US-expectancy Ratings Research Articles

Learned Symptom-Specific Fear Toward a Visceral Sensation and Its Impact on Perceptual Habituation.

Impaired habituation of bodily sensations has been suggested as a contributing factor to chronic pain. We examined in healthy volunteers the influence of fear learning toward a nonpainful sensation in the esophagus on the perceptual habituation of this sensation. In a homoreflexive fear learning paradigm, nonpainful electrical sensations in the esophagus were used as a conditioned stimulus (CS). This sensation was presented 42 times before, during, and after fear learning. In the fear learning group ( n = 41), the CS was paired with a painful electrical sensation in the esophagus (unconditioned stimulus [US]). In the control group ( n = 41), the CS was not paired with the US. Ratings for CS intensity, US expectancy, startle electromyogram (EMG), skin conductance responses (SCR), and event-related potentials (ERPs) to the CS were assessed. Compared to the control group, fear learning was observed in the fear learning group as evidenced by potentiated startle responses after the CS relative to ITI ( t (1327) = 3.231, p = .001) and higher US expectancy ratings ( t (196) = 3.17, p = .002). SCRs did not differ between groups ( F1,817 = 1.241, p = .33). Despite successful fear learning, the fear learning group did not show a distinct pattern of habituation to the visceral CS relative to the control group (intensity ratings: F1,77.731 = 0.532, p = .47; ERPs: F1,520.78 = 0.059, p = .94). Acquired fear to nonpainful esophageal sensations does not affect their perceptual habituation patterns.

The Impact of Continuous and Partial Reinforcement on the Acquisition and Generalization of Human-Conditioned Fear.

Fear over-generalization as a core symptom of anxiety disorders is manifested by fear responses even to safe stimuli that are very dissimilar to the original dangerous stimulus. The present study investigated the effects of two separate conditioned stimuli-unconditioned stimuli (CS-US) pairing procedures on fear acquisition and generalization using a perceptual discrimination fear-conditioning paradigm, with US expectancy ratings and skin conductance response (SCR) as indicators. One group accepted continuous followed by partial CS-US pairings (C-P group); the other group accepted partial followed by continuous CS-US pairings (P-C group). It was found that compared to the P-C group, the C-P group showed stronger perceptual discrimination of CS+ and CS- in the fear acquisition and showed weaker SCRs and stronger extinction of US expectancy in the generalization. These findings emphasize that CS-US pairings significantly influence fear acquisition and generalization and suggest that continuous-following partial CS-US pairings promote individual discrimination of threat and safety signals and inhibit the generalization of conditioned fear. The results of this study have implications for clinical interventions for patients experiencing negative events.

Can glucose facilitate fear exposure? Randomized, placebo-controlled trials on the effects of glucose administration on fear extinction processes

Previous studies showed that glucose has beneficial effects on memory function and can enhance contextual fear learning. To derive potential therapeutic interventions, further research is needed regarding the effects of glucose on fear extinction. In two experimental studies with healthy participants (Study 1: N = 68, 39 females; Study 2: N = 89, 67 females), we investigated the effects of glucose on fear extinction learning and its consolidation. Participants completed a differential fear conditioning paradigm consisting of acquisition, extinction, and return of fear tests: reinstatement, and extinction recall. US-expectancy ratings, skin conductance response (SCR), and fear potentiated startle (FPS) were collected. Participants were pseudorandomized and double-blinded to one of two groups: They received either a drink containing glucose or saccharine 20 min before (Study 1) or immediately after extinction (Study 2). The glucose group showed a significantly stronger decrease in differential FPS during extinction (Study 1) and extinction recall (Study 2). Additionally, the glucose group showed a significantly lower contextual anxiety at test of reinstatement (Study 2). Our findings provide first evidence that glucose supports the process of fear extinction, and in particular the consolidation of fear extinction memory, and thus has potential as a beneficial adjuvant to extinction-based treatments.Registered through the German Clinical Trials Registry (https://www.bfarm.de/EN/BfArM/Tasks/German-Clinical-Trials-Register/_node.html; Study 1: DRKS00010550; Study 2: DRKS00018933).

Fear conditioning and fear generalization in children and adolescents with anxiety disorders

Overgeneralization of conditioned fear is associated with anxiety disorders (AD). Most results stem from studies done in adult patients, but studies with children are rare, although the median onset of anxiety disorders lies already in childhood. Thus, the goal of the present study was to examine fear learning and generalization in youth participants, aged 10–17 years, with AD (n = 39) compared to healthy controls (HC) (n = 40). A discriminative fear conditioning and generalization paradigm was used. Ratings of arousal, valence, and US expectancy (the probability of an aversive noise following each stimulus) were measured, hypothesizing that children with AD compared to HC would show heightened ratings of arousal and US expectancy, and decreased positive valence ratings, respectively, as well as overgeneralization of fear. The results indicated that children with AD rated all stimuli as more arousing and less pleasant, and demonstrated higher US expectancy ratings to all stimuli when compared to HC. Thus, rather than displaying qualitatively different generalization patterns (e.g., a linear vs. quadratic slope of the gradient), differences between groups were more quantitative (similar, but parallel shifted gradient). Therefore, overgeneralization of conditioned fear does not seem to be a general marker of anxiety disorders in children and adolescents.

The excessive generalization of fear affected by perceptual bias in experimental pain individuals: Evidence from an event-related potential study.

Excessiv generalization of fear contributes to the development and maintenance of pain. Prior research has demonstrated the importance of perception in fear generalization and found that individuals in painful conditions exhibited perceptual bias. However, the extent to which perceptual bias in pain affects the generalization of pain-related fear and its underlying neural activity remains unclear. Here, we tested whether perceptual bias in experimental pain individuals led to the overgeneralization of pain-related fear by recording behavioral and neural responses. To this end, we established an experimental pain model by spraying capsaicin on the surface of the seventh cervical vertebra of the participant. A total of 23 experimental pain participants and 23 matched nonpain controls learned fear conditioning and then completed the fear generalization paradigm combined with the perceptual categorization task. We found that the novel and safety cues were more likely to be identified as threat cues in the experimental group, resulting in higher US expectancy ratings compared to the control group. The event-related potential results showed that the experimental group exhibited earlier N1 latency and smaller P1 and late positive potential amplitudes than those in the control group. Our findings suggest that the experimental pain individuals exhibited an excessive generalization of fear affected by perceptual bias and reduced their attentional allocation to pain-related fear stimuli.

Manipulating expectancy violations to strengthen the efficacy of human fear extinction

Recent theoretical and clinical articles have emphasized a role for expectancy violations in improving the effectiveness of exposure therapy. Expectancy violations are critical to extinction learning and strengthening these violations has been suggested to improve the formation and retention of extinction memories, which should result in lasting symptom reductions after treatment. However, more detailed mechanistic insights in this process are needed to better inform clinical interventions. In two separate fear-conditioning experiments, we investigated whether stronger expectancy violations (Exp1) or fostering awareness of expectancy violations (Exp2) during extinction could reduce the subsequent return of fear. We measured fear potentiated startle (FPS) and skin conductance responses (SCR) as physiological indices of fear, and US expectancy ratings to assess our manipulations. While we successfully created stronger expectancy violations in Exp1, we found no evidence that these stronger violations reduced the return of fear at test. Interestingly, fostering awareness of violations (Exp2) reduced differential SCRs, but not FPS responses. These findings provide novel insights into the effect of US expectancies on fear extinction in the lab, but they also illustrate the complexity of capturing clinically relevant processes of change with fear-conditioning studies.

The effect of inherently threatening contexts on visuocortical engagement to conditioned threat.

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.

Generalization gradients for fear and disgust in human associative learning

Previous research indicates that excessive fear is a critical feature in anxiety disorders; however, recent studies suggest that disgust may also contribute to the etiology and maintenance of some anxiety disorders. It remains unclear if differences exist between these two threat-related emotions in conditioning and generalization. Evaluating different patterns of fear and disgust learning would facilitate a deeper understanding of how anxiety disorders develop. In this study, 32 college students completed threat conditioning tasks, including conditioned stimuli paired with frightening or disgusting images. Fear and disgust were divided into two randomly ordered blocks to examine differences by recording subjective US expectancy ratings and eye movements in the conditioning and generalization process. During conditioning, differing US expectancy ratings (fear vs. disgust) were found only on CS-, which may demonstrated that fear is associated with inferior discrimination learning. During the generalization test, participants exhibited greater US expectancy ratings to fear-related GS1 (generalized stimulus) and GS2 relative to disgust GS1 and GS2. Fear led to longer reaction times than disgust in both phases, and the pupil size and fixation duration for fear stimuli were larger than for disgust stimuli, suggesting that disgust generalization has a steeper gradient than fear generalization. These findings provide preliminary evidence for differences between fear- and disgust-related stimuli in conditioning and generalization, and suggest insights into treatment for anxiety and other fear- or disgust-related disorders.

A common genetic variant in fatty acid amide hydrolase is linked to alterations in fear extinction neural circuitry in a racially diverse, nonclinical sample of adults.

Poor fear extinction learning and recall are linked to the development of fear-based disorders, like posttraumatic stress disorder, and are associated with aberrant activation of fear-related neural circuitry. This includes greater amygdala activation during extinction learning and lesser hippocampal and ventromedial prefrontal cortex (vmPFC) activation during recall. Emerging data indicate that genetic variation in fatty acid amide hydrolase (FAAH C385A; rs324420) is associated with increased peripheral endocannabinoid (eCB) levels and lesser threat-related amygdala reactivity. Preclinical studies link increased eCB signaling to better extinction learning and recall, thus FAAH C385A may protect against the development of trauma-related psychopathology by facilitating extinction learning. However, how this FAAH variant affects fear extinction neural circuitry remains unknown. In the present study, we used a novel, immersive-reality fear extinction paradigm paired with functional neuroimaging to assess FAAH C385A effects on fear-related neural circuitry and conditioned fear responding (US expectancy ratings, subjective units of distress, and skin conductance responding) in healthy adults from an urban area (Detroit, MI; N=59; C/C=35, A-carrier=24). We found lesser amygdala activation in A-allele carriers, compared to C/C homozygotes, during early extinction recall. Likewise, we found lesser dorsal anterior cingulate cortex and greater hippocampus activation in early extinction learning in A-carriers compared to C/C homozygotes. We found no effects of FAAH C385A on vmPFC activation or behavioral fear indices. These data support and extend previous findings that FAAH genetic variation, associated with increased eCB signaling and subsequent enhanced fear extinction, may predict individual differences in successful fear learning.

Does the assessment of different combinations of within-phase subjective measures influence electrodermal responding and between-phase subjective ratings during fear conditioning and extinction experiments?

The type and number of dependent measures assessed have varied between fear conditioning and extinction experiments and it remains unclear whether methodological differences influence results. Measuring skin conductance responses (SCRs) and between-phase subjective ratings between four conditions; Con condition had no within-phase ratings; US Exp condition included within-phase US expectancy ratings only; CS Eval condition included within-phase CS evaluations only and All Meas condition included both. All Meas condition exhibited larger SCRs compared to other conditions during acquisition, extinction, and return of differential responding at test. Differential SCRs did not extinguish in CS Eval and Con conditions, and CS Eval condition exhibited smaller CS- SCRs than other conditions throughout phases. US Exp condition revealed differential conditioning, successful extinction, and no return of differential SCRs. Between-phase ratings were not affected by within-phase ratings. Researchers should consider assessing different combinations of within-phase subjective ratings depending on the aims of their research.

Trajectories of fear learning in healthy participants are able to distinguish groups that differ in individual characteristics, chronicity of fear and intrusions

Background and objectivesStudies on the development and treatment of anxiety disorders mostly focus on the comparison of predefined groups. An alternative approach is to use data-driven latent class growth analyses (LCGA) to determine differentiation between groups based on particular mechanistic factors. This study validated the use of LCGA on responses in a compact fear conditioning task and whether specific characteristics are associated with maladaptive fear learning trajectories. MethodsHealthy subjects (N = 300) completed a fear conditioning task that included uninstructed and instructed acquisition and extinction phases. Subjective fearfulness and US expectancy were used as outcome measures. Latent classes in the responses to the CS+ (coupled with a scream) and the CS- (control stimulus) were determined based on trajectories across the experimental phases. State and trait anxiety were measured during testing, and return of fear and intrusions were measured one and six weeks later. ResultsFear learning trajectories of poor extinction in responding to the CS+ and generalization of fear to the CS- were associated with higher state and trait anxiety. Individuals belonging to these trajectories reported more intrusions, fear and had higher US expectancy ratings after 1 week. LimitationsOnly 56% of participants completed the six weeks follow-up measures. ConclusionFear learning trajectories are associated with individual characteristics, return of fear and intrusions. Next, this task will be implemented in clinical practice to assess its predictive power for the extent to which patients benefit from exposure treatments.

Characterizing human safety learning via Pavlovian conditioned inhibition

Deficient safety learning has been implicated in the pathogenesis of anxiety disorders. Despite increased translational interest, there has been limited research on the basis of safety learning in humans. Here, we examined safety learning in seventy-three healthy participants via a modified Pavlovian conditioned inhibition paradigm, featuring a conditioned threat stimulus that was reinforced alone (A+), but not when combined with a second stimulus (the conditioned inhibitor, AX-). During a test phase, X and a control safety cue (C) were combined with a second threat stimulus to assess their inhibition of threat responses, measured via skin conductance (SCRs) and US-expectancy ratings. Both stimuli exhibited conditioned inhibition, but X suppressed ratings by a greater magnitude than C. Trait anxiety also predicted increased US-expectancy ratings of X. These findings suggest that a Pavlovian inhibitor accrues greater safety value than a merely unreinforced safety signal. Conditioned inhibition paradigms may have utility in the ongoing study of safety learning and its relevance to anxious psychopathology.

Measuring fear: Association among different measures of fear learning.

Background and objectivesFear conditioning paradigms use various measures to assess learned fear, including autonomic arousal responses like skin conductance, and self-reports of both associative (US-expectancies) and evaluative (affective ratings) learning. The present study uses a dimensional approach to examine associations among fear indices directly. MethodsSeventy-three participants completed a differential fear conditioning experiment, during which a neutral stimulus (CS+) was paired with an electric shock (US), while another stimulus (CS-) was never paired with the shock (partially instructed fear acquisition). Ten minutes later, both stimuli were presented without any shocks (fear extinction). Skin conductance responses and US-expectancy ratings were recorded during each phase, while self-reported negative affect was assessed for each CS at the end of extinction. ResultsResults showed a positive association among US-expectancy ratings and skin conductance responses during acquisition and early extinction. US-expectancy ratings during overall extinction were positively associated with post-extinction negative affect. LimitationsThe lack of affective ratings post-acquisition may have obscured associations between associative and evaluative learning indices. ConclusionsResults provide evidence for the expected correspondence among different indices of associative fear learning. Findings emphasize the need for incorporating both associative and evaluative learning measures in fear conditioning paradigms.

Conjunctive and Elemental Representations of a Context in Humans.

The dual-process theory assumes that contexts are encoded in an elemental and in a conjunctive representation. However, this theory was developed from animal studies, and we still have to explore if and how elemental and conjunctive representations contribute to, for example, contextual anxiety in humans. Therefore, 28 participants underwent differential context conditioning in a newly developed flip-book paradigm. Virtual rooms were presented similar to a flip-book, that is, as a stream of 49 consecutive screenshots creating the impression of walking through the rooms. This allowed registration of event-related brain potentials triggered by specific screenshots. During two acquisition phases, two rooms were shown in this way for six times each. In one room, the anxiety context (CTX+), mildly painful electric stimuli (unconditioned stimuli [USs]) were administered unpredictably after 12 distinct screenshots, which became threat elements, whereas 12 selected comparable screenshots became nonthreat elements (elemental representation); all screenshots represented the anxiety context (conjunctive representation). In the second room, the safety context (CTX-), no USs were applied; thus, all screenshots created the safety context whereby 12 preselected screenshots represented safety elements. Increased US expectancy ratings for threat versus nonthreat or safety elements reflected elemental representation. Conjunctive representation was evident in differential ratings (arousal and contingency) and increased P100 and early posterior negativity amplitudes for threat and nonthreat CTX+ versus safety CTX- screenshots. These differences disappeared during two test phases without US delivery indicating successful extinction. In summary, we revealed the first piece of evidence for the simultaneous contributions of elemental and conjunctive representation during context conditioning in humans.

Perceptual errors are related to shifts in generalization of conditioned responding.

Studies of perceptual generalization have recently demonstrated a close relationship between stimulus perception and conditioned responding, suggesting that incorrect stimulus perception might account for certain characteristics of generalization gradients. In this study, we investigated whether common phenomena, such as the area and peak shift in conditioned responding, relate to perceptual errors. After a differential conditioning procedure, in which one circle was paired with the presentation of an aversive picture whereas a different-sized circle was not, we combined a generalization test with a three-alternative forced-choice perceptual categorization task where participants had to indicate on every trial whether the presented circle was one of the two circles from the conditioning phase or a different one, after which US-expectancy ratings were collected. The typical peak and area shift were observed when conditioned responses were plotted on a physical dimension. However, when stimulus perception was incorporated generalization gradients diverged from the typical gradient. Both the area and peak shift largely disappeared when accounting for perceptual errors. These findings demonstrate the need to incorporate perceptual mechanisms in associative models.

Generalization of extinction of a generalization stimulus in fear learning

Two experiments examined whether extinction of a generalization stimulus (GS) after single cue fear conditioning would in turn generalize to other stimuli, relative to a control group that received regular extinction of CS + itself. We found only a weak effect of such “generalization of GS extinction” either back to CS + or to a different GS, on either US expectancy or skin conductance measures. In other words, despite extinction trials with a stimulus highly similar to CS+, participants showed a return of fear when tested with CS + or a novel GS. However this responding declined rapidly over non-reinforced test trials. Trait anxious participants showed higher overall US expectancy ratings in the extinction and test phases, and slower extinction of expectancy, relative to low anxious participants. These results may help explain why exposure therapy, which is unlikely to reproduce the exact stimuli present at acquisition, sometimes fails to transfer to other fear-eliciting stimuli subsequently encountered by anxious clients. The generalization of GS extinction paradigm might provide a useful testbed for evaluation of interventions designed to enhance transfer, such as exposure to multiple diverse exemplars.

Hear it, fear it: Fear generalizes from conditioned pictures to semantically related sounds

Fear generalization is thought to be an important mechanism in the acquisition and maintenance of anxiety disorders. Previous studies have investigated fear generalization within one sensory modality - mainly within the visual domain. However, a growing body of evidence shows that emotional information is processed in more than one sensory modality. Based on network theories, we expected that fear may also generalize from stimuli in one sensory modality to another. To test our hypothesis, 42 participants underwent a differential conditioning paradigm, during which pictures were either presented with (vCS+) or without (vCS-) an aversive electric stimulus. After the acquisition phase, generalization was tested in the crossmodal group (n = 21) by presenting sounds which were semantically congruent to the visual vCS+ (i.e., the aGS+) or the vCS- (i.e., the aGS-). As a control, the unimodal group (n = 21) saw the pictures again. For the crossmodal group, we could show that US expectancy ratings generalized from conditioned pictures (vCS+) to semantically related sounds (aGS+). Moreover, when the vCS+ was presented during extinction, fear of the aGS+ extinguished, whereas extinction training with the aGS+ was found to be less effective for the vCS+. The findings are relevant for crossmodal fear acquisition and exposure therapy.

Fear generalization of implicit conditioned facial features – Behavioral and magnetoencephalographic correlates

Acquired fear responses often generalize from conditioned stimuli (CS) towards perceptually similar, but harmless generalization stimuli (GS). Knowledge on similarities between CS and GS may be explicit or implicit. Employing behavioral measures and whole-head magnetoencephalography, we here investigated the neurocognitive mechanisms underpinning implicit fear generalization. Twenty-nine participants underwent a classical conditioning procedure in which 32 different faces were either paired with an aversive scream (16 CS+) or remained unpaired (16 CS-). CS+ and CS- faces systematically differed from each other regarding their ratio of eye distance and mouth width. High versus low values on this “threat-related feature (TF)” implicitly predicted the presence or absence of the aversive scream. In pre- and post-conditioning phases, all CS and 32 novel GS faces were presented. 16 GS+ ​faces shared the TF of the 16 CS+ ​faces, while 16 ​GS- faces shared the TF of the 16 CS- faces. Behavioral tests confirmed that participants were fully unaware of TF-US contingencies. CS+ ​compared to CS- faces revealed higher unpleasantness, arousal and US-expectancy ratings. A generalization of these behavioral fear responses to GS+ ​compared to GS- faces was observed by trend only. Source-estimations of event-related fields showed stronger neural responses to both CS+ and GS+ ​compared to CS- and GS- in anterior temporal (<100 ​ms) and temporo-occipital (<150 ​ms; 553–587 ​ms) ventral brain regions. Reverse effects were found in dorsal frontal areas (<100 ​ms; 173–203 ​ms; 257–290 ​ms). Neural data also revealed selectively enhanced responses to CS+ ​but not GS+ ​stimuli in occipital regions (110–167 ​ms; 330–413 ​ms), indicating perceptual discrimination. Our data suggest that the prioritized perceptual analysis of threat-associated conditioned faces in ventral networks rapidly generalizes to novel faces sharing threat-related features. This generalization process occurs in absence of contingency awareness and may thus contribute to implicit attentional biases. The coexisting perceptual discrimination suggests that fear generalization is not a mere consequence of insufficient stimulus discrimination but rather an active, integrative process.

Validating the use of a smartphone app for remote administration of a fear conditioning paradigm

Fear conditioning models key processes related to the development, maintenance and treatment of anxiety disorders and is associated with group differences in anxiety. However, laboratory administration of tasks is time and cost intensive, precluding assessment in large samplesnecessary for the analysis of individual differences. This study introduces a newly developed smartphone app that delivers a fear conditioning paradigm remotely using a loud human scream as an aversive stimulus. Three groups of participants (total n = 152) took part in three studies involving a differential fear conditioning experiment to assess the reliability and validity of a smartphone administered fear conditioning paradigm. This comprised of fear acquisition, generalisation, extinction, and renewal phases during which online US-expectancy ratings were collected during every trial with evaluative ratings of negative affect at three time points. We show that smartphone app delivery of a fear conditioning paradigm results in a pattern of fear learning comparable to traditional laboratory delivery and is able to detect individual differences in performance that show comparable associations with anxiety to the prior group differences literature.

Characterizing the neural circuitry associated with configural threat learning

Contextual threat learning is often associated with two processes: elemental and configural learning. Few studies have examined configural learning where subjects form a representation of the threat-related context as a gestalt whole from the individual features in the environment. The goal of the current study was to compare and contrast neural circuitry recruited by variation in demands placed on configural threat encoding. Subjects (N = 25) completed a configural threat learning task, where we manipulated the amount of configural encoding required to learn the threat association (low demand: changes to a discrete element of the context; and high demand: rearrangement of elements). US expectancy ratings, skin conductance responses (SCR), and functional magnetic resonance imaging (fMRI) were collected. Subjects successfully learned the configural threat association as measured by US expectancy ratings, SCR, and BOLD activity. Hippocampal and amygdala region of interest analyses indicated differential configural threat learning and predicted SCR measures of learning. Furthermore, whole brain analyses identified four circuits that were impacted by the amount of differential configural encoding required, but none correlated with SCR. These results set the stage for a more detailed understanding of how configural threat learning is instantiated in the brain—an important mechanism associated with PTSD and other fear-related disorders.