764 Neural activation accompanying fear conditioning and extinction in Generalized Anxiety Disorder with and without Insomnia Disorder

Abstract

Introduction We examined associations of sleep quality with neural responses to fear conditioning and extinction in individuals with Generalized Anxiety Disorder (GAD) with (INS) and without (NOI) Insomnia Disorder (ID). We hypothesized fear-related regions would show greater, and emotion-regulatory regions lesser activity in INS versus NOI and across both groups with decreasing sleep quality. Methods Participants were assigned to either an INS group with Insomnia Severity Index (ISI) ≥ 13 (N=21) or NOI with ISI ≤ 12 (N=14). Two weeks of actigraphy and sleep diaries were followed by a 2-session protocol with fMRI. During Session 1, mild electric shock produced conditioned fear to 2 different colors (CS+s) but not a third (CS-) (Fear Conditioning). Immediately afterward, one CS+ (CS+E) but not the other (CS+U) was extinguished (Extinction Learning). All 3 stimuli were presented 24h later (Extinction Recall). An acclimation/diagnostic ambulatory polysomnography (PSG) night was followed by PSGs before Session 1 and between Sessions 1 and 2. Using SPM8, t-tests compared groups, and multiple regressions predicted anterior cerebral activations (as a whole and as ROIs) using ISI, actigraph and diary sleep efficiency (SE) and latency (SOL), and sleep architecture. Results Beginning Fear Conditioning, differential activation to the reinforced stimulus (CS+>CS-) in the right insula was greater in INS than NOI, and greater actigraph SE predicted greater prefrontal activation. Change in activation to the CS+ across Extinction Learning (late CS+>early CS+) did not differentiate groups or correlate with sleep measures. During Extinction Recall, NOI versus INS showed less activation in bilateral amygdala ROIs (CS+E>CS-) but more activation in prefrontal regulatory regions (CS+U>CS-) and bilateral insula ROIs (both contrasts). Greater activation of prefrontal emotion-regulatory areas was associated with greater REM% (CS+E>CS+U and CS+E>CS-), lesser ISI (CS+E>CS- and CS+U>CS-), and greater actigraph SE (CS+U>CS). However for CS+E>CS+U, lesser diary SE and greater ISI were associated with greater prefrontal activity. Conclusion Results, on balance, suggest that persons with GAD and ID activated more fear-related and less prefrontal emotion-regulatory regions during fear conditioning and extinction recall than those with GAD alone. Across groups, greater REM% and sleep quality were associated with greater activity of emotion-regulatory areas. Support (if any) Funding: R21MH115279, R01MH109638