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Fear extinction and sleep across the spectrum of severity in post-traumatic hyperarousal


? DESCRIPTION (provided by applicant): Proposed research will examine interrelationships between hyperarousal, sleep quality and extinction memory among persons who have experienced a severe traumatic event within the past 2 years (excluding the past month). In the aftermath of such an event, sleep disruption is very common and, particularly in the case of REM sleep, can predict the later development of post-traumatic psychological symptoms. Although sleep disruption is commonly classified with waking symptoms of hyperarousal, even mild elevation of baseline arousal can disturb sleep because the circuits and neuromodulators that promote arousal overlap with those that favor wakefulness during the normal sleep-wake cycle. Disturbed sleep may contribute to post-traumatic psychopathology by interfering with sleep-dependent emotional memory processes such as the consolidation and generalization of extinction memory (the ability to remember that what once predicted danger no longer does so). Among participants in the proposed study, a range of psychological health from highly functioning to highly symptomatic will first be obtained with stratified sampling using a composite index derived from 3 trans- diagnostic assessments of psychopathology. Across participants thus selected, the degree of hyperarousal will be assessed so as to generate a continuous range of values at 2 different levels of analysis. First, a canonical self-report hyperarousal measure will be computed from 3 validated questionnaires. Second, a validated acoustic-startle paradigm will measure habituation of physiological reactivity across continuum from rapid (minimal arousal) to absent or slow habituation (maximal arousal). Participants will then complete 2 weeks of sleep diaries with wrist actigraphy followed by a validated fear conditioning and extinction protocol consisting of 2 evening sessions 24 hr. apart. Fear conditioning and extinction learning (Session 1) and extinction recall (Session 2) will be measured physiologically using skin conductance response (SCR). Concurrent activity in 2 neural circuits for the expression of conditioned fear (fear-expression network) and extinction of such fear (extinction-memory network) will be examined using fMRI scanning at 3T. Ambulatory polysomnography will measure sleep quality and architecture on an adaptation night, a baseline night and an extinction-memory consolidation night between the 2 fMRI sessions. Hypotheses are, first, that poor quality of sleep, especially of REM, will be associated with poor extinction recall expressed physiologically by maintained elevation of SCR, and neurally by less activation in extinction-memory and more activation in fear-expression networks. Second, greater hyperarousal at self-report and/or physiological levels will be associated with poorer sleep quality. And third, greater hyperarousal will be associated with less extinction recall and less activation in extinction and more in fear networks. Support for hypotheses in combination will support the possibility that trauma elevates baseline activity in arousal systems resulting in sleep disruption that, in turn, impairs consolidation of extinction memory possibly lowering thresholds for intrusion of fear memories and other post-traumatic symptoms.

Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.