Cited by 184Memory and Neural MechanismsPosttraumatic Stress Disorder ResearchMemory Processes and Influences

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Recent fear is resistant to extinction

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Maren, Stephen, Chang, Chun-hui·2006·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0608398103PMC PMC1693865

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Abstract

In some individuals, fearful experiences (e.g., combat) yield persistent and debilitating psychological disturbances, including posttraumatic stress disorder (PTSD). Early intervention (e.g., debriefing) after psychological trauma is widely practiced and argued to be an effective strategy for limiting subsequent psychopathology, although there has been considerable debate on this point. Here we show in an animal model of traumatic fear that early intervention shortly after an aversive experience yields poor long-term fear reduction. Extinction trials administered minutes after aversive fear conditioning in rats suppressed fear acutely, but fear suppression was not maintained the next day. In contrast, delivering extinction trials 1 day after fear conditioning produced an enduring suppression of fear memory. We further show that the recent experience of an aversive event, not the timing of the extinction intervention per se, inhibits the development of long-term fear extinction. These results reveal that the level of fear present at the time of intervention is a critical factor in the efficacy of extinction. Importantly, our work suggests that early intervention may not yield optimal outcomes in reducing posttraumatic stress, particularly after severe trauma.

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“In addition, the timing of extinction trials relative to conditioning is also a key factor governing the longterm success of extinction training (Maren and Chang, 2006; Myers et al., 2006; Maren, 2014).”
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“When the same animals were tested again 48 h later the conditioned freezing responses recovered (Maren & Chang, 2006; Chang & Maren, 2009).”
Background
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“However, other pharmacological manipulation yielded mixed results (Maren and Chang, 2006; Myers et al., 2006; Parsons and Ressler, 2013).”
Result
Amygdala and ventral anterior cingulate activation predicts treatment response to cognitive behaviour therapy for post-traumatic stress disorder
Bryant, R. A., Felmingham, K., Kemp, A., Das, P., Hughes, G., Peduto, A., & Williams, L. (2008) · Psychological Medicine · doi:10.1017/s0033291707002231 · Cited by 307
“This finding also accords with animal studies that show that rats display impaired extinction learning when extinction is preceded by arousing fear (Maren & Chang, 2006).”
Result
Hippocampal involvement in contextual modulation of fear extinction
Ji, J., & Maren, S. (2007) · Hippocampus · doi:10.1002/hipo.20331 · Cited by 297
“These fearful experiences persist and contribute to, such as, psychological disturbances, post-traumatic stress disorders (PTSD), and panic disorders (Friedman et al., 1994; Maren and Chang, 2006; Feldner et al., 2007).”
Background
Seeking a Spotless Mind: Extinction, Deconsolidation, and Erasure of Fear Memory
Maren, S. (2011) · Neuron · doi:10.1016/j.neuron.2011.04.023 · Cited by 259
Erasing Fear Memories with Extinction Training: Figure 1.
Quirk, G. J., Paré, D., Richardson, R., Herry, C., Monfils, M., Schiller, D., & Vicentic, A. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.4268-10.2010 · Cited by 233
“Subsequent experiments using variations of this protocol have met with limited success (Maren and Chang, 2006; Norrholm et al., 2008; Schiller et al., 2008; Woods and Bouton, 2008), suggesting the involvement of other, as yet unknown, variables.”
Method
Single prolonged stress disrupts retention of extinguished fear in rats.Preprint
Knox, D., George, S. A., Fitzpatrick, C. J., Rabinak, C. A., Maren, S., & Liberzon, I. (2012) · Learning & memory (Cold Spring Harbor, N.Y.) · doi:10.1101/lm.024356.111 · Cited by 202
“These include brief uncontrollable stress (Izquierdo et al. 2006), chronic stress (Miracle et al. 2006; Garcia et al. 2008; Baran et al. 2009; Wilber et al. 2011), and footshock stress (Rau et al. 2005; Maren and Chang 2006).”
Background
Noradrenergic Modulation of Fear Conditioning and Extinction
Giustino, T. F., & Maren, S. (2018) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2018.00043 · Cited by 203
Cannabinoid receptor activation in the basolateral amygdala blocks the effects of stress on the conditioning and extinction of inhibitory avoidance
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“Others have reported that stress reduces cued fear extinction (Shumake et al., 2005; Izquierdo et al., 2006; Maren and Chang, 2006) or impairs its recall (Maren and Chang, 2006; Miracle et al., 2006; Garcia et al., 2008).”
Background
Glutamate Receptors in Extinction and Extinction-Based Therapies for Psychiatric Illness
Myers, K. M., Carlezon, W. A., & Davis, M. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.88 · Cited by 177
“The apparent time-dependent nature of mGluR1 involvement is consistent with evidence from other sources that the mechanisms of short- and long-interval extinction may differ (Cain et al, 2005; Mao et al, 2006; Maren and Chang, 2006; Myers et al, 2006).”
Effects of recent exposure to a conditioned stimulus on extinction of Pavlovian fear conditioningPreprint
Chan, W. Y. M., Leung, H. T., Westbrook, R. F., & McNally, G. P. (2010) · Learning & Memory · doi:10.1101/lm.1912510 · Cited by 156
Can fear extinction be enhanced? A review of pharmacological and behavioral findings
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“Infusion of DCS into infralimbic cortex before “immediate” extinction, a protocol which uses a small time interval between conditioning and extinction that can impair extinction (Maren and Chang, 2006), did not facilitate within-session extinction, but did prime subsequent re-extinction during a drug-free state (Chang…”
Background
Evidence for recovery of fear following immediate extinction in rats and humansPreprint
Schiller, D., Cain, C. K., Curley, N. G., Schwartz, J. S., Stern, S. A., LeDoux, J. E., & Phelps, E. A. (2008) · Learning & Memory · doi:10.1101/lm.909208 · Cited by 150
“The present experiments were designed to assess whether the finding of Myers et al. (2006) would apply to a different behavioral measure in rats and would extend to humans.”
Background
Immunohistochemical Analyses of Long-Term Extinction of Conditioned Fear in Adolescent Rats
Kim, J. H., Li, S., & Richardson, R. (2011) · Cerebral Cortex · doi:10.1093/cercor/bhq116 · Cited by 149
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Sex differences in fear extinction
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“Extinction learning is also sensitive to the timing relative to trauma, and it is typically less effective when given soon after the traumatic experience (Chang, Berke, & Maren, 2010; Fitzgerald, Giustino, Seemann, & Maren, 2015; Kim, Jo, Kim, Kim, & Choi, 2010; Maren, 2014; Maren & Chang, 2006).”
Background
Timing of extinction relative to acquisition: a parametric analysis of fear extinction in humans
Norrholm, S. D., Vervliet, B., Jovanovic, T., Boshoven, W., Myers, K. M., Davis, M., Rothbaum, B., & Duncan, E. J. (2008) · Behavioral Neuroscience · doi:10.1037/a0012604 · Cited by 120
“More recently, Maren and Chang (2006) also reported resistance to spontaneous recovery after immediate (15 min) extinction of conditioned freezing, provided that conditioned fear expression during extinction training is not so high as to prevent extinction from occurring ( Maren & Chang, 2006 ).”
BackgroundInfluential
Conditioning- and time-dependent increases in context fear and generalizationPreprint
Poulos, A. M., Mehta, N., Lu, B., Amir, D., Livingston, B., Santarelli, A., Zhuravka, I., & Fanselow, M. S. (2016) · Learning & Memory · doi:10.1101/lm.041400.115 · Cited by 123
“Other studies examining the time-dependent effects of memory and extinction have focused on auditory fear extinction at shorter times scales from minutes to a few days (Myers et al. 2006; Maren and Chang 2006).”
Background
Psychological and neural mechanisms of experimental extinction: A selective review
Delamater, A. R., & Westbrook, R. F. (2013) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2013.09.016 · Cited by 120
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Giustino, T. F., Ramanathan, K. R., Totty, M. S., Miles, O. W., & Maren, S. (2020) · The Journal of Neuroscience · doi:10.1523/jneurosci.1092-19.2019 · Cited by 110
“Stress-induced increases in BLA activity mediated by LC-NE may be a viable therapeutic target for individuals with PTSD and related disorders. impaired in humans and rodents when it occurs within minutes to hours of fear conditioning (Maren and Chang, 2006; Chang et al., 2010; Kim et al., 2010; Fitzgerald et al., 2015…”
BackgroundInfluential
Contextual-specificity of short-delay extinction in humans: Renewal of fear-potentiated startle in a virtual environment
Alvarez, R. P., Johnson, L., & Grillon, C. (2007) · Learning & Memory · doi:10.1101/lm.493707 · Cited by 110
“Myers et al. (2006) measured conditioned fear using fear-potentiated startle.”
BackgroundResultInfluential
Conditioned fear associated phenotypes as robust, translational indices of trauma-, stressor-, and anxiety-related behaviors
Briscione, M. A., Jovanovic, T., & Norrholm, S. D. (2014) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2014.00088 · Cited by 105
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“Recent work in animal models suggests that early interventions do not yield long-term fear suppression [14,15,57,58,59].”
BackgroundInfluential
Role of Human Ventromedial Prefrontal Cortex in Learning and Recall of Enhanced Extinction
Dunsmoor, J. E., Kroes, M. C. W., Li, J., Daw, N. D., Simpson, H. B., & Phelps, E. A. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.2713-18.2019 · Cited by 110
“It will be of interest to test effects of an immediate versus delayed NFE protocol, as its possible NFE is even more effective at a delay, in keeping with findings of EXT standard extinction (Maren and Chang, 2006; Schiller et al., 2008; Huff et al., 2009).”
Result
Noradrenergic blockade stabilizes prefrontal activity and enables fear extinction under stress
Fitzgerald, P. J., Giustino, T. F., Seemann, J. R., & Maren, S. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1500682112 · Cited by 109
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“…cases, administering extinction trials soon after fear conditioning results in no long-term fear suppression at all – the so-called immediate extinction deficit (Chang, Berke, & Maren, 2010; Chang & Maren, 2009, 2011; Kim, Jo, Kim, Kim, & Choi, 2010; MacPherson et al., 2013; Maren & Chang, 2006).”
Background
Delayed extinction attenuates conditioned fear renewal and spontaneous recovery in humans.
Huff, N. C., Hernandez, J. A., Blanding, N. Q., & LaBar, K. S. (2009) · Behavioral Neuroscience · doi:10.1037/a0016511 · Cited by 109
“Additionally, other rodent studies have demonstrated that immediate extinction fails to yield long-term fear suppression (Maren & Chang, 2006).”
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Kim, S. C., Jo, Y. S., Kim, I. H., Kim, H., & Choi, J.-S. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.4145-09.2010 · Cited by 96
“Recent studies have demonstrated that extinction training administered shortly after the acquisition session does not effectively induce long-term suppression of the fear response (Maren and Chang, 2006; Woods and Bouton, 2008; Chang and Maren, 2009) [but see Myers et al.”
BackgroundResultInfluential
Effect of Conditioned Stimulus Exposure during Slow Wave Sleep on Fear Memory Extinction in Humans
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Animal Models of Fear Relapse
Goode, T. D., & Maren, S. (2014) · ILAR Journal · doi:10.1093/ilar/ilu008 · Cited by 93
“Stress prior to conditioning has been shown to facilitate fear learning in rodents and to make fear responding more resistant to attenuation under certain conditions (Corley et al. 2012; Long and Fanselow 2012; Maren and Chang 2006; Rau et al. 2005; Rau and Fanselow 2009; Rodrigues et al. 2009).”
Background
Making translation work: Harmonizing cross-species methodology in the behavioural neuroscience of Pavlovian fear conditioning
Haaker, J., Maren, S., Andreatta, M., Merz, C. J., Richter, J., Richter, S. H., Drexler, S. M., Lange, M. D., Jüngling, K., Nees, F., et al. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.09.020 · Cited by 92
Modulation of Fear Extinction by Stress, Stress Hormones and Estradiol: A Review
Stockhorst, U., & Antov, M. I. (2016) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00359 · Cited by 96
Consequences of extinction training on associative and non-associative fear in a mouse model of Posttraumatic Stress Disorder (PTSD)
Golub, Y., Mauch, C. P., Dahlhoff, M., & Wotjak, C. T. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.08.019 · Cited by 80
Extinction of Conditioned Fear in Adolescents and Adults: A Human fMRI Study
Ganella, D. E., Drummond, K. D., Ganella, E. P., Whittle, S., & Kim, J. H. (2018) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2017.00647 · Cited by 82
“In adult rodents, findings are mixed with some studies reporting better extinction recall while others reporting worse extinction recall when extinction is given immediately after conditioning (Maren and Chang, 2006; Myers et al., 2006; Monfils et al., 2009).”
Background
Mechanisms of fear learning and extinction: synaptic plasticity–fear memory connection
Luchkina, N. V., & Bolshakov, V. Y. (2018) · Psychopharmacology · doi:10.1007/s00213-018-5104-4 · Cited by 87
Blockade of amygdala metabotropic glutamate receptor subtype 1 impairs fear extinction
Kim, J., Lee, S., Park, H., Song, B., Hong, I., Geum, D., Shin, K., & Choi, S. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.01.125 · Cited by 78
“The failure in retention of the extinguished fear in the present study is consistent with a recent report showing that recent fear is resistant to extinction [22].”
Result
The role of basal forebrain cholinergic neurons in fear and extinction memory
Knox, D. (2016) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2016.06.001 · Cited by 81
Attentional, associative, and configural mechanisms in extinction.
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Immediate extinction causes a less durable loss of performance than delayed extinction following either fear or appetitive conditioning
Woods, A. M., & Bouton, M. E. (2008) · Learning & Memory · doi:10.1101/lm.1078508 · Cited by 70
“Second, the results do not support the possibility that a high level of fear around the time of immediate extinction, rather than the brief conditioning-extinction interval on its own, causes strong recovery after immediate extinction (Maren and Chang 2006).”
BackgroundResultInfluential
Preclinical Assessment for Selectively Disrupting a Traumatic Memory via Postretrieval Inhibition of Glucocorticoid Receptors
Taubenfeld, S. M., Riceberg, J. S., New, A. S., & Alberini, C. M. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.07.005 · Cited by 73
“Similarly, in rodents, recent fear is resistant to extinction (65).”
Fear Extinction in Rodents
Chang, C.-H., Knapska, E., Orsini, C. A., Rabinak, C. A., Zimmerman, J. M., & Maren, S. (2009) · Current Protocols in Neuroscience · doi:10.1002/0471142301.ns0823s47 · Cited by 75
Medial prefrontal cortex activation facilitates re-extinction of fear in ratsPreprint
Chang, C., & Maren, S. (2011) · Learning & Memory · doi:10.1101/lm.2070111 · Cited by 73
Mechanisms to medicines: elucidating neural and molecular substrates of fear extinction to identify novel treatments for anxiety disorders
Bukalo, O., Pinard, C. R., & Holmes, A. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12779 · Cited by 73
“Also of note, performing extinction training soon after conditioning impairs extinction (the ‘immediate extinction effect’) (Maren and Chang, 2006; Myers et al., 2006; Macpherson et al., 2013; Maren, 2014).”
Background
Event segmentation protects emotional memories from competing experiences encoded close in time
Dunsmoor, J. E., Kroes, M. C. W., Moscatelli, C. M., Evans, M. D., Davachi, L., & Phelps, E. A. (2018) · Nature Human Behaviour · doi:10.1038/s41562-018-0317-4 · Cited by 77
Cholinergic neuronal lesions in the medial septum and vertical limb of the diagonal bands of Broca induce contextual fear memory generalization and impair acquisition of fear extinction
Knox, D., & Keller, S. M. (2015) · Hippocampus · doi:10.1002/hipo.22553 · Cited by 70
Early extinction after fear conditioning yields a context-independent and short-term suppression of conditional freezing in rats.Preprint
Chang, C.-H., & Maren, S. (2009) · Learning & memory (Cold Spring Harbor, N.Y.) · doi:10.1101/lm.1085009 · Cited by 65
“Indeed, we found that reducing the number of conditioning trials enabled extinction shortly after conditioning (Maren and Chang 2006).”
BackgroundInfluential
Stress-enhanced fear learning in rats is resistant to the effects of immediate massed extinction
Long, V., & Fanselow, M. S. (2012) · Stress · doi:10.3109/10253890.2011.650251 · Cited by 62
Strain difference in the effect of infralimbic cortex lesions on fear extinction in rats.
Chang, C., & Maren, S. (2010) · Behavioral Neuroscience · doi:10.1037/a0019479 · Cited by 63
“Interestingly, LE rats exhibited much higher levels of contextual fear before the outset of extinction training, and this may have impaired both extinction learning and IL function (Akirav & Maroun, 2007; Correll, Rosenkranz, & Grace, 2005; Izquierdo, Wellman, & Holmes, 2006; Maren & Chang, 2006).”
Translationally relevant modeling of PTSD in rodents
Matar, M. A., Zohar, J., & Cohen, H. (2013) · Cell and Tissue Research · doi:10.1007/s00441-013-1687-6 · Cited by 55
“More recently, impaired extinction learning has been proposed as an alternative mechanism for the formation of PTSD symptoms (Maren and Chang 2006; Myers and Davis 2002).”
Background
Long-Term Neural Correlates of Reversible Fear Learning in the Lateral Amygdala
An, B., Hong, I., & Choi, S. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.3017-12.2012 · Cited by 57
Evidence for the persistence of contextual fear memories following immediate extinction
Archbold, G. E. B., Bouton, M. E., & Nader, K. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07161.x · Cited by 52
Persistent activation of central amygdala CRF neurons helps drive the immediate fear extinction deficit
Jo, Y. S., Namboodiri, V. M. K., Stuber, G. D., & Zweifel, L. S. (2020) · Nature Communications · doi:10.1038/s41467-020-14393-y · Cited by 53
Social buffering enhances extinction of conditioned fear responses in male rats
Mikami, K., Kiyokawa, Y., Takeuchi, Y., & Mori, Y. (2016) · Physiology & Behavior · doi:10.1016/j.physbeh.2016.05.001 · Cited by 51
D-Cycloserine into the BLA reverses the impairing effects of exposure to stress on the extinction of contextual fear, but not conditioned taste aversionPreprint
Akirav, I., Segev, A., Motanis, H., & Maroun, M. (2009) · Learning & Memory · doi:10.1101/lm.1565109 · Cited by 51
“Others have reported that stress reduces cued fear extinction (Shumake et al. 2005; Izquierdo et al. 2006; Maren and Chang 2006) or impairs its recall (Maren and Chang 2006; Miracle et al. 2006; Garcia et al. 2007).”
Background
Neural circuits for the adaptive regulation of fear and extinction memory
Plas, S. L., Tuna, T., Bayer, H., Juliano, V. A. L., Sweck, S. O., Pérez, A. D. A., Hassell, J. E., & Maren, S. (2024) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2024.1352797 · Cited by 55
Autophosphorylation of αCaMKII is differentially involved in new learning and unlearning mechanisms of memory extinctionPreprint
Kimura, R., Silva, A. J., & Ohno, M. (2008) · Learning & Memory · doi:10.1101/lm.1049608 · Cited by 44
Extinction: Behavioral Mechanisms and Their Implications
Bouton, M. E., & Woods, A. M. (2008) · Elsevier eBooks · doi:10.1016/b978-012370509-9.00088-7 · Cited by 46
Parvalbumin-Positive Interneurons in the Medial Prefrontal Cortex Regulate Stress-Induced Fear Extinction Impairments in Male and Female Rats
Binette, A. N., Liu, J., Bayer, H., Crayton, K. L., Melissari, L., Sweck, S. O., & Maren, S. (2023) · Journal of Neuroscience · doi:10.1523/jneurosci.1442-22.2023 · Cited by 48
“It should be noted that a weaker conditioning procedure consisting of either fewer trials (Maren and Chang, 2006) or weaker footshocks (Giustino et al., 2020) does not result in an immediate extinction deficit.”
BackgroundInfluential
Revealing Context-Specific Conditioned Fear Memories with Full Immersion Virtual Reality
Huff, N. C., Hernandez, J. A., Fecteau, M. E., Zielinski, D. J., Brady, R. B., & LaBar, K. S. (2011) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2011.00075 · Cited by 45
“In light of generating translational research, it is important to determine why it is rare to find robust long-term contextually cued fear in humans whereas rodent studies readily demonstrate that fear to a conditioned cue is well remembered in the original context (e.g., Phillips and LeDoux, 1994; Corcoran and Maren,…”
Background
β-Adrenoceptor Blockade in the Basolateral Amygdala, But Not the Medial Prefrontal Cortex, Rescues the Immediate Extinction Deficit
Giustino, T. F., Seemann, J. R., Acca, G. M., Goode, T. D., Fitzgerald, P. J., & Maren, S. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.89 · Cited by 45
Exposure to a fearful context during periods of memory plasticity impairs extinction via hyperactivation of frontal-amygdalar circuitsPreprint
Stafford, J. M., Maughan, D. K., Ilioi, E. C., & Lattal, K. M. (2013) · Learning & Memory · doi:10.1101/lm.029801.112 · Cited by 47
Exposure to extreme stress impairs contextual odour discrimination in an animal model of PTSD
Cohen, H., Liberzon, I., & Richter‐Levin, G. (2008) · The International Journal of Neuropsychopharmacology · doi:10.1017/s146114570800919x · Cited by 44
“, 2006), impaired extinction learning has been proposed as an alternative mechanism for the formation of PTSD symptoms (Blechert et al., 2007 ; Guthrie and Bryant, 2006 ; Maren and Chang, 2006 ; Myers and Davis, 2002).”
BackgroundInfluential
Generating new neurons to circumvent your fears: the role of IGF signaling
Agís‐Balboa, R. C., & Fischer, A. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1316-2 · Cited by 43
Low-Frequency Stimulation Depresses the Primate Anterior-Cingulate-Cortex and Prevents Spontaneous Recovery of Aversive Memories
Klavir, O., Genud-Gabai, R., & Paz, R. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.6481-11.2012 · Cited by 43
“…Bouton, 1993; Monfils et al., 2009), and here, we chose to use extinction that immediately follows acquisition, because several studies have observed significant recovery in this protocol (Rescorla, 2004; Maren and Chang, 2006; Alvarez et al., 2007; Schiller et al., 2008; Woods and Bouton, 2008).”
BackgroundMethod
Modulating reconsolidation and extinction to regulate drug reward memory
Liu, J., Tian, J., & Li, J. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14072 · Cited by 42
Associative Learning and Conditioning Theory
Laborda, M. A., McConnell, B. L., & Miller, R. R. (2011) · Cited by 36
The interhemispheric CA1 circuit governs rapid generalisation but not fear memory
Zhou, H., Xiong, G.-J., Jing, L., Song, N., Pu, D.-L., Tang, X., He, X.-B., Xu, F., Huang, J., Li, L., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-02315-4 · Cited by 37
Maintaining the Clinical Relevance of Animal Models in Translational Studies of Post-Traumatic Stress Disorder
Cohen, H., Matar, M., & Zohar, J. (2014) · ILAR Journal · doi:10.1093/ilar/ilu006 · Cited by 37
The exclusive induction of extinction is gated by BDNF
Kirtley, A., & Thomas, K. L. (2010) · Learning & Memory · doi:10.1101/lm.1877010 · Cited by 37
“…Alvarez et al. 2007; Schiller et al. 2008; Archbold et al. 2010), the interval between extinction and test (Bouton 1993, 2004; Quirk 2002), the level of fear behavior at extinction (Maren and Chang 2006), and the number and pattern of nonreinforced trails (Cain et al. 2003; Urcelay et al. 2009).”
Background
Involvement of CRFR 1 in the Basolateral Amygdala in the Immediate Fear Extinction Deficit
Hollis, F., Sevelinges, Y., Grosse, J., Zanoletti, O., & Sandi, C. (2016) · eNeuro · doi:10.1523/eneuro.0084-16.2016 · Cited by 35
“Although pre-tone freezing levels for the immediate extinction groups were high, we found this behavior to be common in the literature when extinction training sessions were given shortly after fear conditioning (Maren and Chang, 2006; Chang and Maren, 2009; Chan et al., 2010; Goode et al., 2015).”
BackgroundResultInfluential
Distinct populations of corticotropin-releasing factor (CRF) neurons mediate divergent yet complementary defensive behaviors in response to a threat
Chudoba, R., & Dabrowska, J. (2023) · Neuropharmacology · doi:10.1016/j.neuropharm.2023.109461 · Cited by 38
Aversive-Bias and Stage-Selectivity in Neurons of the Primate Amygdala during Acquisition, Extinction, and Overnight Retention
Livneh, U., & Paz, R. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.0323-12.2012 · Cited by 36
“Several studies have recently shown that immediate extinction-training results in less extinction consolidation and higher levels of the original memory in the following day (Maren and Chang, 2006; Schiller et al., 2008; Woods and Bouton, 2008).”
Background
Social buffering enhances extinction of conditioned fear responses by reducing corticosterone levels in male rats
Mikami, K., Kiyokawa, Y., Ishii, A., & Takeuchi, Y. (2019) · Hormones and Behavior · doi:10.1016/j.yhbeh.2019.104654 · Cited by 31
Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit
Maren, S. (2022) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2022.888461 · Cited by 37
“Similarly, limiting conditioned freezing before an immediate extinction session by reducing the number of conditioning trials or US intensity eliminates the IED (Maren and Chang, 2006; Jo and Choi, 2020).”
BackgroundMethodInfluential
Targeted Memory Reactivation During REM Sleep in Patients With Social Anxiety Disorder
Borghese, F., Henckaerts, P., Guy, F., Mayo, C., Delplanque, S., Schwartz, S., & Perogamvros, L. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.904704 · Cited by 33
“986] and no main effect of group [F(1,44) = 0.”
Background
Differential impact of the first and second wave of a stress response on subsequent fear conditioning in healthy men
Antov, M. I., Wölk, C., & Stockhorst, U. (2013) · Biological Psychology · doi:10.1016/j.biopsycho.2013.08.007 · Cited by 36
A Contemporary Behavioral Perspective on Extinction
Vurbic, D., & Bouton, M. E. (2014) · Wiley eBooks · doi:10.1002/9781118468135.ch3 · Cited by 33
Fear extinction in humans: Effects of acquisition–extinction delay and masked stimulus presentations
Golkar, A., & Öhman, A. (2012) · Biological Psychology · doi:10.1016/j.biopsycho.2012.07.007 · Cited by 36
Computational Models of Conditioning
Schmajuk, N. A. (2010) · Cambridge University Press eBooks · doi:10.1017/cbo9780511760402 · Cited by 33
Inactivating the infralimbic but not prelimbic medial prefrontal cortex facilitates the extinction of appetitive Pavlovian conditioning in Long-Evans rats
Mendoza, J. A., Sanio, C., & Chaudhri, N. (2014) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2014.12.006 · Cited by 31
“However, the extinction of aversive conditioning is typically assessed using Pavlovian learning models (Garcia, Chang, & Maren, 2006; Maren & Chang, 2006; Milad & Quirk, 2002; Quirk & Mueller, 2008), whereas the extinction of appetitive conditioning is largely tested using instrumental conditioning…”
A review of boundary conditions and variables involved in the prevention of return of fear after post-retrieval extinction
Zuccolo, P. F., & Hunziker, M. H. L. (2019) · Behavioural Processes · doi:10.1016/j.beproc.2019.01.011 · Cited by 32
Immediate extinction promotes the return of fear
Merz, C. J., Hamacher‐Dang, T. C., & Wolf, O. T. (2016) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2016.03.013 · Cited by 33
Nyctophobia: From Imagined to Realistic Fears of the Dark
Levos, J., & Zacchilli, T. L. (2015) · Psi Chi Journal of Psychological Research · doi:10.24839/2164-8204.jn20.2.102 · Cited by 28
Temporal factors in the extinction of fear in inbred mouse strains differing in extinction efficacy
MacPherson, K. P., Whittle, N., Camp, M., Gunduz‐Cinar, O., Singewald, N., & Holmes, A. (2013) · Biology of Mood & Anxiety Disorders · doi:10.1186/2045-5380-3-13 · Cited by 31
“Some studies report a facilitatory effect of ‘immediate’ extinction [24], while others have observed impaired extinction [23,25,36].”
BackgroundMethodResultInfluential
The role of context in the re-extinction of learned fear
Langton, J. M., & Richardson, R. (2009) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2009.06.008 · Cited by 28
Microglial activation and neuroinflammation in acute and chronic cognitive deficits in sepsis
Denver, P., & Cunningham, C. M. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.110285 · Cited by 33
Sex differences in the immediate extinction deficit and renewal of extinguished fear in rats
Binette, A. N., Totty, M. S., & Maren, S. (2022) · PLoS ONE · doi:10.1371/journal.pone.0264797 · Cited by 26
“Because the IED has not previously been studied in Wistar rats, we used a no-extinction control similar to our previously published work in Long-Evans rats [26].”
BackgroundMethod
Extinction: Behavioral Mechanisms and Their Implications ☆
Bouton, M. E. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809324-5.21006-7 · Cited by 25

Authors: Maren, S., & Chang, C.-H.
Affiliations: University of Michigan (US)
*Department of Psychology and
ORCID: Maren, Stephen
Chang, Chun-hui
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2006-11-21
Volume: 103
Issue: 47
Pages: 18020-18025
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0608398103
PMC: PMC1693865
OpenAlex: W1991036243
Cited by: 184
References: 43
Citations by year: 2026: 1 · 2025: 4 · 2024: 5 · 2023: 9 · 2022: 8 · 2021: 4 · 2020: 6 · 2019: 12 · 2018: 12 · 2017: 7 · 2016: 11 · 2015: 11 · 2014: 12 · 2013: 13 · 2012: 10
FWCI: 5.51
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Deep Blue (University of Michigan) (submittedVersion)
Funders: National Institutes of Health
National Institute of Mental Health (R01MH065961)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
Keywords: fear extinction, post-traumatic stress disorder, fear conditioning, early intervention, debriefing, extinction time, fear memory consolidation, war injuries
MeSH terms: Animals, Behavior, Conditioning, Classical, Extinction, Psychological, Fear, Humans, Male, Stress Disorders, Post-Traumatic, Rats, Long-Evans, Rats

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