Differential Fear Conditioning Paradigm Research Articles

Impairment in acquisition of conditioned fear in people with depressive symptoms.

Depression is one of the primary global public health issues, and there has been a dramatic increase in depression levels among young people over the past decade. The neuroplasticity theory of depression postulates that a malfunction in neural plasticity, which is responsible for learning, memory, and adaptive behavior, is the primary source of the disorder's clinical manifestations. Nevertheless, the impact of depression symptoms on associative learning remains underexplored. We used the differential fear conditioning paradigm to investigate the effects of depressive symptoms on fear acquisition and extinction learning. Skin conductance response (SCR) is an objective evaluation indicator, and ratings of nervousness, likeability, and unconditioned stimuli (US) expectancy are subjective evaluation indicators. In addition, we used associability generated by a computational reinforcement learning model to characterize the skin conductance response. The findings indicate that individuals with depressive symptoms exhibited significant impairment in fear acquisition learning compared to those without depressive symptoms based on the results of the skin conductance response. Moreover, in the discrimination fear learning task, the skin conductance response was positively correlated with associability, as estimated by the hybrid model in the group without depressive symptoms. Additionally, the likeability rating scores improved post-extinction learning in the group without depressive symptoms, and no such increase was observed in the group with depressive symptoms. The study highlights that individuals with pronounced depressive symptoms exhibit impaired fear acquisition and extinction learning, suggesting a possible deficit in associative learning. Employing the hybrid model to analyze the learning process offers a deeper insight into the associative learning processes of humans, thus allowing for improved comprehension and treatment of these mental health problems.

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).

Individual patterns of visual exploration predict the extent of fear generalization in humans.

Generalization of fear is considered an important mechanism contributing to the etiology and maintenance of anxiety disorders. Although previous studies have identified the importance of stimulus discrimination for fear generalization, it is still unclear to what degree overt attention to relevant stimulus features might mediate its magnitude. To test the prediction that visual preferences for distinguishing stimulus aspects are associated with reduced fear generalization, we developed a set of facial stimuli that was meticulously manipulated such that pairs of faces could either be distinguished by looking into the eyes or into the region around mouth and nose, respectively. These pairs were then employed as CS + and CS- in a differential fear conditioning paradigm followed by a generalization test with morphs in steps of 20%. Shock expectancy ratings indicated a moderately curved fear generalization gradient that is typical for healthy samples, but its shape was altered depending on individual attentional deployment: Particpants who dwelled on the distinguishing facial features faster and for longer periods of time exhibited less fear generalization. Although both pupil and heart rate responses also showed a generalization gradient, with pupil diameter and heart rate deceleration increasing as a function of threat, these responses were not significantly related to visual exploration. In total, the current results indicate that the extent of explicit fear generalization depends on individual patterns of attentional deployment. Future studies evaluating the efficacy of perceptual trainings that aim to augment stimulus discriminability in order to reduce (over)generalization seem desirable. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Fear conditioning is preserved in very preterm-born young adults despite increased anxiety levels

Very preterm birth is associated with an increased risk for anxiety disorders. Abnormal brain development may result in disordered fear learning processes, which may be exacerbated by environmental risk factors and persist in adulthood. We tested the hypotheses that very preterm-born young adults displayed higher levels of fear conditioning, less differentiation between threat (CS+) and safety (CS−) signals, and stronger resistance to extinction relative to term-born controls. A group of 37 very preterm-born young adults and 31 age- and sex-matched term-born controls performed a differential fear conditioning paradigm on two consecutive days. Acquisition and extinction training were performed on day 1. Recall and reinstatement were tested on day 2. Preterm-born participants showed significantly higher levels of anxiety in the Depression-Anxiety-Stress-Scale-21 questionnaire. The fear conditioning outcome measures, skin conductance response amplitudes and anxiety ratings, were overall higher in the preterm-born group compared to controls. Awareness of CS-US contingencies was mildly reduced in preterms. Acquisition, extinction, recall and reinstatement of differential conditioned fear responses (CS+ > CS−), however, were not significantly different between the groups. There were no significant group by stimulus type interactions. The finding of largely preserved associative fear learning in very preterm-born young adults was unexpected and needs to be confirmed in future studies.

The impact of physical exercise on the consolidation of fear extinction memories.

Based on the mechanisms of fear extinction, exposure therapy is the most common treatment for anxiety disorders. However, extinguished fear responses can reemerge even after successful treatment. Novel interventions enhancing exposure therapy efficacy are therefore critically needed. Physical exercise improves learning and memory and was also shown to enhance extinction processes. This study tested whether physical exercise following fear extinction training improves the consolidation of extinction memories. Sixty healthy men underwent a differential fearconditioning paradigm with fear acquisition training on day 1 and fear extinction training followed by an exercise or resting control intervention on day 2. On day 3, retrieval and reinstatement were tested including two additional but perceptually similar stimuli to explore the generalization of exercise effects. Exercise significantly increased heart rate, salivary alpha amylase, and cortisol, indicating successful exercise manipulation. Contrary to our expectations, exercise did not enhance but rather impaired extinction memory retrieval on the next day, evidenced by significantly stronger differential skin conductance responses (SCRs) and pupil dilation (PD). Importantly, although conditioned fear responses were successfully acquired, they did not fully extinguish, explaining why exercise might have boosted the consolidation of the original fear memory trace instead. Additionally, stronger differential SCRs and PD toward the novel stimuli suggest that the memory enhancing effects of exercise also generalized to perceptually similar stimuli. Together, these findings indicate that physical exercise can facilitate both the long-term retrievability and generalization of extinction memories, but presumably only when extinction was successful in the first place.

In safe hands: Attachment figures’ safety properties and the link with attachment style

According to the Learning Theory of Attachment, naturalistic learning experiences about others' responsiveness during distress are an underlying mechanism in the development of attachment. Previous studies have demonstrated attachment figures' unique safety-inducing effects in highly controlled conditioning procedures. Yet, neither have studies examined the presumed influence of safety learning on state attachment, nor have they examined how attachment figures' safety-inducing effects relate to attachment styles. To address these gaps, a differential fear conditioning paradigm was used in which pictures of participants’ attachment figure and two control stimuli served as safety cues (CS-). US-expectancy and distress ratings were measured as indicators of fear responding.Results indicate that attachment figures evoked enhanced safety responding compared to control safety cues at the start of acquisition, which was maintained throughout acquisition and when presented together with a danger cue. Attachment figures' safety-inducing effects were reduced in individuals with higher attachment avoidance, although attachment style did not affect the rate of new safety learning. Finally, safe experiences with the attachment figure in the fear conditioning procedure resulted in diminished anxious state attachment. Adding to previous work, these findings underscore the importance of learning processes for attachment development and attachment figures’ provision of safety.

Systematically investigating the role of context on effect replicability in reinstatement of fear in humans

Context is crucial in guiding behavior in an ever-changing world and contextual information plays a crucial role in associative learning processes. For instance, the return of fear (RoF) after successful extinction, which is used to study the mechanisms underlying relapse phenomena in fear- and stress-related disorders in an experimental model, is known to be context dependent as evident from phenomena such as renewal (contextual change) and reinstatement (re-exposure to an aversive event).Human adaptions of reinstatement paradigms have resulted in mixed findings: CS specific as well as unspecific RoF or unexpected “reinstated” conditioned responding in no reinstatement US control groups. Here, we systematically investigate the role of context (i.e., cue-context compound) on reinstatement-induced RoF in a human differential fear conditioning paradigm using subjective and psychophysiological measures in a large sample (N = 212) including reinstatement and control groups.Overall, response patterns in reinstatement-groups mirrored results from single-cue rodent work. Yet, only generalized, not differential RoF was observed. Remarkably, depending on outcome measure RoF was also observed under identical experimental context conditions without US-re-exposure, underlining effects of contextual change beyond the reinstatement-US and challenging reinstatement research in human subjects and highlight that future reinstatement work should focus on the operationalization of context.

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.

Fear learning and generalization during pandemic fear: How COVID-19-related anxiety affects classical fear conditioning with traumatic film clips

The COVID-19 pandemic greatly disrupted our daily lives. Worldwide, people were confronted with health, financial, and existential fears or trauma-like experiences. Recent studies have identified an increase in stress, anxiety, and fear symptoms in connection with the pandemic. Furthermore, fear learning processes are central mechanisms in the development and maintenance of anxiety disorders. Patients commonly show impairments not only in fear learning but also in its generalization. Thus, pandemic-related anxiety may constitute a risk factor for both enhanced fear acquisition and generalization. In a pre-registered online study with a final sample of 220 healthy university students, we investigated whether participants with higher COVID-19-related anxiety (COVID-Anxiety) show impaired fear learning and generalization. For this purpose, we used a differential fear conditioning paradigm with a traumatic film clip as the unconditioned stimulus (US) and collected US-expectancy as the main measure of interest. Participants with high COVID-Anxiety show a tendency toward poorer discrimination between the reinforced conditioned stimulus (CS+) and the unreinforced conditioned stimulus (CS−) during acquisition and significantly poorer discrimination patterns during generalization. Furthermore, participants with high COVID-Anxiety show greater general fear throughout the whole experiment. Our results show that the subjective effects of the COVID-19 pandemic on psychological well-being are associated with impairments in both fear learning and fear generalization. As expected, high COVID-Anxiety leads to poorer performance in stimulus discrimination and greater levels of fear, which might contribute to a higher risk of anxiety disorders. German clinical trial registerDRKS00022761.

Identifying characteristics of non-completers in fear conditioning paradigms with children and adolescents

The number of studies on fear conditioning in children and adolescents has increased in recent years. Most of these studies exclusively focus on data of completers while dropout rates, reasons for dropout, and specific characteristics of non-completers are underreported. This study systematically investigated data of 283 children and adolescents between 8 and 17 years ( M = 11.10 , SD = 2.14) undergoing a differential fear conditioning paradigm using a female scream as unconditioned stimulus (US). The sample included 230 children and adolescents with a current primary anxiety disorder (separation anxiety disorder, social anxiety disorder, and specific phobia) and 53 non-anxious controls. The dropout rate was 24.1%. The most common reason to discontinue was being afraid of the US (59.1%) followed by the startle probe being too loud (15.2%). Logistic regressions revealed that younger age and a present anxiety disorder predicted dropout. There seem to be distinct characteristics potentially predicting dropout from fear conditioning paradigms. Thus, interpretability and generalizability of those paradigms are limited when non-completers are not considered. Future research should conscientiously look at these data more closely and investigate paradigms that work independent of age and diagnostic status.

The absence of differential electrodermal responding in the second half of acquisition does not indicate the absence of fear learning.

Many contemporary studies of human fear conditioning exclude participants who fail to show differential electrodermal responding during late stages of acquisition training, deeming them to be non-Learners. The current study examined whether non-Learners, defined as those who fail to show larger electrodermal first interval responses to CS+ than to CS- in the second half of acquisition, show differential electrodermal responding early during acquisition or during extinction or evidence of fear-learning on other measures, including rated CS valence and contingency report. In a sample of 351 participants who completed a standard differential fear-conditioning paradigm that employed electrodermal first and second interval responses (FIR, SIR), continuous CS evaluations, and post-experimental contingency reports to assess fear-learning, 74 participants were identified as non-Learners. These non-Learners displayed overall smaller electrodermal responses but showed evidence for differential conditioning during acquisition in electrodermal FIR (block1) and SIR (blocks 2-3) and in CS evaluations during acquisition (blocks 2-4) and extinction (blocks 1-4). Fifty-nine non-Learners correctly reported the contingencies. A lack of differential electrodermal first interval responding during the second half of acquisition does not indicate the absence of fear-learning. Rather, this criterion appears to capture participants who exhibit low physiological arousal and performance decrements toward the end of acquisition. Applying criteria based on "end of acquisition" electrodermal responding to determine "non-learning" results in the exclusion of participants who display fear-learning at other experimental stages or in other measures.

Exposure to acute stress affects the retrieval of out-group related bias in healthy men

Individuals have a tendency to show enhanced vigilance to groups of which they themselves are not a member. Stress can up-regulate hypervigilance towards threatening stimuli and was shown to promote the reinstatement of out-group-related biases in a previous study conducted in women only. The current study examines how exposure to acute stress affects the retrieval of out-group related biases in male participants using a two-day paradigm, in which forty-four Caucasian participants acquired and extinguished fear associations for both in-group (Caucasian) and out-group (Moroccan) faces via a typical differential fear conditioning paradigm (Day1), and exposure to stress (SECPT) or control condition preceded the retrieval test (Day 2). Men showed a specific out-group related bias at the beginning of extinction training indexed by higher SCRs towards out-group faces, especially out-group CS - (t(39)=2.71, p=.010, d=0.87); While stress can lead to a relapse of this extinguished out-group bias: the stress group showed higher SCRs towards out-group faces during retrieval compared to the control (F(1,38)=5.75, p=0.022) and the bias index was negatively related to post-stress cardiovascular recovery. Stress can be severe as a potential risk factor to stimulate social racial prejudice recurrent in conditioning paradigm, along with potential modulation role of sex difference.

Associative learning shapes visual discrimination in a web-based classical conditioning task

Threat detection plays a vital role in adapting behavior to changing environments. A fundamental function to improve threat detection is learning to differentiate between stimuli predicting danger and safety. Accordingly, aversive learning should lead to enhanced sensory discrimination of danger and safety cues. However, studies investigating the psychophysics of visual and auditory perception after aversive learning show divergent findings, and both enhanced and impaired discrimination after aversive learning have been reported. Therefore, the aim of this web-based study is to examine the impact of aversive learning on a continuous measure of visual discrimination. To this end, 205 participants underwent a differential fear conditioning paradigm before and after completing a visual discrimination task using differently oriented grating stimuli. Participants saw either unpleasant or neutral pictures as unconditioned stimuli (US). Results demonstrated sharpened visual discrimination for the US-associated stimulus (CS+), but not for the unpaired conditioned stimuli (CS−). Importantly, this finding was irrespective of the US’s valence. These findings suggest that associative learning results in increased stimulus salience, which facilitates perceptual discrimination in order to prioritize attentional deployment.

Fear Extinction and Predictive Trait-Like Inter-Individual Differences in Rats Lacking the Serotonin Transporter.

Anxiety disorders are associated with a failure to sufficiently extinguish fear memories. The serotonergic system (5-hydroxytryptamine, 5-HT) with the 5-HT transporter (5-HTT, SERT) is strongly implicated in the regulation of anxiety and fear. In the present study, we examined the effects of SERT deficiency on fear extinction in a differential fear conditioning paradigm in male and female rats. Fear-related behavior displayed during acquisition, extinction, and recovery, was measured through quantification of immobility and alarm 22-kHz ultrasonic vocalizations (USV). Trait-like inter-individual differences in novelty-seeking, anxiety-related behavior, habituation learning, cognitive performance, and pain sensitivity were examined for their predictive value in forecasting fear extinction. Our results show that SERT deficiency strongly affected the emission of 22-kHz USV during differential fear conditioning. During acquisition, extinction, and recovery, SERT deficiency consistently led to a reduction in 22-kHz USV emission. While SERT deficiency did not affect immobility during acquisition, genotype differences started to emerge during extinction, and during recovery rats lacking SERT showed higher levels of immobility than wildtype littermate controls. Recovery was reflected in increased levels of immobility but not 22-kHz USV emission. Prominent sex differences were evident. Among several measures for trait-like inter-individual differences, anxiety-related behavior had the best predictive quality.

Impaired fear learning and extinction, but not generalization, in anxious and non-anxious depression

Fear conditioning and generalization are well-known mechanisms in the pathogenesis of anxiety disorders. Extinction of conditioned fear responses is crucial for the psychotherapeutic treatment of these diseases. Anxious depression as a subtype of major depression shares characteristics with anxiety disorders. We therefore aimed to compare fear learning mechanisms in patients with anxious versus non-anxious depression. Fear learning mechanisms in patients with major depression (n = 79; for subgroup analyses n = 41 patients with anxious depression and n = 38 patients with non-anxious depression) were compared to 48 healthy participants. We used a well-established differential fear conditioning paradigm investigating acquisition, generalization, and extinction. Ratings of valence, arousal and probability of expected threat were assessed as well as skin conductance response as an objective psychophysiological measure. Patients with major depression showed impaired acquisition of conditioned fear. In addition, depressed patients showed impaired extinction of conditioned fear responses after successful fear conditioning. Generalization was not affected. However, there was no difference between patients with anxious and non-anxious depression. Results differed between objective and subjective measures. Our findings show altered fear acquisition and extinction in major depression as compared to healthy controls, but they do not favor differential fear learning and extinction mechanisms in the pathogenesis of anxious versus non-anxious depression. The results of impaired extinction warrant future studies addressing extinction learning elements in the treatment of depression.

Poor Mnemonic Discrimination Predicts Overgeneralization of Fear

Anxiety disorders are characterized by difficulty distinguishing safe contexts from previous or imagined threats. Conditioned fears spread beyond what is reasonable or adaptive, leading to broad and interfering anxieties when people overgeneralize their fears. Difficulties with mnemonic discrimination, a component process of memory supporting the integration of old and new experiences, may foster overgeneralization and increase risk for anxiety disorders. Individuals along a spectrum of anxiety severity (n = 117) completed a differential fear conditioning paradigm and the computerized Mnemonic Similarity Task. The task measures mnemonic discrimination by requiring individuals to differentiate between highly similar old and new entities. We predicted that low mnemonic discrimination would be associated with overgeneralization, i.e., flatter slopes of change in response to stimuli increasingly dissimilar to the conditioned stimulus. Conditional growth models showed that as expected, participants with the highest mnemonic discrimination scores also exhibited the steepest declines in fear ratings as stimuli increasingly differed from the conditioned stimulus. Results were unchanged after adjusting for recognition memory, self-reported anxiety, and clinical diagnoses and symptoms. Results support the hypothesis that memory interference (i.e., low mnemonic discrimination) could increase vulnerability for overgeneralization. Findings justify additional exploration of mnemonic discrimination and its role in anxious psychopathology.

State-Dependent TMS over Prefrontal Cortex Disrupts Fear-Memory Reconsolidation and Prevents the Return of Fear

Erasing maladaptive memories has been a challenge for years. A way to change fear memories is to target the process of reconsolidation, during which a retrieved memory transiently returns to a labile state, amenable to modification [1, 2]. Disruption of human fear-memory reconsolidation has been classically attempted with pharmacological [3] or behavioral (e.g., extinction) [4] treatments that, however, do not clarify the underlying brain mechanism. To address this issue, in 84 healthy humans submitted to six experiments, here, we combined a differential fear conditioning paradigm with repetitive transcranial magnetic stimulation (rTMS) administered in a state-dependent manner. In a critical condition, we stimulated the dorsolateral prefrontal cortex (dlPFC) 10min after a reminder cue that reactivated a fear memory acquired 1day before. At testing, 24h after rTMS, participants exhibited decreased physiological expression of fear, as shown by their skin conductance response. Similar reductions were observed when targeting the left and the right dlPFC. In contrast, no decrease was observed in participants tested immediately after dlPFC-rTMS or in participants receiving either control rTMS (i.e., active control site and sham stimulations) or dlPFC-rTMS without preceding fear-memory reactivation, thus showing both the site and time specificity and state dependency of our rTMS intervention. Expression of fear was indeed reduced only when dlPFC-rTMS was administered within the reconsolidation time window. Moreover, dlPFC-rTMS prevented subsequent return of fear after extinction training. These findings highlight the causal role of dlPFC in fear-memory reconsolidation and suggest that rTMS can be used in humans to prevent the return of fear.

Effects of intranasal insulin as an enhancer of fear extinction: a randomized, double-blind, placebo-controlled experimental study.

Fear-extinction based psychotherapy (exposure) is the most effective method for treating anxiety disorders. Notwithstanding, since some patients show impairments in the unlearning of fear and insufficient fear remission, there is a growing interest in using cognitive enhancers as adjuvants to exposure. As insulin plays a critical role in stress processes and acts as a memory enhancer, this study aimed to assess the capacity of intranasal insulin to augment fear extinction. A double-blind, placebo-controlled differential fear-conditioning paradigm was conducted in 123 healthy participants (63 females). Pictures of faces with neutral expressions were used as conditioned stimuli and electric shocks as unconditioned stimuli. The paradigm consisted of four phases presented on three consecutive days: acquisition (day 1), extinction (day 2), reinstatement and re-extinction (day 3). A single intranasal dose of insulin (160 IU) or placebo was applied on day 2, 45 min before fear extinction. Skin conductance response (SCR), fear-potentiated startle (FPS) and expectancy ratings were assessed. During extinction, the insulin group (independent of sex) showed a significantly stronger decrease in differential FPS in comparison with the placebo group. Furthermore, a sex-specific effect was found for SCR, with women in the insulin group showing a greater decrease of differential SCR both at early extinction and at late re-extinction. Our results provide first evidence that intranasal insulin facilitates fear extinction processes and is therefore a promising adjuvant for extinction-based therapies in anxiety and related disorders. Sex-specific effects should be taken into consideration in future studies.

"Prepared" fear or socio-cultural learning? Fear conditioned to guns, snakes, and spiders is eliminated by instructed extinction in a within-participant differential fear conditioning paradigm.

Across three experiments, we investigated whether electrodermal responses conditioned to ontogenetic fear-relevant (pointed guns) and phylogenetic fear-relevant stimuli (snakes and spiders) would resist instructed extinction in a within-participant differential fear conditioning paradigm. Instructed extinction involves informing participants before extinction that the unconditional stimulus (US) will no longer be presented. This manipulation has been shown to abolish fear conditioned to fear-irrelevant conditional stimuli, but is said to leave fear conditioned to images of snakes and spiders intact. The latter finding, however, has only been demonstrated when fear-relevance is manipulated between-groups. It is also not known whether instructed extinction affects fear conditioned to ontogenetic fear-relevant stimuli, such as pointed guns. In Experiment 1, we demonstrated that fear conditioned to images of pointed guns does not resist instructed extinction. In Experiment 2, we detected some evidence to suggest that fear conditioned to images of snakes and spiders survives instructed extinction but this evidence was not conclusive. In Experiment 3, we directly compared the effects of instructed extinction on fear conditioned to snakes and spiders and to guns and provide strong evidence that fear conditioned to both classes of stimuli is reduced after instructed extinction with no differences between ontogenetic and phylogenetic stimuli. The current results suggest that when fear relevance is manipulated within-participants fear conditioned to both phylogenetic and ontogenetic, fear-relevant stimuli responds to instructed extinction providing evidence in favor of a socio-cultural explanation for "preparedness" effects.

The cerebellum is involved in processing of predictions and prediction errors in a fear conditioning paradigm.

Prediction errors are thought to drive associative fear learning. Surprisingly little is known about the possible contribution of the cerebellum. To address this question, healthy participants underwent a differential fear conditioning paradigm during 7T magnetic resonance imaging. An event-related design allowed us to separate cerebellar fMRI signals related to the visual conditioned stimulus (CS) from signals related to the subsequent unconditioned stimulus (US; an aversive electric shock). We found significant activation of cerebellar lobules Crus I and VI bilaterally related to the CS+ compared to the CS-. Most importantly, significant activation of lobules Crus I and VI was also present during the unexpected omission of the US in unreinforced CS+ acquisition trials. This activation disappeared during extinction when US omission became expected. These findings provide evidence that the cerebellum has to be added to the neural network processing predictions and prediction errors in the emotional domain.