Anxiety-Related Frontocortical Activity Is Associated With Dampened Stressor Reactivity in the Real World

Abstract

Negative affect is a fundamental dimension of human emotion. When extreme, it contributes to a variety of adverse outcomes, from physical and mental illness to divorce and premature death. Mechanistic work in animals and neuroimaging research in humans and monkeys have begun to reveal the broad contours of the neural circuits governing negative affect, but the relevance of these discoveries to everyday distress remains incompletely understood. Here, we used a combination of approaches—including neuroimaging assays of threat anticipation and emotional-face perception and more than 10,000 momentary assessments of emotional experience—to demonstrate that individuals who showed greater activation in a cingulo-opercular circuit during an anxiety-eliciting laboratory paradigm experienced lower levels of stressor-dependent distress in their daily lives ( ns = 202–208 university students). Extended amygdala activation was not significantly related to momentary negative affect. These observations provide a framework for understanding the neurobiology of negative affect in the laboratory and in the real world.

Adolescent social anxiety is associated with diminished discrimination of anticipated threat and safety in the bed nucleus of the stria terminalis

“…Epochs corresponding to the presentation of the white-noise visual masks and rating prompts were modeled using the same approach and treated as nuisance regressors. Consistent with prior work using shock-reinforced variants of the countdown task in adults (Grogans et al, under review;Hur et al, 2022;Hur et al, 2020;Kim et al, 2023), additional nuisance variates included estimates of volume-to-volume displacement, motion (6 parameters, 0-and 1volume lagged), cerebrospinal fluid (CSF) signal, instantaneous pulse and respiration rates, and ICAderived nuisance signals (e.g. brain edge, CSF edge, global motion, white matter) (Pruim et al, 2015).…”

“…Anatomical Data Processing. Methods are similar to those described in other recent reports by our group (Grogans et al, under review;Hur et al, 2018;Hur et al, 2022;Hur et al, 2020;Kim et al, 2023).…”

“…Items probe the frequency of fear or anxiety symptoms evoked by specific social situations (e.g., "I feel scared when I have to speak or read in front of a group of people") on a 3-point Likert scale ranging from 0 Hur et al, 2022;Hur et al, 2020;Kim et al, 2023), the MSTC paradigm takes the form of a 2 (Valence: Social Threat/Safety) × 2 (Temporal Certainty: Uncertain/Certain) × 2 (Phase:…”

Neuroticism/negative emotionality is associated with increased reactivity to uncertain threat in the bed nucleus of the stria terminalis, not the amygdala

“…Broadband N/NE. As in our prior work Hur et al, 2020a;Hur et al, 2020b;Hur et al, 2022), we used 2 well-established measures of neuroticism (Big Five Inventory-Neuroticism) (John et al, 2008) and trait anxiety (International Personality Item Pool-Trait Anxiety) (Goldberg, 1999;Goldberg et al, 2006) to quantify individual differences in N/NE on three occasions: screening, baseline, and 6-month follow-up (see Figure 1 in the main report). Participants used a 1 (disagree strongly) to 5 (agree strongly) scale to rate a total of 18 items (e.g., depressed or blue, tense, worry, nervous, get distressed easily, fear for the worst, afraid of many things).…”

“…The EAc is an anatomical macrocircuit encompassing the dorsal amygdala in the region of the central nucleus (Ce) and the neighboring bed nucleus of the stria terminalis (BST) (28). Perturbation studies in animals demonstrate that the Ce and BST are critical for orchestrating adaptive defensive responses to a wide variety of threats (29, 30). Large-scale neuroimaging studies (N=592) in monkeys show that Ce and BST reactivity to uncertain threat covaries with stable individual differences in anxious temperament, a core facet of N/NE (31).…”