Unconditioned stimulus devaluation decreases the generalization of costly safety behaviors.

Safety behaviors are often maladaptive in clinical anxiety as they typically persist without realistic threat and cause various impairments. In the laboratory, safety behaviors are modelled by responses to a conditioned stimulus (CS) that reduce the occurrence of an expected aversive unconditioned stimulus (US). Preliminary evidence suggests that US devaluation, a procedure that decreases US aversiveness, devalues the threat value of the CS and thus diminishes safety behaviors to the CS. This study (n = 78) aimed to extend this finding and examined whether US-devaluation can reduce the generalization of safety behaviors to various stimuli. After acquiring safety behaviors to CSs of different categories, the US predicted by one CS category was devalued. In test, participants showed a selective reduction in safety behaviors to novel stimuli of the devalued CS category, reflecting a decrease in generalization of safety behaviors. Trait anxiety was associated with persistent generalized safety behaviors to novel stimuli of the devalued category. We discuss how US devaluation may improve treatment outcome but also the challenges of clinical translation.

High-Anxious People Generalize Costly Pain-Related Avoidance Behavior More to Novel Safe Contexts Compared to Low-Anxious People.

Pain-related avoidance is adaptive when there is a bodily threat, but when it generalizes to safe movements/situations, it may become disabling. Both subclinical anxiety-a vulnerability marker for chronic pain-and chronic pain are associated with excessive fear generalization to safe stimuli/situations. Previous research focused mainly on passive fear correlates (psychophysiological arousal and self-reports) leaving avoidance behavior poorly understood. Therefore, we tested whether high-anxious individuals generalize their pain-related avoidance behavior more to novel, safe contexts than low-anxious people. In a robotic-arm-reaching task, both groups (low vs high trait anxiety) performed 1 of 3 movements to reach a target. In the threat context (black background), a painful stimulus could be partly/completely prevented by performing more effortful trajectories (longer and more force needed); in the safe context (white background), no pain occurred. Generalization of avoidance was tested in 2 novel contexts (light/dark gray backgrounds). We assessed pain expectancy, pain-related fear, startle eyeblink responses for all trajectories, and avoidance behavior (ie, maximal deviation from shortest trajectory). Results indicated that differential fear and expectancy selectively generalized to the novel context resembling the original threat context in both groups. Interestingly and in contrast with the verbal reports, high-anxious participants avoided more in the novel context resembling the original safe context, but not in the 1 resembling the threat context. No generalization emerged in the startle data. Because excessive pain-related avoidance specifically may cause withdrawal from daily life activities, these findings suggest that high-anxious individuals may be vulnerable to developing chronic pain disability. PERSPECTIVE: This paper shows that high-anxious people do not overgeneralize pain-related fear and pain expectancy learned in a threat context more to novel, safe contexts than low-anxious individuals, but that they do avoid more in those contexts. These findings suggest that high-anxious individuals may be vulnerable to developing chronic pain disability.

Distinct circuits in anterior cingulate cortex encode safety assessment and mediate flexibility of fear reactions.

Safety assessment and threat evaluation are crucial for animals to live and survive in the wilderness. However, neural circuits underlying safety assessment and their transformation to mediate flexibility of fear-induced defensive behaviors remain largely unknown. Here, we report that distinct neuronal populations in mouse anterior cingulate cortex (ACC) encode safety status by selectively responding under different contexts of auditory threats, with one preferably activated when an animal staysing in a self-deemed safe zone and another specifically activated in more dangerous environmental settings that led to escape behavior. The safety-responding neurons preferentially target the zona incerta (ZI), which suppresses the superior colliculus (SC) via its GABAergic projection, while the danger-responding neurons preferentially target and excite SC. These distinct corticofugal pathways antagonistically modulate SC responses to threat, resulting in context-dependent expression of fear reactions. Thus, ACC serves as a critical node to encode safety/danger assessment and mediate behavioral flexibility through differential top-down circuits.

Reduction of costly safety behaviors after extinction with a generalization stimulus is determined by individual differences in generalization rules.

Exposure-based treatment involves repeated presentation of feared stimuli or situations in the absence of perceived threat (i.e., extinction learning). However, the stimulus or situation of fear acquisition (CS+) is highly unlikely to be replicated and presented during treatment. Thereby, stimuli that resemble the CS+ (generalization stimuli; GSs) are typically presented. Preliminary evidence suggests that depending on how one generalizes fear (i.e., different generalization rules), presenting the same GS in extinction leads to differential effectiveness of extinction learning. The current study aimed to extend this finding to safety behaviors. After differential fear and avoidance conditioning, participants exhibited discrete generalization gradients that were consistent with their reported generalization rules (Similarity vs Linear). The Linear group showed stronger safety behaviors to a selected GS compared to the Similarity group, presumably due to higher threat expectancy. After extinction learning to this GS, the Linear group exhibited stronger reduction in safety behaviors generalization compared to the Similarity group. The results show that identifying distinct generalization rules allows one to predict expectancy violation to the extinction stimulus, in addition to corroborating the idea that strongly violating threat expectancy leads to better extinction learning and its generalization. With regard to clinical implications, identifying one's generalization rule (e.g., threat beliefs) help designing exposure sessions that evoke strong expectancy violation, enhancing the reduction in the generalization of maladaptive safety behaviors.

Fear learning and extinction predicts anxiety in daily life: a study of Pavlovian conditioning and ecological momentary assessment.

BACKGROUND: The association between anxious mood and aberrant fear learning mechanisms has not been fully elucidated. Studying how fear conditioning and extinction constructs relate to anxiety symptoms and reactivity to stressful and benign moments in everyday life provides a powerful addition to experimental paradigms. METHOD: Fifty-one young adults completed laboratory-based differential conditioning and extinction tasks with (CS + ) and without (CS-) an aversive unconditional stimulus (US). Electrodermal skin conductance responses were measured during each phase, followed by ecological momentary assessment (EMA) tapping anxiety and stressors six times daily for seven days (2, 142 moments). RESULTS: Conditioned electrodermal reactivity to the CS + and overgeneralisation to the CS- were associated with greater change in anxiety (measured via EMA), across non-stressful situations, remaining the same across stressful situations. Likewise, during extinction when the CS + is now safe, more electrodermal reactivity to the CS + was associated with more anxiety change across non-stressful situations and remained the same across stressful situations. Also, during extinction when threat is absent, more electrodermal reactivity at the late stage of the CS- was associated with less momentary anxiety change in response to stressful situations; more electrodermal activity at the late stage of the CS + was associated with more anxiety change across non-stressful situations and remained the same across stressful situations. CONCLUSIONS: Sampling 'in vivo' emotion and stress experiences, study findings revealed links between conditioned electrodermal reactivity and overgeneralisation to safe stimuli and heightened anxious reactivity during non-stressful (i.e. safe) moments in daily life, coupled with less change in response to actual stressors.

Longitudinal assessment of amygdala activity in mice susceptible to trauma.

Resilience to consequences of trauma exposure contains relevant information about the processes that contribute to the maintenance of mental health in the face of adversity; information that is essential to improve treatment success of stress-related mental diseases. Prior literature has implicated aberrant amygdala (re)activity as potential factor contributing to trauma susceptibility. However, it remains to be resolved which amygdalar subregions and neuronal subclasses are involved, and when - i.e., pre-, peri- or post-trauma exposure - and under what conditions changes in amygdala (re)activity manifest themselves. Here, we implemented a preclinical rodent model for PTSD that entailed exposure to a traumatic event (severe, unpredictable foot shock) followed by a trigger (mild, predictable foot shock). Using behavioral phenotyping, trauma susceptible vs. resilient mice were identified and pre-, peri- or post-trauma amygdala activity was compared. Neuronal activity was tagged in living mice by the use of the ArcTRAP transgenic mouse line, labeling all activated (i.e., Arc-expressing) neurons by a systemic injection of tamoxifen. Furthermore, we assessed amygdala responses during fear memory recall, induced by either (re-)exposure to the trauma, trigger, or a novel, yet similar context, and analyzed behavioral fear responses under these conditions, as well as basal anxiety in the mice. Results revealed no major differences dissociating susceptible vs. resilient mice prior to trauma exposure, but exaggerated activity in specifically the basolateral amygdala (BLA) peri-trauma that predicted susceptibility to later PTSD-like symptoms. Post-trauma, susceptible mice did not display altered basal amygdala activity, but BLA hyperreactivity in response to trigger context re-exposure, and BLA hyporesponsivity in response to the trauma context. Exposure to the novel, similar context evoked a differential temporal pattern of freezing behavior in susceptible mice and an increased activity of amygdalar somatostatin-expressing neurons specifically. As such, these results for the first time show that deviant BLA activity during fear learning predicts susceptibility to its long-term consequences and that aberrant subsequent BLA responses to stressful contexts depend on the exact context.

Sustained threat and phasic fear in the laboratory and cognitive-emotional processes of anxiety in everyday life - An ambulatory assessment study.

Fear is a phasic state of apprehension to an imminent threat, whereas anxiety is a more sustained state of expecting a potential threat leading to tension and worry. The NPU-threat test is a laboratory startle paradigm allowing a reliable and valid assessment of both, fear- and anxiety-potentiated reactions. It is suggested to differentiate between anxiety disorders, but little is known on associations with everyday life experiences of cognitive-emotional processes regarding anxiety in non-clinical samples. In the present project, the NPU-threat test was applied in three studies with (1) unselected healthy individuals, (2) participants with extreme manifestations of trait anxiety (low vs. high) and (3) individuals preparing for a high-stakes exam. Self-reported states of emotionality and worry were assessed during a four-day ambulatory assessment (AA). Overall, NPU-threat test measures did not significantly differ between studies, while the AA dependent measures were sufficiently sensitive to capture differences between groups. However, there was no significant association between psychophysiological measures of the NPU-threat test and AA state measures across participants. In participants recruited for low vs. high trait anxiety we found an association with AA worry and emotionality, but no interaction with potentiated startle. The present findings do not support the idea of a link between our laboratory biomarker and adaptive regulation of cognitive-emotional states in everyday life in healthy individuals. We speculate that an association between laboratory physiological measures and everyday experience of anxious states may be detectable in clinical samples.

Indoor or Outdoor? Generalization of Costly Pain-Related Avoidance Behavior to Conceptually Related Contexts.

When pain persists beyond healing time and becomes a "false alarm" of bodily threat, protective strategies, such as avoidance, are no longer adaptive. More specifically, generalization of avoidance based on conceptual knowledge may contribute to chronic pain disability. Using an operant robotic-arm avoidance paradigm, healthy participants (N = 50), could perform more effortful movements in the threat context (eg, pictures of outdoor scenes) to avoid painful stimuli, whereas no pain occured in the safe context (eg, pictures of indoor scenes). Next, we investigated avoidance generalization to conceptually related contexts (ie, novel outdoor/indoor scenes). As expected, participants avoided more when presented with novel contexts conceptually related to the threat context than in novel exemplars of the safe context. Yet, exemplars belonging to one category (outdoor/indoor scenes) were not interchangeable; there was a generalization decrement. Posthoc analyses revealed that contingency-aware participants (n = 27), but not non-aware participants (n = 23), showed the avoidance generalization effect and also generalized their differential pain-expectancy and pain-related fear more to novel background scenes conceptually related to the original threat context. In contrast, the fear-potentiated startle response was not modulated by context. PERSPECTIVE: This article provides evidence for contextual modulation of avoidance behavior and its generalization to novel exemplars of the learned categories based on conceptual relatedness. Our findings suggest that category-based generalization is a plausible mechanism explaining why patients display avoidance behavior in novel situations that were never directly associated with pain.

Heart rate variability analysis for the assessment of immersive emotional arousal using virtual reality: Comparing real and virtual scenarios.

Many affective computing studies have developed automatic emotion recognition models, mostly using emotional images, audio and videos. In recent years, virtual reality (VR) has been also used as a method to elicit emotions in laboratory environments. However, there is still a need to analyse the validity of VR in order to extrapolate the results it produces and to assess the similarities and differences in physiological responses provoked by real and virtual environments. We investigated the cardiovascular oscillations of 60 participants during a free exploration of a real museum and its virtualisation viewed through a head-mounted display. The differences between the heart rate variability features in the high and low arousal stimuli conditions were analysed through statistical hypothesis testing; and automatic arousal recognition models were developed across the real and the virtual conditions using a support vector machine algorithm with recursive feature selection. The subjects' self-assessments suggested that both museums elicited low and high arousal levels. In addition, the real museum showed differences in terms of cardiovascular responses, differences in vagal activity, while arousal recognition reached 72.92% accuracy. However, we did not find the same arousal-based autonomic nervous system change pattern during the virtual museum exploration. The results showed that, while the direct virtualisation of a real environment might be self-reported as evoking psychological arousal, it does not necessarily evoke the same cardiovascular changes as a real arousing elicitation. These contribute to the understanding of the use of VR in emotion recognition research; future research is needed to study arousal and emotion elicitation in immersive VR.

Breathing-driven prefrontal oscillations regulate maintenance of conditioned-fear evoked freezing independently of initiation.

Brain-body interactions are thought to be essential in emotions but their physiological basis remains poorly understood. In mice, regular 4 Hz breathing appears during freezing after cue-fear conditioning. Here we show that the olfactory bulb (OB) transmits this rhythm to the dorsomedial prefrontal cortex (dmPFC) where it organizes neural activity. Reduction of the respiratory-related 4 Hz oscillation, via bulbectomy or optogenetic perturbation of the OB, reduces freezing. Behavioural modelling shows that this is due to a specific reduction in freezing maintenance without impacting its initiation, thus dissociating these two phenomena. dmPFC LFP and firing patterns support the region's specific function in freezing maintenance. In particular, population analysis reveals that network activity tracks 4 Hz power dynamics during freezing and reaches a stable state at 4 Hz peak that lasts until freezing termination. These results provide a potential mechanism and a functional role for bodily feedback in emotions and therefore shed light on the historical James-Cannon debate.

Neural adaptation of cingulate and insular activity during delayed fear extinction: A replicable pattern across assessment sites and repeated measurements.

Adapting threat-related memories towards changing environments is a fundamental ability of organisms. One central process of fear reduction is suggested to be extinction learning, experimentally modeled by extinction training that is repeated exposure to a previously conditioned stimulus (CS) without providing the expected negative consequence (unconditioned stimulus, US). Although extinction training is well investigated, evidence regarding process-related changes in neural activation over time is still missing. Using optimized delayed extinction training in a multicentric trial we tested whether: 1) extinction training elicited decreasing CS-specific neural activation and subjective ratings, 2) extinguished conditioned fear would return after presentation of the US (reinstatement), and 3) results are comparable across different assessment sites and repeated measures. We included 100 healthy subjects (measured twice, 13-week-interval) from six sites. 24 h after fear acquisition training, extinction training, including a reinstatement test, was applied during fMRI. Alongside, participants had to rate subjective US-expectancy, arousal and valence. In the course of the extinction training, we found decreasing neural activation in the insula and cingulate cortex as well as decreasing US-expectancy, arousal and negative valence towards CS+. Re-exposure to the US after extinction training was associated with a temporary increase in neural activation in the anterior cingulate cortex (exploratory analysis) and changes in US-expectancy and arousal ratings. While ICCs-values were low, findings from small groups suggest highly consistent effects across time-points and sites. Therefore, this delayed extinction fMRI-paradigm provides a solid basis for the investigation of differences in neural fear-related mechanisms as a function of anxiety-pathology and exposure-based treatment.

When Do We Not Face Our Fears? Investigating the Boundary Conditions of Costly Pain-Related Avoidance Generalization.

Excessive generalization of fear and avoidance are hallmark symptoms of chronic pain disability, yet research focusing on the mechanisms underlying generalization of avoidance specifically, is scarce. Two experiments investigated the boundary conditions of costly pain-related avoidance generalization in healthy participants who learned to avoid pain by performing increasingly effortful (in terms of deviation and force) arm-movements using a robot-arm (acquisition). During generalization, novel, but similar arm-movements, without pain, were tested. Experiment 1 (N = 64) aimed to facilitate generalization to these movements by reducing visual contextual changes between acquisition and generalization, whereas Experiment 2 (N = 70) aimed to prevent extinction by increasing pain uncertainty. Both experiments showed generalization of pain-expectancies and pain-related fear. However, Experiment 2 was the first and only to also demonstrate generalization of avoidance, ie, choosing the novel effortful arm-movements in the absence of pain. These results suggest that uncertainty about the occurrence of pain may delay recovery, due to reduced disconfirmation of threat beliefs when exploring, resulting in persistent avoidance. PERSPECTIVE: This article demonstrates generalization of instrumentally acquired costly pain-related avoidance in healthy people under conditions of uncertainty. The results suggest that targeting pain-related uncertainty may be a useful tool for clinicians adopting a psychological approach to treating excessive pain-related avoidance in chronic pain.

State anxiety reduces working memory capacity but does not impact filtering cost for neutral distracters.

Current theories propose that anxiety adversely impacts working memory (WM) by restricting WM capacity and interfering with efficient filtering of task-irrelevant information. The current study investigated the effect of shock-induced state anxiety on WM capacity and the ability to filter task-irrelevant neutral stimuli. We measured the contralateral delay activity (CDA), an event-related potential that indexes the number of items maintained in WM, while participants completed a lateralized change detection task. The task included low and high WM loads, as well as a low load plus distracter condition. This design was used to assess WM capacity for low and high loads and investigate an individual's ability to filter neutral task-irrelevant stimuli. Participants completed the task under two conditions, threat of shock and safe. We observed a reduced CDA in the threat compared to the safe condition that was specific for high memory load. However, we did not find any differences in CDA filtering cost between threat and safe conditions. In addition, we did not find any differences in behavioral performance between the threat and safe conditions. These findings suggest that being in an anxious state reduces the neural representation for large amounts of information in WM, but have little effect on the filtering of neutral distracters.

Assessment of conditioned fear extinction in male and female adolescent rats.

Pavlovian fear conditioning and extinction have been widely studied across many species to understand emotional learning and memory. Importantly, it is becoming clear that these processes are affected by sex and age. In adult rodents and humans, sex differences are evident in extinction, with estradiol playing a significant role. In adolescence, an extinction deficit has been reported in rodents and humans. However, the influence of sex on extinction during adolescence is unknown. This is surprising, since adolescence coincides with the onset of hormone cycling, and therefore it might be expected that hormones fluctuations exert a more profound effect at this time. Therefore, we examined Pavlovian fear conditioning and extinction in adolescent male and female rats. In experiment 1, 35-day-old male and female rats were exposed to 6 pairings of a conditioned stimulus (CS, a tone) with an aversive unconditioned stimulus (US, a footshock). The next day they were extinguished in a contextually distinct chamber, via 60 presentations of the CS without the US. Extinction recall was tested 24 hours later in the extinction context. Estrous phase was monitored by cytology on vaginal smears taken 1 hour after each behavioral session. In experiment 2, male and female rats were given sham surgery or gonadectomy at 21 days of age. They were then trained and tested as for experiment 1. We observed that females in proestrus or met/diestrus during extinction showed delayed extinction and impaired extinction recall the next day compared to males. Ovariectomy enhanced extinction for female rats, but orchidectomy delayed extinction for males. Plasma analyses showed that met/di/proestrus phases were associated with high estradiol levels. These findings suggest that high plasma estradiol levels impair extinction for adolescent females. These results contradict what is reported in adult animals, suggesting that hormonal influences on extinction are dependent on age. Given that impaired extinction is widely used as a model to understand resistance to exposure-based therapies, our findings have important implications for understanding mental health treatments in adolescents.

Costly avoidance triggered by categorical fear generalization.

Fear generalization refers to the spread of acquired fear to novel stimuli that resemble the original fear-related stimulus. Preliminary evidence suggests that excessive fear generalization is a pathogenic feature of anxiety disorders, however, it remains unclear how fear generalization affects pathological avoidance. The current study thus aimed to examine the link between categorical fear generalization and costly avoidance. By combining a fear acquisition training phase and an avoidance test, the current findings showed that acquired fear spreads to novel stimuli that belonged to the same category of the original fear-related stimuli, but not to those that belonged to the fear-irrelevant categories. Importantly, participants avoided these fear-related novel stimuli despite costs. The current findings indicate that categorical fear generalization triggers costly avoidance. In terms of clinical implication, a decrease in costly avoidance aligned with a decrease in US expectancies. This emphasizes that behavioral approach may initiate extinction learning.

Is There Equivalence Between the Electronic and Paper Version of the Questionnaires for Assessment of Patients With Chronic Low Back Pain?

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To investigate the equivalence of electronic and paper version of self-report questionnaires for the assessment of disability, pain, fear of movement, depression, and physical activity of patients with chronic low back pain (LBP). SUMMARY OF BACKGROUND DATA: Paper and electronic versions of self-report questionnaires are commonly used for assessment of patients with LBP. However, the equivalence of self-report questionnaires commonly used for assessment of patients with chronic LBP remains unclear. METHODS: Seventy-nine individuals with chronic LBP seeking physiotherapy care were recruited. Participants attended the clinic twice with an interval of 1 week and completed the self-reported questionnaires in a random order. The following questionnaires were administered: Roland Morris Disability Questionnaire (RMDQ); 11-point numerical rating scale (NRS); Tampa Scale for Kinesiophobia (TSK); Center for Epidemiological Studies-Depression (CES-D), and Baecke Habitual Physical Activity Questionnaire (BPAQ). To investigate the equivalence between the two questionnaire versions, intraclass correlation coefficient with 95% confidence interval and Bland-Altman plotting was used. RESULTS: The paper and electronic versions of the RMDQ, TSK, and CES-D showed good reliability and the showed moderate reliability. In contrast, the NRS showed poor reliability between the electronic and paper versions. CONCLUSION: Our findings support that the electronic version of the RMDQ, TSK, CES-D, and BPAQ can be administered in clinical and research settings for assessment of patients with chronic LBP. Nevertheless, electronic version of the NRS for assessment of pain intensity should not be used interchangeably in clinical practice in patients with chronic LBP. LEVEL OF EVIDENCE: 3.

Costly avoidance in anxious individuals: Elevated threat avoidance in anxious individuals under high, but not low competing rewards.

BACKGROUND AND OBJECTIVES: When avoiding threat conflicts with approaching rewards, balanced responses to threat and reward information is required to guide functional behavior. Elevated threat avoidance characterizes anxious psychopathology. However, little is known about the mutual impact of threat and reward information on approach-avoidance behavior and its link to anxiety. METHODS: High trait-anxious and low-anxious individuals (N = 74) repeatedly choose between two options. A threat/high-reward option was linked to two outcomes: a varying chance to receive an aversive stimulus and a varying high reward. A safe/low-reward option was linked to absence of the aversive stimulus and a low reward. RESULTS: Avoidance of the threat/high-reward option increased with increasing threat. Despite threat, low-anxious individuals increasingly approached the threat/high-reward option when rewards increased. High- compared to low-anxious individuals showed elevated avoidance, but only in the presence of high competing rewards. LIMITATIONS: Future research should examine boundary conditions by manipulating type and motivational value of appetitive and aversive outcomes (e.g., food as primary reinforcer). CONCLUSIONS: These findings suggest that a weaker impact of rewards competing with threat contributes to elevated threat avoidance in anxious psychopathology. Costly avoidance may thus be a factor involved in anxious psychopathology.

Negative life experiences contribute to racial differences in the neural response to threat.

Threat-related emotional function is supported by a neural circuit that includes the prefrontal cortex (PFC), hippocampus, and amygdala. The function of this neural circuit is altered by negative life experiences, which can potentially affect threat-related emotional processes. Notably, Black-American individuals disproportionately endure negative life experiences compared to White-American individuals. However, the relationships among negative life experiences, race, and the neural substrates that support threat-related emotional function remains unclear. Therefore, the current study investigated whether the brain function that supports threat-related emotional processes varies with racial differences in negative life experiences. In the present study, adolescent violence exposure, family income, and neighborhood disadvantage were measured prospectively (i.e., at 11-19 years of age) for Black-American and White-American volunteers. Participants then, as young adults (i.e., 18-23 years of age), completed a Pavlovian fear conditioning task during functional magnetic resonance imaging (fMRI). Cued and non-cued threats were presented during the conditioning task and behavioral (threat expectancy) and psychophysiological responses (skin conductance response; SCR) were recorded simultaneously with fMRI. Racial differences were observed in neural (fMRI activity), behavioral (threat expectancy), and psychophysiological (SCR) responses to threat. These threat-elicited responses also varied with negative life experiences (violence exposure, family income, and neighborhood disadvantage). Notably, racial differences in brain activity to threat were smaller after accounting for negative life experiences. The present findings suggest that racial differences in the neural and behavioral response to threat are due, in part, to exposure to negative life experiences and may provide new insight into the mechanisms underlying racial disparities in mental health.

Relief from incidental fear evokes exuberant risk taking.

Incidental emotions are defined as feelings that are unrelated to a decision task at hand and thereby not normatively relevant for making choices. The precise influence and formal theoretical implications of incidental emotions regarding financial risk taking are still largely unclear. An effect of incidental emotion on decision-making would challenge the main extant formal theoretical economic models because such models do not allow for an effect of incidental emotions. As financial risk taking is pervasive in modern economies, the role of incidental emotions is an important issue. The goal of this experimental study is threefold. First, we examine the impact of incidental fear on the choice between a sure and a risky monetary option. A well-validated method of fear induction, using electric shocks, is employed for that purpose. Based on emotion studies we hypothesize less risk taking under fear and more risk taking when relieved of fear. Our second goal is to investigate the relative performance of the main existing formal theoretical economic models (based on Expected Utility Theory, Prospect Theory, or the Mean-Variance model) in explaining the behavioral data. We also investigate how these models can be adjusted to accommodate any observed influence of incidental emotion. For that reason, we first theoretically model the potential pathways of incidental fear (and the relief thereof) via the valuation of the choice option rewards or risk-assessment. We then estimate the relevant parameters allowing for both additive as well as interactive effects. Our third and final goal is to explore the neural basis of any observed influence of incidental emotions on decision-making by means of a model-based fMRI analysis, using the findings of existing neuroeconomic studies as the basis for our hypotheses. Our results indicate that the relief of fear can give a substantial boost to financial risk taking (suggestive of exuberance). This impact is best captured by Prospect Theory if we allow for an increase in participants' valuation of option outcomes when relieved of fear. Moreover, this impact is manifested at the neural level by the activity of the ventromedial prefrontal cortex (vmPFC), a brain area widely regarded as being central for valuation.

Assessment of fear and anxiety associated behaviors, physiology and neural circuits in rats with reduced serotonin transporter (SERT) levels.

Genetic variation in serotonin transporter (SERT) that reduces transcriptional efficiency is associated with higher anxiety and fear traits and a greater incidence of post traumatic stress disorder (PTSD). Although previous studies have shown that rats with no expression of SERT (SERT-/-) have increased baseline anxiety behaviors, SERT+/- rats with low SERT expression (and more relevant to the clinical condition with low SERT expression) do not. Yet, no systematic studies of fear acquisition/extinction or their underlying neural mechanisms have been conducted in this preclinical genetic SERT+/- model. Here we sought to determine if SERT+/- or SERT-/-, compared to wildtype, rats would show exacerbated panic responses and/or persistent conditioned fear responses that may be associated with PTSD or phobia vulnerability. Results: Only SERT-/- rats showed increased baseline anxiety-like behaviors with heightened panic respiratory responses. However SERT+/- (also SERT-/-) rats showed enhanced acquisition of fear and delayed extinction of fear that was associated with changes in serotonergic-related genes (e.g., reduced 5-HT1A receptor) and disrupted inhibition within the basolateral amygdala (BLA). Furthermore, the disrupted fear responses in SERT+/- rats were normalized with 5HT1A antagonist infusions into the BLA. Enhanced acquisition and failure to extinguish fear memories displayed by both SERT-/- and SERT+/- rats are cardinal symptoms of disabling anxiety disorders such as phobias and PTSD. The data here support the hypothesis that reduced SERT function is a genetic risk that disrupts select gene expression and network properties in the amygdala that could result in vulnerability to these syndromes.