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Generalized anxiety disorder is characterized by disruptions in decision-making, including an enhanced aversion to uncertain outcomes (i.e., risk aversion), which is not specific to negative outcomes (i.e., no loss aversion). It is unknown if this uncertainty bias is a trait-like causal factor contributing to anxiety symptoms, or a state-like feature triggered by anxiety symptoms such as worry chains. Here, in-patients with Major Depression Disorder (MDD), with (N = 16) or without (N = 24) Generalized anxiety (GA) symptoms, and healthy controls (N = 23), completed an economic decision-making task before and after worry induction. They were asked to choose between a certain monetary payoff, and an uncertain gamble, allowing for estimation of risk and loss aversion through a computational prospect-theoretic model. There were no significant differences in risk and loss aversion between any of the three groups at baseline. After worry induction, patients with GA symptoms, compared to those without, showed increased risk aversion. This increase was modulated by the severity of anxiety symptoms. These findings suggest that decision-making disruptions in anxiety disorder may be driven by anxiety symptoms such as worry, rather than causing them. This could shape etiological models, motivate standardization of emotional state in research on decision-making in anxiety disorders, support treatment strategies primarily aimed at worry management, and could guide novel interventions focusing on uncertainty exposure across aversive and appetitive domains., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Fear and anxiety are adaptive emotions that serve important defensive functions, yet in excess, they can be debilitating and lead to poor mental health. Computational modelling of behaviour provides a mechanistic framework for understanding the cognitive and neurobiological bases of fear and anxiety, and has seen increasing interest in the field. In this brief review, we discuss recent developments in the computational modelling of human fear and anxiety. Firstly, we describe various reinforcement learning strategies that humans employ when learning to predict or avoid threat, and how these relate to symptoms of fear and anxiety. Secondly, we discuss initial efforts to explore, through a computational lens, approach-avoidance conflict paradigms that are popular in animal research to measure fear- and anxiety-relevant behaviours. Finally, we discuss negative biases in decision-making in the face of uncertainty in anxiety., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: Computational psychiatry studies have investigated how reinforcement learning may be different in individuals with mood and anxiety disorders compared with control individuals, but results are inconsistent., Objective: To assess whether there are consistent differences in reinforcement-learning parameters between patients with depression or anxiety and control individuals., Data Sources: Web of Knowledge, PubMed, Embase, and Google Scholar searches were performed between November 15, 2019, and December 6, 2019, and repeated on December 3, 2020, and February 23, 2021, with keywords (reinforcement learning) AND (computational OR model) AND (depression OR anxiety OR mood)., Study Selection: Studies were included if they fit reinforcement-learning models to human choice data from a cognitive task with rewards or punishments, had a case-control design including participants with mood and/or anxiety disorders and healthy control individuals, and included sufficient information about all parameters in the models., Data Extraction and Synthesis: Articles were assessed for inclusion according to MOOSE guidelines. Participant-level parameters were extracted from included articles, and a conventional meta-analysis was performed using a random-effects model. Subsequently, these parameters were used to simulate choice performance for each participant on benchmarking tasks in a simulation meta-analysis. Models were fitted, parameters were extracted using bayesian model averaging, and differences between patients and control individuals were examined. Overall effect sizes across analytic strategies were inspected., Main Outcomes and Measures: The primary outcomes were estimated reinforcement-learning parameters (learning rate, inverse temperature, reward learning rate, and punishment learning rate)., Results: A total of 27 articles were included (3085 participants, 1242 of whom had depression and/or anxiety). In the conventional meta-analysis, patients showed lower inverse temperature than control individuals (standardized mean difference [SMD], -0.215; 95% CI, -0.354 to -0.077), although no parameters were common across all studies, limiting the ability to infer differences. In the simulation meta-analysis, patients showed greater punishment learning rates (SMD, 0.107; 95% CI, 0.107 to 0.108) and slightly lower reward learning rates (SMD, -0.021; 95% CI, -0.022 to -0.020) relative to control individuals. The simulation meta-analysis showed no meaningful difference in inverse temperature between patients and control individuals (SMD, 0.003; 95% CI, 0.002 to 0.004)., Conclusions and Relevance: The simulation meta-analytic approach introduced in this article for inferring meta-group differences from heterogeneous computational psychiatry studies indicated elevated punishment learning rates in patients compared with control individuals. This difference may promote and uphold negative affective bias symptoms and hence constitute a potential mechanistic treatment target for mood and anxiety disorders.

Anxiety alters how we perceive the world and can alter aspects of cognitive performance. Prominent theories of anxiety suggest that the effect of anxiety on cognition is due to anxious thoughts "overloading" limited cognitive resources, competing with other processes. If this is so, then a cognitive load manipulation should impact performance of a task in the same way as induced anxiety. Thus, we examined the impact of a load manipulation on a time perception task that we have previously shown to be reliably impacted by anxiety. In contrast with our prediction, across 3 studies we found that time perception was insensitive to our load manipulation. Our results do not therefore support the idea that anxiety impacts temporal cognition by overloading limited cognitive resources, at least as induced by a commonly used load manipulation. Thus, anxiety might affect temporal cognition in a unique way, via an evolutionary-preserved defense survival system, as suggested by animal-inspired theories of anxiety, rather than competing for limited attentional resources. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Negative affective biases are thought to be a key symptom driving and upholding many psychiatric disorders. When presented with ambiguous information, anxious individuals, for example, tend to anticipate lower rewards than asymptomatic individuals (Aylward et al., 2019. Translating a rodent measure of negative bias into humans: the impact of induced anxiety and unmedicated mood and anxiety disorders. Psychological Medicine ). The assumption is that this is because anxious individuals assume "worse" outcomes. However, predictions are often made about high and low rewards, so it is not clear whether the bias is due to the valence (the "worse" option) or just magnitude (the lower number). We therefore explored the roles of valence and magnitude in a translational measure of negative affective bias. We adapted a two-alternative forced choice (2AFC) "reward-reward" task into a "punishment-punishment" paradigm, and followed up with "high reward-high punishment" and "low reward-high punishment" variants. The results from the "punishment-punishment" paradigm - a bias towards higher punishments in healthy controls - suggest that it is outcome magnitude that is important. However, this is qualified by the other variants which indicate that both valence and magnitude are important. Overall, our results temper the assumption that negative affective biases observed in tasks using numeric outcomes are solely as a result of subjective outcome valence.

Anxiety is an adaptive response that promotes harm avoidance, but at the same time excessive anxiety constitutes the most common psychiatric complaint. Moreover, current treatments for anxiety-both psychological and pharmacological-hover at around 50% recovery rates. Improving treatment outcomes is nevertheless difficult, in part because contemporary interventions were developed without an understanding of the underlying neurobiological mechanisms that they modulate. Recent advances in experimental models of anxiety in humans, such as threat of unpredictable shock, have, however, enabled us to start translating the wealth of mechanistic animal work on defensive behaviour into humans. In this article, we discuss the distinction between fear and anxiety, before reviewing translational research on the neural circuitry of anxiety in animal models and how it relates to human neuroimaging studies across both healthy and clinical populations. We highlight the roles of subcortical regions (and their subunits) such as the bed nucleus of the stria terminalis, the amgydala, and the hippocampus, as well as their connectivity to cortical regions such as dorsal medial and lateral prefrontal/cingulate cortex and insula in maintaining anxiety responding. We discuss how this circuitry might be modulated by current treatments before finally highlighting areas for future research that might ultimately improve treatment outcomes for this common and debilitating transdiagnostic symptom., Competing Interests: Competing interests: OJR has completed consultancy work for Ieso Digital Health and Brainbow and is running an Investigator Initiated Trial with Lundbeck. He holds an MRC Industrial Collaboration Award with Cambridge Cognition., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Animal models of anxiety disorders are important for elucidating neurobiological defense mechanisms. However, animal models are limited when it comes to understanding the more complex processes of anxiety that are unique to humans (e.g., worry) and to screen new treatments. In this review, we outline how the Experimental Psychopathology approach, based on experimental models of anxiety in healthy subjects, can mitigate these limitations and complement research in animals. Experimental psychopathology can bridge basic research in animals and clinical studies, as well as guide and constrain hypotheses about the nature of psychopathology, treatment mechanisms, and treatment targets. This review begins with a brief review of the strengths and limitations of animal models before discussing the need for human models of anxiety, which are especially necessary to probe higher-order cognitive processes. This can be accomplished by combining anxiety-induction procedures with tasks that probe clinically relevant processes to identify neurocircuits that are potentially altered by anxiety. The review then discusses the validity of experimental psychopathology and introduces a methodological approach consisting of five steps: (1) select anxiety-relevant cognitive or behavioral operations and associated tasks, (2) identify the underlying neurocircuits supporting these operations in healthy controls, 3) examine the impact of experimental anxiety on the targeted operations in healthy controls, (4) utilize findings from step 3 to generate hypotheses about neurocircuit dysfunction in anxious patients, and 5) evaluate treatment mechanisms and screen novel treatments. This is followed by two concrete illustrations of this approach and suggestions for future studies.

Dysfunctional memory processes are widely reported in anxiety disorders, but the underlying neurocognitive mechanisms are unclear. Recent work shows that the impact of anxiety on memory depends on the context and memory modality. For instance, threat of shock, a translational within-subject anxiety induction, has been shown to impair the encoding of facial stimuli, while improving spatial working memory (WM) accuracy. The present study aimed to delineate the neural circuitry regulating these opposing behavioural effects. Thirty-three healthy volunteers performed the previously assessed facial recognition and a spatial WM tasks inside an fMRI scanner, under alternating within-subject conditions of threat or safe from shock across encoding and retrieval. Facial recognition impairments were replicated when threat was selectively induced at encoding. Neuroimaging results suggest that this effect was driven by increased competition for attentional resources within the anterior cingulate cortex, in which activation correlated positively with stress levels. The impact of threat on spatial WM performance did not, however, replicate in the fMRI environment. Nevertheless, state-dependent hippocampal activation was observed in both tasks. These findings suggest a neurocognitive mechanism by which anxiety impairs facial recognition as well as a state-dependent hippocampal activation pattern, which may putatively underline retrieval of negative experiences in anxiety., (© The Author(s) 2019. Published by Oxford University Press.)

Background: During intensive care unit (ICU) admission, patients and their carers experience physical and psychological stressors that may result in psychological conditions including anxiety, depression, and post-traumatic stress disorder (PTSD). Improving communication between healthcare professionals, patients, and their carers may alleviate these disorders. Communication may include information or educational interventions, in different formats, aiming to improve knowledge of the prognosis, treatment, or anticipated challenges after ICU discharge., Objectives: To assess the effects of information or education interventions for improving outcomes in adult ICU patients and their carers., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, and PsycINFO from database inception to 10 April 2017. We searched clinical trials registries and grey literature, and handsearched reference lists of included studies and related reviews., Selection Criteria: We included randomised controlled trials (RCTs), and planned to include quasi-RCTs, comparing information or education interventions presented to participants versus no information or education interventions, or comparing information or education interventions as part of a complex intervention versus a complex intervention without information or education. We included participants who were adult ICU patients, or their carers; these included relatives and non-relatives, including significant representatives of patients., Data Collection and Analysis: Two review authors independently assessed studies for inclusion, extracted data, assessed risk of bias, and applied GRADE criteria to assess certainty of the evidence., Main Results: We included eight RCTs with 1157 patient participants and 943 carer participants. We found no quasi-RCTs. We identified seven studies that await classification, and three ongoing studies.Three studies designed an intervention targeted at patients, four at carers, and one at both patients and carers. Studies included varied information: standardised or tailored, presented once or several times, and that included verbal or written information, audio recordings, multimedia information, and interactive information packs. Five studies reported robust methods of randomisation and allocation concealment. We noted high attrition rates in five studies. It was not feasible to blind participants, and we rated all studies as at high risk of performance bias, and at unclear risk of detection bias because most outcomes required self reporting.We attempted to pool data statistically, however this was not always possible due to high levels of heterogeneity. We calculated mean differences (MDs) using data reported from individual study authors where possible, and narratively synthesised the results. We reported the following two comparisons.Information or education intervention versus no information or education intervention (4 studies)For patient anxiety, we did not pool data from three studies (332 participants) owing to unexplained substantial statistical heterogeneity and possible clinical or methodological differences between studies. One study reported less anxiety when an intervention was used (MD -3.20, 95% confidence interval (CI) -3.38 to -3.02), and two studies reported little or no difference between groups (MD -0.40, 95% CI -4.75 to 3.95; MD -1.00, 95% CI -2.94 to 0.94). Similarly, for patient depression, we did not pool data from two studies (160 patient participants). These studies reported less depression when an information or education intervention was used (MD -2.90, 95% CI -4.00 to -1.80; MD -1.27, 95% CI -1.47 to -1.07). However, it is uncertain whether information or education interventions reduce patient anxiety or depression due to very low-certainty evidence.It is uncertain whether information or education interventions improve health-related quality of life due to very low-certainty evidence from one study reporting little or no difference between intervention groups (MD -1.30, 95% CI -4.99 to 2.39; 143 patient participants). No study reported adverse effects, knowledge acquisition, PTSD severity, or patient or carer satisfaction.We used the GRADE approach and downgraded certainty of the evidence owing to study limitations, inconsistencies between results, and limited data from few small studies.Information or education intervention as part of a complex intervention versus a complex intervention without information or education (4 studies)One study (three comparison groups; 38 participants) reported little or no difference between groups in patient anxiety (tailored information pack versus control: MD 0.09, 95% CI -3.29 to 3.47; standardised general ICU information versus control: MD -0.25, 95% CI -4.34 to 3.84), and little or no difference in patient depression (tailored information pack versus control: MD -1.26, 95% CI -4.48 to 1.96; standardised general ICU information versus control: MD -1.47, 95% CI -6.37 to 3.43). It is uncertain whether information or education interventions as part of a complex intervention reduce patient anxiety and depression due to very low-certainty evidence.One study (175 carer participants) reported fewer carer participants with poor comprehension among those given information (risk ratio 0.28, 95% CI 0.15 to 0.53), but again this finding is uncertain due to very low-certainty evidence.Two studies (487 carer participants) reported little or no difference in carer satisfaction; it is uncertain whether information or education interventions as part of a complex intervention increase carer satisfaction due to very low-certainty evidence. Adverse effects were reported in only one study: one participant withdrew because of deterioration in mental health on completion of anxiety and depression questionnaires, but the study authors did not report whether this participant was from the intervention or comparison group.We downgraded certainty of the evidence owing to study limitations, and limited data from few small studies.No studies reported severity of PTSD, or health-related quality of life., Authors' Conclusions: We are uncertain of the effects of information or education interventions given to adult ICU patients and their carers, as the evidence in all cases was of very low certainty, and our confidence in the evidence was limited. Ongoing studies may contribute more data and introduce more certainty when incorporated into future updates of the review.

Anxiety can be an adaptive response to potentially threatening situations. However, if experienced in inappropriate contexts, it can also lead to pathological and maladaptive anxiety disorders. Experimentally, anxiety can be induced in healthy individuals using the threat of shock (ToS) paradigm. Accumulating work with this paradigm suggests that anxiety promotes harm-avoidant mechanisms through enhanced inhibitory control. However, the specific cognitive mechanisms underlying anxiety-linked inhibitory control are unclear. Critically, behavioral inhibition can arise from at least 2 interacting valuation systems: instrumental (a goal-directed system) and Pavlovian (a "hardwired" reflexive system). The present study (N = 62) replicated a study showing improved response inhibition under ToS in healthy participants, and additionally examined the impact of ToS on aversive and appetitive Pavlovian-instrumental interactions in a reinforced go/no-go task. When Pavlovian and instrumental systems were in conflict, ToS increased inhibition to aversive events, while leaving appetitive interactions unperturbed. We argue that anxiety promotes avoidant behavior in potentially harmful situations by potentiating aversive Pavlovian reactions (i.e., promoting avoidance in the face of threats). Critically, such a mechanism would drive adaptive harm-avoidant behavior in threatening situations where Pavlovian and instrumental processes are aligned, but at the same time, result in maladaptive behaviors when misaligned and where instrumental control would be advantageous. This has important implications for our understanding of the mechanisms that underlie pathological anxiety. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Background: Serious and debilitating symptoms of anxiety are the most common mental health problem worldwide, accounting for around 5% of all adult years lived with disability in the developed world. Avoidance behavior-avoiding social situations for fear of embarrassment, for instance-is a core feature of such anxiety. However, as for many other psychiatric symptoms the biological mechanisms underlying avoidance remain unclear., Methods: Reinforcement learning models provide formal and testable characterizations of the mechanisms of decision making; here, we examine avoidance in these terms. A total of 101 healthy participants and individuals with mood and anxiety disorders completed an approach-avoidance go/no-go task under stress induced by threat of unpredictable shock., Results: We show an increased reliance in the mood and anxiety group on a parameter of our reinforcement learning model that characterizes a prepotent (pavlovian) bias to withhold responding in the face of negative outcomes. This was particularly the case when the mood and anxiety group was under stress., Conclusions: This formal description of avoidance within the reinforcement learning framework provides a new means of linking clinical symptoms with biophysically plausible models of neural circuitry and, as such, takes us closer to a mechanistic understanding of mood and anxiety disorders., (Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Anxiety disorders are the most common mental health disorders, and daily transient feelings of anxiety (or "stress") are ubiquitous. However, the precise impact of both transient and pathological anxiety on higher-order cognitive functions, including short- and long-term memory, is poorly understood. A clearer understanding of the anxiety-memory relationship is important as one of the core symptoms of anxiety, most prominently in post-traumatic stress disorder (PTSD), is intrusive reexperiencing of traumatic events in the form of vivid memories. This study therefore aimed to examine the impact of induced anxiety (threat of shock) on memory encoding and retrieval. Eighty-six healthy participants completed tasks assessing: visuospatial working memory, verbal recognition, face recognition, and associative memory. Critically, anxiety was manipulated within-subjects: information was both encoded and retrieved under threat of shock and safe (no shock) conditions. Results revealed that visuospatial working memory was enhanced when information was encoded and subsequently retrieved under threat, and that threat impaired the encoding of faces regardless of the condition in which it was retrieved. Episodic memory and verbal short-term recognition were, however, unimpaired. These findings indicate that transient anxiety in healthy individuals has domain-specific, rather than domain-general, impacts on memory. Future studies would benefit from expanding these findings into anxiety disorder patients to delineate the differences between adaptive and maladaptive responding., (© 2017 Bolton and Robinson; Published by Cold Spring Harbor Laboratory Press.)

Background: Anxiety disorders are associated with disruptions in both emotional processing and decision making. As a result, anxious individuals often make decisions that favor harm avoidance. However, this bias could be driven by enhanced aversion to uncertainty about the decision outcome (e.g., risk) or aversion to negative outcomes (e.g., loss). Distinguishing between these possibilities may provide a better cognitive understanding of anxiety disorders and hence inform treatment strategies., Methods: To address this question, unmedicated individuals with pathological anxiety (n = 25) and matched healthy control subjects (n = 23) completed a gambling task featuring a decision between a gamble and a safe (certain) option on every trial. Choices on one type of gamble-involving weighing a potential win against a potential loss (mixed)-could be driven by both loss and risk aversion, whereas choices on the other type-featuring only wins (gain only)-were exclusively driven by risk aversion. By fitting a computational prospect theory model to participants' choices, we were able to reliably estimate risk and loss aversion and their respective contribution to gambling decisions., Results: Relative to healthy control subjects, pathologically anxious participants exhibited enhanced risk aversion but equivalent levels of loss aversion., Conclusions: Individuals with pathological anxiety demonstrate clear avoidance biases in their decision making. These findings suggest that this may be driven by a reduced propensity to take risks rather than a stronger aversion to losses. This important clarification suggests that psychological interventions for anxiety should focus on reducing risk sensitivity rather than reducing sensitivity to negative outcomes per se., (Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Anxiety can be broken down into multiple facets including behavioral components, such as defensive reactivity, and cognitive components, such as distracting anxious thoughts. In a previous study, we showed that anticipation of unpredictable shocks facilitated response inhibition to infrequent no-go trials during a go/no-go task. The present study extends this work to examine the distinct contribution of defensive reactivity, measures with fear-potentiated startle, and anxious thought, assessed with thought probes, on go and no-go performance. Consistent with our prior findings, shock anticipation facilitated response inhibition (i.e., reduced errors of commission) on the no-go trials. Regression analyses showed that (a) no-go accuracy was positively associated with fear-potentiated startle and negatively associated with threat-related/task-unrelated thoughts and (b) go accuracy correlated negatively with fear-potentiated startle. Thus, while the present findings confirm the influence of anxiety on response inhibition, they also show that such influence reflects the balance between the positive effect of defensive reactivity and the negative effect of distracting anxious thoughts. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Response to stress or external threats is a key factor in mood and anxiety disorder aetiology. Current measures of anxious responding to threats are limited because they largely rely on retrospective self-report. Objectively quantifying individual differences in threat response would be a valuable step towards improving our understanding of anxiety disorder vulnerability. Our goal is to therefore develop a reliable, objective, within-subject 'stress-test' of anxious responding. To this end, we examined threat-potentiated performance on an inhibitory control task from baseline to 2-4 weeks (n = 50) and again after 5-9 months (n = 22). We also describe single session data for a larger sample (n = 157) to provide better population-level estimates of task performance variance. Replicating previous findings, threat of shock improved distractor accuracy and slowed target reaction time on our task. Critically, both within-subject self-report measures of anxiety (ICC = 0.66) and threat-potentiated task performance (ICC = 0.58) showed clinically useful test-retest reliability. Threat-potentiated task performance may therefore hold promise as a non-subjective measure of individual anxious responding.

Anxiety can have both detrimental and facilitatory cognitive effects. This study investigates the neural substrates of a replicated facilitatory effect of anxiety on sustained attention and response inhibition. This effect consisted of improved performance on the Sustained Attention to Response Task (a Go-NoGo task consisting of 91% Go and 9% NoGo trials) in threat (unpredictable electrical shock) vs safe (no shock) conditions. This study uses the same experimental design with fMRI and relies on an event-related analysis of BOLD signal changes. Findings reveal that threat-related cognitive facilitation (improved NoGo accuracy) is associated with greater activation of a right-lateralized frontoparietal group of regions previously implicated in sustained attention and response inhibition. Moreover, these same regions show decreased activation in the Go trials preceding NoGo errors. During NoGo trials, striatal activity is also greater in the threat vs safe condition, consistent with the notion of enhanced inhibitory processing under threat. These findings identify potential mechanisms by which threat of unpredictable shock can facilitate distinct cognitive functions. A greater understanding of the complex interaction of the anxious state and cognitive processes may have critical clinical implications., (Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the United States.)

Pathological anxiety is associated with disrupted cognitive processing, including working memory and decision-making. In healthy individuals, experimentally-induced state anxiety or high trait anxiety often results in the deployment of adaptive harm-avoidant behaviours. However, how these processes affect cognition is largely unknown. To investigate this question, we implemented a translational within-subjects anxiety induction, threat of shock, in healthy participants reporting a wide range of trait anxiety scores. Participants completed a gambling task, embedded within an emotional working memory task, with some blocks under unpredictable threat and others safe from shock. Relative to the safe condition, threat of shock improved recall of threat-congruent (fearful) face location, especially in highly trait anxious participants. This suggests that threat boosts working memory for mood-congruent stimuli in vulnerable individuals, mirroring memory biases in clinical anxiety. By contrast, Bayesian analysis indicated that gambling decisions were better explained by models that did not include threat or treat anxiety, suggesting that: (i) higher-level executive functions are robust to these anxiety manipulations; and (ii) decreased risk-taking may be specific to pathological anxiety. These findings provide insight into the complex interactions between trait anxiety, acute state anxiety and cognition, and may help understand the cognitive mechanisms underlying adaptive anxiety.

Anxiety has wide-reaching and complex effects on cognitive performance. Although it can intrude on cognition and interfere with performance, it can also facilitate information processing and behavioural responses. In a previous study, we showed that anxiety induced by threat of shock facilitates performance on the Sustained Attention to Response Task, a vigilance test, which probes response inhibition to infrequent nogo stimuli. The present study sought to identify factors that may have contributed to such improved performance, including on- and off-task thinking (assessed with thought probes) and individual differences in attention control, as measured with the Attention Control Scale. Replicating our prior finding, we showed that shock threat significantly reduced errors of commission on the nogo trials. However, we extended this finding in demonstrating that this effect was driven by subjects with low attention control. We therefore confirm that anxiety increases inhibitory control of prepotent responses--a mechanism which is adaptive under threat--and show that this effect is greater in those who rely more upon such prepotent responding, i.e., those with low attentional control.

Background: Neuroimaging research has traditionally explored fear and anxiety in response to discrete threat cues (e.g., during fear conditioning). However, anxiety is a sustained aversive state that can persist in the absence of discrete threats. Little is known about mechanisms that maintain anxiety states over a prolonged period. Here, we used a robust translational paradigm (threat of shock) to induce sustained anxiety. Recent translational work has implicated an amygdala-prefrontal cortex (PFC) circuit in the maintenance of anxiety in rodents. To explore the functional homologues of this circuitry in humans, we used a novel paradigm to examine the impact of sustained anticipatory anxiety on amygdala-PFC intrinsic connectivity., Methods: Task-independent fMRI data were collected in healthy participants during long-duration periods of shock anticipation and safety. We examined intrinsic functional connectivity., Results: Our study involved 20 healthy participants. During sustained anxiety, amygdala activity was positively coupled with dorsomedial PFC (DMPFC) activity. High trait anxiety was associated with increased amygdala-DMPFC coupling. In addition, induced anxiety was associated with positive coupling between regions involved in defensive responding, and decreased coupling between regions involved in emotional control and the default mode network., Limitations: Inferences regarding anxious pathology should be made with caution because this study was conducted in healthy participants., Conclusion: Findings suggest that anticipatory anxiety increases intrinsic amygdala-DMPFC coupling and that the DMPFC may serve as a functional homologue for the rodent prefrontal regions by sustaining anxiety. Future research may use this defensive neural context to identify biomarkers of risk for anxious pathology and target these circuits for therapeutic intervention.

Serotonin is strongly implicated in the mammalian stress response, but surprisingly little is known about its mode of action. Recent data suggest that serotonin can inhibit aversive responding in humans, but this remains underspecified. In particular, data in rodents suggest that global serotonin depletion may specifically increase long-duration bed nucleus of the stria terminalis (BNST)-mediated aversive responses (ie, anxiety), but not short-duration BNST-independent responses (ie, fear). Here, we extend these findings to humans. In a balanced, placebo-controlled crossover design, healthy volunteers (n=20) received a controlled diet with and without the serotonin precursor tryptophan (acute tryptophan depletion; ATD). Aversive states were indexed by translational acoustic startle measures. Fear and anxiety were operationally defined as the increase in startle reactivity during short- and long-duration threat periods evoked by predictable shock (fear-potentiated startle) and by the context in which the shocks were administered (anxiety-potentiated startle), respectively. ATD significantly increased long-duration anxiety-potentiated startle but had no effect on short-duration fear-potentiated startle. These results suggest that serotonin depletion in humans selectively increases anxiety but not fear. Current translational frameworks support the proposition that ATD thus disinhibits dorsal raphé-originating serotonergic control of corticotropin-releasing hormone-mediated excitation of the BNST. This generates a candidate neuropharmacological mechanism by which depleted serotonin may increase response to sustained threats, alongside clear implications for our understanding of the manifestation and treatment of mood and anxiety disorders.

Functionally, anxiety serves to increase vigilance towards aversive stimuli and improve the ability to detect and avoid danger. We have recently shown, for instance, that anxiety increases the ability to a) detect and b) instigate defensive responses towards aversive and not appetitive face stimuli in healthy individuals. This is arguably the key adaptive function of anxiety, yet the neural circuitry underlying this valence-specific effect is unknown. In the present translational study, we sought evidence for the proposition that dorsomedial regions of the prefrontal (DMPFC) and cingulate cortex constitute the human homologue of the rodent prelimbic and are thus associated with increased amygdala responding during this adaptive threat bias in anxiety. To this end, we applied a novel functional connectivity analysis to healthy subjects (N=20) identifying the emotion of fearful and happy faces in an fMRI scanner under anxious (threat of unpredictable foot shock) and non-anxious (safe) conditions. We showed that anxiety significantly increased positive DMPFC-amygdala connectivity during the processing of fearful faces. This effect was a) valence-specific (it was not seen for happy faces), b) paralleled by faster behavioral response to fearful faces, and c) correlated positively with trait anxiety. As such we provide the first experimental support for an anxiety-mediated, valence-specific, DMPFC-amygdala aversive amplification mechanism in healthy humans. This may be homologous to the rodent prelimbic-amygdala circuit and may, given the relationship with trait anxiety, underlie vulnerability to anxiety disorders. This study thus pinpoints a key neural mechanism in adaptive anxiety and highlights its potential link to maladaptive anxiety., (Published by Elsevier Inc.)

Individuals with anxiety disorders demonstrate altered cognitive performance including (1) cognitive biases towards negative stimuli (affective biases) and (2) increased cognitive rigidity (e.g., impaired conflict adaptation) on affective Stroop tasks. Threat of electric shock is frequently used to induce anxiety in healthy individuals, but the extent to which this manipulation mimics the cognitive impairment seen in anxiety disorders is unclear. In this study, 31 healthy individuals completed an affective Stroop task under safe and threat-of-shock conditions. We showed that threat (1) enhanced aversive processing and abolished a positive affective bias but (2) had no effect on conflict adaptation. Threat of shock thus partially models the effects of anxiety disorders on affective Stroop tasks. We suggest that the affective state of anxiety-which is common to both threat and anxiety disorders-modulates the neural inhibition of subcortical aversive processing, whilst pathologies unique to anxiety disorders modulate conflict adaptation.

There is currently an unmet need in higher education for a structured, pre-emptive programme of support to help students enhance their resilience to stress. This article presents a mixed-methods evaluation of a transferable biopsychosocial resilience intervention for students -- the "Resilience Enhancement Programme for Students" (REP-S). In Study 1, a randomised control trial showed that participating in the intervention was associated with significantly decreased perceived stress, decreased trait neuroticism and enhanced self-esteem over a period of one month. In Study 2, written and focus-group qualitative data from students provided evidence that the intervention led to perceived positive changes, including sleeping better, dealing more effectively with assessments and managing interpersonal challenges. Future steps in the evaluation of the REP-S are discussed.

Background: Selective serotonin reuptake inhibitors (SSRIs) are used for the treatment of several conditions including anxiety disorders, but the basic neurobiology of serotonin function remains unclear. The amygdala and prefrontal cortex are strongly innervated by serotonergic projections and have been suggested to play an important role in anxiety expression. However, serotonergic function in behaviour and SSRI-mediated neurobiological changes remain incompletely understood. Aims: To investigate the neural correlates of subchronic antidepressant administration. Methods: We investigated whether the 2- to 3-week administration of a highly selective SSRI (escitalopram) would alter brain activation on a task robustly shown to recruit the bilateral amygdala and frontal cortices in a large healthy volunteer sample. Participants performed the task during a functional magnetic resonance imaging acquisition before (n = 96) and after subchronic escitalopram (n = 46, days of administration mean (SD) = 15.7 (2.70)) or placebo (n = 40 days of administration mean (SD) = 16.2 (2.90)) self-administration. Results: Compared to placebo, we found an elevation in right amygdala activation to the task after escitalopram administration without significant changes in mood. This effect was not seen in the left amygdala, the dorsomedial region of interest, the subgenual anterior cingulate cortex or the right fusiform area. There were no significant changes in connectivity between the dorsomedial cortex and amygdala or the subgenual anterior cingulate cortex after escitalopram administration. Conclusions: To date, this most highly powered study of subchronic SSRI administration indicates that, contrary to effects often seen in patients with anxiety disorders, subchronic SSRI treatment may increase amygdala activation in healthy controls. This finding highlights important gaps in our understanding of the functional role of serotonin. [ABSTRACT FROM AUTHOR]

Background: Anxiety and depression are leading causes of disability worldwide, yet individuals are often unable to access appropriate treatment. There is a need to develop effective interventions that can be delivered remotely. Previous research has suggested that emotional processing biases are a potential target for intervention, and these may be altered through brief training programs. Methods: We report two experimental medicine studies of emotional bias training in two samples: individuals from the general population (n = 522) and individuals currently taking antidepressants to treat anxiety or depression (n = 212). Participants, recruited online, completed four sessions of EBT from their own home. Mental health and cognitive functioning outcomes were assessed at baseline, immediately post-training, and at 2-week follow-up. Results: In both studies, our intervention successfully trained participants to perceive ambiguous social information more positively. This persisted at a 2-week follow-up. There was no clear evidence that this change in emotional processing transferred to improvements in symptoms in the primary analyses. However, in both studies, there was weak evidence for improved quality of life following EBT amongst individuals with more depressive symptoms at baseline. No clear evidence of transfer effects was observed for self-reported daily stress, anhedonia or depressive symptoms. Exploratory analyses suggested that younger participants reported greater treatment gains. Conclusions: These studies demonstrate the effectiveness of delivering a multi-session online training program to promote lasting cognitive changes. Given the inconsistent evidence for transfer effects, EBT requires further development before it can be considered as a treatment for anxiety and depression. [ABSTRACT FROM AUTHOR]

A well‐documented amygdala‐dorsomedial prefrontal circuit is theorized to promote attention to threat ("threat vigilance"). Prior research has implicated a relationship between individual differences in trait anxiety/vigilance, engagement of this circuitry, and anxiogenic features of the environment (e.g., through threat‐of‐shock and movie‐watching). In the present study, we predicted that—for those scoring high in self‐reported anxiety and a behavioral measure of threat vigilance—this circuitry is chronically engaged, even in the absence of anxiogenic stimuli. Our analyses of resting‐state fMRI data (N = 639) did not, however, provide evidence for such a relationship. Nevertheless, in our planned exploratory analyses, we saw a relationship between threat vigilance behavior (but not self‐reported anxiety) and intrinsic amygdala‐periaqueductal gray connectivity. Here, we suggest this subcortical circuitry may be chronically engaged in hypervigilant individuals, but that amygdala‐prefrontal circuitry may only be engaged in response to anxiogenic stimuli. [ABSTRACT FROM AUTHOR]

Anxiety and stress are adaptive responses to threat that promote harm avoidance. In particular, prior work has shown that anxiety induced in humans using threat of unpredictable shock promotes behavioral inhibition in the face of harm. This is consistent with the idea that anxiety promotes passive avoidance—that is, withholding approach actions that could lead to harm. However, harm can also be avoided through active avoidance, where a (withdrawal) action is taken to avoid harm. Here, we provide the first direct within‐study comparison of the effects of threat of shock on active and passive avoidance. We operationalize passive avoidance as withholding a button press response in the face of negative outcomes, and active avoidance as lifting/releasing a button press in the face of negative outcomes. We explore the impact of threat of unpredictable shock on the learning of these behavioral responses (alongside matched responses to rewards) within a single cognitive task. We predicted that threat of shock would promote both active and passive avoidance, and that this would be driven by increased reliance on Pavlovian bias, as parameterized within reinforcement‐learning models. Consistent with our predictions, we provide evidence that threat of shock promotes passive avoidance as conceptualized by our task. However, inconsistent with predictions, we found no evidence that threat of shock promoted active avoidance, nor evidence of elevated Pavlovian bias in any condition. One hypothetical framework with which to understand these findings is that anxiety promotes passive over active harm avoidance strategies in order to conserve energy while avoiding harm. [ABSTRACT FROM AUTHOR]

Setting external reminders provides a convenient way to reduce cognitive demand and ensure accurate retrieval of information for prospective tasks. Recent experimental evidence has demonstrated that the decision to offload cognitive information to external resources is guided by metacognitive belief, that is, individuals' confidence in their unaided ability. Other work has also suggested a relationship between metacognitive belief and trait anxiety. In the present study (N = 300), we bridged these two areas by investigating whether trait anxiety correlated with metacognitive belief and—consequently—propensity to offload information in a delayed intentions paradigm. Participants received a financial reward based on their ability to remember targets. However, participants could take a reduced reward per target if they decided to use reminders. We replicated previous findings that participants were biased to use more reminders than would be optimal, and this bias was correlated with metacognitive judgements. However, we show no evidence that trait anxiety held a relationship with metacognitive belief or reminder usage. Indeed, Bayesian analyses strongly favoured the null. Therefore, variation in self-reported trait anxiety does not necessarily influence confidence and strategy when participants remember delayed intentions. [ABSTRACT FROM AUTHOR]

Background: Mood and anxiety disorders are ubiquitous but current treatment options are ineffective for many sufferers. Moreover, a number of promising pre-clinical interventions have failed to translate into clinical efficacy in humans. Improved treatments are unlikely without better animal–human translational pipelines. Here, we translate a rodent measure of negative affective bias into humans, exploring its relationship with (1) pathological mood and anxiety symptoms and (2) transient induced anxiety. Methods: Adult participants (age = 29 ± 11) who met criteria for mood or anxiety disorder symptomatology according to a face-to-face neuropsychiatric interview were included in the symptomatic group. Study 1 included N = 77 (47 = asymptomatic [female = 21]; 30 = symptomatic [female = 25]), study 2 included N = 47 asymptomatic participants (25 = female). Outcome measures were choice ratios, reaction times and parameters recovered from a computational model of reaction time – the drift diffusion model (DDM) – from a two-alternative-forced-choice task in which ambiguous and unambiguous auditory stimuli were paired with high and low rewards. Results: Both groups showed over 93% accuracy on unambiguous tones indicating intact discrimination, but symptomatic individuals demonstrated increased negative affective bias on ambiguous tones [proportion high reward = 0.42 (s.d. = 0.14)] relative to asymptomatic individuals [0.53 (s.d. = 0.17)] as well as a significantly reduced DDM drift rate. No significant effects were observed for the within-subjects anxiety-induction. Conclusions: Humans with pathological anxiety symptoms directly mimic rodents undergoing anxiogenic manipulation. The lack of sensitivity to transient anxiety suggests the paradigm might be more sensitive to clinically relevant symptoms. Our results establish a direct translational pipeline (and candidate therapeutics screen) from negative affective bias in rodents to pathological mood and anxiety symptoms in humans. [ABSTRACT FROM AUTHOR]

BACKGROUND: Neuroimaging research has traditionally explored fear and anxiety in response to discrete threat cues (e.g., during fear conditioning). However, anxiety is a sustained aversive state that can persist in the absence of discrete threats. Little is known about mechanisms that maintain anxiety states over a prolonged period. Here, we used a robust translational paradigm (threat of shock) to induce sustained anxiety. Recent translational work has implicated an amygdala-prefrontal cortex (PFC) circuit in the maintenance of anxiety in rodents. To explore the functional homologues of this circuitry in humans, we used a novel paradigm to examine the impact of sustained anticipatory anxiety on amygdala-PFC intrinsic connectivity. METHODS: Task-independent fMRI data were collected in healthy participants during long-duration periods of shock anticipation and safety. We examined intrinsic functional connectivity. RESULTS: Our study involved 20 healthy participants. During sustained anxiety, amygdala activity was positively coupled with dorsomedial PFC (DMPFC) activity. High trait anxiety was associated with increased amygdala-DMPFC coupling. In addition, induced anxiety was associated with positive coupling between regions involved in defensive responding, and decreased coupling between regions involved in emotional control and the default mode network. LIMITATIONS: Inferences regarding anxious pathology should be made with caution because this study was conducted in healthy participants. CONCLUSION: Findings suggest that anticipatory anxiety increases intrinsic amygdala-DMPFC coupling and that the DMPFC may serve as a functional homologue for the rodent prefrontal regions by sustaining anxiety. Future research may use this defensive neural context to identify biomarkers of risk for anxious pathology and target these circuits for therapeutic intervention. [ABSTRACT FROM AUTHOR]

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. • Using 'movie fMRI', we tested whether trait anxiety correlates with face-dependent amygdala-prefrontal coupling. • We observed altered superior parietal activation to faces and auditory cortex activation to speech as a function of anxiety. • We failed to find evidence for anxiety-dependent amygdala-dmPFC connectivity in stimulus-dependent or -independent analyses. • Our findings highlight the importance of testing the generalizability of neuroimaging findings outside of the original context. [ABSTRACT FROM AUTHOR]

Anxiety disorders constitute a sizeable worldwide health burden with profound social and economic consequences. The symptoms are wide-ranging; from hyperarousal to difficulties with concentrating. This latter effect falls under the broad category of altered cognitive performance which is the focus of this review. Specifically, we examine the interaction between anxiety and cognition focusing on the translational threat of unpredictable shock paradigm; a method previously used to characterize emotional responses and defensive mechanisms that is now emerging as valuable tool for examining the interaction between anxiety and cognition. In particular, we compare the impact of threat of shock on cognition in humans to that of pathological anxiety disorders. We highlight that both threat of shock and anxiety disorders promote mechanisms associated with harm avoidance across multiple levels of cognition (from perception to attention to learning and executive function)-a "hot" cognitive function which can be both adaptive and maladaptive depending upon the circumstances. This mechanism comes at a cost to other functions such as working memory, but leaves some functions, such as planning, unperturbed. We also highlight a number of cognitive effects that differ across anxiety disorders and threat of shock. These discrepant effects are largely seen in "cold" cognitive functions involving control mechanisms and may reveal boundaries between adaptive (e.g., response to threat) and maladaptive (e.g., pathological) anxiety. We conclude by raising a number of unresolved questions regarding the role of anxiety in cognition that may provide fruitful avenues for future research. [ABSTRACT FROM AUTHOR]

People often say that during unpleasant events, e.g. traumatic incidents such as car accidents, time slows down (i.e. time is overestimated). However aversive events can elicit at least two dissociable subtypes of reactions: fear (transient and relating to an imminent event) and anxiety (diffuse and relating to an unpredictable event). We hypothesised that anxiety might have an opposite effect on time perception compared to fear. To test this we combined a robust anxiety manipulation (threat-of-shock) with a widely used timing task in which participants judged whether the duration of a stimulus was long or short. In line with our hypothesis, across three experiments (with varying stimulus timings and shock levels), participants significantly underestimated time under inducted anxiety, as indicated by a rightward shift of the psychophysical function (meta-analytic effect size: d = 0.68, 95% confidence interval: 0.42-0.94). In two further studies, we were unable to replicate previous findings that fear leads to time overestimation, after adapting our temporal cognition task, which suggests a dissociation between fear and anxiety on how they affect time perception. Our results suggest that experimentally inducing anxiety leads to underestimating the duration of temporal intervals, which might be a starting point in explaining different subjective experiences of disorders related to fear (e.g. post-traumatic stress disorder) and anxiety (e.g. generalised anxiety disorder). [ABSTRACT FROM AUTHOR]