The DOI matches its Crossref record; 117 of the 118 references it cites were found in a registry or an index.
Brain mediators of cardiovascular responses to social threat, part II: prefrontal–subcortical pathways and relationship with anxiety
Open accessAbstract
Social evaluative threat (SET) is a potent stressor in humans that causes autonomic changes, endocrine responses, and multiple health problems. Neuroimaging has recently begun to elucidate the brain correlates of SET, but as yet little is known about the mediating cortical-brainstem pathways in humans. This paper replicates and extends findings in a companion paper (Wager et al., 2009) using an independent cohort of participants and different image acquisition parameters. Here, we focused specifically on relationships between the medial prefrontal cortex (MPFC), midbrain periaqueductal gray (PAG), and heart rate (HR). We applied multi-level path analysis to localize brain mediators of SET effects on HR and self-reported anxiety. HR responses were mediated by opposing signals in two distinct sub-regions of the MPFC-increases in rostral dorsal anterior cingulate cortex (rdACC) and de-activation in ventromedial prefrontal cortex (vmPFC). In addition, HR responses were mediated by PAG. Additional path analyses provided support for two cortical-subcortical pathways: one linking vmPFC, PAG, and HR, and another linking rdACC, thalamus, and HR. PAG responses were linked with HR changes both before and during SET, whereas cortical regions showed stronger connectivity with HR during threat. Self-reported anxiety showed a partially overlapping, but weaker, pattern of mediators, including the vmPFC, dorsomedial prefrontal cortex, and lateral frontal cortex, as well as substantial individual differences that were largely unexplained. Taken together, these data suggest pathways for the translation of social threats into both physiological and experiential responses, and provide targets for future research on the generation and regulation of emotion.
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“The top-down view nevertheless remains strong in cognitive neuroscience where the expression and regulation of emotion is putatively grounded in the frontal lobe regulation of subcortical emotion regions, including autonomic source nuclei (Roy et al., 2012;Wager et al., 2009).”
From Physiological feelings (2019) · cites this paper as Wager et al., 2009
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“In a pair of studies [64,65], speech preparation elicited activity increases in dorsal vmPFC/dACC and decreases in ventral vmPFC (figure 1j).”
From Ventromedial prefrontal–subcortical systems and the generation of affective meaning (2012) · cites this paper as [65]
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“Both effects tracked the individual time course of autonomic changes during the challenge, and the relationships between vmPFC and autonomic changes were mediated in part by activity in PAG.”
From Ventromedial prefrontal–subcortical systems and the generation of affective meaning (2012) · cites this paper as [65]
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“By comparison, other components of the extended dACC/medial wall response are likely to represent the direct interaction between autonomic and cognitive states.36,37”
From Neural signatures of human fear conditioning: an updated and extended meta-analysis of fMRI studies (2016) · cites this paper as [37]
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“Therefore, the processes that are abnormal in patients with anxiety disorders (evidenced in part by increased responsivness in amygdala and insula (Etkin & Wager, 2007) may be quite different from the anxiety reported in normal individuals during SET.”
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Metadata
- Authors
- Wager, T. D., van Ast, V. A., Hughes, B. L., Davidson, M. L., Lindquist, M. A., & Ochsner, K. N.
- Affiliations
- Columbia University (US)
- Corresponding author
- Wager, Tor D.
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 47
- Issue
- 3
- Pages
- 836-851
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC4169880
- OpenAlex
- W2105639637
- Cited by
- 264
- References
- 118
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 7 · 2023: 10 · 2022: 14 · 2021: 15 · 2020: 15 · 2019: 19 · 2018: 21 · 2017: 14 · 2016: 20 · 2015: 25 · 2014: 14 · 2013: 17 · 2012: 29
- FWCI
- 10.00
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- National Institute of Mental Health (MH076136, MH082308, R01MH076137, R01MH076136, R21MH082308, MH076137)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD069178)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- social-evaluative threat, heart rate, anxiety, medial prefrontal cortex, periaqueductal gray, ventromedial prefrontal cortex, dorsal anterior cingulate cortex, thalamus, brainstem, emotion regulation, individual differences
- MeSH terms
- Anxiety, Autonomic Nervous System, Brain Mapping, Cardiovascular Physiological Phenomena, Female, Heart Rate, Humans, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Male, Periaqueductal Gray, Prefrontal Cortex, Young Adult
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