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Regionally specific alterations in functional connectivity of the anterior cingulate cortex in major depressive disorder

Published online by Cambridge University Press:  09 March 2012

C. G. Davey ,
B. J. Harrison ,
M. Yücel  and
N. B. Allen
C. G. Davey*
Affiliation:
Orygen Youth Health Research Centre, The University of Melbourne, Australia Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Australia
B. J. Harrison
Affiliation:
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Australia
M. Yücel
Affiliation:
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Australia
N. B. Allen
Affiliation:
Orygen Youth Health Research Centre, The University of Melbourne, Australia Department of Psychological Sciences, The University of Melbourne, Australia
*
*Address for correspondence: Dr C. G. Davey, Orygen Youth Health Research Centre, The University of Melbourne, Parkville, Victoria 3052, Australia. (Email: [email protected])
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Abstract

Background

Depression has been associated with functional alterations in several areas of the cingulate cortex. In this study we have taken a systematic approach to examining how alterations in functional connectivity vary across the functionally diverse subregions of the rostral cingulate cortex.

Method

Eighteen patients with major depressive disorder, aged 15 to 24 years, were matched with 20 healthy control participants. Using resting-state functional connectivity magnetic resonance imaging (fcMRI), we systematically investigated the functional connectivity of four subregions of the rostral cingulate cortex. Voxelwise statistical maps of each subregion's connectivity with other brain areas were compared between the patient and control groups.

Results

The depressed participants showed altered patterns of connectivity with ventral cingulate subregions. They showed increased connectivity between subgenual anterior cingulate cortex (ACC) and dorsomedial frontal cortex, with connectivity strength showing positive correlation with illness severity. Depressed participants also showed increased connectivity between pregenual ACC and left dorsolateral frontal cortex, and decreased connectivity between pregenual ACC and the caudate nucleus bilaterally.

Conclusions

The results reinforce the importance of subgenual ACC for depression, and show a close link between brain regions that support self-related processes and affective visceromotor function. The pregenual ACC also has an important role, with its increased connectivity with dorsolateral frontal cortex suggesting heightened cognitive regulation of affect; and reduced connectivity with the caudate nucleus potentially underlying symptoms such as anhedonia, reduced motivation and psychomotor dysfunction.

Keywords

Adolescenceanterior cingulate cortexfMRIfunctional connectivitymajor depressive disorder
Type
Original Articles
Information
Psychological Medicine , Volume 42 , Issue 10 , October 2012 , pp. 2071 - 2081
Copyright
Copyright © Cambridge University Press 2012

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References

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
Auer, DP, Pütz, B, Kraft, E, Lipinski, B, Schill, J, Holsboer, F (2000). Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study. Biological Psychiatry 47, 305–313.CrossRefGoogle Scholar
Beck, AT, Steer, RA, Brown, GK (1996). Manual for the Beck Depression Inventory-II. Psychological Corporation: San Antonio, TX.Google Scholar
Bench, CJ, Friston, KJ, Brown, RG, Scott, LC, Frackowiak, RS, Dolan, RJ (1992). The anatomy of melancholia – focal abnormalities of cerebral blood flow in major depression. Psychological Medicine 22, 607–615.CrossRefGoogle ScholarPubMed
Berman, MG, Peltier, S, Nee, DE, Kross, E, Deldin, PJ, Jonides, J (2010). Depression, rumination and the default network. Social Cognitive and Affective Neuroscience 6, 548–555.CrossRefGoogle ScholarPubMed
Bluhm, R, Williamson, P, Lanius, R, Théberge, J, Densmore, M, Bartha, R, Neufeld, R, Osuch, E (2009). Resting state default-mode network connectivity in early depression using a seed region-of-interest analysis: decreased connectivity with caudate nucleus. Psychiatry and Clinical Neurosciences 63, 754–761.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
Caetano, SC, Kaur, S, Brambilla, P, Nicoletti, M, Hatch, JP, Sassi, RB, Mallinger, AG, Keshavan, MS, Kupfer, DJ, Frank, E, Soares, JC (2006). Smaller cingulate volumes in unipolar depressed patients. Biological Psychiatry 59, 702–706.CrossRefGoogle ScholarPubMed
Carney, RM, Freedland, KE, Veith, RC (2005). Depression, the autonomic nervous system, and coronary heart disease. Psychosomatic Medicine 67 (Suppl. 1), S29–S33.CrossRefGoogle ScholarPubMed
Cullen, KR, Gee, DG, Klimes-Dougan, B, Gabbay, V, Hulvershorn, L, Mueller, BA, Camchong, J, Bell, CJ, Houri, A, Kumra, S, Lim, KO, Castellanos, FX, Milham, MP (2009). A preliminary study of functional connectivity in comorbid adolescent depression. Neuroscience Letters 460, 227–231.CrossRefGoogle ScholarPubMed
Davey, CG, Yucel, M, Allen, NB (2008). The emergence of depression in adolescence: development of the prefrontal cortex and the representation of reward. Neuroscience and Biobehavioral Reviews 32, 1–19.CrossRefGoogle ScholarPubMed
David, O (2011). fMRI connectivity, meaning and empiricism. Comments on: Roebroeck et al. The identification of interacting networks in the brain using fMRI: model selection, causality and deconvolution. NeuroImage 58, 306–309; author reply 310–311.CrossRefGoogle ScholarPubMed
Dosenbach, NU, Nardos, B, Cohen, AL, Fair, DA, Power, JD, Church, JA, Nelson, SM, Wig, GS, Vogel, AC, Lessov-Schlaggar, CN, Barnes, KA, Dubis, JW, Feczko, E, Coalson, RS, Pruett, Jr. JR, Barch, DM, Petersen, SE, Schlaggar, BL (2010). Prediction of individual brain maturity using fMRI. Science 329, 1358–1361.CrossRefGoogle ScholarPubMed
Drevets, WC, Price, JL, Furey, ML (2008 a). Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression. Brain Structure and Function 213, 93–118.CrossRefGoogle ScholarPubMed
Drevets, WC, Savitz, J, Trimble, M (2008 b). The subgenual anterior cingulate cortex in mood disorders. CNS Spectrums 13, 663–681.CrossRefGoogle ScholarPubMed
Elliott, R, Rubinsztein, JS, Sahakian, BJ, Dolan, RJ (2002). The neural basis of mood-congruent processing biases in depression. Archives of General Psychiatry 59, 597–604.CrossRefGoogle ScholarPubMed
Fair, DA, Cohen, AL, Dosenbach, NU, Church, JA, Miezin, FM, Barch, DM, Raichle, ME, Petersen, SE, Schlaggar, BL (2008). The maturing architecture of the brain's default network. Proceedings of the National Academy of Sciences USA 105, 4028–4032.CrossRefGoogle ScholarPubMed
Fair, DA, Cohen, AL, Power, JD, Dosenbach, NU, Church, JA, Miezin, FM, Schlaggar, BL, Petersen, SE (2009). Functional brain networks develop from a ‘local to distributed’ organization. PLoS Computational Biology 5, e1000381.CrossRefGoogle ScholarPubMed
Fair, DA, Dosenbach, NU, Church, JA, Cohen, AL, Brahmbhatt, S, Miezin, FM, Barch, DM, Raichle, ME, Petersen, SE, Schlaggar, BL (2007). Development of distinct control networks through segregation and integration. Proceedings of the National Academy of Sciences USA 104, 13507–13512.CrossRefGoogle ScholarPubMed
First, MB, Spitzer, RL, Gibbon, M, Williams, JBW (1997). Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Biometrics Research Department, New York State Psychiatric Institute: New York.Google Scholar
Fornito, A, Bullmore, ET (2010). What can spontaneous fluctuations of the blood oxygenation-level-dependent signal tell us about psychiatric disorders? Current Opinion in Psychiatry 23, 239–249.CrossRefGoogle ScholarPubMed
Fox, MD, Corbetta, M, Snyder, AZ, Vincent, JL, Raichle, ME (2006). Spontaneous neuronal activity distinguishes human dorsal and ventral attention systems. Proceedings of the National Academy of Sciences USA 103, 10046–10051.CrossRefGoogle ScholarPubMed
Fox, MD, Greicius, M (2010). Clinical applications of resting state functional connectivity. Frontiers in Systems Neuroscience 4, 19.Google ScholarPubMed
Freedman, LJ, Insel, TR, Smith, Y (2000). Subcortical projections of area 25 (subgenual cortex) of the macaque monkey. Journal of Comparative Neurology 421, 172–188.3.0.CO;2-8>CrossRefGoogle ScholarPubMed
Gabbay, V, Mao, X, Klein, RG, Ely, BA, Babb, JS, Panzer, AM, Alonso, CM, Shungu, DC (2012). Anterior cingulate cortex γ-aminobutyric acid in depressed adolescents: relationship to anhedonia. Archives of General Psychiatry 69, 139–149.CrossRefGoogle ScholarPubMed
Grant, MM, Thase, ME, Sweeney, JA (2001). Cognitive disturbance in outpatient depressed younger adults: evidence of modest impairment. Biological Psychiatry 50, 35–43.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, 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, 2617–2627.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
Hansen, RA, Moore, CG, Dusetzina, SB, Leinwand, BI, Gartlehner, G, Gaynes, BN (2009). Controlling for drug dose in systematic review and meta-analysis: a case study of the effect of antidepressant dose. Medical Decision Making 29, 91–103.CrossRefGoogle ScholarPubMed
Harrison, BJ, Pujol, J, López-Solà, M, Hernández-Ribas, R, Deus, J, Ortiz, H, Soriano-Mas, C, Yücel, M, Pantelis, C, Cardoner, N (2008 a). Consistency and functional specialization in the default mode brain network. Proceedings of the National Academy of Sciences USA 105, 9781–9786.CrossRefGoogle ScholarPubMed
Harrison, BJ, Pujol, J, Ortiz, H, Fornito, A, Pantelis, C, Yücel, M (2008 b). Modulation of brain resting-state networks by sad mood induction. PLoS One 3, e1794.CrossRefGoogle ScholarPubMed
Harrison, BJ, Soriano-Mas, C, Pujol, J, Ortiz, H, López-Solà, M, Hernández-Ribas, R, Deus, J, Alonso, P, Yücel, M, Pantelis, C, Menchon, JM, Cardoner, N (2009). Altered corticostriatal functional connectivity in obsessive-compulsive disorder. American Journal of Physiology 66, 1189–1200.Google ScholarPubMed
Ito, H, Kawashima, R, Awata, S, Ono, S, Sato, K, Goto, R, Koyama, M, Sato, M, Fukuda, H (1996). Hypoperfusion in the limbic system and prefrontal cortex in depression: SPECT with anatomic standardization technique. Journal of Nuclear Medicine 37, 410–414.Google ScholarPubMed
Kelly, AM, Di Martino, A, Uddin, LQ, Shehzad, Z, Gee, DG, Reiss, PT, Margulies, DS, Castellanos, FX, Milham, MP (2009). Development of anterior cingulate functional connectivity from late childhood to early adulthood. Cerebral Cortex 19, 640–657.CrossRefGoogle ScholarPubMed
Kyte, ZA, Goodyer, IM, Sahakian, BJ (2005). Selected executive skills in adolescents with recent first episode major depression. Journal of Child Psychology and Psychiatry 46, 995–1005.CrossRefGoogle ScholarPubMed
Lévesque, J, Eugène, F, Joanette, Y, Paquette, V, Mensour, B, Beaudoin, G, Leroux, JM, Bourgouin, P, Beauregard, M (2003). Neural circuitry underlying voluntary suppression of sadness. Biological Psychiatry 53, 502–510.CrossRefGoogle ScholarPubMed
MacLean, PD (1955). The limbic system (visceral brain) in relation to central gray and reticulum of the brain stem: evidence of interdependence in emotional processes. Psychosomatic Medicine 17, 355–366.CrossRefGoogle ScholarPubMed
Margulies, DS, Kelly, AM, Uddin, LQ, Biswal, BB, Castellanos, FX, Milham, MP (2007). Mapping the functional connectivity of anterior cingulate cortex. NeuroImage 37, 579–588.CrossRefGoogle ScholarPubMed
Mayberg, HS, Liotti, M, Brannan, SK, McGinnis, S, Mahurin, RK, Jerabek, PA, Silva, JA, Tekell, JL, Martin, CC, Lancaster, JL, Fox, PT (1999). Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. American Journal of Psychiatry 156, 675–682.CrossRefGoogle ScholarPubMed
McGorry, P (1998). Beyond adolescent psychiatry: the logic of a youth mental health model. Australian and New Zealand Journal of Psychiatry 32, 138–140.Google ScholarPubMed
Ochsner, KN, Bunge, SA, Gross, JJ, Gabrieli, JD (2002). Rethinking feelings: an FMRI study of the cognitive regulation of emotion. Journal of Cognitive Neuroscience 14, 1215–1229.CrossRefGoogle ScholarPubMed
Ochsner, KN, Ray, RD, Cooper, JC, Robertson, ER, Chopra, S, Gabrieli, JD, Gross, JJ (2004). For better or for worse: neural systems supporting the cognitive down- and up-regulation of negative emotion. NeuroImage 23, 483–499.CrossRefGoogle ScholarPubMed
Phan, KL, Fitzgerald, DA, Nathan, PJ, Moore, GJ, Uhde, TW, Tancer, ME (2005). Neural substrates for voluntary suppression of negative affect: a functional magnetic resonance imaging study. Biological Psychiatry 57, 210–219.CrossRefGoogle ScholarPubMed
Phan, KL, Wager, T, Taylor, SF, Liberzon, I (2002). Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI. NeuroImage 16, 331–348.CrossRefGoogle ScholarPubMed
Price, JL, Drevets, WC (2010). Neurocircuitry of mood disorders. Neuropsychopharmacology 35, 192–216.CrossRefGoogle ScholarPubMed
Rogers, RD, Ramnani, N, Mackay, C, Wilson, JL, Jezzard, P, Carter, CS, Smith, SM (2004). Distinct portions of anterior cingulate cortex and medial prefrontal cortex are activated by reward processing in separable phases of decision-making cognition. Biological Psychiatry 55, 594–602.CrossRefGoogle ScholarPubMed
Shackman, AJ, Salomons, TV, Slagter, HA, Fox, AS, Winter, JJ, Davidson, RJ (2011). The integration of negative affect, pain and cognitive control in the cingulate cortex. Nature Reviews Neuroscience 12, 154–167.CrossRefGoogle ScholarPubMed
Shehzad, Z, Kelly, AM, Reiss, PT, Gee, DG, Gotimer, K, Uddin, LQ, Lee, SH, Margulies, DS, Roy, AK, Biswal, BB, Petkova, E, Castellanos, FX, Milham, MP (2009). The resting brain: unconstrained yet reliable. Cerebral Cortex 19, 2209–2229.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
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, Bandettini, PA, Miller, KL, Behrens, TE, Friston, KJ, David, O, Liu, T, Woolrich, MW, Nichols, TE (2012). The danger of systematic bias in group-level FMRI-lag-based causality estimation. NeuroImage 59, 1228–1229.CrossRefGoogle ScholarPubMed
Supekar, K, Musen, M, Menon, V (2009). Development of large-scale functional brain networks in children. PLoS Biology 7, e1000157.CrossRefGoogle ScholarPubMed
Vogt, BA (2005). Pain and emotion interactions in subregions of the cingulate gyrus. Nature Reviews Neuroscience 6, 533–544.CrossRefGoogle ScholarPubMed
Vogt, BA, Vogt, L (2003). Cytology of human dorsal midcingulate and supplementary motor cortices. Journal of Chemical Neuroanatomy 26, 301–309.CrossRefGoogle ScholarPubMed
Wagner, G, Sinsel, E, Sobanski, T, Köhler, S, Marinou, V, Mentzel, HJ, Sauer, H, Schlösser, 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
Zhang, D, Raichle, ME (2010). Disease and the brain's dark energy. Nature Reviews Neurology 6, 15–28.CrossRefGoogle ScholarPubMed
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