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No Influence of Threat Uncertainty on Fear Generalization
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Abstract
Fear overgeneralization and perceived uncertainty about future outcomes have been suggested as risk factors for clinical anxiety. However, little is known regarding how they influence each other. In this study, we investigated whether different levels of threat uncertainty influence fear generalization. Three groups of healthy participants underwent a differential fear conditioning protocol followed by a generalization test. All groups learned to associate one female face (conditioned stimulus, CS+) with a female scream (unconditioned stimulus, US) while the other face (CS-) was not associated with the scream. In order to manipulate threat uncertainty, one group (low uncertainty, n = 26) received 80%, the second group (moderate uncertainty, n = 32) received 60%, and the third group (high uncertainty, n = 30) 40% CS-US contingency. In the generalization test, all groups saw CS+ and CS- again as well as four morphs that varied in similarity with the CS+ in steps of 20%. Subjective (expectancy, valence, and arousal ratings), psychophysiological (skin conductance response, SCR), and visuocortical (steady-state visual evoked potentials, ssVEPs) indices of fear were registered. Participants expected the US in accordance with their reinforcement schedules but displayed stronger skin conductance with more uncertainty. However, acquisition of conditioned fear was not evident in ssVEPs. During the generalization test, we found no effect of threat uncertainty in any of the measured variables, but the strength of generalization for threat expectancy ratings was positively correlated with dispositional intolerance of uncertainty. This study suggests that mere threat uncertainty does not modulate fear generalization.
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A hallmark symptom of fear and anxiety disorder is generalization of fear to essentially innocuous stimuli and situations. Such generalization can occur through both perceptual and conceptually similarities. Recent studies indicate that perceptual generalization is inflated in anxiety patients and individuals prone to develop anxiety disorders, suggesting that perceptual generalization may be involved in the etiology of anxiety disorders. In the current Registered Report, we wanted to address whether conceptual generalization is potentially implicated in the development of anxiety disorders as well. Therefore, we used a novel paradigm in which the Dutch word mini [tiny] or enorm [enormous] was paired with an electric shock and assessed fear to the conceptually related words klein [small], medium [medium], and groot [large]. The sample (N = 120) consisted of healthy university students. As hypothesized, we observed clear conceptual fear generalization gradients using both self-report and psychophysiological measures. However, in contrast to our expectations, these conceptual generalization gradients were not correlated with different anxious traits (i.e., trait anxiety, intolerance of uncertainty, and behavioral inhibition). These results show that fear can generalize conceptually along a gradient, without requiring perceptual errors as postulated by traditional models of fear generalization. Instead, our results correspond well with inferential reasoning theories of fear generalization. Additionally, we discuss potential reasons for the absence of the expected correlations between conceptual fear generalization and anxious traits, such as restricted variability in both the generalization task and the sample. We conclude that the paradigm has promise for further research on conceptual fear generalization.
Research has demonstrated the spreading of fear from threat-related stimuli to perceptually similar, but innocuous, stimuli. Less is known, however, about the generalization of avoidance behavior. Given that stress is known to affect learning and memory, we were interested in the effect of acute stress on (over)generalization of fear and avoidance responses. On the first day, one geometrical shape was paired with a mild electrical stimulus (CS+), whereas another shape was not (CS−). One day later, after participants had been exposed to the Maastricht Acute Stress Test or a control task, generalization of avoidance responses and fear (shock expectancy and skin conductance responses) was tested to a range of perceptual generalization stimuli. Generalization gradients were observed across different outcome measures. Stress enhanced generalization of shock expectancy to the stimulus most similar to the CS+. Our findings confirm that stress can affect the generalization of fear, but further studies are warranted.
Fear generalization - the tendency to interpret ambiguous stimuli as threatening due to perceptual similarity to a learned threat - is an adaptive process. Overgeneralization, however, is maladaptive and has been implicated in a number of anxiety disorders. Neuroimaging research has indicated several regions sensitive to effects of generalization, including regions involved in fear excitation (e.g., amygdala, insula) and inhibition (e.g., ventromedial prefrontal cortex). Research has suggested several other small brain regions may play an important role in this process (e.g., hippocampal subfields, bed nucleus of the stria terminalis [BNST], habenula), but, to date, these regions have not been examined during fear generalization due to limited spatial resolution of standard human neuroimaging. To this end, we utilized the high spatial resolution of 7T fMRI to characterize the neural circuits involved in threat discrimination and generalization. Additionally, we examined potential modulating effects of trait anxiety and intolerance of uncertainty on neural activation during threat generalization. In a sample of 31 healthy undergraduate students, significant positive generalization effects (i.e., greater activation for stimuli with increasing perceptual similarity to a learned threat cue) were observed in the visual cortex, thalamus, habenula and BNST, while negative generalization effects were observed in the dentate gyrus, CA1, and CA3. Associations with individual differences were underpowered, though preliminary findings suggested greater generalization in the insula and primary somatosensory cortex may be correlated with self-reported anxiety. Overall, findings largely support previous neuroimaging work on fear generalization and provide additional insight into the contributions of several previously unexplored brain regions.
Anxiety patients over-generalize fear, possibly because of an incapacity to discriminate threat and safety signals. Discrimination trainings are promising approaches for reducing such fear over-generalization. Here we investigated the efficacy of a fear-relevant vs. a fear-irrelevant discrimination training on fear generalization and whether the effects are increased with feedback during training. Eighty participants underwent two fear acquisition blocks, during which one face (conditioned stimulus, CS+), but not another face (CS−), was associated with a female scream (unconditioned stimulus, US). During two generalization blocks, both CSs plus four morphs (generalization stimuli, GS1–GS4) were presented. Between these generalization blocks, half of the participants underwent a fear-relevant discrimination training (discrimination between CS+ and the other faces) with or without feedback and the other half a fear-irrelevant discrimination training (discrimination between the width of lines) with or without feedback. US expectancy, arousal, valence ratings, and skin conductance responses (SCR) indicated successful fear acquisition. Importantly, fear-relevant vs. fear-irrelevant discrimination trainings and feedback vs. no feedback reduced generalization as reflected in US expectancy ratings independently from one another. No effects of training condition were found for arousal and valence ratings or SCR. In summary, this is a first indication that fear-relevant discrimination training and feedback can improve the discrimination between threat and safety signals in healthy individuals, at least for learning-related evaluations, but not evaluations of valence or (physiological) arousal.
Accurately estimating safety is critical to pursuing nondefensive survival behaviors. However, little attention has been paid to how the human brain computes safety. We conceptualize a model that consists of two components: (i) threat-oriented evaluations that focus on threat value, imminence, and predictability; and (ii) self-oriented evaluations that focus on the agent’s experience, strategies, and ability to control the situation. Our model points to the dynamic interaction between these two components as a mechanism of safety estimation. Based on a growing body of human literature, we hypothesize that distinct regions of the ventromedial prefrontal cortex (vmPFC) respond to threat and safety to facilitate survival decisions. We suggest safety is not an inverse of danger, but reflects independent computations that mediate defensive circuits and behaviors.
Defensive system activation promotes heightened perception of threat signals, and excessive attention to threat signals has been discussed as a contributory factor in the etiology of anxiety disorders. However, a mechanistic account of attentional modulation during fear-relevant processes, especially during fear generalization remains elusive. To test the hypothesis that social fear generalization prompts sharpened tuning in the visuocortical representation of social threat cues, 67 healthy participants underwent differential fear conditioning, followed by a generalization test in which participants viewed faces varying in similarity with the threat-associated face. We found that generalization of social threat sharpens visuocortical tuning of social threat cues, whereas ratings of fearfulness showed generalization, linearly decreasing with decreasing similarity to the threat-associated face. Moreover, individuals who reported greater anxiety in social situations also showed heightened sharpened tuning of visuocortical neurons to facial identity cues, indicating the behavioral relevance of visuocortical tuning during generalization learning.
Background
Generalization of conditioned-fear, a core feature of post-traumatic stress disorder (PTSD), has been the focus of several recent neuroimaging studies. A striking outcome of these studies is the frequency with which neural correlates of generalization fall within hubs of well-established functional networks including salience (SN), central executive (CEN), and default networks (DN). Neural substrates of generalization found to date may thus reflect traces of large-scale brain networks that form more expansive neural representations of generalization. The present study includes the first network-based analysis of generalization and PTSD-related abnormalities therein.
Methods
fMRI responses in established intrinsic connectivity networks (ICNs) representing SN, CEN, and DN were assessed during a generalized conditioned-fear task in male combat veterans ( N = 58) with wide-ranging PTSD symptom severity. The task included five rings of graded size. Extreme sizes served as conditioned danger-cues (CS+: paired with shock) and safety-cues (CS−), and the three intermediate sizes served as generalization stimuli (GSs) forming a continuum-of-size between CS+ and CS–. Generalization-gradients were assessed as behavioral and ICN response slopes from CS+, through GSs, to CS–. Increasing PTSD symptomatology was predicted to relate to less-steep slopes indicative of stronger generalization.
Results
SN, CEN, and DN responses fell along generalization-gradients with levels of generalization within and between SN and CEN scaling with PTSD symptom severity.
Conclusions
Neural substrates of generalized conditioned-fear include large-scale networks that adhere to the functional organization of the brain. Current findings implicate levels of generalization in SN and CEN as promising neural markers of PTSD.
Threat conditioning is a laboratory model of associative learning across species that is often used in research on the etiology and treatment of anxiety disorders. At least 10 different conditioned responses (CR) for quantifying learning in human threat conditioning are found in the literature. In this narrative review, we discuss these CR by considering the following questions: (1) Are the CR indicators of amygdala-dependent threat learning? (2) To what components of formal learning models do the CR relate? (3) How well can threat learning be inferred from the CR? Despite a vast literature, these questions can only be answered for some CR. Among the CR considered, heart period, startle eye-blink and Pavlovian-to-instrumental transfer are most clearly related to amygdala-dependent threat learning. Formal learning models have mostly been studied for skin conductance responses, which are likely to reflect threat prediction and its uncertainty. Startle eye-blink and pupil size appear to best differentiate CS+/CS−, although few direct comparisons between CR exist. We suggest future directions for improving the quantification of threat conditioning.
In this report, we illustrate the considerable impact of researcher degrees of freedom with respect to exclusion of participants in paradimgs with a learning element. We illustrate this empirically through case examples from human fear conditioning research where the exclusion of 'non-learners' and 'non-responders' is common - despite a lack of consensus on how to define these groups. We illustrate the substantial heterogeneity in exclusion criteria based on a systematic literature search and highlight potential problems and pitfalls of different definitions through case examples based on re-analyses of existing data sets. Based on this, we propose a consensus on evidence-based rather than idiosyncratic criteria including clear guidelines on reporting details. Taken together, we illustrate how flexibility in data collection and analysis can be avoided, which will benefit the robustness and replicability of research findings and can be expected to be applicable to other fields of research that involve a learning element.
Learning to predict threat from environmental cues is a fundamental skill in changing environments. This aversive learning process is exemplified by Pavlovian threat conditioning. Despite a plethora of studies on the neural mechanisms supporting the formation of associations between neutral and aversive events, our computational understanding of this process is fragmented. Importantly, different computational models give rise to different and partly opposing predictions for the trial-by-trial dynamics of learning, for example expressed in the activity of the autonomic nervous system (ANS). Here, we investigate human ANS responses to conditioned stimuli during Pavlovian fear conditioning. To obtain precise, trial-by-trial, single-subject estimates of ANS responses, we build on a statistical framework for psychophysiological modelling. We then consider previously proposed non-probabilistic models, a simple probabilistic model, and non-learning models, as well as different observation functions to link learning models with ANS activity. Across three experiments, and both for skin conductance (SCR) and pupil size responses (PSR), a probabilistic learning model best explains ANS responses. Notably, SCR and PSR reflect different quantities of the same model: SCR track a mixture of expected outcome and uncertainty, while PSR track expected outcome alone. In summary, by combining psychophysiological modelling with computational learning theory, we provide systematic evidence that the formation and maintenance of Pavlovian threat predictions in humans may rely on probabilistic inference and includes estimation of uncertainty. This could inform theories of neural implementation of aversive learning.
Prolonged physiological stress responses form an important risk factor for disease. According to neurobiological and evolution-theoretical insights the stress response is a default response that is always “on” but inhibited by the prefrontal cortex when safety is perceived. Based on these insights the Generalized Unsafety Theory of Stress (GUTS) states that prolonged stress responses are due to generalized and largely unconsciously perceived unsafety rather than stressors. This novel perspective necessitates a reconstruction of current stress theory, which we address in this paper. We discuss a variety of very common situations without stressors but with prolonged stress responses, that are not, or not likely to be caused by stressors, including loneliness, low social status, adult life after prenatal or early life adversity, lack of a natural environment, and less fit bodily states such as obesity or fatigue. We argue that in these situations the default stress response may be chronically disinhibited due to unconsciously perceived generalized unsafety. Also, in chronic stress situations such as work stress, the prolonged stress response may be mainly caused by perceived unsafety in stressor-free contexts. Thus, GUTS identifies and explains far more stress-related physiological activity that is responsible for disease and mortality than current stress theories.
The current experiment investigated whether overgeneralization of fear could be due to an inability to perceptually discriminate the initial fear-evoking stimulus from similar stimuli, as fear learning-induced perceptual impairments have been reported but their influence on generalization gradients remain to be elucidated. Three hundred and sixty-eight healthy volunteers participated in a differential fear conditioning paradigm with circles of different sizes as conditioned stimuli (CS), of which one was paired to an aversive IAPS picture. During generalization, each subject was presented with one of 10 different sized circles including the CSs, and were asked to categorize the stimulus as either a CS or as novel after fear responses were recorded. Linear mixed models were used to investigate differences in fear generalization gradients depending on the participant's perception of the test stimulus. We found that the incorrect perception of a novel stimulus as the initial fear-evoking stimulus strongly boosted fear responses. The current findings demonstrate that a significant number of novel stimuli used to assess generalization are incorrectly identified as the initial fear-evoking stimulus, providing a perceptual account for the observed overgeneralization in panic and anxiety disorders. Accordingly, enhancing perceptual processing may be a promising treatment for targeting excessive fear generalization.
Abstract The so-called ‘replicability crisis’ has sparked methodological discussions in many areas of science in general, and in psychology in particular. This has led to recent endeavours to promote the transparency, rigour, and ultimately, replicability of research. Originating from this zeitgeist, the challenge to discuss critical issues on terminology, design, methods, and analysis considerations in fear conditioning research is taken up by this work, which involved representatives from fourteen of the major human fear conditioning laboratories in Europe. This compendium is intended to provide a basis for the development of a common procedural and terminology framework for the field of human fear conditioning. Whenever possible, we give general recommendations. When this is not feasible, we provide evidence-based guidance for methodological decisions on study design, outcome measures, and analyses. Importantly, this work is also intended to raise awareness and initiate discussions on crucial questions with respect to data collection, processing, statistical analyses, the impact of subtle procedural changes, and data reporting specifically tailored to the research on fear conditioning.
Research in nonhuman animals reveals threat-sensitive generalization of defensive behavior that favors widespread generalization when threat intensity is high and limited generalization (i.e., specificity) when threat intensity is low. Here, we used Pavlovian fear conditioning to systematically investigate whether threat intensity widens behavioral generalization gradients to stimuli that decreasingly resemble a learned threat cue. Using a between-subjects design, volunteers underwent fear conditioning with a tone paired with either a high-intensity or low-intensity aversive stimulus prior to a test of fear generalization to novel tones. Results showed no effect of threat intensity on initial acquisition of conditioned fear. However, volunteers who underwent fear conditioning with a high-intensity aversive stimulus exhibited widespread generalization of autonomic arousal (skin conductance responses) as compared to volunteers who received a low-intensity aversive stimulus. These results show a transition from normal (selective) to overgeneralized fear as threat intensity increases, and have implications for understanding overgeneralization characteristic of trauma- and stress-related disorders. (PsycINFO Database Record
One of the frequent questions by users of the mixed model function lmer of the lme4 package has been: How can I get p values for the F and t tests for objects returned by lmer? The lmerTest package extends the 'lmerMod' class of the lme4 package, by overloading the anova and summary functions by providing p values for tests for fixed effects. We have implemented the Satterthwaite's method for approximating degrees of freedom for the t and F tests. We have also implemented the construction of Type I - III ANOVA tables. Furthermore, one may also obtain the summary as well as the anova table using the Kenward-Roger approximation for denominator degrees of freedom (based on the KRmodcomp function from the pbkrtest package). Some other convenient mixed model analysis tools such as a step method, that performs backward elimination of nonsignificant effects - both random and fixed, calculation of population means and multiple comparison tests together with plot facilities are provided by the package as well.
Background
Prior work examining emotional dysregulation observed in posttraumatic stress disorder (PTSD) has primarily been limited to fear-learning processes specific to anticipation, habituation, and extinction of threat. In contrast, the response to threat itself has not been systematically evaluated.
Objective
To explore potential disruption in fear conditioning neurocircuitry in service members with PTSD, specifically in response to predictable versus unpredictable threats.
Method
In the current study, active-duty U.S. Army soldiers with (PTSD group; n = 38) and without PTSD (deployment-exposed controls; DEC; n = 40), participated in a fear-conditioning study in which threat predictability was manipulated by presenting an aversive unconditioned stimulus (UCS) that was either preceded by a conditioned stimulus (i.e., predictable) or UCS alone (i.e., unpredictable). Threat expectation, skin conductance response (SCR), and functional magnetic resonance imaging (fMRI) signal to predictable and unpredictable threats (i.e., UCS) were assessed.
Results
Both groups showed greater threat expectancy and diminished threat-elicited SCRs to predictable compared to unpredictable threat. Significant group differences were observed within the amygdala, hippocampus, insula, and superior and middle temporal gyri. Contrary to our predictions, the PTSD group showed a diminished threat-related response within each of these brain regions during predictable compared to unpredictable threat, whereas the DEC group showed increased activation.
Conclusion
Although, the PTSD group showed greater threat-related diminution, hypersensitivity to unpredictable threat cannot be ruled out. Furthermore, pre-trauma, trait-like factors may have contributed to group differences in activation of the neurocircuitry underpinning fear conditioning.
Like many other primates, humans place a high premium on social information transmission and processing. One important aspect of this information concerns the emotional state of other individuals, conveyed by distinct visual cues such as facial expressions, overt actions, or by cues extracted from the situational context. A rich body of theoretical and empirical work has demonstrated that these socioemotional cues are processed by the human visual system in a prioritized fashion, in the service of optimizing social behavior. Furthermore, socioemotional perception is highly dependent on situational contexts and previous experience. Here, we review current issues in this area of research and discuss the utility of the steady-state visual evoked potential (ssVEP) technique for addressing key empirical questions. Methodological advantages and caveats are discussed with particular regard to quantifying time-varying competition among multiple perceptual objects, trial-by-trial analysis of visual cortical activation, functional connectivity, and the control of low-level stimulus features. Studies on facial expression and emotional scene processing are summarized, with an emphasis on viewing faces and other social cues in emotional contexts, or when competing with each other. Further, because the ssVEP technique can be readily accommodated to studying the viewing of complex scenes with multiple elements, it enables researchers to advance theoretical models of socioemotional perception, based on complex, quasinaturalistic viewing situations.
Fear is elicited by imminent threat and leads to phasic fear responses with selective attention, whereas anxiety is characterized by a sustained state of heightened vigilance due to uncertain danger. In the present study, we investigated attention mechanisms in fear and anxiety by adapting the NPU-threat test to measure steady-state visual evoked potentials (ssVEPs). We investigated ssVEPs across no aversive events (N), predictable aversive events (P), and unpredictable aversive events (U), signaled by four-object arrays (30s). In addition, central cues were presented during all conditions but predictably signaled imminent threat only during the P condition. Importantly, cues and context events were flickered at different frequencies (15Hz vs. 20Hz) in order to disentangle respective electrocortical responses. The onset of the context elicited larger electrocortical responses for U compared to P context. Conversely, P cues elicited larger electrocortical responses compared to N cues. Interestingly, during the presence of the P cue, visuocortical processing of the concurrent context was also enhanced. The results support the notion of enhanced initial hypervigilance to unpredictable compared to predictable threat contexts, while predictable cues show electrocortical enhancement of the cues themselves but additionally a boost of context processing.
The effects of stress are frequently studied, yet its proximal causes remain unclear. Here we demonstrate that subjective estimates of uncertainty predict the dynamics of subjective and physiological stress responses. Subjects learned a probabilistic mapping between visual stimuli and electric shocks. Salivary cortisol confirmed that our stressor elicited changes in endocrine activity. Using a hierarchical Bayesian learning model, we quantified the relationship between the different forms of subjective task uncertainty and acute stress responses. Subjective stress, pupil diameter and skin conductance all tracked the evolution of irreducible uncertainty. We observed a coupling between emotional and somatic state, with subjective and physiological tuning to uncertainty tightly correlated. Furthermore, the uncertainty tuning of subjective and physiological stress predicted individual task performance, consistent with an adaptive role for stress in learning under uncertain threat. Our finding that stress responses are tuned to environmental uncertainty provides new insight into their generation and likely adaptive function.
The current review and synthesis serves to define and contextualize fear of the unknown relative to related constructs, such as intolerance of uncertainty, and contemporary models of emotion, attachment, and neuroticism. The contemporary models appear to share a common core in underscoring the importance of responses to unknowns. A recent surge in published research has explored the transdiagnostic impact of not knowing on anxiety and related pathologies; as such, there appears to be mounting evidence for fear of the unknown as an important core transdiagnostic construct. The result is a robust foundation for transdiagnostic theoretical and empirical explorations into fearing the unknown and intolerance of uncertainty.
Extinction of Pavlovian conditioned fear in humans is a popular paradigm often used to study learning and memory processes that mediate anxiety-related disorders. Fear extinction studies often only pair the conditioned stimulus (CS) and unconditioned stimulus (UCS) on a subset of acquisition trials (i.e., partial reinforcement/pairing) to prolong extinction (i.e., partial reinforcement extinction effect; PREE) and provide more time to study the process. However, there is limited evidence that the partial pairing procedures typically used during fear conditioning actually extend the extinction process, while there is strong evidence these procedures weaken conditioned response (CR) acquisition. Therefore, determining conditioning procedures that support strong CR acquisition and that also prolong the extinction process would benefit the field. The present study investigated 4 separate CS-UCS pairing procedures to determine methods that support strong conditioning and that also exhibit a PREE. One group (C-C) of participants received continuous CS-UCS pairings; a second group (C-P) received continuous followed by partial CS-UCS pairings; a third group (P-C) received partial followed by continuous CS-UCS pairings; and a fourth group (P-P) received partial CS-UCS pairings during acquisition. A strong skin conductance CR was expressed by C-C and P-C groups but not by C-P and P-P groups at the end of the acquisition phase. The P-C group maintained the CR during extinction. In contrast, the CR extinguished quickly within the C-C group. These findings suggest that partial followed by continuous CS-UCS pairings elicit strong CRs and prolong the extinction process following human fear conditioning. (PsycINFO Database Record
Fear conditioning is an established model for investigating posttraumatic stress disorder (PTSD). However, symptom triggers may vaguely resemble the initial traumatic event, differing on a variety of sensory and affective dimensions. We extended the fear-conditioning model to assess generalization of conditioned fear on fear processing neurocircuitry in PTSD. Military veterans (n=67) consisting of PTSD (n=32) and trauma-exposed comparison (n=35) groups underwent functional magnetic resonance imaging during fear conditioning to a low fear-expressing face while a neutral face was explicitly unreinforced. Stimuli that varied along a neutral-to-fearful continuum were presented before conditioning to assess baseline responses, and after conditioning to assess experience-dependent changes in neural activity. Compared with trauma-exposed controls, PTSD patients exhibited greater post-study memory distortion of the fear-conditioned stimulus toward the stimulus expressing the highest fear intensity. PTSD patients exhibited biased neural activation toward high-intensity stimuli in fusiform gyrus (P<0.02), insula (P<0.001), primary visual cortex (P<0.05), locus coeruleus (P<0.04), thalamus (P<0.01), and at the trend level in inferior frontal gyrus (P=0.07). All regions except fusiform were moderated by childhood trauma. Amygdala–calcarine (P=0.01) and amygdala–thalamus (P=0.06) functional connectivity selectively increased in PTSD patients for high-intensity stimuli after conditioning. In contrast, amygdala–ventromedial prefrontal cortex (P=0.04) connectivity selectively increased in trauma-exposed controls compared with PTSD patients for low-intensity stimuli after conditioning, representing safety learning. In summary, fear generalization in PTSD is biased toward stimuli with higher emotional intensity than the original conditioned-fear stimulus. Functional brain differences provide a putative neurobiological model for fear generalization whereby PTSD symptoms are triggered by threat cues that merely resemble the index trauma.
The responses of sensory cortical neurons are shaped by experience. As a result perceptual biases evolve, selectively facilitating the detection and identification of sensory events that are relevant for adaptive behaviour. Here we examine the involvement of human visual cortex in the formation of learned perceptual biases. We use classical aversive conditioning to associate one out of a series of oriented gratings with a noxious sound stimulus. After as few as two grating-sound pairings, visual cortical responses to the sound-paired grating show selective amplification. Furthermore, as learning progresses, responses to the orientations with greatest similarity to the sound-paired grating are increasingly suppressed, suggesting inhibitory interactions between orientation-selective neuronal populations. Changes in cortical connectivity between occipital and fronto-temporal regions mirror the changes in visuo-cortical response amplitudes. These findings suggest that short-term behaviourally driven retuning of human visual cortical neurons involves distal top-down projections as well as local inhibitory interactions.
Individuals with high-trait anxiety frequently report decreased perceived control. However, it is unclear how these processes are instantiated at a neural level. Prior research suggests that individuals prone to anxiety may have exaggerated activity in the anterior insula and altered activity in the cingulate cortex during anticipation of aversive events. Thus, we hypothesized that anxiety proneness influences anterior insula activation during anticipation of unpredictable threat through decreased perceived control. Forty physically healthy adults underwent neuroimaging while they explored computer-simulated contexts associated either with or without the threat of an unpredictable shock. Skin conductance, anxiety ratings and blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging were used to assess responses to threat versus no threat. Perceived control was measured using the Anxiety Control Questionnaire-Revised. Mediation analysis examined how anxiety proneness influenced BOLD activity. Anticipation of unpredictable threat resulted in increased skin conductance responses, anxiety ratings and enhanced activation in bilateral insula, anterior midcingulate cortex (aMCC) and bed nucleus of the stria terminalis. Individuals with greater anxiety proneness and less perceived control showed greater activity in dorsal anterior insula (dAI). Perceived control mediated the relationship between anxiety proneness and dAI activity. Increased dAI activity was associated with increased activity in aMCC, which correlated with increased exploratory behavior. Results provide evidence that exaggerated insula activation during the threat of unpredictable shock is directly related to low perceived control in anxiety-prone individuals. Perceived control thus may constitute an important treatment target to modulate insula activity during anxious anticipation in anxiety-disordered individuals.
Periodic visual stimulation and analysis of the resulting steady-state visual evoked potentials were first introduced over 80 years ago as a means to study visual sensation and perception. From the first single-channel recording of responses to modulated light to the present use of sophisticated digital displays composed of complex visual stimuli and high-density recording arrays, steady-state methods have been applied in a broad range of scientific and applied settings.The purpose of this article is to describe the fundamental stimulation paradigms for steady-state visual evoked potentials and to illustrate these principles through research findings across a range of applications in vision science.
A case is made for the use of hierarchical models in the analysis of generalization gradients. Hierarchical models overcome several restrictions that are imposed by repeated measures analysis-of-variance (rANOVA), the default statistical method in current generalization research. More specifically, hierarchical models allow to include continuous independent variables and overcomes problematic assumptions such as sphericity. We focus on how generalization research can benefit from this added flexibility. In a simulation study we demonstrate the dominance of hierarchical models over rANOVA. In addition, we show the lack of efficiency of the Mauchly's sphericity test in sample sizes typical for generalization research, and confirm how violations of sphericity increase the probability of type I errors. A worked example of a hierarchical model is provided, with a specific emphasis on the interpretation of parameters relevant for generalization research.
The popular paradigm of Pavlovian conditioned fear has been used to study learning and memory processes that mediate anxiety disorder. Fear extinction studies have often paired the conditioned stimulus (CS) and the unconditioned stimulus (US) on a subset of acquisition trials (partial reinforcement) to prolong extinction. However, there have been few studies on the effect of partial reinforcement and continuous reinforcement on fear generalization. To better understand the influence of the CS–US pairing rate on fear generalization, the experimenters used CSs paired with US at 50% (CS50), 75% (CS75), and 100% (CS100) during fear conditioning. A total of 66 participants, who were assigned at random to the different reinforcement rates, underwent fear acquisition and generalization tests on expectancy ratings and skin conductance responses. The continuous reinforcement group (CS100) showed a flatter generalization gradient, while the partial reinforcement groups (CS50, CS75) showed increased generalization magnitudes. These results suggest that the partial reinforcement extinction effect is related to threat intensity, whereas continuous reinforcement produces threat-sensitivity fear generalization, which has been used to explain the overgeneralization of fear.
Processing capabilities for many low-level visual features are experientially malleable, aiding sighted organisms in adapting to dynamic environments. Explicit instructions to attend a specific visual field location influence retinotopic visuocortical activity, amplifying responses to stimuli appearing at cued spatial positions. It remains undetermined both how such prioritization affects surrounding non-prioritized locations, and if a given retinotopic spatial position can attain enhanced cortical representation through experience rather than instruction.The current report examined visuocortical response changes as human observers (N=51, 19 male) learned, through differential classical conditioning, to associate specific screen locations with aversive outcomes. Using dense-array EEG and pupillometry, we tested the pre-registered hypotheses of either sharpening or generalization around an aversively associated location following a single conditioning session. Competing hypotheses tested if mean response changes would take the form of a gaussian (generalization) or difference-of-gaussian (sharpening) distribution over spatial positions, peaking at the viewing location paired with a noxious noise. Occipital 15 Hz steady-state visual evoked potential (ssVEP) responses were selectively heightened when viewing aversively paired locations and displayed a non-linear, difference-of-gaussian profile across neighboring locations, consistent with suppressive surround modulation of non-prioritized positions. Measures of alpha band (8 - 12 Hz) activity were differentially altered in anterior versus posterior locations, while pupil diameter exhibited selectively heightened responses to noise-paired locations but did not evince differences across the non-paired locations. These results indicate that visuocortical spatial representations are sharpened in response to location-specific aversive conditioning, while top-down influences indexed by alpha power reduction exhibit posterior generalization and anterior sharpening.SIGNIFICANCE STATEMENTIt is increasingly recognized that early visual cortex is not a static processor of physical features, but is instead constantly shaped by perceptual experience. It remains unclear, however, to what extent the cortical representation of many fundamental features, including visual field location, is malleable by experience. Using EEG and an aversive classical conditioning paradigm, we observed sharpening of visuocortical responses to stimuli appearing at aversively associated locations along with location-selective facilitation of response systems indexed by pupil diameter and EEG alpha power. These findings highlight the experience-dependent flexibility of retinotopic spatial representations in visual cortex, opening avenues towards novel treatment targets in disorders of attention and spatial cognition.
The amount of fear evoked by potential threats is oftentimes proportional to the overlap in shared features with known threats. An adaptive learning system should therefore extract relevant features from threat stimuli to successfully detect other novel threats in the environment. But what if the most relevant feature of a threat stimulus is emotionally positive? Here, we used Pavlovian fear conditioning to ask whether people extract positive emotional features of a fear conditioned stimulus (CS) to selectively generalize to other stimuli that contain positive features. In a between subjects design, we first paired a picture of a face expressing either a slight amount of happiness or fear with an electrical shock to the wrist. We then tested fear generalization to modified face stimuli of the same identity expressing more or less happiness or fear. Both groups exhibited biased physiological arousal (a peak shift) to a face stimulus with the most exaggerated emotional expression, regardless of valence. Fear generalization diminished to unreinforced happy faces over the course of testing, whereas arousal was maintained to unreinforced fearful faces throughout testing. Finally, subjects fear conditioned to a slightly happy face were accurate at retrospectively identifying the correct CS, whereas subjects fear conditioned to a fearful face retrospectively misidentified a more fearful face as the threat CS. These findings suggest that positive emotional features extracted from a known threat can guide biased fear generalization, but that generalization is maintained by a dimension of increasing fear which also produces retrospective biases in threat intensity estimation.
Intolerance of uncertainty (IU) is a transdiagnostic risk factor for internalizing disorders. Prior work has found that IU may be associated with either increased reactivity to threat or, alternatively, with decreased differential responding between threat and nonthreat/safety cues (i.e., threat generalization). For example, work by Morriss, Macdonald, & van Reekum (2016) found that higher IU was associated with increased threat generalization during acquisition (using skin conductance response (SCR)), as well as less differentiation between acquisition and extinction (using subjective uneasiness ratings). Here, three labs attempted direct and conceptual replications of Morriss, Macdonald, et al. (2016). Results showed that the direct replication failed, despite being conducted at the same lab site as the original study; moreover, in contrast to Morriss, Macdonald, et al. (2016), the direct replication found that higher IU was associated with greater SCR discrimination between threat and safety cues (across acquisition and extinction), as well as greater differences in uneasiness ratings between acquisition and extinction. Nonetheless, in the conceptual replications, higher IU was associated with greater threat generalization, as well as less discrimination between acquisition and extinction, as measured using SCR. Higher IU was also associated with larger late positive potentials to threat versus safety cues during extinction-results that mirror those observed by Morriss, Macdonald, et al. (2016) using SCR. Results are discussed with regards to the challenge involved in defining a successful replication attempt, the benefits of collaborative replication and the use and reliability of multiple measures.
Every day we are bombarded by stimuli that must be assessed for their potential for harm or benefit. Once a stimulus is learned to predict harm, it can elicit fear responses. Such learning can last a lifetime but is not always beneficial for an organism. For an organism to thrive in its environment, it must know when to engage in defensive, avoidance behaviors and when to engage in non-defensive, approach behaviors. Fear should be suppressed in situations that are not dangerous: when a novel, innocuous stimulus resembles a feared stimulus, when a feared stimulus no longer predicts harm, or when there is an option to avoid harm. A cardinal feature of anxiety disorders is the inability to suppress fear adaptively. In PTSD, for instance, learned fear is expressed inappropriately in safe situations and is resistant to extinction. In this review, we discuss mechanisms of suppressing fear responses during stimulus discrimination, fear extinction, and active avoidance, focusing on the well-studied tripartite circuit consisting of the amygdala, medial prefrontal cortex and hippocampus.
Fear generalization, while adaptive, can be detrimental when occurring in excess. To this end a perceptual discrimination training task was created with a goal of decreasing fear overgeneralization. The current study tested the effectiveness of the training task among typically-developing children.
Participants (n = 73) were randomly assigned into a training, placebo or no task group. Following a differential fear-conditioning task, participants in the first two groups underwent the discrimination training or placebo task. An assessment task was then administered. Finally, all participants completed a fear generalization test, consisting of 11 morphs ranging in perceptual similarity from the threat cue to the safety cue. Physiological and self-report measures were collected.
Fear-conditioning was achieved in both physiological and self-report measures. Further, in the assessment task, the training group showed better perceptual discrimination than did the placebo group. Last, the training group exhibited less overgeneralization of affective stimuli as indicated by a physiological measure than did the two control conditions.
Findings suggest that the perceptual discrimination training task effectively moderated fear overgeneralization in children. This adds to previous evidence of the task's effectiveness among adults.
Threat expectancy is the ability to predict an aversive outcome. What is not known is the influence of initial threat responding on the acquisition of verbal, attentional and perceptual biases towards conditioned threat cues. This study evaluated the extent to which initial unconditioned stimulus (UCS) responding was related to trial-by-trial self-reported expectancy, sensory processing (visuocortical EEG) and orienting (heart rate deceleration) to threat cues during extinction learning. Participants (n = 38) viewed oriented Gabor gratings, associated with the presence (CS+) or absence (CS-) of a 96 dB white noise (UCS), flickering at 12 Hz to elicit steady state visually evoked potentials (ssVEPs). Multivariate multiple regression revealed greater initial UCS skin conductance responding to predict extinction responding: enhanced visuocortical discrimination, greater heart rate deceleration to CS+, and greater threat expectancy endorsements. These results suggest that the motivational intensity of initial threat reactivity (sympathetic UCS responding) drives learning-induced defensive dispositions across multiple response systems.
Experimental research has shown that generalization of fear extinction from a generalization stimulus (GS) is minimal compared to generalization of fear extinction from the conditional stimulus itself (CS+). This poses a challenge to extinction-based treatments of anxiety because the exact CS is often not known or unavailable. However, experimental studies failed to disentangle differences in stimulus identity (CS + or GS) from differences in the level of fear (GS typically elicits less fear than CS+). Here, we test the hypothesis that a high level of fear is key to extinction learning and generalization, rather than the identity of the stimulus under extinction (CS + or GS). For that purpose, we took advantage of the peak-shift phenomenon that describes the conditions under which a GS can elicit equal or higher levels of responding, compared to the CS+. Hence, we compared the generalizability of fear extinction following exposure to the CS + itself, to a 'weak' GS that elicits less fear, and to a 'peak' GS that elicits as much fear as the CS+. First, the results replicated, with a new set of stimuli, the observation that extinction of a skin conductance response and US-expectancy generalizes only weakly from a weak GS to CS+. Second, extinction generalized strongly from a peak GS towards CS+, as hypothesized. Third, extinction with the peak GS even outperformed extinction with the CS+, as it generalized more strongly across the generalization gradient. Together, these results support exposure treatment strategies that focus on the fear-eliciting potential of stimuli (often described as a fear hierarchy), rather than their learning history. We propose that stimulus typicality and/or intensity may explain the enhanced effects of a 'peak' GS over the CS+ in enhancing the generalization of fear extinction.
Fear generalisation refers to the spread of conditioned fear to stimuli similar but distinct from the original conditioned stimulus. In this study, participants were presented with repeated pairings of a conditioned stimulus with a shock, in either a single-cue or differential conditioning paradigm. Generalisation of fear was then tested by presenting stimuli that were novel, but similar to the conditioned stimulus along a spatial stimulus dimension. Dependent measures were online shock expectancy ratings and skin conductance level. A diverse range of generalisation gradients was observed, and the shape of the gradients for both expectancy ratings and skin conductance responses corresponded with participants' verbally reported rules. The findings point to an important role for cognitively controlled processes in human fear generalisation, and provide support for a single-system learning model. They also highlight the potential importance of cognitive reappraisal in clinical treatments for over-generalised fear.
Objective:
Heightened generalization of fear from an aversively reinforced conditioned stimulus (CS+, a conditioned danger cue) to resembling stimuli is widely accepted as a pathogenic marker of posttraumatic stress disorder (PTSD). Indeed, a distress response to benign stimuli that "resemble" aspects of the trauma is a central feature of the disorder. To date, the link between overgeneralization of conditioned fear and PTSD derives largely from clinical observations, with limited empirical work on the subject. This represents the first effort to examine behavioral and brain indices of generalized conditioned fear in PTSD using systematic methods developed in animals known as generalization gradients: the gradual decline in conditioned responding as the presented stimulus gradually differentiates from CS+.
Method:
Gradients of conditioned fear generalization were assessed using functional MRI and behavioral measures in U.S. combat veterans who served in Iraq or Afghanistan and had PTSD (N=26), subthreshold PTSD (N=19), or no PTSD (referred to as trauma control subjects) (N=17). Presented stimuli included rings of graded size, with extreme sizes serving as CS+ (paired with shock) and as a nonreinforced conditioned stimulus (CS-, a conditioned safety cue), and with intermediate sizes forming a continuum of similarity between CS+ and CS-. Generalization gradients were assessed as response slopes from CS+, through intermediate ring sizes, to CS-, with less steep slopes indicative of stronger generalization.
Results:
Relative to trauma control subjects, PTSD patients showed stronger conditioned generalization, as evidenced by less steep generalization gradients in both behavioral risk ratings and brain responses in the left and right anterior insula, left ventral hippocampus, dorsolateral and dorsomedial prefrontal cortex, and caudate nucleus. Severity of PTSD symptoms across the three study groups was positively correlated with levels of generalization at two such loci: the right anterior insula and left ventral hippocampus.
Conclusions:
The results point to evidence of brain-based markers of overgeneralized fear conditioning related to PTSD. These findings provide further understanding of a central yet understudied symptom of trauma-related psychopathology.
Although overgeneralization seems to be a hallmark of several anxiety disorders, this until now has not been investigated in social anxiety disorder (SAD). Therefore, we examined fear generalization in 26 SAD patients and 29 healthy controls (HC) using two faces as conditioned stimuli (CS+, CS−), and a loud scream and a fearful face as unconditioned stimulus (US). Generalization was tested by presenting both CS and four morphs of the two faces (generalization stimuli [GSs]), while ratings, heart rate (HR) and skin conductance responses (SCR) were recorded. Results revealed that SAD patients rated all stimuli as less pleasant and more arousing compared to HC. Moreover, ratings and SCR indicated that both groups generalized their acquired fear from the CS+ to GSs. Remarkably, only SAD patients showed generalization in HR responses (fear bradycardia). Overall, SAD seems not to be characterized by strong overgeneralization but discrepancies in fear responses to both conditioned and generalized threat stimuli.
Organisms tend to respond similarly to stimuli that are perceptually close to an event that predicts adversity, a phenomenon known as fear generalization. Greater dissimilarity yields weaker behavioral responses, forming a fear-tuning profile. The perceptual model of fear generalization assumes that behavioral fear tuning results from perceptual similarities, suggesting that brain responses should also exhibit the same fear-tuning profile. Using fMRI and a circular fear-generalization procedure, we tested this prediction. In contrast with the perceptual model, insula responses showed less generalization than behavioral responses and encoded the aversive quality of the conditioned stimulus, as shown by high pattern similarity between the conditioned stimulus and the shock. Also inconsistent with the perceptual model, object-sensitive visual areas responded to ambiguity-related outcome uncertainty. Together these results indicate that fear generalization is not passively driven by perception, but is an active process integrating threat identification and ambiguity-based uncertainty to orchestrate a flexible, adaptive fear response.
The catechol-O-methyltransferase (COMT) val158met single nucleotide polymorphism (SNP) alters metabolic activity of the COMT enzyme regulating catecholamines, with the Val (valine) allele resulting in 40% greater enzymatic activity than the Met (methionine) allele. Previous research has identified systematic inter-individual differences in cognitive and behavioral phenotypes related to this polymorphism, often attributed to the fact that extracellular dopamine in the prefrontal cortex is strongly affected by the COMT enzyme. The neurophysiological mechanisms mediating these inter-individual differences in specific brain systems and task contexts remain to be established however. In the current study, we examined the extent to which physio-mechanistic differences by COMT genotype affect somato-visceral and visual cortical responses to learned threat cues. Classical aversive differential conditioning was implemented using rapidly phase-reversing grating stimuli, previously shown to engage retinotopic visual cortex. Differential response patterns in sensory and autonomic systems were elicited by pairing one grating (CS+, conditioned stimulus), but not the other (CS-), with a noxious stimulus. Dense-array electroencephalography and somato-visceral measures of defensive reactivity were recorded in addition to self-report data. Individuals of the Val/Val genotype, compared to Met allele carriers, reliably showed greater initial enhancement in their visuocortical response to the CS+, accompanied by stronger defensive engagement, indexed by heart rate acceleration and startle potentiation. The finding that COMT polymorphism status affects threat cue reactivity at the visuocortical level is consistent with the notion that sensory processing of threat is facilitated by strong re-entrant bias signals from anterior areas, including the prefrontal cortex.
The partial reinforcement extinction effect (PREE) was analyzed in humans using a quasi-multiple schedule of reinforcement with two discrete trial tasks. The first task was a videogame analog of a shuttle box. Using a joystick, subjects were required to move a cue in one of four directions for reinforcement. The second was a simple concept-formation task consisting of two binary dimensions; responding to one of the four alternatives was reinforced. All subjects were trained on the two tasks on a randomly alternating basis. Two groups were trained on the tasks using either continuous or partial reinforcement schedules for both tasks. An additional two groups received both schedules of reinforcement with continuous reinforcement on one task and partial reinforcement on the other task. Groups exposed to only a single schedule of reinforcement displayed a conventional PREE, with the group receiving only partial reinforcement showing a greater resistance to extinction than the group receiving only continuous reinforcement. In contrast, subjects exposed to both schedules of reinforcement during acquisition did not evidence a conventional PREE; rather their behavior was equally persistent on both tasks and schedules. The data are compared with results of nonhuman within-subjects experiments that indicate a transfer of persistence effects across schedules. Finally, the status of the PREE, as an empirical generalization, is reviewed.
Enhanced fear responses to cues, which were not associated with the threat but share perceptual characteristics with the threat signal, indicate generalization of conditioned fear. Here, we investigated for the first time generalization processes in contextual fear conditioning. Thirty-two participants were guided through two virtual offices (acquisition phases). Mildly painful electric shocks (unconditioned stimulus, US) were unpredictably delivered in one office (anxiety context, CTX +), but never in the other office (safety context, CTX-). During the generalization test, participants were guided through CTX +, CTX-, and the generalization context (G-CTX), which contained features of both the CTX + and the CTX-, but no US was delivered. We found successful contextual fear conditioning (i.e., the CTX + compared to the CTX- elicited potentiated startle responses and was rated with more negative valence, higher arousal and higher anxiety). Importantly, implicit and explicit responses dissociated in the generalization test. Thus, participants rated the G-CTX as more arousing and anxiogenic than the CTX- indicating anxiety generalization, but they showed enhanced startle responses to the CTX + only, while the G-CTX and the CTX- did not differ. In summary, healthy participants on an explicit level responded to the generalization context like to the anxiety context, but on an implicit level responded to the generalization context like to the safety context. Possibly, this dissociation suggests distinct and specific generalization processes underlying contextual fear.
Abnormal fear conditioning processes (including fear acquisition and conditioned fear-generalization) have been implicated in the pathogenesis of anxiety disorders. Previous research has shown that individuals with panic disorder present enhanced conditioned fear-generalization in comparison to healthy controls. Enhanced conditioned fear-generalization could also characterize generalized anxiety disorder (GAD), but research so far is inconclusive. An important confounding factor in previous research is comorbidity. The present study examined conditioned fear-acquisition and fear-generalization in 28 patients with GAD and 30 healthy controls using a recently developed fear acquisition and generalization paradigm assessing fear-potentiated startle and online expectancies of the unconditioned stimulus. Analyses focused on GAD patients without comorbidity but included also patients with comorbid anxiety disorders. Patients and controls did not differ as regards fear acquisition. However, contrary to our hypothesis, both groups did not differ either in most indexes of conditioned fear-generalization. Moreover, dimensional measures of GAD symptoms were not correlated with conditioned fear-generalization indexes. Comorbidity did not have a significant impact on the results. Our data suggest that conditioned fear-generalization is not enhanced in GAD. Results are discussed with special attention to the possible effects of comorbidity on fear learning abnormalities.
Fear generalization is a key process in the development and maintenance of anxiety disorders. Psychobiological investigations of fear generalization have predominately focused on defensive system activation (e.g., startle reflex), and it is unclear whether aberrant attentional processing contributes to fear generalization. The late positive potential (LPP) is an event-related potential component that indexes sustained attention and elaborative processing of motivationally-salient information, and is larger in response to arousing compared to non-arousing stimuli. In the present study 48 participants completed a fear generalization paradigm using electric shocks. The LPP and retrospective risk ratings of shock likelihood were measured in response to the conditioned stimulus (CS +) and multiple generalization stimuli (GS) that varied in perceptual similarity to the CS +. In addition, intolerance of uncertainty (IU) was examined in relation to fear generalization. The LPP was enhanced for the CS + relative to the GS, but the GS did not differ from one another. Thus, overall the LPP did not reflect fear generalization. However, the LPP to the GS differed as a function of IU, such that high Prospective IU was associated with an attenuated LPP to the GS and this was independent of trait anxiety. Risk ratings tracked fear generalization irrespective of IU. We discuss the potential influence of IU and attentional processing on fear generalization. Overall, the present study supports the LPP as a useful tool for examining individual differences in fear generalization.
Social organisms fundamentally rely on experience to successfully navigate in a social world by associating social stimuli with aversive versus safe qualities. Cognitive neuroscience research has shown that visual cues reliably paired with danger are processed more efficiently than neutral cues, and that such facilitated sensory processing extends to low levels of the visual system. The present study aimed at determining the extent to which visual cortical engagement elicited by a face stimulus with learned affective value is modulated by relatively subtle facial features such as gaze direction and emotional expression. To this end, electro-cortical processing of direct-gaze compared to averted-gaze faces serving as CS+ cues was investigated in a differential fear conditioning paradigm. Furthermore it was investigated whether gaze shift interacted with angry facial expressions to confer greater immunity to extinction of learned associations. Behavioral ratings and visually evoked steady-state potentials (ssVEP) were recorded in healthy human participants. As expected, direct-gaze CS+ compared to averted-gaze CS- cues elicited larger ssVEP amplitudes during conditioning, whereas this differentiation was not observed when averted-gaze faces were paired with the aversive US. Importantly, a more fine-grained analysis examining trial-by-trial changes in visual cortical activation across the learning phases revealed that this effect was not necessarily due to a lack of learning per se, but mainly due to a delayed build-up of cortical amplification for the averted-gaze CS+ cues. This suggests that the temporal dynamics of cortical engagement with aversively conditioned faces vary as a function of the cue with gaze direction as an important modulator of the speed of the acquisition of the aversive response.