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Local cortical thinning links to resting-state disconnectivity in major depressive disorder

Published online by Cambridge University Press:  01 November 2013

M.-J. van Tol
Affiliation:
NeuroImaging Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
M. Li
Affiliation:
Leibniz Institute for Neurobiology, Magdeburg, Germany Clinical Affective Neuroimaging Laboratory, Center for Behavioral Brain Sciences, Magdeburg, Germany State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, People's Republic of China
C. D. Metzger
Affiliation:
Leibniz Institute for Neurobiology, Magdeburg, Germany Clinical Affective Neuroimaging Laboratory, Center for Behavioral Brain Sciences, Magdeburg, Germany Department of Psychiatry and Psychotherapy, Otto von Guericke University, Magdeburg, Germany
N. Hailla
Affiliation:
Clinical Affective Neuroimaging Laboratory, Center for Behavioral Brain Sciences, Magdeburg, Germany Department of Psychiatry and Psychotherapy, Otto von Guericke University, Magdeburg, Germany
D. I. Horn
Affiliation:
Clinical Affective Neuroimaging Laboratory, Center for Behavioral Brain Sciences, Magdeburg, Germany Department of Psychiatry and Psychotherapy, Otto von Guericke University, Magdeburg, Germany
W. Li
Affiliation:
Leibniz Institute for Neurobiology, Magdeburg, Germany Clinical Affective Neuroimaging Laboratory, Center for Behavioral Brain Sciences, Magdeburg, Germany State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, People's Republic of China
H. J. Heinze
Affiliation:
Leibniz Institute for Neurobiology, Magdeburg, Germany Department of Neurology, Otto von Guericke University, Magdeburg, Germany
B. Bogerts
Affiliation:
Department of Psychiatry and Psychotherapy, Otto von Guericke University, Magdeburg, Germany
J. Steiner
Affiliation:
Department of Psychiatry and Psychotherapy, Otto von Guericke University, Magdeburg, Germany
H. He*
Affiliation:
State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, People's Republic of China
M. Walter*
Affiliation:
Leibniz Institute for Neurobiology, Magdeburg, Germany Clinical Affective Neuroimaging Laboratory, Center for Behavioral Brain Sciences, Magdeburg, Germany State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, People's Republic of China Department of Psychiatry and Psychotherapy, Otto von Guericke University, Magdeburg, Germany
*
*Address for correspondence: M. Walter, M.D., Ph.D., Department of Psychiatry and Leibniz Institute for Neurobiology, Otto von Guericke University, Brenneckestrasse 6, 39118 Magdeburg, Germany. (Email: martin.walter@med.ovgu.de) [M. Walter] (Email: huiguang.he@ia.ac.cn) [H. He]
*Address for correspondence: M. Walter, M.D., Ph.D., Department of Psychiatry and Leibniz Institute for Neurobiology, Otto von Guericke University, Brenneckestrasse 6, 39118 Magdeburg, Germany. (Email: martin.walter@med.ovgu.de) [M. Walter] (Email: huiguang.he@ia.ac.cn) [H. He]

Abstract

Background

Local structural and metabolic as well as inter-regional connectivity abnormalities have been implicated in the neuropathology of major depressive disorder (MDD). How local tissue properties affect intrinsic functional connectivity is, however, unclear. Using a cross-sectional, multi-modal imaging approach, we investigated the relationship between local cortical tissue abnormalities and intrinsic resting-state functional connectivity (RSFC) in MDD.

Method

A total of 20 MDD in-patients and 20 healthy controls underwent magnetic resonance imaging at 3 T for structural and functional imaging. Whole-brain cortical thickness was calculated and compared between groups. Regions with reduced cortical thickness defined seeds for subsequent whole-brain RSFC analyses. Contributions of structural tissue abnormalities on inter-regional RSFC were explicitly investigated.

Results

Lower cortical thickness was observed in MDD in the right dorsomedial prefrontal cortex (PFC), superior temporal gyrus/temporal pole, middle-posterior cingulate cortex, and dorsolateral PFC. No differences in local fractional amplitude of low-frequency fluctuations were observed. Lower thickness in patients' dorsomedial PFC further directly and selectively affected its RSFC with the precuneus, which was unaffected by symptom severity. No effects of cortical thickness in other regions showing abnormal thickness were observed to influence functional connectivity.

Conclusions

Abnormal cortical thickness in the dorsomedial PFC in MDD patients was observed to selectively and directly affect its intrinsic connectivity with the precuneus in MDD patients independent of depression severity, thereby marking a potential vulnerability for maladaptive mood regulation. Future studies should include an unmedicated sample and replicate findings using independent component analysis to test for morphometric effects on network integrity.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2013 

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References

Ad-Dab'bagh, Y, Einarson, D, Lyttelton, O, Muehlboeck, J-S, Mok, K, Ivanov, O, Vincent, RD, Lepage, C, Lerch, J, Fombonne, E, Evans, AC (2006). The CIVET Image-Processing Environment: a fully automated comprehensive pipeline for anatomical neuroimaging research. Conference Proceeding. The 12th Annual Meeting of the Organization for Human Brain Mapping (OHBM). (www.bic.mni.mcgill.ca/users/yaddab/Yasser-HBM2006-Poster.pdf). Accessed October 2013.Google Scholar
Allison, T, Puce, A, McCarthy, G (2000). Social perception from visual cues: role of the STS region. Trends in Cognitive Sciences 4, 267278.CrossRefGoogle ScholarPubMed
Anand, A, Li, Y, Wang, Y, Lowe, MJ, Dzemidzic, M (2009). Resting state corticolimbic connectivity abnormalities in unmedicated bipolar disorder and unipolar depression. Psychiatry Research 171, 189198.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, 10791088.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, 550562.CrossRefGoogle ScholarPubMed
Arnone, D, McIntosh, AM, Ebmeier, KP, Munafo, MR, Anderson, IM (2012). Magnetic resonance imaging studies in unipolar depression: systematic review and meta-regression analyses. European Neuropsychopharmacology 22, 116.CrossRefGoogle ScholarPubMed
Ashton, JC (2013). Experimental power comes from powerful theories – the real problem in null hypothesis testing. Nature Reviews. Neuroscience 14, 585.CrossRefGoogle ScholarPubMed
Bacchetti, P (2013). Small sample size is not the real problem. Nature Reviews. Neuroscience 14, 585.CrossRefGoogle Scholar
Beck, AT (2008). The evolution of the cognitive model of depression and its neurobiological correlates. American Journal of Psychiatry 165, 969977.CrossRefGoogle ScholarPubMed
Bermpohl, F, Walter, M, Sajonz, B, Lucke, C, Hagele, C, Sterzer, P, Adli, M, Heinz, A, Northoff, G (2009). Attentional modulation of emotional stimulus processing in patients with major depression – alterations in prefrontal cortical regions. Neuroscience Letters 463, 108113.CrossRefGoogle ScholarPubMed
Bluhm, R, Williamson, P, Lanius, R, Theberge, 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, 754761.CrossRefGoogle ScholarPubMed
Bora, E, Harrison, BJ, Davey, CG, Yucel, M, Pantelis, C (2012). Meta-analysis of volumetric abnormalities in cortico-striatal-pallidal-thalamic circuits in major depressive disorder. Psychological Medicine 42, 671681.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 Science 1124, 138.CrossRefGoogle ScholarPubMed
Button, KS, Ioannidis, JP, Mokrysz, C, Nosek, BA, Flint, J, Robinson, ES, Munafo, MR (2013). Power failure: why small sample size undermines the reliability of neuroscience. Nature Reviews. Neuroscience 14, 365376.CrossRefGoogle ScholarPubMed
Chao-Gan, Y, Yu-Feng, Z (2010). DPARSF: a MATLAB toolbox for “pipeline” data analysis of resting-state fMRI. Frontiers in Systems Neuroscience 4, 13.Google ScholarPubMed
Chung, MK, Worsley, KJ, Robbins, S, Paus, T, Taylor, J, Giedd, JN, Rapoport, JL, Evans, AC (2003). Deformation-based surface morphometry applied to gray matter deformation. Neuroimage 18, 198213.CrossRefGoogle ScholarPubMed
Cole, DM, Smith, SM, Beckmann, CF (2010). Advances and pitfalls in the analysis and interpretation of resting-state FMRI data. Frontiers in Systems Neuroscience 4, 8.Google ScholarPubMed
Cox, RW, Hyde, JS (1997). Software tools for analysis and visualization of fMRI data. NMR in Biomedicine 10, 171178.3.0.CO;2-L>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, 227231.CrossRefGoogle ScholarPubMed
Fox, MD, Zhang, D, Snyder, AZ, Raichle, ME (2009). The global signal and observed anticorrelated resting state brain networks. Journal of Neurophysiology 101, 32703283.CrossRefGoogle ScholarPubMed
Friston, K (2012). Ten ironic rules for non-statistical reviewers. Neuroimage 61, 13001310.CrossRefGoogle ScholarPubMed
Frodl, T, Jäger, M, Born, C, Ritter, S, Kraft, E, Zetzsche, T, Bottlender, R, Leinsinger, G, Reiser, M, Müller, HJ, Meisenzahl, E (2008). Anterior cingulate cortex does not differ between patients with major depression and healthy controls, but relatively large anterior cingulate cortex predicts a good clinical course. Psychiatry Research: Neuroimaging 163, 7683.CrossRefGoogle Scholar
Frodl, T, Meisenzahl, EM, Zetzsche, T, Hohne, T, Banac, S, Schorr, C, Jager, M, Leinsinger, G, Bottlender, R, Reiser, M, Moller, HJ (2004). Hippocampal and amygdala changes in patients with major depressive disorder and healthy controls during a 1-year follow-up. Journal of Clinical Psychiatry 65, 492499.CrossRefGoogle ScholarPubMed
Germine, LT, Garrido, L, Bruce, L, Hooker, C (2011). Social anhedonia is associated with neural abnormalities during face emotion processing. Neuroimage 58, 935945.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, 429437.CrossRefGoogle ScholarPubMed
Greicius, MD, Supekar, K, Menon, V, Dougherty, RF (2009). Resting-state functional connectivity reflects structural connectivity in the default mode network. Cerebral Cortex 19, 7278.CrossRefGoogle ScholarPubMed
Grimm, S, Ernst, J, Boesiger, P, Schuepbach, D, Boeker, H, Northoff, G (2011). Reduced negative BOLD responses in the default-mode network and increased self-focus in depression. World Journal of Biological Psychiatry 12, 627637.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, 26172627.CrossRefGoogle ScholarPubMed
Grimm, S, Luborzewski, A, Schubert, F, Merkl, A, Kronenberg, G, Colla, M, Heuser, I, Bajbouj, M (2012). Region-specific glutamate changes in patients with unipolar depression. Journal of Psychiatric Research 46, 10591065.CrossRefGoogle ScholarPubMed
Hamilton, M (1960). A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry 23, 5662.CrossRefGoogle ScholarPubMed
Holtzheimer, PE, Mayberg, HS (2011). Stuck in a rut: rethinking depression and its treatment. Trends in Neurosciences 34, 19.CrossRefGoogle Scholar
Honey, CJ, Sporns, O, Cammoun, L, Gigandet, X, Thiran, JP, Meuli, R, Hagmann, P (2009). Predicting human resting-state functional connectivity from structural connectivity. Proceedings of the National Academy of Sciences USA 106, 20352040.CrossRefGoogle ScholarPubMed
Horn, DI, Yu, C, Steiner, J, Buchmann, J, Kaufmann, J, Osoba, A, Eckert, U, Zierhut, KC, Schiltz, K, He, H, Biswal, B, Bogerts, B, Walter, M (2010). Glutamatergic and resting-state functional connectivity correlates of severity in major depression – the role of pregenual anterior cingulate cortex and anterior insula. Frontiers in Systems Neuroscience 4, 33.Google ScholarPubMed
Jarnum, H, Eskildsen, SF, Steffensen, EG, Lundbye-Christensen, S, Simonsen, CW, Thomsen, IS, Frund, ET, Theberge, J, Larsson, EM (2011). Longitudinal MRI study of cortical thickness, perfusion, and metabolite levels in major depressive disorder. Acta Psychiatrica Scandinavica 124, 435446.CrossRefGoogle ScholarPubMed
Koolschijn, PC, van Haren, NE, Lensvelt-Mulders, GJ, Hulshoff Pol, HE, Kahn, RS (2009). Brain volume abnormalities in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Human Brain Mapping 30, 37193735.CrossRefGoogle ScholarPubMed
Leppanen, JM (2006). Emotional information processing in mood disorders: a review of behavioral and neuroimaging findings. Current Opinion in Psychiatry 19, 3439.CrossRefGoogle ScholarPubMed
Lindquist, MA, Caffo, B, Crainiceanu, C (2013). Ironing out the statistical wrinkles in ‘ten ironic rules’. Neuroimage 81, 499502.CrossRefGoogle ScholarPubMed
Lui, S, Wu, Q, Qiu, L, Yang, X, Kuang, W, Chan, RC, Huang, X, Kemp, GJ, Mechelli, A, Gong, Q (2011). Resting-state functional connectivity in treatment-resistant depression. American Journal of Psychiatry 168, 642648.CrossRefGoogle ScholarPubMed
Ma, C, Ding, J, Li, J, Guo, W, Long, Z, Liu, F, Gao, Q, Zeng, L, Zhao, J, Chen, H (2012). Resting-state functional connectivity bias of middle temporal gyrus and caudate with altered gray matter volume in major depression. PLoS ONE 7, e45263.CrossRefGoogle ScholarPubMed
Mayberg, HS (1997). Limbic–cortical dysregulation: a proposed model of depression. Journal of Neuropsychiatry 9, 471481.Google ScholarPubMed
McKinnon, MC, Yucel, K, Nazarov, A, MacQueen, GM (2009). A meta-analysis examining clinical predictors of hippocampal volume in patients with major depressive disorder. Journal of Psychiatry and Neuroscience 34, 4154.Google ScholarPubMed
Murphy, K, Birn, RM, Handwerker, DA, Jones, TB, Bandettini, PA (2009). The impact of global signal regression on resting state correlations: are anti-correlated networks introduced? Neuroimage 44, 893905.CrossRefGoogle ScholarPubMed
Ochsner, KN, Silvers, JA, Buhle, JT (2012). Functional imaging studies of emotion regulation: a synthetic review and evolving model of the cognitive control of emotion. Annals of the New York Academy of Science 1251, E1E24.CrossRefGoogle ScholarPubMed
Pfleiderer, B, Michael, N, Erfurth, A, Ohrmann, P, Hohmann, U, Wolgast, M, Fiebich, M, Arolt, V, Heindel, W (2003). Effective electroconvulsive therapy reverses glutamate/glutamine deficit in the left anterior cingulum of unipolar depressed patients. Psychiatry Research 122, 185192.CrossRefGoogle ScholarPubMed
Phillips, ML, Drevets, WC, Rauch, SL, Lane, R (2003). Neurobiology of emotion perception II: implications for major psychiatric disorders. Biological Psychiatry 54, 515528.CrossRefGoogle ScholarPubMed
Power, JD, Barnes, KA, Snyder, AZ, Schlaggar, BL, Petersen, SE (2012). Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. Neuroimage 59, 21422154.CrossRefGoogle ScholarPubMed
Price, JL, Drevets, WC (2010). Neurocircuitry of mood disorders. Neuropsychopharmacology 35, 192216.CrossRefGoogle ScholarPubMed
Quinlan, PT (2013). Misuse of power: in defence of small-scale science. Nature Reviews. Neuroscience 14, 585.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, 676682.CrossRefGoogle ScholarPubMed
Rajkowska, G, Miguel-Hidalgo, JJ (2007). Gliogenesis and glial pathology in depression. CNS and Neurological Disorders Drug Targets 6, 219233.CrossRefGoogle ScholarPubMed
Saleem, KS, Kondo, H, Price, JL (2008). Complementary circuits connecting the orbital and medial prefrontal networks with the temporal, insular, and opercular cortex in the macaque monkey. Journal of Comparative Neurology 506, 659693.CrossRefGoogle ScholarPubMed
Seeley, WW, Menon, V, Schatzberg, AF, Keller, J, Glover, GH, Kenna, H, Reiss, AL, Greicius, MD (2007). Dissociable intrinsic connectivity networks for salience processing and executive control. Journal of Neuroscience 27, 23492356.CrossRefGoogle ScholarPubMed
Sheehan, DV, Lecrubier, Y, Sheehan, KH, Amorim, P, Janavs, J, Weiller, E, Hergueta, T, Baker, R, Dunbar, GC (1998). The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry 59 (Suppl. 20), 2233.Google 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, 1102011025.CrossRefGoogle ScholarPubMed
Song, XW, Dong, ZY, Long, XY, Li, SF, Zuo, XN, Zhu, CZ, He, Y, Yan, CG, Zang, YF (2011). REST: a toolkit for resting-state functional magnetic resonance imaging data processing. PLoS ONE 6, e25031.CrossRefGoogle Scholar
Taylor, SF, Kang, J, Brege, IS, Tso, IF, Hosanagar, A, Johnson, TD (2012). Meta-analysis of functional neuroimaging studies of emotion perception and experience in schizophrenia. Biological Psychiatry 71, 136145.CrossRefGoogle ScholarPubMed
van Harmelen, AL, van Tol, MJ, van der Wee, NJ, Veltman, DJ, Aleman, A, Spinhoven, P, van Buchem, MA, Zitman, FG, Penninx, BW, Elzinga, BM (2010). Reduced medial prefrontal cortex volume in adults reporting childhood emotional maltreatment. Biological Psychiatry 68, 832838.CrossRefGoogle ScholarPubMed
van Tol, MJ, van der Wee, NJ, van den Heuvel, OA, Nielen, MM, Demenescu, LR, Aleman, A, Renken, R, van Buchem, MA, Zitman, FG, Veltman, DJ (2010). Regional brain volume in depression and anxiety disorders. Archives of General Psychiatry 67, 10021011.CrossRefGoogle ScholarPubMed
Veer, IM, Beckmann, CF, van Tol, MJ, Ferrarini, L, Milles, J, Veltman, DJ, Aleman, A, van Buchem, MA, van der Wee, NJ, Rombouts, SA (2010). Whole brain resting-state analysis reveals decreased functional connectivity in major depression. Frontiers in Systems Neuroscience 4, 41.CrossRefGoogle ScholarPubMed
Vohn, R, Fimm, B, Weber, J, Schnitker, R, Thron, A, Spijkers, W, Willmes, K, Sturm, W (2007). Management of attentional resources in within-modal and cross-modal divided attention tasks: an fMRI study. Human Brain Mapping 28, 12671275.CrossRefGoogle ScholarPubMed
Walter, M, Henning, A, Grimm, S, Schulte, RF, Beck, J, Dydak, U, Schnepf, B, Boeker, H, Boesiger, P, Northoff, G (2009 a). The relationship between aberrant neuronal activation in the pregenual anterior cingulate, altered glutamatergic metabolism, and anhedonia in major depression. Archives of General Psychiatry 66, 478486.CrossRefGoogle ScholarPubMed
Walter, M, Matthia, C, Wiebking, C, Rotte, M, Tempelmann, C, Bogerts, B, Heinze, HJ, Northoff, G (2009 b). Preceding attention and the dorsomedial prefrontal cortex: process specificity versus domain dependence. Human Brain Mapping 30, 312326.CrossRefGoogle ScholarPubMed
Wang, L, Hermans, DF, Hickie, IB, Lagopoulos, J (2012). A systematic review of resting-state functional-MRI studies in major depression. Journal of Affective Disorders 142, 612.CrossRefGoogle ScholarPubMed
Wang, AT, Lee, SS, Sigman, M, Dapretto, M (2007). Reading affect in the face and voice: neural correlates of interpreting communicative intent in children and adolescents with autism spectrum disorders. Archives of General Psychiatry 64, 698708.CrossRefGoogle ScholarPubMed
Weissenbacher, A, Kasess, C, Gerstl, F, Lanzenberger, R, Moser, E, Windischberger, C (2009). Correlations and anticorrelations in resting-state functional connectivity MRI: a quantitative comparison of preprocessing strategies. Neuroimage 47, 14081416.CrossRefGoogle ScholarPubMed
Whitfield-Gabrieli, S, Ford, JM (2012). Default mode network activity and connectivity in psychopathology. Annual Review of Clinical Psychology 8, 4976.CrossRefGoogle ScholarPubMed
World Health Organization (1992). ICD-10 Classifications of Mental and Behavioural Disorder: Clinical Descriptions and Diagnostic Guidelines. World Health Organization: Geneva.Google Scholar
Yuksel, C, Ongur, D (2010). Magnetic resonance spectroscopy studies of glutamate-related abnormalities in mood disorders. Biological Psychiatry 68, 785794.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, 611617.CrossRefGoogle ScholarPubMed
Zijdenbos, AP, Forghani, R, Evans, AC (2002). Automatic “pipeline” analysis of 3-D MRI data for clinical trials: application to multiple sclerosis. IEEE Transactions on Medical Imaging 21, 12801291.CrossRefGoogle ScholarPubMed
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