Neuropsychology Review

, Volume 29, Issue 2, pp 220–243 | Cite as

The Role of the Amygdala and the Ventromedial Prefrontal Cortex in Emotional Regulation: Implications for Post-traumatic Stress Disorder

  • David G. AndrewesEmail author
  • Lisanne M. Jenkins


The importance of the amygdala as a salience detector and in emotional learning is now well accepted. The mechanisms that regulate and inhibit the amygdala, however, are less well understood. This review provides evidence from imaging and lesion studies to support the role of the ventromedial prefrontal cortex (vmPFC) as a moderator and inhibitor of the amygdala. The dual inhibition model centres on the broadly defined ventromedial prefrontal cortex (vmPFC) and the distinct role of two of its subcomponents, the rostral anterior cingulate cortex and orbitofrontal cortex. The dual inhibition model posits that these two regions, along with their associated inhibitory pathways, must interact for adequate inhibitory control of the amygdala and emotional regulation. Following a description of the model’s experimental support, it is then proposed as a neuropsychological mechanism for post-traumatic stress disorder (PTSD). Flashbacks, as a defining feature of PTSD, are described in terms of a subcortical orienting network. Finally, there is a discussion of how a neuropsychological understanding of post-traumatic stress disorder (PTSD) might inform a clinician’s approach to treatment and how the dual inhibition model might have a more general application to understanding emotional dysregulation.


Ventromedial prefrontal cortex Post traumatic stress disorder PTSD Amygdala Emotion Emotional regulation Treatment Emotional dysregulation Anxiety Neuropsychology Affective neuroscience Brain 



We wish to thank Professor Kim Felmingham for advice during the preparation of this manuscript.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. Admon, R., Leykin, D., Lubin, G., Engert, V., Andrews, J., Pruessner, J., et al. (2013). Stress induced reduction in hippocampal volume and connectivity with the ventromedial prefrontal cortex are related to maladaptive responses to stressful military service. Human Brain Mapping, 34(11), 2808–2816.CrossRefPubMedGoogle Scholar
  2. Admon, R., Lubin, G., Rosenblatt, J. D., Stern, O., Kahn, I., Assaf, M., et al. (2013). Imbalanced neural responsivity to risk and reward indicates stress vulnerability in humans. Cerebral Cortex, 23(1), 28–35.CrossRefPubMedGoogle Scholar
  3. Admon, R., Lubin, G., Stern, O., Rosenberg, K., Sela, L., Ben-Ami, H., et al. (2009). Human vulnerability to stress depends on amygdala’s predisposition and hippocampal plasticity. Proceedings of the National Academy of Sciences USA, 106, 14120–14125.CrossRefGoogle Scholar
  4. Admon, R., Milad, M. R., & Hendler, T. (2013). A causal model of post-traumatic stress disorder: Disentangling predisposed from acquired neural abnormalities. Trends in Cognitive Science, 17, 337–347.CrossRefGoogle Scholar
  5. Adolphs, R. (2013). The biology of fear. Current Biology, 23(2), R79–R93.CrossRefPubMedGoogle Scholar
  6. Adolphs, R., Baron-Cohen, S., & Tranel, D. (2002). Impaired recognition of social emotions following amygdala damage. Journal of Cognitive Neuroscience, 14, 1264–1274.CrossRefGoogle Scholar
  7. Åhs, F., Kragel, P. A., Zielinski, D. J., Brady, R., & LaBar, K. S. (2015). Medial prefrontal pathways for the contextual regulation of extinguished fear in humans. Neuroimage, 122, 262–271.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Allman, J. M., Hakeem, A., Erwin, J. M., Nimchinsky, E., & Hof, P. (2001). The anterior cingulate cortex: The evolution of an interface between emotion and cognition. Annals of the New York Academy of Sciences, 935(1), 107–117.CrossRefPubMedGoogle Scholar
  9. Almeida, I., Soares, S. C., & Castelo-Branco, M. (2015). The distinct role of the amygdala, superior colliculus and pulvinar in processing of central and peripheral snakes. PLoS One, 10(6), e0129949.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 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.CrossRefPubMedGoogle Scholar
  11. Amaral, D. G. (2003). The amygdala, social behavior, and danger detection. Annals of the New York Academy of Sciences, 1000, 337–347.CrossRefPubMedGoogle Scholar
  12. American Psychiatric Association (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC: American Pschiatric Association Publishing.Google Scholar
  13. Amodio, D. M., & Frith, C. D. (2006). Meeting of minds: The medial frontal cortex and social cognition. Nature Reviews Neuroscience, 7(4), 268–277.CrossRefGoogle Scholar
  14. Anastasides, N., Beck, K. D., Pang, K. C., Servatius, R. J., Gilbertson, M. W., Orr, S. P., et al. (2015). Increased generalization of learned associations is related to re-experiencing symptoms in veterans with symptoms of post-traumatic stress. Stress, 18(4), 484–489.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Andrewes, D. G. (2016). Neuropsychology: From theory to practice (2nd ed.). Hove, UK: Routledge. Psychology Press.Google Scholar
  16. Arnsten, A. F., Raskind, M. A., Taylor, F. B., & Connor, D. F. (2015). The effects of stress exposure on prefrontal cortex: Translating basic research into successful treatments for post-traumatic stress disorder. Neurobiology of Stress, 1, 89–99.CrossRefGoogle Scholar
  17. Baldaçara, L., Zugman, A., Araújo, C., Cogo-Moreira, H., Lacerda, A. L., Schoedl, A., et al. (2014). Reduction of anterior cingulate in adults with urban violence-related PTSD. Journal of Affective Disorders, 168, 13–20.CrossRefPubMedGoogle Scholar
  18. Basso, M. A., & May, P. J. (2017). Circuits for action and cognition: A view from the superior colliculus. Annual Review of Visual Science, 3, 197–226.CrossRefGoogle Scholar
  19. Bates, J. F., & Goldman-Rakic, P. S. (1993). Prefrontal connections of medial motor are as in the rhesus monkey. Journal of Comparative Neurolology, 336, 211–228.CrossRefGoogle Scholar
  20. Baxter, M. G., & Murray, E. A. (2002). The amygdala and reward. Nature Reviews Neuroscience, 7, 563–573.CrossRefGoogle Scholar
  21. Bechara, A., Damasio, H., Damasio, A. R., & Lee, G. P. (1999). Different contributions of the human amygdala and ventromedial prefrontal cortex to decision-making. Journal of Neuroscience, 19, 5473–5481.CrossRefPubMedGoogle Scholar
  22. Becker, B., Mihov, Y., Scheele, D., Kendrick, K. M., Feinstein, J. S., Matusch, A., et al. (2012). Fear processing and social networking in the absence of a functional amygdala. Biological Psychiatry, 72(1), 70–77.CrossRefPubMedGoogle Scholar
  23. Beer, J. S., John, O. P., Scabini, D., & Knight, R. T. (2006). Orbitofrontal cortex and social behavior: Integrating self-monitoring and emotion-cognition interactions. Journal of Cognitive Neuroscience, 18, 871–879.CrossRefPubMedGoogle Scholar
  24. Beidel, D. C., Frueh, B. C., Neer, S. M., Bowers, C. A., Trachik, B., Uhde, T. W., et al. (2017). Trauma management therapy with virtual-reality augmented exposure therapy for combat-related PTSD: A randomized controlled trial. Journal of Anxiety Disorders, 53, 23–32.CrossRefGoogle Scholar
  25. Bergström, Z. M., Vogelsang, D. A., Benoit, R. G., & Simons, J. S. (2015). Reflections of oneself: Neurocognitive evidence for dissociable forms of self-referential recollection. Cerebral Cortex, 25(9), 2648–2657.CrossRefPubMedGoogle Scholar
  26. Bittencourt, A. S., Nakamura-Palacios, E. M., Mauad, H., Tufik, S., & Schenberg, L. C. (2005). Organization of electrically and chemically evoked defensive behaviors within the deeper collicular layers as compared to the periaqueductal gray matter of the rat. Neuroscience, 133(4), 873–892.CrossRefPubMedGoogle Scholar
  27. Blair, R. J. (2016). The neurobiology of impulsive aggression. Journal of Child Adolescence Psychopharmacolology, 26(1), 4–9.CrossRefGoogle Scholar
  28. Bonnet, L. A., Comte, L., Tatu, J. L., Millot, T., Moulin, E., Medeiros, T., et al. (2015). The role of the amygdala in the perception of positive emotions: an intensity detector. Frontiers in Behavioural Neuroscience, 9, 178.CrossRefGoogle Scholar
  29. Bradley, R., Greene, J., Russ, E., Dutra, L., & Westen, D. (2005). A multidimensional meta-analysis of psychotherapy for PTSD. American Journal of Psychiatry, 162, 214–227.CrossRefGoogle Scholar
  30. Bremner, J. D. (1999). Acute and chronic responses to psychological trauma: Where do we go from here? American Journal of Psychiatry, 156(3), 349–351.PubMedGoogle Scholar
  31. Bremner, J. D., & Brett, E. (1997). Trauma-related dissociative states and long-term psychopathology in post traumatic stress disorder. Journal of Traumatic Stress, 10, 37–50.PubMedGoogle Scholar
  32. Bremner, J. D., Southwick, S. M., Johnson, D. R., Yehuda, R., & Charney, D. S. (1993). Childhood physical abuse and combat-related post traumatic stress disorder in Vietnam veterans. American Journal of Psychiatry, 150(2), 235–239.CrossRefPubMedGoogle Scholar
  33. Breslau, N. (1998). Epidemiology of trauma and post traumatic stress disorder. In R. Yehuda (Ed.) Psychological trauma (pp. 1–29), Washington, DC: American Psychiatric Press.Google Scholar
  34. Breslau, N., Chilcoat, H. D., Kessler, R. C., & Davis, G. C. (1999). Previous exposure to trauma and PTSD effects of subsequent trauma: Results from the Detroit Area Survey of Trauma. American Journal of Psychiatry, 156(6), 902–907.CrossRefPubMedGoogle Scholar
  35. Brewin, C. R. (2014). Episodic memory, perceptual memory and their interaction: Foundations for a theory of post traumatic stress disorder. Psychological Bulletin, 140(1), 69–97.CrossRefPubMedGoogle Scholar
  36. Brewin, C.R. (2015). Re-experiencing traumatic events in PTSD: new avenues in research on intrusive memories and flashbacks. European Journal of Psychotraumatology, 19, 27180.Google Scholar
  37. Brewin, C. R., Cloitre, M., Hyland, P., Shevlin, M., Maercker, A., Bryant, R. A., et al. (2017). A review of current evidence regarding the ICD-11 proposals for diagnosing PTSD and complex PTSD. Clinical Psychology Review, 58, 1–15.Google Scholar
  38. Brewin, C. R., Gregory, J. D., Lipton, M., & Burgess, N. (2010). Intrusive images in psychological disorders: Characteristics, neural mechanisms and treatment implications. Psychological Review, 117(1), 210–232.CrossRefPubMedPubMedCentralGoogle Scholar
  39. Bridge, H., Harrold, S., Holmes, E. A., Stokes, M., & Kennard, C. (2012). Vivid visual mental imagery in the absence of the primary visual cortex. Journal of Neurology, 259, 1062–1010.CrossRefPubMedGoogle Scholar
  40. Brinkmann, L., Buff, C., Neumeister, P., Tupak, S. V., Becker, M. P., Herrmann, M. J., & Straube, T. (2017). 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.CrossRefPubMedGoogle Scholar
  41. Britton, J. C., Phan, K. L., Taylor, S. F., Fig, L. M., & Liberzon, I. (2005). Corticolimbic blood flow in post traumatic stress disorder during script-driven imagery. Biology Psychiatry, 57, 832–840.CrossRefGoogle Scholar
  42. Bryant, R. A., Creamer, M., O'Donnell, M., Forbes, D., McFarlane, A. C., Silove, D., et al. (2017). Acute and chronic post traumatic stress symptoms in the emergence of post traumatic stress disorder: A network analysis. JAMA Psychiatry, 74(2), 135–142.CrossRefPubMedGoogle Scholar
  43. Bryant, R. A., Felmingham, K., Whitford, T. J., Kemp, A., Hughes, G., Peduto, A., & Williams, L. M. (2008). Rostral anterior cingulate volume predicts treatment response to cognitive-behavioural therapy for post-traumatic stress. Journal of Psychiatry Neuroscience, 33(2), 142–146.PubMedGoogle Scholar
  44. Bryant, R. A., Felmingham, K. L., Kemp, A. H., Barton, M., Peduto, A. S., Rennie, C., et al. (2005). Neural networks of information processing in post traumatic stress disorder: A functional magnetic resonance imaging study. Biological Psychiatry, 58, 111–118.CrossRefPubMedGoogle Scholar
  45. Bryant, R. A., Nickerson, A., Creamer, M., O'Donnell, M., Forbes, D., Galatzer-Levy, I., et al. (2015). Trajectory of post-traumatic stress following traumatic injury: 6-year follow-up. British Journal of Psychiatry, 206(5), 417–423.CrossRefPubMedGoogle Scholar
  46. Buhle, J. T., Silvers, J. A., Wager, T. D., Lopez, R., Onyemekwu, C., Kober, H., et al. (2014). Cognitive reappraisal of emotion: A meta-analysis of human neuroimaging studies. Cerebral Cortex, 24(11), 2981–2990.CrossRefPubMedGoogle Scholar
  47. Burra, N., Hervais-Adelman, A., Celeghin, A., de Gelder, B., & Pegna, A. J. (2017). Affective blindsight relies on low spatial frequencies. Neuropsychologia.
  48. Bush, G., Luu, P., & Posner, M. I. (2000). Cognitive and emotional influences in the anterior cingulate cortex. Trends in Cognitive Neuroscience, 4(6), 215–222.CrossRefGoogle Scholar
  49. Cabeza, R., & St Jacques, P. (2007). Functional neuroimaging of autobiographical memory. Trends in Cognitive Science, 11(5), 219–227.CrossRefGoogle Scholar
  50. Carlsson, K., Petersson, K. M., Lundqvist, D., Karlsson, A., Ingvar, M., & Ohman, A. (2004). Fear and the amygdala: Manipulation of awareness generates differential cerebral responses to phobic and fear-relevant (but nonfeared) stimuli. Emotion, 4(4), 340–353.CrossRefPubMedGoogle Scholar
  51. Cavanna, A. E., & Trimble, M. R. (2008). Behavioral correlates of posteromedial parietal cortex hypometabolism in a family with idiopathic basal ganglia calcifications. Journal of Neurology Science, 266(1-2), 190–191.Google Scholar
  52. Celeghin, A., Bagnis, A., Diano, M., Méndez, C. A., Costa, T., & Tamietto, M. (2018). Functional neuroanatomy of blindsight revealed by activation likelihood estimation meta-analysis. Neuropsychologia.
  53. Cha, L., Weiner, M., & Neylan, T. (2013). Regional cerebral volumes in veterans with current versus remitted post traumatic stress disorder. Psychiatry Research, 213(3), 193–201.CrossRefGoogle Scholar
  54. Chelazzi, L., Miller, E. K., Duncan, J., & Desimone, R. (1993). A neural base for visual search in inferior temporal cortex. Nature, 363, 345–347.CrossRefPubMedGoogle Scholar
  55. Cheung, J., & Bryant, R. A. (2017). The impact of appraisals on intrusive memories. Journal of Behavior Therapy and Experimental Psychiatry, 54, 108–111.CrossRefPubMedGoogle Scholar
  56. Clausen, A. N., Francisco, A. J., Thelen, J., Bruce, J., Martin, L. E., McDowd, J., et al. (2017). PTSD and cognitive symptoms relate to inhibition-related prefrontal activation and functional connectivity. Depression and Anxiety, 34(5), 427–436.CrossRefPubMedPubMedCentralGoogle Scholar
  57. Clauss, J. A., Avery, S. N., van der Klok, R. M., Rogers, B. P., Cowan, R. L., Benningfield, M. M., et al. (2014). Neurocircuitry underlying risk and resilience to social anxiety disorder. Depression and Anxiety, 31(10), 822–833.CrossRefPubMedPubMedCentralGoogle Scholar
  58. Cloitre, M., Jackson, C., & Schmidt, J. A. (2016). Case reports: STAIR for strengthening social support and relationships among veterans with military sexual trauma and PTSD. Military Medicine, 181(2), e183–e187.CrossRefPubMedGoogle Scholar
  59. Cloitre, M., Petkova, E., Wang, J., & Lu Lassel, F. (2012). An examination of the influence of a sequential treatment on the course and impact of dissociation among women with PTSD related to childhood abuse. Depression and Anxiety, 29(8), 709–717.CrossRefPubMedGoogle Scholar
  60. Corbetta, M., Miezin, F. M., & Shulman, G. L. (2002). Control of goal-directed and stimulus-driven attention in the brain. Nature Reviews Neuroscience, 3, 201–215.CrossRefPubMedGoogle Scholar
  61. Corbetta, M., & Shulman, G. L. (2011). Spatial neglect and attention networks. Annual Review of Neuroscience, 34, 569–599.CrossRefPubMedPubMedCentralGoogle Scholar
  62. Costa, V. D., Lang, P. J., Sabatinelli, D., Versace, F., & Bradley, M. M. (2010). Emotional imagery: Assessing pleasure and arousal in the brain's reward circuitry. Human Brain Mapping, 31(9), 1446–1457.CrossRefPubMedPubMedCentralGoogle Scholar
  63. D’Argembeau, A. (2013). On the role of the ventromedial prefrontal cortex in self-processing: the valuation hypothesis. Frontiers in Human Neuroscience, 7, 372.CrossRefPubMedPubMedCentralGoogle Scholar
  64. da Silva, J. A., Almada, R. C., de Figueiredo, R. M., & Coimbra, N. C. (2018). Blockade of synaptic activity in the neostriatum and activation of striatal efferent pathways produce opposite effects on panic attack-like defensive behaviours evoked by GABAergic disinhibition in the deep layers of the superior colliculus. Physiology Behavior, 196, 104–111.CrossRefPubMedGoogle Scholar
  65. Damasio, A. R., & Anderson, S. W. (1993). The frontal Lobes. In K. M. Heilman & K. M. Valenstein (Eds.), Clinical neuropsychology (3rd ed., pp. 409–448). Oxford: Oxford University Press.Google Scholar
  66. Dannlowski, U., Stuhrmann, A., Beutelmann, V., Zwanzger, P., Lenzen, T., Grotegerd, D., et al. (2012). Limbic scars: Long-term consequences of childhood maltreatment revealed by functional and structural magnetic resonance imaging. Biological Psychiatry, 71(4), 286–293.CrossRefPubMedGoogle Scholar
  67. de Gelder, B., Morris, J. S., & Dolan, R. J. (2005). Unconscious fear influences emotional awareness of faces and voices. Proceedings of the National Academy of Science USA, 102, 18682–18687.CrossRefGoogle Scholar
  68. Dedert, E. A., Green, K. T., Calhoun, P. S., Yoash-Gantz, R., Taber, K. H., Mumford, M. M., et al. (2009). Association of trauma exposure with psychiatric morbidity in military veterans who have served since September 11, 2001. Journal of Psychiatric Research, 43(9), 830–836.CrossRefPubMedPubMedCentralGoogle Scholar
  69. Delgado, M. R., Beer, J. S., Fellows, L. K., Huettel, S. A., Platt, M. L., Quirk, G. J., et al. (2016). Viewpoints: Dialogues on the functional role of the ventromedial prefrontal cortex. Nature Neuroscience, 19(12), 1545–1552.CrossRefPubMedGoogle Scholar
  70. Delgado, M. R., Nearing, K. I., Ledoux, J. E., & Phelps, E. A. (2008). Neural circuitry underlying the regulation of conditioned fear and its relation to extinction. Neuron, 59(5), 829–838.CrossRefPubMedPubMedCentralGoogle Scholar
  71. Delgado, M. R., Olsson, A., & Phelps, E. A. (2006). Extending animal models of fear conditioning to humans. Biological Psychology, 73, 39–48.CrossRefPubMedGoogle Scholar
  72. Denny, B. T., Kober, H., Wager, T. D., & Ochsner, K. N. (2012). A meta- analysis of functional neuroimaging studies of self and other judgments reveals a spatial gradient for mentalizing in medial prefrontal cortex. Journal of Cognitive.Neuroscience, 24, 1742–1752.CrossRefPubMedPubMedCentralGoogle Scholar
  73. Denny, B. T., & Ochsner, K. N. (2014). Behavioral effects of longitudinal training in cognitive reappraisal. Emotion, 14(2), 425–433.CrossRefPubMedGoogle Scholar
  74. Desimone, R., & Duncan, J. (1995). Neural mechanisms of selective visual attention. Annual Review of Neuroscience, 18, 193–222.CrossRefPubMedGoogle Scholar
  75. Doré, B. P., Boccagno, C., Burr, D., Hubbard, A., Long, K., Weber, J., et al. (2016). Finding positive meaning in negative experiences engages ventral striatal and ventromedial prefrontal reward regions. Journal of Conitive Neuroscience, 14, 1–10.Google Scholar
  76. Drysdale, A. T., Grosenick, L., Downar, J., Dunlop, K., Mansouri, F., Meng, Y., et al. (2017). Erratum: Resting-state connectivity biomarkers define neurophysiological subtypes of depression. Nature Medicine, 23(2), 264.CrossRefPubMedPubMedCentralGoogle Scholar
  77. Dunlop, B. W., Rajendra, J. K., Craighead, W. E., Kelley, M. E., McGrath, C. L., Choi, K. S., et al. (2017). Functional connectivity of the sub callosal cingulate cortex and differential outcomes to treatment with cognitive-behavioral therapy or antidepressant medication for major depressive disorder. American Journal of Psychiatry, 174(6), 533–545.CrossRefPubMedGoogle Scholar
  78. Dunmore, E., Clark, D. M., & Ehlers, A. (2001). A prospective investigation of the role of cognitive factors in persistent post traumatic stress disorder (PTSD) after physical or sexual assault. Behavior Research and Therapy, 39, 1063–1084.CrossRefGoogle Scholar
  79. Dutra, S. J., & Wolf, E. J. (2017). Perspectives on the conceptualization of the dissociative subtype of PTSD and implications for treatment. Current Opinion in Psychology, 14, 35–39.CrossRefPubMedGoogle Scholar
  80. Ebner-Premier, U., Mauchnik, J., Kleindienst, N., Schmahl, C., Peper, M., Rosenthal, Z., et al. (2009). Emotional learning during dissociative states in borderline personality disorder. Review of Psychiatry Neuroscience, 34, 214–222.Google Scholar
  81. Elsesser, K., Sartory, G., & Tackenberg, A. (2005). Initial symptoms and reactions to trauma-related stimuli and the development of post traumatic stress disorder. Depression and Anxiety, 21(2), 61–70.CrossRefPubMedGoogle Scholar
  82. Engström, M., Karlsson, T., Landtblom, A. M., & Craig, A. D. (2015). Evidence of conjoint activation of the anterior insular and cingulate cortices during effortful tasks. Frontiers in Human Neuroscience, 8, 1071.PubMedPubMedCentralGoogle Scholar
  83. Etkin, A., Buchel, C., & Gross, J. J. (2015). The neural basis of emotion regulation. Nature reviews Neuroscience, 16, 693–700.CrossRefPubMedGoogle Scholar
  84. Etkin, A., Egner, T., & Kalisch, R. (2011). Emotional processing in the anterior cingulate and medial prefrontal cortex. Trends in Cognitive Science, 15(2), 85–93.CrossRefGoogle Scholar
  85. Etkin, A., Klemenhagen, K. C., Dudman, J. T., Rogan, M. T., Hen, R., Kandel, E. R., et al. (2004). Individual differences in trait anxiety predict the response of the basolateral amygdala to unconsciously processed fearful faces. Neuron, 44, 1043–1055.CrossRefPubMedGoogle Scholar
  86. Etkin, A., & Wager, T. D. (2007). Functional neuroimaging of anxiety: A meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. The American Journal of Psychiatry, 164(10), 1476–1488.CrossRefPubMedPubMedCentralGoogle Scholar
  87. Evans, D. A., Stempel, A. V., Vale, R., Ruehle, S., Lefler, Y., & Branco, T. (2018). A synaptic threshold mechanism for computing escape decisions. Nature, 558(7711), 590–594.CrossRefPubMedPubMedCentralGoogle Scholar
  88. Fa, M., Xia, L., Anunu, R., Kehat, O., Kriebel, M., Volkmer, H., et al. (2014). Stress modulation of hippocampal activity spotlight on the dentate gyrus. Neurobiology of Learning and Memory, 112, 53–60.CrossRefPubMedGoogle Scholar
  89. Feinstein, J. S., Adolphs, R., Damasio, A., & Tranel, D. (2011). The human amygdala and the induction and experience of fear. Current Biology, 21, 34–38.CrossRefPubMedGoogle Scholar
  90. Felmingham, K., Kemp, A., & Williams, L. (2007). Anterior cingulate and amygdala changes after cognitive behavior therapy of PTSD. Psychological Science, 18, 127–129.CrossRefPubMedGoogle Scholar
  91. Felmingham, K., Kemp, A. H., Williams, L., Falconer, E., Olivieri, G., Peduto, A., et al. (2008). Dissociative responses to conscious and non-conscious fear impact underlying brain function in post-traumatic stress disorder. Psychological Medicine, 38(12), 1771–1780.CrossRefPubMedGoogle Scholar
  92. Felmingham, K. L., Williams, L. M., Whitford, T. J., Falconer, E., Kemp, A. H., Peduto, A., et al. (2009). Duration of post traumatic stress disorder predicts hippocampal grey matter loss. Neuroreport, 20(16), 1402–1406.CrossRefPubMedGoogle Scholar
  93. Feng, T., Feng, P., & Chen, Z. (2013). Altered resting-state brain activity at functional MRI during automatic memory consolidation of fear conditioning. Brain Research, 1523, 59–67.CrossRefPubMedGoogle Scholar
  94. Forcelli, P. A., Waguespack, H. F., & Malkova, L. (2017). Defensive vocalizations and motor asymmetry triggered by disinhibition of the periaqueductal gray in non-human primates. Frontiers in Neuroscience, 11, 163.CrossRefPubMedPubMedCentralGoogle Scholar
  95. Freton, M., Lemogne, C., Bergouignan, L., Delaveau, P., Lehéricy, S., & Fossati, P. (2014). The eye of the self: Precuneus volume and visual perspective during autobiographical memory retrieval. Brain Structure and Function, 219(3), 959–968.CrossRefPubMedGoogle Scholar
  96. Frewen, P. A., Dozois, D. J. A., Neufeld, R. W. J., Lane, R. D., Densmore, M., Stevens, T. K., et al. (2010). Individual differences in trait mindfulness predict dorsal medial prefrontal and amygdala response during emotional imagery: An fMRI study. Personality and Individual Differences, 49(5), 479–484.CrossRefGoogle Scholar
  97. Frewen, P. A., Pain, C., Dozois, D. J., & Lanius, R. A. (2006). Alexithymia in PTSD: Psychometric and fMRI studies. Annals New York Academy of Sciences, 1071, 397–400.CrossRefGoogle Scholar
  98. Geng, H., Wang, Y., Gu, R., Luo, Y. J., Xu, P., Huang, Y., et al. (2018). Altered brain activation and connectivity during anticipation of uncertain threat in trait anxiety. Human Brain Mapping, 39(10), 3898–3914.CrossRefPubMedGoogle Scholar
  99. Germain, A., McKeon, A. B., & Campbell, R. L. (2017). Sleep in PTSD: Conceptual model and novel directions in brain-based research and interventions. Current Opinion in Psychology, 14, 84–89.CrossRefPubMedGoogle Scholar
  100. Ghashghaei, H. T., Hilgetag, C. C., & Barbas, H. (2007). Sequence of information processing for emotions based on the anatomic dialogue between prefrontal cortex and amygdala. Neuroimage, 34(3), 905–923.CrossRefPubMedGoogle Scholar
  101. Goldin, P. R., McRae, K., Ramel, W., & Gross, J. J. (2008). The neural bases of emotion regulation: Reappraisal and suppression of negative emotion. Biological Psychiatry, 63(6), 577–586.CrossRefGoogle Scholar
  102. Gosselin, N., Peretz, I., Noulhiane, M., Hasboun, D., Beckett, C., Baulac, M., et al. (2005). Impaired recognition of scary music following unilateral temporal lobe excision. Brain, 128(3), 628–640.CrossRefPubMedGoogle Scholar
  103. Grupe, D. W., & Nitschke, J. B. (2013). Uncertainty and anticipation in anxiety: An integrated neurobiological and psychological perspective. Nature Reviews Neuroscience, 14(7), 488–501.CrossRefPubMedPubMedCentralGoogle Scholar
  104. Grupe, D. W., Wielogosz, J., Davidson, R. J., & Nitschke, J. B. (2016). Neurobiological correlates of distinct PTSD symptom profiles during threat anticipation in combat veterans. Psychological Medicine, 46(9), 1885–1895.CrossRefPubMedPubMedCentralGoogle Scholar
  105. Gu, X., Hof, P. R., Friston, K. J., & Fan, J. (2013). Anterior insular cortex and emotional awareness. Journal of Comparative Neurology, 521(15), 3371–3388.CrossRefPubMedGoogle Scholar
  106. Hackmann, A., Ehlers, A., Speckens, A., & Clark, D. M. (2004). Characteristics and content of intrusive memories in PTSD and their changes with treatment. Journal of Traumatic Stress, 17, 231–240.CrossRefPubMedGoogle Scholar
  107. Harricharan, S., Rabellino, D., Frewen, P. A., Densmore, M., Théberge, J., McKinnon, M. C., et al. (2016). fMRI functional connectivity of the periaqueductal gray in PTSD and its dissociative subtype. Brain and Behavior, 6(12), e00579.CrossRefPubMedPubMedCentralGoogle Scholar
  108. Hayes, J. P., Hayes, S. M., & Mikedis, A. M. (2012). Quantitative meta-analysis of neural activity in posttraumatic stress disorder. Biology of Mood & Anxiety Disorders, 2, 9.CrossRefGoogle Scholar
  109. Hellawell, S. J., & Brewin, C. R. (2002). A comparison of flashbacks and ordinary autobiographical memories of trauma: Cognitive resources and behavioural observations. Behaviour Research and Therapy, 40, 1143–1156.CrossRefPubMedGoogle Scholar
  110. Hiser, J., & Koenigs, M. (2018). The multifaceted role of the ventromedial prefrontal cortex in emotion, decision making, social cognition, and psychopathology. Biological Psychiatry, 83(8), 638–647.CrossRefPubMedGoogle Scholar
  111. Holmes, A. L., Forcelli, P. A., DesJardin, J. T., Decker, A. L., Teferra, M., West, E. A., et al. (2012). Superior colliculus mediates cervical dystonia evoked by inhibition of the substantia nigra pars reticulata. Journal of Neuroscience, 32, 13326–13332.CrossRefPubMedGoogle Scholar
  112. Hornak, J., Bramham, J., Rolls, E. T., Morris, R. G., O’Doherty, J., Bullock, P. R., et al. (2003). Changes in emotion after circumscribed surgical lesions of the orbitofrontal and cingulate cortices. Brain, 126, 1691–1712.CrossRefPubMedGoogle Scholar
  113. Hornak, J., O’Doherty, J., Bramham, J., Rolls, E. T., Morris, R. G., Bullock, P. R., et al. (2004). Reward-related reversal learning after surgical excisions in orbitofrontal or dorsolateral prefrontal cortex. Journal of Cognitive Neuroscience, 16, 463–478.CrossRefPubMedGoogle Scholar
  114. Hornak, J., Rolls, E. T., & Wade, D. (1996). Face and voice expression identification in patients with emotional and behavioural changes following ventral frontal lobe damage. Neuropsychologia, 34(4), 247–261.CrossRefPubMedGoogle Scholar
  115. Hourani, L., Tueller, S., Kizakevich, P., Lewis, G., Strange, L., Weimer, B., et al. (2016). Toward preventing post-traumatic stress disorder: Development and testing of a pilot predeployment stress inoculation training program. Military Medicine, 181(9), 1151–1160.CrossRefPubMedGoogle Scholar
  116. Hughes, K. C., & Shin, L. M. (2011). Functional neuroimaging studies of post-traumatic stress disorder. Expert Review of Neurotherapeutics, 11, 275–285.CrossRefPubMedPubMedCentralGoogle Scholar
  117. Hwang, S., Nolan, Z. T., White, S. F., Williams, W. C., Sinclair, S., & Blair, R. J. (2016). Dual neurocircuitry dysfunctions in disruptive behavior disorders: Emotional responding and response inhibition. Psychological Medicine, 46(7), 1485–1496.CrossRefPubMedPubMedCentralGoogle Scholar
  118. Izquierdo, A., & Murray, E. A. (2004). Combined unilateral lesions of the amygdala and orbital prefrontal cortex impair affective processing in rhesus monkeys. Journal of Neurophysiology, 91, 2023–2039.CrossRefPubMedGoogle Scholar
  119. Janak, P. H., & Tye, K. M. (2015). From circuits to behaviour in the amygdala. Nature, 517(7534), 284–292.CrossRefPubMedPubMedCentralGoogle Scholar
  120. Jenkins, L. M., & Andrewes, D. G. (2012). A new set of standardised verbal and nonverbal contemporary film stimuli for the elicitation of emotions. Brain Impairment, 13, 212–227.CrossRefGoogle Scholar
  121. Jenkins, L. M., Andrewes, D. G., Nicholas, C. L., Drummond, K. J., Moffat, B. A., Phal, P., et al. (2014). Social cognition in patients following surgery to the prefrontal cortex. Psychiatry Research, 224(3), 192–203.CrossRefPubMedGoogle Scholar
  122. Jenkins, L. M., Andrewes, D. G., Nicholas, C. L., Drummond, K. J., Moffat, B. A., Phal, P. M., et al. (2018). Emotional reactivity following surgery to the prefrontal cortex. Journal of Neuropsychology, 12(1), 120–141.CrossRefPubMedGoogle Scholar
  123. Jenkins, L. M., Barba, A., Campbell, M., Lamar, M., Shankman, S. A., Leow, A. D., et al. (2016). Shared white matter alterations across emotional disorders: A voxel-based meta-analysis of fractional anisotropy. Neuroimage Clinical, 12, 1022–1034.CrossRefPubMedPubMedCentralGoogle Scholar
  124. Johansen, J. P., Tarpley, J. W., LeDoux, J. E., & Blair, H. T. (2010). Neural substrates for expectation-modulated fear learning in the amygdala and periaqueductal gray. Nature Neuroscience, 13, 979–986.CrossRefPubMedPubMedCentralGoogle Scholar
  125. Johnstone, T., van Reekum, C. M., Urry, H. L., Kalin, N. H., & Davidson, R. J. (2007). Failure to regulate: Counterproductive recruitment of top-down prefrontal-subcortical circuitry in major depression. Journal of Neuroscience, 27(33), 8877–8884.CrossRefPubMedGoogle Scholar
  126. Kalisch, R., Korenfeld, E., Stephan, K. E., Weiskopf, N., Seymour, B., & Dolan, R. J. (2006). Context-dependent human extinction memory is mediated by a ventromedial prefrontal and hippocampal network. Journal of Neuroscience, 26(37), 9503–9511.CrossRefPubMedGoogle Scholar
  127. Kamphausen, S., Schröder, P., Maier, S., Bader, K., Feige, B., Kaller, C.P. et al. (2013). Medial prefrontal dysfunction and prolonged amygdala response during instructed fear processing in borderline personality disorder. World Journal of Biological Psychiatry, 14(4), 307-18.Google Scholar
  128. Ke, J., Zhang, L., Qi, R. F., Xu, Q., Li, W. H., Hou, C. L., et al. (2015). Altered blood oxygen level-dependent signal variability in chronic post-traumatic stress disorder during symptom provocation. Neuropsychiatric Disease and Treatment, 11, 1805–1815.Google Scholar
  129. Kearns, M. C., Ressler, K. J., Zatzick, D., & Rothbaum, B. O. (2012). Early interventions for PTSD: A review. Depression and Anxiety, 29(10), 833–842.CrossRefPubMedPubMedCentralGoogle Scholar
  130. Kim, E. J., Horovitz, O., Pellman, B. A., Tan, L. M., Li, Q., Richter-Levin, G., et al. (2013). Dorsal periaqueductal gray-amygdala pathway conveys both innate and learned fear responses in rats. Proceedings of the National Academy of Sciences USA, 110, 14795–14800.CrossRefGoogle Scholar
  131. Kling, A. S., & Brothers, L. A. (1992). The amygdala and social behavior. In J. P. Aggleton (Ed.), The amygdala: Neurobiological aspects of emotion, memory, and mental dysfunction (pp. 353–377). New York, NY: Wiley-Liss.Google Scholar
  132. Klüver, H., & Bucy, P. C. (1939). Preliminary analysis of the temporal lobes in monkeys. Archives of Neurology and Psychiatry, 42, 979–1000.CrossRefGoogle Scholar
  133. Koenigs, M., & Grafman, J. (2009). Post traumatic stress disorder: The role of medial prefrontal cortex and amygdala. Neuroscientist, 15(5), 540–548.CrossRefPubMedPubMedCentralGoogle Scholar
  134. Koenigs, M., Huey, E. D., Raymont, V., Cheon, B., Solomon, J., Wassermann, E. M., et al. (2008). Focal brain damage protects against post-traumatic stress disorder in combat veterans. Nature Neuroscience, 11, 232–237.CrossRefPubMedGoogle Scholar
  135. Koller, K., Rafal, R. D., Platt, A., & Mitchell, N. D. (2018). Orienting toward threat: Contributions of a subcortical pathway transmitting retinal afferents to the amygdala via the superior colliculus and pulvinar. Neuropsychologia.
  136. Kroes, M. C. W., Whalley, M. G., Rugg, M. D., & Brewin, C. R. (2011). Association between flashbacks and structural brain abnormalities in post traumatic stress disorder. European Psychiatry, 26, 525–531.CrossRefPubMedGoogle Scholar
  137. Kühn, S., & Gallinat, J. (2013). Gray matter correlates of post traumatic stress disorder: A quantitative meta-analysis. Biological Psychiatry, 73(1), 70–74.CrossRefPubMedGoogle Scholar
  138. Kurczek, J., Wechsler, E., Ahuja, S., Jensen, U., Cohen, N. J., Tranel, D., et al. (2015). Differential contributions of hippocampus and medial prefrontal cortex to self-projection and self-referential processing. Neuropsychologia, 73, 116–126.CrossRefPubMedPubMedCentralGoogle Scholar
  139. LaBar, K. S., LeDoux, J. E., Spencer, D. D., & Phelps, E. A. (1995). Impaired fear conditioning following unilateral temporal lobectomy in humans. Journal of Neuroscience, 15, 6846–6855.CrossRefPubMedGoogle Scholar
  140. Langkaas, T. F., Hoffart, A., Øktedalen, T., Ulvenes, P. G., Hembree, E. A., & Smucker, M. (2017). Exposure and non-fear emotions: A randomized controlled study of exposure-based and rescripting-based imagery in PTSD treatment. Behaviour Research and Therapy, 97, 33–42.CrossRefPubMedGoogle Scholar
  141. Lanius, R. A., Bluhm, R., Lanius, U., & Pain, C. (2006). A review of neuroimaging studies in PTSD: Heterogeneity of response to symptom provocation. Journal of Psychiatric Research, 40, 709–729.CrossRefPubMedGoogle Scholar
  142. Lanius, R. A., Bluhm, R. L., & Frewen, P. A. (2011). How understanding the neurobiology of complex post-traumatic stress disorder can inform clinical practice: A social cognitive and affective neuroscience approach. Acta Psychiatrica Scandinavica, 124, 331–348.CrossRefPubMedGoogle Scholar
  143. Lanius, R. A., Williamson, P. C., Boksman, K., Densmore, M., Gupta, M., et al. (2002). Brain activation during script-driven imagery induced dissociative responses in PTSD: A functional magnetic resonance imaging investigation. Biological Psychiatry, 52(4), 305–311.CrossRefPubMedGoogle Scholar
  144. Lanius, R. A., Williamson, P. C., Densmore, M., Boksman, K., Gupta, M., Neufeld, R. W., et al. (2001). Neural correlates of traumatic memories in post traumatic stress disorder: A functional MRI investigation. American Journal of Psychiatry, 158, 1920–1922.CrossRefPubMedGoogle Scholar
  145. Lassalle, A., Åsberg Johnels, J., Zürcher, N. R., Hippolyte, L., Billstedt, E., Ward, N., et al. (2017). Hypersensitivity to low intensity fearful faces in autism when fixation is constrained to the eyes. Human Brain Mapping, 38(12), 5943–5957.CrossRefPubMedGoogle Scholar
  146. LeDoux, J. E. (2000). Emotion circuits in the brain. Annual Review of Neuroscience, 23, 155–184.CrossRefPubMedGoogle Scholar
  147. Lev-Ran, S., Shamay-Tsoory, S. G., Zangen, A., & Levkovitz, Y. (2012). Transcranial magnetic stimulation of the ventromedial prefrontal cortex impairs theory of mind learning. European Psychiatry, 27(4), 285–289.CrossRefPubMedGoogle Scholar
  148. Li, L., Feng, X., Zhou, Z., Zhang, H., Shi, Q., Lei, Z., et al. (2018). Stress accelerates defensive responses to looming in mice and involves a locus coeruleus-superior colliculus projection. Current Biology, 28(6), 859–871.CrossRefPubMedGoogle Scholar
  149. Likhtik, E., Pelletier, J. G., Paz, R., & Paré, D. (2005). Prefrontal control of the amygdala. Journal of Neuroscience, 25(32), 7429–7437.CrossRefPubMedGoogle Scholar
  150. Lin, T., Vaisvaser, S., Fruchter, E., Admon, R., Wald, I., Pine, D. S., et al. (2015). A neurobehavioral account for individual differences in resilience to chronic military stress. Psychological Medicine, 45(5), 1011–1023.CrossRefPubMedGoogle Scholar
  151. Lipinska, M., Timol, R., Kaminer, D., & Thomas, K. G. (2014). Disrupted rapid eye movement sleep predicts poor declarative memory performance in post-traumatic stress disorder. Journal of Sleep Research, 23(3), 309–317.CrossRefPubMedGoogle Scholar
  152. Maguire, E. A. (2014). Memory consolidation in humans: New evidence and opportunities. Experimental Physiology, 99(3), 471–486.CrossRefPubMedPubMedCentralGoogle Scholar
  153. Maier, S. J., Szalkowski, A., Kamphausen, S., Feige, B., Perlov, E., Kalisch, R., et al. (2014). Altered cingulate and amygdala response towards threat and safe cues in attention deficit hyperactivity disorder. Psychological Medicine, 44(1), 85–98.CrossRefPubMedGoogle Scholar
  154. Mancini, A., & Mancini, F. (2018). Rescripting memory, redefining the self: A meta-emotional perspective on the hypothesized mechanism(s) of imagery rescripting. Frontiers in Psychology, 9, 581.CrossRefPubMedPubMedCentralGoogle Scholar
  155. Mao, C. V., Araujo, M. F., Nishimaru, H., Matsumoto, J., Tran, A. H., Hori, E., et al. (2017). Pregenual anterior cingulate gyrus involvement in spontaneous social interactions in primates-evidence from behavioral, pharmacological, neuropsychiatric, and neurophysiological findings. Frontiers in Neuroscience, 11, 34.CrossRefPubMedPubMedCentralGoogle Scholar
  156. McIsaac, H. K., & Eich, E. (2004). Vantage point in traumatic memory. Psychological Science, 15(4), 248–253.CrossRefPubMedGoogle Scholar
  157. McNally, R. J., Bryant, R. A., & Ehlers, A. (2003). Does early psychological intervention promote recovery from posttraumatic stress? Psychological Science in the Public Interest, 4(2), 45–79.CrossRefPubMedGoogle Scholar
  158. Medford, N., & Critchley, H. D. (2010). Conjoint activity of anterior insular and anterior cingulate cortex: Awareness and response. Brain Structure and Function, 214(5-6), 535–549.CrossRefPubMedGoogle Scholar
  159. Medford, N., Sierra, M., Stringaris, A., Giampietro, V., Brammer, M. J., & David, A. S. (2016). Emotional experience and awareness of self: Functional MRI studies of depersonalization disorder. Frontiers in Psychology, 7, 432.CrossRefPubMedPubMedCentralGoogle Scholar
  160. Milad, M. R., Orr, S. P., Lasko, N. B., Chang, Y. C., Rauch, S. L., & Pitman, R. K. (2008). Presence and acquired origin of reduced recall for fear extinction in PTSD: Results of a twin study. Journal of Psychiatric Research, 42(7), 515–520.CrossRefPubMedPubMedCentralGoogle Scholar
  161. Milad, M. R., Pitman, R. K., Ellis, C. B., Gold, A. L., Shin, L. M., Lasko, N. B., et al. (2009). Neurobiological basis of failure to recall extinction memory in post traumatic stress disorder. Biological Psychiatry, 66(12), 1075–1082.CrossRefPubMedPubMedCentralGoogle Scholar
  162. Milad, M. R., & Quirk, G. J. (2002). Neurons in medial prefrontal cortex signal memory for fear extinction. Nature, 420, 70–74.CrossRefPubMedGoogle Scholar
  163. Milad, M. R., Rauch, S. L., Pitman, R. K., & Quirk, G. J. (2006). Fear extinction in rats: Implications for human brain imaging and anxiety disorders. Biological Psychology, 73, 61–71.CrossRefPubMedGoogle Scholar
  164. Minzenberg, M. J., Fan, J., New, A. S., Tang, C. Y., & Siever, L. J. (2007). Fronto-limbic dysfunction in response to facial emotion in borderline personality disorder: An event-related fMRI study. Psychiatry Research, 155(3), 231–243.CrossRefPubMedPubMedCentralGoogle Scholar
  165. Mishkin, M. (1964). Perseveration of central sets after frontal lesions in monkeys. In J. M. Warren & K. Akert (Eds.), The Frontal Granular Cortex and Behavior (pp. 219–241). New York: McGraw-Hill.Google Scholar
  166. Moadab, G., Bliss-Moreau, E., Bauman, M. D., & Amaral, D. G. (2017). Early amygdala or hippocampus damage influences adolescent female social behavior during group formation. Behavioral Neuroscience, 131(1), 68–82.CrossRefPubMedPubMedCentralGoogle Scholar
  167. Mobbs, D., Hagan, C. C., Dalgleish, T., Silston, B., & Prévost, C. (2015). The ecology of human fear: Survival optimization and the nervous system. Frontiers in Neuroscience, 9, 55.CrossRefPubMedPubMedCentralGoogle Scholar
  168. Mobbs, D., Petrovic, P., Marchant, J. L., Hassabis, D., Weiskopf, N., Seymour, B., et al. (2010). When fear is near: Threat imminence elicits prefrontal - periaqueductal grey shifts in humans. Science, 317(5841), 1079–1083.CrossRefGoogle Scholar
  169. Monk, C. S., Weng, S. J., Wiggins, J. L., Kurapati, N., Louro, H. M., Carrasco, M., et al. (2010). Neural circuitry of emotional face processing in autism spectrum disorders. Journal of Psychiatry Neuroscience, 35(2), 105–114.CrossRefPubMedGoogle Scholar
  170. Morey, R. A., Dunsmoor, J. E., Haswell, C. C., Brown, V. M., Vora, A., Weiner, J., et al. (2015). VA Mid-Atlantic MIRECC Workgroup, LaBar KS. Fear learning circuitry is biased toward generalization of fear associations in post traumatic stress disorder. Translational Psychiatry, 5(12), e700.CrossRefPubMedPubMedCentralGoogle Scholar
  171. Morgenthaler, T. I., Auerbach, S., Casey, K. R., Kristo, D., Maganti, R., Ramar, K., et al. (2018). Position paper for the treatment of nightmare disorder in adults: An American Academy of Sleep Medicine position paper. Journal of Clinical Sleep Medicine, 14(6), 1041–1055.CrossRefPubMedPubMedCentralGoogle Scholar
  172. Mørkved, N., Hartmann, K., Aarsheim, L. M., Holen, D., Milde, A. M., Bomyea, J., et al. (2014). A comparison of narrative exposure therapy and prolonged exposure therapy for PTSD. Clinical Psychology Review, 34(6), 453–467.CrossRefPubMedGoogle Scholar
  173. Morrison, S. E., & Salzman, C. D. (2010). Re-valuing the amygdala. Current Opinion in Neurobiology, 20(2), 221–230.CrossRefPubMedPubMedCentralGoogle Scholar
  174. Motzkin, J. C., Philippi, C. L., Wolf, R. C., Baskaya, M. K., & Koenigs, M. (2015). Ventromedial prefrontal cortex is critical for the regulation of amygdala activity in humans. Biological Psychiatry, 77, 276–284.CrossRefPubMedGoogle Scholar
  175. Münsterkötter, A. L., Notzon, S., Redlich, R., Grotegerd, D., Dohm, K., Arolt, V., et al. (2015). Spider or no spider? Neural correlates of sustained and phasic fear in spider phobia. Depression and Anxiety, 32, 656–663.CrossRefPubMedGoogle Scholar
  176. Nardo, D., Högberg, G., Jonsson, C., Jacobsson, H., Hällström, T. & Pagani, M. (2015). Neurobiology of Sleep Disturbances in PTSD Patients and Traumatized Controls: MRI and SPECT Findings. Frontiers of  Psychiatry, 6, 134.Google Scholar
  177. Nelson, M. D., & Tumpap, A. M. (2016). Post traumatic stress disorder symptom severity is associated with left hippocampal volume reduction: A meta-analytic study. CNS Spectrums, 22(4), 363–372.Google Scholar
  178. Nicholson, A. A., Friston, K. J., Zeidman, P., Harricharan, S., McKinnon, M. C., Densmore, M., et al. (2017). Dynamic causal modeling in PTSD and its dissociative subtype: Bottom-up versus top-down processing within fear and emotion regulation circuitry. Human Brain Mapping, 38(11), 5551–5556.CrossRefPubMedGoogle Scholar
  179. Nicholson, A. A., Rabellino, D., Densmore, M., Frewen, P. A., Paret, C., Kluetsch, R., et al. (2017). The neurobiology of emotion regulation in posttraumatic stress disorder: Amygdala down regulation via real-time fMRI neurofeedback. Human Brain Mapping, 38(1), 541–560.CrossRefPubMedGoogle Scholar
  180. Ochsner, K. N., & Gross, J. J. (2005). The cognitive control of emotion. Trends in Cognitive Science, 9, 242–249.CrossRefGoogle Scholar
  181. O'Doherty, D. C. M., Tickell, A., Ryder, W., Chan, C., Hermens, D. F., Bennett, M. R., et al. (2017). Frontal and subcortical grey matter reductions in PTSD. Psychiatry Research, 266, 1–9.CrossRefPubMedGoogle Scholar
  182. O'Donnell, M. L., Creamer, M., Elliott, P., & Bryant, R. (2007). Tonic and phasic heart rate as predictors of post traumatic stress disorder. Psychosomatic Medicine, 69(3), 256–261.CrossRefPubMedGoogle Scholar
  183. Offringa, R., Handwerger Brohawn, K., Staples, L. K., Dubois, S. J., Hughes, K. C., Pfaff, D. L., et al. (2013). Diminished rostral anterior cingulate cortex activation during trauma-unrelated emotional interference in PTSD. Biology of Mood and Anxiety Disorders, 3(1), 10.CrossRefPubMedGoogle Scholar
  184. Ohayon, M. M., & Shapiro, C. M. (2000). Sleep disturbances and psychiatric disorders associated with post traumatic stress disorder in the general population. Comparative Psychiatry, 41, 469–478.CrossRefGoogle Scholar
  185. Ohman, A. (2005). The role of the amygdala in human fear: Automatic detection of threat. Psychoneuroendocrinology, 30(10), 953–958.CrossRefPubMedGoogle Scholar
  186. Ohman, A., Carlsson, K., Lundqvist, D. I., & Ingvar, M. (2007). On the unconscious subcortical origin of human fear. Physiology and Behavior, 92(1-2), 180–185.CrossRefPubMedGoogle Scholar
  187. Ongür, D., & Price, J. L. (2000). The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. Cerebral Cortex, 10(3), 206–219.CrossRefPubMedGoogle Scholar
  188. Onoda, K., & Yamaguchi, S. (2015). Dissociative contributions of the anterior cingulate cortex to apathy and depression: Topological evidence from resting-state functional MRI. Neuropsychologia, 77, 10–18.CrossRefPubMedGoogle Scholar
  189. Osuch, E. A., Benson, B., Geraci, M., Podell, D., Herscovitch, P., McCann, U. D., et al. (2001). Regional cerebral blood flow correlated with flashback intensity in patients with post traumatic stress disorder. Biological Psychiatry, 50(4), 246–253.CrossRefPubMedGoogle Scholar
  190. Pace-Schott, E. F., Germain, A., & Milad, M. R. (2015). Sleep and REM sleep disturbance in the pathophysiology of PTSD: The role of extinction memory. Biology of Mood and Anxiety Disorders, 5, 3.CrossRefPubMedGoogle Scholar
  191. Pace-Schott, E. F., Verga, P. W., Bennett, T. S., & Spencer, R. M. (2012). Sleep promotes consolidation and generalization of extinction learning in simulated exposure therapy for spider fear. Journal of Psychiatric Research, 46, 1036–1044.CrossRefPubMedPubMedCentralGoogle Scholar
  192. Paret, C., Ruf, M., Gerchen, M. F., Kluetsch, R., Demirakca, T., Jungkunz, M., et al. (2016). fMRI neurofeedback of amygdala response to aversive stimuli enhances prefrontal-limbic brain connectivity. Neuroimage, 125, 182–188.CrossRefPubMedGoogle Scholar
  193. Patel, R., Spreng, R. N., Shin, L. M., & Girard, T. A. (2012). Neurocircuitry models of posttraumatic stress disorder and beyond: A meta-analysis of functional neuroimaging studies. Neuroscience and Biobehavioral Reviews, 36(9), 2130–2142.CrossRefPubMedGoogle Scholar
  194. Patterson, K., Nestor, P. J., & Rogers, T. T. (2007). Where do you know what you know? The representation of semantic knowledge in the human brain. Nature Reviews Neuroscience, 8(12), 976–987.CrossRefPubMedGoogle Scholar
  195. Penfield, W. (1957). In W. Penfield & T. Rasmussen (Eds.), The cerebral cortex of man: A clinical study of localization of function (4th ed., pp. 157–181). New York: Macmillan.Google Scholar
  196. Pessoa, L., Kastner, S., & Ungerleider, L. G. (2002). Attentional control of the processing of neural and emotional stimuli. Cognitive Brain Research, 15(1), 31–45.CrossRefPubMedGoogle Scholar
  197. Phelps, E. A., Delgado, M. R., Nearing, K. I., & LeDoux, J. E. (2004). Extinction learning in humans: Role of the amygdala and vmPFC. Neuron, 43(6), 897–905.CrossRefPubMedGoogle Scholar
  198. Philippi, C. L., & Koenigs, M. (2014). The neuropsychology of self-reflection in psychiatric illness. Journal of Psychiatric Research, 54, 55–63.CrossRefPubMedGoogle Scholar
  199. Phillips, M. L., Ladouceur, C. D., & Drevets, W. C. (2008). A neural model of voluntary and automatic emotion regulation: Implications for understanding the pathophysiology and neurodevelopment of bipolar disorder. Molecular Psychiatry, 13(9), 829–857.CrossRefPubMedPubMedCentralGoogle Scholar
  200. Pineles, S. L., Shipherd, J. C., Mostoufi, S. M., Abramovitz, S. M., & YovelI, I. (2009). Attentional biases in PTSD: More evidence for interference. Behaviour Research Therapy, 47(12), 1050.CrossRefPubMedGoogle Scholar
  201. Pitskel, N. B., Bolling, D. Z., Kaiser, M. D., Crowley, M. J., & Pelphrey, K. A. (2011). How grossed out are you? The neural bases of emotion regulation from childhood to adolescence. Developmental Cognitive Neuroscience, 1(3), 324–337.CrossRefPubMedPubMedCentralGoogle Scholar
  202. Powers, M. B., Halpern, J. M., Ferenschak, M. P., Gillihan, S. J., & Foa, E. B. (2010). A meta-analytic review of prolonged exposure for posttraumatic stress disorder. Clinical Psychology Review, 30(6), 635–641.CrossRefPubMedGoogle Scholar
  203. Price, J. L., & Drevets, W. C. (2010). Neurocircuitry of mood disorders. Neuropsychopharmacology, 35(1), 192–216.CrossRefPubMedGoogle Scholar
  204. Pujara, M., & Koenigs, M. (2014). Mechanisms of reward circuit dysfunction in psychiatric illness: Prefrontal-striatal interactions. Neuroscientist, 20(1), 82–95.CrossRefPubMedGoogle Scholar
  205. Quirk, G. J., & Beer, J. S. (2006). Prefrontal involvement in the regulation of emotion: Convergence of rat and human studies. Current Opinion in Neurobiology, 16(6), 723–727.CrossRefPubMedGoogle Scholar
  206. Quirk, G. J., Likhtik, E., Pelletier, J. G., & Pare, D. (2003). Stimulation of medial prefrontal cortex decreases the responsiveness of central amygdala output neurons. Journal of Neuroscience, 23, 8800–8807.CrossRefPubMedGoogle Scholar
  207. Raabe, S., Ehring, T., Marquenie, L., Olff, M., & Kindt, M. (2015). Imagery rescripting as stand-alone treatment for posttraumatic stress disorder related to childhood abuse. Journal of Behavior Therapy and Experimental Psychiatry, 48, 170–176.CrossRefPubMedGoogle Scholar
  208. Raichle, M. E., MacLeod, A. M., Snyder, A. Z., Powers, W. J., Gusnard, D. A., & Shulman, G. L. (2001). A default mode of brain function. Proceedings of the National Academy of Sciences of the United States of America, 98(2), 676–682.CrossRefPubMedPubMedCentralGoogle Scholar
  209. Rauch, S. L., Shin, L. M., & Phelps, E. A. (2006). Neurocircuitry models of post traumatic stress disorder and extinction: Human neuroimaging research- past, present, and future. Biological Psychiatry, 60, 376–382.CrossRefPubMedGoogle Scholar
  210. Resnick, H. S., Kilpatrick, D. G., Dansky, B. S., Saunders, B. E., & Best, C. L. (1993). Prevalence of civilian trauma and post traumatic stress disorder in a representative national sample of women. Journal of Consulting and Clinical Psychology, 61, 984–991.CrossRefPubMedGoogle Scholar
  211. Rigoli, F., Ewbank, M., Dalgleish, T., & Calder, A. (2016). Threat visibility modulates the defensive brain circuit underlying fear and anxiety. Neuroscience Letters, 612, 7–13.CrossRefPubMedPubMedCentralGoogle Scholar
  212. Robinson, O. J., Charney, D. R., Overstreet, C., Vytal, K., & Grillon, C. (2012). The adaptive threat bias in anxiety: Amygdala-dorsomedial prefrontal cortex coupling and aversive amplification. Neuroimage, 60, 523–529.CrossRefPubMedGoogle Scholar
  213. Rolls, E. (2005). Emotions explained. Oxford: Oxford University Press.CrossRefGoogle Scholar
  214. Rose, S., Bisson, J., Churchill, R., & Wessely, S. (2002). Psychological debriefing for preventing post traumatic stress disorder (PTSD). Cochrane Database Systematic Review. 002, Issue 2. Art. No.: CD000560.Google Scholar
  215. Rothbaum, B. O., Kearns, M. C., Price, M., Malcoun, E., Davis, M., Ressler, K. J., et al. (2012). Early intervention may prevent the development of post traumatic stress disorder: A randomized pilot civilian study with modified prolonged exposure. Biological Psychiatry, 72, 957–963.CrossRefPubMedPubMedCentralGoogle Scholar
  216. Roy, M., Shohamy, D., & Wager, T. D. (2012). Ventromedial prefrontal-subcortical systems and the generation of affective meaning. Trends in Cognitive Science, 16, 147–156.CrossRefGoogle Scholar
  217. Sadeh, N., Spielberg, J. M., Miller, M. W., Milberg, W. P., Salat, D. H., Amick, M. M., et al. (2015). Neurobiological indicators of disinhibition in post traumatic stress disorder. Human Brain Mapping, 36(8), 3076–3086.CrossRefPubMedPubMedCentralGoogle Scholar
  218. Sakamoto, H., Fukuda, R., Okuaki, T., Rogers, M., Kasai, K., Machida, T., et al. (2005). Parahippocampal activation evoked by masked traumatic images in post traumatic stress disorder: A functional MRI study. Neuroimage, 26(3), 813–821.CrossRefPubMedGoogle Scholar
  219. Santos, S., Almeida, I., Oliveiros, B., & Castelo-Branco, M. (2016). The role of the amygdala in facial trustworthiness processing: A systematic review and meta-analysis of fMRI Studies. PLoS One, 11(11), e0167276.CrossRefPubMedPubMedCentralGoogle Scholar
  220. Saxe, G., Stoddard, F., Courtney, D., Cunningham, K., Chawla, N., Sheridan, R., et al. (2001). Relationship between acute morphine and the course of PTSD in children with burns. Journal of the American Academy of Child Adolescent Psychiatry, 40(8), 915–921.CrossRefPubMedGoogle Scholar
  221. Schalinski, I., Teicher, M. H., Nischk, D., Hinderer, E., Müller, O., & Rockstroh, B. (2016). Type and timing of adverse childhood experiences differentially affect severity of PTSD, dissociative and depressive symptoms in adult inpatients. BMC Psychiatry, 16, 295.CrossRefPubMedPubMedCentralGoogle Scholar
  222. Schiller, D., & Delgado, M. R. (2010). Overlapping neural systems mediating extinction, reversal and regulation of fear. Trends in Cognitive Science, 14(6), 268–276.CrossRefGoogle Scholar
  223. Schneider, B., & Koenigs, M. (2017). Human lesion studies of ventromedial prefrontal cortex. Neuropsychologia, 107, 84–93.CrossRefPubMedGoogle Scholar
  224. Schumm, J. A., Dickstein, B. D., Walter, K. H., Owens, G. P., & Chard, K. M. (2015). Changes in posttraumatic cognitions predict changes in posttraumatic stress disorder symptoms during cognitive processing therapy. Journal of Consulting and Clinical Psychology, 83(6), 1161–1166.CrossRefPubMedGoogle Scholar
  225. Sebastian, C. L., Fontaine, N. M., Bird, G., Blakemore, S. J., Brito, S. A., McCrory, E. J., et al. (2012). Neural processing associated with cognitive and affective theory of mind in adolescents and adults. Social Cognitive and Affective Neuroscience, 7(1), 53–63.CrossRefPubMedGoogle Scholar
  226. Seeley, W. W., Menon, V., Schatzberg, A. F., Keller, J., Glover, G. H., Kenna, H., et al. (2007). Dissociable intrinsic connectivity networks for salience processing and executive control. Journal of Neuroscience, 27(9), 2349–2356.CrossRefPubMedGoogle Scholar
  227. Shamay-Tsoory, S. G., & Aharon-Peretz, J. (2007). Dissociable prefrontal networks for cognitive and affective theory of mind: A lesion study. Neuropsychologia, 45(13), 3054–3067.CrossRefPubMedGoogle Scholar
  228. Shen, K., Valero, J., Day, G. S., & Paré, M. (2011). Investigating the role of the superior colliculus in active vision with the visual search paradigm. European Journal of Neuroscience, 33(11), 2003–2016.CrossRefPubMedGoogle Scholar
  229. Shin, L. M., Rauch, S. L., & Pitman, R. K. (2006). Amygdala, medial prefrontal cortex, and hippocampal function in PTSD. Annals of New York Academy of Science, 1071, 67–79.CrossRefGoogle Scholar
  230. Shuhama, R., Rondinoni, C., de Araujo, D. B., de Freitas Caetano, G., Dos Santos, A. C., Graeff, F. G., et al. (2016). Behavioral and neuroimaging responses induced by mental imagery of threatening scenarios. Behavior Brain Research, 313, 358–369.CrossRefGoogle Scholar
  231. Silverstein, D. N., & Ingvar, M. (2015). A multi-pathway hypothesis for human visual fear signaling. Frontiers in Systems Neuroscience, 9, 101.CrossRefPubMedPubMedCentralGoogle Scholar
  232. Slofstra, C., Nauta, M. H., Holmes, E. A., & Bockting, C. L. (2016). Imagery rescripting: The impact of conceptual and perceptual changes on aversive autobiographical memories. PLoS One, 11(8), e0160235.CrossRefPubMedPubMedCentralGoogle Scholar
  233. Somerville, L., Whalen, P., & Kelley, W. (2010). Human bed nucleus of the stria terminalis indexes hypervigilant threat monitoring. Biological Psychiatry, 68(5), 416–424.CrossRefPubMedPubMedCentralGoogle Scholar
  234. Sotres-Bayon, F., & Quirk, G. J. (2010). Prefrontal control of fear: More than just extinction. Current Opinion in Neurobiology, 20, 231–235.CrossRefPubMedPubMedCentralGoogle Scholar
  235. Stark, E. A., Parsons, C. E., van Hartevelt, T. J., Charquero-Ballester, M., McManners, H., Ehlers, A., et al. (2015). Post-traumatic stress influences the brain even in the absence of symptoms: A systematic, quantitative meta-analysis of neuroimaging studies. Neuroscience Biobehavioral Review, 56, 207–221.CrossRefGoogle Scholar
  236. Stein, D. J., Koenen, K. C., Friedman, M. J., Hill, E., McLaughlin, K. A., Petukhova, M., et al. (2013). Dissociation in posttraumatic stress disorder: Evidence from the world mental health surveys. Biological Psychiatry, 73(4), 302–312.CrossRefPubMedGoogle Scholar
  237. Stevens, J. S., Jovanovic, T., Fani, N., Ely, T. D., Glover, E. M., Bradley, B., et al. (2013). Disrupted amygdala-prefrontal functional connectivity in civilian women with post traumatic stress disorder. Journal of Psychiatry Research, 47(10), 1469–1478.CrossRefGoogle Scholar
  238. Stoddard, F. J., Jr., Sorrentino, E. A., Ceranoglu, T. A., Saxe, G., Murphy, J. M., Drake, J. E., et al. (2009). Preliminary evidence for the effects of morphine on post traumatic stress disorder symptoms in one- to four-year-olds with burns. Journal of Burn Care Research, 30(5), 836–843.CrossRefPubMedGoogle Scholar
  239. Straube, T., Mentzel, H. J., & Miltner, W. H. R. (2007). Waiting for spiders: Brain activation during anticipatory anxiety in spider phobics. NeuroImage, 37, 1427–1436.CrossRefPubMedGoogle Scholar
  240. Sussman, T. J., Jin, J., & Mohanty, A. (2016). Top-down and bottom-up factors in threat-related perception and attention in anxiety. Biological Psychology, 121(Pt B), 160–172.CrossRefPubMedGoogle Scholar
  241. Sussman, T. J., Weinberg, A., Szekely, A., Hajcak, G., & Mohanty, A. (2017). Here comes trouble: Prestimulus brain activity predicts enhanced perception of threat. Cerebral Cortex, 27(4), 2695–2707.PubMedGoogle Scholar
  242. Svoboda, E., McKinnon, M. C., & Levine, B. (2006). The functional neuroanatomy of autobiographical memory: A meta-analysis. Neuropsychologia, 44, 2189–2208.CrossRefPubMedPubMedCentralGoogle Scholar
  243. Tamietto, M., Pullens, P., deGelder, B., Weiskrantz, L., & Goebel, R. (2012). Subcortical connections to human amygdala and changes following destruction of the visual cortex. Current Biology, 22, 1449–1455.CrossRefPubMedGoogle Scholar
  244. Thomaes, K., Dorrepaal, E., Draijer, N., Jansma, E. P., Veltman, D. J., & van Balkom, A. J. (2014). Can pharmacological and psychological treatment change brain structure and function in PTSD? A systematic review. Journal of Psychiatry Research, 50, 1–15.CrossRefGoogle Scholar
  245. Thome, J., Densmore, M., Frewen, P. A., McKinnon, M. C., Théberge, J., Nicholson, A. A., et al. (2017). Desynchronization of autonomic response and central autonomic network connectivity in post traumatic stress disorder. Human Brain Mapping, 38(1), 27–40.CrossRefPubMedGoogle Scholar
  246. Timbie, C., & Barbas, H. (2014). Specialized pathways from the primate amygdala to posterior orbitofrontal cortex. The Journal of Neuroscience, 34(24), 8106–8118.CrossRefPubMedPubMedCentralGoogle Scholar
  247. Tranel, D., & Hyman, B. T. (1990). Neuropsychological correlates of bilateral amygdala damage. Archives of Neurology, 47, 349–355.CrossRefPubMedGoogle Scholar
  248. van Well, S., Visser, R. M., Scolte, H. S., & Kindt, M. (2012). Neural substrates of individual differences in human fear learning: Evidence from concurrent fMRI, fear-potentiated startle, and US-expectancy data. Cognitive, Affective & Behavioral Neuroscience, 12(3), 499–512.CrossRefGoogle Scholar
  249. Vytal, K. E., Overstreet, C., Charney, D. R., Robinson, O., & Grillon, C. (2014). Sustained anxiety increases amygdala–dorsomedial prefrontal coupling: A mechanism for maintaining an anxious state in healthy adults. Journal of Psychiatry & Neuroscience, 39(5), 321–329.CrossRefGoogle Scholar
  250. Wagner, D. D., Haxby, J. V., & Heatherton, T. F. (2012). The representation of self and person knowledge in the medial prefrontal cortex. Wiley Interdisciplinary Review Cognitive Science, 3(4), 451–470.CrossRefGoogle Scholar
  251. Wallis, J. D. (2007). Orbitofrontal cortex and its contribution to decision-making. Annual Review Neuroscience, 30, 31–56.CrossRefGoogle Scholar
  252. Watson, T. C., Cerminara, N. L., Lumb, B. M., & Apps, R. (2016). Neural correlates of fear in the periaqueductal gray. Journal of Neuroscience, 36(50), 12707–12719.CrossRefPubMedGoogle Scholar
  253. Weiskrantz, L. (1956). Behavioural changes related to the destruction of the amygdaloid complex. Journal of Comparative and Physiological Psychology, 49, 381–391.CrossRefPubMedGoogle Scholar
  254. Whalley, M. G., Kroes, M. C., Huntley, Z., Rugg, M. D., Davis, S. W., & Brewin, C. R. (2013). An fMRI investigation of post traumatic flashbacks. Brain and Cognition, 81(1), 151–159.CrossRefPubMedPubMedCentralGoogle Scholar
  255. Wicking, M., Steiger, F., Nees, F., Diener, S. J., Grimm, O., Ruttorf, M., et al. (2016). Deficient fear extinction memory in post traumatic stress disorder. Neurobiology of Learning and Memory, 136, 116–126.CrossRefPubMedGoogle Scholar
  256. Williams, A. D., & Moulds, M. L. (2007). Cognitive avoidance of intrusive memories: Recall vantage perspective and associations with depression. Behavioural Research and Therapy, 45(6), 1141–1153.CrossRefGoogle Scholar
  257. Williams, L. M., Kemp, A. H., & Felmingham, K. (2006). Trauma modulates amygdala and medial prefrontal responses to consciously attended fear. Neuroimage, 29, 347–357.CrossRefPubMedGoogle Scholar
  258. Winkelmann, T., Grimm, O., Pohlack, S. T., Nees, F., Cacciaglia, R., Dinu-Biringer, R., et al. (2016). Brain morphology correlates of inter individual differences in conditioned fear acquisition and extinction learning. Brain Structure and Function, 221(4), 1927–1937.CrossRefPubMedGoogle Scholar
  259. Wittmann, M.K., Kolling, N., Faber, N.S., Scholl, J., Nelissen, N., Rushworth, M.F. (2016). Self-Other mergence in the frontal cortex during cooperation and competition. Neuron, 91(2), 482–493.Google Scholar
  260. Wolf, E. J., Miller, M. W., Reardon, A. F., Ryabchenko, K. A., Castillo, D., & Freund, R. (2012). A latent class analysis of dissociation and post traumatic stress disorder: Evidence for a dissociative subtype. Archives of General Psychiatry, 69(7), 698–705.Google Scholar
  261. Ye, X., Kapeller-Libermann, D., Travaglia, A., Inda, M. C., & Alberini, C. M. (2017). Direct dorsal hippocampal-prelimbic cortex connections strengthen fear memories. Nature Neuroscience, 20(1), 52–61.CrossRefPubMedGoogle Scholar
  262. Zhang, Y., Xie, B., Chen, H., Li, M., Guo, X., & Chen, H. (2016). Disrupted resting-state insular subregions functional connectivity in post-traumatic stress disorder. Medicine (Baltimore), 95(27), e4083.CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Melbourne Neuropsychiatry Centre, Department of PsychiatryUniversity of MelbourneMelbourneAustralia
  2. 2.Department of Psychiatry and Behavioral SciencesNorthwestern UniversityChicagoUSA

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