Neural correlates of context-dependent extinction recall in social anxiety disorder: relevance of intrusions in response to aversive social experiences.

BACKGROUND: There are phenomenological similarities between social anxiety disorder (SAD) and posttraumatic stress disorder, such as a provoking aversive event, posttraumatic stress symptoms (e.g. intrusions) in response to these events and deficient (context-dependent) fear conditioning processes. This study investigated the neural correlates of context-dependent extinction recall and fear renewal in SAD, specifically in patients with intrusions in response to an etiologically relevant aversive social event. METHODS: During functional magnetic resonance imaging a two-day context-dependent fear conditioning paradigm was conducted in 54 patients with SAD and 54 healthy controls (HC). This included fear acquisition (context A) and extinction learning (context B) on one day, and extinction recall (context B) as well as fear renewal (contexts C and A) one day later. The main outcome measures were blood oxygen level-dependent responses in regions of interest and skin conductance responses. RESULTS: Patients with SAD showed reduced differential conditioned amygdala activation during extinction recall in the safe extinction context and during fear renewal in the acquisition context compared to HC. Patients with clinically relevant intrusions moreover exhibited hypoactivation of the ventromedial prefrontal cortex (vmPFC) during extinction learning, extinction recall, and fear renewal in a novel context, while amygdala activation more strongly decreased during extinction learning and increased during fear renewal in the acquisition context compared with patients without intrusions. CONCLUSIONS: Our study provides first evidence that intrusions in SAD are associated with similar deficits in context-dependent regulation of conditioned fear via the vmPFC as previously demonstrated in posttraumatic stress disorder.

Decontextualized fear memories? Stronger conditioned fear responses during extinction learning and extinction recall in a safe context predict the development of long-term analog intrusions.

BACKGROUND: Difficulties in the context-dependent modulation of conditioned fear are known for posttraumatic stress disorder and may explain the occurrence of intrusive memories in safe contexts. The current study therefore investigated if reduced context-dependent modulation of conditioned fear and its underlying neural circuitry constitute risk factors for the development of analog intrusions in response to an experimental trauma. METHODS: Eighty-five healthy women participated in the trauma film paradigm to investigate the development of analog intrusions as well as explicit memory for an experimental trauma after one week and three months, respectively. Before, participants underwent a context-dependent fear conditioning paradigm during functional magnetic resonance imaging with fear acquisition in context A and extinction training in context B on a first day, as well as extinction recall in context B and fear renewal in a novel context C one day later. Skin conductance responses (SCRs) and blood oxygen level dependent responses were main outcome measures. RESULTS: In addition to stronger fear acquisition in context A, stronger conditioned fear responses in the safe context B, as indicated by stronger conditioned SCRs or stronger activation of fear expressing regions during extinction learning and recall, predicted the development of long-term analog intrusions. CONCLUSIONS: Stronger fear responses in safe and danger contexts were risk factors for the development of long-term analog intrusions and point to decontextualized fear memories and difficulties in the context-dependent modulation of conditioned fear. Altered fear conditioning processes and reduced storage of contextual information may cause the occurrence of fear independent of context.

Weathering the storm of emotions: immediate and lasting effects of reinterpretation and distancing on event-related potentials and their association with habitual use of cognitive reappraisal.

Reinterpretation and distancing, two cognitive reappraisal tactics, are known to effectively reduce negative feelings and event-related potentials (ERPs), such as the P300 and the late positive potential (LPP), in the short-term. Less is known about differential and lasting effects on ERPs as well as their association with habitual reappraisal. Fifty-seven participants were instructed to passively view or reappraise (reinterpretation, distancing) pictures that were repeatedly presented with the same instruction (active regulation phase). Thirty minutes later, these pictures were shown again without instruction for the assessment of lasting effects (re-exposure phase). ERPs were recorded and participants rated the intensity of negative feelings following picture presentation. Reappraisal led to an attenuation of the LPP, and both tactics decreased negative feelings during active regulation, whereby reinterpretation had a stronger impact on the subjective level. Passive re-exposure resulted in reduced negative feelings for previously reappraised pictures but had no lasting effects on ERPs. Higher habitual reappraisal was associated with higher P300 and early LPP amplitudes for emotional reactivity during the active regulation phase. During the re-exposure phase, higher habitual reappraisal was not related to ERPs. The current findings emphasize the effectiveness of both tactics in the short-term and lasting effects on the subjective experience of negative feelings. Enhanced emotional reactivity on the electrocortical level in individuals with a more frequent habitual use of reappraisal might indicate a higher preparedness to regulate.

Behavioral pattern separation is associated with neural and electrodermal correlates of context-dependent fear conditioning.

Hippocampus-dependent pattern separation is considered as a relevant factor for context discrimination and might therefore impact the contextual modulation of conditioned fear. However, the association between pattern separation and context-dependent fear conditioning has not been investigated so far. In the current study, 72 healthy female students completed the Mnemonic Similarity Task, a measure of behavioral pattern separation, in addition to a context-dependent fear conditioning paradigm during functional magnetic resonance imaging. The paradigm included fear acquisition in context A and extinction training in context B on a first day, as well as retrieval testing of the fear and extinction memories in the safe context B (extinction recall) and a novel context C (fear renewal) one day later. Main outcome measures comprised skin conductance responses (SCRs) and blood oxygen level-dependent responses in brain regions of the fear and extinction circuit. Regarding retrieval testing, pattern separation did not correlate with extinction recall, but with stronger dorsal anterior cingulate cortex activation and conditioned SCRs (trend) during fear renewal, indicating a stronger retrieval of the fear memory trace. Our findings suggest that behavioral pattern separation ability seems to be important for context-dependent fear modulation, which is impaired in patients with posttraumatic stress disorder.

Memory representation of aversive social experiences in Social Anxiety Disorder.

Aversive social experiences are proposed to be a risk factor for developing Social Anxiety Disorder (SAD). Many patients with SAD report associated daily life symptoms, such as intrusive re-experiencing (e.g., negatively distorted images of oneself), avoidance, alterations in cognitions and mood, as well as hyperarousal, resembling symptom dimensions of Posttraumatic Stress Disorder (PTSD). These PTSD-like symptoms may result from maladaptive processing and representation of the aversive social experiences in memory. Emotional hyperreactivity during memory retrieval of aversive social experiences is another feature of SAD which was found in previous studies. This study aimed to further investigate PTSD-like symptoms and emotional reactivity associated with etiologically relevant aversive social experiences and shed more light on a potential relationship between both. Eighty-five patients with SAD and 85 healthy controls (HC) participated in this cross-sectional study. It comprised an imagination task with self-report and physiological measures to assess emotional reactivity during the cued recall of the aversive social experience and clinical interviews to assess PTSD-like symptoms. We expected increased emotional reactivity and more severe PTSD-like symptoms in response to the aversive social experience in patients with SAD compared to HC, as well as a positive correlation between emotional reactivity and PTSD-like symptoms in patients with SAD. Indeed, patients with SAD showed emotional hyperreactivity (self-report, physiology) during the cued recall of the aversive social experiences, also when compared to two control memory conditions (neutral, negative non-social) and HC. Patients with SAD furthermore reported more severe PTSD-like symptoms compared to HC and intrusive re-experiencing symptoms were positively correlated with distress during imagery of the social aversive event in patients with SAD. These results might point toward a maladaptive representation of aversive social experiences in memory. Similar to PTSD, this maladaptive memory representation might promote the development of PTSD-like symptoms such as intrusive re-experiencing (e.g., in the form of intrusive self-images in patients with SAD), which might finally lead to and maintain symptoms of SAD.

Social phobic beliefs mediate the relationship between post-event processing regarding the worst socially aversive experience and fear of negative evaluation.

The experience of socially aversive events is proposed to be a critical etiological factor in the development of social anxiety symptoms even though the experience itself is also common among healthy individuals. Rather than the event itself, accompanying factors such as maladaptive processing might be associated with higher levels of social anxiety symptoms. One-hundred-seventy-four individuals participated in this online-survey comprising questionnaires regarding social anxiety symptoms and retrospective reports concerning maladaptive processing of the worst socially aversive event. Structural equation modelling was used to analyze the hypothesized mediation of maladaptive processing and fear of negative evaluation by intrusive re-experiencing and social phobic beliefs. The positive association between retrospectively evaluated maladaptive processing after the worst socially aversive event and fear of negative evaluation was mediated by social phobic beliefs but not by intrusive re-experiencing. These results point towards the relevance of further investigating processing strategies after socially aversive events as a potential influencing factor for SAD development. Trial registration. The trial was registered at the German Clinical Trial Register (DRKS00021502) on June 3rd, 2020. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12144-022-02805-9.

Lasting effects of cognitive emotion regulation: neural correlates of reinterpretation and distancing.

Reinterpretation and distancing are two cognitive reappraisal tactics, used to regulate one's emotions in response to emotion-eliciting stimuli or situations. Relatively less is known about their (differential) lasting effects on emotional responding and related neural correlates. This functional magnetic resonance imaging study investigated 85 healthy females, participating in a 2-day cognitive emotion regulation experiment. On the first day, participants were instructed to passively look at, reinterpret or distance from repeatedly presented aversive pictures. One week later, they were re-exposed to the same stimuli without regulation instruction, in order to assess lasting effects. The main outcome measures comprised ratings of negative feelings and blood-oxygen-level-dependent responses. Lasting effects for reinterpretation compared with looking at aversive pictures during passive re-exposure 1 week later were reflected in stronger activation of the left amygdala, the ventromedial prefrontal cortex (vmPFC) and reduced negative feelings. Neither distancing compared with looking at aversive pictures nor reinterpretation compared with distancing did result in significant effects during re-exposure. These findings indicate that reinterpretation leads to reduced negative feelings 1 week later, which might be mediated by inhibitory vmPFC activation or stronger positive emotions during re-exposure. However, the missing difference compared with distancing questions the specificity of the results and the mechanisms underlying these two cognitive reappraisal tactics.