Intimate stimuli result in fronto-parietal activation changes in anorexia nervosa

  • L. van Zutphen
  • S. Maier
  • N. Siep
  • G. A. Jacob
  • O. Tüscher
  • L. Tebartz van Elst
  • A. Zeeck
  • A. Arntz
  • M.-F. O’Connor
  • H. Stamm
  • M. Hudek
  • Andreas JoosEmail author
Original Article



Intimacy is a key psychological problem in anorexia nervosa (AN). Empirical evidence, including neurobiological underpinnings, is however, scarce.


In this study, we evaluated various emotional stimuli including intimate stimuli experienced in patients with AN and non-patients, as well as their cerebral response.


Functional magnetic resonance imaging was conducted using stimuli with positive, neutral, negative and intimate content. Participants (14 AN patients and 14 non-patients) alternated between passive viewing and explicit emotion regulation.


Intimate stimuli were experienced less positively in AN patients compared to non-patients. AN patients showed decreased cerebral responses in superior parietal cortices in response to positive and intimate stimuli. Intimate stimuli led to stronger activation of the orbitofrontal cortex, and lower activation of the bilateral precuneus in AN patients. Orbitofrontal responses decreased in AN patients during explicit emotion regulation.


These results show that intimate stimuli are of particular importance in AN patients, who show experiential differences compared to non-patients and altered activation of orbitofrontal and parietal brain structures. This supports that AN patients have difficulties with intimacy, attachment, self-referential processing and body perception.

Level of evidence

Level III, case–control study.


Anorexia nervosa Intimacy Neuroimaging fMRI Emotion regulation Orbitofrontal cortex Precuneus 



This study was carried out as part of the study DFG (German Research Foundation) JA1785/3-1 and in preparation of DFG-Grant JO 744-2/1.


Part of project DFG JA1785/3-1.

Compliance with ethical standards

Conflict of interest

There were no potential conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

40519_2017_474_MOESM1_ESM.tif (106 kb)
Supplementary material 1 (TIF 106 KB)
40519_2017_474_MOESM2_ESM.tif (105 kb)
Supplementary material 2 (TIF 105 KB)


  1. 1.
    Smink FRE, van Hoeken D, Hoek HW (2013) Epidemiology, course, and outcome of eating disorders. Curr Opin Psychiatry 26:543–548. CrossRefPubMedGoogle Scholar
  2. 2.
    Couturier J, Lock J (2006) What is recovery in adolescent anorexia nervosa? Int J Eat Disord 39:550–555. CrossRefPubMedGoogle Scholar
  3. 3.
    Zhu Y, Hu X, Wang J et al (2012) Processing of food, body and emotional stimuli in anorexia nervosa: a systematic review and meta-analysis of functional magnetic resonance imaging studies. Eur Eat Disord Rev. CrossRefPubMedGoogle Scholar
  4. 4.
    Uher R, Murphy T, Brammer MJ et al (2004) Medial prefrontal cortex activity associated with symptom provocation in eating disorders. Am J Psychiatry 161:1238–1246. CrossRefPubMedGoogle Scholar
  5. 5.
    Sloan DM, Kring AM (2007) Measuring changes in emotion during psychotherapy: conceptual and methodological issues. Clin Psychol Sci Pract 14:307–322. CrossRefGoogle Scholar
  6. 6.
    Campos JJ, Frankel CB, Camras L (2004) On the nature of emotion regulation. Child Dev 75:377–394. CrossRefPubMedGoogle Scholar
  7. 7.
    Gross JJ (2002) Emotion regulation: affective, cognitive, and social consequences. Psychophysiology 39:281–291. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Joos AA, Cabrillac E, Hartmann A et al (2009) Emotional perception in eating disorders. Int J Eat Disord 42:318–325. CrossRefPubMedGoogle Scholar
  9. 9.
    Rottenberg J, Gross JJ (2007) Emotion and emotion regulation: a map for psychotherapy researchers. Clin Psychol Sci Pract 14:323–328. CrossRefGoogle Scholar
  10. 10.
    Joos AAB, Gille M, Hartmann A et al (2012) Emotional perception in patients with eating disorders in comparison with depressed patients. Eur Eat Disord Rev 20:468–475. CrossRefPubMedGoogle Scholar
  11. 11.
    Smith R, Lane RD (2015) The neural basis of one’s own conscious and unconscious emotional states. Neurosci Biobehav Rev 57:1–29. CrossRefPubMedGoogle Scholar
  12. 12.
    Mikels JA, Fredrickson BL, Larkin GR et al (2005) Emotional category data on images from the international affective picture system. Behav Res Methods 37:626–630CrossRefGoogle Scholar
  13. 13.
    Phillips ML, Drevets WC, Rauch SL, Lane R (2003) Neurobiology of emotion perception I: the neural basis of normal emotion perception. Biol Psychiatry 54:504–514CrossRefGoogle Scholar
  14. 14.
    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. Ann N Y Acad Sci 1251:E1–E24. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Yoo H, Bartle-Haring S, Day RD, Gangamma R (2014) Couple communication, emotional and sexual intimacy, and relationship satisfaction. J Sex Marital Ther 40:275–293. CrossRefPubMedGoogle Scholar
  16. 16.
    Dekel S, Farber BA (2012) Models of intimacy of securely and avoidantly attached young adults: a narrative approach. J Nerv Ment Dis 200:156–162. CrossRefPubMedGoogle Scholar
  17. 17.
    O’Shaughnessy R, Dallos R (2009) Attachment research and eating disorders: a review of the literature. Clin Child Psychol Psychiatry 14:559–574. CrossRefPubMedGoogle Scholar
  18. 18.
    Aron A, Fisher H, Mashek DJ et al (2005) Reward, motivation, and emotion systems associated with early-stage intense romantic love. J Neurophysiol 94:327–337. CrossRefPubMedGoogle Scholar
  19. 19.
    Bruch H (1982) Anorexia Nervosa: therapy and theory. Am J Psychiatry 139:1531–1538CrossRefGoogle Scholar
  20. 20.
    Pinheiro AP, Raney TJ, Thornton LM et al (2010) Sexual functioning in women with eating disorders. Int J Eat Disord 43:123–129. CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Schmidt U, Evans K, Tiller J, Treasure J (1995) Puberty, sexual milestones and abuse: how are they related in eating disorder patients? Psychol Med 25:413–417CrossRefGoogle Scholar
  22. 22.
    Schmidt U (2003) Aetiology of eating disorders in the 21(st) century: new answers to old questions. Eur Child Adolesc Psychiatry 12 Suppl 1:I30–I37.
  23. 23.
    Brockmeyer T, Holtforth MG, Bents H et al (2013) Interpersonal motives in anorexia nervosa: the fear of losing one’s autonomy. J Clin Psychol 69:278–289. CrossRefPubMedGoogle Scholar
  24. 24.
    Ward A, Ramsay R, Turnbull S et al (2001) Attachment in anorexia nervosa: a transgenerational perspective. Br J Med Psychol 74:497–505CrossRefGoogle Scholar
  25. 25.
    Jacob GA, Arntz A, Domes G et al (2011) Positive erotic picture stimuli for emotion research in heterosexual females. Psychiatry Res 190:348–351. CrossRefPubMedGoogle Scholar
  26. 26.
    Walter M, Bermpohl F, Mouras H et al (2008) Distinguishing specific sexual and general emotional effects in fMRI-subcortical and cortical arousal during erotic picture viewing. NeuroImage 40:1482–1494. CrossRefPubMedGoogle Scholar
  27. 27.
    Li Y, Sescousse G, Amiez C, Dreher J-C (2015) Local morphology predicts functional organization of experienced value signals in the human orbitofrontal cortex. J Neurosci 35:1648–1658. CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Wittfoth-Schardt D, Gründing J, Wittfoth M et al (2012) Oxytocin modulates neural reactivity to children’s faces as a function of social salience. Neuropsychopharmacol 37:1799–1807. CrossRefGoogle Scholar
  29. 29.
    Arnow BA, Millheiser L, Garrett A et al (2009) Women with hypoactive sexual desire disorder compared to normal females: a functional magnetic resonance imaging study. Neuroscience 158:484–502. CrossRefPubMedGoogle Scholar
  30. 30.
    van Zutphen L, Siep N, Jacob GA et al (2018) Always on guard: emotion regulation in borderline personality disorder compared to non-patients and patients with cluster-c personality disorder. J Psychiatry Neurosci 43(1):37–47CrossRefGoogle Scholar
  31. 31.
    Noonan MP, Kolling N, Walton ME, Rushworth MFS (2012) Re-evaluating the role of the orbitofrontal cortex in reward and reinforcement. Eur J Neurosci 35:997–1010. CrossRefPubMedGoogle Scholar
  32. 32.
    Wallis JD (2012) Cross-species studies of orbitofrontal cortex and value-based decision-making. Nat Neurosci 15:13–19. CrossRefGoogle Scholar
  33. 33.
    Tettamanti M, Rognoni E, Cafiero R et al (2012) Distinct pathways of neural coupling for different basic emotions. NeuroImage 59:1804–1817. CrossRefPubMedGoogle Scholar
  34. 34.
    Paul T, Thiel A (2005) Eating disorder inventory—2. Hogrefe, GöttingenGoogle Scholar
  35. 35.
    Beck AT, Hautzinger M, Bailer M, Worall H, Keller F (1995) Beck-depressions-inventar (BDI) (Bd. 2). Hogrefe, GöttingenGoogle Scholar
  36. 36.
    Beck AT, Stern RA (2007) Beck-Angst-Inventar (dt. Ehlers, A., Markgraf, J.). Harcout Test Services GmbH, Frankfurt am MainGoogle Scholar
  37. 37.
    Ochsner KN, Bunge SA, Gross JJ, Gabrieli JDE (2002) Rethinking feelings: an FMRI study of the cognitive regulation of emotion. J Cogn Neurosci 14:1215–1229. CrossRefPubMedGoogle Scholar
  38. 38.
    Arnoud Arntz G van H (2009) Schema therapy for borderline personality disorder. Wiley-Blackwell, ChichesterGoogle Scholar
  39. 39.
    Lang PJ, Bradley MM, Cuthbert BN (2005) International affective picture system (IAPS): technical manual and affectve ratings. University of Florida, GainsvilleGoogle Scholar
  40. 40.
    Weiskopf N, Hutton C, Josephs O, Deichmann R (2006) Optimal EPI parameters for reduction of susceptibility-induced BOLD sensitivity losses: a whole-brain analysis at 3 T and 1.5 T. NeuroImage 33:493–504. CrossRefPubMedGoogle Scholar
  41. 41.
    Goebel R, Esposito F, Formisano E (2006) Analysis of functional image analysis contest (FIAC) data with brainvoyager QX: from single-subject to cortically aligned group general linear model analysis and self-organizing group independent component analysis. Hum Brain Mapp 27:392–401. CrossRefPubMedGoogle Scholar
  42. 42.
    Talairach J, Tournoux P (1988) Co-planar stereotaxic atlas of the human brain. Thieme, New YorkGoogle Scholar
  43. 43.
    Lieberman MD, Cunningham WA (2009) Type I and Type II error concerns in fMRI research: re-balancing the scale. Soc Cogn Affect Neurosci 4:423–428. CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Singmann H, Bolker B, Westfall J et al (2015) afex: analysis of factorial experimentsGoogle Scholar
  45. 45.
    R Core Team (2015) R: a language and environment for statistical computingGoogle Scholar
  46. 46.
    Oldershaw A, Lavender T, Sallis H et al (2015) Emotion generation and regulation in anorexia nervosa: a systematic review and meta-analysis of self-report data. Clin Psychol Rev 39:83–95. CrossRefPubMedGoogle Scholar
  47. 47.
    Oldershaw A, Hambrook D, Stahl D et al (2011) The socio-emotional processing stream in Anorexia Nervosa. Neurosci Biobehav Rev 35:970–988. CrossRefPubMedGoogle Scholar
  48. 48.
    Spring VL, Bulik CM (2014) Implicit and explicit affect toward food and weight stimuli in anorexia nervosa. Eat Behav 15:91–94. CrossRefPubMedGoogle Scholar
  49. 49.
    Fenske S, Lis S, Liebke L et al (2015) Emotion recognition in borderline personality disorder: effects of emotional information on negative bias. Borderline Personal Disord Emot Dysregul 2:10. CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Frank GKW (2015) Advances from neuroimaging studies in eating disorders. CNS Spectr 1–10.
  51. 51.
    Fuglset TS, Endestad T, Hilland E et al (2016) Brain volumes and regional cortical thickness in young females with anorexia nervosa. BMC Psychiatry 16:404. CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Titova OE, Hjorth OC, Schiöth HB, Brooks SJ (2013) Anorexia nervosa is linked to reduced brain structure in reward and somatosensory regions: a meta-analysis of VBM studies. BMC Psychiatry 13:110. CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Joos A, Klöppel S, Hartmann A et al (2010) Voxel-based morphometry in eating disorders: correlation of psychopathology with grey matter volume. Psychiatry Res 182:146–151. CrossRefPubMedGoogle Scholar
  54. 54.
    van Kuyck K, Gérard N, Van Laere K et al (2009) Towards a neurocircuitry in anorexia nervosa: evidence from functional neuroimaging studies. J Psychiatr Res 43:1133–1145. CrossRefPubMedGoogle Scholar
  55. 55.
    Demos KE, Heatherton TF, Kelley WM (2012) Individual differences in nucleus accumbens activity to food and sexual images predict weight gain and sexual behavior. J Neurosci 32:5549–5552. CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Rudebeck PH, Murray EA (2011) Balkanizing the primate orbitofrontal cortex: distinct subregions for comparing and contrasting values. Ann N Y Acad Sci 1239:1–13. CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Beer JS, John OP, Scabini D, Knight RT (2006) Orbitofrontal cortex and social behavior: integrating self-monitoring and emotion-cognition interactions. J Cogn Neurosci 18:871–879. CrossRefPubMedGoogle Scholar
  58. 58.
    Cavanna AE, Trimble MR (2006) The precuneus: a review of its functional anatomy and behavioural correlates. Brain 129:564–583. CrossRefPubMedGoogle Scholar
  59. 59.
    Sachdev P, Mondraty N, Wen W, Gulliford K (2008) Brains of anorexia nervosa patients process self-images differently from non-self-images: an fMRI study. Neuropsychologia 46:2161–2168. CrossRefPubMedGoogle Scholar
  60. 60.
    Vocks S, Busch M, Grönemeyer D et al (2010) Neural correlates of viewing photographs of one’s own body and another woman’s body in anorexia and bulimia nervosa: an fMRI study. JPN 35:163–176CrossRefGoogle Scholar
  61. 61.
    Bang L, Rø Ø, Endestad T (2016) Normal gray matter volumes in women recovered from anorexia nervosa: a voxel-based morphometry study. BMC Psychiatry 16:144. CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Joos A, Hartmann A, Glauche V et al (2011) Grey matter deficit in long-term recovered anorexia nervosa patients. Eur Eat Disord Rev 19:59–63. CrossRefPubMedGoogle Scholar
  63. 63.
    Xu J, Harper JA, Van Enkevort EA et al (2016) Neural activations are related to body-shape, anxiety, and outcomes in adolescent anorexia nervosa. J Psychiatr Res 87:1–7. CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Ramnani N, Owen AM (2004) Anterior prefrontal cortex: insights into function from anatomy and neuroimaging. Nat Rev Neurosci 5:184–194. CrossRefPubMedGoogle Scholar
  65. 65.
    Hafeman DM, Chang KD, Garrett AS et al (2012) Effects of medication on neuroimaging findings in bipolar disorder: an updated review. Bipolar Disord 14:375–410. CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • L. van Zutphen
    • 1
  • S. Maier
    • 2
    • 3
  • N. Siep
    • 1
  • G. A. Jacob
    • 4
  • O. Tüscher
    • 5
  • L. Tebartz van Elst
    • 3
  • A. Zeeck
    • 2
  • A. Arntz
    • 1
    • 6
  • M.-F. O’Connor
    • 7
  • H. Stamm
    • 2
  • M. Hudek
    • 2
  • Andreas Joos
    • 2
    • 8
    Email author
  1. 1.Department of Clinical Psychological ScienceMaastricht UniversityMaastrichtThe Netherlands
  2. 2.Department of Psychosomatic Medicine and Psychotherapy, Medical Center, University of Freiburg Faculty of MedicineUniversity of FreiburgFreiburgGermany
  3. 3.Department of Psychiatry and Psychotherapy, Medical Center, University of Freiburg Faculty of MedicineUniversity of FreiburgFreiburgGermany
  4. 4.Institute of PsychologyUniversity of FreiburgFreiburgGermany
  5. 5.Department of Psychiatry and PsychotherapyUniversity of MainzMainzGermany
  6. 6.Department of Clinical PsychologyUniversity of AmsterdamAmsterdamThe Netherlands
  7. 7.Department of PsychologyUniversity of ArizonaTucsonUSA
  8. 8.Department of Psychotherapeutic NeurologyKliniken Schmieder GailingenGailingenGermany

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