Can I see it in the eyes? An investigation of freezing-like motion patterns in response to avoidable threat.

Freezing is one of the most extensively studied defensive behaviors in rodents. Both reduced body and gaze movements during anticipation of threat also occur in humans and have been discussed as translational indicators of freezing but their relationship remains unclear. We thus set out to elucidate body and eye movements and concomitant autonomic dynamics in anticipation of avoidable threat. Specifically, 50 participants viewed naturalistic pictures that were preceded by a colored fixation cross, signaling them whether to expect an inevitable (shock), no (safety), or a potential shock (flight) that could be avoided by a quick button press. Body sway, eye movements, the heart rate and skin conductance were recorded. We replicated previously described reductions in body sway, gaze dispersion, and the heart rate, and a skin conductance increase in flight trials. Stronger reductions in gaze but not in body sway predicted faster motor reactions on a trial-wise basis, highlighting their functional role in action preparation. We failed to find a trait-like relationship between body and gaze movements across participants, but their temporal profiles were positively related within individuals, suggesting that both metrics partly reflect the same construct. However, future research is desirable to assess these response patterns in naturalistic environments. A more ethological examination of different movement dynamics upon threat would not only warrant better comparability between rodent and human research but also help determine whether and how eye-tracking could be implemented as a proxy for fear-related movements in restricted brain imaging environments.

Aversive contexts enhance defensive responses to conditioned threat.

The ability to flexibly transition between defensive states is crucial for adaptive responding in life-threatening situations. Potentially threatening situations typically induce a sustained feeling of apprehension in association with hypervigilance, while acute threat is usually characterized by an intense and transient response to cope with the imminent danger. While potential and acute threat states have traditionally been viewed as mutually exclusive, this distinction is being challenged by a growing body of evidence suggesting a more complex interplay during simultaneous activation of these states. However, the interaction between potential and acute threat on a psychophysiological level remains elusive. To fill this gap, 94 healthy individuals participated in one of two contextual fear-conditioning paradigms. In both paradigms, a differential fear-learning phase was conducted, followed by a test phase in which the conditioned stimuli were presented in front of either conditioned or inherently aversive contextual images compared to neutral contexts. To capture defensive responses, we recorded subjective (threat and expectancy ratings) and physiological (electrodermal and cardiovascular) activity to the conditioned stimuli as a function of contextual threat. Besides indices of successful fear conditioning, our results revealed stronger threat and unconditioned stimulus expectancy ratings, cardiac deceleration, and skin conductance responses for threat and safety cues presented in inherently aversive compared to neutral contexts. Conditioned contexts had less impact on physiological responses to threat and safety cues than inherently aversive contexts. These findings provide new insights into the additive nature of defensive responses to fear cues and situations of contextual threat.

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

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

Centralized gaze as an adaptive component of defensive states in humans.

Adequate defensive responding is crucial for mental health but scientifically not well understood. Specifically, it seems difficult to dissociate defense and approach states based on autonomic response patterns. We thus explored the robustness and threat-specificity of recently described oculomotor dynamics upon threat in anticipation of either threatening or rewarding stimuli in humans. While visually exploring naturalistic images, participants (50 per experiment) expected an inevitable, no, or avoidable shock (Experiment 1) or a guaranteed, no, or achievable reward (Experiment 2) that could be averted or gained by a quick behavioural response. We observed reduced heart rate (bradycardia), increased skin conductance, pupil dilation and globally centralized gaze when shocks were inevitable but, more pronouncedly, when they were avoidable. Reward trials were not associated with globally narrowed visual exploration, but autonomic responses resembled characteristics of the threat condition. While bradycardia and concomitant sympathetic activation reflect not only threat-related but also action-preparatory states independent of valence, global centralization of gaze seems a robust phenomenon during the anticipation of avoidable threat. Thus, instead of relying on single readouts, translational research in animals and humans should consider the multi-dimensionality of states in aversive and rewarding contexts, especially when investigating ambivalent, conflicting situations.

Fear conditioning and stimulus generalization in association with age in children and adolescents.

The aim of the study was to investigate age-related differences in fear learning and generalization in healthy children and adolescents (n = 133), aged 8-17 years, using an aversive discriminative fear conditioning and generalization paradigm adapted from Lau et al. (2008). In the current task, participants underwent 24 trials of discriminative conditioning of two female faces with neutral facial expressions, with (CS+) or without (CS-) a 95-dB loud female scream, presented simultaneously with a fearful facial expression (US). The discriminative conditioning was followed by 72 generalization trials (12 CS+, 12 GS1, 12 GS2, 12 GS3, 12 GS4, and 12 CS-): four generalization stimuli depicting gradual morphs from CS+ to CS- in 20%-steps were created for the generalization phases. We hypothesized that generalization in children and adolescents is negatively correlated with age. The subjective ratings of valence, arousal, and US expectancy (the probability of an aversive noise following each stimulus), as well as skin conductance responses (SCRs) were measured. Repeated-measures ANOVAs on ratings and SCR amplitudes were calculated with the within-subject factors stimulus type (CS+, CS-, GS1-4) and phase (Pre-Acquisition, Acquisition 1, Acquisition 2, Generalization 1, Generalization 2). To analyze the modulatory role of age, we additionally calculated ANCOVAs considering age as covariate. Results indicated that (1) subjective and physiological responses were generally lower with increasing age irrespective to the stimulus quality, and (2) stimulus discrimination improved with increasing age paralleled by reduced overgeneralization in older individuals. Longitudinal follow-up studies are required to analyze fear generalization with regard to brain maturational aspects and clarify whether overgeneralization of conditioned fear promotes the development of anxiety disorders or vice versa.

Idiosyncratic viewing patterns of social scenes reflect individual preferences.

In general, humans preferentially look at conspecifics in naturalistic images. However, such group-based effects might conceal systematic individual differences concerning the preference for social information. Here, we investigated to what degree fixations on social features occur consistently within observers and whether this preference generalizes to other measures of social prioritization in the laboratory as well as the real world. Participants carried out a free viewing task, a relevance taps task that required them to actively select image regions that are crucial for understanding a given scene, and they were asked to freely take photographs outside the laboratory that were later classified regarding their social content. We observed stable individual differences in the fixation and active selection of human heads and faces that were correlated across tasks and partly predicted the social content of self-taken photographs. Such relationship was not observed for human bodies indicating that different social elements need to be dissociated. These findings suggest that idiosyncrasies in the visual exploration and interpretation of social features exist and predict real-world behavior. Future studies should further characterize these preferences and elucidate how they shape perception and interpretation of social contexts in healthy participants and patients with mental disorders that affect social functioning.

Reality in a sphere: A direct comparison of social attention in the laboratory and the real world.

Humans often show reduced social attention in real situations, a finding rarely replicated in controlled laboratory studies. Virtual reality is supposed to allow for ecologically valid and at the same time highly controlled experiments. This study aimed to provide initial insights into the reliability and validity of using spherical videos viewed via a head-mounted display (HMD) to assess social attention. We chose five public places in the city of Würzburg and measured eye movements of 44 participants for 30 s at each location twice: Once in a real environment with mobile eye-tracking glasses and once in a virtual environment playing a spherical video of the location in an HMD with an integrated eye tracker. As hypothesized, participants demonstrated reduced social attention with less exploration of passengers in the real environment as compared to the virtual one. This is in line with earlier studies showing social avoidance in interactive situations. Furthermore, we only observed consistent gaze proportions on passengers across locations in virtual environments. These findings highlight that the potential for social interactions and an adherence to social norms are essential modulators of viewing behavior in social situations and cannot be easily simulated in laboratory contexts. However, spherical videos might be helpful for supplementing the range of methods in social cognition research and other fields. Data and analysis scripts are available at https://osf.io/hktdu/ .

Search for the Unknown: Guidance of Visual Search in the Absence of an Active Template.

Can you efficiently look for something even without knowing what it looks like? According to theories of visual search, the answer is no: A template of the search target must be maintained in an active state to guide search for potential locations of the target. Here, we tested the need for an active template by assessing a case in which this template is improbable: the search for a familiar face among unfamiliar ones when the identity of the target face is unknown. Because people are familiar with hundreds of faces, an active guiding template seems unlikely in this case. Nevertheless, participants (35 Israelis and 33 Germans) were able to guide their search as long as extrafoveal processing of the target features was possible. These results challenge current theories of visual search by showing that guidance can rely on long-term memory and extrafoveal processing rather than on an active search template.

Visuo-tactile congruency influences the body schema during full body ownership illusion.

Previous research showed that full body ownership illusions in virtual reality (VR) can be robustly induced by providing congruent visual stimulation, and that congruent tactile experiences provide a dispensable extension to an already established phenomenon. Here we show that visuo-tactile congruency indeed does not add to already high measures for body ownership on explicit measures, but does modulate movement behavior when walking in the laboratory. Specifically, participants who took ownership over a more corpulent virtual body with intact visuo-tactile congruency increased safety distances towards the laboratory's walls compared to participants who experienced the same illusion with deteriorated visuo-tactile congruency. This effect is in line with the body schema more readily adapting to a more corpulent body after receiving congruent tactile information. We conclude that the action-oriented, unconscious body schema relies more heavily on tactile information compared to more explicit aspects of body ownership.

Investigating overt and covert shifts of attention within social naturalistic scenes.

Eye-tracking studies on social attention have consistently shown that humans prefer to attend to other human beings. Much less is known about whether a similar preference is also evident in covert attentional processes. To enable a direct comparison, this study examined covert and overt attentional guidance within two different experimental setups using complex naturalistic scenes instead of isolated single features. In the first experiment, a modified version of the dot-probe paradigm served as a measure of covert reflexive attention toward briefly presented scenes containing a social feature in one half of the visual field compared to nonsocial elements in the other while controlling for low-level visual saliency. Participants showed a stable congruency effect with faster reaction times and fewer errors for probes presented on the social side of the scene. In a second experiment, we tracked eye movements for the same set of stimuli while manipulating the presentation time to allow for differentiating reflexive and more sustained aspects of overt attention. Supportive of the first results, analyses revealed a robust preference for social features concerning initial saccade direction as well as fixation allocation. Collectively, these experiments imply preferential processing of social features over visually salient aspects for automatic allocation of covert as well as overt attention.

Brain Responses during the Anticipation of Dyspnea.

Dyspnea is common in many cardiorespiratory diseases. Already the anticipation of this aversive symptom elicits fear in many patients resulting in unfavorable health behaviors such as activity avoidance and sedentary lifestyle. This study investigated brain mechanisms underlying these anticipatory processes. We induced dyspnea using resistive-load breathing in healthy subjects during functional magnetic resonance imaging. Blocks of severe and mild dyspnea alternated, each preceded by anticipation periods. Severe dyspnea activated a network of sensorimotor, cerebellar, and limbic areas. The left insular, parietal opercular, and cerebellar cortices showed increased activation already during dyspnea anticipation. Left insular and parietal opercular cortex showed increased connectivity with right insular and anterior cingulate cortex when severe dyspnea was anticipated, while the cerebellum showed increased connectivity with the amygdala. Notably, insular activation during dyspnea perception was positively correlated with midbrain activation during anticipation. Moreover, anticipatory fear was positively correlated with anticipatory activation in right insular and anterior cingulate cortex. The results demonstrate that dyspnea anticipation activates brain areas involved in dyspnea perception. The involvement of emotion-related areas such as insula, anterior cingulate cortex, and amygdala during dyspnea anticipation most likely reflects anticipatory fear and might underlie the development of unfavorable health behaviors in patients suffering from dyspnea.

Memory detection using fMRI - does the encoding context matter?

Recent research revealed that the presentation of crime related details during the Concealed Information Test (CIT) reliably activates a network of bilateral inferior frontal, right medial frontal and right temporal-parietal brain regions. However, the ecological validity of these findings as well as the influence of the encoding context are still unclear. To tackle these questions, three different groups of subjects participated in the current study. Two groups of guilty subjects encoded critical details either only by planning (guilty intention group) or by really enacting (guilty action group) a complex, realistic mock crime. In addition, a group of informed innocent subjects encoded half of the relevant details in a neutral context. Univariate analyses showed robust activation differences between known relevant compared to neutral details in the previously identified ventral frontal-parietal network with no differences between experimental groups. Moreover, validity estimates for average changes in neural activity were similar between groups when focusing on the known details and did not differ substantially from the validity of electrodermal recordings. Additional multivariate analyses provided evidence for differential patterns of activity in the ventral fronto-parietal network between the guilty action and the informed innocent group and yielded higher validity coefficients for the detection of crime related knowledge when relying on whole brain data. Together, these findings demonstrate that an fMRI-based CIT enables the accurate detection of concealed crime related memories, largely independent of encoding context. On the one hand, this indicates that even persons who planned a (mock) crime could be validly identified as having specific crime related knowledge. On the other hand, innocents with such knowledge have a high risk of failing the test, at least when considering univariate changes of neural activation.

Manipulating item proportion and deception reveals crucial dissociation between behavioral, autonomic, and neural indices of concealed information.

Developed as an alternative to traditional deception detection methods, the concealed information test (CIT) assesses recognition of critical (e.g., crime-relevant) "probes." Most often, recognition has been measured as enhanced skin conductance responses (SCRs) to probes compared to irrelevant foils (CIT effect). More recently, also differentially enlarged reaction times (RTs) and increased neural activity in the bilateral inferior frontal gyrus, the right middle frontal gyrus, and the right temporo-parietal junction have been observed. The aims of the current functional magnetic resonance imaging (fMRI) study were to (1) investigate the boundary conditions of the CIT effects in all three measures and thereby (2) gain more insight into the relative contribution of two mechanisms underlying enhanced responding to concealed information (i.e., orienting versus response inhibition). Therefore, we manipulated the proportion of probe versus irrelevant items, and whether suspects were instructed to actively deny recognition of probe knowledge (i.e., deceive) during the test. Results revealed that whereas overt deception was not necessary for the SCR CIT effect, it was crucial for the RT and the fMRI-based CIT effects. The proportion manipulation enhanced the CIT effect in all three measures. The results indicate that different mental processes might underlie the response pattern in the CIT. While skin conductance responding to concealed information may best be explained by orienting theory, it seems that response inhibition drives RT and blood oxygen level dependent responding to concealed information.

Sex differences in conditioned stimulus discrimination during context-dependent fear learning and its retrieval in humans: the role of biological sex, contraceptives and menstrual cycle phases.

BACKGROUND: Anxiety disorders are more prevalent in women than in men. Despite this sexual dimorphism, most experimental studies are conducted in male participants and studies focusing on sex differences are sparse. In addition, the role of hormonal contraceptives and menstrual cycle phase in fear conditioning and extinction processes remain largely unknown. METHODS: We investigated sex differences in context-dependent fear acquisition and extinction (day 1) and their retrieval/expression (day 2). Skin conductance responses (SCRs), fear and unconditioned stimulus expectancy ratings were obtained. RESULTS: We included 377 individuals (261 women) in our study. Robust sex differences were observed in all dependent measures. Women generally displayed higher subjective ratings but smaller SCRs than men and showed reduced excitatory/inhibitory conditioned stimulus (CS+/CS-) discrimination in all dependent measures. Furthermore, women using hormonal contraceptives showed reduced SCR CS discrimination on day 2 than men and free-cycling women, while menstrual cycle phase had no effect. LIMITATIONS: Possible limitations include the simultaneous testing of up to 4 participants in cubicles, which might have introduced a social component, and not assessing postexperimental contingency awareness. CONCLUSION: The response pattern in women shows striking similarity to previously reported sex differences in patients with anxiety. Our results suggest that pronounced deficits in associative discrimination learning and subjective expression of safety information (CS- responses) might underlie higher prevalence and higher symptom rates seen in women with anxiety disorders. The data call for consideration of biological sex and hormonal contraceptive use in future studies and may suggest that targeting inhibitory learning during therapy might aid precision medicine.

Menstrual-cycle dependent fluctuations in ovarian hormones affect emotional memory.

The hormones progesterone and estradiol modulate neural plasticity in the hippocampus, the amygdala and the prefrontal cortex. These structures are involved in the superior memory for emotionally arousing information (EEM effects). Therefore, fluctuations in hormonal levels across the menstrual cycle are expected to influence activity in these areas as well as behavioral memory performance for emotionally arousing events. To test this hypothesis, naturally cycling women underwent functional magnetic resonance imaging during the encoding of emotional and neutral stimuli in the low-hormone early follicular and the high-hormone luteal phase. Their memory was tested after an interval of 48 h, because emotional arousal primarily enhances the consolidation of new memories. Whereas overall recognition accuracy remained stable across cycle phases, recognition quality varied with menstrual cycle phases. Particularly recollection-based recognition memory for negative items tended to decrease from early follicular to luteal phase. EEM effects for both valences were associated with higher activity in the right anterior hippocampus during early follicular compared to luteal phase. Valence-specific modulations were found in the anterior cingulate, the amygdala and the posterior hippocampus. Current findings connect to anxiolytic actions of estradiol and progesterone as well as to studies on fear conditioning. Moreover, they are in line with differential networks involved in EEM effects for positive and negative items.

Emotional effects on time-to-contact judgments: arousal, threat, and fear of spiders modulate the effect of pictorial content.

Recently, responses to looming visual stimuli have been shown to depend on the emotional content of the stimulus. A threatening stimulus is judged to arrive sooner compared to a neutral stimulus, possibly buying the organism time to prepare defensive actions. Here, we explored the underlying mechanism. We found that time-to-contact judgments of threatening pictures did not differ from those of highly arousing pleasant pictures (Experiment 1), suggesting that arousal, not fear, modulates the perception of looming. Specific fear modulated the effects of arousal (Experiment 2): Spider-fearful participants' judgments showed a threat advantage effect, while non-fearful participants' judgments were less affected by emotional content. In Experiment 3, arrival times were less overestimated when pictures induced arousal. However, this effect interacted with the valence of the stimulus: For unpleasant stimuli, arousal induced shorter time-to-contact judgments, whereas for pleasant stimuli, an inverted U-shaped relation was found. We propose a general content effect to explain the overestimation with neutral pictures: Pictorial content may draw visual attention to inner contours instead of to the outer edges of the picture. This could delay time-to-contact judgments according to the known size-arrival effect. Our results add to the growing literature examining affective influences on visual perception.

Detecting deception with artificial intelligence: promises and perils.

Rapid advancements in artificial intelligence (AI) have driven interest in its potential application for lie detection. Unfortunately, the current approaches have primarily focused on technical aspects at the expense of a solid methodological and theoretical foundation. We discuss the implications thereof and offer recommendations for the development and regulation of AI-based deception detection.

The ventromedial prefrontal cortex in response to threat omission is associated with subsequent explicit safety memory.

In order to memorize and discriminate threatening and safe stimuli, the processing of the actual absence of threat seems crucial. Here, we measured brain activity with fMRI in response to both threat conditioned stimuli and their outcomes by combining threat learning with a subsequent memory paradigm. Participants (N = 38) repeatedly saw a variety of faces, half of which (CS+) were associated with an aversive unconditioned stimulus (US) and half of which were not (CS-). When an association was later remembered, the hippocampus had been more active (than when forgotten). However, the ventromedial prefrontal cortex predicted subsequent memory specifically during safe associations (CS- and US omission responses) and the left dorsolateral prefrontal cortex during outcomes in general (US and US omissions). In exploratory analyses of the theoretically important US omission, we found extended involvement of the medial prefrontal cortex and an enhanced functional connectivity to visual and somatosensory cortices, suggesting a possible function in sustaining sensory information for an integration with semantic memory. Activity in visual and somatosensory cortices together with the inferior frontal gyrus also predicted memory performance one week after learning. The findings imply the importance of a close interplay between prefrontal and sensory areas during the processing of safe outcomes-or 'nothing'-to establish declarative safety memory.

Impaired flexible reward learning in ADHD patients is associated with blunted reinforcement sensitivity and neural signals in ventral striatum and parietal cortex.

Reward-based learning and decision-making are prime candidates to understand symptoms of attention deficit hyperactivity disorder (ADHD). However, only limited evidence is available regarding the neurocomputational underpinnings of the alterations seen in ADHD. This concerns flexible behavioral adaption in dynamically changing environments, which is challenging for individuals with ADHD. One previous study points to elevated choice switching in adolescent ADHD, which was accompanied by disrupted learning signals in medial prefrontal cortex. Here, we investigated young adults with ADHD (n = 17) as compared to age- and sex-matched controls (n = 17) using a probabilistic reversal learning experiment during functional magnetic resonance imaging (fMRI). The task requires continuous learning to guide flexible behavioral adaptation to changing reward contingencies. To disentangle the neurocomputational underpinnings of the behavioral data, we used reinforcement learning (RL) models, which informed the analysis of fMRI data. ADHD patients performed worse than controls particularly in trials before reversals, i.e., when reward contingencies were stable. This pattern resulted from 'noisy' choice switching regardless of previous feedback. RL modelling showed decreased reinforcement sensitivity and enhanced learning rates for negative feedback in ADHD patients. At the neural level, this was reflected in a diminished representation of choice probability in the left posterior parietal cortex in ADHD. Moreover, modelling showed a marginal reduction of learning about the unchosen option, which was paralleled by a marginal reduction in learning signals incorporating the unchosen option in the left ventral striatum. Taken together, we show that impaired flexible behavior in ADHD is due to excessive choice switching ('hyper-flexibility'), which can be detrimental or beneficial depending on the learning environment. Computationally, this resulted from blunted sensitivity to reinforcement of which we detected neural correlates in the attention-control network, specifically in the parietal cortex. These neurocomputational findings remain preliminary due to the relatively small sample size.

Heart rate variability, interoceptive accuracy and functional connectivity in middle-aged and older patients with depression.

BACKGROUND AND OBJECTIVE: Major depressive disorder (MDD) is associated with increased cardiac morbidity. Reduced heart rate variability (HRV) as well as lower interoceptive accuracy (IAc) have been observed in MDD as possible sympathomimetic mechanisms related to insula activity. The salience network (SN) anchored by the insula has been posited as a crucial functional network for cardiac sensations and the default mode network (DMN) for MDD. This study aimed to investigate the relation between insula-centered and depression-related brain networks, IAc and HRV in patients with depression as a possible mechanism by which MDD increases cardiac morbidity. METHODS: 30 depressed inpatients and 30 healthy subjects (derived from the population-based "Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression" cohort study, STAAB) all over 50 years were examined. HRV and IAc were assessed via electrocardiogram and a heartbeat perception task prior to a 3 T resting-state functional magnetic resonance imaging. Seed-to-voxel resting-state functional connectivity (FC) analysis was conducted with six seeds in the insula and two seeds in the DMN. RESULTS: Depressed patients on the one hand showed decreased FC between insula cortex and frontal as well occipital cortical brain regions compared to controls. Depressed patients on the other hand exhibited higher FC between the medial prefrontal cortex and the insula cortex compared to controls. However, depressed patients did not differ in HRV nor in IAc compared to controls. CONCLUSION: Thus, differences in insula-related brain networks in depression in our study were not mirrored by differences in HRV and IAc. Future research is needed to define the mechanism by which depression increases cardiac morbidity.