Skip to main content Accessibility help

Altered global brain network topology as a trait marker in patients with anorexia nervosa

  • Daniel Geisler (a1), Viola Borchardt (a2) (a3), Ilka Boehm (a1), Joseph A. King (a1), Friederike I. Tam (a1) (a4), Michael Marxen (a5), Ronald Biemann (a6), Veit Roessner (a4), Martin Walter (a2) (a3) (a7) (a8) and Stefan Ehrlich (a1) (a4)...



Resting state functional magnetic resonance imaging studies have identified functional connectivity patterns associated with acute undernutrition in anorexia nervosa (AN), but few have investigated recovered patients. Thus, a trait connectivity profile characteristic of the disorder remains elusive. Using state-of-the-art graph–theoretic methods in acute AN, the authors previously found abnormal global brain network architecture, possibly driven by local network alterations. To disentangle trait from starvation effects, the present study examines network organization in recovered patients.


Graph–theoretic metrics were used to assess resting-state network properties in a large sample of female patients recovered from AN (recAN, n = 55) compared with pairwise age-matched healthy controls (HC, n = 55).


Indicative of an altered global network structure, recAN showed increased assortativity and reduced global clustering as well as small-worldness compared with HC, while no group differences at an intermediate or local network level were evident. However, using support-vector classifier on local metrics, recAN and HC could be separated with an accuracy of 70.4%.


This pattern of results suggests that long-term recovered patients have an aberrant global brain network configuration, similar to acutely underweight patients. While the finding of increased assortativity may represent a trait marker of AN, the remaining findings could be seen as a scar following prolonged undernutrition.


Corresponding author

Author for correspondence: Stefan Ehrlich, E-mail:


Hide All
Achard, S and Bullmore, E (2007) Efficiency and cost of economical brain functional networks. PLoS Computational Biology 3, e17.
Arbabshirani, MR, Plis, S, Sui, J and Calhoun, VD (2017) Single subject prediction of brain disorders in neuroimaging: promises and pitfalls. NeuroImage 145, 137165.
Armstrong, CC, Moody, TD, Feusner, JD, McCracken, JT, Chang, S, Levitt, JG, Piacentini, JC and O'Neill, J (2016) Graph-theoretical analysis of resting-state fMRI in pediatric obsessive-compulsive disorder. Journal of Affective Disorders 193, 175184.
Bernardoni, F, King, JA, Geisler, D, Stein, E, Jaite, C, Nätsch, D, Tam, FI, Boehm, I, Seidel, M, Roessner, V and Ehrlich, S (2016) Weight restoration therapy rapidly reverses cortical thinning in anorexia nervosa: a longitudinal study. NeuroImage 130, 214222.
Biezonski, D, Cha, J, Steinglass, J and Posner, J (2016) Evidence for thalamocortical circuit abnormalities and associated cognitive dysfunctions in underweight individuals with anorexia nervosa. Neuropsychopharmacology 41, 15601568.
Boehm, I, Geisler, D, King, JA, Ritschel, F, Seidel, M, Deza Araujo, Y, Petermann, J, Lohmeier, H, Weiss, J, Walter, M, Roessner, V and Ehrlich, S (2014) Increased resting state functional connectivity in the fronto-parietal and default mode network in anorexia nervosa. Frontiers in Behavioral Neuroscience 8, 346.
Boehm, I, Geisler, D, Tam, F, King, JA, Ritschel, F, Seidel, M, Bernardoni, F, Murr, J, Goschke, T, Calhoun, VD, Roessner, V and Ehrlich, S (2016) Partially restored resting-state functional connectivity in women recovered from anorexia nervosa. Journal of Psychiatry & Neuroscience: JPN 41, 377385.
Bullmore, E and Sporns, O (2009) Complex brain networks: graph theoretical analysis of structural and functional systems. Nature reviews. Neuroscience 10, 186198.
Bullmore, ET and Bassett, DS (2011) Brain graphs: graphical models of the human brain connectome. Annual Review of Clinical Psychology 7, 113140.
Cabral, J, Hugues, E, Kringelbach, ML and Deco, G (2012) Modeling the outcome of structural disconnection on resting-state functional connectivity. NeuroImage 62, 13421353.
Castellanos, FX, Margulies, DS, Kelly, C, Uddin, LQ, Ghaffari, M, Kirsch, A, Shaw, D, Shehzad, Z, Di Martino, A, Biswal, B, Sonuga-Barke, EJS, Rotrosen, J, Adler, LA and Milham, MP (2008) Cingulate-precuneus interactions: a new locus of dysfunction in adult attention-deficit/hyperactivity disorder. Biological Psychiatry 63, 332337.
Cole, MW and Schneider, W (2007) The cognitive control network: integrated cortical regions with dissociable functions. NeuroImage 37, 343360.
Collantoni, E, Michelon, S, Tenconi, E, Degortes, D, Titton, F, Manara, R, Clementi, M, Pinato, C, Forzan, M, Cassina, M, Santonastaso, P and Favaro, A (2016) Functional connectivity correlates of response inhibition impairment in anorexia nervosa. Psychiatry Research 247, 916.
Cowdrey, FA, Park, RJ, Harmer, CJ and McCabe, C (2011) Increased neural processing of rewarding and aversive food stimuli in recovered anorexia nervosa. Biological Psychiatry 70, 736743.
Cowdrey, FA, Filippini, N, Park, RJ, Smith, SM and McCabe, C (2014) Increased resting state functional connectivity in the default mode network in recovered anorexia nervosa. Human Brain Mapping 35, 483491.
Decker, JH, Figner, B and Steinglass, JE (2015) On weight and waiting: delay discounting in anorexia nervosa pretreatment and posttreatment. Biological Psychiatry 78, 606614.
Dosenbach, NUF, 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, Barch, DM, Petersen, SE and Schlaggar, BL (2010) Prediction of individual brain maturity using fMRI. Science (New York, N.Y.) 329, 13581361.
Ehrlich, S, Lord, AR, Geisler, D, Borchardt, V, Boehm, I, Seidel, M, Ritschel, F, Schulze, A, King, JA, Weidner, K, Roessner, V and Walter, M (2015) Reduced functional connectivity in the thalamo-insular subnetwork in patients with acute anorexia nervosa. Human Brain Mapping 36, 17721781.
Favaro, A, Santonastaso, P, Manara, R, Bosello, R, Bommarito, G, Tenconi, E and Di Salle, F (2012) Disruption of visuospatial and somatosensory functional connectivity in anorexia nervosa. Biological Psychiatry 72, 864870.
Favaro, A, Tenconi, E, Degortes, D, Manara, R and Santonastaso, P (2014) Effects of obstetric complications on volume and functional connectivity of striatum in anorexia nervosa patients. The International Journal of Eating Disorders 47, 686695.
Fladung, A-K, Grön, G, Grammer, K, Herrnberger, B, Schilly, E, Grasteit, S, Wolf, RC, Walter, H and von Wietersheim, J (2010) A neural signature of anorexia nervosa in the ventral striatal reward system. The American Journal of Psychiatry 167, 206212.
Foerde, K, Steinglass, JE, Shohamy, D and Walsh, BT (2015) Neural mechanisms supporting maladaptive food choices in anorexia nervosa. Nature Neuroscience 18, 15711573.
Fornito, A, Bullmore, ET and Zalesky, A (2017) Opportunities and challenges for psychiatry in the connectomic era. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging 2, 919.
Fox, MD, Zhang, D, Snyder, AZ and Raichle, ME (2009) The global signal and observed anticorrelated resting state brain networks. Journal of Neurophysiology 101, 32703283.
Frank, GKW, Shott, ME, Riederer, J and Pryor, TL (2016) Altered structural and effective connectivity in anorexia and bulimia nervosa in circuits that regulate energy and reward homeostasis. Translational Psychiatry 6, e932.
Gaudio, S, Wiemerslage, L, Brooks, SJ and Schiöth, HB (2016) A systematic review of resting-state functional-MRI studies in anorexia nervosa: evidence for functional connectivity impairment in cognitive control and visuospatial and body-signal integration. Neuroscience and Biobehavioral Reviews 71, 578589.
Gaudio, S, Olivo, G, Beomonte Zobel, B and Schiöth, HB (2018) Altered cerebellar-insular-parietal-cingular subnetwork in adolescents in the earliest stages of anorexia nervosa: a network-based statistic analysis. Translational Psychiatry 8, 127.
Geisler, D, Borchardt, V, Lord, AR, Boehm, I, Ritschel, F, Zwipp, J, Clas, S, King, JA, Wolff-Stephan, S, Roessner, V, Walter, M and Ehrlich, S (2016) Abnormal functional global and local brain connectivity in female patients with anorexia nervosa. Journal of Psychiatry & Neuroscience: JPN 41, 615.
Gorgolewski, K, Burns, CD, Madison, C, Clark, D, Halchenko, YO, Waskom, ML and Ghosh, SS (2011) Nipype: a flexible, lightweight and extensible neuroimaging data processing framework in python. Frontiers in Neuroinformatics 5, 13.
Greicius, MD, Krasnow, B, Reiss, AL and Menon, V (2003) Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proceedings of the National Academy of Sciences of the United States of America 100, 253258.
Gunn, SR (1998) Support Vector Machines for Classification and Regression. Technical Report no. 14. Southampton: School of Electronics and Computer Science, pp. 8586.
Holsen, LM, Lawson, EA, Blum, J, Ko, E, Makris, N, Fazeli, PK, Klibanski, A and Goldstein, JM (2012) Food motivation circuitry hypoactivation related to hedonic and nonhedonic aspects of hunger and satiety in women with active anorexia nervosa and weight-restored women with anorexia nervosa. Journal of Psychiatry & Neuroscience: JPN 37, 322332.
Kaye, WH, Wierenga, CE, Bailer, UF, Simmons, AN and Bischoff-Grethe, A (2013) Nothing tastes as good as skinny feels: the neurobiology of anorexia nervosa. Trends in Neurosciences 36, 110120.
King, JA, Geisler, D, Ritschel, F, Boehm, I, Seidel, M, Roschinski, B, Soltwedel, L, Zwipp, J, Pfuhl, G, Marxen, M, Roessner, V and Ehrlich, S (2015) Global cortical thinning in acute anorexia nervosa normalizes following long-term weight restoration. Biological Psychiatry 77, 624632.
King, JA, Frank, GKW, Thompson, PM and Ehrlich, S (2018) Structural neuroimaging of anorexia nervosa: future directions in the quest for mechanisms underlying dynamic alterations. Biological Psychiatry 83, 224234.
Kullmann, S, Giel, KE, Teufel, M, Thiel, A, Zipfel, S and Preissl, H (2014) Aberrant network integrity of the inferior frontal cortex in women with anorexia nervosa. NeuroImage: Clinical 4, 615622.
Lord, A, Ehrlich, S, Borchardt, V, Geisler, D, Seidel, M, Huber, S, Murr, J and Walter, M (2016) Brain parcellation choice affects disease-related topology differences increasingly from global to local network levels. Psychiatry Research 249, 1219.
Lynall, M-E, Bassett, DS, Kerwin, R, McKenna, PJ, Kitzbichler, M, Muller, U and Bullmore, E (2010) Functional connectivity and brain networks in schizophrenia. The Journal of Neuroscience 30, 94779487.
Merle, JV, Haas, V, Burghardt, R, Döhler, N, Schneider, N, Lehmkuhl, U and Ehrlich, S (2011) Agouti-related protein in patients with acute and weight-restored anorexia nervosa. Psychological Medicine 41, 21832192.
Newman, MEJ (2002) Assortative mixing in networks. Physical Review Letters 89, 208701.
Ojala, M and Garriga, GC (2010) Permutation tests for studying classifier performance. Journal of Machine Learning Research 11, 18331863.
Pedregosa, F, Varoquaux, G, Gramfort, A, Michel, V, Thirion, B, Grisel, O, Blondel, M, Prettenhofer, P, Weiss, R and Dubourg, V and others (2011). Scikit-learn: machine learning in python. Journal of Machine Learning Research 12, 28252830.
Pfuhl, G, King, JA, Geisler, D, Roschinski, B, Ritschel, F, Seidel, M, Bernardoni, F, Müller, DK, White, T, Roessner, V and Ehrlich, S (2016) Preserved white matter microstructure in young patients with anorexia nervosa? Human Brain Mapping 37, 40694083.
Power, JD, Barnes, KA, Snyder, AZ, Schlaggar, BL and Petersen, SE (2012) Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. NeuroImage 59, 21422154.
Rubinov, M and Sporns, O (2010) Complex network measures of brain connectivity: uses and interpretations. NeuroImage 52, 10591069.
Schorr, M and Miller, KK (2017) The endocrine manifestations of anorexia nervosa: mechanisms and management. Nature Reviews Endocrinology 13, 174186.
Seeley, WW, Menon, V, Schatzberg, AF, Keller, J, Glover, GH, Kenna, H, Reiss, AL and Greicius, MD (2007) Dissociable intrinsic connectivity networks for salience processing and executive control. The Journal of Neuroscience 27, 23492356.
Steinhausen, H-C (2002) The outcome of anorexia nervosa in the 20th century. The American Journal of Psychiatry 159, 12841293.
van den Heuvel, MP and Sporns, O (2011) Rich-club organization of the human connectome. The Journal of Neuroscience 31, 1577515786.
van den Heuvel, MP, de Lange, SC, Zalesky, A, Seguin, C, Yeo, BTT and Schmidt, R (2017) Proportional thresholding in resting-state fMRI functional connectivity networks and consequences for patient-control connectome studies: issues and recommendations. NeuroImage 152, 437449.
Vatansever, D, Menon, DK, Manktelow, AE, Sahakian, BJ and Stamatakis, EA (2015) Default mode dynamics for global functional integration. The Journal of Neuroscience 35, 1525415262.
Vogel, K, Timmers, I, Kumar, V, Nickl-Jockschat, T, Bastiani, M, Roebroek, A, Herpertz-Dahlmann, B, Konrad, K, Goebel, R and Seitz, J (2016) White matter microstructural changes in adolescent anorexia nervosa including an exploratory longitudinal study. NeuroImage: Clinical 11, 614621.
Wagner, A, Greer, P, Bailer, UF, Frank, GK, Henry, SE, Putnam, K, Meltzer, CC, Ziolko, SK, Hoge, J, McConaha, C and Kaye, WH (2006) Normal brain tissue volumes after long-term recovery in anorexia and bulimia nervosa. Biological Psychiatry 59, 291293.
Whitfield-Gabrieli, S and Ford, JM (2012) Default mode network activity and connectivity in psychopathology. Annual Review of Clinical Psychology 8, 4976.
Wierenga, CE, Bischoff-Grethe, A, Melrose, AJ, Irvine, Z, Torres, L, Bailer, UF, Simmons, A, Fudge, JL, McClure, SM, Ely, A and Kaye, WH (2015) Hunger does not motivate reward in women remitted from anorexia nervosa. Biological Psychiatry 77, 642652.
Zalesky, A, Fornito, A and Bullmore, ET (2010) Network-based statistic: identifying differences in brain networks. NeuroImage 53, 11971207.
Zhang, A, Leow, A, Zhan, L, GadElkarim, J, Moody, T, Khalsa, S, Strober, M and Feusner, JD (2016) Brain connectome modularity in weight-restored anorexia nervosa and body dysmorphic disorder. Psychological Medicine 46, 27852797.


Type Description Title
Supplementary materials

Geisler et al. supplementary material
Geisler et al. supplementary material 1

 PDF (4.0 MB)
4.0 MB


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed