Training discrimination diminishes maladaptive avoidance of innocuous stimuli in a fear conditioning paradigm

RESEARCH ARTICLE Training discrimination diminishes maladaptive avoidance of innocuous stimuli in a fear conditioning paradigm Miriam J. J. Lommen1,2¤*, Mihaela Duta1, Koen Vanbrabant3, Rachel de Jong1,2¤, Keno Juechems1, Anke Ehlers1,2 1 Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom, 2 Oxford Cognitive Health NIHR Clinical Research Facility, University of Oxford, Oxford, United Kingdom, 3 Center for the Psychology of Learning and Experimental Psychopathology, University of Leuven, Leuven, Belgium a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Lommen MJJ, Duta M, Vanbrabant K, de Jong R, Juechems K, Ehlers A (2017) Training discrimination diminishes maladaptive avoidance of innocuous stimuli in a fear conditioning paradigm. PLoS ONE 12(10): e0184485. https:// doi.org/10.1371/journal.pone.0184485 Editor: Simon Dymond, Swansea University, UNITED KINGDOM Received: January 4, 2017 Accepted: August 24, 2017 Published: October 12, 2017 Copyright: © 2017 Lommen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ¤ Current address: Department of Clinical Psychology, University of Groningen, Groningen, the Netherlands * Abstract Anxiety disorders are the most common mental disorder worldwide. Although anxiety disorders differ in the nature of feared objects or situations, they share a common mechanism by which fear generalizes to related but innocuous objects, eliciting avoidance of objects and situations that pose no objective risk. This overgeneralization appears to be a crucial mechanism in the persistence of anxiety psychopathology. In this study we test whether an intervention that promotes discrimination learning reduces generalization of fear, in particular, harm expectancy and avoidance compared to an irrelevant (control) training. Healthy participants (N = 80) were randomly allocated to a training condition. Using a fear conditioning paradigm, participants first learned visual danger and safety signals (set 1). Baseline level of stimulus generalization was tested with ambiguous stimuli on a spectrum between the danger and safety signals. There were no differences between the training groups. Participants then received the stimulus discrimination training or a control training. After training, participants learned a new set of danger and safety signals (set 2), and the level of harm expectancy generalization and behavioural avoidance of ambiguous stimuli was tested. Although the training groups did not differ in fear generalization on a cognitive level (harm expectancy), the results showed a different pattern of avoidance of ambiguous stimuli, with the discrimination training group showing less avoidance of stimuli that resembled the safety signals. These results support the potential of interventions that promote discrimination learning in the treatment of anxiety disorders. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: The study was funded by Wellcome Trust grant 069777 and supported by the Oxford cognitive health NIHR Clinical Research Facility. Competing interests: The authors have declared that no competing interests exist. Introduction Anxiety disorders are the most common mental disorders [1,2] and are characterized by excessive fear and avoidance. While the type of feared stimuli varies across the different anxiety disorders, e.g., social interactions in social anxiety disorder, spiders is spider phobia, intense exercise in panic disorder, a common feature is that the patients’ fear has generalized to PLOS ONE | https://doi.org/10.1371/journal.pone.0184485 October 12, 2017 1 / 14 Training discrimination diminishes avoidance innocuous stimuli or situations and elicits excessive avoidance responses. The fear and avoidance can dominate patients’ lives by impairing physical, social, emotional, and professional functioning [3]. There is a growing interest in the mechanisms of fear generalization. Fear conditioning paradigms have been used to investigate this process in the laboratory. After a conditioning phase, these paradigms measure responses to ambiguous or generalized stimuli (GS) that share features of learned danger (CS+) and safety (CS-) signals to varying degrees. The subjective reaction (e.g., harm expectancy) and the physiological activity these GSs evoke are usually assessed as indicators of the level of fear generalization. Fear generalization is operationalized as the transference of the fear evoked by the danger signal to stimuli that are either perceptually similar to the CS+, or non-perceptually related to the CS+, for example by being semantically or symbolically related to the CS+ (for an overview see [4]). Compared to healthy controls, patients with generalized anxiety disorder [5] or panic disorder [6], tend to show an overgeneralization of fear: they tend to generalize their fear response to stimuli that are less closely related to the CS+, and to a larger number of stimuli in general. One of the ways the overgeneralization is assessed in clinical samples is the shape of the curve when the stimuli (CS-, GSs and CS+) are plotted on the x-axis and the responses to the CSs on the Y-axis: the curve is more quadratic in the healthy control group and more linear in the anxiety patient group (e.g., [5]), reflecting increased responses towards GSs in the anxiety population. Although not all studies have found this overgeneralization effect [7,8], there is substantial evidence for the role of fear generalization in anxiety pathology [4,9]. An important limitation of the research in fear generalization is the scarcity with which overt behaviour or avoidance tendencies have been included as an index of fear [10,11]. Avoidance behaviour in response to innocuous stimuli constitutes one of the major aspects of diagnostic criteria for anxiety disorders [12]. Moreover, avoidance seems to play a crucial role in the maintenance and possibly even exacerbation of pathological anxiety by preventing disconfirmation of irrational or exaggerated danger beliefs[13]. Thus, assessing avoidance behaviour in fear generalization paradigms seems to have important clinical relevance. Thus far, only a few studies have done this by studying learning and generalization of avoidance [14,15], showing support for an association between overgeneralization of fear and overgeneralization of avoidance [11], and enhanced avoidance of GS in anxiety prone individuals (i.e., high neuroticism, [16]). A next challenge in the field of fear generalization is to further insight into interventions that target (over)generalization of fear and avoidance. A first successful attempt has recently been shown in a study in healthy adults. Compared to a control gr (...truncated)