Edward F Pace-Schott

Partners HealthCare

Background Accumulating evidence suggests that rapid eye movement sleep (REM) supports the consolidation of extinction memory. REM is disrupted in posttraumatic stress disorder (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...

Study Objectives Trauma-related nightmares (TRNs) are a hallmark symptom of PTSD and are highly correlated with PTSD severity and poor sleep quality. Given the salience and arousal associated with TRNs, they might be an effective target for imaginal exposures during Prolonged Exposure (PE) therapy. As a first step in this line of research, the curr...

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 de...

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 investigate...

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 const...

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...

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 bot...

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 latt...

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 hypo...

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 symptom...

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 quali...

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...

We present here a unifying framework for affective phenomena: the Human Affectome. By synthesizing a large body of literature, we have converged on definitions that disambiguate the commonly used terms—affect, feeling, emotion, and mood. Based on this definitional foundation, and under the premise that affective states reflect allostatic concerns,...

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 co...

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 no...

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) compl...

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 (S...

Social jetlag (SJ) occurs when sleep-timing irregularities from social or occupational demands conflict with endogenous sleep–wake rhythms. SJ is associated with evening chronotype and poor mental health, but mechanisms supporting this link remain unknown. Impaired ability to retrieve extinction memory is an emotion regulatory deficit observed in s...

Introduction Abnormal interoception is believed to contribute to anxiety disorders as well as possibly to Insomnia Disorder. We therefore hypothesized that interoceptive sensitivity in persons with Generalized Anxiety Disorder (GAD) would vary with sleep quality and would differ between GAD patients with and without insomnia. Methods 29 subjects (...

Introduction Nightmares are a frequent and disturbing symptom of posttraumatic stress disorder (PTSD). They are associated with sleep disruption and increased psychopathology. There is growing evidence that different types of nightmares may differ in their effects on psychopathology. Previous findings suggest that nightmares that are close replicat...

Introduction Individuals with posttraumatic stress disorder (PTSD) exhibit autonomic hyperarousal and nightmares. We hypothesized that REM density (REMD) and REM heart rate variability would predict self-reported hyperarousal, nightmares, and PTSD diagnosis in trauma-exposed individuals. Methods Ninety-nine individuals (aged 18-40, 68 females) exp...

Introduction Hyperarousal and disturbed sleep are intrinsic symptoms of posttraumatic stress disorder (PTSD). We explored whether self-reported indices of hyperarousal predict longitudinally measured objective, subjective, and retrospective evaluations of sleep quality in trauma-exposed individuals. Methods Individuals exposed to a DSM-5 PTSD Crit...

Introduction The current study examined the relationship between pre-sleep processes and sleep in the context of real-world stress exposure in medical students during an internship. Medical students are often exposed to a variety of stressors and potentially traumatic events and have been shown to be at risk to develop psychopathology. Previous res...

Introduction We examined associations of sleep and hyperarousal with neural responses to a fear conditioning and extinction protocol in trauma-exposed individuals. We hypothesized, greater hyperarousal, poorer sleep quality and more nightmares would accompany greater activation of the salience network (associated with fear) and lesser activation of...

Introduction Hyperarousal and abnormal autonomic functioning are among the core manifestations of posttraumatic stress disorder (PTSD). In this study, we examined the association of parasympathetic activity during slow wave sleep (SWS) with self-reported hyperarousal measures in recently traumatized individuals. Methods Individuals exposed to a PT...

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 REM sleep abnormalities and often precedes...

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 qua...

The role of peripheral physiology in the experience of emotion has been debated since the 19th century following the seminal proposal by William James that somatic responses to stimuli determine subjective emotion. Subsequent views have integrated forebrain’s ability to initiate, represent and simulate such physiological events. Modern affective ne...

Introduction Trauma-related nightmares are a distinguishing feature of the “re-experiencing” criteria for posttraumatic stress disorder (PTSD). We examined whether “hyperarousal” criterion features also predict rates of negative dreams in recently traumatized individuals. Methods Seventy participants aged 18-40 (45 females) exposed to a traumatic...

Introduction Trauma-related nightmares are a major re-experiencing symptom of Posttraumatic Stress Disorder (PTSD). Although trauma-related nightmares have been shown to arise in both REM and NREM in persons diagnosed with PTSD, less is known about their occurrence across the full spectrum of post-trauma sequelae. Methods Individuals exposed to a...

Introduction Hyperarousal and abnormal autonomic functioning are core manifestations of posttraumatic stress disorder (PTSD). We examined associations of heart rate variability measures of parasympathetic activity during REM with PTSD diagnosis, self-reported hyperarousal and general psychopathology in recently traumatized individuals. Methods Ind...

Introduction Little is known about associations between cortical thickness and sleep difficulties in posttraumatic stress disorder (PTSD). We examined sleep, hyperarousal, and cortical thickness in trauma-exposed individuals. Methods Individuals exposed to trauma within the past 2 years (N=77) completed the Structured Clinical Interview for DSM, t...

Exposure therapy for social anxiety disorder (SAD) utilizes fear extinction, a memory process enhanced by sleep. We investigated whether naps following exposure sessions might improve symptoms and biomarkers in response to social stress in adults undergoing 5-week exposure-based group SAD therapy. Thirty-two participants aged 18–39 (18 females) wit...

This chapter reviews the commonly observed sleep-related symptoms of posttraumatic stress disorder (PTSD). Sleep disturbances, such as insomnia and trauma-related recurrent nightmares, are extremely common in PTSD and have long been recognized as a core feature of the condition. They appear to play an important role in the development and maintenan...

Study Objectives Insomnia increases risk for anxiety disorders that are also associated with fear-extinction deficits. We compared activation of fear and extinction networks between Insomnia Disorder without comorbidity (ID) and good sleepers (GS). Methods 23 ID age- and sex-matched to 23 GS completed 14 days of actigraphy and diaries, 3 nights of...

We examined whether non-traumatized subjects with Attention Deficit Hyperactivity Disorder (ADHD) have dysfunctional activation in brain structures mediating fear extinction, possibly explaining the statistical association between ADHD and other disorders characterized by aberrant fear processing such as PTSD. Medication naïve, non-traumatized youn...

Seventy-three women with posttraumatic stress disorder (PTSD) resulting from rape or physical assault participated in a loud-tone procedure, while skin conductance (SC), heart rate, and electromyogram responses were recorded. Pearson correlations were examined between each psychophysiological response and Clinician-Administered PTSD Scale (CAPS) sy...

Objective: Exposure-based therapy, an effective treatment for posttraumatic stress disorder (PTSD), relies on extinction learning principles. In PTSD patients, dysfunctional patterns in the neural circuitry underlying fear extinction have been observed using resting-state or functional activation measures. It remains undetermined whether resting a...

Background: Findings about sex differences in the field of fear conditioning and fear extinction have been mixed. At the psychophysiological level, sex differences emerge only when taking estradiol levels of women into consideration. This suggests that this hormone may also influence sex differences with regards to activations of brain regions inv...

Poor ability to remember the extinction of conditioned fear, elevated trait anxiety, and delayed or disrupted nocturnal sleep are reported in anxiety disorders. The current study examines the interrelationship of these factors in healthy young-adult males. Skin-conductance response was conditioned to two differently colored lamps. One color but not...

Post-traumatic stress disorder (PTSD) is accompanied by disturbed sleep and an impaired ability to learn and remember extinction of conditioned fear. Following a traumatic event, the full spectrum of PTSD symptoms typically requires several months to develop. During this time, sleep disturbances such as insomnia, nightmares, and fragmented rapid ey...

We used unique data sets from Dreamboard and SurveyMonkey to test the hypothesis that aggression levels would vary significantly with content of recurrent nightmares, nonrecurrent nightmares, and unpleasant dreams. Exactly 475 nightmares and 433 unpleasant dreams were collected from Dreamboard users, while 135 nightmares were collected from individ...

Learning and memory for extinction of conditioned fear is a basic mammalian mechanism for regulating negative emotion. Sleep promotes both the consolidation of memory and the regulation of emotion. Sleep can influence consolidation and modification of memories associated with both fear and its extinction. After brief overviews of the behavior and n...

Sleep quality and architecture as well as sleep’s homeostatic and circadian controls change with healthy aging. Changes include reductions in slow-wave sleep’s (SWS) percent and spectral power in the sleep electroencephalogram (EEG), number and amplitude of sleep spindles, rapid eye movement (REM) density and the amplitude of circadian rhythms, as...

Within-session habituation and extinction learning co-occur as do subsequent consolidation of habituation (i.e., between-session habituation) and extinction memory. We sought to determine whether, as we predicted: (1) between-session habituation is greater across a night of sleep versus a day awake; (2) time-of-day accounts for differences; (3) bet...

Aging is accompanied by changes in sleep quality that include decreases in total sleep time and sleep efficiency as well as increases in wake time after sleep onset and early-morning awakenings. These changes produce an overall decline in sleep quality that can be further exacerbated by behavioral factors such as increased daytime napping and dimin...

Sleep contains two distinct sub-states-rapid eye movement (REM) and non-REM (NREM) sleep that alternate with a cycle of about 90 min and are measured using electroencephalography (EEG), electrooculography (EOG) and electromyography (EMG), collectively termed polysomnography (PSG). Following sleep onset, NREM first passes through three stages (N1-N3...

Improvements in motor sequence learning come about via goal-based learning of the sequence of visual stimuli and muscle-based learning of the sequence of movement responses. In young adults, consolidation of goal-based learning is observed after intervals of sleep but not following wake, whereas consolidation of muscle-based learning is greater fol...

Dreams create new stories out of nothing. Although dreams contain themes, concerns, dream figures, objects, etc. that correspond closely to waking life, these are only story elements. The story itself weaves these mnemonic items together in a manner far more novel than a simple assemblage or collage, producing an experience having a life-like timef...

Sleep benefits veridical memories, resulting in superior recall relative to off-line intervals spent awake. Sleep also increases false memory recall in the Deese-Roediger-McDermott (DRM) paradigm. Given the suggestion that emotional veridical memories are prioritized for consolidation over sleep, here we examined whether emotion modulates sleep's e...

There have been proposals for REM to have a function of emotional memory consolidation, and also for REM sleep to be involved in the promotion of attachment behaviour. The hormones cortisol and oxytocin, respectively, may be involved in these proposed REM sleep functions. However, there are conflicting reports on whether levels of cortisol differ b...

GABA is increasingly recognized as an important neurotransmitter for the initiation and maintenance of sleep. We sought to measure cortical GABA content through proton magnetic resonance spectroscopy (MRS) in persons with and without primary insomnia, and relate brain GABA levels to polysomnographic sleep measures. Two-group comparison study. Outpa...

Sleep enhances memories, particularly emotional memories. As such, it has been suggested that sleep deprivation may reduce posttraumatic stress disorder. This presumes that emotional memory consolidation is paralleled by a reduction in emotional reactivity, an association that has not yet been examined. In the present experiment, we used an inciden...

Sleep benefits memory across a range of tasks for young adults. However, remarkably little is known of the role of sleep on memory for healthy older adults. We used 2 tasks, 1 assaying motor skill learning and the other assaying nonmotor/declarative learning, to examine off-line changes in performance in young (20-34 years), middle-aged (35-50 year...

Healthy aging is characterized by a diminished quality of sleep with decreased sleep duration and increased time awake after sleep onset. Older adults awaken more frequently and tend to awaken less from rapid eye movement (REM) sleep and more from non-REM (nREM) sleep than young adults. Sleep architecture also begins changing in middle age leading...

This study investigates evidence, from dream reports, for memory consolidation during sleep. It is well-known that events and memories from waking life can be incorporated into dreams. These incorporations can be a literal replication of what occurred in waking life, or, more often, they can be partial or indirect. Two types of temporal relationshi...

Faithful replication of normal sleep through medications--can it be achieved? Departure from normal sleep with the use of drugs--when is it desired? Answers to these questions depend on accurate understanding of sleep and on concrete criteria upon which to define it. Since these elements are evolving sciences, as yet incompletely known, one might t...

Among sleep stages, awakenings from rapid eye movement (REM) sleep produce the greatest number and reported intensity of dream reports. Dreaming is a conscious state that lacks the insight and cognitive control typical of healthy waking but allows the remarkable emergence of coherent narrative, vivid visual imagery, strong emotion, and sometimes ne...

Activity in the prefrontal cortex may distinguish the meta-awareness experienced during lucid dreams from its absence in normal dreams. To examine a possible relationship between dream lucidity and prefrontal task performance, we carried out a prospective study in 28 high school students. Participants performed the Wisconsin Card Sort and Iowa Gamb...

A question of great interest in current sleep research is whether and how sleep might facilitate complex cognitive skills such as decision-making. The Iowa Gambling Task (IGT) was used to investigate effects of sleep on affect-guided decision-making. After a brief standardized preview of the IGT that was insufficient to learn its underlying rule, p...

Based on REM sleep's brain activation patterns and its participation in consolidation of emotional memories, we tested the hypothesis that measures of REM sleep architecture and REM sleep-related mentation would be associated with attachment orientation. After a habituation night in a sleep lab, a convenience sample of 64 healthy volunteers were aw...

Individuals differ greatly in their dream recall frequency, in their incidence of recalling types of dreams, such as nightmares, and in the content of their dreams. This chapter reviews work on the waking life correlates of these differences between people in their experience of dreaming and reviews some of the neurobiological correlates of these i...

Dreaming is a universal human mental state characterized by hallucinatory imagery congruent with a confabulated, temporally ordered, storylike experience. As in waking consciousness, such experiences in both rapid eye movement (REM) and non-REM (NREM) sleep are associated with activation of forebrain structures by ascending arousal systems of the b...

The effects of a daytime nap on inter-session habituation to aversive visual stimuli were investigated. Healthy young adult volunteers viewed repeated presentations of highly negative and emotionally neutral (but equally arousing) International Affective Picture System (IAPS) photographs during two afternoon sessions separated by 2.5h. Half of the...

Dream content may reflect elements of memory processing occurring within a single night and across several days or weeks. One 19-year-old healthy female college student kept a daily diary, a sleep diary, and recorded her dreams for 2 months. A preset alarm clock allowed her to sample dreams from both early NREM-rich and late REM-rich sleep. Dreams...

The purpose of the present study was to determine the effect of morning-dosed modafinil on sleep and daytime sleepiness in chronic cocaine users. Twenty cocaine-dependent participants were randomly assigned to receive modafinil, 400 mg (N=10), or placebo (N=10) every morning at 7:30 a.m. for 16 days in an inpatient, double-blind randomized trial. P...

In clinical drug development, wakefulness and wake-promotion may be assessed by a large number of scales and questionnaires. Objective assessment of wakefulness is most commonly made using sleep latency/maintenance of wakefulness tests, polysomnography and/or behavioral measures. The purpose of the present review is to highlight the degree of overl...

To examine the effects of sleep on fear conditioning, extinction, extinction recall, and generalization of extinction recall in healthy humans. During the Conditioning phase, a mild, 0.5-sec shock followed conditioned stimuli (CS+s), which consisted of 2 differently colored lamps. A third lamp color was interspersed but never reinforced (CS-). Imme...

Young adult male students participated in a naturalistic, group-design experiment to ascertain the effects of one night's total sleep deprivation (TSD) on performance of diverse executive function tasks presented as an extended, multitask battery. On the majority of component tasks in this battery, performance has been reported to be impaired follo...

Disturbances in sleep associated with chronic cocaine use may underlie abstinence-related cognitive dysfunction. We hypothesized that sleep-related cognitive function would be impaired in chronic cocaine users, and that this impairment would be associated with abstinence-related changes in sleep architecture. Twelve chronic cocaine users completed...

Seventeen non-treatment seeking cocaine-dependent individuals participated in three-week longitudinal inpatient studies of cognitive changes during drug use and abstinence. Protocols included three days drug-free baseline, three days cocaine self-administration, and two weeks complete abstinence. A repeatable cognitive battery showed attention and...

Many clinical anecdotes and an experimental study have reported intensification of dreaming by the selective serotonin-reuptake inhibitors (SSRIs). However, no published neurochemical dream model invokes serotonin as a dream-promoting neuromodulator or accounts for serotonergic dream enhancement. An experimental study of normal volunteers showed th...

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Although 20% of myocardial infarctions (MIs) and 15% of sudden cardiac deaths (SCD) occur between midnight and 6:00 A.M., nocturnal cardiac death remains an underappreciated and poorly understood phenomenon. The risk of nocturnal SCD may be-especially high in patients with coronary disease confounded by apnea, heart failure, recent Ml, pause-depend...