Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder.
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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.
Magnetic Resonance Imaging
Stress Disorders, Post-Traumatic
Published Version (Please cite this version)10.1038/tp.2015.196
Publication InfoBrown, VM; Dunsmoor, JE; Haswell, CC; LaBar, Kevin S; Morey, Rajendra A; Stjepanovic, D; ... Weiner, J (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.
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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
Associate 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.
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