Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder.


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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Publication Info

Morey, RA, JE Dunsmoor, CC Haswell, VM Brown, A Vora, J Weiner, D Stjepanovic, HR Wagner, et al. (2015). Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder. Transl Psychiatry, 5. p. e700. 10.1038/tp.2015.196 Retrieved from https://hdl.handle.net/10161/11643.

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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

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.  For the five years subsequent, I continued exploring the mechanisms underlying receptor regulation of brain catecholamine systems within my laboratory at Columbia University.  Following a hiatus, I refocused my research interests away from the laboratory and into statistics and experimental design. This included supplementing a minor area of emphasis in statistics acquired during my doctoral training with extensive course work in biometry through the Division of Biometry within the Department of Community and Family Medicine at Duke University.  Using this background, I have continued to consult for the last two decades in the statistical design and analysis of a wide variety of research projects within the Division of Translational Neuroscience in the Department of Psychiatry and Behavioral Sciences as part of the Duke University School of Medicine; the numerous projects undertaken during this interval have included - but are not limited to - randomized clinical trials, epidemologic surveys, and a seemingly endless variety of quasi-experimental designs.  More recently, I have expanded my duties to include a position as Statistician for the Mental Illness Research, Education, and Clinical Center with the Durham VA Medical Center.


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 resonance imaging (fMRI), machine learning,  and behavioral studies in healthy adults as well as psychiatric patients. This integrative approach capitalizes on recent advances in the field and may lead to new insights into cognitive-emotional interactions in the brain.

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