Safe Stimuli Research Articles

Brief Training to Modify the Breadth of Attention Influences the Generalisation of Fear

BackgroundGeneralisation of fear from dangerous to safe stimuli is an important process associated with anxiety disorders. However, factors that contribute towards fear (over)-generalisation remain poorly understood. The present investigation explored how attentional breadth (global/holistic and local/analytic) influences fear generalisation and, whether people trained to attend in a global vs. local manner show more or less generalisation.MethodsParticipants (N = 39) were shown stimuli which comprised of large ‘global’ letters and smaller ‘local’ letters (e.g. an F comprised of As) and they either had to identify the global or local letter. Participants were then conditioned to fear a face by pairing it with an aversive scream (75% reinforcement schedule). Perceptually similar, but safe, faces, were then shown. Self-reported fear levels and skin conductance responses were measured.ResultsCompared to participants in Global group, participants in Local group demonstrated greater fear for dangerous stimulus (CS +) as well as perceptually similar safe stimuli.ConclusionsParticipants trained to attend to stimuli in a local/analytical manner showed higher magnitude of fear acquisition and generalisation than participants trained to attend in a global/holistic way. Breadth of attentional focus can influence overall fear levels and fear generalisation and this can be manipulated via attentional training.

The impact of prior and ongoing threat on the false alarm threshold for facial discrimination

Background and objectivesPerceptual adaptations that facilitate rapid responses to threats can also lead to false alarms, or the failure to discriminate safe stimuli from signals of threat. We examined the impact of varying degrees of threat on false alarms in the perceptual discrimination of faces along the dimension of emotion (Experiment 1) or identity (Experiment 2). MethodsParticipants first trained to discriminate between a target and nontarget face. Next, we tested their ability to identify the target in randomized presentations of the target, the nontarget, and nine novel stimuli morphed in 10% increments of similarity from the target to the nontarget. The task was completed under one of three randomized conditions: 1) Ongoing-Threat paired the target with an aversive outcome in both phases; 2) Prior-Threat paired the target with an aversive outcome in the training phase only; and 3) No-Threat paired the target with a neutral outcome in the training phase only. ResultsIn Experiment 1 (N = 90), Ongoing-Threat lowered the false alarm threshold for facial discrimination based on anger intensity compared to Prior-Threat and No-Threat. In Experiment 2 (N = 90), Ongoing-Threat and Prior-Threat each lowered the false alarm threshold for identity-based discrimination compared to No-Threat. LimitationsThe experiment did not measure generalization of threat responses. ConclusionAssociating a facial expression or identity with threat leads to faster but less accurate discrimination of faces with similar features, particularly under conditions of ongoing threat. These experiments provide an avenue for examining the parameters that impact false alarms, which play a key role in anxiety disorders.

Divergence in cortical representations of threat generalization in affective versus perceptual circuitry in childhood: Relations with anxiety

Children at risk for anxiety display elevated threat sensitivity and may inaccurately classify safe stimuli as threatening, a process known as overgeneralization. Little is known about whether such overgeneralization might stem from altered sensory representations of stimuli resembling threat, especially in youth. Here we implement representational similarity analysis of fMRI data to examine the similarity of neural representations of threat versus ambiguous or safe stimuli in threat and perceptual neurocircuitry among children at varying levels of anxiety traits. Three weeks after completing threat conditioning and extinction, children underwent an fMRI extinction recall task, during which they viewed the extinguished threat cue (CS+), safety cue (CS-) and generalization stimuli (GS) consisting of CS-/CS+ blends. Multivoxel BOLD signal patterns were measured in seven regions of interest: four affective areas (ventromedial prefrontal cortex (vmPFC), anterior insular cortex (AIC), dorsomedial prefrontal cortex (dmPFC), and amygdala) and three perceptual areas (inferior temporal cortex (ITC) and visual areas V1 and V4). Compared to low anxious children, children with high trait anxiety evidenced less neural pattern differentiation between the CS+ and similar GS, particularly in the vmPFC. Together, these results demonstrate the utility of multivariate neuroimaging approaches in arbitrating the relative contributions of perceptual versus affective sources to threat generalization.

Генерализация страха обстановки зависит от активности серотониновой системы медиальной префронтальной коры

The medial prefrontal cortex (mPFC) is involved in the regulation of fear generalization. We have previously shown that generalized fear formation to auditory cues is under the control of the mPFC serotonin system, as its pharmacological activation during a conditioned fear response acquisition (CFR - a fear model) enhances fear expression to safe auditory stimuli during testing. The aim of this work was to find out whether the mPFC serotonin system is involved in the contextual fear generalization. Using in vivo intracranial microdialysis in Sprague-Dawley rats, it was shown that placing animals in a potentially dangerous box A, in which they had previously acquired CFR (the paired presentation of a conditioned cue and inescapable footshock) was accompanied by an increase in the mPFC extracellular serotonin level and caused animals animals' freezing (a contextual fear measure). Placing the same animals in a safe differentiation box B also led to the extracellular serotonin level rise in the mPFC and caused animals' freezing (a measure of contextual fear generalization). The intra-mPFC infusion of a selective serotonin reuptake inhibitor fluoxetine (1 μM) during the fear response elaboration enhanced, during testing, animals' freezing in differentiation box B but did not affect animals' freezing in box A. The fluoxetine administration during training did not change the testing-induced extracellular serotonin levels rise in the mPFC in boxes A and B. The data indicate that activation of the mPFC serotonin system during fear formation affects the degree of contextual fear generalization. In addition, they suggest that one of the neurochemical manifestations of contextual fear generalization may be an increased activity of the mPFC serotonin system in the safe environment.

The temporal course of over-generalized conditioned threat expectancies in posttraumatic stress disorder

One key conditioning abnormality in posttraumatic stress disorder (PTSD) is heightened generalization of fear from a conditioned danger-cue (CS+) to similarly appearing safe stimuli. The present work represents the first effort to track the time-course of heightened generalization in PTSD with the prediction of heightened PTSD-related over-generalization in earlier but not later trials. This prediction derives from past discriminative fear-conditioning studies providing incidental evidence that over-generalization in PTSD may be reduced with sufficient learning trials. In the current study, we re-analyzed previously published conditioned fear-generalization data (Kaczkurkin et al., 2017) including combat veterans with PTSD (n = 15) or subthreshold PTSD (SubPTSD: n = 18), and trauma controls (TC: n = 19). This re-analysis aimed to identify the trial-by-trial course of group differences in generalized perceived risk across three classes of safe generalization stimuli (GSs) parametrically varying in similarity to a CS+ paired with shock. Those with PTSD and SubPTSD, relative to TC, displayed significantly elevated generalization to all GSs combined in early but not late generalization trials. Additionally, over-generalization in PTSD and SubPTSD persisted across trials to a greater extent for classes of GSs bearing higher resemblance to CS+. Such results suggest that PTSD-related over-generalization of conditioned threat expectancies can be reduced with sufficient exposure to unreinforced GSs and accentuate the importance of analyzing trial-by-trial changes when assessing over-generalization in clinical populations.

Ketamine Alleviates Fear Generalization Through GluN2B-BDNF Signaling in Mice.

Fear memories are critical for survival. Nevertheless, over-generalization of these memories, depicted by a failure to distinguish threats from safe stimuli, is typical in stress-related disorders. Previous studies have supported a protective role of ketamine against stress-induced depressive behavior. However, the effect of ketamine on fear generalization remains unclear. In this study, we investigated the effects of ketamine on fear generalization in a fear-generalized mouse model. The mice were given a single sub-anesthetic dose of ketamine (30mg/kg, i.p.) 1h before, 1week before, immediately after, or 22h after fear conditioning. The behavioral measure of fear (indicated by freezing level) and synaptic protein expression in the basolateral amygdala (BLA) and inferior-limbic pre-frontal cortex (IL-PFC) of mice were examined. We found that only ketamine administered 22h after fear conditioning significantly decreased the fear generalization, and the effect was dose-dependent and lasted for at least 2weeks. The fear-generalized mice showed a lower level of brain-derived neurotrophic factor (BDNF) and a higher level of GluN2B protein in the BLA and IL-PFC, and this was reversed by a single administration of ketamine. Moreover, the GluN2B antagonist ifenprodil decreased the fear generalization when infused into the IL-PFC, but had no effect when infused into the BLA. Infusion of ANA-12 (an antagonist of the BDNF receptor TrkB) into the BLA or IL-PFC blocked the effect of ketamine on fear generalization. These findings support the conclusion that a single dose of ketamine administered 22h after fear conditioning alleviates the fear memory generalization in mice and the GluN2B-related BDNF signaling pathway plays an important role in the alleviation of fear generalization.

Anxious behaviour in a demonstrator affects observational learning

Humans can acquire fear through the observation of others’ (learning models’) threat responses. These responses can be direct responses to aversive stimuli, or anticipatory responses to threats. Most research focuses on learning from observation of direct responses only. Here, we investigated how observational fear conditioning is influenced by a learning model’s typically anxious anticipatory responses. High anxiety individuals often display typically anxious anticipatory behaviour, such as worsened discrimination between safe and unsafe stimuli, characterized by increased threat responses to safe stimuli. We hypothesized that observation of an anxiously behaving model would worsen discriminatory learning. To this end, we developed an observational conditioning paradigm where a learning model was exposed to one safe and one unsafe stimuli. The learning model displayed anticipatory aversion to either to the unsafe stimulus only (Non-Anxious Model group) or to both the safe and unsafe stimuli (Anxious Model group) in addition to reacting directly to an aversive stimulus paired with the unsafe stimulus. Contrary to expectations, discriminatory learning was not worsened in the Anxious Model group compared to the Non-Anxious Model group. Rather, we saw more robust discriminatory learning in the Anxious Model group. The study provides a first step towards understanding the effect of other’s anticipatory responses in general and typically anxious anticipatory responses in particular, on observational fear learning.

Low Perceived Self-Efficacy Impedes Discriminative Fear Learning

Perceived self-efficacy refers to a subject’s expectation about the outcomes his/her behavior will have in a challenging situation. Low self-efficacy has been implicated in the origins and maintenance of phobic behavior. Correlational studies suggest an association between perceived self-efficacy and learning. The experimental manipulation of perceived self-efficacy offers an interesting approach to examine the impact of self-efficacy beliefs on cognitive and emotional functions. Recently, a positive effect of an experimentally induced increased self-efficacy on associative learning has been demonstrated. Changes in associative learning constitute a central hallmark of pathological fear and anxiety. Such alterations in the acquisition and extinction of conditioned fear may be related to cognitive and neurobiological factors that predict a certain vulnerability to anxiety disorders. The present study builds on previous own work by investigating the effect of an experimentally induced low perceived self-efficacy on fear acquisition, extinction and extinction retrieval in a differential fear conditioning task. Our results suggest that a negative verbal feedback, which leads to a decreased self-efficacy, is associated with changes in the acquisition of conditioned fear. During fear acquisition, the negative verbal feedback group showed decreased discrimination of fear responses between the aversive and safe conditioned stimuli (CS) relative to a group receiving a neutral feedback. The effects of the negative verbal feedback on the acquisition of fear discrimination learning were indexed by an impaired ability to discriminate the probability of receiving a shock during acquisition upon presentation of the aversive (CS+) relative to the safe stimuli (CS−). However, the effects of low self-efficacy on discrimination learning were limited to fear acquisition. No differences between the groups were observed during extinction and extinction retrieval. Furthermore, analysis of other outcome measures, i.e., skin conductance responses and CS valence ratings, revealed no group differences during the different phases of fear conditioning. In conclusion, lower perceived self-efficacy alters cognitive/expectancy components of discrimination during fear learning but not evaluative components and physiological responding. The pattern of findings suggests a selective, detrimental role of low(er) self-efficacy on the subject’s ability to learn the association between ambiguous cues and threat/safety.

T18. Trait Anxiety Associated With Differences in BOLD Activation During Fear Generalization Task

Pathological anxiety has been associated with overgeneralization of conditioned fear, wherein safe stimuli are perceived as threatening due to perceptual similarity to a threat. Neuroimaging studies have implicated structures, including the insula, hippocampus, ventromedial prefrontal cortex, and precuneus, to be sensitive to stimulus differentiation.

Anxiety sensitivity and intolerance of uncertainty facilitate associations between generalized Pavlovian fear and maladaptive avoidance decisions.

Generalization of Pavlovian fear to safe stimuli resembling conditioned-danger cues (CS+) is a widely accepted conditioning correlate of clinical anxiety. Though much of the pathogenic influence of such generalization may lie in the associated avoidance, few studies have assessed maladaptive avoidance decisions associated with Pavlovian generalization. Lab-based assessments of this process, here referred to as aversive Pavlovian-instrumental covariation during generalization (APIC-G), have recently begun. The current study represents a next step in this line of work by conducting the first examination of anxiety-related dimensions of personality that may exacerbate APIC-G. Specifically, we test anxiety sensitivity (AS) and intolerance of uncertainty (IU) as moderators of relations between Pavlovian generalization and maladaptive avoidance decisions in 102 undergraduate students with wide-ranging levels of IU and AS. Results indicate a facilitative effect of AS on this APIC-G process, with AS strengthening relations between Pavlovian generalization and maladaptive generalized avoidance whether operationalizing Pavlovian generalization with psychophysiological (fear-potentiated startle) or behavioral measures. Additionally, IU was found to facilitate APIC-G when indexing Pavlovian generalization with behavioral but not fear-potentiated startle measures. Moderating effects of AS were most pronounced for stimulus classes bearing the highest resemblance to CS+, whereas effects of IU were most pronounced for the stimulus class with the highest level of threat ambiguity. Results implicate AS and IU as risk factors for the maladaptive decisional correlates of Pavlovian generalization and suggest that established associations between these traits and clinical anxiety may derive, in part, from their enhancement of maladaptive APIC-G. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

CHARACTERIZING THE ROLE OF ORBITOFRONTAL CORTEX IN SOCIAL MEMORY

Background and Hypothesis: 
 Social-enhanced safety learning is a psychosocial process used to reduce fear or anxiety by learning to discriminate fearful versus safe stimuli via a social safety cue. Learning to associate safety with a social cue requires intact social memory. Preliminary data in rats suggests inhibiting the orbitofrontal cortex (OFC) with pharmacologic agents impairs social memory. However, the specific mechanism by which OFC regulates social memory remains unknown. Because the OFC has broad functional implications including valuation, decision-making, social and emotional behaviors, olfaction, and non-social memory, we hypothesized that OFC inhibition was disrupting one of these specific processes, resulting in social memory impairment. 
 Experimental Design or Project Methods: 
 Cannulated adult male Sprague-Dawley rats were injected bilaterally in OFC with either saline vehicle, or 0.9 mM Muscimol, a GABAA agonist that transiently inhibits local neuronal activity. At 10 minutes post-injection, rats underwent behavior testing for either: social recognition, novel object recognition, social preference (innate gregariousness), or olfactory discrimination. 
 Results: 
 Rats receiving Muscimol injection, but not rats receiving vehicle injection, demonstrated statistically significant impairment of social recognition, observed as a failure to discriminate between two conspecifics. Alternatively, rats receiving Muscimol injection, but not rats receiving vehicle injection, did not demonstrate statistically significant impairment of novel object (non-social) recognition, innate gregariousness, or olfaction, which were all intact in vehicle injected rats. 
 Conclusion and Potential Impact: 
 These data suggest OFC may be part of a unique neural circuit specific to social memory. Delineating the circuitry of social memory from non-social memory offers exciting possibilities in the advancement of precision therapies.

Generalization and Extinction of Concept-BasedPain-Related Fear

In chronic pain, pain-related fear seems to overgeneralize to safe stimuli, thus contributing to excessive fear and avoidance behavior. Evidence shows that pain-related fear can be acquired and generalized based on conceptual knowledge. Using a fear conditioning paradigm, we investigated whether this concept-based pain-related fear could also be extinguished. During acquisition, exemplars of 1 action category (conditioned stimuli [CSs]; eg, opening boxes) were followed by pain (CS+), whereas exemplars of another action category were not (CS–; eg, closing boxes). Participants reported more pain-related fear and expectancy toward exemplars of the CS+ category compared with those of the CS– category. During generalization, fear and expectancy spread to novel exemplars (generalization stimuli [GSs]) of the CS+ category (GS+), but not to those of the CS– category (GS–). During extinction, exemplars of both categories were presented in the absence of pain. At the end of extinction, participants no longer reported elevated fear or expectancy toward CS+ exemplars compared to CS– exemplars. These findings were not replicated in either the eye-blink startle or skin conductance measures. This is the first study to demonstrate extinction of concept-based pain-related fear, thus providing evidence for the potential of extinction-based techniques in the treatment of conceptual pain-related fear. PerspectiveThis study demonstrates the acquisition, generalization, and extinction of concept-based pain-related fear in healthy participants. These are the first results to show that concept-based pain-related fear can be extinguished, suggesting that conceptual relationships between fear-inducing stimuli may also be important to consider in clinical practice.

Coherent Activity between the Prelimbic and Auditory Cortex in the Slow-Gamma Band Underlies Fear Discrimination.

The medial prefrontal cortex and the basolateral amygdala (BLA) are essential for discriminating between harmful and safe stimuli. The primary auditory cortex (Te1) sends projections to both sites, but whether and how it interacts with these areas during fear discrimination are poorly understood. Here we show that in male rats that can differentiate between a new tone and a threatening one, the selective optogenetic inhibition of Te1 axon terminals into the prelimbic (PL) cortex shifted discrimination to fear generalization. Meanwhile, no effects were detected when Te1 terminals were inhibited in the BLA. Using a combination of local field potential and multiunit recordings, we show that in animals that discriminate successfully between a new tone and a harmful one, the activity of the Te1 and the PL cortex becomes immediately and tightly synchronized in the slow-gamma range (40-70 Hz) at the onset of the new tone. This enhanced synchronization was not present in other frequency ranges, such as the theta range. Critically, the level of gamma synchrony predicted the behavioral choice (i.e., no freezing or freezing) of the animals. Moreover, in the same rats, gamma synchrony was absent before the fear-learning trial and when animals should discriminate between an olfactory stimulus and the auditory harmful one. Thus, our findings reveal that the Te1 and the PL cortex dynamically establish a functional connection during auditory fear-discrimination processes, and that this corticocortical oscillatory mechanism drives the behavioral choice of the animals.SIGNIFICANCE STATEMENT Identifying neural networks that infer safety versus danger is of great interest in the scientific field. Fear generalization reduces the chances of an animal's survival and leads to psychiatric diseases, such as post-traumatic stress disorders and phobias in humans. Here we demonstrate that animals able to differentiate a new tone from a previous threating tone showed synchronization between the prefrontal and primary auditory cortices. Critically, this connectivity precedes and predicts the behavioral outcome of the animal. Optogenetic inhibition of this functional connectivity leads to fear generalization. To the best of our knowledge, this study is the first to demonstrate that a corticocortical dialogue occurring between sensory and prefrontal areas is a key node for fear-discrimination processes.

Attention avoidance of the threat conditioned stimulus during extinction increases physiological arousal generalisation and retention

Exposure therapy is a key component of efficacious treatment for anxiety. Biases in the allocation of attention towards versus away from threat assessed prior to exposure-based treatments such as cognitive-behavioural therapy differentially predict treatment outcomes. However, it is unclear whether monitoring versus avoiding threat stimuli influences learning during exposure. Extinction paradigms are the experimental analogue of exposure therapy. Therefore, manipulating attention towards versus away from threat during extinction trials may shed light on the role of attention during exposure therapy. This study utilised a Pavlovian fear conditioning and extinction paradigm to examine whether directing attention towards versus away from the threat conditioned stimulus (CS+) related to differences in extinction, as indexed by skin conductance responses (SCR), CS evaluations and subjective measures of anxiety. Following a fear conditioning phase in which a dog image (CS+) was paired with an aversive tone unconditioned stimulus (US) and another dog image (CS-) was presented alone, 57 participants were randomly assigned to one of three conditions during extinction in which both CSs were presented alone: monitor the CS+ (N = 19), avoid the CS+ and attend to another stimulus (N = 18), no attention manipulation control (N = 20). Eye movements were monitored for visual adherence to assigned location using horizontal electro-oculogram. In the context of the acquisition of differential conditioning and visual adherence during extinction, both active groups exhibited larger SCRs to the CS + relative to the CS- during the first extinction block compared to the control group, and the avoid group exhibited significantly larger SCRs on CS+ and CS- trials throughout the extinction phase compared to the other groups. The avoid group also exhibited less decline in SCRs to the CS+ during the extinction retest phase relative to the control group. No significant group differences were observed in between-phase CS evaluations and subjective anxiety ratings. Avoidance of threat conditioned stimuli may impair extinction learning and increase physiological arousal generalisation to safe stimuli.

Distraction/Suppression and Distress Endurance diminish the extent to which generalized conditioned fear is associated with maladaptive behavioral avoidance

A central conditioning correlate of clinical anxiety is the over-generalization of Pavlovian fear to safe stimuli resembling conditioned danger cues (CS+). Though much of the pathogenic influence of such generalization may lie in the unnecessary behavioral avoidance it evokes, few studies have examined maladaptive avoidance associated with Pavlovian generalization. Lab-based assessments of this process, here referred to as instrumental avoidance from Pavlovian generalization (IAP-G), have recently begun. The current study represents a next step in this line of work by examining personality factors that may reduce maladaptive IAP-G. This is a clinically relevant effort, as such traits may reflect resilience factors, with high levels reducing the likelihood of maladaptive generalized avoidance following Pavlovian generalization. Here we focus on the effects of Distraction/Suppression (DS) and Distress Endurance (DE) on IAP-G. Results indicate that both DS and DE moderate IAP-G by weakening relations between Pavlovian generalization of fear-potentiated startle and maladaptive generalized avoidance. Further, moderating effects of DS were most pronounced for more ambiguous cues of threat (i.e., stimuli moderately resembling CS+), while moderating effects of DE were most pronounced for more certain cues of threat (i.e., stimuli highly resembling CS+, as well as the CS + itself). Results implicate DS and DE as protective factors against the maladaptive behavioral consequences of Pavlovian generalization, and further indicate that the protective influence of these traits may depend on the ambiguity of the threat at hand.

Oxytocin receptor neurotransmission in the dorsolateral bed nucleus of the stria terminalis facilitates the acquisition of cued fear in the fear-potentiated startle paradigm in rats

Oxytocin (OT) is a hypothalamic neuropeptide that modulates fear and anxiety-like behaviors. Dorsolateral bed nucleus of the stria terminalis (BNSTdl) plays a critical role in the regulation of fear and anxiety, and expresses high levels of OT receptor (OTR). However, the role of OTR neurotransmission within the BNSTdl in mediating these behaviors is unknown. Here, we used adult male Sprague-Dawley rats to investigate the role of OTR neurotransmission in the BNSTdl in the modulation of the acoustic startle response, as well as in the acquisition and consolidation of conditioned fear using fear potentiated startle (FPS) paradigm. Bilateral intra-BNSTdl administration of OT (100 ng) did not affect the acquisition of conditioned fear response. However, intra-BNSTdl administration of specific OTR antagonist (OTA), (d(CH2)51, Tyr(Me)2, Thr4, Orn8, des-Gly-NH29)-vasotocin, (200 ng), prior to the fear conditioning session, impaired the acquisition of cued fear, without affecting a non-cued fear component of FPS. Neither OTA, nor OT affected baseline startle or shock reactivity during fear conditioning. Therefore, the observed impairment of cued fear after OTA infusion resulted from the specific effect on the formation of cued fear. In contrast to the acquisition, neither OTA nor OT affected the consolidation of FPS, when administered after the completion of fear conditioning session. Taken together, these results reveal the important role of OTR neurotransmission in the BNSTdl in the formation of conditioned fear to a discrete cue. This study also highlights the role of the BNSTdl in learning to discriminate between threatening and safe stimuli.

Developmental differences in aversive conditioning, extinction, and reinstatement: A study with children, adolescents, and adults

This study investigated developmental differences in aversive conditioning, extinction, and reinstatement (i.e., the recovery of conditioned aversive associations following reexposure to the unconditioned stimulus [US] post-extinction). This study examined these mechanisms in children (Mage=8.8years), adolescents (Mage=16.1years), and adults (Mage=32.3years) using differential aversive conditioning with a geometric shape conditional stimulus (CS+) paired with an aversive sound US and another shape (CS−) presented alone. Following an extinction phase in which both CSs were presented alone, half of the participants in each age group received three US exposures (reinstatement condition) and the other half did not (control condition), followed by all participants completing an extinction retest phase on the same day. Findings indicated (a) significant differences in generalizing aversive expectancies to safe stimuli during conditioning and extinction that persisted during retest in children relative to adults and adolescents, (b) significantly less positive CS reevaluations during extinction that persisted during retest in adolescents relative to adults and children, and (c) reinstatement of US expectancies to the CS+ relative to the CS− in all age groups. Results suggest important differences in stimulus safety learning in children and stimulus valence reevaluation in adolescents relative to adults.

Extinction of Fear Generalization: A Comparison Between Fibromyalgia Patients and Healthy Control Participants.

Pain-related fear and expectancy to movements-varying in similarity with the original painful and nonpainful movement-decrease during extinction in HC and FM. Yet, conditioned responses remain elevated in patients despite corrective feedback, indicating impaired extinction of generalization. Persistent excessive protective responses may contribute to preserving pain disability.

Hyperbaric oxygen and hyperbaric air preconditioning induces ischemic tolerance to transient forebrain ischemia in the gerbil

Ischemic preconditioning with sublethal stress triggers defensive mechanisms against ischemic brain damage; however, such manipulations are potentially dangerous and, therefore, safe stimuli have been sought. Hyperoxia preconditioning by administration of hyperbaric (HBO) or normobaric oxygen (NBO) may have neuroprotective potential. The aim of this study was to determine whether preconditioning with HBO and air (HBA) applied at 2.5 absolute pressure (ATA) or NBO preconditioning induces ischemic tolerance in the brain of gerbils subjected to 3min transient cerebral ischemia. Neuronal cell survival, changes in brain temperature, the generation of factors involved in neurodegeneration and basic behavior in nest building were all tested. Hyperoxic preconditioning prevented ischemia-induced neuronal cell loss, reduced the number of TUNEL positive cells in the CA1 region of the hippocampus and improved the nest building process compared to untreated ischemic animals. Preconditioning also suppressed the production of reactive oxygen species and increased Bax expression normally observed after an ischemic episode. Only HBO preconditioning inhibited ischemia-evoked increases in brain temperature. Our results show that hyperoxic preconditioning results in induction of ischemic tolerance and prevents ischemia-induced neuronal damage in the gerbil brain. Pressurized air preconditioning was as effective as HBO or NBO preconditioning in providing neuroprotection. The observed neuroprotection probably results from mild oxidative stress evoked by increased brain tissue oxidation and activation of antioxidant and antiapoptotic defenses.

Gradients of Fear Potentiated Startle During Generalization, Extinction, and Extinction Recall—and Their Relations With Worry

It is well established that fear conditioning plays a role in the development and maintenance of anxiety disorders. Moreover, abnormalities in fear generalization, extinction, and extinction recall have also been associated with anxiety. The present study used a generalization paradigm to examine fear processing during phases of generalization, extinction, and extinction recall. Specifically, participants were shocked following a CS+ and were also presented with stimuli that ranged in perceptual similarity to the CS+ (i.e., 20%, 40%, or 60% smaller or larger than the CS+) during a fear generalization phase. Participants were also presented with the same stimuli during an extinction phase and an extinction recall phase 1week later; no shocks were presented during extinction or recall. Lastly, participants completed self-report measures of worry and trait anxiety. Results indicated that fear potentiated startle (FPS) to the CS+ and GS±20% shapes was present in generalization and extinction, suggesting that fear generalization persisted into extinction. FPS to the CS+ was also evident 1week later during extinction recall. Higher levels of worry were associated with greater FPS to the CS+ during generalization and extinction phases. Moreover, individuals high in worry had fear response gradients that were steeper during both generalization and extinction. This suggests that high levels of worry are associated with greater discriminative fear conditioning to threatening compared to safe stimuli and less fear generalization to perceptually similar stimuli.