Brain mediators of cardiovascular responses to social threat
Open accessAbstract
Social threat is a key component of mental "stress" and a potent generator of negative emotions and physiological responses in the body. How the human brain processes social context and drives peripheral physiology, however, is relatively poorly understood. Human neuroimaging and animal studies implicate the dorsal medial prefrontal cortex (MPFC), though this heterogeneous region is likely to contain multiple sub-regions with diverse relationships with physiological reactivity and regulation. We used fMRI combined with a novel multi-level path analysis approach to identify brain mediators of the effects of a public speech preparation task (social evaluative threat, SET) on heart rate (HR). This model provides tests of functional pathways linking experimentally manipulated threat, regional fMRI activity, and physiological output, both across time (within person) and across individuals (between persons). It thus integrates time series connectivity and individual difference analyses in the same path model. The results provide evidence for two dissociable, inversely coupled sub-regions of MPFC that independently mediated HR responses. SET caused activity increases in a more dorsal pregenual cingulate region, whose activity was coupled with HR increases. Conversely, SET caused activity decreases in a right ventromedial/medial orbital region, which were coupled with HR increases. Individual differences in coupling strength in each pathway independently predicted individual differences in HR reactivity. These results underscore both the importance and heterogeneity of MPFC in generating physiological responses to threat.
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Subgenual and pregenual regions of the anterior cingulate cortex also play a role in social pain and rejection.
“Recent work highlights a similar role in social pain and rejection for subgenual and pregenual regions of the ACC as well (Rotge et al., 2014; Wager et al., 2009).”
From Neural responses to social threat and predictors of cognitive behavioral therapy and acceptance and commitment therapy in social anxiety disorder (2017) · cites this paper as Wager et al., 2009
The Results (‘Brain responses to SET’) report pregenual ACC activation during social evaluative threat, supporting a role in a related social-stress response. The Discussion says subgenual involvement is only possible and identifies the activated region primarily as pregenual. The study used speech preparation as a threat task; it does not establish a role for both regions in social pain or rejection specifically. Page numbers are unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPregenual ACC has been implicated in social pain and rejection, regulation of emotional conflicts, and responses to social-evaluative threat.
“Like dACC, pregenual ACC has been implicated in social pain and rejection (Rotge et al., 2014), as well as during the regulation of emotional conflicts (Etkin et al., 2011), and responses to social-evaluative threat (Wager et al., 2009).”
From Neural responses to social threat and predictors of cognitive behavioral therapy and acceptance and commitment therapy in social anxiety disorder (2017) · cites this paper as Wager et al., 2009
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 the periaqueductal gray.
“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 [64]
In a pair of studies, speech preparation elicited activity increases in dorsal vmPFC/dACC and decreases in ventral vmPFC.
“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 [64]
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- Critchley HD Mathias CJ Josephs O O'Doherty J Zanini S Dewar BK Human cingulate cortex and autonomic control: converging neuroimaging and clinical evidence Brain 2003 126 Pt 10 2139 2152 12821513
- Gianaros PJ Sheu LK Matthews KA Jennings JR Manuck SB Hariri AR Individual Differences in Stressor-Evoked Blood Pressure Reactivity Vary with Activation, Volume, and Functional Connectivity of the Amygdala Journal of Neuroscience 2008b 28 4 990 18216206 PMC2526972
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- Authors
- Wager, T. D., Waugh, C. E., Lindquist, M., Noll, D. C., Fredrickson, B. L., & Taylor, S. F.
- Affiliations
- Columbia University (US)
- Stanford University (US)
- University of North Carolina at Chapel Hill (US)
- University of Michigan (US)
- Corresponding author
- Wager, Tor D.
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 47
- Issue
- 3
- Pages
- 821-835
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC3275821
- OpenAlex
- W2103729454
- Cited by
- 402
- References
- 180
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 22 · 2023: 15 · 2022: 30 · 2021: 29 · 2020: 35 · 2019: 27 · 2018: 27 · 2017: 35 · 2016: 21 · 2015: 27 · 2014: 35 · 2013: 15 · 2012: 23
- FWCI
- 10.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (MH 59615, R01MH059615, MH076136, R01MH076136, R37MH076136)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Keywords
- social danger, social-evaluative threat, heart rate reactivity, dorsomedial prefrontal cortex, ventromedial prefrontal cortex, heart-brain interaction, individual differences, cardiovascular response
- MeSH terms
- Adult, Brain, Brain Mapping, Female, Heart Rate, Humans, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Male, Models, Neurological, Speech, Stress, Psychological, Prefrontal Cortex
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