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Active Avoidance: Neural Mechanisms and Attenuation of Pavlovian Conditioned Responding.
J Neurosci. 2017 05 03; 37(18):4808-4818.JN

Abstract

Patients with anxiety disorders often experience a relapse in symptoms after exposure therapy. Similarly, threat responses acquired during Pavlovian threat conditioning often return after extinction learning. Accordingly, there is a need for alternative methods to persistently reduce threat responding. Studies in rodents have suggested that exercising behavioral control over an aversive stimulus can persistently diminish threat responses, and that these effects are mediated by the amygdala, ventromedial prefrontal cortex, and striatum. In this fMRI study, we attempted to translate these findings to humans. Subjects first underwent threat conditioning. We then contrasted two forms of safety learning: active avoidance, in which participants could prevent the shock through an action, and yoked extinction, with shock presentation matched to the active condition, but without instrumental control. The following day, we assessed subjects' threat responses (measured by skin conductance) to the conditioned stimuli without shock. Subjects next underwent threat conditioning with novel stimuli. Yoked extinction subjects showed an increase in conditioned response to stimuli from the previous day, but the active avoidance group did not. Additionally, active avoidance subjects showed reduced conditioned responding during novel threat conditioning, but the extinction group did not. We observed between-group differences in striatal BOLD responses to shock omission in Avoidance/Extinction. These findings suggest a differential role for the striatum in human active avoidance versus extinction learning, and indicate that active avoidance may be more effective than extinction in persistently diminishing threat responses.SIGNIFICANCE STATEMENT Extinguished threat responses often reemerge with time, highlighting the importance of identifying more enduring means of attenuation. We compared the effects of active avoidance learning and yoked extinction on threat responses in humans and contrasted the neural circuitry engaged by these two processes. Subjects who learned to prevent a shock through an action maintained low threat responses after safety learning and showed attenuated threat conditioning with novel stimuli, in contrast to those who underwent yoked extinction. The results suggest that experiences of active control over threat engage the striatum and promote a shift from expression of innate defensive responses toward more adaptive behavioral responses to threatening stimuli.

Authors+Show Affiliations

Department of Psychology and.Center for Neural Science, New York University, New York, New York 10003, and.Center for Neural Science, New York University, New York, New York 10003, and. Nathan Kline Institute, Orangeburg, New York 10962.Department of Psychology and. Center for Neural Science, New York University, New York, New York 10003, and. Nathan Kline Institute, Orangeburg, New York 10962.Department of Psychology and cah369@nyu.edu.

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

28408411

Citation

Boeke, Emily A., et al. "Active Avoidance: Neural Mechanisms and Attenuation of Pavlovian Conditioned Responding." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 37, no. 18, 2017, pp. 4808-4818.
Boeke EA, Moscarello JM, LeDoux JE, et al. Active Avoidance: Neural Mechanisms and Attenuation of Pavlovian Conditioned Responding. J Neurosci. 2017;37(18):4808-4818.
Boeke, E. A., Moscarello, J. M., LeDoux, J. E., Phelps, E. A., & Hartley, C. A. (2017). Active Avoidance: Neural Mechanisms and Attenuation of Pavlovian Conditioned Responding. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 37(18), 4808-4818. https://doi.org/10.1523/JNEUROSCI.3261-16.2017
Boeke EA, et al. Active Avoidance: Neural Mechanisms and Attenuation of Pavlovian Conditioned Responding. J Neurosci. 2017 05 3;37(18):4808-4818. PubMed PMID: 28408411.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Active Avoidance: Neural Mechanisms and Attenuation of Pavlovian Conditioned Responding. AU - Boeke,Emily A, AU - Moscarello,Justin M, AU - LeDoux,Joseph E, AU - Phelps,Elizabeth A, AU - Hartley,Catherine A, Y1 - 2017/04/13/ PY - 2016/10/20/received PY - 2017/03/24/revised PY - 2017/03/27/accepted PY - 2017/4/15/pubmed PY - 2017/8/19/medline PY - 2017/4/15/entrez KW - active avoidance KW - anxiety KW - coping KW - instrumental learning KW - resilience KW - threat conditioning SP - 4808 EP - 4818 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J Neurosci VL - 37 IS - 18 N2 - Patients with anxiety disorders often experience a relapse in symptoms after exposure therapy. Similarly, threat responses acquired during Pavlovian threat conditioning often return after extinction learning. Accordingly, there is a need for alternative methods to persistently reduce threat responding. Studies in rodents have suggested that exercising behavioral control over an aversive stimulus can persistently diminish threat responses, and that these effects are mediated by the amygdala, ventromedial prefrontal cortex, and striatum. In this fMRI study, we attempted to translate these findings to humans. Subjects first underwent threat conditioning. We then contrasted two forms of safety learning: active avoidance, in which participants could prevent the shock through an action, and yoked extinction, with shock presentation matched to the active condition, but without instrumental control. The following day, we assessed subjects' threat responses (measured by skin conductance) to the conditioned stimuli without shock. Subjects next underwent threat conditioning with novel stimuli. Yoked extinction subjects showed an increase in conditioned response to stimuli from the previous day, but the active avoidance group did not. Additionally, active avoidance subjects showed reduced conditioned responding during novel threat conditioning, but the extinction group did not. We observed between-group differences in striatal BOLD responses to shock omission in Avoidance/Extinction. These findings suggest a differential role for the striatum in human active avoidance versus extinction learning, and indicate that active avoidance may be more effective than extinction in persistently diminishing threat responses.SIGNIFICANCE STATEMENT Extinguished threat responses often reemerge with time, highlighting the importance of identifying more enduring means of attenuation. We compared the effects of active avoidance learning and yoked extinction on threat responses in humans and contrasted the neural circuitry engaged by these two processes. Subjects who learned to prevent a shock through an action maintained low threat responses after safety learning and showed attenuated threat conditioning with novel stimuli, in contrast to those who underwent yoked extinction. The results suggest that experiences of active control over threat engage the striatum and promote a shift from expression of innate defensive responses toward more adaptive behavioral responses to threatening stimuli. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/28408411/Active_Avoidance:_Neural_Mechanisms_and_Attenuation_of_Pavlovian_Conditioned_Responding_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=28408411 DB - PRIME DP - Unbound Medicine ER -