Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder.
Abstract
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.
Type
Journal articleSubject
AdultBrain
Brain Mapping
Conditioning (Psychology)
Fear
Female
Generalization (Psychology)
Humans
Learning
Magnetic Resonance Imaging
Male
Stress Disorders, Post-Traumatic
United States
Veterans
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https://hdl.handle.net/10161/11643Published Version (Please cite this version)
10.1038/tp.2015.196Publication Info
Morey, RA; Dunsmoor, JE; Haswell, CC; Brown, VM; Vora, A; Weiner, J; ... LaBar, KS (2015). Fear learning circuitry is biased toward generalization of fear associations in posttraumatic
stress disorder. Transl Psychiatry, 5. pp. e700. 10.1038/tp.2015.196. Retrieved from https://hdl.handle.net/10161/11643.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Kevin S. LaBar
Professor of Psychology and Neuroscience
My research focuses on understanding how emotional events modulate cognitive processes
in the human brain. We aim to identify brain regions that encode the emotional properties
of sensory stimuli, and to show how these regions interact with neural systems supporting
social cognition, executive control, and learning and memory. To achieve this goal,
we use a variety of cognitive neuroscience techniques in human subject populations.
These include psychophysiological monitoring, functional magnetic
Rajendra A. Morey
Professor of Psychiatry and Behavioral Sciences
Research in my lab is focused on brain changes associated with posttraumatic stress
disorder (PTSD), traumatic brain injury (TBI), and other neuropsychiatric disorders.
We apply several advanced methods for understanding brain function including functional
MRI, structural MRI, diffusion tensor imaging, and genetic effects.
Henry Ryan Wagner II
Adjunct Associate Professor in the Department of Psychiatry and Behavioral Sciences
My research career into neurobiology and mental health spans two distinct phases.
The first includes doctoral training at the University of New Mexico in psychology
and neurobiology with a major area of emphasis in behavioral neurobiology and two
minor areas of emphasis in learning and memory and statistics and experimental design.
Doctoral training was subsequently supplemented with postdoctoral study in neuropharmacology
at Duke University focusing on brain monoamine systems.&nb
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