Hostname: page-component-f554764f5-68cz6 Total loading time: 0 Render date: 2025-04-21T01:48:01.745Z Has data issue: false hasContentIssue false
  • English
  • Français

Revisiting default mode network function in major depression: evidence for disrupted subsystem connectivity

Published online by Cambridge University Press:  31 October 2013

F. Sambataro ,
N. D. Wolf ,
M. Pennuto ,
N. Vasic  and
R. C. Wolf
F. Sambataro*
Affiliation:
Brain Center for Motor and Social Cognition, Istituto Italiano di Tecnologia@UniPR, Parma, Italy
N. D. Wolf
Affiliation:
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Mannheim, Germany
M. Pennuto
Affiliation:
Dulbecco Telethon Institute Laboratory of Neurodegenerative Diseases, Centre for Integrative Biology, University of Trento, Trento, Italy
N. Vasic
Affiliation:
Department of Psychiatry and Psychotherapy III, University of Ulm, Ulm, Germany
R. C. Wolf*
Affiliation:
Center of Psychosocial Medicine, Department of General Psychiatry, University of Heidelberg, Germany
*
*Address for correspondence: F. Sambataro M.D., Ph.D., Brain Center for Motor and Social Cognition, Istituto Italiano di Tecnologia@UniPR, Via Università 12, Parma, Italy. (Email: [email protected])
(Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Major depressive disorder (MDD) is characterized by alterations in brain function that are identifiable also during the brain's ‘resting state’. One functional network that is disrupted in this disorder is the default mode network (DMN), a set of large-scale connected brain regions that oscillate with low-frequency fluctuations and are more active during rest relative to a goal-directed task. Recent studies support the idea that the DMN is not a unitary system, but rather is composed of smaller and distinct functional subsystems that interact with each other. The functional relevance of these subsystems in depression, however, is unclear.

Method

Here, we investigated the functional connectivity of distinct DMN subsystems and their interplay in depression using resting-state functional magnetic resonance imaging.

Results

We show that patients with MDD exhibit increased within-network connectivity in posterior, ventral and core DMN subsystems along with reduced interplay from the anterior to the ventral DMN subsystems.

Conclusions

These data suggest that MDD is characterized by alterations of subsystems within the DMN as well as of their interactions. Our findings highlight a critical role of DMN circuitry in the pathophysiology of MDD, thus suggesting these subsystems as potential therapeutic targets.

Keywords

Default mode networkfunctional connectivitylow-frequency fluctuationsmajor depressionresting state
Type
Original Articles
Information
Psychological Medicine , Volume 44 , Issue 10 , July 2014 , pp. 2041 - 2051
Copyright
Copyright © Cambridge University Press 2013 

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

Airan, RD, Meltzer, LA, Roy, M, Gong, Y, Chen, H, Deisseroth, K (2007). High-speed imaging reveals neurophysiological links to behavior in an animal model of depression. Science 317, 819–823.CrossRefGoogle ScholarPubMed
Anand, A, Li, Y, Wang, Y, Wu, J, Gao, S, Bukhari, L, Mathews, VP, Kalnin, A, Lowe, MJ (2005). Activity and connectivity of brain mood regulating circuit in depression: a functional magnetic resonance study. Biological Psychiatry 57, 1079–1088.CrossRefGoogle ScholarPubMed
Andrews-Hanna, JR, Reidler, JS, Sepulcre, J, Poulin, R, Buckner, RL (2010). Functional–anatomic fractionation of the brain's default network. Neuron 65, 550–562.CrossRefGoogle ScholarPubMed
Auer, DP (2008). Spontaneous low-frequency blood oxygenation level-dependent fluctuations and functional connectivity analysis of the ‘resting’ brain. Magnetic Resonance Imaging 26, 1055–1064.CrossRefGoogle ScholarPubMed
Baccala, L, Takahashi, D, Sameshima, K (2007). Generalized partial directed coherence. In Proceedings of the 15th International Conference on Digital Signal Processing (DSP2007), pp. 162–166. IEEE Xplore: Cardiff.Google Scholar
Bar, M (2009). A cognitive neuroscience hypothesis of mood and depression. Trends in Cognitive Sciences 13, 456–463.CrossRefGoogle ScholarPubMed
Beckmann, CF, Mackay, C, Filippini, N, Smith, S (2009). Group comparison of resting-state fMRI data using multi-subject ICA and dual regression. Neuroimage 47, 181.CrossRefGoogle Scholar
Berman, MG, Peltier, S, Nee, DE, Kross, E, Deldin, PJ, Jonides, J (2011). Depression, rumination and the default network. Social Cognitive and Affective Neuroscience 6, 548–555.CrossRefGoogle ScholarPubMed
Birn, RM (2012). The role of physiological noise in resting-state functional connectivity. Neuroimage 62, 864–870.CrossRefGoogle ScholarPubMed
Biswal, BB, Mennes, M, Zuo, XN, Gohel, S, Kelly, C, Smith, SM, Beckmann, CF, Adelstein, JS, Buckner, RL, Colcombe, S, Dogonowski, AM, Ernst, M, Fair, D, Hampson, M, Hoptman, MJ, Hyde, JS, Kiviniemi, VJ, Kotter, R, Li, SJ, Lin, CP, Lowe, MJ, Mackay, C, Madden, DJ, Madsen, KH, Margulies, DS, Mayberg, HS, McMahon, K, Monk, CS, Mostofsky, SH, Nagel, BJ, Pekar, JJ, Peltier, SJ, Petersen, SE, Riedl, V, Rombouts, SA, Rypma, B, Schlaggar, BL, Schmidt, S, Seidler, RD, Siegle, GJ, Sorg, C, Teng, GJ, Veijola, J, Villringer, A, Walter, M, Wang, L, Weng, XC, Whitfield-Gabrieli, S, Williamson, P, Windischberger, C, Zang, YF, Zhang, HY, Castellanos, FX, Milham, MP (2010). Toward discovery science of human brain function. Proceedings of the National Academy of Sciences USA 107, 4734–4739.CrossRefGoogle ScholarPubMed
Broyd, SJ, Demanuele, C, Debener, S, Helps, SK, James, CJ, Sonuga-Barke, EJ (2009). Default-mode brain dysfunction in mental disorders: a systematic review. Neuroscience and Biobehavioral Reviews 33, 279–296.CrossRefGoogle ScholarPubMed
Buckner, RL, Andrews-Hanna, JR, Schacter, DL (2008). The brain's default network: anatomy, function, and relevance to disease. Annals of the New York Academy of Sciences 1124, 1–38.CrossRefGoogle ScholarPubMed
Carmichael, ST, Price, JL (1995). Limbic connections of the orbital and medial prefrontal cortex in macaque monkeys. Journal of Comparative Neurology 363, 615–641.CrossRefGoogle ScholarPubMed
Cox, RW (1996). AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Computers and Biomedical Research 29, 162–173.CrossRefGoogle ScholarPubMed
Damoiseaux, JS, Prater, KE, Miller, BL, Greicius, MD (2012). Functional connectivity tracks clinical deterioration in Alzheimer's disease. Neurobiology of Aging 33, 828 e19–e30.CrossRefGoogle ScholarPubMed
Dosenbach, NU, Visscher, KM, Palmer, ED, Miezin, FM, Wenger, KK, Kang, HC, Burgund, ED, Grimes, AL, Schlaggar, BL, Petersen, SE (2006). A core system for the implementation of task sets. Neuron 50, 799–812.CrossRefGoogle ScholarPubMed
Enzi, B, Duncan, NW, Kaufmann, J, Tempelmann, C, Wiebking, C, Northoff, G (2012). Glutamate modulates resting state activity in the perigenual anterior cingulate cortex – a combined fMRI–MRS study. Neuroscience 227, 102–109.CrossRefGoogle ScholarPubMed
Fairhall, SL, Sharma, S, Magnusson, J, Murphy, B (2010). Memory related dysregulation of hippocampal function in major depressive disorder. Biological Psychology 85, 499–503.CrossRefGoogle ScholarPubMed
Greicius, MD, Flores, BH, Menon, V, Glover, GH, Solvason, HB, Kenna, H, Reiss, AL, Schatzberg, AF (2007). Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus. Biological Psychiatry 62, 429–437.CrossRefGoogle ScholarPubMed
Grimm, S, Boesiger, P, Beck, J, Schuepbach, D, Bermpohl, F, Walter, M, Ernst, J, Hell, D, Boeker, H, Northoff, G (2009). Altered negative BOLD responses in the default-mode network during emotion processing in depressed subjects. Neuropsychopharmacology 34, 932–943.CrossRefGoogle ScholarPubMed
Guo, WB, Liu, F, Xue, ZM, Yu, Y, Ma, CQ, Tan, CL, Sun, XL, Chen, JD, Liu, ZN, Xiao, CQ, Chen, HF, Zhao, JP (2011). Abnormal neural activities in first-episode, treatment-naive, short-illness-duration, and treatment-response patients with major depressive disorder: a resting-state fMRI study. Journal of Affective Disorders 135, 326–331.CrossRefGoogle ScholarPubMed
Gutman, DA, Holtzheimer, PE, Behrens, TE, Johansen-Berg, H, Mayberg, HS (2009). A tractography analysis of two deep brain stimulation white matter targets for depression. Biological Psychiatry 65, 276–282.CrossRefGoogle ScholarPubMed
Hamilton, JP, Chen, G, Thomason, ME, Schwartz, ME, Gotlib, IH (2011). Investigating neural primacy in major depressive disorder: multivariate Granger causality analysis of resting-state fMRI time-series data. Molecular Psychiatry 16, 763–772.CrossRefGoogle ScholarPubMed
Hamilton, JP, Chen, MC, Gotlib, IH (2013). Neural systems approaches to understanding major depressive disorder: an intrinsic functional organization perspective. Neurobiology of Disease 52, 4–11.CrossRefGoogle ScholarPubMed
Jafri, MJ, Pearlson, GD, Stevens, M, Calhoun, VD (2008). A method for functional network connectivity among spatially independent resting-state components in schizophrenia. Neuroimage 39, 1666–1681.CrossRefGoogle ScholarPubMed
Johnson, MK, Nolen-Hoeksema, S, Mitchell, KJ, Levin, Y (2009). Medial cortex activity, self-reflection and depression. Social Cognitive and Affective Neuroscience 4, 313–327.CrossRefGoogle ScholarPubMed
Liu, F, Guo, W, Liu, L, Long, Z, Ma, C, Xue, Z, Wang, Y, Li, J, Hu, M, Zhang, J, Du, H, Zeng, L, Liu, Z, Wooderson, SC, Tan, C, Zhao, J, Chen, H (2013). Abnormal amplitude low-frequency oscillations in medication-naive, first-episode patients with major depressive disorder: a resting-state fMRI study. Journal of Affective Disorders 146, 401–406.CrossRefGoogle ScholarPubMed
Lozano, AM, Mayberg, HS, Giacobbe, P, Hamani, C, Craddock, RC, Kennedy, SH (2008). Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression. Biological Psychiatry 64, 461–467.CrossRefGoogle ScholarPubMed
Mantini, D, Perrucci, MG, Del Gratta, C, Romani, GL, Corbetta, M (2007). Electrophysiological signatures of resting state networks in the human brain. Proceedings of the National Academy of Sciences USA 104, 13170–13175.CrossRefGoogle ScholarPubMed
Murrough, JW, Iacoviello, B, Neumeister, A, Charney, DS, Iosifescu, DV (2011). Cognitive dysfunction in depression: neurocircuitry and new therapeutic strategies. Neurobiology of Learning and Memory 96, 553–563.CrossRefGoogle ScholarPubMed
Northoff, G, Wiebking, C, Feinberg, T, Panksepp, J (2011). The ‘resting-state hypothesis’ of major depressive disorder – a translational subcortical–cortical framework for a system disorder. Neuroscience and Biobehavioral Reviews 35, 1929–1945.CrossRefGoogle ScholarPubMed
Oldfield, RC (1971). The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9, 97–113.CrossRefGoogle ScholarPubMed
Price, JL, Drevets, WC (2010). Neurocircuitry of mood disorders. Neuropsychopharmacology 35, 192–216.CrossRefGoogle ScholarPubMed
Raichle, ME, MacLeod, AM, Snyder, AZ, Powers, WJ, Gusnard, DA, Shulman, GL (2001). A default mode of brain function. Proceedings of the National Academy of Sciences USA 98, 676–682.CrossRefGoogle ScholarPubMed
Sambataro, F, Blasi, G, Fazio, L, Caforio, G, Taurisano, P, Romano, R, Di Giorgio, A, Gelao, B, Lo Bianco, L, Papazacharias, A, Popolizio, T, Nardini, M, Bertolino, A (2010 a). Treatment with olanzapine is associated with modulation of the default mode network in patients with schizophrenia. Neuropsychopharmacology 35, 904–912.CrossRefGoogle ScholarPubMed
Sambataro, F, Fazio, L, Taurisano, P, Gelao, B, Porcelli, A, Mancini, M, Sinibaldi, L, Ursini, G, Masellis, R, Caforio, G, Di Giorgio, A, Niccoli-Asabella, A, Popolizio, T, Blasi, G, Bertolino, A (2013). DRD2 genotype-based variation of default mode network activity and of its relationship with striatal DAT binding. Schizophrenia Bulletin 39, 206–216.CrossRefGoogle ScholarPubMed
Sambataro, F, Murty, VP, Callicott, JH, Tan, HY, Das, S, Weinberger, DR, Mattay, VS (2010 b). Age-related alterations in default mode network: impact on working memory performance. Neurobiology of Aging 31, 839–852.CrossRefGoogle ScholarPubMed
Sheline, YI, Barch, DM, Price, JL, Rundle, MM, Vaishnavi, SN, Snyder, AZ, Mintun, MA, Wang, S, Coalson, RS, Raichle, ME (2009). The default mode network and self-referential processes in depression. Proceedings of the National Academy of Sciences USA 106, 1942–1947.CrossRefGoogle ScholarPubMed
Sheline, YI, Price, JL, Yan, Z, Mintun, MA (2010). Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proceedings of the National Academy of Sciences USA 107, 11020–11025.CrossRefGoogle ScholarPubMed
Shmuel, A, Leopold, DA (2008). Neuronal correlates of spontaneous fluctuations in fMRI signals in monkey visual cortex: implications for functional connectivity at rest. Human Brain Mapping 29, 751–761.CrossRefGoogle ScholarPubMed
Siegle, GJ, Thompson, W, Carter, CS, Steinhauer, SR, Thase, ME (2007). Increased amygdala and decreased dorsolateral prefrontal BOLD responses in unipolar depression: related and independent features. Biological Psychiatry 61, 198–209.CrossRefGoogle ScholarPubMed
Smith, SM, Fox, PT, Miller, KL, Glahn, DC, Fox, PM, Mackay, CE, Filippini, N, Watkins, KE, Toro, R, Laird, AR, Beckmann, CF (2009). Correspondence of the brain's functional architecture during activation and rest. Proceedings of the National Academy of Sciences USA 106, 13040–13045.CrossRefGoogle ScholarPubMed
Starck, T, Remes, J, Nikkinen, J, Tervonen, O, Kiviniemi, V (2010). Correction of low-frequency physiological noise from the resting state BOLD fMRI – effect on ICA default mode analysis at 1.5 T. Journal of Neuroscience Methods 186, 179–185.CrossRefGoogle ScholarPubMed
Stevens, MC, Pearlson, GD, Calhoun, VD (2009). Changes in the interaction of resting-state neural networks from adolescence to adulthood. Human Brain Mapping 30, 2356–2366.CrossRefGoogle ScholarPubMed
Surguladze, S, Brammer, MJ, Keedwell, P, Giampietro, V, Young, AW, Travis, MJ, Williams, SC, Phillips, ML (2005). A differential pattern of neural response toward sad versus happy facial expressions in major depressive disorder. Biological Psychiatry 57, 201–209.CrossRefGoogle ScholarPubMed
Uddin, LQ, Kelly, AM, Biswal, BB, Xavier Castellanos, F, Milham, MP (2009). Functional connectivity of default mode network components: correlation, anticorrelation, and causality. Human Brain Mapping 30, 625–637.CrossRefGoogle ScholarPubMed
Vasic, N, Walter, H, Sambataro, F, Wolf, RC (2009). Aberrant functional connectivity of dorsolateral prefrontal and cingulate networks in patients with major depression during working memory processing. Psychological Medicine 39, 977–987.CrossRefGoogle ScholarPubMed
Videbech, P, Ravnkilde, B, Pedersen, TH, Hartvig, H, Egander, A, Clemmensen, K, Rasmussen, NA, Andersen, F, Gjedde, A, Rosenberg, R (2002). The Danish PET/depression project: clinical symptoms and cerebral blood flow. A regions-of-interest analysis. Acta Psychiatrica Scandinavica 106, 35–44.CrossRefGoogle ScholarPubMed
Wagner, G, Sinsel, E, Sobanski, T, Kohler, S, Marinou, V, Mentzel, HJ, Sauer, H, Schlosser, RG (2006). Cortical inefficiency in patients with unipolar depression: an event-related FMRI study with the Stroop task. Biological Psychiatry 59, 958–965.CrossRefGoogle ScholarPubMed
Whitfield-Gabrieli, S, Moran, JM, Nieto-Castanon, A, Triantafyllou, C, Saxe, R, Gabrieli, JD (2011). Associations and dissociations between default and self-reference networks in the human brain. Neuroimage 55, 225–232.CrossRefGoogle ScholarPubMed
Yao, Z, Wang, L, Lu, Q, Liu, H, Teng, G (2009). Regional homogeneity in depression and its relationship with separate depressive symptom clusters: a resting-state fMRI study. Journal of Affective Disorders 115, 430–438.CrossRefGoogle ScholarPubMed
Zhang, J, Wang, J, Wu, Q, Kuang, W, Huang, X, He, Y, Gong, Q (2011). Disrupted brain connectivity networks in drug-naive, first-episode major depressive disorder. Biological Psychiatry 70, 334–342.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, 611–617.CrossRefGoogle ScholarPubMed
Zou, QH, Zhu, CZ, Yang, Y, Zuo, XN, Long, XY, Cao, QJ, Wang, YF, Zang, YF (2008). An improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state fMRI: fractional ALFF. Journal of Neuroscience Methods 172, 137–141.CrossRefGoogle ScholarPubMed
Zuo, XN, Kelly, C, Adelstein, JS, Klein, DF, Castellanos, FX, Milham, MP (2010). Reliable intrinsic connectivity networks: test–retest evaluation using ICA and dual regression approach. Neuroimage 49, 2163–2177.CrossRefGoogle ScholarPubMed
Supplementary material: PDF

Sambataro et al. Supplementary Material

Tables and Figures

Download Sambataro et al. Supplementary Material(PDF)
PDF 5.1 MB