Intolerance of uncertainty is associated with heightened responding in the prefrontal cortex during cue-signalled uncertainty of threat.

Heightened responding to uncertain threat is considered a hallmark of anxiety disorder pathology. We sought to determine whether individual differences in self-reported intolerance of uncertainty (IU), a key transdiagnostic dimension in anxiety-related pathology, underlies differential recruitment of neural circuitry during cue-signalled uncertainty of threat (n = 42). In an instructed threat of shock task, cues signalled uncertain threat of shock (50%) or certain safety from shock. Ratings of arousal and valence, skin conductance response (SCR), and functional magnetic resonance imaging were acquired. Overall, participants displayed greater ratings of arousal and negative valence, SCR, and amygdala activation to uncertain threat versus safe cues. IU was not associated with greater arousal ratings, SCR, or amygdala activation to uncertain threat versus safe cues. However, we found that high IU was associated with greater ratings of negative valence and greater activity in the medial prefrontal cortex and dorsomedial rostral prefrontal cortex to uncertain threat versus safe cues. These findings suggest that during cue-signalled uncertainty of threat, individuals high in IU rate uncertain threat as aversive and engage prefrontal cortical regions known to be involved in safety-signalling and conscious threat appraisal. Taken together, these findings highlight the potential of IU in modulating safety-signalling and conscious appraisal mechanisms in situations with cue-signalled uncertainty of threat, which may be relevant to models of anxiety-related pathology.

Longitudinal change in executive function is associated with impaired top-down frontolimbic regulation during reappraisal in older adults.

Networks in the prefrontal cortex (PFC) that are important for executive function are also engaged in adaptive responding to negative events. These networks are particularly vulnerable to age-related structural atrophy and an associated loss of executive function, yet existing evidence suggests preserved emotion processing ability in ageing. Using longitudinally acquired data from a battery of cognitive tasks, we defined a metric for the rate of decline of executive function. With this metric, we investigated relationships between changes in executive function and emotion reappraisal ability and brain structure, in 34 older adults, using functional and structural MRI. During task-based fMRI, participants were asked to cognitively reappraise negatively valenced images. We hypothesised one of two associations with decreasing executive function over time: 1) a decreased ability to reappraise reflected in decreased PFC and increased amygdala activation, or 2) a neural compensation mechanism characterised by increased PFC activation but no differential amygdala activation. Structurally, for a decreased reappraisal ability, we predicted a decrease in grey matter in PFC and/or a decrease of white matter integrity in amygdala-PFC pathways. Neither of the two hypotheses relating to brain function were completely supported, with the findings indicating a steeper decline in executive function associated with both increased PFC and increased left amygdala activity when reappraising negative stimuli. In addition, white matter integrity of the uncinate fasciculus, a primary white matter tract connecting the amygdala and ventromedial areas of PFC, was lower in those individuals who demonstrated a greater decrease in executive function. These findings highlight the association of diminishing cognitive ability with brain structure and function linked to emotion regulation.

The role of intolerance of uncertainty in the acquisition and extinction of reward.

Individuals, who score high in self-reported intolerance of uncertainty (IU), tend to find uncertainty anxiety-provoking. IU has been reliably associated with disrupted threat extinction. However, it is unclear whether IU would be related to disrupted extinction to other arousing stimuli that are not threatening (i.e., rewarding). We addressed this question by conducting a Pavlovian reward conditioning task with acquisition and extinction training phases (n = 58). In the Pavlovian reward conditioning task, we recorded liking ratings, skin conductance response (SCR), and corrugator supercilii activity (i.e., brow muscle indicative or negative and positive affect) to learned reward (CS+) and neutral (CS-) cues. Typical patterns of reward acquisition and extinction training were observed for liking ratings. There was evidence for conditioning in SCR during the extinction training phase but not the acquisition training phase. However, no evidence of conditioning in either the acquisition or extinction training phase was observed for the corrugator supercilii. IU was not related to any measures during the acquisition or extinction training phases. Taken together, these results suggest that the current Pavlovian reward conditioning task was not sufficient for eliciting a reliable conditioned reward response, and therefore, further research with optimized reward conditioning designs are required to test whether IU-related deficits occur during the extinction of reward.

I don't know where to look: the impact of intolerance of uncertainty on saccades towards non-predictive emotional face distractors.

Attentional bias to uncertain threat is associated with anxiety disorders. Here we examine the extent to which emotional face distractors (happy, angry and neutral) and individual differences in intolerance of uncertainty (IU), impact saccades in two versions of the "follow a cross" task. In both versions of the follow the cross task, the probability of receiving an emotional face distractor was 66.7%. To increase perceived uncertainty regarding the location of the face distractors, in one of the tasks additional non-predictive cues were presented before the onset of the face distractors and target. We did not find IU to impact saccades towards non-cued face distractors. However, we found IU, over Trait Anxiety, to impact saccades towards non-predictive cueing of face distractors. Under these conditions, IU individuals' eyes were pulled towards angry face distractors and away from happy face distractors overall, and the speed of this deviation of the eyes was determined by the combination of the cue and emotion of the face. Overall, these results suggest a specific role of IU on attentional bias to threat during uncertainty. These findings highlight the potential of intolerance of uncertainty-based mechanisms to help understand anxiety disorder pathology and inform potential treatment targets.

What you see is what you want to see: Motivationally relevant stimuli can interrupt current resource allocation.

Arousing stimuli, either threat-related or pleasant, may be selected for priority at different stages within the processing stream. Here we examine the pattern of processing for non-task-relevant threatening (spiders: arousing to some) and pleasant stimuli (babies or chocolate: arousing to all) by recording the gaze of a spider Fearful and Non-fearful group while they performed a simple "follow the cross" task. There was no difference in first saccade latencies. Saccade trajectories showed a general hypervigilance for all stimuli in the Fearful group. Saccade landing positions corresponded to what each group would find arousing, such that the Fearful group deviated towards both types of images whereas the Non-fearful group deviated towards pleasant images. Secondary corrective saccade latencies away from threat-related stimuli were longer for the Fearful group (difficulty in disengaging) compared with the Non-fearful group. These results suggest that attentional biases towards arousing stimuli may occur at different processing stages.

Quantification choices for individual differences: An example of mapping self-report to psychophysiological responses.

A popular focus in affective neuroscience research has been to map the relationships between individual differences (e.g. personality and environmental experiences) and psychophysiological responses, in order to further understand the effect of individual differences upon neurobehavioral systems that support affect and arousal. Despite this trend, there have been a lack of practical examples demonstrating how the quantification of individual differences (e.g. categorical or continuous) impacts the observed relationships between different units of analysis (e.g. self-report > psychophysiological responses). To address this gap, we conducted a two-stage aggregated meta-analysis of self-reported intolerance of uncertainty (IU) and skin conductance responses during threat extinction (k = 18, n = 1006) using different quantification choices for individual differences in self-reported intolerance of uncertainty (continuous, categorical via median split, and categorical via extremes - one standard deviation above/below). Results from the meta-analyses revealed that the different quantification techniques produced some consistent (e.g. higher IU was significantly associated with skin conductance responding during late extinction training) and inconsistent IU-related effects. Furthermore, the number of statistically significant effects and effect sizes varied based on the quantification of individual differences in IU (e.g. categorical, compared to continuous was associated with more statistically significant effects, and larger effect sizes). The current study highlights how conducting different quantification methods for individual differences may help researchers understand the individual difference construct of interest (e.g. characterisation, measurement), as well as examine the stability and reliability of individual difference-based effects and correspondence between various units of analysis.

Intolerance of uncertainty heightens negative emotional states and dampens positive emotional states.

Individuals high in self-reported Intolerance of Uncertainty (IU) tend to view uncertainty as unbearable and stressful. Notably, IU is transdiagnostic, and high levels of IU are observed across many different emotional disorders (e.g., anxiety, depression). Research has primarily focused on how IU evokes and modulates emotional states such as fear and anxiety. However, recent research suggests that IU may have relevance for a broader range of emotional states. Here, an online survey was conducted to examine whether IU evokes and modulates a range of negative (e.g., fear/anxiety, sadness/upset, anger/frustration, disgust) and positive (e.g., happiness/joy, excitement/enthusiasm, surprise/interest) emotional states. Findings within a community sample (n = 231) revealed that individuals with higher levels of IU report: (1) that uncertainty in general and uncertainty under ambiguity are more likely to evoke negative emotional states and less likely to evoke positive emotional states, (2) that uncertainty under risk is less likely to evoke positive emotional states, and (3) that uncertainty heightens existing negative emotional states and dampens existing positive emotional states. Importantly, these IU-related findings remained when controlling for current experiences of general distress, anxious arousal, and anhedonic depression. Taken together, these findings suggest that IU is involved in evoking and modulating a wide array of emotional phenomena, which likely has relevance for transdiagnostic models and treatment plans for emotional disorders.

Consensus design of a calibration experiment for human fear conditioning.

Fear conditioning is a widely used laboratory model to investigate learning, memory, and psychopathology across species. The quantification of learning in this paradigm is heterogeneous in humans and psychometric properties of different quantification methods can be difficult to establish. To overcome this obstacle, calibration is a standard metrological procedure in which well-defined values of a latent variable are generated in an established experimental paradigm. These intended values then serve as validity criterion to rank methods. Here, we develop a calibration protocol for human fear conditioning. Based on a literature review, series of workshops, and survey of N = 96 experts, we propose a calibration experiment and settings for 25 design variables to calibrate the measurement of fear conditioning. Design variables were chosen to be as theory-free as possible and allow wide applicability in different experimental contexts. Besides establishing a specific calibration procedure, the general calibration process we outline may serve as a blueprint for calibration efforts in other subfields of behavioral neuroscience that need measurement refinement.

An examination of Intolerance of Uncertainty and contingency instruction on multiple indices during threat acquisition and extinction training.

Individuals who score high in self-reported Intolerance of Uncertainty (IU) tend to find uncertainty aversive. Prior research has demonstrated that under uncertainty individuals with high IU display difficulties in updating learned threat associations to safety associations. Importantly, recent research has shown that providing contingency instructions about threat and safety contingencies (i.e. reducing uncertainty) to individuals with high IU promotes the updating of learned threat associations to safety associations. Here we aimed to conceptually replicate IU and contingency instruction-based effects by conducting a secondary analysis of self-reported IU, ratings, skin conductance, and functional magnetic resonance imaging (fMRI) data recorded during uninstructed/instructed blocks of threat acquisition and threat extinction training (n = 48). Generally, no significant associations were observed between self-reported IU and differential responding to learned threat and safety cues for any measure during uninstructed/instructed blocks of threat acquisition and threat extinction training. There was some tentative evidence that higher IU was associated with greater ratings of unpleasantness and arousal to the safety cue after the experiment and greater skin conductance response to the safety cue during extinction generally. Potential explanations for these null effects and directions for future research are discussed.

Intolerance of uncertainty and novelty facilitated extinction: The impact of reinforcement schedule.

Individuals who score high in intolerance of uncertainty (IU) display reduced threat extinction. Recently, it was shown that replacing threat associations with novel associations during extinction learning (i.e., presenting a novel tone 100% of the time) can promote threat extinction retention in individuals with high IU. This novelty facilitated extinction (NFE) effect could be driven by the tone's novelty or reliability. Here, we sought to address this question by adjusting the reliability of the novel tone (i.e., the reinforcement rate) during NFE. We measured skin conductance response during an associative learning task in which participants (n = 92) were assigned to one of three experimental groups: standard extinction, NFE 100% reinforcement, or NFE 50% reinforcement. For standard extinction, compared to NFE 100% and 50% reinforcement groups, we observed a trend for greater recovery of the conditioned response during extinction retention. Individuals with high IU relative to low IU in the standard extinction group demonstrated a larger recovery of the conditioned response during extinction retention. These findings tentatively suggest that NFE effects are driven by the novelty rather than the reliability of the new stimulus. The implications of these findings for translational and clinical research in anxiety disorder pathology are discussed.

Effects of intolerance of uncertainty on subjective and psychophysiological measures during fear acquisition and delayed extinction.

Individuals who score high in self-reported Intolerance of Uncertainty (IU) tend to find uncertainty unacceptable and aversive. In recent years, research has shed light on the role of IU in modulating subjective (i.e. expectancy ratings) and psychophysiological responses (i.e. skin conductance) across different classical fear conditioning procedures. In particular, during immediate extinction higher IU is associated with disrupted safety learning. However, there remain gaps in understanding how IU, in comparison to other negative emotionality traits (STAI-T), impact different types of subjective and psychophysiological measures during different classical fear conditioning procedures. In our exploratory study, we analyzed IU, STAI-T, subjective (i.e. fear ratings) and psychophysiological (i.e. skin conductance, auditory startle blink) data recorded during fear acquisition training and 24 h-delayed extinction training (n = 66). Higher IU, controlled for STAI-T, was: (1) significantly associated with greater fear ratings to the learned fear cue during fear acquisition training, and (2) at trend associated with greater fear ratings to the learned fear versus safe cue during delayed extinction training. Null results were observed for both IU and STAI-T in relation to skin conductance and auditory startle blink during fear acquisition training and delayed extinction training. These results add to and extend our current understanding of the role of IU on subjective and physiological measures during different fear conditioning procedures particularly that of subjective fear ratings during acquisition and delayed extinction training. Implications of these findings and future directions are discussed.

Uncertainty Makes Me Emotional: Uncertainty as an Elicitor and Modulator of Emotional States.

Uncertainty and emotion are an inevitable part of everyday life and play a vital role in mental health. Yet, our understanding of how uncertainty and emotion interact is limited. Here, an online survey was conducted (n = 231) to examine whether uncertainty evokes and modulates a range of negative and positive emotions. The data show that uncertainty is predominantly associated with negative emotional states such as fear/anxiety. However, uncertainty was also found to modulate a variety of other negative (i.e., sadness/upset, anger/frustration, and confusion) and positive (i.e., surprise/interest and excited/enthusiastic) emotional states, depending on the valence of an anticipated outcome (i.e., negative and positive) and the sub parameter of uncertainty (i.e., risk and ambiguity). Uncertainty increased the intensity of negative emotional states and decreased the intensity of positive emotional states. These findings support prior research suggesting that uncertainty is aversive and associated with negative emotional states such as fear and anxiety. However, the findings also revealed that uncertainty is involved in eliciting and modulating a wide array of emotional phenomena beyond fear and anxiety. This study highlights an opportunity for further study of how uncertainty and emotion interactions are conceptualised generally and in relation to mental health.

Intolerance of uncertainty and physiological responses during instructed uncertain threat: A multi-lab investigation.

Individuals with high self-reported Intolerance of uncertainty (IU) tend to interpret uncertainty negatively. Recent research has been inconclusive on evidence of an association between IU and physiological responses during instructed uncertain threat. To address this gap, we conducted secondary analyses of IU and physiology data recorded during instructed uncertain threat tasks from two lab sites (Wisconsin-Madison; n = 128; Yale, n = 95). No IU-related effects were observed for orbicularis oculi activity (auditory startle-reflex). Higher IU was associated with: (1) greater corrugator supercilii activity to predictable and unpredictable threat of shock, compared to the safety from shock, and (2) poorer discriminatory skin conductance response between the unpredictable threat of shock, relative to the safety from shock. These findings suggest that IU-related biases may be captured differently depending on the physiological measure during instructed uncertain threat. Implications of these findings for neurobiological models of uncertainty and anticipation in anxiety are discussed.

Just let me check: The role of individual differences in self-reported anxiety and obsessive-compulsive features on subjective, behavioural, and physiological indices during a checking task.

Checking behaviour has been described as a form of preventative behaviour used by an individual to establish control over the environment and avoid future misfortune. However, when compulsive, checking behaviours can become disabling and distressing and have been linked to the maintenance of anxiety and obsessive-compulsive disorders. Despite this, there is limited literature across the field that has assessed the impact of dimensional measures of anxiety and obsessive-compulsive features (i.e., negative affect, uncertainty, and perfectionism) in driving checking behaviour. As such, the present study examined the impact of individual differences in self-reported anxiety and obsessive-compulsive features on subjective, behavioural, and physiological indices during a visual discrimination and checking task (n = 87). Higher self-reported anxiety and obsessive-compulsive features were associated with higher subjective ratings of unpleasantness and the urge to check during the task. Moreover, higher self-reported anxiety and obsessive-compulsive features related to general negative affect, uncertainty, and perfectionism were associated with greater checking frequency during the task. Lastly, stronger obsessional beliefs about perfectionism and the need for certainty were found to predict poorer accuracy, slower reaction times, and higher engagement of the corrugator supercilii during the task. In sum, these findings demonstrate how different anxiety and obsessive-compulsive features, in particular perfectionism and the need for certainty, may relate to and maintain checking behaviour in low threat contexts, which likely has implications for models of excessive and persistent checking in anxiety and obsessive-compulsive disorders.

Intolerance of uncertainty and threat reversal: A conceptual replication of Morriss et al. (2019).

The ability to update responding to threat cues is an important adaptive ability. Recently, Morriss et al. (2019) demonstrated that participants scoring high in Intolerance of Uncertainty (IU) were more capable of threat reversal. The current report aimed to conceptually replicate these results of Morriss et al. (2019) in an independent sample using a comparable paradigm (n = 102). Following a threat conditioning phase, participants were told that cues associated with threat and safety from electric shock would reverse. Responding was measured with skin conductance and fear potentiated startle. We failed to conceptually replicate the results of Morriss et al. (2019). Instead, we found that, for participants who received precise contingency instructions prior to acquisition, lower IUS (controlling for STAI-T) relative to higher IUS was associated with greater threat reversal, indexed via skin conductance responses. These results suggest that IU and contingency instructions differentially modulate the course of threat reversal.

The role of intolerance of uncertainty in classical threat conditioning: Recent developments and directions for future research.

Intolerance of uncertainty (IU), the tendency to find uncertainty aversive, is an important transdiagnostic dimension in mental health disorders. Over the last decade, there has been a surge of research on the role of IU in classical threat conditioning procedures, which serve as analogues to the development, treatment, and relapse of anxiety, obsessive-compulsive, and trauma- and stressor-related disorders. This review provides an overview of the existing literature on IU in classical threat conditioning procedures. The review integrates findings based on the shared or discrete parameters of uncertainty embedded within classical threat conditioning procedures. Under periods of unexpected uncertainty, where threat and safety contingencies change, high IU, over other self-reported measures of anxiety, is specifically associated with poorer threat extinction learning and retention, as well as overgeneralisation. Under periods of estimation and expected uncertainty, where the parameters of uncertainty are being learned or have been learned, such as threat acquisition training and avoidance learning, the findings are mixed for IU. These findings provide evidence that individual differences in IU play a significant role in maintaining learned fear and anxiety, particularly under volatile environments. Recommendations for future research are outlined, with discussion focusing on how parameters of uncertainty can be better defined to capture how IU is involved in the maintenance of learned fear and anxiety. Such work will be crucial for understanding the role of IU in neurobiological models of uncertainty-based maintenance of fear and anxiety and inform translational work aiming to improve the diagnosis and treatment of relevant psychopathology.

I told you it was safe: Associations between intolerance of uncertainty and different parameters of uncertainty during instructed threat of shock.

BACKGROUND AND OBJECTIVES: Self-reported Intolerance of Uncertainty (IU) is the tendency to find uncertainty aversive. There is a lack of empirical research on how IU modulates anticipatory responding during threatening contexts with different parameters of uncertainty. METHODS: Exploratory secondary analyses were conducted on an existing data set (n = 45) to examine whether IU is related to a particular parameter of uncertainty during instructed threat of shock (i.e. certain shock, certain safety from shock, outcome uncertainty of shock, temporal uncertainty of shock). RESULTS: Analyses revealed that IU was associated with larger auditory startle blink during the anticipatory period for the certain safety from shock condition relative to the certain shock condition. LIMITATIONS: The sample was relatively small. CONCLUSIONS: Individuals with higher self-reported IU may be more inclined to generalize threat to safety cues in the context of instructed threat of shock.

I Doubt It Is Safe: A Meta-analysis of Self-reported Intolerance of Uncertainty and Threat Extinction Training.

Background: Intolerance of uncertainty (IU), the tendency to find uncertainty distressing, is an important transdiagnostic dimension in mental health disorders. Higher self-reported IU has been linked to poorer threat extinction training (i.e., the updating of threat to safe associations), a key process that is targeted in exposure-based therapies. However, it remains to be seen whether IU-related effects during threat extinction training are reliably and specifically driven by the IU construct or a particular subcomponent of the IU construct over other self-reported measures of anxiety. Methods: A meta-analysis of studies from different laboratories (18 experiments; sample N = 1006) was conducted on associations between different variants of self-reported IU (i.e., 27-item, 12-item, inhibitory, and prospective subscales), trait anxiety, and threat extinction training via skin conductance response. The specificity of IU and threat extinction training was assessed against measures of trait anxiety. Results: All the self-reported variants of IU, but not trait anxiety, were associated with threat extinction training via skin conductance response (i.e., continued responding to the old threat cue). Specificity was observed for the majority of self-reported variants of IU over trait anxiety. Conclusions: The findings suggest that the IU construct broadly accounts for difficulties in threat extinction training and is specific over other measures of self-reported anxiety. These findings demonstrate the robustness and specificity of IU-related effects during threat extinction training and highlight potential opportunities for translational work to target uncertainty in therapies that rely on threat extinction principles such as exposure therapy.

Intolerance of uncertainty, and not social anxiety, is associated with compromised extinction of social threat.

Extinction-resistant threat is regarded as a central hallmark of pathological anxiety. However, it remains relatively under-studied in social anxiety. Here we sought to determine whether self-reported trait social anxiety is associated with compromised threat extinction learning and retention. We tested this hypothesis within two separate, socially relevant conditioning studies. In the first experiment, a Selective Extinction Through Cognitive Evaluation (SECE) paradigm was used, which included a cognitive component during the extinction phase, while experiment 2 used a traditional threat extinction paradigm. Skin conductance responses and subjective ratings of anxiety (experiment 1 and 2) and expectancy (experiment 2) were collected across both experiments. The findings of both studies demonstrated no effect of social anxiety on extinction learning or retention. Instead, results from experiment 1 indicated that individual differences in Intolerance of Uncertainty (IU) were associated with the ability to use contextual cues to decrease a conditioned response during SECE. However, during extinction retention, high IU predicted greater generalisation across context cues. Findings of experiment 2 revealed that higher IU was associated with impaired extinction learning and retention. The results from both studies suggest that compromised threat extinction is likely to be a characteristic of high levels of IU and not social anxiety.

Your guess is as good as mine: A registered report assessing physiological markers of fear and anxiety to the unknown in individuals with varying levels of intolerance of uncertainty.

Individuals who score high in Intolerance of Uncertainty (IU) have a tendency to find uncertainty and the unknown aversive. However, there is a dearth of literature on the extent to which the known vs. the unknown during threatening contexts induce fear and anxiety in individuals with high IU. In the following registered report we attempted to address this question by manipulating the known and unknown in the threat of predictable and unpredictable aversive events task. Throughout the task, we measured a variety of self-report (ratings of valence and arousal) and physiological indices (skin conductance, pupil dilation, orbicularis oculi, corrugator supercilii). We collected data from 93 participants. Higher IU, relative to lower IU was associated with: (1) less discriminatory orbicularis oculi activity between cue and interstimulus interval periods across conditions, and (2) larger corrugator supercilii activity to the known predictable shock condition and smaller corrugator supercilii activity to the known unpredictable shock condition, compared to the other conditions. These findings provide evidence that IU-related biases manifest differently depending on the physiological marker of fear and anxiety and the type of known-unknown threat i.e. orbicularis oculi activity was related to generalisation across conditions, whilse corrugator supercilii activity reflected distress/relief during conditions with known threat. Ultimately, this research will inform future models of IU in relation to anxiety and stress disorders.