, V. (2010). Dissociable connectivity within human angular gyrus and intraparietal sulcus: Evidence from functional and structural connectivity. Cerebral Cortex, 20(11), 2636–2646. https://doi.org/10.1093/cercor/bhq011.CrossRefGoogle Scholar
- Uddin, L. Q., Supekar, K. S., Ryali, S., & Menon, V. (2011). Dynamic reconfiguration of structural and functional connectivity across core neurocognitive brain networks with development. The Journal of Neuroscience, 31(50), 18578–18589. https://doi.org/10.1523/JNEUROSCI.4465-11.2011.CrossRefGoogle Scholar
- Wang, C., Ji, F., Hong, Z., Poh, J. S., Krishnan, R., Lee, J., Rekhi, G., Keefe, R. S. E., Adcock, R. A., Wood, S. J., Fornito, A., Pasternak, O., Chee, M. W. L., & Zhou, J. (2016b). Disrupted salience network functional connectivity and white-matter microstructure in persons at risk for psychosis: Findings from the LYRIKS study. Psychological Medicine, 46(13), 2771–2783. https://doi.org/10.1017/S0033291716001410.CrossRefGoogle Scholar
- Wang, H., Guo, W., Liu, F., Wang, G., Lyu, H., Wu, R., Chen, J., Wang, S., Li, L., & Zhao, J. (2016a). Patients with first-episode, drug-naive schizophrenia and subjects at ultra-high risk of psychosis shared increased cerebellar-default mode network connectivity at rest. Scientific Reports, 6, 26124. https://doi.org/10.1038/srep26124.CrossRefGoogle Scholar
- Whitfield-Gabrieli, S., & Ford, J. M. (2012). Default mode network activity and connectivity in psychopathology. Annual Review of Clinical Psychology, 8, 49–76. https://doi.org/10.1146/annurev-clinpsy-032511-143049.CrossRefGoogle Scholar
- Wotruba, D., Michels, L., Buechler, R., Metzler, S., Theodoridou, A., Gerstenberg, M., Walitza, S., Kollias, S., Rössler, W., & Heekeren, K. (2014). Aberrant coupling within and across the default mode, task-positive, and salience network in subjects at risk for psychosis. Schizophrenia Bulletin, 40(5), 1095–1104. https://doi.org/10.1093/schbul/sbt161.CrossRefGoogle Scholar
- Zhuo, C., Wang, C., Wang, L., Guo, X., Xu, Q., Liu, Y., et al. (2017). Altered resting-state functional connectivity of the cerebellum in schizophrenia. Brain Imaging Behav. https://doi.org/10.1007/s11682-017-9704-0.