Fear Extinction Learning in Posttraumatic Stress Disorder.
Journal
Current topics in behavioral neurosciences
ISSN: 1866-3370
Titre abrégé: Curr Top Behav Neurosci
Pays: Germany
ID NLM: 101535383
Informations de publication
Date de publication:
2023
2023
Historique:
medline:
20
11
2023
pubmed:
3
8
2023
entrez:
3
8
2023
Statut:
ppublish
Résumé
Impairments in fear extinction processes have been implicated in the genesis and maintenance of debilitating psychopathologies, including Posttraumatic stress disorder (PTSD). PTSD, classified as a trauma- and stressor-related disorder, is characterized by four symptom clusters: intrusive recollections of trauma, avoidance of trauma-related stimuli, alterations in cognition and mood, and hyperarousal. One of the key pathological feature associated with the persistence of these symptoms is impaired fear extinction, as delineated in multiple studies employing Pavlovian fear-conditioning paradigms. These paradigms, comprising fear acquisition, extinction, extinction recall, and fear renewal phases, have illuminated the neurobiological substrates of PTSD. Dysfunctions in the neural circuits that mediate these fear learning and extinction processes can result in failure to extinguish fear responses and retain extinction memory, giving rise to enduring experience of fear and anxiety. The protective avoidance behaviors observed in individuals with PTSD further exacerbate intrusive symptoms and pose challenges to effective treatment strategies. A comprehensive analysis of fear conditioning and extinction processes, along with the underlying neurobiology, could significantly enhance our understanding of PTSD pathophysiology. This chapter delineates the role of fear extinction processes in PTSD, investigates the underlying neurobiological substrates, and underscores the therapeutic implications, while also identifying future research directions.
Identifiants
pubmed: 37535308
doi: 10.1007/7854_2023_436
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
257-270Informations de copyright
© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.
Références
American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric Association, Washington
doi: 10.1176/appi.books.9780890425596
Apergis-Schoute AM, Gillan CM, Fineberg NA, Fernandez-Egea E, Sahakian BJ, Robbins TW (2017) Neural basis of impaired safety signaling in obsessive compulsive disorder. Proc Natl Acad Sci U S A 114(12):3216–3221. https://doi.org/10.1073/pnas.1609194114
doi: 10.1073/pnas.1609194114
pubmed: 28265059
pmcid: 5373407
Bisby MA, Baker KD, Richardson R (2018) Elucidating the mechanisms of fear extinction in developing animals: a special case of NMDA receptor-independent extinction in adolescent rats. Learn Mem 25(4):158–164. https://doi.org/10.1101/lm.047209.117
doi: 10.1101/lm.047209.117
pubmed: 29545387
pmcid: 5855527
Briscione MA, Jovanovic T, Norrholm SD (2014) Conditioned fear associated phenotypes as robust, translational indices of trauma-, stressor-, and anxiety-related behaviors. Front Psych 5:88. https://doi.org/10.3389/fpsyt.2014.00088
doi: 10.3389/fpsyt.2014.00088
Cisler JM, Steele JS, Lenow JK, Smitherman S, Everett B, Messias E, Kilts CD (2014) Functional reorganization of neural networks during repeated exposure to the traumatic memory in posttraumatic stress disorder: an exploratory fMRI study. J Psychiatr Res 48(1):47–55. https://doi.org/10.1016/j.jpsychires.2013.09.013
doi: 10.1016/j.jpsychires.2013.09.013
pubmed: 24139810
Cooper SE, Dunsmoor JE (2021) Fear conditioning and extinction in obsessive-compulsive disorder: a systematic review. Neurosci Biobehav Rev 129:75–94. https://doi.org/10.1016/j.neubiorev.2021.07.026
doi: 10.1016/j.neubiorev.2021.07.026
pubmed: 34314751
pmcid: 8429207
Corcoran KA, Desmond TJ, Frey KA, Maren S (2005) Hippocampal inactivation disrupts the acquisition and contextual encoding of fear extinction. J Neurosci 25(39):8978–8987. https://doi.org/10.1523/JNEUROSCI.2246-05.2005
doi: 10.1523/JNEUROSCI.2246-05.2005
pubmed: 16192388
pmcid: 6725608
Cusack K, Jonas DE, Forneris CA, Wines C, Sonis J, Middleton JC et al (2016) Psychological treatments for adults with posttraumatic stress disorder: a systematic review and meta-analysis. Clin Psychol Rev 43:128–141. https://doi.org/10.1016/j.cpr.2015.10.003
doi: 10.1016/j.cpr.2015.10.003
pubmed: 26574151
de Kleine RA, Hendriks GJ, Kusters WJ, Broekman TG, van Minnen A (2012) A randomized placebo-controlled trial of D-cycloserine to enhance exposure therapy for posttraumatic stress disorder. Biol Psychiatry 71(11):962–968. https://doi.org/10.1016/j.biopsych.2012.02.033
doi: 10.1016/j.biopsych.2012.02.033
pubmed: 22480663
Difede J, Cukor J, Jayasinghe N, Patt I, Jedel S, Spielman L et al (2007) Virtual reality exposure therapy for the treatment of posttraumatic stress disorder following September 11, 2001. J Clin Psychiatry 68(11):1639–1647
doi: 10.4088/JCP.v68n1102
pubmed: 18052556
Fani N, King TZ, Brewster R, Srivastava A, Stevens JS, Glover EM et al (2015) Fear-potentiated startle during extinction is associated with white matter microstructure and functional connectivity. Cortex 64:249–259. https://doi.org/10.1016/j.cortex.2014.11.006
doi: 10.1016/j.cortex.2014.11.006
pubmed: 25522360
Feng P, Feng T, Chen Z, Lei X (2014) Memory consolidation of fear conditioning: bi-stable amygdala connectivity with dorsal anterior cingulate and medial prefrontal cortex. Soc Cogn Affect Neurosci 9(11):1730–1737. https://doi.org/10.1093/scan/nst170
doi: 10.1093/scan/nst170
pubmed: 24194579
Foa EB, McLean CP (2016) The efficacy of exposure therapy for anxiety-related disorders and its underlying mechanisms: the case of OCD and PTSD. Annu Rev Clin Psychol 12:1–28. https://doi.org/10.1146/annurev-clinpsy-021815-093533
doi: 10.1146/annurev-clinpsy-021815-093533
pubmed: 26565122
Garfinkel SN, Abelson JL, King AP, Sripada RK, Wang X, Gaines LM, Liberzon I (2014) Impaired contextual modulation of memories in PTSD: an fMRI and psychophysiological study of extinction retention and fear renewal. J Neurosci 34(40):13435–13443. https://doi.org/10.1523/JNEUROSCI.4287-13.2014
doi: 10.1523/JNEUROSCI.4287-13.2014
pubmed: 25274821
pmcid: 4262698
Glotzbach E, Ewald H, Andreatta M, Pauli P, Muhlberger A (2012) Contextual fear conditioning predicts subsequent avoidance behaviour in a virtual reality environment. Cognit Emot 26(7):1256–1272. https://doi.org/10.1080/02699931.2012.656581
doi: 10.1080/02699931.2012.656581
Greco JA, Liberzon I (2016) Neuroimaging of fear-associated learning. Neuropsychopharmacology 41(1):320–334. https://doi.org/10.1038/npp.2015.255
doi: 10.1038/npp.2015.255
pubmed: 26294108
Harnett NG, Goodman AM, Knight DC (2020) PTSD-related neuroimaging abnormalities in brain function, structure, and biochemistry. Exp Neurol 330:113331. https://doi.org/10.1016/j.expneurol.2020.113331
doi: 10.1016/j.expneurol.2020.113331
pubmed: 32343956
Hoffman AN, Lorson NG, Sanabria F, Foster Olive M, Conrad CD (2014) Chronic stress disrupts fear extinction and enhances amygdala and hippocampal Fos expression in an animal model of post-traumatic stress disorder. Neurobiol Learn Mem 112:139–147. https://doi.org/10.1016/j.nlm.2014.01.018
doi: 10.1016/j.nlm.2014.01.018
pubmed: 24508064
pmcid: 4051860
Jin J, Maren S (2015) Fear renewal preferentially activates ventral hippocampal neurons projecting to both amygdala and prefrontal cortex in rats. Sci Rep 5:8388. https://doi.org/10.1038/srep08388
doi: 10.1038/srep08388
pubmed: 25669753
pmcid: 4323647
Karsen EF, Watts BV, Holtzheimer PE (2014) Review of the effectiveness of transcranial magnetic stimulation for post-traumatic stress disorder. Brain Stimul 7(2):151–157. https://doi.org/10.1016/j.brs.2013.10.006
doi: 10.1016/j.brs.2013.10.006
pubmed: 24486424
Knight DC, Smith CN, Cheng DT, Stein EA, Helmstetter FJ (2004) Amygdala and hippocampal activity during acquisition and extinction of human fear conditioning. Cogn Affect Behav Neurosci 4(3):317–325. https://doi.org/10.3758/CABN.4.3.317
doi: 10.3758/CABN.4.3.317
pubmed: 15535167
Knox D, Perrine SA, George SA, Galloway MP, Liberzon I (2010) Single prolonged stress decreases glutamate, glutamine, and creatine concentrations in the rat medial prefrontal cortex. Neurosci Lett 480(1):16–20. https://doi.org/10.1016/j.neulet.2010.05.052
doi: 10.1016/j.neulet.2010.05.052
pubmed: 20546834
pmcid: 2902659
Leutgeb S, Leutgeb JK (2007) Pattern separation, pattern completion, and new neuronal codes within a continuous CA3 map. Learn Mem 14(11):745–757. https://doi.org/10.1101/lm.703907
doi: 10.1101/lm.703907
pubmed: 18007018
Liberzon I, Abelson JL (2016) Context processing and the neurobiology of post-traumatic stress disorder. Neuron 92(1):14–30. https://doi.org/10.1016/j.neuron.2016.09.039
doi: 10.1016/j.neuron.2016.09.039
pubmed: 27710783
pmcid: 5113735
Liberzon I, Krstov M, Young EA (1997) Stress-restress: effects on ACTH and fast feedback. Psychoneuroendocrinology 22(6):443–453. https://doi.org/10.1016/s0306-4530(97)00044-9
doi: 10.1016/s0306-4530(97)00044-9
pubmed: 9364622
Linnman C, Zeffiro TA, Pitman RK, Milad MR (2011) An fMRI study of unconditioned responses in post-traumatic stress disorder. Biol Mood Anxiety Disord 1(1):8. https://doi.org/10.1186/2045-5380-1-8
doi: 10.1186/2045-5380-1-8
pubmed: 22738227
pmcid: 3384234
Lokshina Y, Sheynin J, Liberzon I (2021) Post-trauma brain: a commentary on functional brain alterations after trauma and implications to posttraumatic stress disorder. Curr Res Psychiatry 1(3):44–47. https://doi.org/10.46439/Psychiatry.1.015
doi: 10.46439/Psychiatry.1.015
Maples-Keller J, Watkins LE, Nylocks KM, Yasinski C, Coghlan C, Black K et al (2022) Acquisition, extinction, and return of fear in veterans in intensive outpatient prolonged exposure therapy: a fear-potentiated startle study. Behav Res Ther 154:104124. https://doi.org/10.1016/j.brat.2022.104124
doi: 10.1016/j.brat.2022.104124
pubmed: 35642990
pmcid: 10191243
Maren S, Holmes A (2016) Stress and fear extinction. Neuropsychopharmacology 41(1):58–79. https://doi.org/10.1038/npp.2015.180
doi: 10.1038/npp.2015.180
pubmed: 26105142
Maren S, Phan KL, Liberzon I (2013) The contextual brain: implications for fear conditioning, extinction and psychopathology. Nat Rev Neurosci 14(6):417–428. https://doi.org/10.1038/nrn3492
doi: 10.1038/nrn3492
pubmed: 23635870
pmcid: 5072129
Marin MF, Camprodon JA, Dougherty DD, Milad MR (2014) Device-based brain stimulation to augment fear extinction: implications for PTSD treatment and beyond. Depress Anxiety 31(4):269–278. https://doi.org/10.1002/da.22252
doi: 10.1002/da.22252
pubmed: 24634247
Marin MF, Zsido RG, Song H, Lasko NB, Killgore WDS, Rauch SL et al (2017) Skin conductance responses and neural activations during fear conditioning and extinction recall across anxiety disorders. JAMA Psychiatry 74(6):622–631. https://doi.org/10.1001/jamapsychiatry.2017.0329
doi: 10.1001/jamapsychiatry.2017.0329
pubmed: 28403387
pmcid: 5539837
Marin MF, Hammoud MZ, Klumpp H, Simon NM, Milad MR (2020) Multimodal categorical and dimensional approaches to understanding threat conditioning and its extinction in individuals with anxiety disorders. JAMA Psychiatry 77(6):618–627. https://doi.org/10.1001/jamapsychiatry.2019.4833
doi: 10.1001/jamapsychiatry.2019.4833
pubmed: 32022832
Marusak HA, Hehr A, Bhogal A, Peters C, Iadipaolo A, Rabinak CA (2021) Alterations in fear extinction neural circuitry and fear-related behavior linked to trauma exposure in children. Behav Brain Res 398:112958. https://doi.org/10.1016/j.bbr.2020.112958
doi: 10.1016/j.bbr.2020.112958
pubmed: 33069739
Mattera A, Pagani M, Baldassarre G (2020) A computational model integrating multiple phenomena on cued fear conditioning, extinction, and reinstatement. Front Syst Neurosci 14:569108. https://doi.org/10.3389/fnsys.2020.569108
doi: 10.3389/fnsys.2020.569108
pubmed: 33132856
pmcid: 7550679
McHugh TJ, Jones MW, Quinn JJ, Balthasar N, Coppari R, Elmquist JK et al (2007) Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network. Science 317(5834):94–99. https://doi.org/10.1126/science.1140263
doi: 10.1126/science.1140263
pubmed: 17556551
Milad MR, Rauch SL (2012) Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways. Trends Cogn Sci 16(1):43–51. https://doi.org/10.1016/j.tics.2011.11.003
doi: 10.1016/j.tics.2011.11.003
pubmed: 22138231
Milad MR, Orr SP, Lasko NB, Chang Y, Rauch SL, Pitman RK (2008) Presence and acquired origin of reduced recall for fear extinction in PTSD: results of a twin study. J Psychiatr Res 42(7):515–520. https://doi.org/10.1016/j.jpsychires.2008.01.017
doi: 10.1016/j.jpsychires.2008.01.017
pubmed: 18313695
pmcid: 2377011
Milad MR, Pitman RK, Ellis CB, Gold AL, Shin LM, Lasko NB et al (2009) Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder. Biol Psychiatry 66(12):1075–1082. https://doi.org/10.1016/j.biopsych.2009.06.026
doi: 10.1016/j.biopsych.2009.06.026
pubmed: 19748076
pmcid: 2787650
Milad MR, Furtak SC, Greenberg JL, Keshaviah A, Im JJ, Falkenstein MJ et al (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
doi: 10.1001/jamapsychiatry.2013.914
pubmed: 23740049
Milad MR, Rosenbaum BL, Simon NM (2014) Neuroscience of fear extinction: implications for assessment and treatment of fear-based and anxiety related disorders. Behav Res Ther 62:17–23. https://doi.org/10.1016/j.brat.2014.08.006
doi: 10.1016/j.brat.2014.08.006
pubmed: 25204715
Moench KM, Wellman CL (2015) Stress-induced alterations in prefrontal dendritic spines: implications for post-traumatic stress disorder. Neurosci Lett 601:41–45. https://doi.org/10.1016/j.neulet.2014.12.035
doi: 10.1016/j.neulet.2014.12.035
pubmed: 25529195
Morena M, Berardi A, Colucci P, Palmery M, Trezza V, Hill MN, Campolongo P (2018) Enhancing endocannabinoid neurotransmission augments the efficacy of extinction training and ameliorates traumatic stress-induced behavioral alterations in rats. Neuropsychopharmacology 43(6):1284–1296. https://doi.org/10.1038/npp.2017.305
doi: 10.1038/npp.2017.305
pubmed: 29265107
pmcid: 5916373
Moustafa AA, Gilbertson MW, Orr SP, Herzallah MM, Servatius RJ, Myers CE (2013) A model of amygdala-hippocampal-prefrontal interaction in fear conditioning and extinction in animals. Brain Cogn 81(1):29–43. https://doi.org/10.1016/j.bandc.2012.10.005
doi: 10.1016/j.bandc.2012.10.005
pubmed: 23164732
Ngo CT, Michelmann S, Olson IR, Newcombe NS (2021) Pattern separation and pattern completion: behaviorally separable processes? Mem Cognit 49(1):193–205. https://doi.org/10.3758/s13421-020-01072-y
doi: 10.3758/s13421-020-01072-y
pubmed: 32728851
Otto MW, Tolin DF, Simon NM, Pearlson GD, Basden S, Meunier SA et al (2010) Efficacy of d-cycloserine for enhancing response to cognitive-behavior therapy for panic disorder. Biol Psychiatry 67(4):365–370. https://doi.org/10.1016/j.biopsych.2009.07.036
doi: 10.1016/j.biopsych.2009.07.036
pubmed: 19811776
Paredes D, Morilak DA (2019) A rodent model of exposure therapy: the use of fear extinction as a therapeutic intervention for PTSD. Front Behav Neurosci 13:46. https://doi.org/10.3389/fnbeh.2019.00046
doi: 10.3389/fnbeh.2019.00046
pubmed: 30914932
pmcid: 6421316
Radell ML, Myers CE, Sheynin J, Moustafa AA (2017) Computational models of post-traumatic stress disorder (PTSD). In: Moustafa AA (ed) Computational models of brain and behavior. Wiley, New York, pp 43–55. https://doi.org/10.1002/9781119159193.ch4
doi: 10.1002/9781119159193.ch4
Rauch SA, Eftekhari A, Ruzek JI (2012) Review of exposure therapy: a gold standard for PTSD treatment. J Rehabil Res Dev 49(5):679–687. https://doi.org/10.1682/jrrd.2011.08.0152
doi: 10.1682/jrrd.2011.08.0152
pubmed: 23015579
Rodrigues SM, Schafe GE, LeDoux JE (2001) Intra-amygdala blockade of the NR2B subunit of the NMDA receptor disrupts the acquisition but not the expression of fear conditioning. J Neurosci 21(17):6889–6896. https://doi.org/10.1523/JNEUROSCI.21-17-06889.2001
doi: 10.1523/JNEUROSCI.21-17-06889.2001
pubmed: 11517276
pmcid: 6763096
Rodriguez-Romaguera J, Do Monte FH, Quirk GJ (2012) Deep brain stimulation of the ventral striatum enhances extinction of conditioned fear. Proc Natl Acad Sci U S A 109(22):8764–8769. https://doi.org/10.1073/pnas.1200782109
doi: 10.1073/pnas.1200782109
pubmed: 22586125
pmcid: 3365168
Rothbaum BO, Davis M (2003) Applying learning principles to the treatment of post-trauma reactions. Ann N Y Acad Sci 1008:112–121. https://doi.org/10.1196/annals.1301.012
doi: 10.1196/annals.1301.012
pubmed: 14998877
Rougemont-Bucking A, Linnman C, Zeffiro TA, Zeidan MA, Lebron-Milad K, Rodriguez-Romaguera J et al (2011) Altered processing of contextual information during fear extinction in PTSD: an fMRI study. CNS Neurosci Ther 17(4):227–236. https://doi.org/10.1111/j.1755-5949.2010.00152.x
doi: 10.1111/j.1755-5949.2010.00152.x
pubmed: 20406268
Santini E, Muller RU, Quirk GJ (2001) Consolidation of extinction learning involves transfer from NMDA-independent to NMDA-dependent memory. J Neurosci 21(22):9009–9017. https://doi.org/10.1523/JNEUROSCI.21-22-09009.2001
doi: 10.1523/JNEUROSCI.21-22-09009.2001
pubmed: 11698611
pmcid: 6762277
Senn V, Wolff SB, Herry C, Grenier F, Ehrlich I, Grundemann J et al (2014) Long-range connectivity defines behavioral specificity of amygdala neurons. Neuron 81(2):428–437. https://doi.org/10.1016/j.neuron.2013.11.006
doi: 10.1016/j.neuron.2013.11.006
pubmed: 24462103
Shin LM, Liberzon I (2010) The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology 35(1):169–191. https://doi.org/10.1038/npp.2009.83
doi: 10.1038/npp.2009.83
pubmed: 19625997
Shvil E, Sullivan GM, Schafer S, Markowitz JC, Campeas M, Wager TD et al (2014) Sex differences in extinction recall in posttraumatic stress disorder: a pilot fMRI study. Neurobiol Learn Mem 113:101–108. https://doi.org/10.1016/j.nlm.2014.02.003
doi: 10.1016/j.nlm.2014.02.003
pubmed: 24560771
pmcid: 4053517
Sierra-Mercado D, Padilla-Coreano N, Quirk GJ (2011) Dissociable roles of prelimbic and infralimbic cortices, ventral hippocampus, and basolateral amygdala in the expression and extinction of conditioned fear. Neuropsychopharmacology 36(2):529–538. https://doi.org/10.1038/npp.2010.184
doi: 10.1038/npp.2010.184
pubmed: 20962768
Sotres-Bayon F, Quirk GJ (2010) Prefrontal control of fear: more than just extinction. Curr Opin Neurobiol 20(2):231–235. S0959-4388(10)00027-9 [pii]. https://doi.org/10.1016/j.conb.2010.02.005
doi: 10.1016/j.conb.2010.02.005
pubmed: 20303254
pmcid: 2878722
Sripada RK, Garfinkel SN, Liberzon I (2013) Avoidant symptoms in PTSD predict fear circuit activation during multimodal fear extinction. Front Hum Neurosci 7:672. https://doi.org/10.3389/fnhum.2013.00672
doi: 10.3389/fnhum.2013.00672
pubmed: 24146643
pmcid: 3797966
Stidd DA, Vogelsang K, Krahl SE, Langevin JP, Fellous JM (2013) Amygdala deep brain stimulation is superior to paroxetine treatment in a rat model of posttraumatic stress disorder. Brain Stimul 6(6):837–844. https://doi.org/10.1016/j.brs.2013.05.008
doi: 10.1016/j.brs.2013.05.008
pubmed: 23835167
Suarez-Jimenez B, Albajes-Eizagirre A, Lazarov A, Zhu X, Harrison BJ, Radua J et al (2020) Neural signatures of conditioning, extinction learning, and extinction recall in posttraumatic stress disorder: a meta-analysis of functional magnetic resonance imaging studies. Psychol Med 50(9):1442–1451. https://doi.org/10.1017/S0033291719001387
doi: 10.1017/S0033291719001387
pubmed: 31258096
Swartz JR, Monk CS (2014) The role of corticolimbic circuitry in the development of anxiety disorders in children and adolescents. Neurobiol Childhood:133–148. https://doi.org/10.1007/7854_2013_242
VanElzakker MB, Dahlgren MK, Davis FC, Dubois S, Shin LM (2014) From Pavlov to PTSD: the extinction of conditioned fear in rodents, humans, and anxiety disorders. Neurobiol Learn Mem 113:3–18. https://doi.org/10.1016/j.nlm.2013.11.014
doi: 10.1016/j.nlm.2013.11.014
pubmed: 24321650
Walker DL, Ressler KJ, Lu KT, Davis M (2002) Facilitation of conditioned fear extinction by systemic administration or intra-amygdala infusions of D-cycloserine as assessed with fear-potentiated startle in rats. J Neurosci 22(6):2343–2351. https://doi.org/10.1523/JNEUROSCI.22-06-02343.2002
doi: 10.1523/JNEUROSCI.22-06-02343.2002
pubmed: 11896173
pmcid: 6758267
Wang Q, Jin J, Maren S (2016) Renewal of extinguished fear activates ventral hippocampal neurons projecting to the prelimbic and infralimbic cortices in rats. Neurobiol Learn Mem 134 Pt A:38–43. https://doi.org/10.1016/j.nlm.2016.04.002
doi: 10.1016/j.nlm.2016.04.002
pubmed: 27060752
Wen L, Han F, Shi Y (2015) Changes in the glucocorticoid receptor and Ca(2)(+)/calreticulin-dependent signalling pathway in the medial prefrontal cortex of rats with post-traumatic stress disorder. J Mol Neurosci 56(1):24–34. https://doi.org/10.1007/s12031-014-0464-7
doi: 10.1007/s12031-014-0464-7
pubmed: 25407822
Wen Z, Chen ZS, Milad MR (2021) Fear extinction learning modulates large-scale brain connectivity. Neuroimage 238:118261. https://doi.org/10.1016/j.neuroimage.2021.118261
doi: 10.1016/j.neuroimage.2021.118261
pubmed: 34126211
Wen Z, Seo J, Pace-Schott EF, Milad MR (2022) Abnormal dynamic functional connectivity during fear extinction learning in PTSD and anxiety disorders. Mol Psychiatry 27(4):2216–2224. https://doi.org/10.1038/s41380-022-01462-5
doi: 10.1038/s41380-022-01462-5
pubmed: 35145227
pmcid: 9126814
Wicking M, Steiger F, Nees F, Diener SJ, Grimm O, Ruttorf M et al (2016) Deficient fear extinction memory in posttraumatic stress disorder. Neurobiol Learn Mem 136:116–126. https://doi.org/10.1016/j.nlm.2016.09.016
doi: 10.1016/j.nlm.2016.09.016
pubmed: 27686278
Zhang X, Kim J, Tonegawa S (2020) Amygdala reward neurons form and store fear extinction memory. Neuron 105(6):1077–1093 e1077. https://doi.org/10.1016/j.neuron.2019.12.025
doi: 10.1016/j.neuron.2019.12.025
pubmed: 31952856
Zuj DV, Palmer MA, Lommen MJ, Felmingham KL (2016) The centrality of fear extinction in linking risk factors to PTSD: a narrative review. Neurosci Biobehav Rev 69:15–35. https://doi.org/10.1016/j.neubiorev.2016.07.014
doi: 10.1016/j.neubiorev.2016.07.014
pubmed: 27461912