Anticipation Of Threat Research Articles

Neurochemically distinct populations of the bed nucleus of stria terminalis modulate innate fear response to weak threat evoked by predator odor stimuli

Anxiety and trauma-related disorders are characterized by significant alterations in threat detection, resulting in inadequate fear responses evoked by weak threats or safety stimuli. Recent research pointed out the important role of the bed nucleus of stria terminalis (BNST) in threat anticipation and fear modulation under ambiguous threats, hence, exaggerated fear may be traced back to altered BNST function. To test this hypothesis, we chemogenetically inhibited specific BNST neuronal populations (corticotropin-releasing hormone - BNSTCRH and somatostatin - BNSTSST expressing neurons) in a predator odor-evoked innate fear paradigm. The rationale for this paradigm was threefold: (1) predatory cues are particularly strong danger signals for all vertebrate species evoking defensive responses on the flight-avoidance-freezing dimension (conservative mechanisms), (2) predator odor can be presented in a scalable manner (from weak to strong), and (3) higher-order processing of olfactory information including predatory odor stimuli is integrated by the BNST. Accordingly, we exposed adult male mice to low and high predatory threats presented by means of cat urine, or low- and high-dose of 2-methyl-2-thiazoline (2MT), a synthetic derivate of a fox anogenital product, which evoked low and high fear response, respectively. Then, we tested the impact of chemogenetic inhibition of BNSTCRH and BNSTSST neurons on innate fear responses using crh- and sst-ires-cre mouse lines. We observed that BNSTSST inhibition was effective only under low threat conditions, resulting in reduced avoidance and increased exploration of the odor source. In contrast, BNSTCRH inhibition had no impact on 2MT-evoked responses, but enhanced fear responses to cat odor, representing an even weaker threat stimulus. These findings support the notion that BNST is recruited by uncertain or remote, potential threats, and CRH and SST neurons orchestrate innate fear responses in complementary ways.

Attenuated beta-adrenergic response to stress and increased anticipation and perception of social threat in women high on perceived criticism

A large amount of literature has demonstrated that Perceived Criticism (PC)—that is, how critical a person believes a given relative is of him or her—is associated with negative clinical outcomes in a broad range of psychiatric disorders (e.g., relapse or recurrence of symptoms). A possible mechanism behind the predictive value of PC might be its association with the stress regulation process. This is the first study to investigate differences in the psychophysiological response to a social stress task in young women (mean age = 21.66, SD = 4.33) with high (n = 40) and low (n = 39) PC. The physiological response was investigated by measuring two markers of sympathetic activity mediated by acetylcholine (skin conductance levels; SCL) and adrenaline (pre-ejection period; PEP) levels, respectively, and one marker of the vagally-mediated parasympathetic system (heart rate variability; HRV). Moreover, we investigated the anticipation and perception of social threat, in the form of criticism, during the stressor. No differences in HRV and SCL were observed. However, individuals high in PC mobilized fewer cardiovascular resources to deal with the stressor, reflected in an attenuated beta-adrenergic response (i.e., lower PEP response). Women high in PC also expected and perceived more criticism during the stress task. Together, our results indicate that women high in PC make heightened social threat anticipation and interpretations, and they tend to engage in less active coping when exposed to socially evaluated stressful events. Our findings indicate that PC is associated with underlying stress-related psychobiological vulnerabilities that may contribute to its association with negative clinical outcomes.

Human defensive freezing: Associations with hair cortisol and trait anxiety

The anticipation of threat facilitates innate defensive behaviours including freezing reactions. Freezing in humans is characterised by reductions in body sway and heart rate. Limited evidence suggests that individual differences in freezing reactions are associated with predictors of anxiety-related psychopathology including trait anxiety and hypothalamic-pituitary-adrenal (HPA) axis activity. However, previous human studies focused on acutely circulating cortisol levels, leaving the link between freezing and more stable, individual trait markers of HPA axis activity unclear. We investigated whether individual differences in anticipatory freezing reactions are predicted by accumulated hair cortisol concentrations (HCC) and trait anxiety, in a well-powered mixed sample of police recruits at the start of the police training, and age, sex and education matched controls (total N = 419, mean age = 24, Nwomen = 106, Npolice recruits = 337). Freezing-related reactions were assessed with posturographic and heart rate measurements during an active shooting task under threat of shock. The anticipation of threat of shock elicited the expected reductions in body sway and heart rate, indicative of human freezing. Individual differences in threat-related reductions in body sway, but not heart rate, were related to lower HCC and higher trait anxiety. The observed links between postural freezing and predictors of anxiety-related psychopathology suggest the potential value of defensive freezing as a somatic marker for individual differences in stress-vulnerability and resilience. Data availabilityThe datasets analysed during the current study are available from the corresponding authors upon reasonable request.

A Compassion-Focused Ecological Momentary Intervention for Enhancing Resilience in Help-Seeking Youth: Uncontrolled Pilot Study.

BackgroundDigital interventions offer new avenues for low-threshold prevention and treatment in young people. Ecological momentary interventions (EMIs) represent a powerful approach that allows for adaptive, real-time, and real-world delivery of intervention components in daily life by real-time processing of ecological momentary assessment (EMA) data. Compassion-focused interventions (CFIs) may be particularly amenable to translation into an EMI to strengthen emotional resilience and modify putative risk mechanisms, such as stress sensitivity, in the daily lives of young help-seeking individuals.ObjectiveThis study aims to investigate the feasibility, safety, and initial therapeutic effects of a novel, accessible, transdiagnostic, ecological momentary CFI for improving emotional resilience to stress (EMIcompass).MethodsIn this uncontrolled pilot study, help-seeking youth with psychotic, depressive, or anxiety symptoms were offered the EMIcompass intervention in addition to treatment as usual. The EMIcompass intervention consisted of a 3-week EMI (including enhancing, consolidating, and EMA-informed interactive tasks) administered through a mobile health app and three face-to-face sessions with a trained psychologist intended to provide guidance and training on the CFI exercises presented in the app (ie, training session, follow-up booster session, and review session).ResultsIn total, 10 individuals (mean age 20.3 years, SD 3.8; range 14-25) were included in the study. Most (8/10, 80%) participants were satisfied and reported a low burden of app usage. No adverse events were observed. In approximately one-third of all EMAs, individuals scored high on stress, negative affect, or threat anticipation during the intervention period, resulting in real-time, interactive delivery of the CFI intervention components in addition to weekly enhancing and daily consolidating tasks. Although the findings should be interpreted with caution because of the small sample size, reduced stress sensitivity, momentary negative affect, and psychotic experiences, along with increased positive affect, were found at postintervention and the 4-week follow-up. Furthermore, reductions in psychotic, anxiety, and depressive symptoms were found (r=0.30-0.65).ConclusionsOur findings provide evidence on the feasibility and safety of the EMIcompass intervention for help-seeking youth and lend initial support to beneficial effects on stress sensitivity and mental health outcomes. An exploratory randomized controlled trial is warranted to establish the feasibility and preliminary evidence of its efficacy.

BNST and amygdala connectivity are altered during threat anticipation in schizophrenia

In schizophrenia, impairments in affect are prominent and anxiety disorders are prevalent. Neuroimaging studies of fear and anxiety in schizophrenia have focused on the amygdala and show alterations in connectivity. Emerging evidence suggests that the bed nucleus of the stria terminalis (BNST) also plays a critical role in anxiety, especially during anticipation of an unpredictable threat; however, previous studies have not examined the BNST in schizophrenia. In the present study, we examined BNST function and connectivity in people with schizophrenia (n = 31; n = 15 with comorbid anxiety) and controls (n = 15) during anticipation of unpredictable and predictable threat. A secondary analysis tested for differences in activation and connectivity of the central nucleus of the amygdala (CeA), which has also been implicated in threat anticipation. Analyses tested for group differences in both activation and connectivity during anticipation of unpredictable threat and predictable threat (p < .05). Relative to controls, individuals with schizophrenia showed stronger BNST-middle temporal gyrus (MTG) connectivity during unpredictable threat anticipation and stronger BNST-MTG and BNST-dorsolateral prefrontal connectivity during predictable threat anticipation. Comparing subgroups of individuals with schizophrenia and a comorbid anxiety disorder (SZ+ANX) to those without an anxiety disorder (SZ-ANX) revealed broader patterns of altered connectivity. During unpredictable threat anticipation, the SZ+ANX group had stronger BNST connectivity with regions of the salience network (insula, dorsal anterior cingulate cortex). During predictable threat anticipation, the SZ+ANX group had stronger BNST connectivity with regions associated with fear processing (insula, extended amygdala, prefrontal cortex). A secondary CeA analysis revealed a different pattern; the SZ+ANX group had weaker CeA connectivity across multiple brain regions during threat anticipation compared to the SZ-ANX group. These findings provide novel evidence for altered functional connectivity during threat anticipation in schizophrenia, especially in individuals with comorbid anxiety.

Aberrant anterior cingulate processing of anticipated threat as a mechanism for psychosis

Stress and abnormal stress response are associated with schizophrenia spectrum disorder (SSD), but the brain mechanisms linking stress to symptomatology remain unclear. In this study, we used a stress-based functional neuroimaging task, reverse-translated from preclinical studies, to test the hypothesis that abnormal corticolimbic processing of stressful threat anticipation is associated with psychosis and affective symptoms in SSD. Participants underwent an MRI-compatible ankle-shock task (AST) in which the threat of mild electrical shock was anticipated. We compared functional brain activations during anticipatory threat periods from N = 18 participants with SSD (10 M/8F) to those from N = 12 community controls (9 M/3F). After family-wise error correction, only one region, the ventral anterior cingulate cortex (vACC), showed significantly reduced activation compared with controls. vACC activation significantly correlated with clinical symptoms measured by the Brief Psychiatric Rating Scale total score (r = 0.54) and the psychosis subscale (r = 0.71), and inversely correlated with trait depression measured by the Maryland Trait and State Depression scale (r=-0.48). Deficient activation in vACC under stress of anticipated threat may lead to aberrant interpretation of such threat, contributing to psychosis and mood symptoms in SSD. This experimental paradigm has translational potential and may identify circuitry-level mechanisms of stress-related mental illness, leading to more targeted treatment.

Temporal Dynamics of Anticipatory Physiological Responding in Pediatric Anxiety Disorders

Anxiety disorders feature excessive fear responding in anticipation of threat, indexed by increased psychophysiological response in anxious vs. healthy individuals during evoked threat-anticipatory states. The temporal dynamics of threat-anticipatory responding are unspecified; these could elucidate psychobiological mechanisms mediating excessive fears in anxiety. We examine whether anticipatory psychophysiological differentially covaries with threat imminence in pediatric anxiety.

Anticipated Threat fMRI Stress Task Reveals Dysfunctional Ventral Anterior Cingulate Activation Associated With Psychosis and Depression Symptom Burden

Stress and abnormal stress response are associated with many psychiatric illnesses including schizophrenia spectrum disorder (SSD), but the brain mechanisms linking stress to psychiatric disorders remain unclear. We used a stress-based functional neuroimaging task, reverse-translated from preclinical studies of stress, to test the hypothesis that abnormal limbic processing of stressful threat anticipation is associated with psychosis and affective symptoms in patients with SSD.

Altered Anxiety Neural Circuit in Combat Veterans With PTSD

Post-traumatic stress disorder (PTSD) affects more than 30% of Veterans returning from modern wars. Unfortunately, PTSD is often resistant to current treatments, such as SSRIs and exposure therapy, that target fear neurocircuitry. One possible explanation is that the neurobiology of PTSD extends beyond fear neurocircuitry and includes alterations in neural circuits that underlie anxiety. In this study, we investigated the bed nucleus of the stria terminalis (BNST), a brain region implicated in the anxiety, hypervigilance and threat anticipation response that is characteristic of PTSD.

Tactile P300 to unpredictable electric shocks: Association with anxiety symptoms, intolerance of uncertainty, and neuroticism

The no, predictable, and unpredictable threat (NPU-threat) task is an experimental paradigm that delineates the anticipation of predictable vs. unpredictable threat. The current literature suggests that heightened defensive motivation in anticipation of unpredictable threat is associated with anxiety disorders and increased symptoms. Few investigations have examined whether a heightened response to actual threat is also associated with anxiety-related phenomenology. The present study examined the relationship between the tactile P300 to shock delivery during the NPU-threat task and individual differences in anxiety symptoms, intolerance of uncertainty, and neuroticism. Overall, the tactile P300 was enhanced in response to unpredictable shocks relative to predictable shocks. Greater tactile P300 enhancement to unpredictable shocks was associated with greater anxiety symptoms, intolerance of uncertainty, and neuroticism. The present study suggests that temporal unpredictability enhances attentional engagement to threat, which is greater in individuals characterized by narrow and broad anxiety constructs.

Threat-anticipatory psychophysiological response is enhanced in youth with anxiety disorders and correlates with prefrontal cortex neuroanatomy.

BackgroundThreat anticipation engages neural circuitry that has evolved to promote defensive behaviours; perturbations in this circuitry could generate excessive threat-anticipation response, a key characteristic of pathological anxiety. Research into such mechanisms in youth faces ethical and practical limitations. Here, we use thermal stimulation to elicit pain-anticipatory psychophysiological response and map its correlates to brain structure among youth with anxiety and healthy youth.MethodsYouth with anxiety (n = 25) and healthy youth (n = 25) completed an instructed threat-anticipation task in which cues predicted nonpainful or painful thermal stimulation; we indexed psychophysiological response during the anticipation and experience of pain using skin conductance response. High-resolution brain-structure imaging data collected in another visit were available for 41 participants. Analyses tested whether the 2 groups differed in their psychophysiological cue-based pain-anticipatory and pain-experience responses. Analyses then mapped psychophysiological response magnitude to brain structure.ResultsYouth with anxiety showed enhanced psychophysiological response specifically during anticipation of painful stimulation (b = 0.52, p = 0.003). Across the sample, the magnitude of psychophysiological anticipatory response correlated negatively with the thickness of the dorsolateral prefrontal cortex (pFWE < 0.05); psychophysiological response to the thermal stimulation correlated positively with the thickness of the posterior insula (pFWE < 0.05).LimitationsLimitations included the modest sample size and the cross-sectional design.ConclusionThese findings show that threat-anticipatory psychophysiological response differentiates youth with anxiety from healthy youth, and they link brain structure to psychophysiological response during pain anticipation and experience. A focus on threat anticipation in research on anxiety could delineate relevant neural circuitry.

Adaptive function and correlates of anxiety during a pandemic

Background and objectivesMost studies to date have focused on the negative aspects of anxiety. Anxiety, however, is an evolved emotional response that can provide protection in the face of risk. Pandemics are characterized by increased mortality risk coupled with future uncertainties, which both cause heightened anxiety. Here, we examine the factors associated with anxiety levels and risk avoidance behaviours during the first wave of the COVID-19 pandemic. We asked how individual time perspectives (future-oriented consideration and attention to present moment experience) affect anxiety in uncertain times, and whether anxiety reduces mortality risk by promoting risk avoidance behaviour.MethodologyWe conducted an online survey in the UK (N = 1088) and Turkey (N = 3935) and measured participants’ generalized and pandemic-related anxiety levels, future-oriented consideration, mindfulness, intolerance of uncertainty, risk perception and risk avoidance behaviours.ResultsWe found that people less tolerant of uncertainties had higher levels of pandemic anxiety. Those with higher pandemic anxiety exhibited risk avoidance behaviours more frequently. Mindfulness and increased financial satisfaction reduced pandemic anxiety. People in Turkey reported higher levels of generalized and pandemic anxiety and greater engagement in risk avoidance behaviours than people in the UK.Conclusions and implicationsOur study shows an elevated anxiety response can help mitigate infection risk during pandemics and emphasizes the importance of the underlying situation in understanding whether an anxiety response is adaptive or pathological. Maintaining a healthy level of anxiety can promote engagement in protective behaviours. Therapies addressing anxiety can focus on increasing tolerance to future uncertainties.Lay summaryAnxiety is an emotional response triggered in the anticipation of a possible threat. We found that intolerance of uncertainty strongly predicted anxiety and that people with elevated anxiety levels engaged in protective behaviours more frequently during the COVID-19 pandemic, suggesting that anxiety can help mitigate mortality risk.

Anticipated Attack Slows Responses in a Cued Virtual Attack Emotional Sternberg Task.

Threatening stimuli have varying effects, including reaction time (RT) increase in working memory tasks. This could reflect disruption of working memory or, alternatively, a reversible state of freezing. In the current series of experiments, reversible slowing due to anticipated threat was studied using the cued Virtual Attack Emotional Sternberg Task (cVAEST). In this task visually neutral cues indicate whether a future virtual attack could or could not occur during the maintenance period of a Sternberg task. Three studies (N = 47, 40, and 40, respectively) were performed by healthy adult participants online. The primary hypothesis was that the cVAEST would evoke anticipatory slowing. Further, the studies aimed to explore details of this novel task, in particular the interval between the cue and probe stimuli and the memory set size. In all studies it was found that threat anticipation slowed RTs on the working memory task. Further, Study 1 (memory set size 3) showed a decrease in RT when the attack occurred over all Cue Stimulus Intervals (CSIs). In Study 2 a minimal memory set of one item was used, under which circumstances RTs following attacks were only faster shortly after cue presentation (CSI 200 and 500 ms), when RTs were high for both threat and safe cues. Study 3 replicated results of Study 2 with more fine-grained time intervals. The results confirm that anticipation of attack stimuli can reversibly slow responses on an independent working memory task. The cVAEST may provide a useful method to study such threat-induced response slowing.

Human capital neurodiversity: an examination of stereotype threat anticipation

PurposeThe purpose of the study was to test the assumption of similarities between neurodivergents and other minority groups regarding their reaction to stereotype threat. In addition, it aimed to identify the source of stereotype threat and the neurodivergent's response to it.Design/methodology/approachTwo studies were conducted. Study 1 employed three exercises consisting of brochures, learning sets and posters to test organisational cues, notions of intelligence and situational cues. It collected data from 53 participants to establish whether stereotype threat observed in visible difference such as race, gender and intelligence is equally relevant to neurodiversity. Study 2 consisted of interviews with 44 participants to establish stereotype threat source, reaction and effect on declaration of invisible difference.FindingsNeurodivergents, defined by their invisible difference, react similarly to those with a visible difference with respect to organisational cues and stereotype threat. They will cognisantly define their behaviours depending upon those cues and stereotype threat. In doing so, they draw upon previous personal and work experiences. After the event, they will make a comparison to their assessment. If it is similar to their assessment, it reinforces it; however, if it is dissimilar, the neurodivergent will make an adjustment to the assessment. In both cases, the experience will form part of a future threat assessment.Research limitations/implicationsThe research is limited by its interpretivist nature and sample comprising personnel within a UK government organisation.Practical implicationsThe research has practical implications for employers, providing managers with a model to understand the impact a neurodivergents' previous experiences can have on their ability to interact within the workplace. Such understanding can provide insight into how best to utilise human capital.Originality/valueThis study makes a contribution to theory by expanding knowledge of neurodiversity in the workplace and by identifying the neurodivergents' reaction to the anticipation of a stereotype threat. In addition, it offers the stereotype threat anticipation conceptual model as a representation of the cognitive decisions made by neurodivergents to conceal or reveal their invisible difference.

Self-Reported Fears by Hospice Patients at the End of Life

Fear is a common emotion that involves the intense anticipation of threat to a person. At end of life, this fear is often conceptualized as existential distress, which suggests a connection to spirituality. Processing impending death is essential to end-of-life closure and acceptance. Existing evidence suggests that spirituality is associated with greater coping, better psychosocial well-being, and dignified dying; however, the relationship between fear and spirituality at end of life, as well as the specific fears experienced, are not known. The purpose of this study was to explore the relationship between fear and spirituality in patients upon hospice admission. In this retrospective study, admission records from 154 hospice patients were reviewed. Hospice admission data from the psychosocial and spiritual assessments were analyzed using descriptive statistics, inferential statistics, and logistic regression. The average patient age was 81 years of age. A slight majority (51.3%) of patients admitted to fears upon hospice admission. Patients reported a range of one to six fears, with the most common fear being “pain and/or suffering.” Forty-seven percent of the patients identified as being “spiritually active.” Correlation analysis revealed no statistically significant relationship between fear and spiritually. Logistic regression analysis revealed some significant relationships between age and certain fears. Fear is a common symptom at the end of life, and appropriate emotional and psychological support should be provided to mitigate the fears. This study suggests that fears may be different for older adults.

Psychophysiological correlates of anxious apprehension: Trait worry is associated with startle response to threat

Worry is a form of repetitive negative thought that is closely associated with anxiety disorders. Worry has been described as anxious apprehension and conceptualized as reflecting heightened anticipation of potentially threatening future events. However, it is unclear whether people who tend to worry show heightened physiological reactivity when anticipating threat, especially if the threat is uncertain. In the current study, community participants (n = 52) completed a threat anticipation task featuring uncertain threat, certain threat, and safety while the startle response to auditory probes was measured. Self-reported tendency to worry was assessed using the Penn State Worry Questionnaire, and anxiety disorder status was assessed via a clinical interview. A repeated-measures general linear model showed a main effect of threat level on the startle response, as well as a significant three-way interaction among threat level, worry, and anxiety disorder status. Follow-up tests showed that higher worry was associated with blunted startle responses to threat but particularly to uncertain threat among participants with a history of anxiety disorders. Worry did not moderate startle responding in participants without a history of anxiety disorders. These results indicate that psychophysiological correlates of worry depend on clinical status and suggest that trait worry is associated with physiological blunting to threat in individuals with a history of anxiety disorders, particularly when threat is uncertain. Implications for theoretical models of worry are discussed.

Anxiety and the Neurobiology of Temporally Uncertain Threat Anticipation.

When extreme, anxiety-a state of distress and arousal prototypically evoked by uncertain danger-can be debilitating. Uncertain anticipation is a shared feature of situations that elicit signs and symptoms of anxiety across psychiatric disorders, species, and assays. Despite the profound significance of anxiety for human health and wellbeing, the neurobiology of uncertain-threat anticipation remains unsettled. Leveraging a paradigm adapted from animal research and optimized for fMRI signal decomposition, we examined the neural circuits engaged during the anticipation of temporally uncertain and certain threat in 99 men and women. Results revealed that the neural systems recruited by uncertain and certain threat anticipation are anatomically colocalized in frontocortical regions, extended amygdala, and periaqueductal gray. Comparison of the threat conditions demonstrated that this circuitry can be fractionated, with frontocortical regions showing relatively stronger engagement during the anticipation of uncertain threat, and the extended amygdala showing the reverse pattern. Although there is widespread agreement that the bed nucleus of the stria terminalis and dorsal amygdala-the two major subdivisions of the extended amygdala-play a critical role in orchestrating adaptive responses to potential danger, their precise contributions to human anxiety have remained contentious. Follow-up analyses demonstrated that these regions show statistically indistinguishable responses to temporally uncertain and certain threat anticipation. These observations provide a framework for conceptualizing anxiety and fear, for understanding the functional neuroanatomy of threat anticipation in humans, and for accelerating the development of more effective intervention strategies for pathological anxiety.SIGNIFICANCE STATEMENT Anxiety-an emotion prototypically associated with the anticipation of uncertain harm-has profound significance for public health, yet the underlying neurobiology remains unclear. Leveraging a novel neuroimaging paradigm in a relatively large sample, we identify a core circuit responsive to both uncertain and certain threat anticipation, and show that this circuitry can be fractionated into subdivisions with a bias for one kind of threat or the other. The extended amygdala occupies center stage in neuropsychiatric models of anxiety, but its functional architecture has remained contentious. Here we demonstrate that its major subdivisions show statistically indistinguishable responses to temporally uncertain and certain threat. Collectively, these observations indicate the need to revise how we think about the neurobiology of anxiety and fear.

BNST and amygdala activation to threat: Effects of temporal predictability and threat mode

Recent animal and human studies highlight the uncertainty about the onset of an aversive event as a crucial factor for the involvement of the centromedial amygdala (CM) and bed nucleus of the stria terminalis (BNST) activity. However, studies investigating temporally predictable or unpredictable threat anticipation and confrontation processes are rare. Furthermore, the few existing fMRI studies analyzing temporally predictable and unpredictable threat processes used small sample sizes or limited fMRI paradigms. Therefore, we measured functional brain activity in 109 predominantly female healthy participants during a temporally predictable-unpredictable threat paradigm, which aimed to solve limited aspects of recent studies. Results showed higher BNST activity compared to the CM during the cue indicating that the upcoming confrontation is aversive relative to the cue indicating an upcoming neutral confrontation. Both the CM and BNST showed higher activity during the confrontation with unpredictable and aversive stimuli, but the reaction to aversive confrontation relative to neutral confrontation was stronger in the CM compared to the BNST. Additional modulation analyses by NPSR1 rs324981 genotype revealed higher BNST activity relative to the CM in unpredictable anticipation relative to predictable anticipation in T-carriers compared to AA carriers. Our results indicate that during the confrontation with aversive or neutral stimuli, temporal unpredictability modulates CM and BNST activity. Further, there is a differential activity concerning threat processing, as BNST is more involved when focussing on fear-related anticipation processes and CM is more involved when focussing on threat confrontation.

Hippocampal Representation of Threat Features and Behavior in a Human Approach-Avoidance Conflict Anxiety Task.

Decisions under threat are crucial to survival and require integration of distinct situational features, such as threat probability and magnitude. Recent evidence from human lesion and neuroimaging studies implicated anterior hippocampus (aHC) and amygdala in approach–avoidance decisions under threat, and linked their integrity to cautious behavior. Here we sought to elucidate how threat dimensions and behavior are represented in these structures. Twenty human participants (11 female) completed an approach–avoidance conflict task during high-resolution fMRI. Participants could gather tokens under threat of capture by a virtual predator, which would lead to token loss. Threat probability (predator wake-up rate) and magnitude (amount of token loss) varied on each trial. To disentangle effects of threat features, and ensuing behavior, we performed a multifold parametric analysis. We found that high threat probability and magnitude related to BOLD signal in left aHC/entorhinal cortex. However, BOLD signal in this region was better explained by avoidance behavior than by these threat features. A priori ROI analysis confirmed the relation of aHC BOLD response with avoidance. Exploratory subfield analysis revealed that this relation was specific to anterior CA2/3 but not CA1. Left lateral amygdala responded to low and high, but not intermediate, threat probability. Our results suggest that aHC BOLD signal is better explained by avoidance behavior than by threat features in approach–avoidance conflict. Rather than representing threat features in a monotonic manner, it appears that aHC may compute approach–avoidance decisions based on integration of situational threat features represented in other neural structures.SIGNIFICANCE STATEMENT An effective threat anticipation system is crucial to survival across species. Natural threats, however, are diverse and have distinct features. To be able to adapt to different modes of danger, the brain needs to recognize these features, integrate them, and use them to modify behavior. Our results disclose the human anterior hippocampus as a likely arbiter of approach–avoidance decisions harnessing compound environmental information while partially replicating previous findings and blending into recent efforts to illuminate the neural basis of approach–avoidance conflict in humans.

Gender differences in anxiety: The mediating role of sensitivity to unpredictable threat

Anxiety disorders and symptoms disproportionately impact women relative to men, but it is unclear what mechanism(s) contribute to this phenomenon. The present study examined sensitivity to unpredictable threat as a potential mechanism of gender differences in panic symptoms. The sample included 67 participants (35 women) who completed the no, predictable, and unpredictable threat (NPU-threat) startle paradigm with electric shocks as the aversive stimulus. Participants also completed the self-report Inventory of Depression and Anxiety Symptoms to assess current panic and depression symptoms. Results indicated that women, relative to men, reported greater panic symptoms and demonstrated increased startle potentiation in anticipation of predictable and unpredictable threat. Furthermore, across all participants increased startle potentiation in anticipation of unpredictable (but not predictable) threat was associated with greater panic symptoms, but there was no relationship with depression symptoms. Finally, the gender difference in panic symptoms was mediated by startle potentiation in anticipation of unpredictable (but not predictable) threat. The present study suggests that a heightened sensitivity to unpredictable threat might be a mechanism that contributes to increased anxiety in women.