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Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit

Therapeutic interventions for disorders of fear and anxiety rely on behavioral approaches that reduce pathological fear memories. For example, learning that threat-predictive stimuli are no longer associated with aversive outcomes is central to the extinction of conditioned fear responses. Unfortuna...

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Autor principal: Maren, Stephen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9062589/
https://www.ncbi.nlm.nih.gov/pubmed/35520882
http://dx.doi.org/10.3389/fnsys.2022.888461
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author Maren, Stephen
author_facet Maren, Stephen
author_sort Maren, Stephen
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description Therapeutic interventions for disorders of fear and anxiety rely on behavioral approaches that reduce pathological fear memories. For example, learning that threat-predictive stimuli are no longer associated with aversive outcomes is central to the extinction of conditioned fear responses. Unfortunately, fear memories are durable, long-lasting, and resistant to extinction, particularly under high levels of stress. This is illustrated by the “immediate extinction deficit,” which is characterized by a poor long-term reduction of conditioned fear when extinction procedures are attempted within hours of fear conditioning. Here, I will review recent work that has provided new insight into the neural mechanisms underlying resistance to fear extinction. Emerging studies reveal that locus coeruleus norepinephrine modulates amygdala-prefrontal cortical circuits that are critical for extinction learning. These data suggest that stress-induced activation of brain neuromodulatory systems biases fear memory at the expense of extinction learning. Behavioral and pharmacological strategies to reduce stress in patients undergoing exposure therapy might improve therapeutic outcomes.
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spelling pubmed-90625892022-05-04 Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit Maren, Stephen Front Syst Neurosci Systems Neuroscience Therapeutic interventions for disorders of fear and anxiety rely on behavioral approaches that reduce pathological fear memories. For example, learning that threat-predictive stimuli are no longer associated with aversive outcomes is central to the extinction of conditioned fear responses. Unfortunately, fear memories are durable, long-lasting, and resistant to extinction, particularly under high levels of stress. This is illustrated by the “immediate extinction deficit,” which is characterized by a poor long-term reduction of conditioned fear when extinction procedures are attempted within hours of fear conditioning. Here, I will review recent work that has provided new insight into the neural mechanisms underlying resistance to fear extinction. Emerging studies reveal that locus coeruleus norepinephrine modulates amygdala-prefrontal cortical circuits that are critical for extinction learning. These data suggest that stress-induced activation of brain neuromodulatory systems biases fear memory at the expense of extinction learning. Behavioral and pharmacological strategies to reduce stress in patients undergoing exposure therapy might improve therapeutic outcomes. Frontiers Media S.A. 2022-04-19 /pmc/articles/PMC9062589/ /pubmed/35520882 http://dx.doi.org/10.3389/fnsys.2022.888461 Text en Copyright © 2022 Maren. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Systems Neuroscience
Maren, Stephen
Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit
title Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit
title_full Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit
title_fullStr Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit
title_full_unstemmed Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit
title_short Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit
title_sort unrelenting fear under stress: neural circuits and mechanisms for the immediate extinction deficit
topic Systems Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9062589/
https://www.ncbi.nlm.nih.gov/pubmed/35520882
http://dx.doi.org/10.3389/fnsys.2022.888461
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