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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

Correlations between percent signal change in the right amygdala and psychophysiology measures. Correlations between percent signal change in the right amygdala and psychophysiology measures. The response in the right amygdala is significantly correlated with SCR magnitude and at trend with pupil dilation, suggesting correspondence between measures of fear expression. SCR magnitude (μS), skin conductance magnitude measured in microSiemens; pupil dilation (Δmm) measured in delta millimetres
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Fig5: Correlations between percent signal change in the right amygdala and psychophysiology measures. Correlations between percent signal change in the right amygdala and psychophysiology measures. The response in the right amygdala is significantly correlated with SCR magnitude and at trend with pupil dilation, suggesting correspondence between measures of fear expression. SCR magnitude (μS), skin conductance magnitude measured in microSiemens; pupil dilation (Δmm) measured in delta millimetres

Mentions: Percent BOLD signal difference (CS+ vs. CS−) in the right amygdala correlated positively with SCR magnitude during early, r(12) = .540, p = .046, and late extinction, r(12) = .652, p = .012.(see Fig. 5). Percent BOLD signal in the right amygdala was not correlated with pupil dilation during early extinction, r(18) = .540, p = .246, but did correlate positively during late extinction, r(18) = .540, p = .052 (see Fig. 5).Fig. 5


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

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

Correlations between percent signal change in the right amygdala and psychophysiology measures. Correlations between percent signal change in the right amygdala and psychophysiology measures. The response in the right amygdala is significantly correlated with SCR magnitude and at trend with pupil dilation, suggesting correspondence between measures of fear expression. SCR magnitude (μS), skin conductance magnitude measured in microSiemens; pupil dilation (Δmm) measured in delta millimetres
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig5: Correlations between percent signal change in the right amygdala and psychophysiology measures. Correlations between percent signal change in the right amygdala and psychophysiology measures. The response in the right amygdala is significantly correlated with SCR magnitude and at trend with pupil dilation, suggesting correspondence between measures of fear expression. SCR magnitude (μS), skin conductance magnitude measured in microSiemens; pupil dilation (Δmm) measured in delta millimetres
Mentions: Percent BOLD signal difference (CS+ vs. CS−) in the right amygdala correlated positively with SCR magnitude during early, r(12) = .540, p = .046, and late extinction, r(12) = .652, p = .012.(see Fig. 5). Percent BOLD signal in the right amygdala was not correlated with pupil dilation during early extinction, r(18) = .540, p = .246, but did correlate positively during late extinction, r(18) = .540, p = .052 (see Fig. 5).Fig. 5

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