Fear Extinction as a Model for Translational Neuroscience: Ten Years of Progress

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, 02129, USA.
Annual Review of Psychology (Impact Factor: 21.81). 01/2012; 63(1):129-51. DOI: 10.1146/annurev.psych.121208.131631
Source: PubMed


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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    • "This may reflect differences in basal levels of NE at the 297 onset of extinction (high in " immediate " extinction (i.e., when extinction is carried out minutes 298 to several hours after fear conditioning, and relatively low in delayed extinction). In line with 299 this hypothesis, it is well established that elevated NE signaling impairs prefrontal function 300 (Arnsten, 2009) and that the prelimbic (PL) and infralimbic (IL) subdivisions of the medial prefrontal cortex (mPFC) crucially regulate fear and its extinction (Giustino & Maren, 2015;302Milad & Quirk, 2012;Quirk & Beer, 2006;Riga et al., 2014;Sotres-Bayon & Quirk, 2010). "
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    ABSTRACT: Posttraumatic stress disorder (PTSD) has been described as the only neuropsychiatric disorder with a known cause, yet effective behavioral and pharmacotherapies remain elusive for many afflicted individuals. PTSD is characterized by heightened noradrenergic signaling, as well as a resistance to extinction learning. Research aimed at promoting more effective treatment of PTSD has focused on memory erasure (disrupting reconsolidation) and/or enhancing extinction retention through pharmacological manipulations. Propranolol, a β-adrenoceptor antagonist, has received considerable attention for its therapeutic potential in PTSD, although its impact on patients is not always effective. In this review, we briefly examine the consequences of β-noradrenergic manipulations on both reconsolidation and extinction learning in rodents and in humans. We suggest that propranolol is effective as a fear-reducing agent when paired with behavioral therapy soon after trauma when psychological stress is high, possibly preventing or dampening the later development of PTSD. In individuals who have already suffered from PTSD for a significant period of time, propranolol may be less effective at disrupting reconsolidation of strong fear memories. Also, when PTSD has already developed, chronic treatment with propranolol may be more effective than acute intervention, given that individuals with PTSD tend to experience long-term, elevated noradrenergic hyperarousal.
    Full-text · Article · Jan 2016 · Neurobiology of Learning and Memory
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    • "Frontiers in Behavioral Neuroscience | 2 December 2015 | Volume 9 | Article 340 interplay of conditioned pain-related danger and safety signals drives maladaptive avoidance behavior in chronic pain. Whereas the relevance of classically-conditioned fear is wellestablished in the context of anxiety disorders (Milad and Quirk, 2012; Tovote et al., 2015 "
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    ABSTRACT: Learning to predict pain based on internal or external cues constitutes a fundamental and highly adaptive process aimed at self-protection. Pain-related fear is an essential component of this response, which is formed by associative and instrumental learning processes. In chronic pain, pain-related fear may become maladaptive, drive avoidance behaviors and contribute to symptom chronicity. Pavlovian fear conditioning has proven fruitful to elucidate associative learning and extinction involving aversive stimuli, including pain, but studies in chronic pain remain scarce. Stress demonstrably exerts differential effects on emotional learning and memory processes, but this has not been transferred to pain-related fear. Within this perspective, we propose that stress could contribute to impaired pain-related associative learning and extinction processes and call for interdisciplinary research. Specifically, we suggest to test the hypotheses that: (1) extinction-related phenomena inducing a re-activation of maladaptive pain-related fear (e.g., reinstatement, renewal) likely occur in everyday life of chronic pain patients and may alter pain processing, impair perceptual discrimination and favor overgeneralization; (2) acute stress prior to or during acquisition of pain-related fear may facilitate the formation and/or consolidation of pain-related fear memories; (3) stress during or after extinction may impair extinction efficacy resulting in greater reinstatement or context-dependent renewal of pain-related fear; and (4) these effects could be amplified by chronic stress due to early adversity and/or psychiatric comorbidity such depression or anxiety in patients with chronic pain.
    Preview · Article · Jan 2016 · Frontiers in Behavioral Neuroscience
    • "This theoretical view has become the standard explanation for many learning effects related to extinction and to interference in general, both within the animal conditioning tradition and in human learning research. It also provides an excellent background to understand why psychological treatments for anxiety and fear disorders (usually based in ideas taken from the extinction and interference literatures) sometimes fail to prevent the resurgence of clinical symptoms (Milad and Quirk 2012;Vervliet et al. 2013). However, a missing detail in this general framework is explaining why the associations learned during extinction and interference become context dependent in first instance. "
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    ABSTRACT: It has been suggested that people and nonhuman animals protect their knowledge from interference by shifting attention towards the context when presented with information that contradicts their previous beliefs. Despite that suggestion, no studies have directly measured changes in attention while participants are exposed to an interference treatment. In the present experiments, we adapted a dot-probe task to track participants’ attention to cues and contexts while they were completing a simple category learning task. The results support the hypothesis that interference produces a change in the allocation of attention to cues and contexts.
    No preview · Article · Jan 2016 · Learning & Memory
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