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      Contextual Fear Conditioning and Fear Generalization in Individuals With Panic Attacks

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          Abstract

          Context conditioning is characterized by unpredictable threat and its generalization may constitute risk factors for panic disorder (PD). Therefore, we examined differences between individuals with panic attacks (PA; N = 21) and healthy controls (HC, N = 22) in contextual learning and context generalization using a virtual reality (VR) paradigm. Successful context conditioning was indicated in both groups by higher arousal, anxiety and contingency ratings, and increased startle responses and skin conductance levels (SCLs) in an anxiety context (CTX+) where an aversive unconditioned stimulus (US) occurred unpredictably vs. a safety context (CTX−). PA compared to HC exhibited increased differential responding to CTX+ vs. CTX− and overgeneralization of contextual anxiety on an evaluative verbal level, but not on a physiological level. We conclude that increased contextual conditioning and contextual generalization may constitute risk factors for PD or agoraphobia contributing to the characteristic avoidance of anxiety contexts and withdrawal to safety contexts and that evaluative cognitive process may play a major role.

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          Most cited references32

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          Publication recommendations for electrodermal measurements.

          This committee was appointed by the SPR Board to provide recommendations for publishing data on electrodermal activity (EDA). They are intended to be a stand-alone source for newcomers and experienced users. A short outline of principles for electrodermal measurement is given, and recommendations from an earlier report (Fowles et al., ) are incorporated. Three fundamental techniques of EDA recording are described: (1) endosomatic recording without the application of an external current, (2) exosomatic recording with direct current (the most widely applied methodology), and (3) exosomatic recording with alternating current-to date infrequently used but a promising future methodology. In addition to EDA recording in laboratories, ambulatory recording has become an emerging technique. Specific problems that come with this recording of EDA in the field are discussed, as are those emerging from recording EDA within a magnetic field (e.g., fMRI). Recommendations for the details that should be mentioned in publications of EDA methods and results are provided. Copyright © 2012 Society for Psychophysiological Research.
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            Overgeneralization of conditioned fear as a pathogenic marker of panic disorder.

            Classical conditioning features prominently in many etiological accounts of panic disorder. According to such accounts, neutral conditioned stimuli present during panic attacks acquire panicogenic properties. Conditioned stimuli triggering panic symptoms are not limited to the original conditioned stimuli but are thought to generalize to stimuli resembling those co-occurring with panic, resulting in the proliferation of panic cues. The authors conducted a laboratory-based assessment of this potential correlate of panic disorder by testing the degree to which panic patients and healthy subjects manifest generalization of conditioned fear. Nineteen patients with a DSM-IV-TR diagnosis of panic disorder and 19 healthy comparison subjects were recruited for the study. The fear-generalization paradigm consisted of 10 rings of graded size presented on a computer monitor; one extreme size was a conditioned danger cue, the other extreme a conditioned safety cue, and the eight rings of intermediary size created a continuum of similarity from one extreme to the other. Generalization was assessed by conditioned fear potentiating of the startle blink reflex as measured with electromyography (EMG). Panic patients displayed stronger conditioned generalization than comparison subjects, as reflected by startle EMG. Conditioned fear in panic patients generalized to rings with up to three units of dissimilarity to the conditioned danger cue, whereas generalization in comparison subjects was restricted to rings with only one unit of dissimilarity. The findings demonstrate a marked proclivity toward fear overgeneralization in panic disorder and provide a methodology for laboratory-based investigations of this central, yet understudied, conditioning correlate of panic. Given the putative molecular basis of fear conditioning, these results may have implications for novel treatments and prevention in panic disorder.
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              Models and mechanisms of anxiety: evidence from startle studies.

              Preclinical data indicates that threat stimuli elicit two classes of defensive behaviors, those that are associated with imminent danger and are characterized by flight or fight (fear), and those that are associated with temporally uncertain danger and are characterized by sustained apprehension and hypervigilance (anxiety). The objectives of the study are to (1) review evidence for a distinction between fear and anxiety in animal and human experimental models using the startle reflex as an operational measure of aversive states, (2) describe experimental models of anxiety, as opposed to fear, in humans, (3) examine the relevance of these models to clinical anxiety. The distinction between phasic fear to imminent threat and sustained anxiety to temporally uncertain danger is suggested by psychopharmacological and behavioral evidence from ethological studies and can be traced back to distinct neuroanatomical systems, the amygdala and the bed nucleus of the stria terminalis. Experimental models of anxiety, not fear, are relevant to non-phobic anxiety disorders. Progress in our understanding of normal and abnormal anxiety is critically dependent on our ability to model sustained aversive states to temporally uncertain threat.
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                Author and article information

                Contributors
                Journal
                Front Behav Neurosci
                Front Behav Neurosci
                Front. Behav. Neurosci.
                Frontiers in Behavioral Neuroscience
                Frontiers Media S.A.
                1662-5153
                17 July 2019
                2019
                : 13
                : 152
                Affiliations
                [1] 1Department of Psychology (Biological Psychology, Clinical Psychology, and Psychotherapy), University of Würzburg , Würzburg, Germany
                [2] 2Center for Mental Health, Medical Faculty, University of Würzburg , Würzburg, Germany
                Author notes

                Edited by: Seth Davin Norrholm, Emory University School of Medicine, United States

                Reviewed by: Jeffrey B. Rosen, University of Delaware, United States; Travis D. Goode, Harvard University, United States

                *Correspondence: Paul Pauli pauli@ 123456psychologie.uni-wuerzburg.de
                Article
                10.3389/fnbeh.2019.00152
                6653660
                11cd171e-648f-4a21-b32d-df5c25ebd71c
                Copyright © 2019 Neueder, Andreatta and Pauli.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 01 February 2019
                : 21 June 2019
                Page count
                Figures: 4, Tables: 1, Equations: 30, References: 46, Pages: 10, Words: 5675
                Funding
                Funded by: Deutsche Forschungsgemeinschaft 10.13039/501100001659
                Award ID: 44541416
                Funded by: Julius-Maximilians-Universität Würzburg 10.13039/501100008769
                Categories
                Neuroscience
                Original Research

                Neurosciences
                contextual fear conditioning,anxiety generalization,startle response,panic disorder,virtual reality

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