0311 DIFFERENCES IN ACTIVATION OF FEAR AND EXTINCTION CIRCUITRY IN INDIVIDUALS WITH PRIMARY INSOMNIA

• Published in: Sleep (New York, N.Y.) N.Y.), 2017-04, Vol.40 (suppl_1), p.A115-A115
• Main Authors: Moore, KN, Bottary, RM, Gazecki, S, Lasko, NB, Zsido, R, Bianchi, MT, Gannon, K, Milad, MR, Pace-Schott, EF
• Format: Article
• Language: English
• Subjects: Extinction (Learning); Insomnia
• ISSN: 0161-8105; 1550-9109
• DOI: 10.1093/sleepj/zsx050.310

Abstract Introduction: Insomnia is a predisposing factor for anxiety disorders which are associated with fear extinction deficits. In good sleepers (GS) and persons with Primary Insomnia (PI), we examined neural activation in regions implicated in fear and extinction learning (amygdala, insula, anterior cingulate, vmPFC, hippocampus). We hypothesized that PI, relative to GS, would demonstrate abnormalities of fear- and/or extinction-learning networks. Methods: Twenty-four participants completed diagnostic assessments and were classified as PI (N=12, 2males, average 32.9y) or GS (N=12, 2males, average 36y). Subjects underwent a validated fear conditioning/extinction paradigm in an fMRI scanner with simultaneous skin conductance responses recording. Functional activation during conditioning and extinction learning was quantified via BOLD signal. An ROI approach focused on a priori fear/extinction regions (cluster-determining threshold: p=0.005, cluster-size threshold:10 voxels). Contrasts compared GS and PI BOLD signal between the reinforced (CS+) and non-reinforced (CS-) conditioned stimuli at the beginning (early) and/or end (late) of learning as well as the CS+ between early and late time points. Results: In responses to late vs. early CS+ across fear conditioning, GS showed greater activation in the left insula (cluster size: 68voxels) relative to PI. GS also showed greater activation than PI to CS+ vs. CS- in bilateral insula (R 176voxels, L 42vox) and dorsal ACC (dACC, 15voxels) in late conditioning. At early extinction, PI showed greater activation than GS to CS+ vs. CS- in the left insula (56vox) and dACC (56vox). However, in responses to CS+ vs CS- in late extinction, GS showed greater bilateral insula activation (R 50vox, L 61vox) relative to PI. In responses to late vs. early CS+ across extinction, GS again showed greater activation than PI in the left insula (32voxels) and rostral ACC (rACC, 10,38,18; 491voxels). Conclusion: In PI, the lesser activation of fear-related structures during late fear learning phases and greater activation of these same structures during early extinction suggests disturbed encoding of fear memory. Greater rACC activation in GS across extinction learning suggests that GS may exert better top-down control over fear circuitry. A larger sample size is necessary to answer outstanding questions. Support (If Any): R21MH101567; 2015–2016 Harvard Mind/Brain/Behavior Interfaculty Initiative.