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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.
The serotonin (5-HT) and neuropeptide S (NPS) systems are discussed as important genetic modulators of fear and sustained anxiety contributing to the etiology of anxiety disorders. Sustained anxiety is a crucial characteristic of most anxiety disorders which likely develops through contextual fear conditioning. This study investigated if and how genetic alterations of the 5-HT and the NPS systems as well as their interaction modulate contextual fear conditioning; specifically, function polymorphic variants in the genes coding for the 5-HT transporter (5HTT) and the NPS receptor (NPSR1) were studied. A large group of healthy volunteers was therefore stratified for 5HTTLPR (S+ vs. LL carriers) and NPSR1 rs324981 (T+ vs. AA carriers) polymorphisms resulting in four genotype groups (S+/T+, S+/AA, LL/T+, LL/AA) of 20 participants each. All participants underwent contextual fear conditioning and extinction using a virtual reality (VR) paradigm. During acquisition, one virtual office room (anxiety context, CXT+) was paired with an unpredictable electric stimulus (unconditioned stimulus, US), whereas another virtual office room was not paired with any US (safety context, CXT−). During extinction no US was administered. Anxiety responses were quantified by fear-potentiated startle and ratings. Most importantly, we found a gene × gene interaction on fear-potentiated startle. Only carriers of both risk alleles (S+/T+) exhibited higher startle responses in CXT+ compared to CXT−. In contrast, anxiety ratings were only influenced by the NPSR1 polymorphism with AA carriers showing higher anxiety ratings in CXT+ as compared to CXT−. Our results speak in favor of a two level account of fear conditioning with diverging effects on implicit vs. explicit fear responses. Enhanced contextual fear conditioning as reflected in potentiated startle responses may be an endophenotype for anxiety disorders.
Anxiety is characterized by anxious anticipation and heightened vigilance to uncertain threat. However, if threat is not reliably indicated by a specific cue, the context in which threat was previously experienced becomes its best predictor, leading to anxiety. A suitable means to induce anxiety experimentally is context conditioning: In one context (CTX+), an unpredictable aversive stimulus (US) is repeatedly presented, in contrast to a second context (CTX−), in which no US is ever presented. In this EEG study, we investigated attentional mechanisms during acquisition and extinction learning in 38 participants, who underwent a context conditioning protocol. Flickering video stimuli (32 s clips depicting virtual offices representing CTX+/−) were used to evoke steady‐state visual evoked potentials (ssVEPs) as an index of visuocortical engagement with the contexts. Analyses of the electrocortical responses suggest a successful induction of the ssVEP signal by video presentation in flicker mode. Furthermore, we found clear indices of context conditioning and extinction learning on a subjective level, while cortical processing of the CTX+ was unexpectedly reduced during video presentation. The differences between CTX+ and CTX− diminished during extinction learning. Together, these results indicate that the dynamic sensory input of the video presentation leads to disruptions in the ssVEP signal, which is greater for motivationally significant, threatening contexts.
Threat detection plays a vital role in adapting behavior to changing environments. A fundamental function to improve threat detection is learning to differentiate between stimuli predicting danger and safety. Accordingly, aversive learning should lead to enhanced sensory discrimination of danger and safety cues. However, studies investigating the psychophysics of visual and auditory perception after aversive learning show divergent findings, and both enhanced and impaired discrimination after aversive learning have been reported. Therefore, the aim of this web-based study is to examine the impact of aversive learning on a continuous measure of visual discrimination. To this end, 205 participants underwent a differential fear conditioning paradigm before and after completing a visual discrimination task using differently oriented grating stimuli. Participants saw either unpleasant or neutral pictures as unconditioned stimuli (US). Results demonstrated sharpened visual discrimination for the US-associated stimulus (CS+), but not for the unpaired conditioned stimuli (CS-). Importantly, this finding was irrespective of the US's valence. These findings suggest that associative learning results in increased stimulus salience, which facilitates perceptual discrimination in order to prioritize attentional deployment.
The effect of inherently threatening contexts on visuocortical engagement to conditioned threat
(2023)
Fear and anxiety are crucial for adaptive responding in life‐threatening situations. Whereas fear is a phasic response to an acute threat accompanied by selective attention, anxiety is characterized by a sustained feeling of apprehension and hypervigilance during situations of potential threat. In the current literature, fear and anxiety are usually considered mutually exclusive, with partially separated neural underpinnings. However, there is accumulating evidence that challenges this distinction between fear and anxiety, and simultaneous activation of fear and anxiety networks has been reported. Therefore, the current study experimentally tested potential interactions between fear and anxiety. Fifty‐two healthy participants completed a differential fear conditioning paradigm followed by a test phase in which the conditioned stimuli were presented in front of threatening or neutral contextual images. To capture defense system activation, we recorded subjective (threat, US‐expectancy), physiological (skin conductance, heart rate) and visuocortical (steady‐state visual evoked potentials) responses to the conditioned stimuli as a function of contextual threat. Results demonstrated successful fear conditioning in all measures. In addition, threat and US‐expectancy ratings, cardiac deceleration, and visuocortical activity were enhanced for fear cues presented in threatening compared with neutral contexts. These results are in line with an additive or interactive rather than an exclusive model of fear and anxiety, indicating facilitated defensive behavior to imminent danger in situations of potential threat.
Emotion regulation dysfunctions are assumed to contribute to the development of tobacco addiction and relapses among smokers attempting to quit. To further examine this hypothesis, the present study compared heavy smokers with non-smokers (NS) in a reappraisal task. Specifically, we investigated whether non-deprived smokers (NDS) and deprived smokers (DS) differ from non-smokers in cognitive emotion regulation and whether there is an association between the outcome of emotion regulation and the cigarette craving. Sixty-five participants (23 non-smokers, 22 NDS, and 20 DS) were instructed to down-regulate emotions by reappraising negative or positive pictorial scenarios. Self-ratings of valence, arousal, and cigarette craving as well as facial electromyography and electroencephalograph activities were measured. Ratings, facial electromyography, and electroencephalograph data indicated that both NDS and DS performed comparably to nonsmokers in regulating emotional responses via reappraisal, irrespective of the valence of pictorial stimuli. Interestingly, changes in cigarette craving were positively associated with regulation of emotional arousal irrespective of emotional valence. These results suggest that heavy smokers are capable to regulate emotion via deliberate reappraisal and smokers' cigarette craving is associated with emotional arousal rather than emotional valence. This study provides preliminary support for the therapeutic use of reappraisal to replace maladaptive emotion-regulation strategies in nicotine addicts.