When fear is near: threat imminence elicits prefrontal periaqueductal gray shifts in humans.
Open accessAbstract
Humans, like other animals, alter their behavior depending on whether a threat is close or distant. We investigated spatial imminence of threat by developing an active avoidance paradigm in which volunteers were pursued through a maze by a virtual predator endowed with an ability to chase, capture, and inflict pain. Using functional magnetic resonance imaging, we found that as the virtual predator grew closer, brain activity shifted from the ventromedial prefrontal cortex to the periaqueductal gray. This shift showed maximal expression when a high degree of pain was anticipated. Moreover, imminence-driven periaqueductal gray activity correlated with increased subjective degree of dread and decreased confidence of escape. Our findings cast light on the neural dynamics of threat anticipation and have implications for the neurobiology of human anxiety-related disorders.
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The periaqueductal grey contributes to non-conscious emotion perception and reflexive behaviors aimed at helping to escape threatening situations.
“A small region in the brainstem, the periaqueductal grey, contributes to non-conscious emotion perception and reflexive behaviors aimed at helping to escape threatening situations [145,150].”
From Treatment of dissociative identity disorder: leveraging neurobiology to optimize success (2024) · cites this paper as [145]
In the supplied passage labeled “When Fear Is Near > Abstract” (page unavailable), the paper identifies the PAG as a midbrain region implicated in reflexive escape behavior and reports increased PAG activity as threat became proximal. The copy does not establish a role for the PAG in non-conscious emotion perception. (LLM, conf=0.88)
Experimental — accuracy not yet measuredUnder typical circumstances, cortical structures like vmPFC and limbic regions like amygdala and periaqueductal grey have a balanced relationship and can influence the activity of the other flexibly based on need and context.
“Under typical circumstances, cortical structures like the ventromedial prefrontal cortex (vmPFC) and limbic regions like the amygdala and periaqueductal grey have a balanced relationship and can influence the activity of the other flexibly based on need and context [145,146].”
From Treatment of dissociative identity disorder: leveraging neurobiology to optimize success (2024) · cites this paper as [145]
The paper’s ‘When Fear Is Near’ section describes a balance between forebrain and midbrain responses to threat: vmPFC activity is greater with distal threat, PAG activity with proximal threat, and each may affect the other’s control of defensive responses. It also describes connections involving the amygdala. It does not establish that all three regions have a generally balanced, mutually influential relationship under typical circumstances outside threat responses. (LLM, conf=0.84)
Experimental — accuracy not yet measuredA bias towards looming and approaching stimuli has been observed in structures directly involved in orchestrating the behavioral response to pain and threatening stimuli, such as the periaqueductal grey.
“Supporting this hypothesis, a bias towards looming and approaching stimuli has been also observed in structures directly involved in orchestrating the behavioral response to pain and threatening stimuli, such as the periaqueductal grey (Mobbs et al. 2007; Coker-Appiah et al. 2013; Vieira et al. 2020).”
From Neuroanatomical correlates of peripersonal space: bridging the gap between perception, action, emotion and social cognition (2024) · cites this paper as Mobbs et al. 2007
In the indexed copy (When Fear Is Near > Abstract; page unavailable), PAG activity increased as a virtual predator approached, particularly when more pain was anticipated. This supports a response to an approaching threat, but the study did not test looming stimuli or approaching stimuli generally. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe periaqueductal gray is responsible for generating primitive affective sensations and plays a critical role in maintaining autonomic and physiological homeostasis.
“In addition, the periaqueductal gray is another midbrain structure that is responsible for generating primitive affective sensations and plays a critical role in maintaining autonomic and physiological homeostasis (Bandler and Shipley, 1994; Behbehani, 1995; Mobbs et al., 2007).”
From How Processing of Sensory Information From the Internal and External Worlds Shape the Perception and Engagement With the World in the Aftermath of Trauma: Implications for PTSD (2021) · cites this paper as Mobbs et al., 2007
The indexed copy (When Fear Is Near > Abstract; page not provided) reports that PAG activity increased as threat approached and correlated with subjective dread, supporting a role in affective threat responses. It does not establish that the PAG generates primitive affective sensations or maintains autonomic and physiological homeostasis; its mention of autonomic functioning concerns connected regions, not that claimed PAG role. (LLM, conf=0.85)
Experimental — accuracy not yet measuredMobbs et al. (2007) showed increases in periaqueductal gray activity while prefrontal cortex activity simultaneously decreases when threat is imminent, suggesting that extreme arousal responses can interrupt the transmission of fear-related stimuli to prefrontal regions.
“Interestingly, Mobbs et al. (2007) showed increases in periaqueductal gray activity while prefrontal cortex activity simultaneously decreases when threat is imminent, suggesting that extreme arousal responses can interrupt the transmission of fear-related stimuli to prefrontal regions.”
From How Processing of Sensory Information From the Internal and External Worlds Shape the Perception and Engagement With the World in the Aftermath of Trauma: Implications for PTSD (2021) · cites this paper as Mobbs et al., 2007
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fMRI studies have demonstrated anterior cingulate cortex activation when subjects are exposed to looming threatening stimuli such as virtual predators, tarantulas, or threatening avatars.
“In line with this hypothesis, fMRI studies have demonstrated ACC activation when subjects are exposed to looming threatening stimuli, such as virtual predators, tarantulas, or threatening avatars (Mobbs et al. 2007, 2010; Vieira et al. 2020; de Borst and de Gelder 2022).”
From Neuroanatomical correlates of peripersonal space: bridging the gap between perception, action, emotion and social cognition (2024) · cites this paper as Mobbs et al. 2007
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References 23 · Cited by 951
Research works printed but not linked: 1
- [5]Rau V Fanselow MS Kirmayer LJ Lemelson R Barad M Understanding Trauma: Integrating Biological, Clinical, and Cultural Perspectives 2007 27 40 Cambridge Univ. Press New York
- Authors
- Mobbs, D., Petrovic, P., Marchant, J. L., Hassabis, D., Weiskopf, N., Seymour, B., Dolan, R. J., & Frith, C. D.
- Affiliations
- Wellcome Centre for Human Neuroimaging (GB)
- Wellcome Trust Centre for Neuroimaging, Functional Imaging Laboratory, University College London, London WC1N 3BG, UK.
- Corresponding author
- Mobbs, Dean
- Venue
- Science
- Published
- 2007-08-24
- Volume
- 317
- Issue
- 5841
- Pages
- 1079-1083
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2648508
- OpenAlex
- W2024988985
- Cited by
- 951
- References
- 23
- Citations by year
- 2026: 25 · 2025: 49 · 2024: 76 · 2023: 54 · 2022: 52 · 2021: 59 · 2020: 51 · 2019: 53 · 2018: 58 · 2017: 68 · 2016: 57 · 2015: 51 · 2014: 38 · 2013: 48 · 2012: 52
- FWCI
- 18.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- Max Planck Digital Library (submittedVersion, other-oa)
- Cambridge University Engineering Department Publications Database (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (078865)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- threat anticipation, periaqueductal gray, ventromedial prefrontal cortex, avoidance behavior, pain anticipation, dread, anxiety disorders
- MeSH terms
- Anxiety, Avoidance Learning, Behavior, Brain Mapping, Escape Reaction, Fear, Gyrus Cinguli, Humans, Oxygen, Pain, Periaqueductal Gray, Prefrontal Cortex
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