Skip to main content
SpringerLink
Log in

Cerebellar Contributions to Different Phases of Visceral Aversive Extinction Learning

  • Original Paper
  • Published:
The Cerebellum Aims and scope Submit manuscript

Abstract

The cerebellum is increasingly recognized to contribute to non-motor functions, including cognition and emotion. Although fear conditioning has been studied for elucidating the pathophysiology of anxiety, the putative role of the cerebellum is still unknown. Fear conditioning could also be important in the etiology of chronic abdominal pain which often overlaps with anxiety. Hence, in this exploratory analysis, we investigated conditioned anticipatory activity in the cerebellum in a visceral aversive fear conditioning paradigm using functional magnetic resonance imaging. We extended and reanalyzed a previous dataset for different learning phases, i.e., acquisition, extinction, and reinstatement, utilizing an advanced normalizing method of the cerebellum. In 30 healthy humans, visual conditioned stimuli (CS+) were paired with painful rectal distensions as unconditioned stimuli (US), while other visual stimuli (CS−) were presented without US. During extinction, all CSs were presented without US, whereas during reinstatement, a single, unpaired US was presented. During acquisition, posterolateral cerebellar areas including Crus I, Crus II, and VIIb and parts of the dentate nucleus were activated in response to the CS+ compared to the CS−. During extinction, activation related to CS+ presentation was detected in Crus I, Crus II, IV, V, VI, VIIb, IX, and vermis. Neural correlates of reinstatement were found in Crus I, Crus II, IV, V, and IX. We could show for the first time that the cerebellum is involved in abdominal pain-related associative learning processes. Together, these findings contribute to our understanding of the cerebellum in aversive learning and memory processes relevant to the pathophysiology of chronic abdominal pain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Ramnani N. The primate cortico-cerebellar system: anatomy and function. Nat Rev Neurosci. 2006;7(7):511–22. Epub 2006/06/23.

    Article  CAS  PubMed  Google Scholar 

  2. Timmann D, Drepper J, Frings M, Maschke M, Richter S, Gerwig M, et al. The human cerebellum contributes to motor, emotional and cognitive associative learning. A review. Cortex. J Devoted Study Nerv System Behav. 2010;46(7):845–57. Epub 2009/08/12.

    Article  CAS  Google Scholar 

  3. Maschke M, Drepper J, Burgerhoff K, Calabrese S, Kolb FP, Daum I, et al. Differences in trace and delay visuomotor associative learning in cerebellar patients. Exp Brain Res Experimentelle Hirnforschung Exp Cerebrale. 2002;147(4):538–48. Epub 2002/11/22.

    Article  Google Scholar 

  4. Thoma P, Bellebaum C, Koch B, Schwarz M, Daum I. The cerebellum is involved in reward-based reversal learning. Cerebellum. 2008;7(3):433–43. Epub 2008/07/02.

    Article  PubMed  Google Scholar 

  5. Maschke M, Schugens M, Kindsvater K, Drepper J, Kolb FP, Diener HC, et al. Fear conditioned changes of heart rate in patients with medial cerebellar lesions. J Neurol Neurosurg Psychiatry. 2002;72(1):116–8. Epub 2002/01/11.

    Article  CAS  PubMed  Google Scholar 

  6. Maschke M, Drepper J, Kindsvater K, Kolb FP, Diener HC, Timmann D. Fear conditioned potentiation of the acoustic blink reflex in patients with cerebellar lesions. J Neurol Neurosurg Psychiatry. 2000;68(3):358–64. Epub 2000/02/16.

    Article  CAS  PubMed  Google Scholar 

  7. Damasio AR, Grabowski TJ, Bechara A, Damasio H, Ponto LL, Parvizi J, et al. Subcortical and cortical brain activity during the feeling of self-generated emotions. Nat Neurosci. 2000;3(10):1049–56. Epub 2000/10/04.

    Article  CAS  PubMed  Google Scholar 

  8. Hermans D, Dirikx T, Vansteenwegen D, Vansteenwegenin D, Baeyens F, Van den Bergh O, et al. Reinstatement of fear responses in human aversive conditioning. Behav Res Ther. 2005;43(4):533–51.

    Article  PubMed  Google Scholar 

  9. LaBar KS, Phelps EA. Reinstatement of conditioned fear in humans is context dependent and impaired in amnesia. Behav Neurosci. 2005;119(3):677–86.

    Article  PubMed  Google Scholar 

  10. Quirk GJ, Pare D, Richardson R, Herry C, Monfils MH, Schiller D, et al. Erasing fear memories with extinction training. J Neurosci. 2010;30(45):14993–7. Epub 2010/11/12.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Tyler K, Moriceau S, Sullivan RM, Greenwood-van MB. Long-term colonic hypersensitivity in adult rats induced by neonatal unpredictable vs predictable shock. Neurogastroenterol Motil. 2007;19(9):761–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Wang Z, Bradesi S, Charles JR, Pang RD, Maarek JM, Mayer EA, et al. Functional brain activation during retrieval of visceral pain-conditioned passive avoidance in the rat. Pain. 2011;152(12):2746–56.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Nozu T, Kudaira M, Kitamori S, Uehara A. Repetitive rectal painful distention induces rectal hypersensitivity in patients with irritable bowel syndrome. J Gastroenterol. 2006;41(3):217–22.

    Article  PubMed  Google Scholar 

  14. Kattoor J, Gizewski ER, Kotsis V, Benson S, Gramsch C, Theysohn N, et al. Fear conditioning in an abdominal pain model: neural responses during associative learning and extinction in healthy subjects. PLoS One. 2013;8(2):e51149. Epub 2013/03/08.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Schutter DJ, van Honk J. The cerebellum on the rise in human emotion. Cerebellum. 2005;4(4):290–4. Epub 2005/12/03.

    Article  PubMed  Google Scholar 

  16. Supple Jr WF, Sebastiani L, Kapp BS. Purkinje cell responses in the anterior cerebellar vermis during Pavlovian fear conditioning in the rabbit. Neuroreport. 1993;4(7):975–8. Epub 1993/07/01.

    Article  PubMed  Google Scholar 

  17. Mills NP, Delbello MP, Adler CM, Strakowski SM. MRI analysis of cerebellar vermal abnormalities in bipolar disorder. Am J Psychiat. 2005;162(8):1530–2.

    Article  PubMed  Google Scholar 

  18. Sacchetti B, Scelfo B, Tempia F, Strata P. Long-term synaptic changes induced in the cerebellar cortex by fear conditioning. Neuron. 2004;42(6):973–82. Epub 2004/06/23.

    Article  CAS  PubMed  Google Scholar 

  19. Herrmann-Lingen C, Buss U, Snaith RP. Hospital anxiety and depression scale (HADS). Bern: Hans Huber; 2005. Deutsche Version.

    Google Scholar 

  20. Diedrichsen J. A spatially unbiased atlas template of the human cerebellum. NeuroImage. 2006;33(1):127–38. Epub 2006/08/15.

    Article  PubMed  Google Scholar 

  21. Friston KJ, Penny WD, Ashburner JT, Kiebel SJ, Nichols TE, editors. Statistical parametric mapping. Statistical parametric mapping: the analysis of functional brain images. London: Academic; 2007. p. 10–31.

    Google Scholar 

  22. Amaro E, Barker GJ. Study design in fMRI: basic principles. Brain Cogn. 2006;60(3):220–32.

    Article  PubMed  Google Scholar 

  23. Sehlmeyer C, Schöning S, Zwitserlood P, Pfleiderer B, Kircher T, Arolt V, et al. Human fear conditioning and extinction in neuroimaging: a systematic review. PLoS One. 2009;4(6):e5865.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Diedrichsen J, Balsters JH, Flavell J, Cussans E, Ramnani N. A probabilistic MR atlas of the human cerebellum. NeuroImage. 2009;46(1):39–46. Epub 2009/05/22.

    Article  PubMed  Google Scholar 

  25. Elsenbruch S, Rosenberger C, Enck P, Forsting M, Schedlowski M, Gizewski ER. Affective disturbances modulate the neural processing of visceral pain stimuli in irritable bowel syndrome: an fMRI study. Gut. 2010;59(4):489–95. Epub 2009/08/05.

    Article  CAS  PubMed  Google Scholar 

  26. Rosenberger C, Thurling M, Forsting M, Elsenbruch S, Timmann D, Gizewski ER. Contributions of the cerebellum to disturbed central processing of visceral stimuli in irritable bowel syndrome. Cerebellum. 2013;12(2):194–8.

    Article  PubMed  Google Scholar 

  27. Ploghaus A, Tracey I, Clare S, Gati JS, Rawlins JN, Matthews PM. Learning about pain: the neural substrate of the prediction error for aversive events. Proc Natl Acad Sci U S A. 2000;97(16):9281–6. Epub 2000/07/26.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Sacchetti B, Scelfo B, Strata P. The cerebellum: synaptic changes and fear conditioning. Rev J Bringing Neurobiol, Neurol Psychiatry. 2005;11(3):217–27. Epub 2005/05/25; The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

    Google Scholar 

  29. Stoodley CJ, Schmahmann JD. Functional topography in the human cerebellum: a meta-analysis of neuroimaging studies. NeuroImage. 2009;44(2):489–501. Epub 2008/10/07.

    Article  PubMed  Google Scholar 

  30. Sacchetti B, Sacco T, Strata P. Reversible inactivation of amygdala and cerebellum but not perirhinal cortex impairs reactivated fear memories. Eur J Neurosci. 2007;25(9):2875–84. Epub 2007/05/01.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This project was funded by the German Research Foundation (Deutsche Forschungsgemeinschaft), grant numbers EL 236/9-1 and TI 239/10-1 within the research consortium “Extinction Learning: Neural Mechanisms, Behavioral Manifestations, and Clinical Implications”: FOR 1581.

Conflict of Interest

All authors declare no conflicts of interest.

Author information

Authors and Affiliations

  1. Institute of Medical Psychology & Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany

    Joswin Kattoor & Sigrid Elsenbruch

  2. Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

    Markus Thürling & Dagmar Timmann

  3. Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

    Michael Forsting

  4. Clinic for Neuroradiology, University of Innsbruck, Innsbruck, Austria

    Elke R. Gizewski

Authors
  1. Joswin Kattoor
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Markus Thürling
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elke R. Gizewski
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael Forsting
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dagmar Timmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sigrid Elsenbruch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sigrid Elsenbruch.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kattoor, J., Thürling, M., Gizewski, E.R. et al. Cerebellar Contributions to Different Phases of Visceral Aversive Extinction Learning. Cerebellum 13, 1–8 (2014). https://doi.org/10.1007/s12311-013-0512-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12311-013-0512-9

Keywords

Search

Navigation