title: Dissociated neural effects of cortisol depending on threat escapability.
abstract: Evolution has provided us with a highly flexible neuroendocrine threat system which, depending on threat imminence, switches between active escape and passive freezing. Cortisol, the "stress-hormone", is thought to play an important role in both fear behaviors, but the exact mechanisms are not understood. Using pharmacological functional magnetic resonance imaging we investigated how cortisol modulates the brain's fear systems when humans are under virtual-predator attack. We show dissociated neural effects of cortisol depending on whether escape from threat is possible. During inescapable threat cortisol reduces fear-related midbrain activity, whereas in anticipation of active escape cortisol boosts activity in the frontal salience network (insula and anterior cingulate cortex), which is involved in autonomic control, visceral perception and motivated action. Our findings suggest that cortisol adjusts the human neural threat system from passive fear to active escape, which illuminates the hormone's crucial role in the adaptive flexibility of fear behaviors.
authors.affiliation: Department of Experimental Psychology, Utrecht University, Utrecht, CS, 3584, The Netherlands.
authors.forename: Estrella R
authors.initials: ER
authors.lastname: Montoya
authors.affiliation: Department of Experimental Psychology, Utrecht University, Utrecht, CS, 3584, The Netherlands.|Department of Psychiatry, University of Cape Town, Cape Town, 7925, South Africa.|Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, 7925, South Africa.
authors.forename: Jack
authors.initials: J
authors.lastname: van Honk
authors.affiliation: Department of Experimental Psychology, Utrecht University, Utrecht, CS, 3584, The Netherlands.|Department of Psychiatry, University of Cape Town, Cape Town, 7925, South Africa.
authors.forename: Peter A
authors.identifier: http://orcid.org/0000-0001-8944-0181
authors.initials: PA
authors.lastname: Bos
authors.affiliation: Department of Experimental Psychology, Utrecht University, Utrecht, CS, 3584, The Netherlands.|Department of Psychiatry, University of Cape Town, Cape Town, 7925, South Africa.
authors.forename: David
authors.initials: D
authors.lastname: Terburg
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008636:Mesencephalon / Q000378:metabolism / Q000502:physiology*; D055815:Young Adult
chemical_list: D006854:Hydrocortisone
keywords: cortisol; salience network; threat escape