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Sub-regional anterior cingulate cortex functional connectivity revealed default network subsystem dysfunction in patients with major depressive disorder

Published online by Cambridge University Press:  10 March 2020

Xiaolong Peng
Affiliation:
Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China Department of Neuroscience, Medical University of South Carolina, Charleston, USA
Xiaoping Wu
Affiliation:
Department of Radiology, The Affiliated Xi'an Central Hospital of Xi'an Jiaotong University, Xi'an, China
Ruxue Gong
Affiliation:
Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
Rui Yang
Affiliation:
Department of Psychiatry, The Affiliated Xi'an Central Hospital of Xi'an Jiaotong University, Xi'an, China
Xiang Wang
Affiliation:
Medical Psychological Center, The Second Xiangya Hospital of Central South University, Changsha, China
Wenzhen Zhu*
Affiliation:
Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Pan Lin*
Affiliation:
Department of Psychology, Hunan Normal University, Changsha, China Cognition and Human Behavior Key Laboratory of Hunan Province, Hunan Normal University, Changsha, China
*
Author for correspondence: Pan Lin, E-mail: [email protected]; Wenzhen Zhu, E-mail: [email protected]
Author for correspondence: Pan Lin, E-mail: [email protected]; Wenzhen Zhu, E-mail: [email protected]

Abstract

Background

Major depressive disorder (MDD) is a prevalent mental disorder characterized by impairments in affect, behaviour and cognition. Previous studies have indicated that the anterior cingulate cortex (ACC) may play an essential role in the pathophysiology of depression. In this study, we systematically identified changes in functional connectivity (FC) for ACC subdivisions that manifest in MDD and further investigated the relationship between these changes and the clinical symptoms of depression.

Methods

Sub-regional ACC FC was estimated in 41 first-episode medication-naïve MDD patients compared to 43 healthy controls. The relationships between depressive symptom severity and aberrant FC of ACC subdivisions were investigated. In addition, we conducted a meta-analysis to generate the distributions of MDD-related abnormal regions from previously reported results and compared them to FC deficits revealed in this study.

Results

In MDD patients, the subgenual and perigenual ACC demonstrated decreased FC with the posterior regions of the default network (DN), including the posterior inferior parietal lobule and posterior cingulate cortex. FC of these regions was negatively associated with the Automatic Thoughts Questionnaire scores and largely overlapped with previously reported abnormal regions. In addition, reduced FC between the caudal ACC and precuneus was negatively correlated with the Hamilton Anxiety Scale scores. We also found increased FC between the rostral ACC and dorsal medial prefrontal cortex.

Conclusions

Our findings confirmed that functional interaction changes in different ACC sub-regions are specific and associated with distinct symptoms of depression. Our findings provide new insights into the role of ACC sub-regions and DN in the pathophysiology of MDD.

Type
Original Article
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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References

Amodio, D. M., & Frith, C. D. (2006). Meeting of minds: The medial frontal cortex and social cognition. Nature Reviews Neuroscience, 7(4), 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(4), 550562.CrossRefGoogle ScholarPubMed
Ballmaier, M., Toga, A. W., Blanton, R. E., Sowell, E. R., Lavretsky, H., Peterson, J., … Kumar, A. (2004). Anterior cingulate, gyrus rectus, and orbitofrontal abnormalities in elderly depressed patients: An MRI-based parcellation of the prefrontal cortex. American Journal of Psychiatry, 161(1), 99108.CrossRefGoogle ScholarPubMed
Belmaker, R., & Agam, G. (2008). Major depressive disorder. New England Journal of Medicine, 358(1), 5568.CrossRefGoogle ScholarPubMed
Buckner, R. L., Andrews-Hanna, J. R., & Schacter, D. L. (2008). The brain's default network. Annals of the New York Academy of Sciences, 1124(1), 138.CrossRefGoogle ScholarPubMed
Chana, G., Landau, S., Beasley, C., Everall, I. P., & Cotter, D. (2003). Two-dimensional assessment of cytoarchitecture in the anterior cingulate cortex in major depressive disorder, bipolar disorder, and schizophrenia: Evidence for decreased neuronal somal size and increased neuronal density. Biological Psychiatry, 53(12), 10861098.10.1016/S0006-3223(03)00114-8CrossRefGoogle ScholarPubMed
Connolly, C. G., Wu, J., Ho, T. C., Hoeft, F., Wolkowitz, O., Eisendrath, S., … Paulus, M. P. (2013). Resting-state functional connectivity of subgenual anterior cingulate cortex in depressed adolescents. Biological Psychiatry, 74(12), 898907.CrossRefGoogle ScholarPubMed
Craig, M. M., Manktelow, A. E., Sahakian, B. J., Menon, D. K., & Stamatakis, E. A. (2018). Spectral diversity in default mode network connectivity reflects behavioral state. Journal of Cognitive Neuroscience, 30(4), 526539.10.1162/jocn_a_01213CrossRefGoogle ScholarPubMed
D'argembeau, A., Collette, F., Van der Linden, M., Laureys, S., Del Fiore, G., Degueldre, C., … Salmon, E. (2005). Self-referential reflective activity and its relationship with rest: A PET study. NeuroImage, 25(2), 616624.CrossRefGoogle ScholarPubMed
D'Argembeau, A., Stawarczyk, D., Majerus, S., Collette, F., Van der Linden, M., Feyers, D., … Salmon, E. (2010). The neural basis of personal goal processing when envisioning future events. Journal of Cognitive Neuroscience, 22(8), 17011713.CrossRefGoogle ScholarPubMed
Davey, C., Harrison, B., Yücel, M., & Allen, N. (2012). Regionally specific alterations in functional connectivity of the anterior cingulate cortex in major depressive disorder. Psychological Medicine, 42(10), 20712081.CrossRefGoogle ScholarPubMed
Davidson, R. J., Pizzagalli, D., Nitschke, J. B., & Putnam, K. (2002). Depression: Perspectives from affective neuroscience. Annual Review of Psychology, 53(1), 545574.CrossRefGoogle ScholarPubMed
Fales, C. L., Barch, D. M., Rundle, M. M., Mintun, M. A., Snyder, A. Z., Cohen, J. D., … Sheline, Y. I. (2008). Altered emotional interference processing in affective and cognitive-control brain circuitry in major depression. Biological Psychiatry, 63(4), 377384.CrossRefGoogle ScholarPubMed
Fox, M. D., & Raichle, M. E. (2007). Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nature Reviews Neuroscience, 8(9), 700.CrossRefGoogle ScholarPubMed
Gotlib, I. H., & Joormann, J. (2010). Cognition and depression: Current status and future directions. Annual Review of Clinical Psychology, 6, 285312.CrossRefGoogle ScholarPubMed
Greicius, M. D., Flores, B. H., Menon, V., Glover, G. H., Solvason, H. B., Kenna, H., … Schatzberg, A. F. (2007). Resting-state functional connectivity in major depression: Abnormally increased contributions from subgenual cingulate cortex and thalamus. Biological Psychiatry, 62(5), 429437.CrossRefGoogle ScholarPubMed
Grimm, S., Ernst, J., Boesiger, P., Schuepbach, D., Hell, D., Boeker, H., & Northoff, G. (2009). Increased self-focus in major depressive disorder is related to neural abnormalities in subcortical-cortical midline structures. Human Brain Mapping, 30(8), 26172627.CrossRefGoogle ScholarPubMed
Hagler, D. J. Jr, Saygin, A. P., & & Sereno, M. I. (2006). Smoothing and cluster thresholding for cortical surface-based group analysis of fMRI data. NeuroImage, 33(4), 10931103.CrossRefGoogle ScholarPubMed
Hamilton, M. (1980). Rating depressive patients. The Journal of Clinical Psychiatry, 41(12, Sec 2), 2124.Google ScholarPubMed
Hamilton, J. P., Farmer, M., Fogelman, P., & Gotlib, I. H. (2015). Depressive rumination, the default-mode network, and the dark matter of clinical neuroscience. Biological Psychiatry, 78(4), 224230.CrossRefGoogle ScholarPubMed
Hirschfeld, R., Montgomery, S. A., Keller, M. B., Kasper, S., Schatzberg, A. F., Möller, H.-J., … Versiani, M. (2000). Social functioning in depression: A review. The Journal of Clinical Psychiatry, 64(4), 268275.CrossRefGoogle Scholar
Hollon, S. D., & Kendall, P. C. (1980). Cognitive self-statements in depression: Development of an automatic thoughts questionnaire. Cognitive Therapy and Research, 4(4), 383395.CrossRefGoogle Scholar
Johansen-Berg, H., Gutman, D., Behrens, T., Matthews, P., Rushworth, M., Katz, E., … Mayberg, H. (2007). Anatomical connectivity of the subgenual cingulate region targeted with deep brain stimulation for treatment-resistant depression. Cerebral Cortex, 18(6), 13741383.CrossRefGoogle ScholarPubMed
Kaiser, R. H., Andrews-Hanna, J. R., Wager, T. D., & Pizzagalli, D. A. (2015). Large-scale network dysfunction in major depressive disorder: A meta-analysis of resting-state functional connectivity. JAMA Psychiatry, 72(6), 603611.CrossRefGoogle ScholarPubMed
Kelly, A. C., Di Martino, A., Uddin, L. Q., Shehzad, Z., Gee, D. G., Reiss, P. T., … Milham, M. P. (2008). Development of anterior cingulate functional connectivity from late childhood to early adulthood. Cerebral Cortex, 19(3), 640657.CrossRefGoogle ScholarPubMed
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), 567574.CrossRefGoogle ScholarPubMed
Koski, L., & Paus, T. (2000). Functional connectivity of the anterior cingulate cortex within the human frontal lobe: A brain-mapping meta-analysis. In WX, Schneider, AM, Owen, & J, Duncan (Eds.), Executive control and the frontal lobe: Current issues (pp. 5565). Berlin, Heidelberg: Springer.CrossRefGoogle Scholar
Lee, Y., Rosenblat, J. D., Lee, J., Carmona, N. E., Subramaniapillai, M., Shekotikhina, M., … Ho, R. C. (2018). Efficacy of antidepressants on measures of workplace functioning in major depressive disorder: A systematic review. Journal of Affective Disorders, 227, 406415.CrossRefGoogle ScholarPubMed
Li, B., Liu, L., Friston, K. J., Shen, H., Wang, L., Zeng, L.-L., & Hu, D. (2013). A treatment-resistant default mode subnetwork in major depression. Biological Psychiatry, 74(1), 4854.CrossRefGoogle ScholarPubMed
Lombardo, M. V., Chakrabarti, B., Bullmore, E. T., Wheelwright, S. J., Sadek, S. A., Suckling, J., … Baron-Cohen, S. (2010). Shared neural circuits for mentalizing about the self and others. Journal of Cognitive Neuroscience, 22(7), 16231635.CrossRefGoogle ScholarPubMed
Maier, W., Buller, R., Philipp, M., & Heuser, I. (1988). The Hamilton anxiety scale: Reliability, validity and sensitivity to change in anxiety and depressive disorders. Journal of Affective Disorders, 14(1), 6168.CrossRefGoogle ScholarPubMed
Margulies, D. S., Kelly, A. C., Uddin, L. Q., Biswal, B. B., Castellanos, F. X., & Milham, M. P. (2007). Mapping the functional connectivity of anterior cingulate cortex. NeuroImage, 37(2), 579588.CrossRefGoogle ScholarPubMed
Mayberg, H. S., Lozano, A. M., Voon, V., McNeely, H. E., Seminowicz, D., Hamani, C., … Kennedy, S. H. (2005). Deep brain stimulation for treatment-resistant depression. Neuron, 45(5), 651660.CrossRefGoogle ScholarPubMed
Mayberg, H. S., Riva-Posse, P., & Crowell, A. L. (2016). Deep brain stimulation for depression: Keeping an eye on a moving target. JAMA Psychiatry, 73(5), 439440.CrossRefGoogle ScholarPubMed
Menon, V. (2011). Large-scale brain networks and psychopathology: A unifying triple network model. Trends in Cognitive Sciences, 15(10), 483506.CrossRefGoogle ScholarPubMed
Milham, M. P., & Banich, M. T. (2005). Anterior cingulate cortex: An fMRI analysis of conflict specificity and functional differentiation. Human Brain Mapping, 25(3), 328335.CrossRefGoogle ScholarPubMed
Nolen-Hoeksema, S. (2000). The role of rumination in depressive disorders and mixed anxiety/depressive symptoms. Journal of Abnormal Psychology, 109(3), 504.CrossRefGoogle ScholarPubMed
Olvet, D. M., Delaparte, L., Yeh, F. C., DeLorenzo, C., McGrath, P. J., Weissman, M. M., … McInnis, M. G. (2016). A comprehensive examination of white matter tracts and connectometry in major depressive disorder. Depression and Anxiety, 33(1), 5665.CrossRefGoogle ScholarPubMed
Öngür, D., Ferry, A. T., & Price, J. L. (2003). Architectonic subdivision of the human orbital and medial prefrontal cortex. Journal of Comparative Neurology, 460(3), 425449.CrossRefGoogle ScholarPubMed
Organization, W. H. (2017). Depression and other common mental disorders: global health estimates. Geneva, Switzerland: World Health Organization.Google Scholar
Palomero-Gallagher, N., Hoffstaedter, F., Mohlberg, H., Eickhoff, S. B., Amunts, K., & Zilles, K. (2018). Human pregenual anterior cingulate cortex: Structural, functional, and connectional heterogeneity. Cerebral Cortex, 29(6), 25522574.CrossRefGoogle Scholar
Paus, T. (2001). Primate anterior cingulate cortex: Where motor control, drive and cognition interface. Nature Reviews Neuroscience, 2(6), 417.CrossRefGoogle ScholarPubMed
Peng, X., Lin, P., Wu, X., Gong, R., Yang, R., & Wang, J. (2018). Insular subdivisions functional connectivity dysfunction within major depressive disorder. Journal of Affective Disorders, 227, 280288.CrossRefGoogle ScholarPubMed
Pizzagalli, D. A., Peccoralo, L. A., Davidson, R. J., & Cohen, J. D. (2006). Resting anterior cingulate activity and abnormal responses to errors in subjects with elevated depressive symptoms: A 128-channel EEG study. Human Brain Mapping, 27(3), 185201.CrossRefGoogle ScholarPubMed
Riva-Posse, P., Choi, K., Holtzheimer, P. E., Crowell, A. L., Garlow, S. J., Rajendra, J. K., … Mayberg, H. S. (2018). A connectomic approach for subcallosal cingulate deep brain stimulation surgery: Prospective targeting in treatment-resistant depression. Molecular Psychiatry, 23(4), 843.CrossRefGoogle ScholarPubMed
Roiser, J. P., Elliott, R., & Sahakian, B. J. (2012). Cognitive mechanisms of treatment in depression. Neuropsychopharmacology, 37(1), 117.CrossRefGoogle ScholarPubMed
Rolls, E. T., Cheng, W., Gong, W., Qiu, J., Zhou, C., Zhang, J., … Cheng, K. (2018). Functional connectivity of the anterior cingulate cortex in depression and in health. Cerebral Cortex, 1, 14.Google Scholar
Rotge, J.-Y., Lemogne, C., Hinfray, S., Huguet, P., Grynszpan, O., Tartour, E., … Fossati, P. (2014). A meta-analysis of the anterior cingulate contribution to social pain. Social Cognitive and Affective Neuroscience, 10(1), 1927.CrossRefGoogle ScholarPubMed
Sacchet, M. D., Ho, T. C., Connolly, C. G., Tymofiyeva, O., Lewinn, K. Z., Han, L. K., … Frank, G. K. (2016). Large-scale hypoconnectivity between resting-state functional networks in unmedicated adolescent major depressive disorder. Neuropsychopharmacology, 41(12), 2951.CrossRefGoogle ScholarPubMed
Sadaghiani, S., & D'Esposito, M. (2014). Functional characterization of the cingulo-opercular network in the maintenance of tonic alertness. Cerebral Cortex, 25(9), 27632773.CrossRefGoogle ScholarPubMed
Saxe, R., Moran, J. M., Scholz, J., & Gabrieli, J. (2006). Overlapping and non-overlapping brain regions for theory of mind and self reflection in individual subjects. Social Cognitive and Affective Neuroscience, 1(3), 229234.CrossRefGoogle ScholarPubMed
Schacter, D. L., Addis, D. R., & Buckner, R. L. (2007). Remembering the past to imagine the future: The prospective brain. Nature Reviews Neuroscience, 8(9), 657.10.1038/nrn2213CrossRefGoogle ScholarPubMed
Schaeffer, D. J., Gilbert, K. M., Ghahremani, M., Gati, J. S., Menon, R. S., & Everling, S. (2019). Intrinsic functional clustering of anterior cingulate cortex in the common marmoset. NeuroImage, 186, 301307.CrossRefGoogle ScholarPubMed
Sheline, Y. I., Barch, D. M., Price, J. L., Rundle, M. M., Vaishnavi, S. N., Snyder, A. Z., … Raichle, M. E. (2009). The default mode network and self-referential processes in depression. Proceedings of the National Academy of Sciences, 106(6), 19421947.CrossRefGoogle ScholarPubMed
Smith, S. M., Fox, P. T., Miller, K. L., Glahn, D. C., Fox, P. M., Mackay, C. E., … Laird, A. R. (2009). Correspondence of the brain's functional architecture during activation and rest. Proceedings of the National Academy of Sciences, 106(31), 1304013045.CrossRefGoogle Scholar
Spreng, R. N., Mar, R. A., & Kim, A. S. (2009). The common neural basis of autobiographical memory, prospection, navigation, theory of mind, and the default mode: A quantitative meta-analysis. Journal of Cognitive Neuroscience, 21(3), 489510.CrossRefGoogle ScholarPubMed
Strikwerda-Brown, C., Davey, C. G., Whittle, S., Allen, N. B., Byrne, M. L., Schwartz, O. S., … Harrison, B. J. (2014). Mapping the relationship between subgenual cingulate cortex functional connectivity and depressive symptoms across adolescence. Social Cognitive and Affective Neuroscience, 10(7), 961968.CrossRefGoogle ScholarPubMed
Taylor, S. F., Martis, B., Fitzgerald, K. D., Welsh, R. C., Abelson, J. L., Liberzon, I., … Gehring, W. J. (2006). Medial frontal cortex activity and loss-related responses to errors. Journal of Neuroscience, 26(15), 40634070.CrossRefGoogle ScholarPubMed
Van Essen, D. C. (2005). A population-average, landmark-and surface-based (PALS) atlas of human cerebral cortex. NeuroImage, 28(3), 635662.CrossRefGoogle Scholar
Vatansever, D., Manktelow, A. E., Sahakian, B. J., Menon, D. K., & Stamatakis, E. A. (2016). Cognitive flexibility: A default network and basal ganglia connectivity perspective. Brain Connectivity, 6(3), 201207.CrossRefGoogle ScholarPubMed
Vatansever, D., Menon, D. K., & Stamatakis, E. A. (2017). Default mode contributions to automated information processing. Proceedings of the National Academy of Sciences, 114(48), 1282112826.10.1073/pnas.1710521114CrossRefGoogle ScholarPubMed
Wang, D., Buckner, R. L., Fox, M. D., Holt, D. J., Holmes, A. J., Stoecklein, S., … Li, K. (2015). Parcellating cortical functional networks in individuals. Nature Neuroscience, 18(12), 1853.CrossRefGoogle ScholarPubMed
Wang, L., Hermens, D., Hickie, I., & Lagopoulos, J. (2012). A systematic review of resting-state functional-MRI studies in major depression. Journal of Affective Disorders, 142(1–3), 612.10.1016/j.jad.2012.04.013CrossRefGoogle ScholarPubMed
Wise, T., Radua, J., Via, E., Cardoner, N., Abe, O., Adams, T., … Périco, C. D. A. M. (2017). Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: Evidence from voxel-based meta-analysis. Molecular Psychiatry, 22(10), 1455.CrossRefGoogle ScholarPubMed
Yarkoni, T., Poldrack, R. A., Nichols, T. E., Van Essen, D. C., & Wager, T. D. (2011). Large-scale automated synthesis of human functional neuroimaging data. Nature Methods, 8(8), 665.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(3), 11251165. doi:10.1152/jn.00338.2011.Google ScholarPubMed
Yokoyama, S., Okamoto, Y., Takagaki, K., Okada, G., Takamura, M., Mori, A., … Yamawaki, S. (2018). Effects of behavioral activation on default mode network connectivity in subthreshold depression: A preliminary resting-state fMRI study. Journal of Affective Disorders, 227, 156163.CrossRefGoogle ScholarPubMed
Yucel, K., McKinnon, M. C., Chahal, R., Taylor, V. H., Macdonald, K., Joffe, R., & MacQueen, G. M. (2008). Anterior cingulate volumes in never-treated patients with major depressive disorder. Neuropsychopharmacology, 33(13), 3157.CrossRefGoogle ScholarPubMed
Zhu, X., Wang, X., Xiao, J., Liao, J., Zhong, M., Wang, W., & Yao, S. (2012). Evidence of a dissociation pattern in resting-state default mode network connectivity in first-episode, treatment-naive major depression patients. Biological Psychiatry, 71(7), 611617.CrossRefGoogle ScholarPubMed
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