Abstract
White matter (WM) alteration is considered to be a vital neurological mechanism of obsessive-compulsive disorder (OCD). However, little is known regarding the changes in topological organization of WM structural network in OCD. We acquired diffusion tensor imaging (DTI) datasets from 28 drug-naïve OCD patients and 28 well-matched healthy controls (HC). A deterministic fiber tracking approach was used to construct the whole-brain structural connectome. Group differences in global and nodal topological properties as well as rich-club organizations were compared by using graph theory analysis. The relationship between the altered network metrics and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was calculated. Compared with controls, OCD patients exhibited a significantly decreased small-worldness (σ), normalized clustering coefficient (γ) and shortest path length (Lp), as well as an increased global efficiency (Eglob). The nodal efficiency (Enodal) was found to be reduced in the left middle frontal gyrus, and increased in the right parahippocampal gyrus and bilateral putamen in OCD patients. Besides, OCD patients showed increased rich-club, feeder and local connection strength, and the connection strength of the rich-club was positively correlated with the total Y-BOCS score. Our findings emphasized a central role for the complicatedly changed topological architecture of brain structural networks in the pathological mechanism underlying OCD.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Armstrong, C. C., Moody, T. D., Feusner, J. D., McCracken, J. T., Chang, S., Levitt, J. G. et al. (2016). Graph-theoretical analysis of resting-state fMRI in pediatric obsessive–compulsive disorder. Journal of Affective Disorders, 193, 175–184. https://doi.org/10.1016/j.jad.2015.12.071
Bellec, P., Lavoie-Courchesne, S., Dickinson, P., Lerch, J. P., Zijdenbos, A. P., & Evans, A. C. (2012). The pipeline system for Octave and Matlab (PSOM): a lightweight scripting framework and execution engine for scientific workflows. Frontiers in Neuroinform, 6, 7. https://doi.org/10.3389/fninf.2012.00007
Benedetti, F., Giacosa, C., Radaelli, D., Poletti, S., Pozzi, E., Dallaspezia, S. et al. (2013). Widespread changes of white matter microstructure in obsessive-compulsive disorder: effect of drug status. European neuropsychopharmacology, 23(7), 581–593. https://doi.org/10.1016/j.euroneuro.2012.07.002.
Betzel, R. F., Byrge, L., He, Y., Goni, J., Zuo, X. N., & Sporns, O. (2014). Changes in structural and functional connectivity among resting-state networks across the human lifespan. Neuroimage, 102 Pt, 2, 345–357. https://doi.org/10.1016/j.neuroimage.2014.07.067
Bora, E., Harrison, B. J., Fornito, A., Cocchi, L., Pujol, J., Fontenelle, L. F. et al. (2011). White matter microstructure in patients with obsessive-compulsive disorder. Journal of Psychiatry and Neuroscience: JPN, 36(1), 42–46. https://doi.org/10.1503/jpn.100082
Bullmore, E., & Sporns, O. (2009). Complex brain networks: graph theoretical analysis of structural and functional systems. Nature Reviews Neuroscience, 10(3), 186–198. https://doi.org/10.1038/nrn2575
Colizza, V., Flammini, A., Serrano, M. A., & Vespignani, A. (2006). Detecting rich-club ordering in complex networks. Nature Physics, 2(2), 110–115. https://doi.org/10.1038/nphys209
Cui, Z., Zhong, S., Xu, P., He, Y., & Gong, G. (2013). PANDA: a pipeline toolbox for analyzing brain diffusion images. Forntiers in Human Neuroscience, 7, 42. https://doi.org/10.3389/fnhum.2013.00042
Dai, Z., Lin, Q., Li, T., Wang, X., Yuan, H., Yu, X. et al. (2019). Disrupted structural and functional brain networks in Alzheimer’s disease. Neurobiology of Aging, 75, 71–82. https://doi.org/10.1016/j.neurobiolaging.2018.11.005
de Jong, L. W., van der Hiele, K., Veer, I. M., Houwing, J. J., Westendorp, R. G., Bollen, E. L. et al. (2008). Strongly reduced volumes of putamen and thalamus in Alzheimer’s disease: an MRI study. Brain, 131(Pt 12), 3277–3285. https://doi.org/10.1093/brain/awn278
Fan, S., van den Heuvel, O. A., Cath, D. C., van der Werf, Y. D., de Wit, S. J., de Vries, F. E. et al. (2016). Mild White Matter Changes in Un-medicated Obsessive-Compulsive Disorder Patients and Their Unaffected Siblings. Frontiers in Neuroscience, 9. https://doi.org/10.3389/fnins.2015.00495
Fornito, A., Zalesky, A., & Breakspear, M. (2015). The connectomics of brain disorders. Nature Reviews Neuroscience, 16(3), 159–172. https://doi.org/10.1038/nrn3901
Frydman, I., de Salles Andrade, J. B., Vigne, P., & Fontenelle, L. F. (2016). Can Neuroimaging Provide Reliable Biomarkers for Obsessive-Compulsive Disorder? A Narrative Review. Current Psychiatry Reports, 18(10), 90. https://doi.org/10.1007/s11920-016-0729-7
Gan, J., Zhong, M., Fan, J., Liu, W., Niu, C., Cai, S. et al. (2017). Abnormal white matter structural connectivity in adults with obsessive-compulsive disorder. Translational Psychiatry, 7(3), e1062. https://doi.org/10.1038/tp.2017.22
Gong, Q., & He, Y. (2015). Depression, neuroimaging and connectomics: a selective Overview. Biological Psychiatry, 77(3), 223–235. https://doi.org/10.1016/j.biopsych.2014.08.009.
Hall, J. M., Shine, J. M., Martens, E., Gilat, K. A., Broadhouse, M., Szeto, K. M. et al. (2018). Alterations in white matter network topology contribute to freezing of gait in Parkinson’s disease. Journal of Neurology, 265(6), 1353–1364. https://doi.org/10.1007/s00415-018-8846-3
Jayarajan, R. N., Venkatasubramanian, G., Viswanath, B., Janardhan Reddy, Y. C., Srinath, S., Vasudev, M. K. et al. (2012). White matter abnormalities in children and adolescents with obsessive-compulsive disorder: a diffusion tensor imaging study. Depression and Anxiety, 29(9), 780–788. https://doi.org/10.1002/da.21890.
Jenkinson, M., Bannister, P., Brady, M., & Smith, S. (2002). Improved Optimization for the Robust and Accurate Linear Registration and Motion Correction of Brain Images. Neuroimage, 17(2), 825–841. https://doi.org/10.1006/nimg.2002.1132
Jung, W. H., Yucel, M., Yun, J. Y., Yoon, Y. B., Cho, K. I., Parkes, L. et al. (2017). Altered functional network architecture in orbitofronto-striato-thalamic circuit of unmedicated patients with obsessive-compulsive disorder. Human Brain Mapping, 38(1), 109–119. https://doi.org/10.1002/hbm.23347
Kim, S. G., Jung, W. H., Kim, S. N., Jang, J. H., & Kwon, J. S. (2013). Disparity between dorsal and ventral networks in patients with obsessive-compulsive disorder: evidence revealed by graph theoretical analysis based on cortical thickness from MRI. Frontiers in Human Neuroscience, 7, 302. https://doi.org/10.3389/fnhum.2013.00302
Klauser, P., Baker, S. T., Cropley, V. L., Bousman, C., Fornito, A., Cocchi, L. et al. (2017). White Matter Disruptions in Schizophrenia Are Spatially Widespread and Topologically Converge on Brain Network Hubs. Schizophrenia Bulletin, 43(2), 425–435. https://doi.org/10.1093/schbul/sbw100
Koch, K., Reess, T. J., Rus, O. G., Zimmer, C., & Zaudig, M. (2014). Diffusion tensor imaging (DTI) studies in patients with obsessive-compulsive disorder (OCD): a review. Journal of Psychiatric Research, 54, 26–35. https://doi.org/10.1016/j.jpsychires.2014.03.006
Korgaonkar, M. S., Fornito, A., Williams, L. M., & Grieve, S. M. (2014). Abnormal structural networks characterize major depressive disorder: a connectome analysis. Biological Psychiatry, 76(7), 567–574. https://doi.org/10.1016/j.biopsych.2014.02.018
Li, C., Huang, B., Zhang, R., Ma, Q., Yang, W., Wang, L. et al. (2017). Impaired topological architecture of brain structural networks in idiopathic Parkinson’s disease: a DTI study. Brain Imaging and Behavior, 11(1), 113–128. https://doi.org/10.1007/s11682-015-9501-6
Li, X., Steffens, D. C., Potter, G. G., Guo, H., Song, S., & Wang, L. (2017). Decreased between-hemisphere connectivity strength and network efficiency in geriatric depression. Human Brain Mapping, 38(1), 53–67. https://doi.org/10.1002/hbm.23343
Lo, C. Y., Wang, P. N., Chou, K. H., Wang, J., He, Y., & Lin, C. P. (2010). Diffusion tensor tractography reveals abnormal topological organization in structural cortical networks in Alzheimer’s disease. The Journal of Neuroscience, 30(50), 16876–16885. https://doi.org/10.1523/JNEUROSCI.4136-10.2010.
Long, Z., Duan, X., Wang, Y., Liu, F., Zeng, L., Zhao, J. P. et al. (2015). Disrupted structural connectivity network in treatment-naive depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 56, 18–26. https://doi.org/10.1016/j.pnpbp.2014.07.007
Lu, Y., Shen, Z., Cheng, Y., Yang, H., He, B., Xie, Y. et al. (2017). Alternations of White Matter Structural Networks in First Episode Untreated Major Depressive Disorder with Short Duration. Frontiers in Psychiatry, 8, 205. https://doi.org/10.3389/fpsyt.2017.00205
Megevand, P., Groppe, D. M., Goldfinger, M. S., Hwang, S. T., Kingsley, P. B., Davidesco, I. et al. (2014). Seeing scenes: topographic visual hallucinations evoked by direct electrical stimulation of the parahippocampal place area. The Journal of Neuroscience, 34(16), 5399–5405. https://doi.org/10.1523/JNEUROSCI.5202-13.2014.
Mori, S., Crain, B. J., Chacko, V. P., & Zijl, P. C. M. V. (1999). Three-dimensional tracking of axonal projections in the brain by magnetic resonance imaging. Annals of Neurology, 45(265–269), https://doi.org/10.1002/1531-8249(199902)45:2<265::AID-ANA21>3.0.CO;2-3
Nakamaea, T., Narumoto, J., Sakai, Y., Nishida, S., Yamadab, K., Nishimura, T. et al. (2011). Diffusion tensor imaging and tract-based spatial statistics in obsessive-compulsive disorder. Journal of Psychiatric Research, 45(5), 687–690. https://doi.org/10.1016/j.jpsychires.2010.09.016
O’Donoghue, S., Kilmartin, L., O’Hora, D., Emsell, L., Langan, C., McInerney, S. et al. (2017). Anatomical integration and rich-club connectivity in euthymic bipolar disorder. Psychological Medicine, 47(9), 1609–1623. https://doi.org/10.1017/S0033291717000058
Piras, F., Piras, F., Abe, Y., Agarwal, S. M., Anticevic, A., Ameis, S., et al. (2019). White Matter Microstructure and its Relation to Clinical Features of Obsessive-Compulsive Disorder: Findings from the ENIGMA OCD Working Group. bioRxiv 855916, https://doi.org/10.1101/855916.
Piras, F., Piras, F., Caltagirone, C., & Spalletta, G. (2013). Brain circuitries of obsessive compulsive disorder: a systematic review and meta-analysis of diffusion tensor imaging studies. Neuroscience and Biobehavioral Reviews, 37(10 Pt 2), 2856–2877. https://doi.org/10.1016/j.neubiorev.2013.10.008.
Piras, F., Piras, F., Chiapponi, C., Girardi, P., Caltagirone, C., & Spalletta, G. (2015). Widespread structural brain changes in OCD: a systematic review of voxel-based morphometry studies. Cortex, 62, 89–108. https://doi.org/10.1016/j.cortex.2013.01.016.
Ray, S., Miller, M., Karalunas, S., Robertson, C., Grayson, D. S., Cary, R. P. et al. (2014). Structural and functional connectivity of the human brain in autism spectrum disorders and attention-deficit/hyperactivity disorder: A rich club-organization study. Human Brain Mapping, 35(12), 6032–6048. https://doi.org/10.1002/hbm.22603
Reess, T. J., Rus, O. G., Schmidt, R., de Reus, M. A., Zaudig, M., Wagner, G. et al. (2016). Connectomics-based structural network alterations in obsessive-compulsive disorder. Translational Psychiatry, 6(9), e882. https://doi.org/10.1038/tp.2016.163
Rorden, C., Karnath, H. -O., & Bonilha, L. (2007). Improving lesion-symptom mapping. Journal of Cognitive Neuroscience, 19(7), 1081–1088. https://doi.org/10.1162/jocn.2007.19.7.1081
Rubinov, M., & Sporns, O. (2010). Complex network measures of brain connectivity: uses and interpretations. Neuroimage, 52(3), 1059–1069. https://doi.org/10.1016/j.neuroimage.2009.10.003
Sexton, C. E., Mackay, C. E., & Ebmeier, K. P. (2009). A systematic review of diffusion tensor imaging studies in affective disorders. Biological Psychiatry, 66(9), 814–823. https://doi.org/10.1016/j.biopsych.2009.05.024
Shin, D. J., Jung, W. H., He, Y., Wang, J., Shim, G., Byun, M. S. et al. (2014). The effects of pharmacological treatment on functional brain connectome in obsessive-compulsive disorder. Biological Psychiatry, 75(8), 606–614. https://doi.org/10.1016/j.biopsych.2013.09.002
Shu, N., Duan, Y., Huang, J., Ren, Z., Liu, Z., Dong, H. et al. (2018). Progressive brain rich-club network disruption from clinically isolated syndrome towards multiple sclerosis. Neuroimage Clinical, 19, 232–239. https://doi.org/10.1016/j.nicl.2018.03.034
Smith, S. M. (2002). Fast robust automated brain extraction. Human Brain Mapping, 17(3), 143–155. https://doi.org/10.1002/hbm.10062
Smith, S. M., Jenkinson, M., Woolrich, M. W., Beckmann, C. F., Behrens, T. E., Johansen-Berg, H., et al. (2004). Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage, 23(Suppl 1), S208–S219. doi:https://doi.org/10.1016/j.neuroimage.2004.07.051.
Spalletta, G., Piras, F., Fagioli, S., Caltagirone, C., & Piras, F. (2014). Brain microstructural changes and cognitive correlates in patients with pure obsessive compulsive disorder. Brain and Behavior, 4(2), 261–277. https://doi.org/10.1002/brb3.212
Sporns, O. (2011). The human connectome: a complex network. Annals of the New York Academy of Sciences, 1224, 109–125. https://doi.org/10.1111/j.1749-6632.2010.05888.x
Sporns, O. (2013). Network attributes for segregation and integration in the human brain. Current Opinion in Neurobiology, 23(2), 162–171. https://doi.org/10.1016/j.conb.2012.11.015
Sporns, O., Tononi, G., & Kötter, R. (2005). The Human Connectome: A Structural Description of the Human Brain. PLoS Computational Biology, 1(4), e42. https://doi.org/10.1371/journal.pcbi.0010042
Sun, Y., Chen, Y., Collinson, S. L., Bezerianos, A., & Sim, K. (2017). Reduced Hemispheric Asymmetry of Brain Anatomical Networks Is Linked to Schizophrenia: A Connectome Study. Cerebral Cortex, 27(1), 602–615. https://doi.org/10.1093/cercor/bhv255.
Suo, X., Lei, D., Li, L., Li, W., Dai, J., Wang, S. et al. (2018). Psychoradiological patterns of small-world properties and a systematic review of connectome studies of patients with 6 major psychiatric disorders. Journal of Psychiatry and Neuroscience, 43(5), 170214. https://doi.org/10.1503/jpn.170214.
Talati, A., & Hirsch, J. (2005). Functional specialization within the medial frontal gyrus for perceptual go/no-go decisions based on “what,” “when,” and “where” related information: an fMRI study. Journal of Cognitive Neuroscience, 17(7), 981–993. https://doi.org/10.1162/0898929054475226
Togao, O., Yoshiura, T., Nakao, T., Nabeyama, M., Sanematsu, H., Nakagawa, A. et al. (2010). Regional gray and white matter volume abnormalities in obsessive–compulsive disorder: A voxel-based morphometry study. Psychiatry Research: Neuroimaging, 184(1), 29–37. https://doi.org/10.1016/j.pscychresns.2010.06.011
Tuladhar, A. M., Lawrence, A., Norris, D. G., Barrick, T. R., Markus, H. S., & de Leeuw, F. E. (2017). Disruption of rich club organisation in cerebral small vessel disease. Human Brain Mapping, 38(4), 1751–1766. https://doi.org/10.1002/hbm.23479
Tzourio-Mazoyer, N., Landeau, B., Papathanassiou, D., Crivello, F., Etard, O., Delcroix, N. et al. (2002). Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage, 15(1), 273–289. https://doi.org/10.1006/nimg.2001.0978
van den Heuvel, M. P., Kahn, R. S., Goni, J., & Sporns, O. (2012). High-cost, high-capacity backbone for global brain communication. Proceedings of National Academy of Sciences of the United States of America, 109(28), 11372–11377. https://doi.org/10.1073/pnas.1203593109.
van den Heuvel, M. P., & Sporns, O. (2011). Rich-club organization of the human connectome. The Journal of Neuroscience, 31(44), 15775–15786. https://doi.org/10.1523/JNEUROSCI.3539-11.2011
van den Heuvel, M. P., Sporns, O., Collin, G., Scheewe, T., Mandl, R. C., Cahn, W. et al. (2013). Abnormal rich club organization and functional brain dynamics in schizophrenia. JAMA Psychiatry, 70(8), 783–792. https://doi.org/10.1001/jamapsychiatry.2013.1328
van den Heuvel, O. A., van Wingen, G., Soriano-Mas, C., Alonso, P., Chamberlain, S. R., Nakamae, T. et al. (2016). Brain circuitry of compulsivity. European Neuropsychopharmacology, 26(5), 810–827. https://doi.org/10.1016/j.euroneuro.2015.12.005
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. https://doi.org/10.3389/fnhum.2015.00386.
Wang, R., Benner, T., Sorensen, A. G., & Wedeen, V. J. (2007). Diffusion toolkit: A software package for diffusion imaging data processing and tractography. Proceedings of the International Society for Magnetic Resonance in Medicine. 15, 3720.
Wang, X., Qin, J., Zhu, J., Bi, K., Zhang, S., Yan, R. et al. (2019). Rehabilitative compensatory mechanism of hierarchical subnetworks in major depressive disorder: A longitudinal study across multi-sites. European Psychiatry: the Journal of the Association of European Psychiatrist, 58, 54–62. https://doi.org/10.1016/j.eurpsy.2019.02.004
Wang, Y., Deng, F., Jia, Y., Wang, J., Zhong, S., Huang, H. et al. (2019). Disrupted rich club organization and structural brain connectome in unmedicated bipolar disorder. Psychological Medicine, 49(3), 510–518. https://doi.org/10.1017/S0033291718001150
Watts, D. J., & Strogatz, S. H. (1998). Collective dynamics of 'small-world' networks. Nature, 393(6684), 440–442.
Xia, M., Wang, J., & He, Y. (2013). BrainNet Viewer: a network visualization tool for human brain connectomics. PLoS One, 8(7), e68910. https://doi.org/10.1371/journal.pone.0068910
Zhang, T., Wang, J., Yang, Y., Wu, Q., Li, B., Chen, L. et al. (2011). Abnormal small-world architecture of top-down control networks in obsessive-compulsive disorder. European Psychiatry and Neuroscience: JPN, 36(1), 23–31. https://doi.org/10.1503/jpn.100006
Zhao, X., Tian, L., Yan, J., Yue, W., Yan, H., & Zhang, D. (2017). Abnormal Rich-Club Organization Associated with Compromised Cognitive Function in Patients with Schizophrenia and Their Unaffected Parents. Neuroscience Bulletin, 33(4), 445–454. https://doi.org/10.1007/s12264-017-0151-0
Zhong, Z., Zhao, T., Luo, J., Guo, Z., Guo, M., Li, P. et al. (2014). Abnormal topological organization in white matter structural networks revealed by diffusion tensor tractography in unmedicated patients with obsessive–compulsive disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 51, 39–50. https://doi.org/10.1016/j.pnpbp.2014.01.005
Zhou, C., Cheng, Y., Ping, L., Xu, J., Shen, Z., Jiang, L., et al. (2018a). Support Vector Machine Classification of Obsessive-Compulsive Disorder Based on Whole-Brain Volumetry and Diffusion Tensor Imaging. Front Psychiatry, 9, https://doi.org/10.3389/fpsyt.2018.00524.
Zhou, C., Xu, J., Ping, L., Zhang, F., Chen, W., Shen, Z. et al. (2018). Cortical thickness and white matter integrity abnormalities in obsessive-compulsive disorder: A combined multimodal surface-based morphometry and tract-based spatial statistics study. Depress Anxiety, 35(8), 742–751. https://doi.org/10.1002/da.22758
Funding
This study was funded by the National Natural Science Foundation of China (81560233, 81660237), National Clinical Research Center for Mental Disorders (2015BAI13B02), Founding of Yunnan Provincial Health Science and Technology Plan (2016NS026), Yunnan Applied Basic Research Projects-Union Foundation [2017FE467(-167)], Innovative Research Team of Kunming Medical University (CXTD201705), and Middle and Young Aged Academic and Technology Leaders Reserve Personnel Foundation of Yunnan Province (2018HB021).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
All authors claim that there are no conflict of interest.
Ethical approval
This cross-sectional study was approved by the Ethics Review Board of Kunming Medical University (ClinicalTrials. -gov: NCT01298622). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Electronic supplementary material
ESM 1
(DOC 40.0 kb)
Rights and permissions
About this article
Cite this article
Zhou, C., Ping, L., Chen, W. et al. Altered white matter structural networks in drug-naïve patients with obsessive-compulsive disorder. Brain Imaging and Behavior 15, 700–710 (2021). https://doi.org/10.1007/s11682-020-00278-7
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11682-020-00278-7