A neural mediator of human anxiety sensitivity

Abstract

Advances in the neuroscientific understanding of bodily autonomic awareness, or interoception, have led to the hypothesis that human trait anxiety sensitivity (AS)-the fear of bodily autonomic arousal-is primarily mediated by the anterior insular cortex. Despite broad appeal, few experimental studies have comprehensively addressed this hypothesis. We recruited 55 individuals exhibiting a range of AS and assessed them with functional magnetic resonance imaging (fMRI) during aversive fear conditioning. For each participant, three primary measures of interest were derived: a trait Anxiety Sensitivity Index score; an in-scanner rating of elevated bodily anxiety sensations during fear conditioning; and a corresponding estimate of whole-brain functional activation to the conditioned versus nonconditioned stimuli. Using a voxel-wise mediation analysis framework, we formally tested for 'neural mediators' of the predicted association between trait AS score and in-scanner anxiety sensations during fear conditioning. Contrary to the anterior insular hypothesis, no evidence of significant mediation was observed for this brain region, which was instead linked to perceived anxiety sensations independently from AS. Evidence for significant mediation was obtained for the dorsal anterior cingulate cortex-a finding that we argue is more consistent with the hypothesized role of human cingulofrontal cortex in conscious threat appraisal processes, including threat-overestimation. This study offers an important neurobiological validation of the AS construct and identifies a specific neural substrate that may underlie high AS clinical phenotypes, including but not limited to panic disorder.

Brain responses to uncertainty about upcoming rectal discomfort in quiescent Crohn's disease – a fMRI study

“…These findings are consistent with a growing number of studies indicating that anticipatory anxiety during the expectation of threatening stimuli leads to different behavioral tendencies depending on the perceived level of threat and the subject's level of trait‐anxiety . During low to moderate perceived threat levels, healthy subjects are able to shift their attention away from the expected source of threat, by increasing a default processing state .…”

“…Upon stronger perceived threat, there is a shift to a hypervigilant state . This relationship between threat level, behavioral tendencies and brain activity is moderated by individual differences in anxiety levels . This mechanism might account for the hyperactivations that we demonstrated in our patients, especially as these hyperactivations were highly correlated with the patient's VSI and anxiety‐trait scores.…”

“…Harrison et al . identified the anterior insular cortex as a mediator between fear‐evoked brain activation and self‐reported anxiety sensations . Likewise, the critical role of the right anterior insula in mediating awareness of interoceptive information, thus contributing to emotional feelings, has been shown by Critchley et al .…”

“…showed that unpredictability and uncontrollability modulate the neural response to threat in healthy controls. Likewise, subjects prone to anxiety demonstrate higher activation of cingulofrontal cortex during fear conditioning . Finally, anxiety was also reported to affect neural responses during abdominal pain‐related memory formation and reinstatement …”

Mapping the sequence of brain events in response to disgusting food

“…However, the use of group average data in the strategy of comparing activation between high and moderate disgusting scenes may, to some extent, circumvent this limitation as was the case in pain studies [Wager et al, ]. This analysis confirmed a correspondence between the intensity of subjective disgust and activation in relevant core elements such as the insula, amygdala and PAG, in addition to the ACC (a key site for the conscious appraisal of threat [Harrison et al, ]) and visual areas. Importantly, higher disgust intensity was associated with lower activation in the orbitofrontal cortex in this analysis, which may express a dual effect of disgusting stimulation on this brain area, with initial enhancement of (aversion‐related) activity and later inhibition of (appetite‐related) activity during the most intense scenes.…”