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

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.

SUBMITTER: Lommen MJJ

PROVIDER: S-EPMC5638232 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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

Lommen Miriam J J MJJ Duta Mihaela M Vanbrabant Koen K de Jong Rachel R Juechems Keno K Ehlers Anke A

PloS one 20171012 10

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 ...[more]

PMID: 29023466

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Project description:The extinction of contextual fear is commonly an essential requirement for successful exposure therapy for fear disorders. However, experimental work on extinction of contextual fear is limited, and there little or no directly relevant theoretical work. Here, we extend BACON, a neurocomputational model of context fear conditioning that provides plausible explanations for a number of aspects of context fear conditioning, to deal with extinction (calling the model BaconX). In this model, contextual representations are formed in the hippocampus and association of fear to them occurs in the amygdala. Representation creation, conditionability, and development of between-session extinction are controlled by degree of confidence (assessed by the Bayesian weight of evidence) that an active contextual representation is in fact that of the current context (i.e., is "valid"). The model predicts that: (1) extinction which persists between sessions will occur only if at a sessions end there is high confidence that the active representation is valid. It follows that the shorter the context placement-to-US (shock) interval ("PSI") and the less is therefore learned about context, the longer extinction sessions must be for enduring extinction to occur, while too short PSIs will preclude successful extinction. (2) Short-PSI deficits can be rescued by contextual exposure even after conditioning has occurred. (3) Learning to discriminate well between a conditioned and similar safe context requires representations of each to form, which may not occur if PSI was too short. (4) Extinction-causing inhibition must be applied downstream of the conditioning locus for reasonable generalization properties to be generated. (5) Context change tends to cause return of extinguished contextual fear. (6). Extinction carried out in the conditioning context generalizes better than extinction executed in contexts to which fear has generalized (as done in exposure therapy). (7) BaconX suggests novel approaches to exposure therapy.

Project description:The hygiene hypothesis or "Old Friends" hypothesis proposes that inflammatory diseases are increasing in modern urban societies, due in part to reduced exposure to microorganisms that drive immunoregulatory circuits and a failure to terminate inappropriate inflammatory responses. Inappropriate inflammation is also emerging as a risk factor for anxiety disorders, affective disorders, and trauma-and stressor-related disorders, including posttraumatic stress disorder (PTSD), which is characterized as persistent re-experiencing of the trauma after a traumatic experience. Traumatic experiences can lead to long-lasting fear memories and fear potentiation of the acoustic startle reflex. The acoustic startle reflex is an ethologically relevant reflex and can be potentiated in both humans and rats through Pavlovian conditioning. Mycobacterium vaccae is a soil-derived bacterium with immunoregulatory and anti-inflammatory properties that has been demonstrated to enhance fear extinction in the fear-potentiated startle paradigm when given prior to fear conditioning. To determine if immunization with M. vaccae after fear conditioning also has protective effects, adult male Sprague Dawley rats underwent fear conditioning on days -37 and -36 followed by immunizations (3x), once per week beginning 24 h following fear conditioning, with a heat-killed preparation of M. vaccae NCTC 11659 (0.1 mg, s.c., in 100 µl borate-buffered saline) or vehicle, and, then, 3 weeks following the final immunization, were tested in the fear-potentiated startle paradigm (n = 12 per group). Rats underwent fear extinction training on days 1 through 6 followed by spontaneous recovery 14 days later (day 20). Rats were euthanized on day 21 and brain tissue was sectioned for analysis of Tph2, Htr1a, Slc6a4, Slc22a3, and Crhr2 mRNA expression throughout the brainstem dorsal and median raphe nuclei. Immunization with M. vaccae did not affect fear expression on day 1. However, M. vaccae-immunized rats showed enhanced enhanced within-session fear extinction on day 1 and enhanced between-session fear extinction beginning on day 2, relative to vehicle-immunized controls. Immunization with M. vaccae and fear-potentiated startle had minimal effects on serotonergic gene expression when assessed 42 days after the final immunization. Together with previous studies, these data are consistent with the hypothesis that immunoregulatory strategies, such as immunization with M. vaccae, have potential for both prevention and treatment of trauma- and stressor-related psychiatric disorders.

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

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

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