School of Medicine Publications and Presentations
Document Type
Article
Publication Date
1-2022
Abstract
Excessive expression of fear responses in anticipation of threat occurs in anxiety, but understanding of underlying pathophysiological mechanisms is limited. Animal research indicates that threat-anticipatory defensive responses are dynamically organized by threat imminence and rely on conserved circuitry. Insight from basic neuroscience research in animals on threat imminence could guide mechanistic research in humans mapping abnormal function in this circuitry to aberrant defensive responses in pathological anxiety.
50 pediatric anxiety patients and healthy-comparisons (33 females) completed an instructed threat-anticipation task whereby cues signaled delivery of painful (threat) or non-painful (safety) thermal stimulation. Temporal changes in skin-conductance indexed anxiety effects on anticipatory responding as function of threat imminence. Multivariate network analyses of resting-state functional connectivity data from a subsample were used to identify intrinsic-function correlates of anticipatory-response dynamics, within a specific, distributed network derived from translational research on defensive responding.
By considering threat imminence, analyses revealed specific anxiety effects. Importantly, pathological anxiety was associated with excessive deployment of anticipatory physiological response as threat, but not safety, outcomes became more imminent. Magnitude of increase in threat-anticipatory physiological responses corresponded with magnitude of intrinsic connectivity within a cortical-subcortical circuit. Moreover, more severe anxiety was associated with stronger associations between anticipatory physiological responding and connectivity that ventromedial prefrontal cortex showed with hippocampus and basolateral amygdala, regions implicated in animal models of anxiety.
These findings link basic and clinical research, highlighting variations in intrinsic function in conserved defensive circuitry as a potential pathophysiological mechanism in anxiety.
Recommended Citation
Abend, R., Ruiz, S. G., Bajaj, M. A., Harrewijn, A., Linke, J. O., Atlas, L. Y., Winkler, A. M., & Pine, D. S. (2022). Threat imminence reveals links among unfolding of anticipatory physiological response, cortical-subcortical intrinsic functional connectivity, and anxiety. Neurobiology of stress, 16, 100428. https://doi.org/10.1016/j.ynstr.2022.100428
Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.
Publication Title
Neurobiology of stress
DOI
10.1016/j.ynstr.2022.100428
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
Copyright © 2022 Published by Elsevier Inc.