Altered interoceptive activation before, during, and after aversive breathing load in women remitted from anorexia nervosa
Open accessAbstract
Background: The neural mechanisms of anorexia nervosa (AN), a severe and chronic psychiatric illness, are still poorly understood. Altered body state processing, or interoception, has been documented in AN, and disturbances in aversive interoception may contribute to distorted body perception, extreme dietary restriction, and anxiety. As prior data implicate a potential mismatch between interoceptive expectation and experience in AN, we examined whether AN is associated with altered brain activation before, during, and after an unpleasant interoceptive state change. Methods: Adult women remitted from AN (RAN; n = 17) and healthy control women (CW; n = 25) underwent functional magnetic resonance imaging during an inspiratory breathing load paradigm. Results: During stimulus anticipation, the RAN group, relative to CW, showed reduced activation in right mid-insula. In contrast, during the aversive breathing load, the RAN group showed increased activation compared with CW in striatum and cingulate and prefrontal cortices (PFC). The RAN group also showed increased activation in PFC, bilateral insula, striatum, and amygdala after stimulus offset. Time course analyses indicated that RAN responses in interoceptive processing regions during breathing load increased more steeply than those of CW. Exploratory analyses revealed that hyperactivation after breathing load was associated with markers of past AN severity. Conclusions: Anticipatory deactivation with a subsequent exaggerated brain response during and after an aversive body state may contribute to difficulty predicting and adapting to internal state fluctuation. Because eating changes our interoceptive state, restriction may be one method of avoiding aversive, unpredictable internal change in AN.
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Dysfunction of interoception is increasingly recognized as an important component of anxiety disorders, mood disorders, eating disorders, addictive disorders, and somatic symptom disorders.
“Dysfunction of interoception is increasingly recognized as an important component of different mental health conditions, including anxiety disorders, mood disorders, eating disorders, addictive disorders, and somatic symptom disorders.”
From Interoception and Mental Health: A Roadmap. (2018) · cites this paper as [98]
The Introduction links aberrant interoception to symptoms of anorexia nervosa, and the Discussion’s Clinical Implications section mentions theories linking interoceptive prediction error to anxiety (page numbers unavailable). Our copy does not establish the broader claim about mood, addictive, or somatic symptom disorders, or describe interoceptive dysfunction as an important component across all the listed conditions. (LLM, conf=0.86)
Experimental — accuracy not yet measuredEating disorders show behavioral and neural abnormalities in interoceptive processing, particularly in the context of caloric anticipation.
“Eating disorders show behavioral and neural abnormalities in interoceptive processing, particularly in the context of caloric anticipation (72,98–100), although it remains unclear whether this is due to altered afferent signaling, altered central sensory processing, abnormal temperament, and/or metacognition.”
From Interoception and Mental Health: A Roadmap. (2018) · cites this paper as [98]
The Introduction (page not provided) reports difficulty distinguishing anticipated from actual sensations in anorexia nervosa, altered neural activation during anticipation of sucrose tastes, and dysphoric responses to anticipating eating. These passages support the behavioral and neural aspects of the claim in anorexia nervosa, but do not establish the claim for eating disorders more broadly. (LLM, conf=0.82)
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Cites
Neural systems supporting interoceptive awareness
Critchley, H. D., Wiens, S., Rotshtein, P., Öhman, A., & Dolan, R. J. (2004) · Nature Neuroscience · doi:10.1038/nn1176 · Cited by 3,406 · cited 1× · see citing works
“Projections from anterior and mid-cingulate and orbitofrontal and lateral PFC to anterior insula may modulate cognitive reactions during the stimulus (Craig 2002; Critchley et al. 2004; Hayes & Northoff 2012; Khalsa et al. 2009; Simmons et al. 2013).”
Interoception: the sense of the physiological condition of the body
(Bud) Craig, A. (2003) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(03)00090-4 · Cited by 2,556 · see citing works
Paulus, M. P., & Stein, M. B. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.03.042 · Cited by 1,325 · see citing works
Self-citationFrank, G. K., Bailer, U. F., Henry, S. E., Drevets, W., Meltzer, C. C., Price, J. C., Mathis, C. A., Wagner, A., Hoge, J., Ziolko, S., et al. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.05.003 · Cited by 361 · see citing works
Self-citationAltered Reward Processing in Women Recovered From Anorexia Nervosa
Wagner, A., Aizenstein, H., Venkatraman, V. K., Fudge, J., May, J. C., Mazurkewicz, L., Frank, G. K., Bailer, U. F., Fischer, L., Nguyen, V., et al. (2007) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2007.07040575 · Cited by 342 · see citing works
Self-citationAnorexia nervosa and obesity are associated with opposite brain reward response
Frank, G. K. W., Reynolds, J. R., Shott, M. E., Jappe, L., Yang, T. T., Tregellas, J. R., & O'Reilly, R. C. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.51 · Cited by 311 · see citing works
Wagner, A., Aizenstein, H., Mazurkewicz, L., Fudge, J., Frank, G. K., Putnam, K., Bailer, U. F., Fischer, L., & Kaye, W. H. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301443 · Cited by 261 · see citing works
Self-citationError awareness and the insula: links to neurological and psychiatric diseases
Klein, T. A., Ullsperger, M., & Danielmeier, C. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00014 · Cited by 210 · see citing works
Khalsa, S. S., Craske, M. G., Li, W., Vangala, S., Strober, M., & Feusner, J. D. (2015) · International Journal of Eating Disorders · doi:10.1002/eat.22387 · Cited by 191 · see citing works
Bailer, U. F., Frank, G. K., Henry, S. E., Price, J. C., Meltzer, C. C., Weissfeld, L., Mathis, C. A., Drevets, W. C., Wagner, A., Hoge, J., et al. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.9.1032 · Cited by 182 · cited 1× · see citing works
“AN remission was defined as in prior studies (Bailer et al. 2005; Bailer et al. 2004; Frank et al. 2005; Strigo et al. 2013; Wagner et al. 2008; Wagner et al. 2007; Wierenga et al. 2015).”
Self-citationPre-meal anxiety and food intake in anorexia nervosa
Steinglass, J. E., Sysko, R., Mayer, L., Berner, L. A., Schebendach, J., Wang, Y., Chen, H., Albano, A. M., Simpson, H. B., & Walsh, B. T. (2010) · Appetite · doi:10.1016/j.appet.2010.05.090 · Cited by 153 · see citing works
Self-citationMindfulness-based training attenuates insula response to an aversive interoceptive challenge.
Haase, L., Thom, N. J., Shukla, A., Davenport, P. W., Simmons, A. N., Stanley, E. A., Paulus, M. P., & Johnson, D. C. (2016) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsu042 · Cited by 124 · cited 5× · see citing works
“Region selection was also informed by control activation documented in the breathing load task (Berk et al. 2015; Galli et al. 2013; Haase et al. 2014; Paulus et al. 2012; Stewart et al. 2014) and locations of altered anticipatory and processing-related activation in women remitted from AN during…”
InfluentialAnorexia nervosa and the insula
Nunn, K., Frampton, I., Fuglset, T. S., Törzsök-Sonnevend, M., & Lask, B. (2011) · Medical Hypotheses · doi:10.1016/j.mehy.2010.10.038 · Cited by 122 · see citing works
Paulus, M. P., Flagan, T., Simmons, A. N., Gillis, K., Kotturi, S., Thom, N., Johnson, D. C., Van Orden, K. F., Davenport, P. W., & Swain, J. L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0029394 · Cited by 100 · cited 10× · see citing works
“The well-validated task has been shown to activate regions of the insula, PFC, striatum, and anterior cingulate (Paulus et al. 2012; Galli et al. 2013; Stewart et al. 2014; Berk et al. 2015).”
InfluentialGreater insula white matter fiber connectivity in women recovered from anorexia nervosa
Shott, M. E., Pryor, T. L., Yang, T. T., & Frank, G. K. W. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.172 · Cited by 62 · see citing works
Flagged first, then by citations
Research works printed but not linked: 34
- Bailer UF Price JC Meltzer CC Mathis CA Frank GK Weissfeld L McConaha CW Henry SE Brooks-Achenbach S Barbarich NC Kaye WH 2004 Altered 5-HT(2A) receptor binding after recovery from bulimia-type anorexia nervosa: relationships to harm avoidance and drive for thinness Neuropsychopharmacology 29 1143 55 15054474 PMC4301578
- Barrett LF Simmons WK 2015 Interoceptive predictions in the brain Nature Reviews Neuroscience 16 419 429 26016744 PMC4731102
- Berk L Stewart JL May AC Wiers RW Davenport PW Paulus MP Tapert SF 2015 Under pressure: adolescent substance users show exaggerated neural processing of aversive interoceptive stimuli Addiction 110 2025 2036 26234745 PMC4644498
- Brand-Gothelf A Parush S Eitan Y Admoni S Gur E Stein D 2016 Sensory modulation disorder symptoms in anorexia nervosa and bulimia nervosa: A pilot study International Journal of Eating Disorders 49 59 68 26354076
- Courty A Godart N Lalanne C Berthoz S 2015 Alexithymia, a compounding factor for eating and social avoidance symptoms in anorexia nervosa Comprehensive Psychiatry 56 217 228 25443977
- Cowdrey FA Park RJ Harmer CJ McCabe C 2011 Increased neural processing of rewarding and aversive food stimuli in recovered anorexia nervosa Biological Psychiatry 70 736 43 21714958
- Craig AD 2002 How do you feel? Interoception: the sense of the physiological condition of the body Nature Reviews Neuroscience 3 655 666 12154366
- Desikan RS Ségonne F Fischl B Quinn BT Dickerson BC Blacker D Buckner RL Dale AM Maguire RP Hyman BT Albert MS Killiany RJ 2006 An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest Neuroimage 31 968 980 16530430
- Eklund A Nichols T Knutsson H 2016 Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates Proceedings of the National Academy of Science 113 7900 7905 PMC4948312 27357684
- Frank GK Collier S Shott ME O’Reilly RC 2016 Prediction error and somatosensory insula activation in women recovered from anorexia nervosa Journal of Psychiatry and Neuroscience 41 150103 PMC5008919 26836623
- Frank GKW 2015 Advances from neuroimaging studies in eating disorders CNS Spectrums 20 391 400 25902917 PMC4989857
- Galli G Shukla A Simmons AN Davenport PW Paulus MP 2013 Sex Differences in the Neural Processing of Aversive Interoceptive Events: The Benefit of Relief PLoS ONE 8 e84044 24386327 PMC3875519
- Haase L May AC Falahpour M Isakovic S Simmons AN Hickman SD Liu TT Paulus MP 2015 A pilot study investigating changes in neural processing after mindfulness training in elite athletes Frontiers in Behavioral Neuroscience 9 229 26379521 PMC4550788
- Haase L Stewart JL Youssef B May AC Isakovic S Simmons AN Johnson DC Potterat EG Paulus MP 2016 When the brain does not adequately feel the body: Links between low resilience and interoception Biological Psychology 113 37 45 26607442 PMC6559799
- Hayes DJ Northoff G 2012 Common brain activations for painful and non-painful aversive stimuli BMC Neuroscience 13 60 22676259 PMC3464596
- Huber P 1964 Robust Estimation of Location Parameter Annals of Mathematical Statistics 35
- Kerr KL Moseman SE Avery JA Bodurka J Zucker NL Simmons WK 2016 Altered Insula Activity during Visceral Interoception in Weight-Restored Patients with Anorexia Nervosa Neuropsychopharmacology 41 521 8 26084229 PMC5130127
- Khalsa SS Rudrauf D Feinstein JS Tranel D 2009 The pathways of interoceptive awareness Nature Neuroscience 12 1494 6 19881506 PMC2787640
- Leknes S Lee M Berna C Andersson J Tracey I 2011 Relief as a Reward: Hedonic and Neural Responses to Safety from Pain PLoS ONE 6 e17870 21490964 PMC3072382
- Merwin RM Moskovich AA Wagner HR Ritschel LA Craighead LW Zucker NL 2013 Emotion regulation difficulties in anorexia nervosa: Relationship to self-perceived sensory sensitivity Cognition and Emotion 27 441 52 22963392 PMC3593757
- Oberndorfer T Simmons A McCurdy D Strigo I Matthews S Yang T Irvine Z Kaye W 2013a Greater anterior insula activation during anticipation of food images in women recovered from anorexia nervosa versus controls Psychiatry Research: Neuroimaging 214 132 141 PMC3880160 23993362
- Oberndorfer TA Frank GK Simmons AN Wagner A McCurdy D Fudge JL Yang TT Paulus MP Kaye WH 2013b Altered insula response to sweet taste processing after recovery from anorexia and bulimia nervosa The American Journal of Psychiatry 170 1143 51 23732817 PMC3971875
- Paulus MP Stein MB 2010 Interoception in anxiety and depression Brain Structure and Function 214 451 463 20490545 PMC2886901
- Peiffer C 2009 Dyspnea relief: more than just the perception of a decrease in dyspnea Respiratory Physiology & Neurobiology 167 61 71 19428315
- Pollatos O Kurz A-L Albrecht J Schreder T Kleemann A Schopf V Kopietz R Weismann M Schandry R 2008 Reduced perception of bodily signals in anorexia nervosa Eating Behaviors 9 381 388 18928900
- Schultz W Dayan P Montague PR 1997 A neural substrate of prediction and reward Science 275 1593 9 9054347
- Seidel E Pfabigan DM Hahn A Sladky R Grahl A Paul K Kraus C Kublbock M Kranz GS Hummer A Lanzenberger R Windischberger C Lamm C 2015 Uncertainty during pain anticipation: the adaptive value of preparatory processes Human Brain Mapping 36 744 755 25324216 PMC6869185
- Simmons WK Avery JA Barcalow JC Bodurka J Drevets WC Bellgowan P 2013 Keeping the body in mind: Insula functional organization and functional connectivity integrate interoceptive, exteroceptive, and emotional awareness Human Brain Mapping 34 2944 2958 22696421 PMC6870113
- Spielberger CD Gorsuch RL Lushene RD 1970 State-Trait Anxiety Inventory Manual Consulting Psychologists Press Palo Alto, CA
- Stewart JL May AC Poppa T Davenport PW Tapert SF Paulus MP 2014 You are the danger: Attenuated insula response in methamphetamine users during aversive interoceptive decision-making Drug and Alcohol Dependence 142 110 119 24993186 PMC4127120
- Strigo IA Matthews SC Simmons AN Oberndorfer T Klabunde M Reinhardt LE Kaye WH 2013 Altered insula activation during pain anticipation in individuals recovered from anorexia nervosa: Evidence of interoceptive dysregulation International Journal of Eating Disorders 46 23 33 22836447 PMC3507323
- Tchanturia K Davies H Roberts M Harrison A Nakazato M Schmidt U Treasure J Morris R 2012 Poor Cognitive Flexibility in Eating Disorders: Examining the Evidence using the Wisconsin Card Sorting Task PLoS ONE 7 e28331 22253689 PMC3257222
- Wierenga CE Bischoff-Grethe A Melrose AJ Irvine Z Torres L Bailer UF Simmons A Fudge JL McClure SM Ely A 2015 Hunger does not motivate reward in women remitted from anorexia nervosa Biological Psychiatry 77 642 652 25481622 PMC4359668
- Zucker NL Merwin RM Bulik CM Moskovich A Wildes JE Groh J 2013 Subjective experience of sensation in anorexia nervosa Behaviour Research and Therapy 51 256 265 23523866 PMC3955712
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Interoception and Mental Health: A Roadmap.
Khalsa, S. S., Adolphs, R., Cameron, O. G., Critchley, H. D., Davenport, P. W., Feinstein, J. S., Feusner, J. D., Garfinkel, S. N., Lane, R. D., Mehling, W. E., et al. (2018) · Biological psychiatry. Cognitive neuroscience and neuroimaging · doi:10.1016/j.bpsc.2017.12.004 · Cited by 1,453 · see citing works
Self-citationDisrupted Dorsal Mid-Insula Activation During Interoception Across Psychiatric Disorders
Nord, C. L., Lawson, R. P., & Dalgleish, T. (2021) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2020.20091340 · Cited by 171 · see citing works
Schaumberg, K., Reilly, E. E., Gorrell, S., Levinson, C. A., Farrell, N. R., Brown, T. A., Smith, K. M., Schaefer, L. M., Essayli, J. H., Haynos, A. F., et al. (2021) · Clinical Psychology Review · doi:10.1016/j.cpr.2020.101952 · Cited by 121 · see citing works
Alexithymia mediates the relationship between interoceptive sensibility and anxiety
Palser, E. R., Palmer, C. E., Galvez-Pol, A., Hannah, R., Fotopoulou, A., & Kilner, J. M. (2018) · PLOS ONE · doi:10.1371/journal.pone.0203212 · Cited by 86 · see citing works
Heim, N., Bobou, M., Tanzer, M., Jenkinson, P. M., Steinert, C., & Fotopoulou, A. (2023) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.13576 · Cited by 61 · see citing works
Richter, F., García, A. M., Rodriguez Arriagada, N., Yoris, A., Birba, A., Huepe, D., Zimmer, H., Ibáñez, A., & Sedeño, L. (2021) · Human Brain Mapping · doi:10.1002/hbm.25288 · Cited by 46 · see citing works
Espel-Huynh, H. M., Muratore, A. F., Virzi, N., Brooks, G., & Zandberg, L. J. (2019) · Eating Behaviors · doi:10.1016/j.eatbeh.2019.101308 · Cited by 40 · see citing works
Matiz, A., Guzzon, D., Crescentini, C., Paschetto, A., & Fabbro, F. (2020) · European Journal of Integrative Medicine · doi:10.1016/j.eujim.2020.101168 · Cited by 11 · see citing works
- Authors
- Berner, L. A., Simmons, A. N., Wierenga, C. E., Bischoff-Grethe, A., Paulus, M. P., Bailer, U. F., Ely, A. V., & Kaye, W. H.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Kaye, W. H.
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2017-07-17
- Volume
- 48
- Issue
- 1
- Pages
- 142-154
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- PMC
- PMC5990016
- OpenAlex
- W2735014229
- Cited by
- 87
- References
- 15
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 8 · 2023: 8 · 2022: 10 · 2021: 10 · 2020: 17 · 2019: 10 · 2018: 6 · 2017: 2
- FWCI
- 11.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Hilda and Preston Davis Foundation
- National Institute of Mental Health (R01MH092793, F32MH108311, R01MH042984)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- anorexia nervosa, interoception, insula, striatum, prefrontal cortex, amygdala, women
- MeSH terms
- Adult, Anorexia Nervosa, Brain Mapping, Breath Tests, Cerebral Cortex, Corpus Striatum, Female, Humans, Magnetic Resonance Imaging, Neuropsychological Tests, Psychomotor Performance, Regression Analysis, Respiration, Case-Control Studies
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