Abstract
Bulimia nervosa (BN) is characterized by dysregulated intake of food, which may indicate homeostatic imbalance. Critically important for homeostatic regulation is interoception, or the sensing and processing of body-relevant information. A well-documented link between avoidance of unpleasant body sensations and BN symptoms suggests that aversive interoceptive experiences may be particularly relevant to BN pathophysiology. This study examined whether individuals with a history of BN show aberrant neural processing of aversive interoceptive stimuli. Using a cued inspiratory breathing load paradigm, we compared women remitted from BN (RBN; n = 24; to reduce the confounding effects of active bulimic symptoms) and control women (CW; n = 25). During breathing load anticipation, the RBN group, relative to CW, showed increased activation in mid-insula, superior frontal gyrus, putamen, dorsal anterior cingulate, posterior cingulate, and amygdala. However, over the course of the aversive experience, neural activation in RBN relative to CW showed an aberrant decline in most of these regions. Exploratory analyses indicated that greater activation during breathing load anticipation was associated with past bulimic symptom severity and the duration of symptom remission. An exaggerated anticipatory response and an abnormally decreasing response during aversive homeostatic perturbations may promote hallmark bulimic behaviors—binge eating, dietary restriction, and purging. Our findings support a role for homeostatic instability in BN, and these altered patterns of brain activation may serve as novel targets for pharmacological, neuromodulatory, and behavioral interventions.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: Fifth Edition (DSM-5). Washington. DC: American Psychiatric Association; 2013.
Santangelo P, Reinhard I, Mussgay L, Steil R, Sawitzki G, Klein C, et al. Specificity of affective instability in patients with borderline personality disorder compared to posttraumatic stress disorder, bulimia nervosa, and healthy controls. J Abnorm Psychol. 2014;123:258–72. https://doi.org/10.1037/a0035619.
Craig A. Interoception: the sense of the physiologial condition of the body. Curr Opin Neurobiol. 2003;13:500–5.
Craig A. Interoception and emotion: a neuroanatomical perspective, In: Lewis, M., Haviland-Jones, J. M. and Barrett, L. F., editors. Handbook of Emotions, The Guildford Press; New York, 2008.
Klabunde M, Collado D, Bohon C. An interoceptive model of bulimia nervosa: a neurobiological systematic review. J Psychiatr Res. 2017;94:36–46. https://doi.org/10.1016/j.jpsychires.2017.06.009.
Lautenbacher S, Pauls AM, Strian F, Pirke K-M, Krieg J-C. Pain sensitivity in anorexia nervosa and bulimia nervosa. Biol Psychiatry. 1991;29:1073–8. https://doi.org/10.1016/0006-3223(91)90249-L.
Stein D, Kaye W, Matsunaga H, Myers D, Orbach I, Har-Even D, et al. Pain perception in recoverd bulimia nervosa patients. Int J Eat Disord. 2003;34:331–6.
Walsh BT, Zimmerli E, Devlin MJ, Guss J, Kissileff HR. A disturbance of gastric function in bulimia nervosa. Biol Psychiatry. 2003;54:929–33.
Klabunde M, Acheson D, Boutelle K, Matthews S, Kaye W. Interoceptive sensitivity deficits in women recovered from bulimia nervosa. Eat Behav. 2013;14:488–92.
Pollatos O, Georgiou E. Normal interoceptive accuracy in women with bulimia nervosa. Psychiatry Res. 2016;240:328–32. https://doi.org/10.1016/j.psychres.2016.04.072.
Khalsa SS, Adolphs R, Cameron OG, Critchley HD, Davenport PW, Feinstein JS, et al. Interoception and mental health: a roadmap. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018;3:501–13. https://doi.org/10.1016/j.bpsc.2017.12.004.
Barrett LF, Simmons WK. Interoceptive predictions in the brain. Nat Rev Neurosci. 2015;16:419–29. https://doi.org/10.1038/nrn3950.
Menon M, Jensen J, Vitcu I, Graff-Guerrero A, Crawley A, Smith M, et al. Temporal difference modeling of the blood-oxygen level dependent response during aversive conditioning in humans: effects of dopaminergic modulation. Biol Psychiatry. 2007;62:765–72.
Delgado M, Li J, Schiller D, Phelps E. The role of the striatum in aversive learning and aversive prediction errors. Philos Trans R Soc B. 2008;363:3787–800.
Simmons WK, Avery JA, Barcalow JC, Bodurka J, Drevets WC, Bellgowan P. Keeping the body in mind: insula functional organization and functional connectivity integrate interoceptive, exteroceptive, and emotional awareness. Human Brain Mapp. 2013;34:2944–58. https://doi.org/10.1002/hbm.22113.
Hayes DJ, Northoff G. Common brain activations for painful and non-painful aversive stimuli. BMC Neurosci. 2012;13:60. https://doi.org/10.1186/1471-2202-13-60.
Critchley HD, Wiens S, Rotshtein P, Ohman A, Dolan RJ. Neural systems supporting interoceptive awareness. Nat Neurosci. 2004;7:189–95.
Peiffer C. Dyspnea relief: more than just the perception of a decrease in dyspnea. Respir Physiol Neurobiol. 2009;167:61–71.
Frank G, Shott M, Hagman J, Mittal V. Alterations in brain structures related to taste reward circuitry in ill and recovered anorexia nervosa and in bulimia nervosa. Am J Psychiatry. 2013;170:1152–60. https://doi.org/10.1176/appi.ajp.2013.12101294.
Frank GKW, Shott ME, Riederer J, Pryor TL. Altered structural and effective connectivity in anorexia and bulimia nervosa in circuits that regulate energy and reward homeostasis. Transl Psychiatry. 2016;6:e932. https://doi.org/10.1038/tp.2016.199.
Frank G, Wagner A, Brooks-Achenbach S, McConaha C, Skovira K, Aizenstein H, et al. Altered brain activity in women recovered from bulimic type eating disorders after a glucose challenge. A pilot study. Int J Eat Disord. 2006;39:76–9.
Wagner A, Simmons AN, Oberndorfer TA, Frank GKW, McCurdy-McKinnon D, Fudge JL, et al. Altered sensitization patterns to sweet food stimuli in patients recovered from anorexia and bulimia nervosa. Psychiatry Res: Neuroimaging. 2015;234:305–13. https://doi.org/10.1016/j.pscychresns.2015.10.010.
Monteleone AM, Monteleone P, Esposito F, Prinster A, Volpe U, Cantone E, et al. Altered processing of rewarding and aversive basic taste stimuli in symptomatic women with anorexia nervosa and bulimia nervosa: An fMRI study. J Psychiatr Res. 2017;90:94–101. https://doi.org/10.1016/j.jpsychires.2017.02.013.
Bohon C, Stice E. Reward abnormalities among women with full and subthreshold bulimia nervosa: a functional magnetic resonance imaging study. Int J Eat Disord. 2011;44:585–95. https://doi.org/10.1002/eat.20869.
Oberndorfer T, Frank G, Fudge J, Simmons A, Paulus M, Wagner A, et al. Altered insula response to sweet taste processing after recovery from anorexia and bulimia nervosa. Am J Psychiatry. 2013;214:132–41. https://doi.org/10.1176/appi.ajp.2013.11111745.
Ceunen E, Vlaeyen JWS, Van Diest I. On the origin of interoception. Front Psychol. 2016;7:743. https://doi.org/10.3389/fpsyg.2016.00743.
Heatherton T, Baumeister T. Binge eating as an escape from self-awareness. Psychol Bull. 1991;110:86–108.
Hayaki J. Negative reinforcement eating expectancies, emotion dysregulation, and symptoms of bulimia nervosa. Int J Eat Disord. 2009;42:552–6. https://doi.org/10.1002/eat.20646.
Culbert KM, Racine SE, Klump KL. Research review: what we have learned about the causes of eating disorders–a synthesis of sociocultural, psychological, and biological research. J Child Psychol Psychiatry. 2015;56:1141–64.
Penas-Lledo E, Vaz FJ, Ramos MI, Waller G. Impulsive behaviors in bulimic patients: relation to general psychopathology. Int J Eat Disord. 2002;32:98–102.
Stewart JL, Juavinett AL, May AC, Davenport PW, Paulus MP. Do you feel alright? Attenuated neural processing of aversive interoceptive stimuli in current stimulant users. Psychophysiology. 2015;52:249–62.
Stewart JL, May AC, Poppa T, Davenport PW, Tapert SF, Paulus MP. You are the danger: attenuated insula response in methamphetamine users during aversive interoceptive decision-making. Drug Alcohol Depend. 2014;142:110–9. https://doi.org/10.1016/j.drugalcdep.2014.06.003.
Berner LA, Simmons AN, Wierenga CE, Bischoff-Grethe A, Paulus MP, Bailer UF, et al. Altered interoceptive activation before, during, and after aversive breathing load in women remitted from anorexia nervosa. Psychol Med. 2018;48:142–54. https://doi.org/10.1017/s0033291717001635.
Kaye W, Wierenga C, Bailer U, Simmons A, Wagner A, Bischoff-Grethe A. Does a shared neurobiology for foods and drugs of abuse contribute to extremes of food ingestion in anorexia and bulimia nervosa? Biol Psychiatry. 2013;73:836–42. https://doi.org/10.1016/j.biopsych.2013.01.002.
Dawe S, Loxton N. The role of impulsivity in the development of substance use and eating disorders. Neurosci Biobehav Rev. 2004;29:343–51.
Moscarello JM, LeDoux JE. The contribution of the amygdala to aversive and appetitive pavlovian processes. Emot Rev. 2013;5:248–53. https://doi.org/10.1177/1754073913477508.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: Fouth Edition (DSM-IV). Washington, DC: American Psychiatric Association; 1994.
Haase L, May AC, Falahpour M, Isakovic S, Simmons AN, Hickman SD, et al. A pilot study investigating changes in neural processing after mindfulness training in elite athletes. Front Behav Neurosci. 2015;9:229. https://doi.org/10.3389/fnbeh.2015.00229.
Paulus MP, Flagan T, Simmons AN, Gillis K, Kotturi S, Thom N, et al. Subjecting elite athletes to inspiratory breathing load reveals behavioral and neural signatures of optimal performers in extreme environments. PloS ONE. 2012;7:e29394.
Galli G, Shukla A, Simmons AN, Davenport PW, Paulus MP. Sex differences in the neural processing of aversive interoceptive events: the benefit of relief. PLoS ONE. 2013;8:e84044. https://doi.org/10.1371/journal.pone.0084044.
Berk L, Stewart JL, May AC, Wiers RW, Davenport PW, Paulus MP, et al. Under pressure: adolescent substance users show exaggerated neural processing of aversive interoceptive stimuli. Addiction. 2015;110:2025–36. https://doi.org/10.1111/add.13090.
Haase L, Thom NJ, Shukla A, Davenport PW, Simmons AN, Paulus MP, et al. Mindfulness-based training attenuates insula response to an aversive interoceptive challenge. Soc Cogn Affect Neurosci. 2014;11:nsu042.
Garner DM. Eating Disorder Inventory-2 Professional Manual. Odessa: Psychological Assessment Resources; 1991.
Beck AT, Steer RA, Brown GK. Manual for the Beck Depression Inventory-II. San Antonio: Psychological Corporation; 1996.
Cloninger CR, Przybeck TR, Svrakic DM. The Temperament and Character Inventory (TCI): A guide to its development and use: Center for Psychobiology of Personality. St. Louis: Washington University; 1994.
Spielberger CD, Gorsuch RL, Lushene RD. State-Trait Anxiety Inventory Manual. Palo Alto: Consulting Psychologists Press; 1970.
Chen G, Saad ZS, Britton JC, Pine DS, Cox RW. Linear mixed-effects modeling approach to FMRI group analysis. NeuroImage. 2013;73:176–90. https://doi.org/10.1016/j.neuroimage.2013.01.047.
Desikan RS, Ségonne F, Fischl B, Quinn BT, Dickerson BC, Blacker D, et al. An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage. 2006;31:968–80. https://doi.org/10.1016/j.neuroimage.2006.01.021.
Bissonette GB, Gentry RN, Padmala S, Pessoa L, Roesch MR. Impact of appetitive and aversive outcomes on brain responses: linking the animal and human literatures. Front Syst Neurosci. 2014;8:24. https://doi.org/10.3389/fnsys.2014.00024.
Eklund A, Nichols T, Knutsson H. Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates. Proc Natl Acad Sci USA. 2016;113:7900–5. https://doi.org/10.1073/pnas.1602413113.
Huber P. Robust estimation of location parameter. Ann Math Stat. 1964;35:73–101.
Nichols T, Brett M, Anderson J, Wager T, Poline J. Valid conjunction inference with the minimum statistic. Neuroimage. 2005;25:653–60.
Simmons A, Matthews SC, Stein MB, Paulus MP. Anticipation of emotionally aversive visual stimuli activates right insula. Neuroreport. 2004;15:2261–5.
Carlson JM, Greenberg T, Rubin D, Mujica-Parodi LR. Feeling anxious: anticipatory amygdalo-insular response predicts the feeling of anxious anticipation. Soc Cogn Affect Neurosci. 2011;6:74–81. https://doi.org/10.1093/scan/nsq017.
DeVille DC, Kerr KL, Avery JA, Burrows K, Bodurka J, Feinstein J, et al. The neural bases of interoceptive encoding and recall in healthy adults and adults with depression. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018;3:546–54. https://doi.org/10.1016/j.bpsc.2018.03.010.
Frank GKW, Reynolds JR, Shott ME, O’Reilly RC. Altered temporal difference learning in bulimia nervosa. Biol Psychiatry. 2011;70:728–35.
Hayes D, Ducana N, Xua J, Northoff G. A comparison of neural responses to appetitive and aversive stimuli in humans and other mammals. Neuro Biobehav Rev. 2014;45:350–68. https://doi.org/10.1016/j.neubiorev.2014.06.018.
Craig AD. Forebrain emotional asymmetry: a neuroanatomical basis? Trends Cogn Sci. 2005;9:566–71. https://doi.org/10.1016/j.tics.2005.10.005.
Strigo IA, Craig AD. Interoception, homeostatic emotions and sympathovagal balance. Philos Trans R Soc B Biol Sci. 2016;371:pii: 20160010.
Strigo IA, Simmons AN, Matthews SC, Craig A, Paulus MP. Association of major depressive disorder with altered functional brain response during anticipation and processing of heat pain. Arch Gen Psychiatry. 2008;65:1275–84. https://doi.org/10.1001/archpsyc.65.11.1275.
Paulus MP, Stein MB. Interoception in anxiety and depression. Brain Struct Funct. 2010;214:451–63. https://doi.org/10.1007/s00429-010-0258-9.
Haase L, Stewart JL, Youssef B, May AC, Isakovic S, Simmons AN, et al. When the brain does not adequately feel the body: links between low resilience and interoception. Biol Psychol. 2016;113:37–45. https://doi.org/10.1016/j.biopsycho.2015.11.004.
Holtz K, Pané-Farré CA, Wendt J, Lotze M, Hamm AO. Brain activation during anticipation of interoceptive threat. NeuroImage. 2012;61:857–65. https://doi.org/10.1016/j.neuroimage.2012.03.019.
Yágüez L, Coen S, Gregory LJ, Amaro E, Altman C, Brammer MJ, et al. Brain response to visceral aversive conditioning: a functional magnetic resonance imaging study. Gastroenterology. 2005;128:1819–29. https://doi.org/10.1053/j.gastro.2005.02.068.
Kleckner IR, Zhang J, Touroutoglou A, Chanes L, Xia C, Simmons WK, et al. Evidence for a large-scale brain system supporting allostasis and interoception in humans. Nat Human Behav. 2017;1:0069. https://doi.org/10.1038/s41562-017-0069.
Wierenga C, Ely A, Bischoff-Grethe A, Bailer U, Simmons A, Kaye W. Are extremes of consumption in eating disorders related to an altered balance between reward and inhibition? Front Behav Neurosci. 2014;9:410. https://doi.org/10.3389/fnbeh.2014.00410.
Marsh R, Steinglass JE, Gerber AJ, O’Leary KG, Walsh BT, Peterson BS. Deficient activity in the neural systems that mediate self-regulatory control in bulimia nervosa. Arch General Psychiatry. 2009;66:1–13.
Sinha R, Lacadie CM, Constable RT, Seo D. Dynamic neural activity during stress signals resilient coping. Proc Natl Acad Sci USA. 2016;113:8837–42. https://doi.org/10.1073/pnas.1600965113.
Garfinkel SN, Manassei MF, Hamilton-Fletcher G, In den Bosch Y, Critchley HD, Engels M. Interoceptive dimensions across cardiac and respiratory axes. Philos Trans R Soc B Biol Sci. 2016;371:pii: 20160014.
Strigo I, Matthews S, Simmons A, Oberndorfer T, Reinhardt L, Klabunde M, et al. Altered insula activation during pain anticipation in individuals recovered from anorexia nervosa: evidence of interocetive dysregulation. Int J Eat Disord. 2013;46:23–33. https://doi.org/10.1002/eat.22045.
Khalsa S, Craske M, Li W, Vangala S, Strober M, Feusner J. Altered interoceptive awareness in anorexia nervosa: effects of meal anticipation, consumption and bodily arousal. Int J Eat Disord. 2015;48:889–97. https://doi.org/10.1002/eat.22387.
Pearson CM, Chester DS, Powell D, Wonderlich SA, Smith GT. Investigating the reinforcing value of binge anticipation. Int J Eat Disord. 2016;49:539–41. https://doi.org/10.1002/eat.22547.
Paulus MP, Stein MB. An insular view of anxiety. Biol Psychiatry. 2006;60:383–7. https://doi.org/10.1016/j.biopsych.2006.03.042.
Pearson CM, Wonderlich SA, Smith GT. A risk and maintenance model for bulimia nervosa: from impulsive action to compulsive behavior. Psychol Rev. 2015;122:516–35. https://doi.org/10.1037/a0039268.
Linardon J, Wade TD. How many individuals achieve symptom abstinence following psychological treatments for bulimia nervosa? A meta-analytic review. Int J Eat Disord. 2018;51:287–94. https://doi.org/10.1002/eat.22838.
Acknowledgements
The authors thank Miki Ogasawara for assistance with fMRI data collection and pre-processing. We also thank Daria Orlowska, Grace Rasmusson, Laura Greathouse, Raesana Williams, and Jocelyn Danielle Bulante for assistance with participant screening and data collection. Finally, we thank the women who participated in this study for their time.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
About this article
Cite this article
Berner, L.A., Simmons, A.N., Wierenga, C.E. et al. Altered anticipation and processing of aversive interoceptive experience among women remitted from bulimia nervosa. Neuropsychopharmacol. 44, 1265–1273 (2019). https://doi.org/10.1038/s41386-019-0361-4
Received:
Revised:
Accepted:
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1038/s41386-019-0361-4
This article is cited by
-
Self-reported interoceptive sensibility across eating disorder symptoms: associations with sociodemographic factors
Journal of Eating Disorders (2026)
-
Global, regional and national level burden of bulimia nervosa from 1990 to 2021 and their projections to 2030: analysis of the global burden of disease study
Journal of Eating Disorders (2025)
-
Neuroimaging studies of resting-state functional magnetic resonance imaging in eating disorders
BMC Medical Imaging (2024)
-
Evaluating the predictions of an interoceptive inference model of bulimia nervosa
Journal of Eating Disorders (2024)
-
Relationship Between Interoception and Autistic Traits: A Resting-State Functional Connectivity Study
Journal of Autism and Developmental Disorders (2024)
