Abstract

Abstract Introduction We examined associations of sleep and hyperarousal with neural responses to a fear conditioning and extinction protocol in trauma-exposed individuals. We hypothesized, greater hyperarousal, poorer sleep quality and more nightmares would accompany greater activation of the salience network (associated with fear) and lesser activation of the prefrontal cortex (PFC; associated with fear regulation) throughout this protocol. Methods Persons exposed to trauma within the past 2 years (N=119, 43 with Post-traumatic stress disorder; PTSD) completed the PTSD Checklist-5 (PCL-5), two weeks of actigraphy and sleep/nightmare diaries, and a 2-day fear-conditioning and extinction protocol during fMRI. Hyperarousal items from PCL-5, sleep quality, and nightmare frequency were used to predict fMRI contrasts representing (1) initial activations to reinforced conditioned stimuli (CS+) during fear conditioning, (2) change in neural activation to CS+s across extinction learning, and, (3) after 24 hours (extinction recall), selective activation to an extinguished (CS+E) versus an un-extinguished CS+. Results During fear conditioning, hyperarousal was positively correlated with activation to the CS+ in the right lateral PFC, whereas nightmare frequency was negatively correlated with activations in bilateral orbitofrontal cortex (OFC). Across extinction learning, sleep onset latency (SOL) was negatively correlated with increased activation to CS+ in bilateral insular and dorsal and middle anterior cingulate cortices (salience regions). At extinction recall, nightmare frequency was negatively correlated with selective activation to the CS+E in the left insular cortex. Conclusion Except that fewer nightmares predicted greater OFC activation during fear conditioning, results did not support hypothesized relationships of hyperarousal, poor sleep and nightmares with increased salience network and decreased PFC activation to fear-related stimuli. Support Funding: R01MH109638

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