Publication
Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder
Publisher:
Springer Science and Business Media LLC
Date:
15-12-2015
DOI:
10.1038/TP.2015.196
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 .02), insula ( P .001), primary visual cortex ( P .05), locus coeruleus ( P .04), thalamus ( P .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.