Contextual fear conditioning predicts subsequent avoidance behaviour in a virtual reality environment

Avoidance behaviour is a crucial component of fear and is importantly involved in the maintenance of anxiety disorders. Presumably, fear conditioning leads to avoidance of the feared object or context. A virtual reality contextual fear conditioning paradigm was used to investigate the association between explicit conditioning effects and subsequent avoidance behaviour. Mild electric shocks were administered in one context (anxiety context), but never in a second context (safety context). Subsequent avoidance behaviour was assessed by asking participants to choose two out of three contexts (a neutral context was added) to visit again. Participants avoided the anxiety context, but did not prefer the safety over the neutral context. Participants with substantial conditioning effects, as reflected in differential valence, arousal and anxiety ratings, avoided the anxiety context but not the safety context. In sum, we demonstrated an association between context conditioning effects on an explicit level and later avoidance behaviour.     

Pentylenetetrazole as an unconditioned stimulus for olfactory and contextual fear conditioning in rats

The association of five footshocks with a neutral odor is able to establish an olfactory fear conditioning in rats. The present study sought to investigate whether the systemic administration of pentylenetetrazole (PTZ; 3.75–15 mg/kg) would turn the coffee odor in a conditioned stimulus in the fear conditioning paradigm. The results showed that rats started to display risk assessment and avoidance after PTZ (15 mg/kg)–coffee odor pairing. When three mild footshocks (0.4 mA for 2 s) were delivered during this pairing, the conditioned response exhibited was greater than before. In both cases, however, pretreatment with the benzodiazepine midazolam (MDZ. 0.5 mg/kg i.p.) fully counteracted the expression of these defensive behaviors. Moreover, after being paired with 15 mg/kg of PTZ alone or combined with footshocks, the coffee odor was able to promote a new fear conditioning related to the context where it was re-exposed. The present findings point out the usefulness of PTZ as an unconditioned stimulus to promote fear conditioning to olfactory and contextual cues in rats.     

Attentional and behavioural responses of spider fearfuls to virtual spiders

This study employed an immersed virtual environment (IVE) in the Nijmegen RIVERlab to study spider fearfuls’ attentional and motor reactions to virtual spiders. The participants were exposed to virtual spiders while completing an unrelated task, walking freely through a virtual museum. Compared to non-fearful controls, spider fearfuls showed an increase in state anxiety, they spent more time looking at spiders, and they exhibited spontaneous behavioural avoidance of spiders and visually similar objects. The results extend, and to some degree contradict, those of earlier studies with static pictures, and they speak to the usefulness of state-of-the-art IVEs in fundamental anxiety research.     

Generalisation of fear and avoidance along a semantic continuum

Directly conditioned fear and avoidance readily generalises to dissimilar but conceptually related stimuli. Here, for the first time, we examined the conceptual/semantic generalisation of both fear and avoidance using real words (synonyms). Participants were first exposed to a differential fear conditioning procedure in which one word (e.g., “broth”; CS+) was followed with brief electric shock [unconditioned stimulus (US)] and another was not (e.g., “assist”; CS–). Next, an instrumental conditioning phase taught avoidance in the presence the CS+ but not the CS–. During generalisation testing, synonyms of the CS+ (e.g., “soup”; GCS+) and CS– (e.g., “help”; GCS–) were presented in the absence of shock. Conditioned fear and avoidance, measured via skin conductance responses, behavioural avoidance and US expectancy ratings, generalised to the semantically related, but not to the semantically unrelated, synonyms. Findings have implications for how natural language categories and concepts mediate the expansion of fear and avoidance repertoires in clinical contexts.     

The effects of the presence of others during a rowing exercise in a virtual reality environment

ObjectivesThe aim of the study was to test the performance, motivational, and affective impact of aerobic exercise within an immersive virtual reality environment experienced alone or with another individual.DesignSixty female participants aged 18–30 years were assigned to one of three conditions: no virtual reality (NVR), individual virtual reality (IVR), or companion virtual reality (CVR).MethodParticipants completed 9 min of self-paced rowing on an ergometer without any visual input or performance feedback (NVR), individually within a virtual reality environment (IVR), or within a virtual reality environment that included a companion depicted as an avatar (CVR).ResultsThe two virtual reality groups rowed a further distance and at a higher power output than the NVR group. Furthermore, the CVR group outperformed the IVR group in distance and had a higher heart rate. Participants in the virtual reality groups did not perceive themselves to be exerting more physical effort and rated the task as more enjoyable than participants in the NVR group.ConclusionsVirtual reality improves performance and the affective response to aerobic exercise, and performance effects are further enhanced by the presence of others in the virtual environment.     

Contextual control of human fear associations in a renewal paradigm

The original model of behavior change suggests that extinction is context dependent whereas fear acquisition is context independent [Bouton, M. E. & Ricker, S. T. (1994). Renewal of extinguished responding in a second context. Animal Learning and Behavior, 22, 317-324]. Supportive evidence stems mainly from animal studies, showing that after acquisition (conditioned stimulus-unconditioned stimulus (CS-US)) in Context A and extinction in Context B, fear is renewed by presenting the CS in acquisition Context A (ABA renewal) or in a novel Context C (ABC renewal). By implication, the model predicts equal ABA and ABC renewal. However, there is also evidence to suggest that the context dependency of extinction and the context independency of acquisition may be less stringent than originally proposed. The present study investigated renewal in humans using a differential fear conditioning paradigm with a shock US and online shock expectancy ratings and electrodermal responses as dependent variables. Experiment 1 compared an ABA condition with an AAA condition. Experiment 2 compared three conditions: ABA, ABC, and AAA. Both experiments demonstrated ABA renewal. Most importantly, Experiment 2 showed larger ABA than ABC renewal. Overall, results for expectancy ratings were more convincing than for electrodermal responses. In line with the extinction model, the present findings support the context dependency of extinction in humans. In contrast to the model, the findings suggest that in humans not only extinction learning, but also fear acquisition is controlled by its current context.     

Return of fear in a human differential conditioning paradigm caused by a return to the original acquistion context

In a differential human fear conditioning paradigm evidence for ABA-renewal was obtained manipulating the lighting in the experimental room. During acquisition in either a dark or illuminated room, one neutral slide was sometimes paired with a loud aversive noise whereas another slide was not. Subsequently, extinction took place in the opposite lighting context. When afterwards the participants were tested again in the original acquisition context, measurements revealed a recovery of the conditioned electrodermal response and an increase in the retrospective verbal US-expectancy ratings. No response recovery was obtained in an AAA-group that received acquisition, extinction and test trials in one and the same context. Several theoretical explanations for this type of return of fear as well as implications for clinical practice are discussed.     

The time course of location-avoidance learning in fear of spiders

Two experiments were designed to study the time course of avoidance learning in spider fearfuls (SFs) under controlled experimental conditions. To achieve this, we employed an immersive virtual environment (IVE): While walking freely through a virtual art museum to search for specific paintings, the participants were exposed to virtual spiders. Unbeknown to the participants, only two of four museum rooms contained spiders, allowing for avoidance learning. Indeed, the more SF the participants were, the faster they learned to avoid the rooms that contained spiders (Experiment. 1), and within the first six trials, high fearfuls already developed a preference for starting their search task in rooms without spiders (Experiment 2). These results illustrate the time course of avoidance learning in SFs, and they speak to the usefulness of IVEs in fundamental anxiety research.     

The spread of fear: Symbolic generalization mediates graded threat-avoidance in specific phobia

Overgeneralization of fear and threat-avoidance represents a formidable barrier to successful clinical treatment of anxiety disorders. While stimulus generalization along quantifiable physical dimensions has been studied extensively, less consideration has been given to symbolic generalization, in which stimuli are indirectly and arbitrarily related. The present study examined whether the magnitude and extent of symbolic generalization of threat-avoidance and threat-beliefs differed between spider-phobic and nonphobic individuals. Initially, participants learned two sets of stimulus equivalence relations (A1?=?B1?=?C1; A2?=?B2?=?C2). Next, one cue (B1) was established as a conditioned stimulus (CS?+?; threat) that signalled onset of spider images and prompted avoidance, and another cue (B2) was established as a CS– (safety cue) that signalled the absence of such images. Subsequent testing showed that phobics compared to nonphobics exhibited greater symbolic generalization of threat-avoidance to threat cues A1 and C1 (indirect CS+ threat cues related via symmetry and equivalence, respectively), while all individuals showed nonavoidance to indirect safety cues A2 and C2. The enhanced symbolic generalization of threat-beliefs and avoidance behaviour observed in spider phobics warrants further investigation.     

Heart rate reactivity in HAD and LAD rats during Pavlovian fear conditioning

Recently, we reported that High-Alcohol-Drinking (HAD) rats exhibited selective deficits in active avoidance learning under alcohol-naive conditions, and that administration of moderate doses of alcohol (0.5 and 1.0 g/kg) facilitated learning in these rats (Blankenship et al., 2000; Rorick et al., 2003b). We hypothesized that the deficits resulted from excessive fear in the aversive learning context and that the anxiolytic properties of alcohol may have contributed to the improved learning that was observed after alcohol administration. This hypothesis was supported by a recent study in which prolonged freezing in HAD rats was seen after a classical fear conditioning procedure (Rorick et al., 2003a). To provide additional evidence that HAD rats indeed exhibit behaviors consistent with the expression of increased fear in aversive learning contexts, we employed a Pavlovian fear conditioning task to measure heart rate in HAD and Low-Alcohol-Drinking (LAD) rats. In this study, HAD (HAD-1 and HAD-2) and LAD (LAD-1 and LAD-2) rats were assigned to one of three pre-exposure conditions: Context Only, Context/Tone, or Sequential (Context Only followed by Context/Tone) Pre-Exposure. Following pre-exposure, fear conditioning acquisition and extinction procedures were identical for all groups. Results indicated that although no baseline differences were observed between HAD and LAD rats, HAD rats receiving Context-Only pre-exposure exhibited excessive heart rate reactivity to the tone conditional stimulus during fear conditioning acquisition, compared to LAD rats receiving the same pre-exposure conditions. These findings support the hypothesis that HAD rats exhibit behaviors consistent with increased fear in aversive learning contexts, as measured by autonomic conditioning.     

The effects of sub-threshold vibratory noise on visuomotor entrainment during human walking and standing in a virtual reality environment

Humans will naturally synchronize their posture to the motion of a visual surround, but it is unclear if this visuomotor entrainment can be attenuated with an increased sensitivity to somatosensory information. Sub-threshold vibratory noise applied to the Achilles tendons has proven to enhance ankle proprioception through the phenomenon of stochastic resonance. Our purpose was to compare visuomotor entrainment during walking and standing, and to understand how this entrainment might be attenuated by applying sub-threshold vibratory noise over the Achilles tendons. We induced visuomotor entrainment during standing and treadmill walking for ten subjects (24.5 ± 2.9 years) using a speed-matched virtual hallway with continuous mediolateral perturbations at three different frequencies. Vibrotactile motors over the Achilles tendons provided noise (0–400 Hz) with an amplitude set to 90% of each participant’s sensory threshold. Mediolateral sacrum, C7, and head motion was greatly amplified (4–8× on average) at the perturbation frequencies during walking, but was much less pronounced during standing. During walking, individuals with greater mediolateral head motion at the fastest perturbation frequency saw the greatest attenuation of that motion with applied noise. Similarly, during standing, individuals who exhibited greater postural sway (as measured by the center of pressure) also saw the greatest reductions in sway with sub-threshold noise applied in three of our summary metrics. Our results suggest that, at least for healthy young adults, sub-threshold vibratory noise over the Achilles tendons can slightly improve postural control during disruptive mediolateral visual perturbations, but the applied noise does not substantially attenuate visuomotor entrainment during walking or standing.     

Biphasic ERK1/2 activation in both the hippocampus and amygdala may reveal a system consolidation of contextual fear memory

There is accumulating evidences to suggest that memory consolidation in some conditions involves two waves of neuronal plastic change. Using two fear conditioning procedures in male C57BL/6J mice, we have recently shown that consolidation of the foreground contextual fear memory required two waves of ERK1/2 activation in hippocampal CA1, while consolidation of cue conditioning was only associated with the early phase of activation. The present experiment further showed that this bi-phasic pattern of ERK1/2 activation was not restricted to hippocampal CA1, but could also be observed in other fear memory-related brain areas. The unpaired conditioning procedure (context in foreground) induced two waves of ERK1/2 activation in hippocampal CA1 and CA3, as well as in the LA and BLA nuclei of the amygdala. In contrast, the paired conditioning procedure (context in background) led to a transient early phase only in hippocampal CA1 and LA. In addition, ERK1/2 phosphorylation in the hippocampus was found to correlate with that in the amygdala nuclei specifically after the unpaired procedure. Taken together, our data suggest that the observed biphasic pattern of neuronal plastic events may reflect the interplay between hippocampal and amygdala activity-dependent plasticity critical for the system consolidation of contextual fear memory.     

Effectiveness of virtual reality distraction during a painful medical procedure in pediatric oncology patients

The effectiveness of virtual reality (VR) as a behavioral intervention designed to decrease distress during port access procedure was examined in 20 7- to 14-year-old pediatric oncology patients. Children were randomized to either engage in an immersive VR environment during the procedure or to a no VR control condition. Children's distress was assessed through subjective self-ratings and objective physiological and behavioral ratings. Narrative accounts of the experience were used as a measure of how well the child coped with the procedure. VR was effective in reducing children's distress on all measures. Implications of these findings for intervention are discussed.     

Fear and avoidance of driving among drivers involved in a road traffic crash. The role of traumatic fear and driving cognitions

Fear and avoidance of driving are possible consequences of involvement in road traffic crashes (RTCs). Few studies have assessed the factors associated with fear and avoidance of driving after an RTC. The aim of this present study is to investigate the relations among trauma appraisals of fear, negative driving cognitions, fear and avoidance of driving in a sample of people who experienced vehicle crashes. Further, the mediating role of negative driving cognitions in the relation between trauma appraisals, fear of driving and avoidance of driving was assessed. The sample was comprised of 116 drivers who had been involved in an RTC in the past two years. Negative driving cognitions positively predicted fear of driving and avoidance of driving. Moreover, negative driving cognitions mediated the relation among trauma appraisals of fear with fear of driving and avoidance of driving. The theoretical and practical implications of these results are discussed.     

The effect of age and sensation seeking on pedestrian crossing safety in a virtual reality street

A wide range of individual, interpersonal and environmental factors influence the safety of pedestrians crossing the street, including human development (children take more risks than adolescents and adults) and sensation seeking (individuals higher in sensation seeking have greater risk). The interaction between those two variables has not been carefully studied, however. Does the effect of sensation seeking on pedestrian safety vary across human development as cognitive and other skills improve? This study investigated the primary effects of age and sensation seeking, plus their joint effects, on pedestrian crossing in a virtual reality environment. 209 children (10–13 years old), adolescents (14–18 years old) and young adults (20–24 years old) screened to be high and low level in sensation seeking participated. A 3 (age group: child vs adolescent vs young adult) × 2 (sensation seeking: high vs low) × 2 (traffic condition: easy vs harder crossing) mixed factorial design was conducted. Three pedestrian safety outcomes – start delay, missed opportunities and dangerous crossings – were considered. Results showed that when the traffic condition was easier to cross within, the start delay to enter traffic gaps was significantly shorter for children than for adolescents and young adults. There were no significant differences across age groups when the traffic condition was harder to cross within. Pedestrians also missed more opportunities to cross the road when the traffic condition was harder to cross within. Pedestrians low in sensation seeking missed more opportunities to cross than those high in sensation seeking. All age groups had more dangerous crossings during the harder crossing scenario than in the easier one, and adolescents had more dangerous crossings than young adults or children. Finally, the results of hierarchical regression models predicting dangerous crossings showed that traffic condition had a significant predictive effect on children's dangerous crossing behavior, and both high sensation seeking and harder traffic conditions predicted adolescents’ dangerous crossing behavior. No included variables significantly predicted adults' dangerous crossing behavior. We conclude that both age and sensation-seeking contribute to pedestrian safety. The effect of sensation seeking does not vary widely by age group, but its effect on adolescents was somewhat stronger than in the other age groups studied.     

Both exposure to a novel context and associative learning induce an upregulation of AKAP150 protein in mouse hippocampus

A-kinase anchoring protein 150 (AKAP150) is a multi-enzyme signaling complex that coordinates the action of PKA, PKC, and PP2B at neuronal membranes and synapses. We measured levels of AKAP150 protein in the hippocampus 6h after training mice in a contextual fear conditioning paradigm. In contextual fear conditioning mice learn to associate a context with a footshock presentation. Mice were divided in four experimental groups with different training protocols: naive, no footshock exposure, immediate footshock exposure, and footshock 3min after exposure to the context. We found that AKAP150 protein levels were increased upon exposing mice to the novel context independent of the training protocol. However, when the animals were habituated to the experimental context, only mice that learned to associate the context with the footshock showed an upregulation of AKAP150. We suggest that upregulated levels of AKAP150 contribute to processing the exposure to a novel context and associative learning.     

Classical fear conditioning in the anxiety disorders: a meta-analysis

Fear conditioning represents the process by which a neutral stimulus comes to evoke fear following its repeated pairing with an aversive stimulus. Although fear conditioning has long been considered a central pathogenic mechanism in anxiety disorders, studies employing lab-based conditioning paradigms provide inconsistent support for this idea. A quantitative review of 20 such studies, representing fear-learning scores for 453 anxiety patients and 455 healthy controls, was conducted to verify the aggregated result of this literature and to assess the moderating influences of study characteristics. Results point to modest increases in both acquisition of fear learning and conditioned responding during extinction among anxiety patients. Importantly, these patient-control differences are not apparent when looking at discrimination studies alone and primarily emerge from studies employing simple, single-cue paradigms where only danger cues are presented and no inhibition of fear to safety cues is required.     

Contextual information in situations of uncertainty: The value of explicit-information provision depends on expertise level,knowledge acquisition and prior-action congruency

In behavioral control, contextual information is used alongside incoming sensory inputs to reduce uncertainties about the unfolding situation. However, our understanding of this weighting process is limited; particularly regarding the applied question of whether individuals should be provided with information or whether they should rather generate it by themselves. We thus compared the provision of more or less valid (i.e., “true”) contextual information with a self-generation condition by examining the performance of elite and near-elite youth handball players (N = 30 + 27) in a virtual-reality defensive task. We measured response correctness, positioning as a function of the teammates’ defensive behaviors and the degree to which the experimentally induced patterns in the teammates’ strengths were detected. The results show that providing individuals with uncertain information neither enhances nor harms performance decisively. However, valid information enhances performance in congruent situations while degrading performance in incongruent situations, more pronouncedly in elite than in near-elite players. Consequently, individuals should be provided with explicit contextual information only if (i) their expertise level is not adequate enough to rely on self-generation, (ii) the situation-specific knowledge base cannot be sufficiently self-generated, and (iii) the instructor is sufficiently certain that the explicit information actually meets the upcoming situation.     

Development of a cognitive function test using virtual reality technology: examination in healthy participants

We developed a virtual reality test to assess the cognitive function of Japanese people in near-daily-life environment, namely, a virtual shopping test (VST). In this test, participants were asked to execute shopping tasks using touch panel operations in a “virtual shopping mall.” We examined differences in VST performances among healthy participants of different ages and correlations between VST and screening tests, such as the Mini–Mental State Examination (MMSE) and Everyday Memory Checklist (EMC). We included 285 healthy participants between 20 and 86 years of age in seven age groups. Therefore, each VST index tended to decrease with advancing age; differences among age groups were significant. Most VST indices had a significantly negative correlation with MMSE and significantly positive correlation with EMC. VST may be useful for assessing general cognitive decline; effects of age must be considered for proper interpretation of the VST scores.     

Stronger renewal in human fear conditioning when tested with an acquisition retrieval cue than with an extinction retrieval cue

It was previously demonstrated in our laboratory that conditioned fear in humans can renew after extinction, when this procedure took place in a different context (ABA-renewal [Vansteenwegen et al. (2005). Return of fear in a human differential conditioning paradigm caused by a return to the original acquisition context. Behaviour Research and Therapy, 43(3), 323–336]). Using the same experimental design, we now tested the power of retrieval cues to interact with this contextual renewal phenomenon. Two groups went through acquisition and extinction (in a different context). They were then tested in the original acquisition context and in the presence of a retrieval cue. In the acquisition-cue group, this cue previously featured during the acquisition procedure; in the extinction-cue group, the cue previously featured during the extinction procedure. As expected, renewal of conditioned electro-dermal responding and retrospective expectancy ratings was strongest in the acquisition-cue group. Theoretical and clinical implications of this finding are discussed.