Associations of sleep measures with neural activations accompanying fear conditioning and extinction learning and memory in trauma-exposed individuals

Abstract

Study Objectives: Sleep disturbances increase risk of posttraumatic stress disorder (PTSD). Sleep effects on extinction may contribute to such risk. Neural activations to fear extinction were examined in trauma-exposed participants and associated with sleep variables. Methods: Individuals trauma-exposed within the past 2 years (N = 126, 63 PTSD) completed 2 weeks actigraphy and sleep diaries, three nights ambulatory polysomnography and a 2-day fMRI protocol with Fear-Conditioning, Extinction-Learning and, 24 h later, Extinction-Recall phases. Activations within the anterior cerebrum and regions of interest (ROI) were examined within the total, PTSD-diagnosed and trauma-exposed control (TEC) groups. Sleep variables were used to predict activations within groups and among total participants. Family wise error was controlled at p < 0.05 using nonparametric analysis with 5,000 permutations. Results: Initially, Fear Conditioning activated broad subcortical and cortical anterior-cerebral regions. Within-group analyses showed: (1) by end of Fear Conditioning activations decreased in TEC but not PTSD; (2) across Extinction Learning, TEC activated medial prefrontal areas associated with emotion regulation whereas PTSD did not; (3) beginning Extinction Recall, PTSD activated this emotion-regulatory region whereas TEC did not. However, the only between-group contrast reaching significance was greater activation of a hippocampal ROI in TEC at Extinction Recall. A greater number of sleep variables were associated with cortical activations in separate groups versus the entire sample and in PTSD versus TEC. Conclusions: PTSD nonsignificantly delayed extinction learning relative to TEC possibly increasing vulnerability to pathological anxiety. The influence of sleep integrity on brain responses to threat and extinction may be greater in more symptomatic individuals. Statement of Significance Fear conditioning is a model for acquiring the disabling fears following psychological trauma characteristic of PTSD. Fear extinction - learning and remembering that what once signaled danger no longer does so - is the neurocognitive underpinning of natural recovery from trauma as well as exposure-based therapies for PTSD. Sleep-dependent processes support consolidation of memory in multiple neural systems including those that support extinction. PTSD is characterized by chronic sleep disruptions that may contribute to failure to learn or remember extinction. Understanding associations between normal and abnormal features of sleep and neural activity during the processes of acquiring fear, and learning and remembering not to fear, will assist development of sleep-based interventions for PTSD that target specific symptoms and their neural bases.