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Beyond Fear, Extinction, and Freezing: Strategies for Improving the Translational Value of Animal Conditioning Research

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Fear Extinction

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 64))

Abstract

Translational neuroscience for anxiety has had limited success despite great progress in understanding the neurobiology of Pavlovian fear conditioning and extinction. This chapter explores the idea that conditioning paradigms have had a modest impact on translation because studies in animals and humans are misaligned in important ways. For instance, animal conditioning studies typically use imminent threats to assess short-duration fear states with single behavioral measures (e.g., freezing), whereas human studies typically assess weaker or more prolonged anxiety states with physiological (e.g., skin conductance) and self-report measures. A path forward may be more animal research on conditioned anxiety phenomena measuring dynamic behavioral and physiological responses in more complex environments. Exploring transitions between defensive brain states during extinction, looming threats, and post-threat recovery may be particularly informative. If care is taken to align paradigms, threat levels, and measures, this strategy may reveal stable patterns of non-conscious defense in animals and humans that correlate better with conscious anxiety. This shift in focus is also warranted because anxiety is a bigger problem than fear, even in disorders defined by dysfunctional fear or panic reactions.

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Acknowledgments

Thanks to Rob Sears for helpful comments on drafts of this manuscript and Joseph LeDoux for permission to publish data collected in his lab during my post-doctoral fellowship (Fig. 5b). The project described was supported by Award Number R01MH114931 to C.K.C. from the U.S. National Institutes of Health. The content is solely the responsibility of the author and does not necessarily represent the official views of the National Institute of Health and National Institute of Mental Health.

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  1. Department of Child and Adolescent Psychiatry, NYU Langone Health, New York, NY, USA

    Christopher K. Cain

  2. Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA

    Christopher K. Cain

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  1. Department of Psychiatry and Behavioral Sciences, UTHealth Houston, Houston, TX, USA

    Mohammed R. Milad

  2. Psychiatry and Behav Neurosciences, Wayne State University, Detroit, MI, USA

    Seth D. Norrholm

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Cain, C.K. (2023). Beyond Fear, Extinction, and Freezing: Strategies for Improving the Translational Value of Animal Conditioning Research. In: Milad, M.R., Norrholm, S.D. (eds) Fear Extinction. Current Topics in Behavioral Neurosciences, vol 64. Springer, Cham. https://doi.org/10.1007/7854_2023_434

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