Jayne Morriss

Intolerance of uncertainty predicts fear extinction in amygdala-ventromedial prefrontal cortical circuitry

BackgroundCoordination of activity between the amygdala and ventromedial prefrontal cortex (vmPFC) is important for fear-extinction learning. Aberrant recruitment of this circuitry is associated with anxiety disorders. Here, we sought to determine if individual differences in future threat uncertainty sensitivity, a potential risk factor for anxiety disorders, underly compromised recruitment of fear extinction circuitry.Twenty-two healthy subjects completed a cued fear conditioning task with acquisition and extinction phases. During the task, pupil dilation, skin conductance response, and functional magnetic resonance imaging were acquired. We assessed the temporality of fear extinction learning by splitting the extinction phase into early and late extinction. Threat uncertainty sensitivity was measured using self-reported intolerance of uncertainty (IU).ResultsDuring early extinction learning, we found low IU scores to be associated with larger skin conductance responses and right amygdala activity to learned threat vs. safety cues, whereas high IU scores were associated with no skin conductance discrimination and greater activity within the right amygdala to previously learned safety cues. In late extinction learning, low IU scores were associated with successful inhibition of previously learned threat, reflected in comparable skin conductance response and right amgydala activity to learned threat vs. safety cues, whilst high IU scores were associated with continued fear expression to learned threat, indexed by larger skin conductance and amygdala activity to threat vs. safety cues. In addition, high IU scores were associated with greater vmPFC activity to threat vs. safety cues in late extinction. Similar patterns of IU and extinction learning were found for pupil dilation. The results were specific for IU and did not generalize to self-reported trait anxiety.ConclusionsOverall, the neural and psychophysiological patterns observed here suggest high IU individuals to disproportionately generalize threat during times of uncertainty, which subsequently compromises fear extinction learning. More broadly, these findings highlight the potential of intolerance of uncertainty-based mechanisms to help understand pathological fear in anxiety disorders and inform potential treatment targets.

Nothing is safe: Intolerance of uncertainty is associated with compromised fear extinction learning

Highlights • We tested how fear extinction learning varied with Intolerance of Uncertainty (IU).• High IU predicted threat generalization during early extinction.• High IU predicted continued responding to learned threat during late extinction.• Future threat uncertainty may maintain learned fear in the anxiety disorders.

Still feeling it: the time course of emotional recovery from an attentional perspective

Emotional reactivity and the time taken to recover, particularly from negative, stressful, events, are inextricably linked, and both are crucial for maintaining well-being. It is unclear, however, to what extent emotional reactivity during stimulus onset predicts the time course of recovery after stimulus offset. To address this question, 25 participants viewed arousing (negative and positive) and neutral pictures from the International Affective Picture System (IAPS) followed by task-relevant face targets, which were to be gender categorized. Faces were presented early (400–1500 ms) or late (2400–3500 ms) after picture offset to capture the time course of recovery from emotional stimuli. Measures of reaction time (RT), as well as face-locked N170 and P3 components were taken as indicators of the impact of lingering emotion on attentional facilitation or interference. Electrophysiological effects revealed negative and positive images to facilitate face-target processing on the P3 component, regardless of temporal interval. At the individual level, increased reactivity to: (1) negative pictures, quantified as the IAPS picture-locked Late Positive Potential (LPP), predicted larger attentional interference on the face-locked P3 component to faces presented in the late time window after picture offset. (2) Positive pictures, denoted by the LPP, predicted larger facilitation on the face-locked P3 component to faces presented in the earlier time window after picture offset. These results suggest that subsequent processing is still impacted up to 3500 ms after the offset of negative pictures and 1500 ms after the offset of positive pictures for individuals reacting more strongly to these pictures, respectively. Such findings emphasize the importance of individual differences in reactivity when predicting the temporality of emotional recovery. The current experimental model provides a novel basis for future research aiming to identify profiles of adaptive and maladaptive recovery.

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

ABSTRACT 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.

Out with the old and in with the new: The role of intolerance of uncertainty in reversal of threat and safety

The ability to learn and reverse threat associations is crucial for survival. The extent to which old threat associations are inhibited and new threat associations are formed may depend on sensitivity to future threat uncertainty. To assess the extent to which Intolerance of Uncertainty (IU) predicts threat learning and reversal, we recorded expectancy ratings and skin conductance in 44 healthy participants during an associative learning paradigm, where threat and safety contingencies were reversed. During acquisition and reversal, we observed larger SCR magnitude and expectancy ratings for threat vs. safety cues. However, during reversal higher IU was associated with larger SCR magnitude to new threat vs. new safety cues, compared to lower IU. These results were specific to IU-related variance, over shared variance with trait anxiety (STAIX-2). Overall, these findings suggest that individuals high in IU are able to reverse threat and safety associations in the presence of direct threat. Such findings help us understand the recently revealed link between IU and threat extinction, where direct threat is absent. Moreover, these findings highlight the potential relevance of IU in clinical intervention and treatment for anxiety disorders.

Multimodal evidence for delayed fear extinction in adolescence and young adulthood.

Previous research in rodents and humans points to an evolutionarily conserved profile of blunted fear extinction during adolescence, underpinned by brain structures such as the amygdala and medial prefrontal cortex (mPFC). In this study, we examine age-related effects on the function and structural connectivity of this system in fear extinction in adolescence and young adulthood. Younger age was associated with greater amygdala activity and delayed mPFC engagement to learned threat cues as compared to safety cues. Furthermore, greater structural integrity of the uncinate fasciculus, a white matter tract that connects the amygdala and mPFC, mediated the relationship between age and acceleration of mPFC engagement during extinction. These findings suggest that age-related changes in the structure and function of amygdala-mPFC circuitry may underlie the protracted maturation of fear regulatory processes, rendering younger individuals more vulnerable to anxiety disorders, which emerge during development.

Social domain based modulation of neural responses to threat: The different roles of romantic partners versus friends

ABSTRACT The neural circuitry associated with threat regulation in the absence of other people is well established. An examination of threat regulatory processes with people from different domains of an individual’s social world is key to understanding social emotion regulation and personality functioning conceptualised as social domain organisation. In this study, 42 healthy female participants completed functional magnetic imaging sessions in which they underwent a scan in the presence of a romantic partner or friend, whilst completing a threat of shock task. In the presence of a romantic partner vs. friend, we found a reduction in amygdala activation to threat vs. safe trials over time. Furthermore, in the presence of a romantic partner vs. friend we observed greater subgenual anterior cingulate cortex and ventromedial prefrontal cortex activation to threat vs. safe trials overall. The results support the hypothesis that recruitment of threat regulation circuitry is modulated by romantic partner relative to another person well-known to the individual. Future work needs to examine neural responses to a wider range of stimuli across more social domains, and implications of failures of this neural organisation for psychopathology.

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

ABSTRACT 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.

Escape the bear and fall to the lion: The impact of avoidance availability on threat acquisition and extinction

Pervasive avoidance behaviour is a core feature of anxiety disorders. However, little is known about how the availability of avoidance modulates learned threat responding. To assess this question, we recorded avoidance behaviour, electrodermal activity and expectancy ratings in 53 healthy participants during an associative learning paradigm with embedded unavoidable and avoidable trials. When avoidance was available, we observed greater avoidance behaviour for threat versus safety cues, as well as reduced differential skin conductance responses for unavoidable threat versus safety cues. When avoidance was unavailable, as during the extinction phase, we observed sustained differential skin conductance responses for threat versus safety cues. For all phases, we found greater expectancy ratings for threat versus safe cues. Furthermore, greater avoidance behaviour predicted larger differential skin conductance responses to threat versus safety cues during extinction. Overall, the results show that the conditioned response is attenuated during situations where avoidance is available, but it recovers when avoidance is unavailable, subsequently prolonging threat extinction.