Distributed neural representations of conditioned threat in the human brain.

Detecting and responding to threat engages several neural nodes including the amygdala, hippocampus, insular cortex, and medial prefrontal cortices. Recent propositions call for the integration of more distributed neural nodes that process sensory and cognitive facets related to threat. Integrative, sensitive, and reproducible distributed neural decoders for the detection and response to threat and safety have yet to be established. We combine functional MRI data across varying threat conditioning and negative affect paradigms from 1465 participants with multivariate pattern analysis to investigate distributed neural representations of threat and safety. The trained decoders sensitively and specifically distinguish between threat and safety cues across multiple datasets. We further show that many neural nodes dynamically shift representations between threat and safety. Our results establish reproducible decoders that integrate neural circuits, merging the well-characterized 'threat circuit' with sensory and cognitive nodes, discriminating threat from safety regardless of experimental designs or data acquisition parameters.

Transcranial focused ultrasound of the amygdala modulates fear network activation and connectivity.

BACKGROUND: Current noninvasive brain stimulation methods are incapable of directly modulating subcortical brain regions critically involved in psychiatric disorders. Transcranial Focused Ultrasound (tFUS) is a newer form of noninvasive stimulation that could modulate the amygdala, a subcortical region implicated in fear. OBJECTIVE: We investigated the effects of active and sham tFUS of the amygdala on fear circuit activation, skin conductance responses (SCR), and self-reported anxiety during a fear-inducing task. We also investigated amygdala tFUS' effects on amygdala-fear circuit resting-state functional connectivity. METHODS: Thirty healthy individuals were randomized in this double-blinded study to active or sham tFUS of the left amygdala. We collected fMRI scans, SCR, and self-reported anxiety during a fear-inducing task (participants viewed red or green circles which indicated the risk of receiving an aversive stimulus), as well as resting-state scans, before and after tFUS. RESULTS: Compared to sham tFUS, active tFUS was associated with decreased (pre to post tFUS) blood-oxygen-level-dependent fMRI activation in the amygdala (F(1,25) = 4.86, p = 0.04, η2 = 0.16) during the fear task, and lower hippocampal (F(1,27) = 4.41, p = 0.05, η2 = 0.14), and dorsal anterior cingulate cortex (F(1,27) = 6.26, p = 0.02; η2 = 0.19) activation during the post tFUS fear task. The decrease in amygdala activation was correlated with decreased subjective anxiety (r = 0.62, p = 0.03). There was no group effect in SCR changes from pre to post tFUS (F(1,23) = 0.85, p = 0.37). The active tFUS group also showed decreased amygdala-insula (F(1,28) = 4.98, p = 0.03) and amygdala-hippocampal (F(1,28) = 7.14, p = 0.01) rsFC, and increased amygdala-ventromedial prefrontal cortex (F(1,28) = 3.52, p = 0.05) resting-state functional connectivity. CONCLUSIONS: tFUS can change functional connectivity and brain region activation associated with decreased anxiety. Future studies should investigate tFUS' therapeutic potential for individuals with clinical levels of anxiety.

The Human Affectome.

Over the last decades, theoretical perspectives in the interdisciplinary field of the affective sciences have proliferated rather than converged due to differing assumptions about what human affective phenomena are and how they work. These metaphysical and mechanistic assumptions, shaped by academic context and values, have dictated affective constructs and operationalizations. However, an assumption about the purpose of affective phenomena can guide us to a common set of metaphysical and mechanistic assumptions. In this capstone paper, we home in on a nested teleological principle for human affective phenomena in order to synthesize metaphysical and mechanistic assumptions. Under this framework, human affective phenomena can collectively be considered algorithms that either adjust based on the human comfort zone (affective concerns) or monitor those adaptive processes (affective features). This teleologically-grounded framework offers a principled agenda and launchpad for both organizing existing perspectives and generating new ones. Ultimately, we hope the Human Affectome brings us a step closer to not only an integrated understanding of human affective phenomena, but an integrated field for affective research.

REM Sleep Measures and REM Vagal Activity Predict Extinction Recall in Trauma-Exposed Individuals.

Accumulating evidence suggests that rapid eye movement sleep (REM) supports the consolidation of extinction memory. REM is disrupted in PTSD, and REM abnormalities after traumatic events increase the risk of developing PTSD. Therefore, it was hypothesized that abnormal REM in trauma-exposed individuals may pave the way for PTSD by interfering with the processing of extinction memory. In addition, PTSD patients display reduced vagal activity. Vagal activity contributes to the strengthening of memories, including fear extinction memory, and recent studies show that the role of vagus in memory processing extends to memory consolidation during sleep. Therefore, it is plausible that reduced vagal activity during sleep in trauma-exposed individuals may be an additional mechanism that impairs extinction memory consolidation. However, to date, the contribution of sleep vagal activity to the consolidation of extinction memory or any emotional memory has not been investigated. To test these hypotheses, we examined the association of extinction memory with REM characteristics and REM vagal activity (indexed as high-frequency heart rate variability; HF-HRV) in a large sample of trauma-exposed individuals (n=113). Consistent with our hypotheses, REM sleep characteristics (increased REM density and shortened REM latency) were associated with poorer physiological and explicit extinction memory. Furthermore, higher HF-HRV during REM was associated with better explicit extinction memory. These findings support the notion that disrupted REM may contribute to PTSD by impairing the consolidation of extinction memory and indicate the potential utility of interventions that target REM sleep characteristics and REM vagal activity in fear-related disorders.

The Impact of Sleep on Fear Extinction.

Sleep plays a crucial role in the consolidation of memories, including those for fear acquisition and extinction training. This chapter reviews findings from studies testing this relationship in laboratory, naturalistic, and clinical settings. While evidence is mixed, several studies in humans have linked fear and extinction recall/retention to both rapid eye-movement and slow wave sleep. Sleep appears to further aid in the processing of both simulated and actual trauma and improves psychotherapeutic treatment outcomes in those with anxiety and trauma- and stressor-related disorders. This chapter concludes with a discussion of the current challenges facing sleep and emotional memory research in addition to suggestions for improving future research.

Multiverse analyses of fear acquisition and extinction retention in posttraumatic stress disorder.

Persistent fear is a cardinal feature of posttraumatic stress disorder (PTSD), and deficient fear extinction retention is a proposed illness mechanism and target of exposure-based therapy. However, evidence for deficient fear extinction in PTSD has been mixed using laboratory paradigms, which may relate to underidentified methodological variation across studies. We reviewed the literature to identify parameters that differ across studies of fear extinction retention in PTSD. We then performed Multiverse Analysis in a new sample, to quantify the impact of those methodological parameters on statistical findings. In 25 PTSD patients (15 female) and 36 trauma-exposed non-PTSD controls (TENC) (20 female), we recorded skin conductance response (SCR) during fear acquisition and extinction learning (day 1) and extinction recall (day 2). A first Multiverse Analysis examined the effects of methodological parameters identified by the literature review on comparisons of SCR-based fear extinction retention in PTSD versus TENC. A second Multiverse Analysis examined the effects of those methodological parameters on comparisons of SCR to a danger cue (CS+) versus safety cue (CS-) during fear acquisition. Both the literature review and the Multiverse Analysis yielded inconsistent findings for fear extinction retention in PTSD versus TENC, and most analyses found no statistically significant group difference. By contrast, significantly elevated SCR to CS+ versus CS- was consistently found across all analyses in the literature review and the Multiverse Analysis of new data. We discuss methodological parameters that may most contribute to inconsistent findings of fear extinction retention deficit in PTSD and implications for future clinical research.

Rapid eye movement sleep parasympathetic activity predicts wake hyperarousal symptoms following a traumatic event.

Heart rate variability (HRV) can be used to assess changes in output of the parasympathetic nervous system (PNS). Considering that patients with post-traumatic stress disorder (PTSD) often experience disturbances in sleep, arousal, and autonomic functioning, we sought to explore the association of PNS activity during sleep with hyperarousal symptoms of PTSD. Because a broad literature supports the importance of rapid eye movement (REM) sleep in PTSD, REM-sleep features were specifically examined as predictors of PTSD symptom severity. A total of 90 participants, primarily civilian and female, aged 18-40 years who had experienced a traumatic event in the last 2 years, underwent an ambulatory polysomnography (PSG) acclimation night followed by a second PSG night from which sleep physiological measures were computed. Participants underwent an ambulatory polysomnography (PSG) acclimation night followed by a second PSG night from which sleep physiological measures were computed. PTSD severity was measured using the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (PCL-5). Dependent variables were total PCL-5 score as well as its hyperarousal symptom subscore. Predictors included REM latency, percentage, density, segment length, and an index of parasympathetic tone (root mean square of the successive differences in the R-R interval or RMSSD). Hierarchical regression models were conducted to analyse the association of REM features with PCL-5 total and hyperarousal subscales. Using hierarchical regression, REM-sleep RMSSD accounted for a significant proportion of the variation in outcome variables, even when accounting for other REM-sleep features. The present findings support hypothesised relationships between PTSD symptomatology and REM-sleep physiology and, specifically, that lowered parasympathetic tone in REM may be an important associate of the hyperarousal symptom cluster in PTSD.

The influence of sleep on fear extinction in trauma-related disorders.

In Posttraumatic Stress Disorder (PTSD), fear and anxiety become dysregulated following psychologically traumatic events. Regulation of fear and anxiety involves both high-level cognitive processes such as cognitive reattribution and low-level, partially automatic memory processes such as fear extinction, safety learning and habituation. These latter processes are believed to be deficient in PTSD. While insomnia and nightmares are characteristic symptoms of existing PTSD, abundant recent evidence suggests that sleep disruption prior to and acute sleep disturbance following traumatic events both can predispose an individual to develop PTSD. Sleep promotes consolidation in multiple memory systems and is believed to also do so for low-level emotion-regulatory memory processes. Consequently sleep disruption may contribute to the etiology of PTSD by interfering with consolidation in low-level emotion-regulatory memory systems. During the first weeks following a traumatic event, when in the course of everyday life resilient individuals begin to acquire and consolidate these low-level emotion-regulatory memories, those who will develop PTSD symptoms may fail to do so. This deficit may, in part, result from alterations of sleep that interfere with their consolidation, such as REM fragmentation, that have also been found to presage later PTSD symptoms. Here, sleep disruption in PTSD as well as fear extinction, safety learning and habituation and their known alterations in PTSD are first briefly reviewed. Then neural processes that occur during the early post-trauma period that might impede low-level emotion regulatory processes through alterations of sleep quality and physiology will be considered. Lastly, recent neuroimaging evidence from a fear conditioning and extinction paradigm in patient groups and their controls will be considered along with one possible neural process that may contribute to a vulnerability to PTSD following trauma.

Call to action: Addressing sleep disturbances, a hallmark symptom of PTSD, for refugees, asylum seekers, and internally displaced persons.

Sleep difficulty is a recognized hallmark symptom of post-traumatic stress disorder (PTSD) yet often remains an enduring and neglected problem post-treatment. Around 4.4%- 88.0% of refugees, asylum seekers, and internally displaced persons report PTSD, of which 39%- 99% report sleep difficulties. These percentages substantially exceed those of the general population. Yet there has been a lack of research examining evidence-based stand-alone and add-on treatments for PTSD and related sleep disturbances among this population. Barriers to treatment encountered by this population often vary by their legal status or location, but generally include lack of access due to insufficient evidence-based treatments or mental health practitioner shortages, lack of psychoeducation on mental health, cultural stigma, language barriers, situational instability, and racial bias. The refugee population has been on the rise over the past 10 years, and the United Nations estimated the recent Ukraine-Russia conflict would lead to an additional 12 million people needing humanitarian assistance inside Ukraine and more than 6.9 million refugees fleeing to neighboring countries in the coming months. Given that refugees, asylum seekers, and internally displaced persons repeatedly encounter barriers to mental health care specific to their predicament, interventions designed to accommodate their situation are imperative for improving their sleep and mental health. We therefore call for there to be more research on integrative programs incorporating evidence-based treatments that allow for scalability, adaptability, and rapid dissemination to maximize impact in this population. Further, we encourage trainings among clinicians and researchers to increase knowledge and confidence in working with this population.

Revisiting sex differences in the acquisition and extinction of threat conditioning in humans.

Findings pertaining to sex differences in the acquisition and extinction of threat conditioning, a paradigm widely used to study emotional homeostasis, remain inconsistent, particularly in humans. This inconsistency is likely due to multiple factors, one of which is sample size. Here, we pooled functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) data from multiple studies in healthy humans to examine sex differences during threat conditioning, extinction learning, and extinction memory recall. We observed increased functional activation in males, relative to females, in multiple parietal and frontal (medial and lateral) cortical regions during acquisition of threat conditioning and extinction learning. Females mainly exhibited higher amygdala activation during extinction memory recall to the extinguished conditioned stimulus and also while responding to the unconditioned stimulus (presentation of the shock) during threat conditioning. Whole-brain functional connectivity analyses revealed that females showed increased connectivity across multiple networks including visual, ventral attention, and somatomotor networks during late extinction learning. At the psychophysiological level, a sex difference was only observed during shock delivery, with males exhibiting higher unconditioned responses relative to females. Our findings point to minimal to no sex differences in the expression of conditioned responses during acquisition and extinction of such responses. Functional MRI findings, however, show some distinct functional activations and connectivities between the sexes. These data suggest that males and females might use different neural mechanisms, mainly related to cognitive processing, to achieve comparable levels of acquired conditioned responses to threating cues.

Morning blue light treatment improves sleep complaints, symptom severity, and retention of fear extinction memory in post-traumatic stress disorder.

Disrupted sleep is a major feature in numerous clinical disorders and is related to decrements in affective memory processing. The prevalence of sleep disruption in post-traumatic stress disorder (PTSD) is suggested to be a key feature that exacerbates the impaired ability to recall extinction memories during experimental fear conditioning. We hypothesized that an intervention employing blue-wavelength light therapy (BLT) to regulate sleep and stabilize circadian rhythms in patients with PTSD (i.e., via regulated morning exposure) would be associated with PTSD symptom improvement, decreased sleep-related complaints, as well as improved consolidation and retention of extinction memories relative to a fear conditioning/extinction paradigm. Eighty-two individuals with PTSD underwent a well-validated fear conditioning/extinction protocol with subsequent assignment to receive morning BLUE (BLT) or placebo AMBER (ALT) light therapy daily for 30-min over 6-weeks. Participants returned after the intervention for post-treatment extinction recall, comprised of exposure to the previously conditioned stimuli, with the difference in skin conductance response between the "extinguished" and the "never-extinguished" stimuli at follow-up. Participants also viewed previously conditioned stimuli in a novel context during a functional magnetic resonance imaging (fMRI) scan. BLUE light therapy was associated with improvements relative to correlated decreases between PTSD symptoms and sleep-related complaints. Participants receiving BLT also sustained retention of the extinction memory, while those in the placebo amber light treatment group showed impairment, characterized by the restoration of the extinguished fear response after 6-weeks. Participants in the ALT also demonstrated greater reactivity in the left insula when viewing the previously extinguished fear-conditioned stimuli in a novel context. Daily BLUE-wavelength morning light exposure was associated with greater retention of extinction learning in patients with PTSD when compared to ALT, as supported by both autonomic and neurobiological reactivity. We speculate that improved sleep facilitated by a stabilized circadian rhythm, after fear-learning, led to greater consolidation of the fear extinction memory, decreased PTSD symptom presentation, and associated decreases in sleep-related complaints. Prominent exposure treatments for PTSD incorporate principles of fear extinction, and our findings suggest that blue light treatment may facilitate treatment gains by promoting the consolidation of extinction memories via improved sleep.

Sleep Quality Impairment Is Associated With Pandemic Attitudes During the Coronavirus Disease 2019 (COVID-19) Circuit Breaker Lockdown in England: A Cross-Sectional Study.

Objectives: The COVID-19 pandemic has been associated with sleep quality impairment and psychological distress, and the general public has responded to the pandemic and quarantine requirements in a variety of ways. We aimed to investigate whether sleep quality is low during a short-term (circuit break) quarantine restriction, and whether sleep quality is associated with respondents' overall attitudes to the pandemic using a validated scale. Design and Setting: Online cross-sectional study in England in November 2020. Participants: The study included 502 respondents over the age of 18. Measurements: Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), and pandemic attitudes were assessed using the Oxford Pandemic Attitudes Scale-COVID-19 (OPAS-C), a validated 20-item, 7-domain scale that assesses pandemic-related stress, fear, loneliness, sense of community, sense of exaggerated concern, non-pharmaceutical interventions, and vaccine hesitancy. Unadjusted and multivariable logistic regression odds ratios of association were assessed between the dependent variable of poor sleep quality (PSQI>5) and risk factors, including OPAS-C score, age, sex, educational status, and income. Results: The mean (SD) PSQI score was 7.62 (3.49). Overall, 68.9% of respondents met criteria for poor sleep quality using the PSQI cutoff of >5. The mean (SD) OPAS-C score was 60.3 (9.1). There was a significantly increased odds of poor sleep quality in the highest vs. lowest OPAS-C quartiles (OR 4.94, 95% CI [2.67, 9.13], p < 0.0001). Age, sex, income, political leaning, employment status, and education attainment were not associated with poor sleep quality. Conclusions: More than two-thirds of respondents met criteria for poor sleep quality. The odds of poor sleep quality increased in a dose-response relationship with pandemic attitudes (such as higher levels of pandemic-related stress, fear, or loneliness). The association between poor sleep quality and pandemic attitudes suggests opportunities for public health and sleep medicine interventions, and highlights the need for further research.

Temporally and anatomically specific contributions of the human amygdala to threat and safety learning.

Neural plasticity in subareas of the rodent amygdala is widely known to be essential for Pavlovian threat conditioning and safety learning. However, less consistent results have been observed in human neuroimaging studies. Here, we identify and test three important factors that may contribute to these discrepancies: the temporal profile of amygdala response in threat conditioning, the anatomical specificity of amygdala responses during threat conditioning and safety learning, and insufficient power to identify these responses. We combined data across multiple studies using a well-validated human threat conditioning paradigm to examine amygdala involvement during threat conditioning and safety learning. In 601 humans, we show that two amygdala subregions tracked the conditioned stimulus with aversive shock during early conditioning while only one demonstrated delayed responding to a stimulus not paired with shock. Our findings identify cross-species similarities in temporal- and anatomical-specific amygdala contributions to threat and safety learning, affirm human amygdala involvement in associative learning and highlight important factors for future associative learning research in humans.

Abnormal dynamic functional connectivity during fear extinction learning in PTSD and anxiety disorders.

Examining the neural circuits of fear/threat extinction advanced our mechanistic understanding of several psychiatric disorders, including anxiety disorders (AX) and posttraumatic stress disorder (PTSD). More is needed to understand the interplay of large-scale neural networks during fear extinction in these disorders. We used dynamic functional connectivity (FC) to study how FC might be perturbed during conditioned fear extinction in individuals with AX or PTSD. We analyzed neuroimaging data from 338 individuals that underwent a two-day fear conditioning and extinction paradigm. The sample included healthy controls (HC), trauma-exposed non-PTSD controls, and patients diagnosed with AX or PTSD. Dynamic FC during extinction learning gradually increased in the HC group but not in patient groups. The lack of FC change in patients was predominantly observed within and between the default mode, frontoparietal control, and somatomotor networks. The AX and PTSD groups showed impairments in different, yet partially overlapping connections especially involving the dorsolateral prefrontal cortex. Extinction-induced FC predicted ventromedial prefrontal cortex activation and FC during extinction memory recall only in the HC group. FC impairments during extinction learning correlated with fear- and anxiety-related clinical measures. These findings suggest that relative to controls, individuals with AX or PTSD exhibited widespread abnormal FC in higher-order cognitive and attention networks during extinction learning and failed to establish a link between neural signatures during extinction learning and memory retrieval. This failure might underlie abnormal processes related to the conscious awareness, attention allocation, and sensory processes during extinction learning and retrieval in fear- and anxiety-related disorders.

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

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.

Sleep Power Spectral Density and Spindles in PTSD and Their Relationship to Symptom Severity.

Sleep disturbances are common in post-traumatic stress disorder (PTSD), although which sleep microarchitectural characteristics reliably classify those with and without PTSD remains equivocal. Here, we investigated sleep microarchitectural differences (i.e., spectral power, spindle activity) in trauma-exposed individuals that met (n = 45) or did not meet (n = 52) criteria for PTSD and how these differences relate to post-traumatic and related psychopathological symptoms. Using ecologically-relevant home sleep polysomnography recordings, we show that individuals with PTSD exhibit decreased beta spectral power during NREM sleep and increased fast sleep spindle peak frequencies. Contrary to prior reports, spectral power in the beta frequency range (20.31-29.88 Hz) was associated with reduced PTSD symptoms, reduced depression, anxiety and stress and greater subjective ability to regulate emotions. Increased fast frequency spindle activity was not associated with individual differences in psychopathology. Our findings may suggest an adaptive role for beta power during sleep in individuals exposed to a trauma, potentially conferring resilience. Further, we add to a growing body of evidence that spindle activity may be an important biomarker for studying PTSD pathophysiology.

Partial and Total Sleep Deprivation Interferes With Neural Correlates of Consolidation of Fear Extinction Memory.

BACKGROUND: We assessed the impact of total and partial sleep loss on neural correlates of fear conditioning, extinction learning, and extinction recall in healthy young adults. METHODS: Participants (56.3% female, age 24.8 ± 3.4 years) were randomized to a night of normal sleep (NS) (n = 48), sleep restriction (SR) (n = 53), or sleep deprivation (SD) (n = 53). All completed fear conditioning and extinction learning phases the following morning. Extinction recall was tested in the evening of the same day. Task-based contrasts were modeled at the beginning of, at the end of, and across the fear conditioning and extinction learning phases, and at the beginning of extinction recall. These contrasts were compared among the 3 groups by means of analysis of variance. Nonparametric permutation corrected analyses using a cluster-determining threshold of p < .005 and a familywise error of p < .05. RESULTS: At the end of fear conditioning, NS activated medial prefrontal regions, SR activated motor areas, and participants in the SD group showed no significant activations. Across extinction learning, only NS activated both salience (fear) and extinction (regulatory) areas. For extinction recall, SD activated similar regions as NS across extinction learning, while SR activated salience and motor areas. During early fear conditioning, compared with NS, SD activated more medial prefrontal and SR activated more salience network areas. For extinction recall, NS activated more prefrontal areas and SD activated more of both salience- and extinction-related areas than SR. CONCLUSIONS: Relative to NS, SR may enhance fear-related and diminish extinction-related activity, whereas SD may delay engagement of extinction learning. Findings may have clinical implications for populations and occupations in which sleep loss is common.

Fear extinction memory is negatively associated with REM sleep in insomnia disorder.

STUDY OBJECTIVES: Formation and maintenance of fear-extinction memories are disrupted in post-traumatic stress disorder (PTSD) and anxiety disorders. Sleep contributes to emotional memory consolidation and emotion regulation. Insomnia disorder (ID) is characterized by persistent sleep disturbance as well as rapid eye movement (REM) sleep abnormalities and often precedes or develops in parallel with PTSD and anxiety disorders. Here, we explore the impact of chronic poor sleep and sleep immediately following fear conditioning and extinction learning on preservation of extinction memories. METHODS: Twenty-four ID age- and sex-matched to 24 healthy, good sleeper controls (GS) completed up to 2 weeks of habitual sleep monitoring with daily sleep-wake diaries and actigraphy, and then participated in a two-session fear conditioning, extinction learning and extinction recall procedure. Fear Conditioning and Extinction Learning occurred during session 1, followed by Extinction Recall approximately 24 hours later. Skin-conductance responses (SCR) and shock expectancies were recorded throughout all experimental phases to evaluate associative learning and memory. Overnight sleep between sessions 1 and 2 was recorded using ambulatory polysomnography. RESULTS: ID showed greater physiological reactivity during Fear Conditioning. REM sleep physiology was associated with poorer extinction memory in ID but better extinction memory in GS. CONCLUSION: REM sleep physiology may differentially support emotional memory retention and expression in ID and GS. In the former, REM may enhance retention of fear memories, while in the later, REM may enhance the expression of extinction memories.

In Trauma-Exposed Individuals, Self-reported Hyperarousal and Sleep Architecture Predict Resting-State Functional Connectivity in Frontocortical and Paralimbic Regions.

BACKGROUND: Symptoms of posttraumatic stress disorder (PTSD) reflect abnormalities in large-scale brain networks. In individuals with recent trauma exposure, we examined associations of seed-based resting-state functional connectivity (rs-FC) with posttraumatic symptoms and sleep. We hypothesized that more severe PTSD symptoms and poorer sleep quality would predict 1) greater rs-FC between fear-related seeds and other fear-related regions and 2) lesser rs-FC between fear-related seeds and emotion-regulatory regions. METHODS: Seventy-four participants who had experienced a DSM-5 criterion A stressor within the past 2 years and ranged from asymptomatic to fully meeting criteria for PTSD diagnosis underwent 14 days of actigraphy and sleep diaries, a night of ambulatory polysomnography, and a functional magnetic resonance imaging resting-state scan at 3T. rs-FC measures of 5 fear-related seeds and 1 emotion regulatory seed with regions of the anterior cerebrum were correlated with PTSD symptoms, objective and subjective habitual sleep quality, and sleep architecture. RESULTS: Longer objective habitual sleep onset latency was associated with greater connectivity between fear-related seeds and other regions of the salience network. Greater PTSD symptoms were associated with less connectivity between fear-related seeds and anterior emotion regulatory regions, whereas greater percent slow wave sleep was associated with more connectivity between these regions. However, other objective and subjective measures reflecting better habitual sleep quality were associated with less rs-FC between these regions. CONCLUSIONS: Longer sleep onset latency predicted greater rs-FC among fear-related areas. More severe PTSD symptoms predicted less rs-FC between fear and fear regulatory regions reflecting putatively reduced top-down fear regulation. Some (e.g., percent slow wave sleep), but not all sleep indices predicted greater top-down fear regulation.