Hostname: page-component-6bb9c88b65-6vlrh Total loading time: 0 Render date: 2025-07-23T20:57:51.929Z Has data issue: false hasContentIssue false
  • English
  • Français

Functional disconnection between subsystems of the default mode network in schizophrenia

Published online by Cambridge University Press:  13 November 2020

Fengmei Fan Open the ORCID record for Fengmei Fan [Opens in a new window] ,
Shuping Tan ,
Junchao Huang ,
Song Chen ,
Hongzhen Fan ,
Zhiren Wang ,
Chiang-Shan R. Li  and
Yunlong Tan
Fengmei Fan
Affiliation:
Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China State Key Laboratory of Cognitive Neuroscience and Learning & International Data Group/McGovern Institute for Brain Research, Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing 100875, China
Shuping Tan
Affiliation:
Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China
Junchao Huang
Affiliation:
Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China
Song Chen
Affiliation:
Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China
Hongzhen Fan
Affiliation:
Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China
Zhiren Wang
Affiliation:
Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China
Chiang-Shan R. Li
Affiliation:
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
Yunlong Tan*
Affiliation:
Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China
*
Author for correspondence: Yunlong Tan, E-mail: yltan21@126.com
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

A dysfunctional default mode network (DMN) has been reported in patients with schizophrenia. However, the stability of the deficits has not been determined across different stages of the disorder.

Methods

We examined the functional connectivity of the DMN subsystems of 125 patients with first-episode schizophrenia (FES) or recurrent schizophrenia (RES), compared to that of 82 healthy controls. We tested the robustness of the findings in an independent cohort of 158 patients and 39 healthy controls. We performed resting-state functional connectivity analysis, and examined the strength of the connections within and between the three subsystems of the DMN (core, dorsal medial prefrontal cortex [dMPFC], and medial temporal lobe [MTL]). We also analyzed the connectivity correlations to symptoms and illness duration.

Results

We found reduced connectivity strength between the core and MTL subsystems in schizophrenia patients compared to controls, with no differences between the FES and RES patient groups; these findings were validated in the second sample. Schizophrenia patients also showed a significant reduction in connectivity within the MTL and between the dMPFC−MTL subsystems, similarly between FES and RES groups. The connectivity strength within the core subsystem was negatively correlated with clinical symptoms in schizophrenia. There was no significant correlation between the DMN subsystem connectivity and illness duration.

Conclusions

DMN subsystem connectivity deficits are present in schizophrenia, and the homochronicity of their appearance indicates the trait-like nature of these alterations. The DMN deficit may be useful for early diagnosis, and MTL dysfunction may be a crucial mechanism underlying schizophrenia.

Keywords

Default mode networkfunctional connectivityfunctional MRIresting stateschizophrenia

Information

Type
Original Article
Information
Psychological Medicine , Volume 52 , Issue 12 , September 2022 , pp. 2270 - 2280
Check for updates
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Akil, M., Pierri, J. N., Whitehead, R. E., Edgar, C. L., Mohila, C., Sampson, A. R., & Lewis, D. A. (1999). Lamina-specific alterations in the dopamine innervation of the prefrontal cortex in schizophrenic subjects. American Journal of Psychiatry, 156, 1580–1589.CrossRefGoogle ScholarPubMed
Alexiadou, A., Bozikas, V. P., Kosmidis, M. H., Parlapani, E., Kiosseoglou, G., & Fokas, K. (2018). The effect of impaired verbal memory retrieval on autobiographical memory across different life periods in schizophrenia. Comprehensive Psychiatry, 80, 81–88.CrossRefGoogle Scholar
Allen, P., Moore, H., Corcoran, C. M., Gilleen, J., Kozhuharova, P., Reichenberg, A., & Malaspina, D. (2019). Emerging temporal lobe dysfunction in people at clinical high risk for psychosis. Frontiers in Psychiatry, 10, 298.CrossRefGoogle ScholarPubMed
Alonso-Solis, A., Vives-Gilabert, Y., Grasa, E., Portella, M. J., Rabella, M., Sauras, R. B., … Corripio, I. (2015). Resting-state functional connectivity alterations in the default network of schizophrenia patients with persistent auditory verbal hallucinations. Schizophrenia Research, 161, 261–268.CrossRefGoogle ScholarPubMed
Andrews-Hanna, J. R., Reidler, J. S., Sepulcre, J., Poulin, R., & Buckner, R. L. (2010). Functional-anatomic fractionation of the brain's default network. Neuron, 65, 550–562.CrossRefGoogle ScholarPubMed
Andrews-Hanna, J. R., Saxe, R., & Yarkoni, T. (2014). Contributions of episodic retrieval and mentalizing to autobiographical thought: Evidence from functional neuroimaging, resting-state connectivity, and fMRI meta-analyses. Neuroimage, 91, 324–335.CrossRefGoogle ScholarPubMed
Benes, F. M., & Todtenkopf, M. S. (1999). Effect of age and neuroleptics on tyrosine hydroxylase-IR in sector CA2 of schizophrenic brain. Neuroreport, 10, 3527–3530.CrossRefGoogle ScholarPubMed
Benoit, R. G., Szpunar, K. K., & Schacter, D. L. (2014). Ventromedial prefrontal cortex supports affective future simulation by integrating distributed knowledge. Proceedings of the National Academy of Sciences of the United States of America, 111, 16550–16555.CrossRefGoogle ScholarPubMed
Berna, F., Potheegadoo, J., Alle, M. C., Coutelle, R., & Danion, J. M. (2017). [Autobiographical memory and self-disorders in schizophrenia]. L'Encephale, 43, 47–54.CrossRefGoogle Scholar
Bluhm, R. L., Miller, J., Lanius, R. A., Osuch, E. A., Boksman, K., Neufeld, R. W., … Williamson, P. (2007). Spontaneous low-frequency fluctuations in the BOLD signal in schizophrenic patients: Anomalies in the default network. Schizophrenia Bulletin, 33, 1004–1012.CrossRefGoogle ScholarPubMed
Bluhm, R. L., Miller, J., Lanius, R. A., Osuch, E. A., Boksman, K., Neufeld, R. W., … Williamson, P. C. (2009). Retrosplenial cortex connectivity in schizophrenia. Psychiatry Research, 174, 17–23.CrossRefGoogle Scholar
Calabrese, D. R., Wang, L., Harms, M. P., Ratnanather, J. T., Barch, D. M., Cloninger, C. R., … Csernansky, J. G. (2008). Cingulate gyrus neuroanatomy in schizophrenia subjects and their non-psychotic siblings. Schizophrenia Research, 104, 61–70.CrossRefGoogle ScholarPubMed
Camchong, J., MacDonald, A. W., 3rd, Bell, C., Mueller, B. A., & Lim, K. O. (2011). Altered functional and anatomical connectivity in schizophrenia. Schizophrenia Bulletin, 37, 640–650.CrossRefGoogle Scholar
Dale, A. M., Fischl, B., & Sereno, M. I. (1999). Cortical surface-based analysis. I. Segmentation and surface reconstruction. Neuroimage, 9, 179–194.CrossRefGoogle ScholarPubMed
Dodell-Feder, D., Delisi, L. E., & Hooker, C. I. (2014). The relationship between default mode network connectivity and social functioning in individuals at familial high-risk for schizophrenia. Schizophrenia Research, 156, 87–95.CrossRefGoogle ScholarPubMed
Fan, F., Tan, Y., Wang, Z., Yang, F., Fan, H., Xiang, H., … Zuo, X. N. (2019). Functional fractionation of default mode network in first episode schizophrenia. Schizophrenia Research, 210, 115–121.CrossRefGoogle ScholarPubMed
Fan, F. M., Tan, S. P., Yang, F. D., Tan, Y. L., Zhao, Y. L., Chen, N., … Zuo, X. N. (2013). Ventral medial prefrontal functional connectivity and emotion regulation in chronic schizophrenia: A pilot study. Neuroscience Bulletin, 29, 59–74.CrossRefGoogle ScholarPubMed
Fischl, B. (2012). Freesurfer. Neuroimage, 62, 774–781.CrossRefGoogle ScholarPubMed
Fischl, B., Salat, D. H., Busa, E., Albert, M., Dieterich, M., Haselgrove, C., … Dale, A. M. (2002). Whole brain segmentation: Automated labeling of neuroanatomical structures in the human brain. Neuron, 33, 341–355.CrossRefGoogle ScholarPubMed
Fischl, B., Sereno, M. I., & Dale, A. M. (1999). Cortical surface-based analysis. II: Inflation, flattening, and a surface-based coordinate system. Neuroimage, 9, 195–207.CrossRefGoogle Scholar
Friston, K. J. (1999). Schizophrenia and the disconnection hypothesis. Acta Psychiatrica Scandinavica. Supplementum, 395, 68–79.CrossRefGoogle ScholarPubMed
Friston, K. J., & Frith, C. D. (1995). Schizophrenia: A disconnection syndrome? Clinical Neuroscience, 3, 89–97.Google ScholarPubMed
Garrity, A. G., Pearlson, G. D., McKiernan, K., Lloyd, D., Kiehl, K. A., & Calhoun, V. D. (2007). Aberrant “default mode” functional connectivity in schizophrenia. American Journal of Psychiatry, 164, 450–457.CrossRefGoogle Scholar
Greicius, M. D., Supekar, K., Menon, V., & Dougherty, R. F. (2009). Resting-state functional connectivity reflects structural connectivity in the default mode network. Cerebral Cortex, 19, 72–78.CrossRefGoogle ScholarPubMed
Greve, D. N., & Fischl, B. (2009). Accurate and robust brain image alignment using boundary-based registration. Neuroimage, 48, 63–72.CrossRefGoogle ScholarPubMed
Hu, M. L., Zong, X. F., Mann, J. J., Zheng, J. J., Liao, Y. H., Li, Z. C., … Tang, J. S. (2017). A review of the functional and anatomical default mode network in schizophrenia. Neuroscience Bulletin, 33, 73–84.CrossRefGoogle Scholar
Kobayashi, Y., & Amaral, D. G. (2003). Macaque monkey retrosplenial cortex: II. Cortical afferents. Journal of Comparative Neurology, 466, 48–79.CrossRefGoogle ScholarPubMed
Liao, W., Zhang, Z., Pan, Z., Mantini, D., Ding, J., Duan, X., … Chen, H. (2011). Default mode network abnormalities in mesial temporal lobe epilepsy: A study combining fMRI and DTI. Human Brain Mapping, 32, 883–895.CrossRefGoogle ScholarPubMed
Liu, H., Kaneko, Y., Ouyang, X., Li, L., Hao, Y., Chen, E. Y., … Liu, Z. (2012). Schizophrenic patients and their unaffected siblings share increased resting-state connectivity in the task-negative network but not its anticorrelated task-positive network. Schizophrenia Bulletin, 38, 285–294.CrossRefGoogle Scholar
Liu, H., Stufflebeam, S. M., Sepulcre, J., Hedden, T., & Buckner, R. L. (2009). Evidence from intrinsic activity that asymmetry of the human brain is controlled by multiple factors. Proceedings of the National Academy of Sciences of the United States of America, 106, 20499–20503.CrossRefGoogle ScholarPubMed
Mannell, M. V., Franco, A. R., Calhoun, V. D., Canive, J. M., Thoma, R. J., & Mayer, A. R. (2010). Resting state and task-induced deactivation: A methodological comparison in patients with schizophrenia and healthy controls. Human Brain Mapping, 31, 424–437.Google ScholarPubMed
Molent, C., Olivo, D., Wolf, R. C., Balestrieri, M., & Sambataro, F. (2019). Functional neuroimaging in treatment resistant schizophrenia: A systematic review. Neuroscience and Biobehavioral Reviews, 104, 178–190.CrossRefGoogle ScholarPubMed
Painter, J. M., & Kring, A. M. (2016). Toward an understanding of anticipatory pleasure deficits in schizophrenia: Memory, prospection, and emotion experience. Journal of Abnormal Psychology, 125, 442–452.CrossRefGoogle ScholarPubMed
Parvizi, J., Van Hoesen, G. W., Buckwalter, J., & Damasio, A. (2006). Neural connections of the posteromedial cortex in the macaque. Proceedings of the National Academy of Sciences of the United States of America, 103, 1563–1568.CrossRefGoogle ScholarPubMed
Pomarol-Clotet, E., Salvador, R., Sarro, S., Gomar, J., Vila, F., Martinez, A., … McKenna, P. J. (2008). Failure to deactivate in the prefrontal cortex in schizophrenia: Dysfunction of the default mode network? Psychological Medicine, 38, 1185–1193.CrossRefGoogle ScholarPubMed
Power, J. D., Barnes, K. A., Snyder, A. Z., Schlaggar, B. L., & Petersen, S. E. (2012). Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. Neuroimage, 59, 2142–2154.CrossRefGoogle ScholarPubMed
Pruim, R. H. R., Mennes, M., Buitelaar, J. K., & Beckmann, C. F. (2015 a). Evaluation of ICA-AROMA and alternative strategies for motion artifact removal in resting state fMRI. Neuroimage, 112, 278–287.CrossRefGoogle ScholarPubMed
Pruim, R. H. R., Mennes, M., van Rooij, D., Llera, A., Buitelaar, J. K., & Beckmann, C. F. (2015 b). ICA-AROMA: A robust ICA-based strategy for removing motion artifacts from fMRI data. Neuroimage, 112, 267–277.CrossRefGoogle ScholarPubMed
Raffard, S., Esposito, F., Boulenger, J. P., & Van der Linden, M. (2013). Impaired ability to imagine future pleasant events is associated with apathy in schizophrenia. Psychiatry Research, 209, 393–400.CrossRefGoogle Scholar
Raichle, M. E., MacLeod, A. M., Snyder, A. Z., Powers, W. J., Gusnard, D. A., & Shulman, G. L. (2001). A default mode of brain function. Proceedings of the National Academy of Sciences of the United States of America, 98, 676–682.CrossRefGoogle ScholarPubMed
Ricarte, J. J., Ros, L., Latorre, J. M., & Watkins, E. (2017). Mapping autobiographical memory in schizophrenia: Clinical implications. Clinical Psychology Review, 51, 96–108.CrossRefGoogle ScholarPubMed
Rotarska-Jagiela, A., van de Ven, V., Oertel-Knochel, V., Uhlhaas, P. J., Vogeley, K., & Linden, D. E. (2010). Resting-state functional network correlates of psychotic symptoms in schizophrenia. Schizophrenia Research, 117, 21–30.CrossRefGoogle Scholar
Salgado-Pineda, P., Fakra, E., Delaveau, P., McKenna, P. J., Pomarol-Clotet, E., & Blin, O. (2011). Correlated structural and functional brain abnormalities in the default mode network in schizophrenia patients. Schizophrenia Research, 125, 101–109.CrossRefGoogle ScholarPubMed
Sambataro, F., Blasi, G., Fazio, L., Caforio, G., Taurisano, P., Romano, R., … Bertolino, A. (2010). Treatment with olanzapine is associated with modulation of the default mode network in patients with schizophrenia. Neuropsychopharmacology, 35, 904–912.CrossRefGoogle ScholarPubMed
Satterthwaite, T. D., Wolf, D. H., Loughead, J., Ruparel, K., Elliott, M. A., Hakonarson, H., … Gur, R. E. (2012). Impact of in-scanner head motion on multiple measures of functional connectivity: Relevance for studies of neurodevelopment in youth. Neuroimage, 60, 623–632.CrossRefGoogle ScholarPubMed
Segonne, F., Dale, A. M., Busa, E., Glessner, M., Salat, D., Hahn, H. K., & Fischl, B. (2004). A hybrid approach to the skull stripping problem in MRI. Neuroimage, 22, 1060–1075.CrossRefGoogle Scholar
Shim, G., Oh, J. S., Jung, W. H., Jang, J. H., Choi, C. H., Kim, E., … Kwon, J. S. (2010). Altered resting-state connectivity in subjects at ultra-high risk for psychosis: An fMRI study. Behavioral and Brain Functions, 6, 58.CrossRefGoogle Scholar
Shimizu, E., Hashimoto, K., Ochi, S., Fukami, G., Fujisaki, M., Koike, K., … Iyo, M. (2007). Posterior cingulate gyrus metabolic changes in chronic schizophrenia with generalized cognitive deficits. Journal of Psychiatric Research, 41, 49–56.CrossRefGoogle ScholarPubMed
Van Dijk, K. R., Sabuncu, M. R., & Buckner, R. L. (2012). The influence of head motion on intrinsic functional connectivity MRI. Neuroimage, 59, 431–438.CrossRefGoogle ScholarPubMed
Wang, J., Wang, X., Xia, M., Liao, X., Evans, A., & He, Y. (2015). GRETNA: A graph theoretical network analysis toolbox for imaging connectomics. Frontiers in Human Neuroscience, 9, 386.Google ScholarPubMed
Whitfield-Gabrieli, S., Thermenos, H. W., Milanovic, S., Tsuang, M. T., Faraone, S. V., McCarley, R. W., … Seidman, L. J. (2009). Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia. Proceedings of the National Academy of Sciences of the United States of America, 106, 1279–1284.CrossRefGoogle ScholarPubMed
Woods, S. W. (2003). Chlorpromazine equivalent doses for the newer atypical antipsychotics. Journal of Clinical Psychiatry, 64, 663–667.CrossRefGoogle ScholarPubMed
Xia, M., Wang, J., & He, Y. (2013). Brainnet viewer: A network visualization tool for human brain connectomics. PloS One, 8, e68910.CrossRefGoogle ScholarPubMed
Xing, X. X., Zhou, Y. L., Adelstein, J. S., & Zuo, X. N. (2011). PDE-based spatial smoothing: A practical demonstration of impacts on MRI brain extraction, tissue segmentation and registration. Magnetic Resonance Imaging, 29, 731–738.CrossRefGoogle ScholarPubMed
Xu, T., Yang, Z., Jiang, L., Xing, X.-X., & Zuo, X.-N. (2015). A connectome computation system for discovery science of brain. Science Bulletin, 60, 9.CrossRefGoogle Scholar
Yang, Z. Y., Zhang, R. T., Li, Y., Wang, Y., Wang, Y. M., Wang, S. K., … Chan, R. C. K. (2019). Functional connectivity of the default mode network is associated with prospection in schizophrenia patients and individuals with social anhedonia. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 92, 412–420.CrossRefGoogle ScholarPubMed
Yeo, B. T., Krienen, F. M., Sepulcre, J., Sabuncu, M. R., Lashkari, D., Hollinshead, M., … Buckner, R. L. (2011). The organization of the human cerebral cortex estimated by intrinsic functional connectivity. Journal of Neurophysiology, 106, 1125–1165.Google ScholarPubMed
Zalesky, A., Fornito, A., & Bullmore, E. T. (2010). Network-based statistic: Identifying differences in brain networks. Neuroimage, 53, 1197–1207.CrossRefGoogle ScholarPubMed
Zhao, Z., Li, X., Feng, G., Shen, Z., Li, S., Xu, Y., … Xu, D. (2018). Altered effective connectivity in the default network of the brains of first-episode, drug-naive schizophrenia patients with auditory verbal hallucinations. Frontiers in Human Neuroscience, 12, 456.CrossRefGoogle ScholarPubMed
Zuo, X. N., & Xing, X. X. (2011). Effects of non-local diffusion on structural MRI preprocessing and default network mapping: Statistical comparisons with isotropic/anisotropic diffusion. PloS One, 6, e26703.CrossRefGoogle ScholarPubMed
Supplementary material: File

Fan et al. supplementary material

Fan et al. supplementary material

Download Fan et al. supplementary material(File)
File 2.3 MB