CoChat
Sign Up
Cited by 48Memory and Neural MechanismsNeural and Behavioral Psychology StudiesAnxiety, Depression, Psychometrics, Treatment, Cognitive Processes

Human Responses to Visually Evoked Threat

Open access
Yilmaz Balban, Melis, Cafaro, Erin, Saue-Fletcher, Lauren, Washington, Marlon J., Bijanzadeh, Maryam, Lee, A. Moses, Chang, Edward F., Huberman, Andrew D.·2021·Current Biology
DOI 10.1016/j.cub.2020.11.035PMC PMC8407368
Open this paper in CoChat — free accountOpen PDF

Abstract

Vision is the primary sense humans use to evaluate and respond to threats. Understanding the biological underpinnings of the human threat response has been hindered by lack of realistic in-lab threat paradigms. We established an immersive virtual reality (VR) platform to simultaneously measure behavior, physiological state, and neural activity from the human brain using chronically implanted electrodes. Subjects with high anxiety showed increased visual scanning in response to threats as compared to healthy controls. In both healthy and anxious subjects, the amount of scanning behavior correlated with the magnitude of physiological arousal, suggesting that visual scanning behavior is directly linked to internal state. Intracranial electroencephalography (iEEG) recordings from three subjects suggested that high-frequency gamma activity in the insula positively correlates with physiological arousal induced by visual threats and that low-frequency theta activity in the orbitofrontal cortex (OFC) negatively correlates with physiological arousal induced by visual threats. These findings reveal a key role of eye movements and suggest that distinct insula and OFC activation dynamics may be important for detecting and adjusting human stress in response to visually perceived threats.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.cub.2020.11.035

Cites

9 of 9 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Different emotional and cognitive states alter the depth and frequency of breathing, which impacts emotional state in part by regulation of carbon dioxide levels.

    “It is also clear that different emotional and cognitive states alter the depth and frequency of breathing,8,9,10,11,12 which likewise impacts emotional state, in part by regulation of carbon dioxide levels.13,14,15,16,17”

    From Brief structured respiration practices enhance mood and reduce physiological arousal (2023) · cites this paper as [11]

    The Results section, “Virtual Heights Reliably Trigger Physiological Arousal and Visual Scanning in Healthy Humans” (page unavailable), reports increased tidal breath volume during exposure to heights, supporting an effect of a threatening experience on breathing depth. The paper does not establish that different emotional and cognitive states alter both breathing depth and frequency. The sentence attaches other citations, not this source, to the subsequent claim about carbon dioxide and emotional state. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 47

  1. [2]Buff C, Brinkmann L, Neumeister P, Feldker K, Heitmann C, Gathmann B, Andor T, and Straube T (2016). Specifically altered brain responses to threat in generalized anxiety disorder relative to social anxiety disorder and panic disorder. Neuroimage Clin. 12, 698– 706. 27761400 PMC5065042
  2. [3]Feldker K, Heitmann CY, Neumeister P, Tupak SV, Schrammen E, Moeck R, Zwitserlood P, Bruchmann M, and Straube T (2017). Transdiagnostic brain responses to disorder-related threat across four psychiatric disorders. Psychol. Med 47, 730– 743. 27869064
  3. [4]Yilmaz M, and Meister M (2013). Rapid innate defensive responses of mice to looming visual stimuli. Curr. Biol 23, 2011– 2015. 24120636 PMC3809337
  4. [5]Salay LD, Ishiko N, and Huberman AD (2018). A midline thalamic circuit determines reactions to visual threat. Nature 557, 183– 189. 29720647 PMC8442544
  5. [6]Li L, Feng X, Zhou Z, Zhang H, Shi Q, Lei Z, Shen P, Yang Q, Zhao B, Chen S, (2018). Stress accelerates defensive responses to looming in mice and involves a locus coeruleus-superior colliculus projection. Curr. Biol 28, 859– 871.e5. 29502952
  6. [8]Kalmbach DA, Cuamatzi-Castelan AS, Tonnu CV, Tran KM, Anderson JR, Roth T, and Drake CL (2018). Hyperarousal and sleep reactivity in insomnia: current insights. Nat. Sci. Sleep 10, 193– 201. 30046255 PMC6054324
  7. [9]Grisanzio KA, Goldstein-Piekarski AN, Wang MY, Rashed Ahmed AP, Samara Z, and Williams LM (2018). Transdiagnostic symptom clusters and associations with brain, behavior, and daily function in mood, anxiety, and trauma disorders. JAMA Psychiatry 75, 201– 209. 29197929 PMC5838569
  8. [10]De Franceschi G, Vivattanasarn T, Saleem AB, and Solomon SG (2016). Vision guides selection of freeze or flight defense strategies in mice. Curr. Biol 26, 2150– 2154. 27498569
  9. [11]Kim JJ, and Jung MW (2018). Fear paradigms: the times they are a-changin’. Curr. Opin. Behav. Sci 24, 38– 43. 30140717 PMC6101258
  10. [12]Qi S, Hassabis D, Sun J, Guo F, Daw N, and Mobbs D (2018). How cognitive and reactive fear circuits optimize escape decisions in humans. Proc. Natl. Acad. Sci. USA 115, 3186– 3191. 29507207 PMC5866541
  11. [13]Mobbs D, Petrovic P, Marchant JL, Hassabis D, Weiskopf N, Seymour B, Dolan RJ, and Frith CD (2007). When fear is near: threat imminence elicits prefrontal-periaqueductal gray shifts in humans. Science 317, 1079– 1083. 17717184 PMC2648508
  12. [14]Adolphs R (2008). Fear, faces, and the human amygdala. Curr. Opin. Neurobiol 18, 166– 172. 18655833 PMC2580742
  13. [15]Öhman A, Carlsson K, Lundqvist D, and Ingvar M (2007). On the unconscious subcortical origin of human fear. Physiol. Behav 92, 180– 185. 17599366
  14. [16]Blanchard DC, Hynd AL, Minke KA, Minemoto T, and Blanchard RJ (2001). Human defensive behaviors to threat scenarios show parallels to fear- and anxiety-related defense patterns of non-human mammals. Neurosci. Biobehav. Rev 25, 761– 770. 11801300
  15. [17]Harrison LA, Ahn C, and Adolphs R (2015). Exploring the structure of human defensive responses from judgments of threat scenarios. PLoS ONE 10, e0133682. 26296201 PMC4546605
  16. [18]Bach DR, Guitart-Masip M, Packard PA, Miró J, Falip M, Fuentemilla L, and Dolan RJ (2014). Human hippocampus arbitrates approach-avoidance conflict. Curr. Biol 24, 541– 547. 24560572 PMC3969259
  17. [19]Camerer C, and Mobbs D (2017). Differences in behavior and brain activity during hypothetical and real choices. Trends Cogn. Sci 21, 46– 56. 27979604 PMC7769501
  18. [20]M Aghajan Z, Schuette P, Fields TA, Tran ME, Siddiqui SM, Hasulak NR, Tcheng TK, Eliashiv D, Mankin EA, Stern J, (2017). Theta oscillations in the human medial temporal lobe during real-world ambulatory movement. Curr. Biol 27, 3743– 3751.e3. 29199073 PMC5937848
  19. [21]Reggente N, Essoe JK-Y, Aghajan ZM, Tavakoli AV, McGuire JF, Suthana NA, and Rissman J (2018). Enhancing the ecological validity of fMRI memory research using virtual reality. Front. Neurosci 12, 408. 29962932 PMC6013717
  20. [24]Rizzo A, and Shilling R (2017). Clinical virtual reality tools to advance the prevention, assessment, and treatment of PTSD. Eur. J. Psychotraumatol 8 (sup5), 1414560. 29372007 PMC5774399
  21. [25]Gonçalves R, Pedrozo AL, Coutinho ESF, Figueira I, and Ventura P (2012). Efficacy of virtual reality exposure therapy in the treatment of PTSD: a systematic review. PLoS ONE 7, e48469. 23300515 PMC3531396
  22. [27]Blanchard DC, Blanchard RJ, and Rodgers RJ (1991). Risk assessment and animal models of anxiety. In Animal Models in Psychopharmacology, Olivier B, Mos J, and Slangen L, eds. (Springer), pp. 117– 134.
  23. [28]Blanchard DC, Griebel G, Pobbe R, and Blanchard RJ (2011). Risk assessment as an evolved threat detection and analysis process. Neurosci. Biobehav. Rev 35, 991– 998. 21056591
  24. [30]Allcoat D, Greville WJ, Newton PM, and Dymond S (2015). Frozen with fear: conditioned suppression in a virtual reality model of human anxiety. Behav. Processes 118, 98– 101. 26115568
  25. [32]Yu Q, Zhuang Q, Wang B, Liu X, Zhao G, and Zhang M (2018). The effect of anxiety on emotional recognition: evidence from an ERP study. Sci. Rep 8, 16146. 30385790 PMC6212571
  26. [33]Critchley HD, Wiens S, Rotshtein P, Ohman A, and Dolan RJ (2004). Neural systems supporting interoceptive awareness. Nat. Neurosci 7, 189– 195. 14730305
  27. [35]Bechara A, Damasio H, and Damasio AR (2000). Emotion, decision making and the orbitofrontal cortex. Cereb. Cortex 10, 295– 307. 10731224
  28. [37]Rudebeck PH, and Rich EL (2018). Orbitofrontal cortex. Curr. Biol 28, R1083– R1088. 30253144 PMC9253859
  29. [38]Allman JM, Hakeem A, Erwin JM, Nimchinsky E, and Hof P (2001). The anterior cingulate cortex. The evolution of an interface between emotion and cognition. Ann. N Y Acad. Sci 935, 107– 117. 11411161
  30. [39]Adhikari A, Topiwala MA, and Gordon JA (2010). Synchronized activity between the ventral hippocampus and the medial prefrontal cortex during anxiety. Neuron 65, 257– 269. 20152131 PMC2822726
  31. [40]Kirkby LA, Luongo FJ, Lee MB, Nahum M, Van Vleet TM, Rao VR, Dawes HE, Chang EF, and Sohal VS (2018). An amygdala-hippocampus subnetwork that encodes variation in human mood. Cell 175, 1688– 1700.e14. 30415834
  32. [42]Namkung H, Kim S-H, and Sawa A (2017). The insula: an underestimated brain area in clinical neuroscience, psychiatry, and neurology. Trends Neurosci. 40, 200– 207. 28314446 PMC5538352
  33. [43]Zhang Y, Zhou W, Wang S, Zhou Q, Wang H, Zhang B, Huang J, Hong B, and Wang X (2019). The roles of subdivisions of human insula in emotion perception and auditory processing. Cereb. Cortex 29, 517– 528. 29342237
  34. [44]Kugler G, Huppert D, Eckl M, Schneider E, and Brandt T (2014). Visual exploration during locomotion limited by fear of heights. PLoS ONE 9, e105906. 25165822 PMC4148313
  35. [45]Kugler G, Huppert D, Schneider E, and Brandt T (2014). Fear of heights freezes gaze to the horizon. J. Vestib. Res 24, 433– 441. 25564086
  36. [46]Won AS, Perone B, Friend M, and Bailenson JN (2016). Identifying anxiety through tracked head movements in a virtual classroom. Cyberpsychol. Behav. Soc. Netw 19, 380– 387. 27327065
  37. [47]Li BJ, Bailenson JN, Pines A, Greenleaf WJ, and Williams LM (2017). A public database of immersive VR videos with corresponding ratings of arousal, valence, and correlations between head movements and self report measures. Front. Psychol 8, 2116. 29259571 PMC5723428
  38. [49]Koban L, and Pourtois G (2014). Brain systems underlying the affective and social monitoring of actions: an integrative review. Neurosci. Biobehav. Rev 46, 71– 84. 24681006
  39. [50]Phan KL, Wager T, Taylor SF, and Liberzon I (2002). Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI. Neuroimage 16, 331– 348. 12030820
  40. [51]Etkin A, and Wager TD (2007). Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. Am. J. Psychiatry 164, 1476– 1488. 17898336 PMC3318959
  41. [52]Wang W, Zhornitsky S, Li CS-P, Le TM, Joormann J, and Li CR (2019). Social anxiety, posterior insula activation, and autonomic response during self-initiated action in a Cyberball game. J. Affect. Disord 255, 158– 167. 31153052 PMC6591038
  42. [54]Ghaziri J, Tucholka A, Girard G, Boucher O, Houde J-C, Descoteaux M, Obaid S, Gilbert G, Rouleau I, and Nguyen DK (2018). Subcortical structural connectivity of insular subregions. Sci. Rep 8, 8596. 29872212 PMC5988839
  43. [55]Wu H, Miller KJ, Blumenfeld Z, Williams NR, Ravikumar VK, Lee KE, Kakusa B, Sacchet MD, Wintermark M, Christoffel DJ, (2018). Closing the loop on impulsivity via nucleus accumbens deltaband activity in mice and man. Proc. Natl. Acad. Sci. USA 115, 192– 197. 29255043 PMC5776799
  44. [56]Mesgarani N, and Chang EF (2012). Selective cortical representation of attended speaker in multi-talker speech perception. Nature 485, 233– 236. 22522927 PMC3870007
  45. [57]Fischl B (2012). FreeSurfer. Neuroimage 62, 774– 781. 22248573 PMC3685476
  46. [58]Greco A, Valenza G, Lanata A, Scilingo EP, and Citi L (2016). cvxEDA: a convex optimization approach to electrodermal activity processing. IEEE Trans. Biomed. Eng 63, 797– 804. 26336110
  47. [60]Ashburner J, and Friston K (1997). Multimodal image coregistration and partitioning–a unified framework. Neuroimage 6, 209– 217. 9344825

Cited by

Sorted by citations

Authors
Yilmaz Balban, M., Cafaro, E., Saue-Fletcher, L., Washington, M. J., Bijanzadeh, M., Lee, A. M., Chang, E. F., & Huberman, A. D.
Affiliations
  • Stanford Medicine (US)
  • University of California, San Francisco (US)
Corresponding author
Huberman, Andrew D.
ORCID
Venue
Current Biology
Publisher
Elsevier BV
Published
2021-02
Volume
31
Issue
3
Pages
601-612.e3
ISSN
0960-9822 (ISSN-L)
DOI
10.1016/j.cub.2020.11.035
PMC
PMC8407368
OpenAlex
W3106565212
Cited by
48
References
9
Citations by year
2026: 8 · 2025: 10 · 2024: 12 · 2023: 11 · 2022: 2 · 2021: 5
FWCI
2.42
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Stanford University
  • University of California, San Francisco
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Keywords
threat response, anxiety, eye movements, physiological arousal, gamma oscillations, insula, theta oscillations, orbitofrontal cortex, intracranial EEG, chronic electrode implantation, stress regulation
MeSH terms
Anxiety, Anxiety Disorders, Brain, Eye Movements, Humans, Vision, Ocular, Prefrontal Cortex

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review