Human fear conditioning: From neuroscience to the clinic
Introduction
When in 1920, John B. Watson and Rosalie Rayner conditioned a young child who would become known as “Little Albert”, they could not have imagined the extraordinary impact that their experiment would have in our current conceptualization of anxiety-related disorders, almost a century later. Over the past two decades, in particular, this legacy has been strengthened by the ‘happy marriage’ between neuroscientists and clinicians interested in the topic of fear conditioning phenomena, although it must be said, love took a while to emerge. In this review, we will briefly reflect on some of the history of this relationship and the specific progress that has been made in translating the neuroscientific study of human fear conditioning models to the management and treatment of anxiety-related disorders (including panic disorder/agoraphobia; specific phobia; social anxiety disorder, SAD; generalized anxiety disorder, GAD; obsessive-compulsive disorder, OCD; and post-traumatic stress disorder, PTSD). We will also address some of the conceptual and practical challenges that have been faced during this process and will offer some suggestions for future research in the field.
Section snippets
How did we get here? From Watson to FMRI
Watson is considered one of the founding fathers of behaviorism as a scientific movement or paradigm. Besides introducing behaviorism, Watson's emphasis on environmental influences sharpened the focus of experimental psychology on the construct of ‘learning’ and on the formulation of ‘laws of behavior’, a focus which endured for at least three decades. During that period, experimental psychology was also heavily influenced by research in laboratory animals (Kazdin, 1978; Krasner, 1990).
Translating neuroscience to the clinic
There continue to be pioneering advances in the neuroscience of learning and memory using fear conditioning models, especially in rodents. And with technological developments—such as the use of activity-dependent neural tagging and optogenetics—the fine-scale microcircuitry within and between the amygdala, hippocampus, and medial prefrontal cortex is coming into view (Janak & Tye, 2015; Krabbe et al., 2018; Tovote et al., 2015). But an important and highly interesting question going forward is
Conceptual challenges
The beauty of human fear conditioning paradigms is their simplicity and possibility to translate across various mammal and non-mammal species, such that molecular and cellular knowledge garnered in other species can be leveraged for developing treatments. Nevertheless, the paradigm models only some aspects and symptoms of anxiety-related disorders.
For example, for many specific phobias, there is no consistent evidence that they emerge in the way that Watson proposed: an early traumatic
Computational approaches
The idea that alterations in basic fear conditioning and/or extinction contribute to etiology or maintenance of anxiety-related disorders is appealing and has high face validity for clinicians. Nevertheless, studies in controlled laboratory circumstances have so far not been able to identify reproducible characteristic alterations in patient groups. A meta-analysis including over 900 anxiety patients and over 1200 controls has revealed an inconsistent pattern despite the very large sample size (
Declaration of competing interest
The authors declare no conflicts of interest.
Acknowledgements
MAF is supported by Carlos III Health Institute and FEDER grant (PI16/00144). JED is supported in part from NIH R00MH106719 and a National Science Foundation CAREER award (1844792). HSS is supported by an Australian Government Research Training Program (RTP) Scholarship. DRB is supported by funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant agreement No. ERC-2018 CoG-816564 ActionContraThreat). BJH is supported by a
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