Test–Retest Reliability during Fear Acquisition and Fear Extinction in Humans

Department of Veterans Affairs Medical Center, Research Service, Manchester, New Hampshire, UK
CNS Neuroscience & Therapeutics (Impact Factor: 3.93). 02/2011; 18(4):313 - 317. DOI: 10.1111/j.1755-5949.2011.00238.x


Aims: Classical fear conditioning and extinction has been used to understand the neurobiology of fear learning and its inhibition. The recall of an extinction memory involves the ventromedial prefrontal cortex and the amygdala, and patients with posttraumatic stress disorder (PTSD) have been shown to exhibit deficits in this process. Furthermore, extinction forms the basis of exposure therapies commonly used to treat PTSD patients. It is possible that effective pharmacological and/or psychological treatment regimens could influence the activity of these regions, and thereby increase the ability to retain an extinction memory. However, to test this, a fear conditioning and extinction paradigm must demonstrate within-subject reproducibility over time. We, therefore, sought to test the within-subject reliability of a previously used 2-day, classical fear conditioning and extinction paradigm. Methods: Eighteen healthy participants participated in a 2-day paradigm on three occasions, each separated by at least 12 weeks. Conditioning and extinction took place on Day 1, and extinction recall and fear renewal were evaluated on Day 2 on each of the three occasions. The conditioned stimulus was a visual cue and the unconditioned stimulus was a mild electric shock to the fingers. Skin conductance was recorded throughout the experiment to measure conditioned responses. Results: We found that conditioning and extinction recall were not significantly different across time and were correlated within subjects. Conclusion: These data illustrate the reliability of this paradigm and its potential usefulness in evaluating the influence of a given treatment on the fear extinction network in longitudinal within-subject designs.

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Available from: Darin D Dougherty, Apr 14, 2014
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    • "rodent studies). Importantly, Zeidan et al. (2011) "
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    ABSTRACT: Exposure-based treatments for clinical anxiety generally are very effective, but relapse is not uncommon. Likewise, laboratory studies have shown that conditioned fears are easy to extinguish, but they recover easily. This analogy is striking, and numerous fear extinction studies have been published that highlight the processes responsible for the extinction and return of acquired fears. This review examines and integrates the most important results from animal and human work. Overall, the results suggest that fear extinction is relatively easy to "learn" but difficult to "remember." It follows that treatments will benefit from an enhanced focus on the long-term retrieval of fear extinction. We review the available studies on the prevention of return of fear and the prospects of weakening fear memories forever. We show that the behavioral principles outlined in learning theory provide a continuous inspiration for preclinical (neurobiological) and clinical research on the extinction and return of fear.
    Annual Review of Clinical Psychology 03/2013; 9(1):215-48. DOI:10.1146/annurev-clinpsy-050212-185542 · 12.67 Impact Factor
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    • "For example, improvements in fear inhibition after treatment may not be due to treatment efficacy, but rather to a practice effect from patients remembering the previously administered training paradigms. A recent study with fear acquisition and fear extinction tests spaced 12 weeks apart demonstrated good test–retest reliability on these measures (Zeidan et al., 2011); this is a crucial first step to developing treatment outcome measures. "
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    ABSTRACT: Posttraumatic stress disorder (PTSD) can develop in some individuals who are exposed to an event that causes extreme fear, horror, or helplessness (APA, 1994). PTSD is a complex and heterogeneous disorder, which is often co-morbid with depression, substance abuse, and anxiety disorders such as panic or social phobia. Given this complexity, progress in the field can be greatly enhanced by focusing on phenotypes that are more proximal to the neurobiology of the disorder. Such neurobiological intermediate phenotypes can provide investigative tools to increase our understanding of the roots of the disorder and develop better prevention or intervention programs. In the present paper, we argue that the inhibition of fear responses is an intermediate phenotype that is related to both the neurocircuitry associated with the disorder, and is linked to its clinical symptoms. An advantage of focusing on fear inhibition is that the neurobiology of fear has been well investigated in animal models providing the necessary groundwork in understanding alterations. Furthermore, because many paradigms can be tested across species, fear inhibition is an ideal translational tool. Here we review both the behavioral tests and measures of fear inhibition and the related neurocircuitry in neuroimaging studies with both healthy and clinical samples.
    Frontiers in Behavioral Neuroscience 07/2011; 5:44. DOI:10.3389/fnbeh.2011.00044 · 3.27 Impact Factor
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    ABSTRACT: The main behavioral signature of fear extinction is its fragility. This is exemplified by the renewal effect, where a change in the background context produces recovery of fear to a conditioned-and-extinguished stimulus. Renewal is the backbone of a widely accepted theory of extinction in animal research, as well as an important experimental model to screen novel treatment techniques. This has led to an explosion of fear renewal research in humans. However, the mere observation of return of fear in a renewal procedure is not sufficient to validate this particular theory of extinction in the tested sample/procedure. Here, we systematically outline a set of experimental tests that aid in evaluating alternative extinction/renewal mechanisms. We examine published renewal studies in human fear conditioning and conclude that the prevailing theory of extinction is often taken for granted, but critical tests are lacking. Including these tests in future research will not only reveal the fear extinction mechanism in humans, but also inspire further developments in extinction treatment research.
    Biological psychology 01/2012; 92(1). DOI:10.1016/j.biopsycho.2012.01.006 · 3.40 Impact Factor
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