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Slow escape decisions are swayed by trait anxiety

Abstract

Theoretical models distinguish between neural responses elicited by distal threats and those evoked by more immediate threats1,2,3. Specifically, slower ‘cognitive’ fear responses towards distal threats involve a network of brain regions including the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC), while immediate ‘reactive’ fear responses rely on regions such as the periaqueductal grey4,5. However, it is unclear how anxiety and its neural substrates relate to these distinct defensive survival circuits. We tested whether individual differences in trait anxiety would impact escape behaviour and neural responses to slow and fast attacking predators: conditions designed to evoke cognitive and reactive fear, respectively. Behaviourally, we found that trait anxiety was not related to escape decisions for fast threats, but individuals with higher trait anxiety escaped earlier during slow threats. Functional magnetic resonance imaging showed that when subjects faced slow threats, trait anxiety positively correlated with activity in the vHPC, mPFC, amygdala and insula. Furthermore, the strength of functional coupling between two components of the cognitive circuit—the vHPC and mPFC—was correlated with the degree of trait anxiety. This suggests that anxiety predominantly affects cognitive fear circuits that are involved in volitional strategic escape.

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Fig. 1: FID experiment and behavioural results.
Fig. 2: Neural activity.

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Data availability

Behavioural data can be found on the Open Science Framework (https://osf.io/c4qbr/). fMRI data are available from the corresponding author on reasonable request.

Code availability

Code for all behavioural analyses can be found on the Open Science Framework (https://osf.io/c4qbr/). fMRI analysis code is available from the corresponding author on reasonable request.

References

  1. Mathews, A. & Mackintosh, B. A cognitive model of selective processing in anxiety. Cogn. Ther. Res. 22, 539–560 (1998).

    Article  Google Scholar 

  2. Mobbs, D., Hagan, C. C., Dalgleish, T., Silston, B. & Prevost, C. The ecology of human fear: survival optimization and the nervous system.Front. Neurosci. 9, 55 (2015).

    Article  Google Scholar 

  3. Mobbs, D. The ethological deconstruction of fear(s).Curr. Opin. Behav. Sci. 24, 32–37 (2018).

    Article  Google Scholar 

  4. Mobbs, D. et al. When fear is near: threat imminence elicits prefrontal-periaqueductal gray shifts in humans. Science 317, 1079–1083 (2007).

    Article  CAS  Google Scholar 

  5. Qi, S. et al. How cognitive and reactive fear circuits optimize escape decisions in humans.Proc. Natl Acad. Sci. USA 115, 3186–3191 (2018).

    Article  CAS  Google Scholar 

  6. Mobbs, D. & Kim, J. J. Neuroethological studies of fear, anxiety, and risky decision-making in rodents and humans. Curr. Opin. Behav. Sci. 5, 8–15 (2015).

    Article  Google Scholar 

  7. LeDoux, J. Rethinking the emotional brain. Neuron 73, 653–676 (2012).

    Article  CAS  Google Scholar 

  8. Blanchard, R. J., Yudko, E. B., Rodgers, R. J. & Blanchard, D. C. Defense system psychopharmacology: an ethological approach to the pharmacology of fear and anxiety. Behav. Brain Res. 58, 155–165 (1993).

    Article  CAS  Google Scholar 

  9. Fanselow, M. S. & Lester, L. S. in Evolution and Learning (eds Bolles, R. C. & Beecher, M.) 185–211 (Lawrence Erlbaum Associates, 1988).

  10. Calhoon, G. G. & Tye, K. M. Resolving the neural circuits of anxiety. Nat. Neurosci. 18, 1394–1404 (2015).

    Article  CAS  Google Scholar 

  11. Adhikari, A., Topiwala, M. A. & Gordon, J. A. Single units in the medial prefrontal cortex with anxiety-related firing patterns are preferentially influenced by ventral hippocampal activity. Neuron 71, 898–910 (2011).

    Article  CAS  Google Scholar 

  12. Adhikari, A., Topiwala, M. A. & Gordon, J. A. Synchronized activity between the ventral hippocampus and the medial prefrontal cortex during anxiety. Neuron 65, 257–269 (2010).

    Article  CAS  Google Scholar 

  13. Padilla-Coreano, N. et al. Direct ventral hippocampal-prefrontal input is required for anxiety-related neural activity and behavior. Neuron 89, 857–866 (2016).

    Article  CAS  Google Scholar 

  14. Benoit, R. G., Davies, D. J. & Anderson, M. C. Reducing future fears by suppressing the brain mechanisms underlying episodic simulation. Proc. Natl Acad. Sci. USA 113, E8492–E8501 (2016).

    Article  CAS  Google Scholar 

  15. Jimenez, J. C. et al. Anxiety cells in a hippocampal-hypothalamic circuit. Neuron 97, 670–683.e6 (2018).

    Article  CAS  Google Scholar 

  16. McNaughton, N. & Corr, P. J. Survival circuits and risk assessment. Curr. Opin. Behav. Sci. 24, 14–20 (2018).

    Article  Google Scholar 

  17. Spielberger, C., Gorsuch, R., Lushene, R., Vagg, P. & Jacobs, G. Manual for the State-Trait Anxiety Inventory (Consulting Psychologists Press, 1983).

  18. McLaren, D. G., Ries, M. L., Xu, G. & Johnson, S. C. A generalized form of context-dependent psychophysiological interactions (gPPI): a comparison to standard approaches. NeuroImage 61, 1277–1286 (2012).

    Article  Google Scholar 

  19. McHugh, S., Deacon, R., Rawlins, J. & Bannerman, D. M. Amygdala and ventral hippocampus contribute differentially to mechanisms of fear and anxiety. Behav. Neurosci. 118, 63–78 (2004).

    Article  CAS  Google Scholar 

  20. Fanselow, M. S. & Dong, H.-W. Are the dorsal and ventral hippocampus functionally distinct structures? Neuron 65, 7–19 (2010).

    Article  CAS  Google Scholar 

  21. Moser, M.-B. & Moser, E. I. Functional differentiation in the hippocampus. Hippocampus 8, 608–619 (1998).

    Article  CAS  Google Scholar 

  22. Lima, S. L. & Dill, L. M. Behavioral decisions made under the risk of predation: a review and prospectus. Can. J. Zool. 68, 619–640 (1990).

    Article  Google Scholar 

  23. Davis, M., Walker, D. L., Miles, L. & Grillon, C. Phasic vs sustained fear in rats and humans: role of the extended amygdala in fear vs anxiety. Neuropsychopharmacology 35, 105–135 (2010).

    Article  Google Scholar 

  24. Graeff, F. G. Neuroanatomy and neurotransmitter regulation of defensive behaviors and related emotions in mammals. Braz. J. Med. Biol. Res. 27, 811–829 (1994).

    CAS  PubMed  Google Scholar 

  25. Blanchard, R. J. & Blanchard, D. C. An experimental analysis of defense, fear, and anxiety. In Otago Conference Series No. 1. Anxiety (eds McNaughton, N. & Andrews, G.) 124–133 (Univ. Otago Press, 1990).

  26. McNaughton, N. & Corr, P. J. A two-dimensional neuropsychology of defense: fear/anxiety and defensive distance. Neurosci. Biobehav. Rev. 28, 285–305 (2004).

    Article  Google Scholar 

  27. Young, C. K. & McNaughton, N. Coupling of theta oscillations between anterior and posterior midline cortex and with the hippocampus in freely behaving rats. Cereb. Cortex 19, 24–40 (2008).

    Article  Google Scholar 

  28. Khemka, S., Barnes, G., Dolan, R. J. & Bach, D. R. Dissecting the function of hippocampal oscillations in a human anxiety model. J. Neurosci. 37, 6869–6876 (2017).

    Article  CAS  Google Scholar 

  29. Parent, M. A., Wang, L., Su, J., Netoff, T. & Yuan, L.-L. Identification of the hippocampal input to medial prefrontal cortex in vitro. Cereb. Cortex 20, 393–403 (2009).

    Article  Google Scholar 

  30. Vertes, R. P. Differential projections of the infralimbic and prelimbic cortex in the rat. Synapse 51, 32–58 (2004).

    Article  CAS  Google Scholar 

  31. Felix-Ortiz, A. C. et al. BLA to vHPC inputs modulate anxiety-related behaviors. Neuron 79, 658–664 (2013).

    Article  CAS  Google Scholar 

  32. Felix-Ortiz, A. C. & Tye, K. M. Amygdala inputs to the ventral hippocampus bidirectionally modulate social behavior. J. Neurosci. 34, 586–595 (2014).

    Article  CAS  Google Scholar 

  33. Malvaez, M. et al. Basolateral amygdala rapid glutamate release encodes an outcome-specific representation vital for reward-predictive cues to selectively invigorate reward-seeking actions. Sci. Rep. 5, 12511 (2015).

    Article  CAS  Google Scholar 

  34. Indovina, I., Robbins, T. W., Núñez-Elizalde, A. O., Dunn, B. D. & Bishop, S. J. Fear-conditioning mechanisms associated with trait vulnerability to anxiety in humans. Neuron 69, 563–571 (2011).

    Article  CAS  Google Scholar 

  35. Bach, D. R. et al. Human hippocampus arbitrates approach–avoidance conflict. Curr. Biol. 24, 541–547 (2014).

    Article  CAS  Google Scholar 

  36. Ito, R. & Lee, A. C. The role of the hippocampus in approach–avoidance conflict decision-making: evidence from rodent and human studies. Behav. Brain Res. 313, 345–357 (2016).

    Article  Google Scholar 

  37. Oehrn, C. R. et al. Human hippocampal dynamics during response conflict. Curr. Biol. 25, 2307–2313 (2015).

    Article  CAS  Google Scholar 

  38. Mathews, A. Why worry? The cognitive function of anxiety. Behav. Res. Ther. 28, 455–468 (1990).

    Article  CAS  Google Scholar 

  39. Perkins, A. M. & Corr, P. J. in The Positive Side of Negative Emotions (ed. Parrott, G.) 37 (Guilford Press, 2014).

  40. Maner, J. K. et al. Dispositional anxiety and risk-avoidant decision-making. Pers. Indiv. Differ. 42, 665–675 (2007).

    Article  Google Scholar 

  41. Meacham, F. & T. Bergstrom, C. Adaptive behavior can produce maladaptive anxiety due to individual differences in experience. Evol. Med. Public Health 2016, 270–285 (2016).

    Article  Google Scholar 

  42. Marks, If & Nesse, R. M. Fear and fitness: an evolutionary analysis of anxiety disorders. Ethol. Sociobiol. 15, 247–261 (1994).

    Article  Google Scholar 

  43. Carver, C. S. & White, T. L. Behavioral inhibition, behavioral activation, and affective responses to impending reward and punishment: the BIS/BAS scales. J. Pers. Soc. Psychol. 67, 319–333 (1994).

    Article  Google Scholar 

  44. R Development Core Team R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, 2013).

  45. Lawrence, M. A. ez: Easy analysis and visualization of factorial experiments. R package version 4.4-0 (2016).

  46. Therneau, T. M. coxme: Mixed effects cox models. R package version 2.2-5 (2015).

  47. Bates, D., Machler, M., Bolker, B. & Walker, S. Fitting linear mixed-effects models using lme4. J. Stat. Softw. 67, 1–48 (2015).

    Article  Google Scholar 

  48. Genovese, C. R., Lazar, N. A. & Nichols, T. Thresholding of statistical maps in functional neuroimaging using the false discovery rate. NeuroImage 15, 870–878 (2002).

    Article  Google Scholar 

  49. Gray, J. A. The psychophysiological basis of introversion–extraversion. Behav. Res. Ther. 8, 249–266 (1970).

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by the National Institute of Mental Health (grant 2P50MH094258 to D.M.) and funds from the Tianqiao and Chrissy Chen Institute (P2026052 to D.M.). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Contributions

S.Q., D.H., N.D. and D.M. contributed to the conception and design of the experiment. S.Q. conducted the experiment and collected the data. S.Q. and B.J.F. analysed the data. B.J.F., S.Q. and D.M. drafted the manuscript. All authors reviewed the manuscript and gave final approval for publication.

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Correspondence to Bowen J. Fung or Dean Mobbs.

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Supplementary Information

Supplementary Methods, Supplementary Tables 1–4, Supplementary Figs. 1–2 and Supplementary References.

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Supplementary Code

This file contains R script for the behavioural analyses reported in the article.

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Fung, B.J., Qi, S., Hassabis, D. et al. Slow escape decisions are swayed by trait anxiety. Nat Hum Behav 3, 702–708 (2019). https://doi.org/10.1038/s41562-019-0595-5

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