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

Morriss J, Christakou A, van Reekum CM - Biol Mood Anxiety Disord (2015)

Bottom Line: During 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 addition, high IU scores were associated with greater vmPFC activity to threat vs. safety cues in late extinction.The results were specific for IU and did not generalize to self-reported trait anxiety.

View Article: PubMed Central - PubMed

Affiliation: Centre for Integrative Neuroscience and Neurodynamics, School of Psychology and Clinical Language Sciences, University of Reading, Earley Gate, Whiteknights Campus, RG6 6AH Reading, UK.

ABSTRACT

Background: Coordination 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).

Results: During 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.

Conclusions: Overall, 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.

No MeSH data available.


Related in: MedlinePlus

Conditioning task design
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Fig1: Conditioning task design

Mentions: The acquisition phase consisted of 24 trials (12 CS+, 12 CS−), the extinction phase 32 trials (16 CS+, 16 CS−) and the reacquisition phase 60 trials (8 CS+, 24 CS+unpaired, 28 CS−; data not presented here) (see Fig. 1). Experimental trials were pseudo randomized into an order, which resulted in no more than three presentations of the same stimulus in a row. Colour-sound contingencies were counterbalanced across the sample.Fig. 1


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

Morriss J, Christakou A, van Reekum CM - Biol Mood Anxiety Disord (2015)

Conditioning task design
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4496864&req=5

Fig1: Conditioning task design
Mentions: The acquisition phase consisted of 24 trials (12 CS+, 12 CS−), the extinction phase 32 trials (16 CS+, 16 CS−) and the reacquisition phase 60 trials (8 CS+, 24 CS+unpaired, 28 CS−; data not presented here) (see Fig. 1). Experimental trials were pseudo randomized into an order, which resulted in no more than three presentations of the same stimulus in a row. Colour-sound contingencies were counterbalanced across the sample.Fig. 1

Bottom Line: During 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 addition, high IU scores were associated with greater vmPFC activity to threat vs. safety cues in late extinction.The results were specific for IU and did not generalize to self-reported trait anxiety.

View Article: PubMed Central - PubMed

Affiliation: Centre for Integrative Neuroscience and Neurodynamics, School of Psychology and Clinical Language Sciences, University of Reading, Earley Gate, Whiteknights Campus, RG6 6AH Reading, UK.

ABSTRACT

Background: Coordination 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).

Results: During 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.

Conclusions: Overall, 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.

No MeSH data available.


Related in: MedlinePlus