Distal Threat Research Articles

Examining Brain Activity Responses during Rat Ultrasonic Vocalization Playback: Insights from a Novel fMRI Translational Paradigm.

Despite decades of preclinical investigation, there remains limited understanding of the etiology and biological underpinnings of anxiety disorders. Sensitivity to potential threat is characteristic of anxiety-like behavior in humans and rodents, but traditional rodent behavioral tasks aimed to assess threat responsiveness lack translational value, especially with regard to emotionally valenced stimuli. Therefore, development of novel preclinical approaches to serve as analogues to patient assessments is needed. In humans, the fearful face task is widely used to test responsiveness to socially communicated threat signals. In rats, ultrasonic vocalizations (USVs) are analogous social cues associated with positive or negative affective states that can elicit behavioral changes in the receiver. It is therefore likely that when rats hear aversive alarm call USVs (22 kHz), they evoke translatable changes in brain activity comparable with the fearful face task. We used functional magnetic resonance imaging in male and female rats to assess changes in BOLD activity induced by exposure to aversive 22 kHz alarm calls emitted in response to threatening stimuli, prosocial (55 kHz) USVs emitted in response to appetitive stimuli, or a computer-generated 22 kHz tone. Results show patterns of regional activation that are specific to each USV stimulus. Notably, limbic regions clinically relevant to psychiatric disorders (e.g., amygdala, bed nucleus of the stria terminalis) are preferentially activated by either aversive 22 kHz or appetitive 55 kHz USVs. These results support the use of USV playback as a promising translational tool to investigate affective processing under conditions of distal threat in preclinical rat models.

The impact of anthropogenic climate change on pediatric viral diseases.

The adverse effects of climate change on human health are unfolding in real time. Environmental fragmentation is amplifying spillover of viruses from wildlife to humans. Increasing temperatures are expanding mosquito and tick habitats, introducing vector-borne viruses into immunologically susceptible populations. More frequent flooding is spreading water-borne viral pathogens, while prolonged droughts reduce regional capacity to prevent and respond to disease outbreaks with adequate water, sanitation, and hygiene resources. Worsening air quality and altered transmission seasons due to an increasingly volatile climate may exacerbate the impacts of respiratory viruses. Furthermore, both extreme weather events and long-term climate variation are causing the destruction of health systems and large-scale migrations, reshaping health care delivery in the face of an evolving global burden of viral disease. Because of their immunological immaturity, differences in physiology (e.g., size), dependence on caregivers, and behavioral traits, children are particularly vulnerable to climate change. This investigation into the unique pediatric viral threats posed by an increasingly inhospitable world elucidates potential avenues of targeted programming and uncovers future research questions to effect equitable, actionable change. IMPACT: A review of the effects of climate change on viral threats to pediatric health, including zoonotic, vector-borne, water-borne, and respiratory viruses, as well as distal threats related to climate-induced migration and health systems. A unique focus on viruses offers a more in-depth look at the effect of climate change on vector competence, viral particle survival, co-morbidities, and host behavior. An examination of children as a particularly vulnerable population provokes programming tailored to their unique set of vulnerabilities and encourages reflection on equitable climate adaptation frameworks.

Reducing avoidance of learnt fear: Extinction of an imminent threat signal partly decreases costly avoidance to a distal threat signal

In the interplay of fear and avoidance, not only imminent threat signals that directly predict potential threat evoke avoidance, but also distal threat signals that predict these imminent threat signals. Avoidance of learnt fear refers to avoidance to a distal threat signal that prevents the occurrence of an imminent threat signal. In clinical anxiety, it is often pathological given its persistence in the absence of threat and the impairments it inflicts. The current study examined whether fear extinction to an imminent threat signal would effectively reduce avoidance of learnt fear in a sensory preconditioning procedure. Three neutral preconditioning stimuli (PSs), serving as distal threat or safety signals, were paired with three neutral to-be conditioned stimuli (CSs), serving as imminent threat or safety signals. After assessing baseline levels of costly avoidance to the PSs, two CSs were paired with threat. One of these CSs then ceased to predict threat during extinction training. In test, participants showed limited avoidance to the PS that signaled the extinguished CS, however, the level of avoidance was still stronger compared to a PS that signaled a safety CS. Results suggest that exposure to an imminent threat signal partly reduces avoidance to a distal threat.

Crossing the line: The violating effects of illegitimate interruptions from work and the differential impact on work‐to‐family conflict by gender

SummaryDespite interruptions from work being increasingly common for many employees, their inherently disruptive nature induces strain on the work–life interface; yet, it remains unclear why the experienced strain is not universal. Drawing on role identity and Stress‐as‐Offense‐to‐Self theories, illegitimate interruptions from work (IIWs) are inappropriate, avoidable, unnecessary, or unreasonable interruptions that carry an added meaning of disrespect, thereby presenting a threat to the self and potentially inducing additional unnecessary strain. Differential value placed on professional and personal roles likely shapes attributions of illegitimacy. We collected event‐based data over 5 days from 182 employees (432 interruptions). Our multilevel moderated mediation model established IIW's indirect effect on work‐to‐family conflict (WFC) via boundary violation, above and beyond the negative effects of interruptions themselves. Thus, subjectively ascribed illegitimacy induces further but potentially unnecessary negative strain. Men were more likely to experience boundary violation in reaction to IIWs and subsequently reported more WFC as compared to women. Yet, although results suggest that IIWs may be a more salient immediate threat to men, it is possible that women's higher threshold for IIWs may present a more distal threat for gender parity. We offer guidance for developing strategies to reduce IIWs and mitigate their impact.

A Multimethod Evaluation of Tobacco Treatment Trial Recruitment Messages for Current Smokers Recently Diagnosed With Cancer: Pilot Factorial Randomized Controlled Trial.

BackgroundA cancer diagnosis can catalyze motivation to quit smoking. Tobacco treatment trials offer cessation resources but have low accrual rates. Digital outreach may improve accrual, but knowledge of how best to recruit smokers with recent diagnoses is limited.ObjectiveThis study aims to identify the message frames that were most effective in promoting intent to talk to a physician about participating in a tobacco treatment trial for smokers recently diagnosed with cancer.MethodsFrom February to April 2019, current smokers diagnosed within the past 24 months were recruited from a national web-based panel for a multimethod pilot randomized trial (N=99). Participants were randomized to a 2×3 plus control factorial design that tested 3 unique message frames: proximal versus distal threats of smoking, costs of continued smoking versus benefits of quitting, and gains of participating versus losses of not participating in a tobacco treatment trial. The primary outcome was intent to talk to a physician about participating in a tobacco treatment trial. In phase 1, the main effect within each message factor level was examined using ANOVA and compared with the control condition. Other message evaluation and effectiveness measures were collected and explored in a multivariable model predicting intent to talk to a physician. In phase 2, open-text evaluations of the messages were analyzed using natural language processing software (Leximancer) to generate a thematic concept map and Linguistic Inquiry Word Count to identify and compare the prevalence of linguistic markers among message factors.ResultsOf the 99 participants, 76 (77%) completed the intervention. Participants who received the cost of continued smoking frame were significantly more likely to intend to talk to their physician about participating in a tobacco treatment trial than those who received the benefits of the quitting frame (mean costs 5.13, SD 1.70 vs mean benefits 4.23, SD 1.86; P=.04). Participants who received the proximal risks of continued smoking frame were significantly more likely to seek more information about participating (mean distal 4.83, SD 1.61 vs mean proximal 5.55, SD 1.15; P=.04), and those who received the losses of not participating frame reported significantly improved perceptions of smoking cessation research (mean gain 3.98, SD 0.83 vs mean loss 4.38, SD 0.78; P=.01). Male participants (P=.006) and those with greater message relevancy (P=.001) were significantly more likely to intend to talk to their physician. Participants’ perceptions of their smoking habits, as well as their motivation to quit smoking, were prevalent themes in the open-text data. Differences in the percentages of affective words across message frames were identified.ConclusionsMultimethod approaches are needed to develop evidence-based recruitment messages for patients recently diagnosed with cancer. Future tobacco treatment trials should evaluate the effectiveness of different message frames on smoker enrollment rates.Trial RegistrationClinicaltrials.gov NCT05471284; https://clinicaltrials.gov/ct2/show/NCT05471284

Location-dependent threat and associated neural abnormalities in clinical anxiety

Anxiety disorders are characterized by maladaptive defensive responses to distal or uncertain threats. Elucidating neural mechanisms of anxiety is essential to understand the development and maintenance of anxiety disorders. In fMRI, patients with pathological anxiety (ANX, n = 23) and healthy controls (HC, n = 28) completed a contextual threat learning paradigm in which they picked flowers in a virtual environment comprising a danger zone in which flowers were paired with shock and a safe zone (no shock). ANX compared with HC showed 1) decreased ventromedial prefrontal cortex and anterior hippocampus activation during the task, particularly in the safe zone, 2) increased insula and dorsomedial prefrontal cortex activation during the task, particularly in the danger zone, and 3) increased amygdala and midbrain/periaqueductal gray activation in the danger zone prior to potential shock delivery. Findings suggest that ANX engage brain areas differently to modulate context-appropriate emotional responses when learning to discriminate cues within an environment.

5-HT2C agonists and antagonists block different components of behavioral responses to potential, distal, and proximal threat in zebrafish

Serotonin (5-HT) receptors have been implicated in responses to aversive stimuli in mammals and fish, but its precise role is still unknown. Moreover, since at least seven families of 5-HT receptors exist in vertebrates, the role of specific receptors is still debated. Aversive stimuli can be classified as indicators of proximal, distal, or potential threat, initiating responses that are appropriate for each of these threat levels. Responses to potential threat usually involve cautious exploration and increased alertness, while responses to distal and proximal threat involve a fight-flight-freeze reaction. We exposed adult zebrafish to a conspecific alarm substance (CAS) and observed behavior during (distal threat) and after (potential threat) exposure, and treated with the 5-HT2C receptor agonists MK-212 or WAY-161503 or with the antagonist RS-102221. The agonists blocked CAS-elicited defensive behavior (distal threat), but not post-exposure increases in defensive behavior (potential threat), suggesting inhibition of responses to distal threat. MK-212 blocked changes in freezing elicited by acute restraint stress, a model of proximal threat, while RS-102221 blocked changes in geotaxis elicited this stressor. We also found that RS-102221, a 5-HT2C receptor antagonist, produced small effect on behavior during and after exposure to CAS.Preprint: https://www.biorxiv.org/content/10.1101/2020.10.04.324202; Data and scripts: https://github.com/lanec-unifesspa/5-HT-CAS/tree/master/data/5HT2C

Differential Effects of the Inactivation of Anterior and Posterior Orbitofrontal Cortex on Affective Responses to Proximal and Distal Threat, and Reward Anticipation in the Common Marmoset.

Structural and functional abnormalities of the orbitofrontal cortex (OFC) have been implicated in affective disorders that manifest anxiety-related symptoms. However, research into the functions of primate OFC has predominantly focused on reward-oriented rather than threat-oriented responses. To redress this imbalance, the present study performed a comprehensive analysis of the independent role of 2 distinct subregions of the central OFC (anterior area 11; aOFC and posterior area 13; pOFC) in the processing of distal and proximal threat. Temporary inactivation of both aOFC and pOFC heightened responses to distal threat in the form of an unknown human, but not to proximal threat assessed in a discriminative Pavlovian conditioning task. Inactivation of the aOFC, however, did unexpectedly blunt conditioned threat responses, although the effect was not valence-specific, as conditioned appetitive responses were similarly blunted and appeared restricted to a discriminative version of the task (when both CS− and CS+ are present within a session). Inactivation of the pOFC did not affect conditioned responses to either proximal threat or reward and basal cardiovascular activity was unaffected by manipulations of activity in either subregion. The results highlight the contribution of aOFC and pOFC to regulation of responses to more distal uncertain but not proximal, certain threat and reveal their opposing contribution to that of the immediately adjacent medial OFC, area 14.

Differential Contribution of Anterior and Posterior Midcingulate Subregions to Distal and Proximal Threat Reactivity in Marmosets.

The midcingulate cortex (MCC) is associated with cognition and emotion regulation. Structural and correlational functional evidence suggests that rather than being homogenous, the MCC may have dissociable functions that can be mapped onto distinct subregions. In this study, we use the marmoset monkey to causally investigate the contributions of two proposed subregions of the MCC: the anterior and posterior midcingulate cortices (aMCC and pMCC) to behavioral and cardiovascular correlates of threat processing relevant to anxiety disorders. Transient inactivation of the aMCC decreased anxiety-like responses to a postencounter distal threat, namely an unfamiliar human intruder, while inactivation of the pMCC showed a mild but opposing effect. Furthermore, although inactivation of neither MCC subregions had any effect on basal cardiovascular activity, aMCC inactivation blunted the expression of both cardiovascular and behavioral conditioned responses to a predictable proximal threat (a rubber snake) during the extinction in a Pavlovian conditioning task, with pMCC inactivation having again an opposing effect, but primarily on the behavioral response. These findings suggest that the MCC is indeed functionally heterogeneous with regards to its role in threat processing, with aMCC providing a marked facilitative contribution to the expression of the emotional response to both proximal and distal threat.

Attentive immobility in the face of inevitable distal threat-Startle potentiation and fear bradycardia as an index of emotion and attention.

During fear conditioning, a cue (CS) signals an inevitable distal threat (US) and evokes a conditioned response that can be described as attentive immobility (freezing). The organism remains motionless and monitors the source of danger while startle responses are potentiated, indicating a state of defensive hypervigilance. Although in animals vagally mediated fear bradycardia is also reliably observed under such circumstances, results are mixed in human fear conditioning. Using a single-cue fear conditioning and extinction protocol, we tested cardiac reactivity and startle potentiation indexing low-level defensive strategies in a fear-conditioned (n=40; paired presentations of CS and US) compared with a non-conditioned control group (n=40; unpaired presentations of CS and US). Additionally, we assessed shock expectancy ratings on a trial-by-trial basis indexing declarative knowledge of the previous contingencies. Half of each group underwent extinction under sham or active transcutaneous vagus nerve stimulation (tVNS), serving as additional proof of concept. We found stronger cardiac deceleration during CS presentation in the fear learning relative to the control group. This learned fear bradycardia was positively correlated with conditioned startle potentiation but not with declarative knowledge of CS-US contingencies. TVNS abolished differences in heart rate changes between both groups and removed the significant correlation between late cardiac deceleration and startle potentiation in the fear learning group. Results suggest, fear-conditioned cues evoke attentive immobility in humans, characterized by cardiac deceleration and startle potentiation. Such defensive response pattern is elicited by cues predicting inevitable distal threat and resembles conditioned fear responses observed in rodents.

On the nature of eco-anxiety: How constructive or unconstructive is habitual worry about global warming?

Three studies investigated habitual worry about global warming as an example of 'eco-anxiety'. The key question was whether such worrying is constructive (a motivated pro-environmental response) or unconstructive (a symptom of pathological worry). Pathological worry and worry about global warming were assessed together with two other worry sources, that is, personal issues and the world economy (Study 1) and personal issues and the corona virus (Study 2). In both studies a statistically significant correlation was found between pathological worry and global warming worry. However, this relationship was nonsignificant when controlled for the other two worry sources. Comparisons between Studies 1 and 2 conducted one month before and during the COVID-19 crisis, respectively, as well as between order conditions within Study 2 suggested that global warming worry was unaffected by the COVID-19 context. Study 3 demonstrated that global warming worry was associated with the perception of a proximal as well as a distal threat, and correlated positively with determinants of pro-environmental behaviour, that is, a pro-ecological worldview, pro-environmental values, past pro-environmental behaviour and a 'green' identity. Global warming worry also correlated positively with emotion clusters signifying determination, anxiety, and anger, respectively. The three studies together suggest that while habitual global warming worry may be unconstructive and part of intrapersonal dysfunction for some individuals, for many others it is a constructive adaptive pro-environmental response.

Over-activation of primate subgenual cingulate cortex enhances the cardiovascular, behavioral and neural responses to threat

Stress-related disorders such as depression and anxiety are characterized by enhanced negative emotion and physiological dysfunction. Whilst elevated activity within area 25 of the subgenual anterior cingulate cortex (sgACC/25) has been implicated in these illnesses, it is unknown whether this over-activity is causal. By combining targeted intracerebral microinfusions with cardiovascular and behavioral monitoring in marmosets, we show that over-activation of sgACC/25 reduces vagal tone and heart rate variability, alters cortisol dynamics during stress and heightens reactivity to proximal and distal threat. 18F-FDG PET imaging shows these changes are accompanied by altered activity within a network of brain regions including the amygdala, hypothalamus and dorsolateral prefrontal cortex. Ketamine, shown to have rapid antidepressant effects, fails to reverse elevated arousal to distal threat contrary to the beneficial effects we have previously demonstrated on over-activation induced reward blunting, illustrating the symptom-specificity of its actions.

Between Conspiracy Beliefs, Ingroup Bias, and System Justification: How People Use Defense Strategies to Cope With the Threat of COVID-19.

The current situation around coronavirus disease 2019 (COVID-19) portrays a threat to us in several ways: It imposes uncertainty and a lack of control and reminds us of our own mortality. People around the world have reacted to these threats in seemingly unrelated ways: From stockpiling yeast and toilet paper to favoring nationalist ideas or endorsing conspiratorial beliefs. According to the General Process Model of Threat and Defense, the confrontation with a threat – a discrepant experience – makes humans react with both proximal and distal threat responses. While the proximal response manifests in behavioral inhibition that leads to heightened anxious arousal and vigilance, distal responses seek to lower behavioral inhibition and the associated state of anxiety and vigilance through engaging in distal defenses. In the present research, we propose that the reactions to COVID-19 may represent distal defense strategies to the pandemic and, therefore, can be explained and forecasted by the model. Thus, we hypothesized increased perceived COVID-19 threat to lead to a proximal threat response in the form of heightened behavioral inhibition. This, in return, should enhance the use of distal defenses (i.e., several ingroup biases, system justification, and conspiratorial beliefs) overlapping with the reactions observed as a response to COVID-19. This hypothesized mediated effect of increased perceived COVID-19 threat on distal defenses was tested in two preregistered studies: In Study 1 (N = 358), results showed perceived COVID-19 threat to be related to behavioral inhibition and, in turn, to be associated with increased distal defenses (i.e., higher entitativity, control restoration motivation, passive party support). In Study 2 (N = 348), we manipulated COVID-19 threat salience and found results suggesting the distal defenses of ingroup entitativity, system justification, and conspiratorial beliefs to be mediated by the proximal threat response. The results of the present research hint toward a common mechanism through which the seemingly unrelated reactions to COVID-19 can be explained. The results might help to predict future behavior during the COVID-19 pandemic and to design measures to counteract the detrimental effects of the pandemic.

Ventromedial prefrontal area 14 provides opposing regulation of threat and reward-elicited responses in the common marmoset

The ventromedial prefrontal cortex (vmPFC) is a key brain structure implicated in mood and anxiety disorders, based primarily on evidence from correlational neuroimaging studies. Composed of a number of brain regions with distinct architecture and connectivity, dissecting its functional heterogeneity will provide key insights into the symptomatology of these disorders. Focusing on area 14, lying on the medial and orbital surfaces of the gyrus rectus, this study addresses a key question of causality. Do changes in area 14 activity induce changes in threat- and reward-elicited responses within the nonhuman primate, the common marmoset, similar to that seen in mood and anxiety disorders? Area 14 overactivation was found to induce heightened responsivity to uncertain, low-imminence threat while blunting cardiovascular and behavioral anticipatory arousal to high-value food reward. Conversely, inactivation enhanced the arousal to high-value reward cues while dampening the acquisition of cardiovascular and behavioral responses to a Pavlovian threat cue. Basal cardiovascular activity, including heart rate variability and sympathovagal balance, which are dysfunctional in mood and anxiety disorders, are insensitive to alterations in area 14 activity as is the extinction of conditioned threat responses. The distinct pattern of dysregulation compared to neighboring region area 25 highlights the heterogeneity of function within vmPFC and reveals how the effects of area 14 overactivation on positive and negative reactivity mirror symptoms of anhedonia and anxiety that are so often comorbid in mood disorders.

Help or flight? Increased threat imminence promotes defensive helping in humans.

In humans and other mammals, defensive responses to danger vary with threat imminence, but it is unknown how those responses affect decisions to help conspecifics. Here, we manipulated threat imminence to investigate the impact of different defensive states on human helping behaviour. Ninety-eight healthy adult participants made trial-by-trial decisions about whether to help a co-participant avoid an aversive shock, at the risk of receiving a shock themselves. Helping decisions were prompted under imminent or distal threat, based on temporal distance to the moment of shock administration to the co-participant. Results showed that, regardless of how likely participants were to also receive a shock, they helped the co-participant more under imminent than distal threat. Reaction times and cardiac changes during the task supported the efficacy of the threat imminence manipulation in eliciting dissociable defensive states, with faster responses and increased heart rate during imminent compared to distal threats. Individual differences in empathic concern were specifically correlated with helping during imminent threats. These results suggest that defensive states driving active escape from immediate danger may also facilitate decisions to help others, potentially by engaging neurocognitive systems implicated in caregiving across mammals.

Space, Time, and Fear: Survival Computations along Defensive Circuits.

Naturalistic observations show that decisions to avoid or escape predators occur at different spatiotemporal scales and that they are supported by different computations and neural circuits. At their extremes, proximal threats are addressed by a limited repertoire of reflexive and myopic actions, reflecting reduced decision and state spaces and model-free (MF) architectures. Conversely, distal threats allow increased information processing supported by model-based (MB) operations, including affective prospection, replay, and planning. However, MF and MB computations are often intertwined, and under conditions of safety the foundations for future effective reactive execution can be laid through MB instruction of MF control. Together, these computations are associated with distinct population codes embedded within a distributed defensive circuitry whose goal is to determine and realize the best policy.

Slow escape decisions are swayed by trait anxiety.

Theoretical models distinguish between neural responses elicited by distal threats and those evoked by more immediate threats1-3. Specifically, slower 'cognitive' fear responses towards distal threats involve a network of brain regions including the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC), while immediate 'reactive' fear responses rely on regions such as the periaqueductal grey4,5. However, it is unclear how anxiety and its neural substrates relate to these distinct defensive survival circuits. We tested whether individual differences in trait anxiety would impact escape behaviour and neural responses to slow and fast attacking predators: conditions designed to evoke cognitive and reactive fear, respectively. Behaviourally, we found that trait anxiety was not related to escape decisions for fast threats, but individuals with higher trait anxiety escaped earlier during slow threats. Functional magnetic resonance imaging showed that when subjects faced slow threats, trait anxiety positively correlated with activity in the vHPC, mPFC, amygdala and insula. Furthermore, the strength of functional coupling between two components of the cognitive circuit-the vHPC and mPFC-was correlated with the degree of trait anxiety. This suggests that anxiety predominantly affects cognitive fear circuits that are involved in volitional strategic escape.

The recall of dementia-related and neutral words by people with dementia: The ironic process of thought suppression.

Thought suppression may not work effectively when people have a cognitive impairment. This study tests whether participants with dementia showed lessened or enhanced recall and recognition of dementia-related words compared with a control population. Fifty participants living with dementia with mild levels of cognitive impairment and a control group of 52 participants without a diagnosis of dementia took part. A list of 12 words, composed of six dementia-related and six neutral words matched for frequency and length, was read out on four occasions, with the word order being varied for each presentation. Recognition was also assessed. There was an interaction between word-type and participant group at both recall and recognition. While control participants recalled more neutral than dementia-related words, there was no difference for dementia participants. However, dementia participants recognised a significantly higher proportion of the dementia-related words, while there was no difference in word-type recognition for control participants. This study adapts a social psychological paradigm to explore whether an important psychological mechanism for reducing distress can be affected by cognitive impairment. Our findings suggest that for people living with dementia, thought suppression may be either ineffective in reducing conscious awareness of distal threats or operate in an ironic fashion. While threatening proximal material may be repressed from awareness, distal threats may return into implicit awareness. This casts new light on research and has clinical implications.

Avoid-approach conflict behaviors differentially affected by anxiolytics: implications for a computational model of risky decision-making.

Whether fear or anxiety is expressed is thought to depend on an animal's proximity to threat. In general, fear is elicited when threat is proximal, while anxiety is a response to threat that is distal and uncertain. This threat gradient model suggests that fear and anxiety involve non-overlapping neural circuitry, yet few behavioral paradigms exist that elicit both states. We studied avoid-approach conflict in rats that were behaving in a predator-inhabited foraging arena task that involved tangible threat and reward incentives. In the task, rats exhibited a variety of both fearful and anxious behaviors corresponding to proximal and distal threat, respectively. We then administered ethanol or diazepam to the rats in order to study how anxiolytics affected these fear and anxiety behaviors. We discovered that both ethanol and diazepam attenuated proximal-threat fear-like behaviors. Furthermore, we found that diazepam, but not ethanol, increased distal-threat anxiety-like behavior but also made rats less risk-averse. Finally, we describe how decisional conflict can be modeled as a partially observable Markov decision process and characterize a potential relationship between anxious behavior, diazepam's ability to suppress hippocampal theta oscillations, and hippocampal representations of the future.

Aversive responding to safety signals in panic disorder: The moderating role of intolerance of uncertainty

An inability to inhibit aversive responding during conditions that signal safety may be a core dysfunction associated with anxiety disorders. However, there has been inconsistent evidence as to whether individuals with panic disorder (PD) exhibit aversive responding during safety signals. It is therefore possible that only certain subgroups of PD patients, particularly those with high levels of intolerance of uncertainty (IU), evidence this type of abnormal responding. The aim of the current study was to examine whether IU moderates the association between PD and startle potentiation during (a) safety and (b) threat periods during a threat-of-shock task. Participants included 172 adults, 74 of which had current diagnoses of PD. Results indicated that at high levels of IU, PD was associated with greater startle potentiation during safety. At low levels of IU, PD was not associated with startle potentiation during safety. IU did not moderate the effect of PD on threat responding. These results suggest that PD patients with high levels of IU fail to inhibit aversive responding during safety, possibly due to a tendency to interpret distal threat as distressing.