Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder.
Journal Article (Journal Article)
Fear conditioning is an established model for investigating posttraumatic stress disorder (PTSD). However, symptom triggers may vaguely resemble the initial traumatic event, differing on a variety of sensory and affective dimensions. We extended the fear-conditioning model to assess generalization of conditioned fear on fear processing neurocircuitry in PTSD. Military veterans (n=67) consisting of PTSD (n=32) and trauma-exposed comparison (n=35) groups underwent functional magnetic resonance imaging during fear conditioning to a low fear-expressing face while a neutral face was explicitly unreinforced. Stimuli that varied along a neutral-to-fearful continuum were presented before conditioning to assess baseline responses, and after conditioning to assess experience-dependent changes in neural activity. Compared with trauma-exposed controls, PTSD patients exhibited greater post-study memory distortion of the fear-conditioned stimulus toward the stimulus expressing the highest fear intensity. PTSD patients exhibited biased neural activation toward high-intensity stimuli in fusiform gyrus (P<0.02), insula (P<0.001), primary visual cortex (P<0.05), locus coeruleus (P<0.04), thalamus (P<0.01), and at the trend level in inferior frontal gyrus (P=0.07). All regions except fusiform were moderated by childhood trauma. Amygdala-calcarine (P=0.01) and amygdala-thalamus (P=0.06) functional connectivity selectively increased in PTSD patients for high-intensity stimuli after conditioning. In contrast, amygdala-ventromedial prefrontal cortex (P=0.04) connectivity selectively increased in trauma-exposed controls compared with PTSD patients for low-intensity stimuli after conditioning, representing safety learning. In summary, fear generalization in PTSD is biased toward stimuli with higher emotional intensity than the original conditioned-fear stimulus. Functional brain differences provide a putative neurobiological model for fear generalization whereby PTSD symptoms are triggered by threat cues that merely resemble the index trauma.
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Duke Authors
- Beckham, Jean Crowell
- Brancu, Mira
- Calhoun, Patrick Shields
- Fairbank, John A.
- LaBar, Kevin S.
- Marx, Christine Elizabeth
- Morey, Rajendra A.
- Naylor, Jennifer C.
- Van Voorhees, Elizabeth E.
- Wagner II, Henry Ryan
Cited Authors
- Morey, RA; Dunsmoor, JE; Haswell, CC; Brown, VM; Vora, A; Weiner, J; Stjepanovic, D; Wagner, HR; VA Mid-Atlantic MIRECC Workgroup, ; LaBar, KS
Published Date
- December 15, 2015
Published In
Volume / Issue
- 5 / 12
Start / End Page
- e700 -
PubMed ID
- 26670285
Pubmed Central ID
- PMC5068591
Electronic International Standard Serial Number (EISSN)
- 2158-3188
Digital Object Identifier (DOI)
- 10.1038/tp.2015.196
Language
- eng
Conference Location
- United States