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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

Intolerance of uncertainty predicts vmPFC activation during fear extinction. a vmPFC small volume correction from the (CS− > CS+)early > (CS− > CS+)late × IU contrast in extinction. b Significant correlations between percent signal change in the vmPFC for CS+ − CS− and IU scores during early and late extinction. During late extinction, high IU scores were associated with increased recruitment of the vmPFC to the CS+, relative to the CS−, suggesting attempts to down regulate fearful associations. MNI coordinates: R right, L left
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Fig4: Intolerance of uncertainty predicts vmPFC activation during fear extinction. a vmPFC small volume correction from the (CS− > CS+)early > (CS− > CS+)late × IU contrast in extinction. b Significant correlations between percent signal change in the vmPFC for CS+ − CS− and IU scores during early and late extinction. During late extinction, high IU scores were associated with increased recruitment of the vmPFC to the CS+, relative to the CS−, suggesting attempts to down regulate fearful associations. MNI coordinates: R right, L left

Mentions: As expected, areas within the right amygdala and the vmPFC significantly correlated with IU scores during extinction (see Table 2, Figs. 3 and 4). We performed follow-up correlations to identify the source of the interaction effect from the significant IU × (CS+ vs. CS−)early > (CS+ vs. CS−)late contrast. During early extinction, higher IU predicted increased activation to the CS−, relative to CS+ for the right amygdala cluster, r(19) = −.58, p = .005 (see Fig. 3). There were no significant effects of IU in the vmPFC cluster during early extinction however, r(19) = −0.106, p = .646. During late extinction, IU was positively associated with activation to the CS+ relative to the CS− for the right amygdala cluster, r(19) = .47, p = .030 (see Fig. 3), and, unexpectedly, for the vmPFC cluster, r(19) = .62, p = .002 (see Fig. 4). In addition, higher IU predicted relative higher right amygdala activity from CS− early to CS− late, r(19) = .631, p = .002, suggesting generalization of threat to the CS− at the start of extinction. All other condition and time difference scores were not significant for the right amygdala and vmPFC, p’s > .125. Furthermore, the BOLD response in areas associated with vigilance, such as the opercular cortex, cingulate gyrus, lateral occipital cortex and precentral gyrus, significantly differed over time as a function of IU scores during extinction (see Table 2).Fig. 3


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

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

Intolerance of uncertainty predicts vmPFC activation during fear extinction. a vmPFC small volume correction from the (CS− > CS+)early > (CS− > CS+)late × IU contrast in extinction. b Significant correlations between percent signal change in the vmPFC for CS+ − CS− and IU scores during early and late extinction. During late extinction, high IU scores were associated with increased recruitment of the vmPFC to the CS+, relative to the CS−, suggesting attempts to down regulate fearful associations. MNI coordinates: R right, L left
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig4: Intolerance of uncertainty predicts vmPFC activation during fear extinction. a vmPFC small volume correction from the (CS− > CS+)early > (CS− > CS+)late × IU contrast in extinction. b Significant correlations between percent signal change in the vmPFC for CS+ − CS− and IU scores during early and late extinction. During late extinction, high IU scores were associated with increased recruitment of the vmPFC to the CS+, relative to the CS−, suggesting attempts to down regulate fearful associations. MNI coordinates: R right, L left
Mentions: As expected, areas within the right amygdala and the vmPFC significantly correlated with IU scores during extinction (see Table 2, Figs. 3 and 4). We performed follow-up correlations to identify the source of the interaction effect from the significant IU × (CS+ vs. CS−)early > (CS+ vs. CS−)late contrast. During early extinction, higher IU predicted increased activation to the CS−, relative to CS+ for the right amygdala cluster, r(19) = −.58, p = .005 (see Fig. 3). There were no significant effects of IU in the vmPFC cluster during early extinction however, r(19) = −0.106, p = .646. During late extinction, IU was positively associated with activation to the CS+ relative to the CS− for the right amygdala cluster, r(19) = .47, p = .030 (see Fig. 3), and, unexpectedly, for the vmPFC cluster, r(19) = .62, p = .002 (see Fig. 4). In addition, higher IU predicted relative higher right amygdala activity from CS− early to CS− late, r(19) = .631, p = .002, suggesting generalization of threat to the CS− at the start of extinction. All other condition and time difference scores were not significant for the right amygdala and vmPFC, p’s > .125. Furthermore, the BOLD response in areas associated with vigilance, such as the opercular cortex, cingulate gyrus, lateral occipital cortex and precentral gyrus, significantly differed over time as a function of IU scores during extinction (see Table 2).Fig. 3

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