Advertisement

Neuropsychology Review

, Volume 29, Issue 2, pp 181–185 | Cite as

Distinct Activity Patterns of the Human Bed Nucleus of the Stria Terminalis and Amygdala during Fear Learning

  • Kelly Luyck
  • Travis D. Goode
  • Haemy Lee Masson
  • Laura LuytenEmail author
Review

Abstract

The amygdala and, more recently, also the bed nucleus of the stria terminalis, have been widely implicated in fear and anxiety. Much of our current knowledge is derived from animal studies and suggests an intricate convergence and divergence in functions related to defensive responding. In a recent paper, Klumpers and colleagues set out to examine these functions in a human fear learning procedure using functional magnetic resonance imaging. Their main findings were a role for the bed nucleus of the stria terminalis in threat anticipation, and for the amygdala in threat confrontation. Here, we provide a critical summary of this interesting study and point out some important issues that were not addressed by its authors. In particular, we first take a closer look at the striking differences between both samples that were combined for the study, and, secondly, we provide an in-depth discussion of their findings in relation to existing neurobehavioral models.

Keywords

Bed nucleus of the stria terminalis Amygdala Fear learning fMRI Human Defensive responses 

Notes

Acknowledgements

We acknowledge the financial support of the Research Foundation – Flanders (FWO) (Research Projects G0C9817N and G088216 N), the National Institute of Mental Health (F31MH107113), as well as the European Research Council (CoG 64817). We thank Prof. Bram Vervliet and our colleagues at the KU Leuven Psychology Department for the helpful discussions during the preparation of this manuscript.

Compliance with Ethical Standards

Conflict of Interest

The authors declare no competing financial interests.

References

  1. Alheid, G. F., Beltramino, C. A., De Olmos, J. S., Forbes, M. S., Swanson, D. J., & Heimer, L. (1998). The neuronal organization of the supracapsular part of the stria terminalis in the rat: the dorsal component of the extended amygdala. Neuroscience, 84(4), 967–996.CrossRefGoogle Scholar
  2. Alvarez, R. P., Chen, G., Bodurka, J., Kaplan, R., & Grillon, C. (2011). Phasic and sustained fear in humans elicits distinct patterns of brain activity. Neuroimage, 55(1), 389–400.  https://doi.org/10.1016/j.neuroimage.2010.11.057.CrossRefGoogle Scholar
  3. Asok, A., Draper, A., Hoffman, A. F., Schulkin, J., Lupica, C. R., & Rosen, J. B. (2017). Optogenetic silencing of a corticotropin-releasing factor pathway from the central amygdala to the bed nucleus of the stria terminalis disrupts sustained fear. Molecular Psychiatry, 23(4), 914–922.  https://doi.org/10.1038/mp.2017.79.CrossRefGoogle Scholar
  4. Atlas, L. Y., Doll, B. B., Li, J., Daw, N. D., & Phelps, E. A. (2016). Instructed knowledge shapes feedback-driven aversive learning in striatum and orbitofrontal cortex, but not the amygdala. Elife, 5.  https://doi.org/10.7554/eLife.15192.
  5. Brinkmann, L., Buff, C., Feldker, K., Tupak, S. V., Becker, M. P. I., Herrmann, M. J., & Straube, T. (2017a). Distinct phasic and sustained brain responses and connectivity of amygdala and bed nucleus of the stria terminalis during threat anticipation in panic disorder. Psychological Medicine, 47(15), 2675–2688.  https://doi.org/10.1017/S0033291717001192.CrossRefGoogle Scholar
  6. Brinkmann, L., Buff, C., Neumeister, P., Tupak, S. V., Becker, M. P., Herrmann, M. J., & Straube, T. (2017b). Dissociation between amygdala and bed nucleus of the stria terminalis during threat anticipation in female post-traumatic stress disorder patients. Human Brain Mapping, 38(4), 2190–2205.  https://doi.org/10.1002/hbm.23513.CrossRefGoogle Scholar
  7. Button, K. S., Ioannidis, J. P. A., Mokrysz, C., Nosek, B. A., Flint, J., Robinson, E. S. J., & Munafò, M. R. (2013). Power failure: why small sample size undermines the reliability of neuroscience. [research]. Nature Reviews Neuroscience, 14(5), 365.  https://doi.org/10.1038/nrn3475.CrossRefGoogle Scholar
  8. Crestani, C.C., Alves, F.H.F., Gomes, F.V., Resstel, L.B.M., Correa, F.M.A., Herman, J.P. (2013). Mechanisms in the bed nucleus of the stria terminalis involved in control of autonomic and neuroendocrine functions: a review. Current Neuropharmacology 11, 141–159.Google Scholar
  9. Daldrup, T., Lesting, J., Meuth, P., Seidenbecher, T., & Pape, H. C. (2016). Neuronal correlates of sustained fear in the anterolateral part of the bed nucleus of stria terminalis. Neurobiology of Learning and Memory, 131, 137–146.  https://doi.org/10.1016/j.nlm.2016.03.020.CrossRefGoogle Scholar
  10. Daniel, S. E. & Rainnie, D. G. (2016). Stress Modulation of Opposing Circuits in the Bed Nucleus of the Stria Terminalis. Neuropsychopharmacology 41, 103–125.Google Scholar
  11. Davis, M., Walker, D. L., Miles, L., & Grillon, C. (2010). Phasic vs sustained fear in rats and humans: role of the extended amygdala in fear vs anxiety. [review]. Neuropsychopharmacology, 35(1), 105–135.  https://doi.org/10.1038/npp.2009.109.CrossRefGoogle Scholar
  12. Fanselow, M. S. (1994). Neural organization of the defensive behavior system responsible for fear. Psychonomic Bulletin & Review, 1(4), 429–438.  https://doi.org/10.3758/bf03210947.CrossRefGoogle Scholar
  13. Goode, T. D., & Maren, S. (2017). Role of the bed nucleus of the stria terminalis in aversive learning and memory. Learning & Memory, 24(9), 480–491.  https://doi.org/10.1101/lm.044206.116.CrossRefGoogle Scholar
  14. Grillon, C., & Ameli, R. (1998). Effects of threat and safety signals on startle during anticipation of aversive shocks, sounds, or airblasts. Journal of Psychophysiology, 12(4), 329–337.Google Scholar
  15. Gungor, N. Z., & Paré, D. (2016). Functional heterogeneity in the bed nucleus of the Stria terminalis. The Journal of Neuroscience, 36(31), 8038–8049.  https://doi.org/10.1523/JNEUROSCI.0856-16.2016.CrossRefGoogle Scholar
  16. Klucken, T., Kagerer, S., Schweckendiek, J., Tabbert, K., Vaitl, D., & Stark, R. (2009). Neural, electrodermal and behavioral response patterns in contingency aware and unaware subjects during a picture-picture conditioning paradigm. Neuroscience, 158(2), 721–731.  https://doi.org/10.1016/j.neuroscience.2008.09.049.CrossRefGoogle Scholar
  17. Klumpers, F., van Gerven, J. M., Prinssen, E. P., Niklson, I., Roesch, F., Riedel, W. J., et al. (2010). Method development studies for repeatedly measuring anxiolytic drug effects in healthy humans. Journal of Psychopharmacology, 24(5), 657–666.  https://doi.org/10.1177/0269881109103115.CrossRefGoogle Scholar
  18. Klumpers, F., Kroes, M. C., Heitland, I., Everaerd, D., Akkermans, S. E., Oosting, R. S., et al. (2015). Dorsomedial prefrontal cortex mediates the impact of serotonin transporter linked polymorphic region genotype on anticipatory threat reactions. Biological Psychiatry, 78(8), 582–589.  https://doi.org/10.1016/j.biopsych.2014.07.034.CrossRefGoogle Scholar
  19. Klumpers, F., Kroes, M. C. W., Baas, J. M. P., & Fernandez, G. (2017). How human amygdala and bed nucleus of the Stria terminalis may drive distinct defensive responses. The Journal of Neuroscience, 37(40), 9645–9656.  https://doi.org/10.1523/jneurosci.3830-16.2017.CrossRefGoogle Scholar
  20. LaBar, K. S., & Cabeza, R. (2006). Cognitive neuroscience of emotional memory. Nature Reviews. Neuroscience, 7(1), 54–64.  https://doi.org/10.1038/nrn1825.CrossRefGoogle Scholar
  21. Lang, P. J., Davis, M., & Ohman, A. (2000). Fear and anxiety: animal models and human cognitive psychophysiology. Journal of Affective Disorders, 61(3), 137–159.CrossRefGoogle Scholar
  22. Lebow, M. A., & Chen, A. (2016). Overshadowed by the amygdala: the bed nucleus of the stria terminalis emerges as key to psychiatric disorders. Molecular Psychiatry, 21(4), 450–463.  https://doi.org/10.1038/mp.2016.1.CrossRefGoogle Scholar
  23. Lissek, S., Baas, J. M., Pine, D. S., Orme, K., Dvir, S., Nugent, M., et al. (2005). Airpuff startle probes: an efficacious and less aversive alternative to white-noise. Biological Psychology, 68(3), 283–297.  https://doi.org/10.1016/j.biopsycho.2004.07.007.CrossRefGoogle Scholar
  24. Lonsdorf, T. B., Menz, M. M., Andreatta, M., Fullana, M. A., Golkar, A., Haaker, J., Heitland, I., Hermann, A., Kuhn, M., Kruse, O., Meir Drexler, S., Meulders, A., Nees, F., Pittig, A., Richter, J., Römer, S., Shiban, Y., Schmitz, A., Straube, B., Vervliet, B., Wendt, J., Baas, J. M. P., & Merz, C. J. (2017). Don't fear 'fear conditioning': Methodological considerations for the design and analysis of studies on human fear acquisition, extinction, and return of fear. Neuroscience and Biobehavioral Reviews, 77, 247–285.  https://doi.org/10.1016/j.neubiorev.2017.02.026.CrossRefGoogle Scholar
  25. Luyck, K., Nuttin, B., & Luyten, L. (2018). Electrolytic post-training lesions of the bed nucleus of the stria terminalis block startle potentiation in a cued fear conditioning procedure. Brain Structure & Function, 223(4), 1839–1848.  https://doi.org/10.1007/s00429-017-1591-z.Google Scholar
  26. Luyten, L., Casteels, C., Vansteenwegen, D., van Kuyck, K., Koole, M., Van Laere, K., & Nuttin, B. (2012). Micro-positron emission tomography imaging of rat brain metabolism during expression of contextual conditioning. The Journal of Neuroscience, 32(1), 254–263.  https://doi.org/10.1523/JNEUROSCI.3701-11.2012.CrossRefGoogle Scholar
  27. Luyten, L., Hendrickx, S., Raymaekers, S., Gabriëls, L., & Nuttin, B. (2016). Electrical stimulation in the bed nucleus of the stria terminalis alleviates severe obsessive-compulsive disorder. Molecular Psychiatry, 21(9), 1272–1280.  https://doi.org/10.1038/mp.2015.124.CrossRefGoogle Scholar
  28. McGaugh, J. L. (2000). Memory--a century of consolidation. Science, 287(5451), 248–251.CrossRefGoogle Scholar
  29. Mechias, M. L., Etkin, A., & Kalisch, R. (2010). A meta-analysis of instructed fear studies: Implications for conscious appraisal of threat. Neuroimage, 49(2), 1760–1768.  https://doi.org/10.1016/j.neuroimage.2009.09.040.CrossRefGoogle Scholar
  30. Milad, M. R., Furtak, S. C., Greenberg, J. L., Keshaviah, A., Im, J. J., Falkenstein, M. J., Jenike, M., Rauch, S. L., & Wilhelm, S. (2013). Deficits in conditioned fear extinction in obsessive-compulsive disorder and neurobiological changes in the fear circuit. JAMA Psychiatry, 70(6), 608–618; quiz 554.  https://doi.org/10.1001/jamapsychiatry.2013.914.CrossRefGoogle Scholar
  31. Ohman, A., & Mineka, S. (2001). Fears, phobias, and preparedness: toward an evolved module of fear and fear learning. Psychological Review, 108(3), 483–522.CrossRefGoogle Scholar
  32. Perusini, J. N., & Fanselow, M. S. (2015). Neurobehavioral perspectives on the distinction between fear and anxiety. Learning & Memory, 22(9), 417–425.  https://doi.org/10.1101/lm.039180.115.CrossRefGoogle Scholar
  33. Shackman, A. J., & Fox, A. S. (2016). Contributions of the central extended amygdala to fear and anxiety. The Journal of Neuroscience, 36(31), 8050–8063.  https://doi.org/10.1523/jneurosci.0982-16.2016.CrossRefGoogle Scholar
  34. Stefanova, N., & Ovtscharoff, W. (2000). Sexual dimorphism of the bed nucleus of the stria terminalis and the amygdala. Advances in Anatomy Embryology and Cell Biology, 158, Iii-x 1-78.Google Scholar
  35. Tabbert, K., Stark, R., Kirsch, P., & Vaitl, D. (2006). Dissociation of neural responses and skin conductance reactions during fear conditioning with and without awareness of stimulus contingencies. Neuroimage, 32(2), 761–770.  https://doi.org/10.1016/j.neuroimage.2006.03.038.CrossRefGoogle Scholar
  36. Zeidan, M. A., Lebron-Milad, K., Thompson-Hollands, J., Im, J. J., Dougherty, D. D., Holt, D. J., et al. (2012). Test-retest reliability during fear acquisition and fear extinction in humans. CNS Neuroscience & Therapeutics, 18(4), 313–317.  https://doi.org/10.1111/j.1755-5949.2011.00238.x.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Laboratory of Experimental Neurosurgery and NeuroanatomyKU LeuvenLeuvenBelgium
  2. 2.Institute for Neuroscience and Department of Psychological and Brain SciencesTexas A&M UniversityCollege StationUSA
  3. 3.Laboratory for Biological PsychologyKU LeuvenLeuvenBelgium
  4. 4.Centre for Psychology of Learning and Experimental PsychopathologyKU LeuvenLeuvenBelgium

Personalised recommendations