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Fear Extinction as a Model for Translational Neuroscience: Ten Years of Progress
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The psychology of extinction has been studied for decades. Approximately 10 years ago, however, there began a concerted effort to understand the neural circuits of extinction of fear conditioning, in both animals and humans. Progress during this period has been facilitated by a high degree of coordination between rodent and human researchers examining fear extinction. Here we review the major advances and highlight new approaches to understanding and exploiting fear extinction. Research in fear extinction could serve as a model for translational research in other areas of behavioral neuroscience.
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“A deficit in the ability to encode, consolidate, or retrieve extinction memory is believed to play a role in the development and perpetuation of such disorders [6, 59, 61, 87].”
From Sleep and REM sleep disturbance in the pathophysiology of PTSD: the role of extinction memory (2015) · cites this paper as [59]
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In the citing paper
“A closely related domain of research on conditioning and extinction in both rodents and humans also suggests that ventromedial PFC (vmPFC), an area neighboring rACC, supports extinction while cACC supports increased aversive processing (Milad and Quirk, 2012; see Figure 7).”
From Top-Down Dysregulation—From ADHD to Emotional Instability (2016) · cites this paper as Milad and Quirk, 2012
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In the citing paper
“The vmPFC is proposed to be the homologue for the IL in rodents [87] and serves to inhibit threat responses produced by the amygdala.”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [87]
The cited source says what the claim attributes to it.
In the citing paper
“The vmPFC is thought to modulate amygdala processing of conditioned fear by suppressing fear responses through a set of amygdala neurons in the intercalated region between the basolateral and central amygdala nucleus (Milad and Quirk, 2012).”
From Top-Down Dysregulation—From ADHD to Emotional Instability (2016) · cites this paper as Milad and Quirk, 2012
In the citing paper
“The vmPFC is activated during retrieval of extinction learning and down-regulates the amygdala”
From Childhood adversity and neural development: Deprivation and threat as distinct dimensions of early experience (2014) · cites this paper as Milad and Quirk, 2012
In the citing paper
“Therefore, in PTSD, there is both hyperactivation of the fear expression and hypoactivation of the extinction memory networks [59, 60].”
From Sleep and REM sleep disturbance in the pathophysiology of PTSD: the role of extinction memory (2015) · cites this paper as [59]
In the citing paper
“However, rather than erasing the CS-US association, extinction represents formation of a new memory, an “extinction memory,” signifying “CS-no US,” that competitively inhibits the memory of the CS-US contingency and expression of its associated CR when the CS is again encountered [51–59].”
From Sleep and REM sleep disturbance in the pathophysiology of PTSD: the role of extinction memory (2015) · cites this paper as [59]
In the citing paper
“Neuroimaging research using de novo fear-conditioning and extinction paradigms has revealed areas in the brain associated with experiencing conditioned fear (a “fear expression network”) in the amygdala and dorsal anterior cingulate cortex (dACC) and other areas associated with memory for the extinction (inhibition) of this fear (an “extinction memory network”) that includes the hippocampus and”
From Sleep and REM sleep disturbance in the pathophysiology of PTSD: the role of extinction memory (2015) · cites this paper as [59]
In the citing paper
“Brain circuitry at the core of threat discrimination learning includes areas within the amygdala and medial prefrontal cortex (mPFC)1.”
From Multimodal evidence for delayed threat extinction learning in adolescence and young adulthood (2019) · cites this paper as [1]
In the citing paper
“During threat extinction training, the CS is presented without the aversive outcome, which results in reduced amygdala responses to the CS over time3, with the mPFC playing a critical role1,4,5.”
From Multimodal evidence for delayed threat extinction learning in adolescence and young adulthood (2019) · cites this paper as [1]
In the citing paper
“During threat extinction training, the CS is presented without the aversive outcome, which results in reduced amygdala responses to the CS over time3, with the mPFC playing a critical role1,4,5.”
From Multimodal evidence for delayed threat extinction learning in adolescence and young adulthood (2019) · cites this paper as [1]
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Pitman, R. K., Rasmusson, A. M., Koenen, K. C., Shin, L. M., Orr, S. P., Gilbertson, M. W., Milad, M. R., & Liberzon, I. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3339 · Cited by 1,529
Self-citationMcLaughlin, K. A., Sheridan, M. A., & Lambert, H. K. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.10.012 · Cited by 1,389
“, 2004), and increased vmPFC activity during such recall is associated with dampened amygdala activity (Milad et al., 2007, 2009; Milad and Quirk, 2012).”
BackgroundUsing Neuroscience to Help Understand Fear and Anxiety: A Two-System Framework
LeDoux, J. E., & Pine, D. S. (2016) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2016.16030353 · Cited by 1,035
Metadata
- Authors
- Milad, M. R., & Quirk, G. J.
- Affiliations
- Harvard University (US)
- University of Puerto Rico, Medical Sciences Campus (PR)
- Venue
- Annual Review of Psychology
- Publisher
- Annual Reviews
- Published
- 2012-01-10
- Volume
- 63
- Issue
- 1
- Pages
- 129-151
- ISSN
- 0066-4308 (ISSN-L)
- 1545-2085
- PMC
- PMC4942586
- OpenAlex
- W2160253364
- Semantic Scholar
- 3e1b47b5a0d8ab9823c918aa6f6ce64eb2eba033
- Cited by
- 1,466
- References
- 228
- Citations by year
- 2026: 105 · 2025: 96 · 2024: 80 · 2023: 96 · 2022: 110 · 2021: 114 · 2020: 131 · 2019: 120 · 2018: 109 · 2017: 102 · 2016: 100 · 2015: 105 · 2014: 88 · 2013: 73 · 2012: 36
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Psychology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5p50mh086400-05, 5r01mh081975-05)
- National Institute of Mental Health (P-50-MH-086400, K01-MH08036, R01-MH081975, R01MH058883, K01MH080346)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- fear extinction, fear conditioning, neural circuits, translational neuroscience, psychobiology, anxiety disorders
- MeSH terms
- Brain, Conditioning, Psychological, Extinction, Psychological, Fear, Humans, Magnetic Resonance Imaging, Neurosciences
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