Threat Processing Research Articles

Anxiety and amygdala connectivity during movie-watching

Rodent and human studies have implicated an amygdala-prefrontal circuit during threat processing. One possibility is that while amygdala activity underlies core features of anxiety (e.g. detection of salient information), prefrontal cortices (i.e. dorsomedial prefrontal/anterior cingulate cortex) entrain its responsiveness. To date, this has been established in tightly controlled paradigms (predominantly using static face perception tasks) but has not been extended to more naturalistic settings. Consequently, using ‘movie fMRI’—in which participants watch ecologically-rich movie stimuli rather than constrained cognitive tasks—we sought to test whether individual differences in anxiety correlate with the degree of face-dependent amygdala-prefrontal coupling in two independent samples. Analyses suggested increased face-dependent superior parietal activation and decreased speech-dependent auditory cortex activation as a function of anxiety. However, we failed to find evidence for anxiety-dependent connectivity, neither in our stimulus-dependent or -independent analyses. Our findings suggest that work using experimentally constrained tasks may not replicate in more ecologically valid settings and, moreover, highlight the importance of testing the generalizability of neuroimaging findings outside of the original context.

Moderating effects of environmental stressors on the development of attention to threat in infancy.

An attention bias to threat has been linked to psychosocial outcomes across development, including anxiety (Pérez-Edgar, K., Bar-Haim, Y., McDermott, J. M., Chronis-Tuscano, A., Pine, D. S., & Fox, N. A. (2010). Attention biases to threat and behavioral inhibition in early childhood shape adolescent social withdrawal. Emotion (Washington, D.C.), 10(3), 349). Although some attention biases to threat are normative, it remains unclear how these biases diverge into maladaptive patterns of emotion processing for some infants. Here, we examined the relation between household stress, maternal anxiety, and attention bias to threat in a longitudinal sample of infants tested at 4, 8, and 12months. Infants were presented with a passive viewing eye-tracking task in which angry, happy, or neutral facial configurations appeared in one of the four corners of a screen. We measured infants' latency to fixate each target image and collected measures of parental anxiety and daily hassles at each timepoint. Intensity of daily parenting hassles moderated patterns of attention bias to threat in infants over time. Infants exposed to heightened levels of parental hassles became slower to detect angry (but not happy) facial configurations compared with neutral faces between 4 and 12months of age, regardless of parental anxiety. Our findings highlight the potential impact of the environment on the development of infants' early threat processing and the need to further investigate how early environmental factors shape the development of infant emotion processing.

Does irritability predict attention biases toward threat among clinically anxious youth?

Aberrant threat processing is a known cognitive characteristic of anxiety disorders and irritability. Youth with more severe symptomatology show greater allocation of attention towards threat relative to neutral stimuli. Although irritability contributes to poorer outcomes among anxious youths, irritability has not been considered as a contributing factor to threat processing in anxiety disorders. Thus, the current study examined the role of irritability in predicting attention biases for threat among clinically anxious youth. Our study included 84 clinically anxious youth (M = 9.31years old, SD = 2.44) who completed a dot-probe task to determine attention biases. Anxiety disorders were assessed using semi-structured diagnostic interviews. Well validated measures were used to assess the severity of anxiety and irritability symptoms via child- and parent-report, respectively. Findings indicated that more severe irritability predicted greater attention biases toward threat among clinically anxious youth, covarying for age, anxiety severity, and the number of comorbid diagnoses. At a trend-level, anxiety severity also predicted attention bias for threat. Among clinically anxious youth, irritability severity was the strongest predictor of attention bias toward threat. Findings point to the salience of irritability, and to some extent anxiety severity, in relation to threat processing among youth with clinical anxiety disorders.

Event-related potentials to acoustic startle probes during unpredictable threat are associated with individual differences in intolerance of uncertainty

Individual differences in sensitivity to unpredictable threat may be a critical mechanism for internalizing psychopathology phenotypes. The present study examined whether the startle probe-elicited N100 and P300 during unpredictable threat – two event-related potentials indexing early and elaborative attentional processing of unpredictable threat – may be endophenotypes for internalizing psychopathology, including fear and distress/misery disorders and intolerance of uncertainty (IU), a clinical trait that is transdiagnostically associated with internalizing disorders. A large sample of adult siblings (N = 375) completed the no, predictable, and unpredictable threat task, during which the N100 and P300 were recorded. Relative to the no threat condition, N100 was more strongly enhanced in anticipation of unpredictable than predictable threat while P300 was suppressed to both predictable and unpredictable threat. While neither N100 enhancement nor P300 suppression to unpredictable threat was associated with fear or distress/misery disorders, they were negatively linked to inhibitory IU (a facet of IU). Thus, individuals high in inhibitory IU showed reduced attentional engagement with the threatening context when it was unpredictable. Further, N100 enhancement and, to a lesser degree, P300 suppression to unpredictable threat showed familial aggregation – a key criterion for determining whether a biomarker is an endophenotype. In sum, N100 enhancement and P300 suppression to unpredictable threat may be endophenotypes for dimensional measures of internalizing psychopathology.

Distributed and Multifaceted Effects of Threat and Safety.

In the present fMRI study, we examined how anxious apprehension is processed in the human brain. A central goal of the study was to test the prediction that a subset of brain regions would exhibit sustained response profiles during threat periods, including the anterior insula, a region implicated in anxiety disorders. A second important goal was to evaluate the responses in the amygdala and the bed nucleus of the stria terminals, regions that have been suggested to be involved in more transient and sustained threat, respectively. A total of 109 participants performed an experiment in which they encountered "threat" or "safe" trials lasting approximately 16 sec. During the former, they experienced zero to three highly unpleasant electrical stimulations, whereas in the latter, they experienced zero to three benign electrical stimulations (not perceived as unpleasant). The timing of the stimulation during trials was randomized, and as some trials contained no stimulation, stimulation delivery was uncertain. We contrasted responses during threat and safe trials that did not contain electrical stimulation, but only the potential that unpleasant (threat) or benign (safe) stimulation could occur. We employed Bayesian multilevel analysis to contrast responses to threat and safe trials in 85 brain regions implicated in threat processing. Our results revealed that the effect of anxious apprehension is distributed across the brain and that the temporal evolution of the responses is quite varied, including more transient and more sustained profiles, as well as signal increases and decreases with threat.

The Association Between Spiritual Wellbeing and Dietary Intake Among Overweight and Obese Female University Student: A Cross-Sectional Study

Introduction: Obesity has become a public health threat worldwide and processing a high burden to the healthcare system. This study aimed to determine the association between spiritual wellbeing and dietary intake among overweight and obese female students in a university in Peninsular Malaysia. Methods: This is a cross-sectional study involving 100 female students from a public university in the East Coast Region of Peninsular Malaysia. The participants are selected based on inclusion and exclusion criteria. Spiritual wellbeing is measured using an adapted and validated spirituality questionnaire, while the dietary intake was calculated using a 24-hour dietary intake questionnaire. Data were analysed using SPSS version 23 and Nutritionist Pro. Pearson correlation is applied to measure the association between spiritual wellbeing and dietary intake. Results: Spiritual wellbeing was negatively correlated with dietary intake (r= -0.026, p=0.797). The results showed no significant association between spiritual wellbeing and dietary intake (p>0.05). Conclusion: To conclude, there is no significant association between spiritual wellbeing and dietary intake among overweight and obese female students. Future research could add other variables such as the micronutrients and macronutrients into the study can help to get a more significant result. Besides, a large-scale study is also warranted to observe the association between spiritual wellbeing and dietary intake among overweight and obese female university students in Malaysia.

Distinct networks of periaqueductal gray columns in pain and threat processing

Noxious events that can cause physical damage to the body are perceived as threats. In the brainstem, the periaqueductal gray (PAG) ensures survival by generating an appropriate response to these threats. Hence, the experience of pain is coupled with threat signaling and interfaces in the dl/l and vlPAG columns. In this study, we triangulate the functional circuits of the dl/l and vlPAG by using static and time-varying functional connectivity (FC) in multiple fMRI scans in healthy participants (n = 37, 21 female). The dl/l and vlPAG were activated during cue, heat, and rating periods when the cue signaled a high threat of experiencing heat pain and when the incoming intensity of heat pain was unknown. Responses were significantly lower after low threat cues. The two regions responded similarly to the cued conditions but showed prominent distinctions in the extent of FC with other brain regions. Thus, both static and time-varying FC showed significant differences in the functional circuits of dl/l and vlPAG in rest and task scans. The dl/lPAG consistently synchronized with the salience network and the thalamus, suggesting a role in threat detection, while the vlPAG exhibited more widespread synchronization and frequently connected with memory/language and sensory regions. Hence, these two PAG regions process heat pain when stronger pain is expected or when it is uncertain, and preferentially synchronize with distinct brain circuits in a reproducible manner. The dl/lPAG seems more directly involved in salience detection, while the vlPAG seems engaged in contextualizing threats.

Individual differences in threat and reward neural circuitry activation: Testing dimensional models of early adversity, anxiety and depression.

Altered functioning of the brain's threat and reward circuitry has been linked to early life adversity and to symptoms of anxiety and depression. To date, however, these relationships have been studied largely in isolation and in categorical‐based approaches. It is unclear to what extent early life adversity and psychopathology have unique effects on brain functioning during threat and reward processing. We examined functional brain activity during a face processing task in threat (amygdala and ventromedial prefrontal cortex) and reward (ventral striatum and orbitofrontal cortex) regions of interest among a sample (N = 103) of young adults (aged 18–19 years) in relation to dimensional measures of early life adversity and symptoms of anxiety and depression. Results demonstrated a significant association between higher scores on the deprivation adversity dimension and greater activation of reward neural circuitry during viewing of happy faces, with the largest effect sizes observed in the orbitofrontal cortex. We found no significant associations between the threat adversity dimension, or symptom dimensions of anxiety and depression, and neural activation in threat or reward circuitries. These results lend partial support to theories of adversity‐related alterations in neural activation and highlight the importance of testing dimensional models of adversity and psychopathology in large sample sizes to further our understanding of the biological processes implicated.

Subfornical organ interleukin 1 receptor: A novel regulator of spontaneous and conditioned fear associated behaviors in mice

Impaired threat responding and fear regulation is a hallmark of psychiatric conditions such as post-traumatic stress disorder (PTSD) and Panic Disorder (PD). Most studies have focused on external psychogenic threats to study fear, however, accumulating evidence suggests a primary role of homeostatic perturbations and interoception in regulating emotional behaviors. Heightened reactivity to interoceptive threat carbon dioxide (CO2) inhalation associates with increased risk for developing PD and PTSD, however, contributory mechanisms and molecular targets are not well understood. Previous studies from our group suggested a potential role of interleukin 1 receptor (IL-1R1) signaling within BBB-devoid sensory circumventricular organ, the subfornical organ (SFO) in CO2-evoked fear. However, the necessity of SFO-IL-1R1 in regulating CO2-associated spontaneous fear as well as, long-term fear potentiation relevant to PD/PTSD has not been investigated. The current study tested male mice with SFO-targeted microinfusion of the IL-1R1 antagonist (IL-1RA) or vehicle in a recently developed CO2-startle-fear conditioning-extinction paradigm. Consistent with our hypothesis, SFO IL-1RA treatment elicited significant attenuation of freezing and increased rearing during CO2 inhalation suggesting SFO-IL1R1 regulation of spontaneous fear to CO2. Intriguingly, SFO IL-1RA treatment normalized CO2-associated potentiation of conditioned fear and impaired extinction a week later suggesting modulation of long-term fear by SFO-IL-1R1 signaling. Post behavior FosB mapping revealed recruitment of prefrontal cortex-amygdala-periaqueductal gray (PAG) areas in SFO-IL-1RA mediated effects. Additionally, we localized cellular IL-1R1 expression within the SFO to blood vessel endothelial cells and observed CO2-induced alterations in IL-1β/IL-1R1 expression in peripheral mononuclear cells and SFO. Lastly, CO2-evoked microglial activation was attenuated in SFO-IL-1RA treated mice. These observations suggest a peripheral monocyte-endothelial-microglia interplay in SFO-IL-1R1 modulation of CO2-associated spontaneous fear and delayed fear memory. Collectively, our data highlight a novel, “bottom-up” neuroimmune mechanism that integrates interoceptive and exteroceptive threat processing of relevance to fear-related pathologies.

Frozen with Fear? Attentional Mechanisms in Children with Selective Mutism

BackgroundChildren with selective mutism (SM) are consistently unable to speak in certain social situations. Due to an overlap between SM and social anxiety disorder (SAD) in children, similar mechanisms could apply to both disorders. Especially biased attentional processing of threat and fear-induced reduced visual exploration (referred to as attentive freezing) appear promising in SM.MethodsA total of N = 84 children (8–12 years, SM: n = 28, SAD: n = 28, typical development (TD): n = 28) participated in an eye-tracking paradigm with videos of a social counterpart expressing a question, a social evaluation or a neutral statement. We investigated gaze behavior towards the social counterpart’s eye-region and the extent of visual exploration (length of scanpath), across conditions.ResultsThere were no group differences regarding gaze behavior on the eye region. Neither gaze behavior with respect to the eye region nor visual exploration were dependent on the video condition. Compared to children with TD, children with SM generally showed less visual exploration, however children with SAD did not.ConclusionReduced visual exploration might be due to the mechanism of attentive freezing, which could be part of an extensive fear response in SM that might also affect speech-production. Interventions that counteract the state of freezing could be promising for the therapy of SM.

Modulation of threat extinction by working memory load: An event-related potential study

Distraction is typically discouraged during exposure therapy for anxiety, because it is thought to interfere with extinction learning by diverting attention away from anxiety-provoking stimuli. Working memory load is one form of distraction that might interfere with extinction learning. Alternatively, working memory load might reduce threat responding and benefit extinction learning by engaging prefrontal brain regions that have a reciprocal relationship with brain circuits involved in threat detection and processing. Prior work examining the effect of working memory load on threat extinction has been limited and has found mixed results. Here, we used the late positive potential (LPP), an event-related potential that is larger for threatening compared to non-threatening stimuli to assess the effect of working memory load on threat extinction. After acquisition, 38 participants performed three blocks of an extinction task interspersed with low and high working memory load trials. Results showed that overall, the LPP was reduced under high compared to low working memory load, and that working memory load slowed extinction learning. Results provide empirical evidence in support of limiting distraction during exposure therapy in order to optimize extinction learning efficiency.

Conceptual Models of Startle, Surprise and Automation Bias Analyzed Through Recent Aviation Accident Reports

This work aims to analyze three conceptual models of startle, surprise and automation bias found in the literature: Conceptual Model of Startle and Surprise, Integrated Model of Complacency, and Automation Bias and Conceptual Model of Threat, Appraisal and Information Processing. Afterwards, an analysis of accidents reports of Lion Air 43, Lion Air 610 (737-MAX), Emirates 407 and TAM 3054 is carried out using the selected conceptual models. The aim is to deepen the knowledge about startle, surprise and automation bias by means of an analysis of how they are found in recent accidents, disseminate the subject to the aeronautical community and reinforce their importance for aviation safety.

Beyond adaptive security coping behaviors: Theory and empirical evidence

Extant research seldom focuses on maladaptive security coping behaviors. Applying the extended parallel process model, this study has developed a research model to reveal the processes underlying users’ adaptive and maladaptive security coping behaviors. The model is empirically examined along with alternative models. Results show that perceived coping efficacy is the most influencing factor promoting adaptive coping behaviors and deterring maladaptive coping behaviors. Fear plays a mediating role in the threat appraisal process and leads to adaptive and maladaptive coping behaviors. Trust in the Internet as the contextual factor influences the threat and coping appraisal processes and adaptive coping behaviors.

Microbiota links to neural dynamics supporting threat processing.

There is growing recognition that the composition of the gut microbiota influences behaviour, including responses to threat. The cognitive‐interoceptive appraisal of threat‐related stimuli relies on dynamic neural computations between the anterior insular (AIC) and the dorsal anterior cingulate (dACC) cortices. If, to what extent, and how microbial consortia influence the activity of this cortical threat processing circuitry is unclear. We addressed this question by combining a threat processing task, neuroimaging, 16S rRNA profiling and computational modelling in healthy participants. Results showed interactions between high‐level ecological indices with threat‐related AIC‐dACC neural dynamics. At finer taxonomic resolutions, the abundance of Ruminococcus was differentially linked to connectivity between, and activity within the AIC and dACC during threat updating. Functional inference analysis provides a strong rationale to motivate future investigations of microbiota‐derived metabolites in the observed relationship with threat‐related brain processes.

Sex differences in neural mechanisms of social and non-social threat monitoring

Adolescent males and females differ in their responses to social threat. Yet, threat processing is often probed in non-social contexts using the error-related negativity (ERN; Flanker EEG Task), which does not yield sex-specific outcomes. fMRI studies show inconsistent patterns of sex-specific neural engagement during threat processing. Thus, the relation between threat processing in non-social and social contexts across sexes and the effects perceived level of threat on brain function are unclear. We tested the interactive effect of non-social threat-vigilance (ERN), sex (N = 69; Male=34; 11–14-year-olds), and perceived social threat on brain function while anticipating feedback from ‘unpredictable’, ‘nice’, or ‘mean’ purported peers (fMRI; Virtual School Paradigm). Whole-brain analyses revealed differential engagement of precentral and inferior frontal gyri, putamen, anterior cingulate cortex, and insula. Among males with more threat-vigilant ERNs, greater social threat was associated with increased activation when anticipating unpredictable feedback. Region of interest analyses revealed this same relation in females in the amygdala and anterior hippocampus when anticipating mean feedback. Thus, non-social threat vigilance relates to neural engagement depending on perceived social threat, but peer-based social contexts and brain regions engaged, differ across sexes. This may partially explain divergent psychosocial outcomes in adolescence.

Bed nucleus of the stria terminalis and amygdala responses to unpredictable threat in children.

Substantial evidence from studies in humans suggests the amygdala is pivotal for anxiety. Findings from animal models and translational studies suggests the bed nucleus of the stria terminalis (BNST) is also critical for anxiety and the anticipation of unpredictable threat in adults. However, it remains unknown whether the BNST is involved in unpredictable threat anticipation in children. Forty-two 8-10-year-olds completed resting-state functional magnetic resonance imaging (fMRI) scans and an unpredictable threat fMRI task in which they were trained to associate cues with images. Intrinsic connectivity analyses were performed to establish functional BNST and amygdala networks. BNST and amygdala activation to cues and images was tested. Significant findings were followed by task-based functional connectivity analyses. Children showed evidence for BNST and amygdala intrinsic connectivity that was similar to previous patterns observed in adults. In response to unpredictable cues relative to neutral face cues, children had a significant amygdala response but no response in the BNST. The amygdala, but not the BNST, also showed a significantly greater response to fear face images relative to neutral images. Thus, unpredictable threat activated the amygdala, but not BNST, in children. This finding is contrary to studies showing robust BNST activation to unpredictable threat in adults and may suggest that the BNST's role in threat processing emerges later in development.

Associations of Irritability With Functional Connectivity of Amygdala and Nucleus Accumbens in Adolescents and Young Adults With ADHD

Objective Irritability is a common characteristic in ADHD. We examined whether dysfunction in neural connections supporting threat and reward processing was related to irritability in adolescents and young adults with ADHD. Method We used resting-state fMRI to assess connectivity of amygdala and nucleus accumbens seeds in those with ADHD (n = 34) and an age- and gender-matched typically-developing comparison group (n = 34). Results In those with ADHD, irritability was associated with atypical functional connectivity of both seed regions. Amygdala seeds showed greater connectivity with right inferior frontal gyrus and caudate/putamen, and less connectivity with precuneus. Nucleus accumbens seeds showed altered connectivity with middle temporal gyrus and precuneus. Conclusion The irritability-ADHD presentation is associated with atypical functional connectivity of reward and threat processing regions with cognitive control and emotion processing regions. These patterns provide novel evidence for irritability-associated neural underpinnings in adolescents and young adults with ADHD. The findings suggest cognitive and behavioral treatments that address response to reward, including omission of an expected reward and irritability, may be beneficial for ADHD.

Danger or dislike: Distinguishing threat from negative valence as sources of automatic anti-Black bias.

The Dual Implicit Process Model (March et al., 2018b) distinguishes the implicit processing of physical threat (i.e., "Can it hurt or kill me?") from valence (i.e., "Do I dislike/like it?"). Five studies tested whether automatic anti-Black bias is due to White Americans associating Black men with threat, negative valence, or both. Studies 1 and 2 assessed how quickly White participants decided whether positive, negative, and threatening images were good versus bad when primed by Black versus White male-faces. Studies 3 and 4 assessed how early in the decision process White participants began deciding whether Black and White (and, in Study 3, Asian) male-faces displaying anger, sadness, happiness, or no emotion were, in Study 3, dangerous, depressed, cheerful, or calm or, in Study 4, dangerous, negative, or positive. Study 5 assessed how quickly White participants decided whether negative and threatening words were negative versus dangerous when primed by Black versus White male-names. All studies indicated that White Americans automatically associate Black men with physical threat. Study 3 indicated the association is unique to Black men and did not extend to Asian men as a general intergroup effect. Studies 3, 4, and 5, which simultaneously paired threat against negativity, indicated that the Black-threat association is stronger than a Black-negative association. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Limbic links to paranoia: increased resting-state functional connectivity between amygdala, hippocampus and orbitofrontal cortex in schizophrenia patients with paranoia

Paranoia is a frequent and highly distressing experience in psychosis. Models of paranoia suggest limbic circuit pathology. Here, we tested whether resting-state functional connectivity (rs-fc) in the limbic circuit was altered in schizophrenia patients with current paranoia. We collected MRI scans in 165 subjects including 89 patients with schizophrenia spectrum disorders (schizophrenia, schizoaffective disorder, brief psychotic disorder, schizophreniform disorder) and 76 healthy controls. Paranoia was assessed using a Positive And Negative Syndrome Scale composite score. We tested rs-fc between bilateral nucleus accumbens, hippocampus, amygdala and orbitofrontal cortex between groups and as a function of paranoia severity. Patients with paranoia had increased connectivity between hippocampus and amygdala compared to patients without paranoia. Likewise, paranoia severity was linked to increased connectivity between hippocampus and amygdala. Furthermore, paranoia was associated with increased connectivity between orbitofrontal and medial prefrontal cortex. In addition, patients with paranoia had increased functional connectivity within the frontal hubs of the default mode network compared to healthy controls. These results demonstrate that current paranoia is linked to aberrant connectivity within the core limbic circuit and prefrontal cortex reflecting amplified threat processing and impaired emotion regulation. Future studies will need to explore the association between limbic hyperactivity, paranoid ideation and perceived stress.

Impact of daily entrepreneurial stressors on long-term transformational leader behaviors and well-being: Differences in experienced and nascent entrepreneurs

Emerging evidence documents that entrepreneurs’ transformational leader behaviors exert positive influences on ventures and followers. However, knowledge of antecedents of such effective leadership and associated consequences on entrepreneurs themselves is sorely lacking. Moreover, leader behaviors are considered dynamic and affected by transient factors. Drawing on conservation of resources theory, this study demonstrates a resource threat, loss, and gain process by exploring how transformational leader behaviors manifest across stressful contexts, thus impacting their well-being, utilizing a time-lag design. Results revealed that exposure to entrepreneurial stressors and heightened reactivity to them has negative, indirect effects on well-being by impairing leader behaviors. Further, there are individual differences regarding how experienced and nascent entrepreneurs react to stressful experiences, subsequently affecting leader behaviors and well-being. We consider the theoretical and practical implications of these findings.