Sex differences in objective measures of sleep in post‐traumatic stress disorder and healthy control subjects

A growing literature shows prominent sex effects for risk for post‐traumatic stress disorder and associated medical comorbid burden. Previous research indicates that post‐traumatic stress disorder is associated with reduced slow wave sleep, which may have implications for overall health, and abnormalities in rapid eye movement sleep, which have been implicated in specific post‐traumatic stress disorder symptoms, but most research has been conducted in male subjects. We therefore sought to compare objective measures of sleep in male and female post‐traumatic stress disorder subjects with age‐ and sex‐matched control subjects. We used a cross‐sectional, 2 × 2 design (post‐traumatic stress disorder/control × female/male) involving83 medically healthy, non‐medicated adults aged 19–39 years in the inpatient sleep laboratory. Visual electroencephalographic analysis demonstrated that post‐traumatic stress disorder was associated with lower slow wave sleep duration (F_(3,82) = 7.63, P = 0.007) and slow wave sleep percentage (F_(3,82) = 6.11, P = 0.016). There was also a group × sex interaction effect for rapid eye movement sleep duration (F_(3,82) = 4.08, P = 0.047) and rapid eye movement sleep percentage (F_(3,82) = 4.30, P = 0.041), explained by greater rapid eye movement sleep in post‐traumatic stress disorder females compared to control females, a difference not seen in male subjects. Quantitative electroencephalography analysis demonstrated that post‐traumatic stress disorder was associated with lower energy in the delta spectrum (F_(3,82) = 6.79, P = 0.011) in non‐rapid eye movement sleep. Slow wave sleep and delta findings were more pronounced in males. Removal of post‐traumatic stress disorder subjects with comorbid major depressive disorder, who had greater post‐traumatic stress disorder severity, strengthened delta effects but reduced rapid eye movement effects to non‐significance. These findings support previous evidence that post‐traumatic stress disorder is associated with impairment in the homeostatic function of sleep, especially in men with the disorder. These findings suggest that group × sex interaction effects on rapid eye movement may occur with more severe post‐traumatic stress disorder or with post‐traumatic stress disorder comorbid with major depressive disorder.     

Disrupted rapid eye movement sleep predicts poor declarative memory performance in post‐traumatic stress disorder

Successful memory consolidation during sleep depends on healthy slow‐wave and rapid eye movement sleep, and on successful transition across sleep stages. In post‐traumatic stress disorder, sleep is disrupted and memory is impaired, but relations between these two variables in the psychiatric condition remain unexplored. We examined whether disrupted sleep, and consequent disrupted memory consolidation, is a mechanism underlying declarative memory deficits in post‐traumatic stress disorder. We recruited three matched groups of participants: post‐traumatic stress disorder (n = 16); trauma‐exposed non‐post‐traumatic stress disorder (n = 15); and healthy control (n = 14). They completed memory tasks before and after 8 h of sleep. We measured sleep variables using sleep‐adapted electroencephalography. Post‐traumatic stress disorder‐diagnosed participants experienced significantly less sleep efficiency and rapid eye movement sleep percentage, and experienced more awakenings and wake percentage in the second half of the night than did participants in the other two groups. After sleep, post‐traumatic stress disorder‐diagnosed participants retained significantly less information on a declarative memory task than controls. Rapid eye movement percentage, wake percentage and sleep efficiency correlated with retention of information over the night. Furthermore, lower rapid eye movement percentage predicted poorer retention in post‐traumatic stress disorder‐diagnosed individuals. Our results suggest that declarative memory consolidation is disrupted during sleep in post‐traumatic stress disorder. These data are consistent with theories suggesting that sleep benefits memory consolidation via predictable neurobiological mechanisms, and that rapid eye movement disruption is more than a symptom of post‐traumatic stress disorder.     

Evidence that non‐dreamers do dream: a REM sleep behaviour disorder model

To determine whether non‐dreamers do not produce dreams or do not recall them, subjects were identified with no dream recall with dreamlike behaviours during rapid eye movement sleep behaviour disorder, which is typically characterised by dream‐enacting behaviours congruent with sleep mentation. All consecutive patients with idiopathic rapid eye movement sleep behaviour disorder or rapid eye movement sleep behaviour disorder associated with Parkinson's disease who underwent a video‐polysomnography were interviewed regarding the presence or absence of dream recall, retrospectively or upon spontaneous arousals. The patients with no dream recall for at least 10 years, and never‐ever recallers were compared with dream recallers with rapid eye movement sleep behaviour disorder regarding their clinical, cognitive and sleep features. Of the 289 patients with rapid eye movement sleep behaviour disorder, eight (2.8%) patients had no dream recall, including four (1.4%) patients who had never ever recalled dreams, and four patients who had no dream recall for 10–56 years. All non‐recallers exhibited, daily or almost nightly, several complex, scenic and dreamlike behaviours and speeches, which were also observed during rapid eye movement sleep on video‐polysomnography (arguing, fighting and speaking). They did not recall a dream following sudden awakenings from rapid eye movement sleep. These eight non‐recallers with rapid eye movement sleep behaviour disorder did not differ in terms of cognition, clinical, treatment or sleep measures from the 17 dreamers with rapid eye movement sleep behaviour disorder matched for age, sex and disease. The scenic dreamlike behaviours reported and observed during rapid eye movement sleep in the rare non‐recallers with rapid eye movement sleep behaviour disorder (even in the never‐ever recallers) provide strong evidence that non‐recallers produce dreams, but do not recall them. Rapid eye movement sleep behaviour disorder provides a new model to evaluate cognitive processing during dreaming and subsequent recall.     

The effects of sleep deprivation in humans: topographical electroencephalogram changes in non‐rapid eye movement (NREM) sleep versus REM sleep

Studies on homeostatic aspects of sleep regulation have been focussed upon non‐rapid eye movement (NREM) sleep, and direct comparisons with regional changes in rapid eye movement (REM) sleep are sparse. To this end, evaluation of electroencephalogram (EEG) changes in recovery sleep after extended waking is the classical approach for increasing homeostatic need. Here, we studied a large sample of 40 healthy subjects, considering a full‐scalp EEG topography during baseline (BSL) and recovery sleep following 40 h of wakefulness (REC). In NREM sleep, the statistical maps of REC versus BSL differences revealed significant fronto‐central increases of power from 0.5 to 11 Hz and decreases from 13 to 15 Hz. In REM sleep, REC versus BSL differences pointed to significant fronto‐central increases in the 0.5–7 Hz and decreases in the 8–11 Hz bands. Moreover, the 12–15 Hz band showed a fronto‐parietal increase and that at 22–24 Hz exhibited a fronto‐central decrease. Hence, the 1–7 Hz range showed significant increases in both NREM sleep and REM sleep, with similar topography. The parallel change of NREM sleep and REM sleep EEG power is related, as confirmed by a correlational analysis, indicating that the increase in frequency of 2–7 Hz possibly subtends a state‐aspecific homeostatic response. On the contrary, sleep deprivation has opposite effects on alpha and sigma activity in both states. In particular, this analysis points to the presence of state‐specific homeostatic mechanisms for NREM sleep, limited to <2 Hz frequencies. In conclusion, REM sleep and NREM sleep seem to share some homeostatic mechanisms in response to sleep deprivation, as indicated mainly by the similar direction and topography of changes in low‐frequency activity.     

Suppression of interictal spikes during phasic rapid eye movement sleep: a quantitative stereo‐electroencephalography study

Tonic and phasic rapid eye movement (REM) sleep seem to represent two different brain states exerting different effects on epileptic activity. In particular, interictal spikes are suppressed strongly during phasic REM sleep. The reason for this effect is not understood completely. A different level of synchronization in phasic and tonic REM sleep has been postulated, yet never measured directly. Here we assessed the interictal spike rate across non‐REM (NREM) sleep, phasic and tonic REM sleep in nine patients affected by drug resistant focal epilepsy: five with type II focal cortical dysplasia and four with hippocampal sclerosis. Moreover, we applied different quantitative measures to evaluate the level of synchronization at the local and global scale during phasic and tonic REM sleep. We found a lower spike rate in phasic REM sleep, both within and outside the seizure onset zone. This effect seems to be independent from the histopathological substrate and from the brain region, where epileptic activity is produced (temporal versus extra‐temporal). A higher level of synchronization was observed during tonic REM sleep both on a large (global) and small (local) spatial scale. Phasic REM sleep appears to be an interesting model for understanding the mechanisms of suppression of epileptic activity.     

Amygdaloid kindling during rapid eye movement (REM) sleep in cats

Development of amygdaloid kindling was analyzed during REM sleep and during wakefulness. Daily evolution of electrographic and behavioral changes was significantly delayed in REM kindled rats. The number of kindling trials required to reach the first generalized convulsive seizure was also significantly increased in comparison with awake kindled animals. Changes in sleep organization were measured under REM kindling conditions. A significant increase in total sleep time and in the percentage of light slow-wave sleep was found during the kindling process. No significant sleep changes were observed in REM-established kindling. REM inhibitory influence over epileptogenesis is discussed.     

Rapid eye movement fragmentation,not slow‐wave sleep,predicts neutral declarative memory consolidation in posttraumatic stress disorder

Individuals diagnosed with posttraumatic stress disorder (PTSD) experience disruption at both slow‐wave sleep (SWS) and rapid‐eye movement (REM) sleep stages and demonstrate marked memory impairment. A small group of studies suggests that, within the disorder, there is a mechanistic relation between these sleep and memory impairments. This study sought to extend that literature by examining whether, in PTSD‐diagnosed individuals, memory‐retention deficits are present after a sleep‐filled (but not after a wake‐filled) delay (i.e., whether memory deficits can be traced to interruptions of sleep‐dependent memory consolidation). Moreover, we investigated whether SWS‐ or REM‐based disturbances, or both, contribute to retention deficits. We recruited participants into three groups: PTSD (n = 21), trauma‐exposed non‐PTSD (TE; n = 19) and healthy control (HC; n = 20). Using a crossover design, we assessed memory recall before and after an 8‐hr period of polysomnography‐monitored sleep and an 8‐hr period of regular waking activity. PTSD‐diagnosed participants retained less information than controls over the sleep‐filled (but not wake‐filled) delay. Furthermore, increased REM fragmentation predicted postsleep memory retention in PTSD‐diagnosed individuals only. No SWS parameter was associated with or predictive of the amount of information retained postsleep. We conclude that specific REM‐related changes in PTSD‐diagnosed individuals affected sleep‐dependent neutral declarative memory consolidation. Generally, these findings extend the literature suggesting that the co‐occurrence of sleep and memory difficulties in PTSD is not accidental, but that these two symptom clusters are meaningfully related. Specifically, the study illustrates that subtle REM‐related disruptions contribute most strongly to memory impairment in PTSD.     

Implications of neuroscientific evidence for the cognitive models of post‐traumatic stress disorder

Brewin's dual representation theory, Ehlers and Clark's cognitive appraisal model, and Dalgleish's schematic, propositional, analogue and associative representational systems model are considered in the light of recent evidence on the neural substrates of post‐traumatic stress disorder (PTSD). The models' proposals about the cognitive mechanism of memory dysfunction in PTSD are described and evaluated against current knowledge about the neural pathways and functions disrupted in PTSD. A dual pathway model of memory is consistent with neuroscience of memory. The appraisal model also provides an account of the top‐down modulation of memory and arousal problems consistent with current neuroscientific evidence of PTSD. Dalgleish's model is less consistent with the evidence because it relies upon assumptions that cannot yet be tested neuroscientifically. All three models under‐specify the causal and maintaining influence of hyperarousal relative to the role it plays in current neuroscientific models of PTSD. Implications of the evidence for improving treatment and prevention are discussed.     

Phasic brain activity related to the onset of rapid eye movements during rapid eye movement sleep: study of event‐related potentials and standardized low‐resolution brain electromagnetic tomography

The function of rapid eye movements (REMs) during REM sleep is still a matter that is open to debate. In a previous study, we found positive brain potential (P200r) time‐locked to the onset of REMs. This potential was not observed during saccades of wakefulness. In this study, we estimated the electrical generation of this potential to investigate the phasic brain activity related to REMs. Data were collected in a sleep laboratory from nine healthy university students. REMs during REM sleep were recorded during natural nocturnal sleep. Event‐related potential time‐locked to the onset of REMs were averaged. Standardized low‐resolution brain electromagnetic tomography (sLORETA) was used to identify the current sources of P200r. The results showed that P200r have neuronal generators in the left premotor area, left primary motor and sensory cortices, left inferior parietal lobule and bilateral occipital areas (precuneus, cuneus and lingual gyrus). All these areas are known to contribute to visuomotor processing. These phasic brain activities might play a key role in explaining the function of REMs during REM sleep.     

Eye movements in idiopathic rapid eye movement sleep behaviour disorder: High antisaccade error rate reflects prefrontal cortex dysfunction

Abnormalities of eye movements have been reported in patients with Parkinson's disease (PD). However, it is unclear if they occur in the prodromal stage of synucleinopathy represented by idiopathic rapid eye movement sleep behaviour disorder (iRBD). We thus aimed to study eye movements in subjects with iRBD and in de novo PD, to assess if their abnormalities may serve as a clinical biomarker of neurodegeneration. Fifty subjects with polysomnography‐confirmed iRBD (46 male, age 40–79 years), 18 newly diagnosed, untreated PD patients (13 male, age 43–75 years) and 25 healthy controls (20 male, age 42–79 years) were prospectively enrolled. Horizontal and vertical ocular prosaccades and antisaccades were investigated with video‐oculography. All patients completed the MDS‐UPDRS and the Montreal Cognitive Assessment. In addition, a neuropsychological battery was performed on iRBD subjects. When compared with healthy controls, both de novo PD patients and iRBD subjects showed increased error rates in the horizontal antisaccade task (p < 0.01, p < 0.05 respectively). In the iRBD group, the error rates in horizontal and vertical antisaccades correlated with performances in the Prague Stroop Test and the Grooved Pegboard Test, as well as with motor scores of the MDS‐UPDRS. De novo PD patients showed a lower gain (p < 0.01) compared with controls. In conclusion, the increased error rate in the antisaccade task of iRBD and PD patients reflects a dysfunction of the dorsolateral prefrontal cortex and is related to the impairment of executive functions and attention.     

Elevated PEM (phasic electromyographic metric) rates identify rapid eye movement behavior disorder patients on nights without behavioral abnormalities

OBJECTIVE: To determine the validity of the phasic electromyographic metric (PEM) to differentiate patients with a history suggestive of rapid eye movement behavior disorder (REMBD) on laboratory nights without overt dream-enactment behavior. METHODS: PEM was quantified as the % of 2.5-sec intervals with phasic muscle activity of 100-msec duration with an amplitude of at least 4 times background activity in 11 patients and 31 elderly controls. Data were derived from both REM and NREM sleep from 5 muscle groups (mentalis, left/right anterior tibialis, left/right brachioradialis). RESULTS: Relative to controls, REMBD patients had significantly higher levels of PEM activity in all recordings. The largest differences occurred during REM sleep for the mentalis and brachioradialis channels. Similar results were obtained by limiting quantification of PEM to the final REM period of the night and could be accomplished by individuals with no previous familiarity with polysomnography. DISCUSSION: PEM may be a useful metric to characterize the REM related phasic muscle activity on patients with a history of REMBD, even when no overt dream-enactment behaviors are detected on a laboratory night.     

A quantitative statistical analysis of the submentalis muscle EMG amplitude during sleep in normal controls and patients with REM sleep behavior disorder

The aim of this study was to evaluate quantitatively the amplitude of the submentalis muscle EMG activity during sleep in controls and in patients with idiopathic REM sleep behavior disorder (RBD) or with RBD and multiple system atrophy (MSA). We recruited 21 patients with idiopathic RBD, 10 with MSA, 10 age-matched and 24 young normal controls. The average amplitude of the rectified submentalis muscle EMG signal was used for the assessment of atonia and a Sleep Atonia Index was developed; moreover, also chin muscle activations were detected and their duration and interval analyzed. The Sleep Atonia Index was able to distinguish clearly REM from NREM sleep in normal controls with values very close to 1 in young normal subjects and only slightly (but significantly) lower in old controls. Idiopathic RBD patients showed a further significant decrease of this index; MSA patients showed the lowest values of REM Sleep Atonia Index, which were very well distinguishable from those of normal controls and of idiopathic RBD patients. The distribution of the duration of chin activations was monomodal in all groups, with idiopathic RBD patients showing the highest levels. This study is a really quantitative attempt to provide practical indices for the objective evaluation of EMG atonia during REM sleep and of EMG activations. Our proposed Sleep Atonia Index can have a practical application in the clinical evaluations of patients and represents an additional useful parameters to be used in conjunction with the other criteria for the diagnosis of this sleep motor disorder.     

Analysis of suicidal behaviour in Israeli veterans and terror victims with post‐traumatic stress disorder by using the computerised Gottschalk‐Gleser scales

The primary objective of this study was to identify the vulnerability factors for suicide attempts in an Israeli sample, with the help of the Gottschalk‐Gleser content analysis scales. The respondents were divided into four groups: suicide attempters; controls; post‐traumatic stress disorder and depressed patients who did not report suicidal behaviour; and suicide ideators. The significant results represent conscious and unconscious psychological states, which suicide attempters have in common and can be seen as potential suicide risk factors. The main recurring risk‐related themes are hopelessness, sickness, deterrents, frustrated dependency strivings, total anxiety and total depression.     

The sleep physiology of nightmares in veterans with psychological trauma: Evaluation of a dominant model using participant-applied electroencephalography in the home environment

Nightmares are a core feature of posttraumatic stress disorder, are poorly understood, and are associated with serious negative outcomes. Their biology has been difficult to study, and the feasibility of capturing them in the naturalistic home environment has been poor. This said, the published research and dominant scientific model has focused on nightmares as a manifestation of noradrenergic hyperarousal during rapid eye movement sleep. The current study used at-home, participant-applied devices to measure nightmare physiology in posttraumatic stress disorder treatment-seeking veterans, by examining heartrate measures as indicators of noradrenergic tone, and sleep-stage characteristics and stability in the sleep preceding time-stamped nightmare awakenings. Our data indicate the high feasibility of participant-administered, at-home measurement, and showed an unexpected stability of -rapid eye movement sleep along with no evidence of heartrate elevations in sleep preceding nightmare awakenings. Altogether, these data highlight new opportunities for the study of nightmares while questioning the sufficiency of dominant models, which to date are largely theoretically based.     

Developments of prolonged exposure in treatment effect of post‐traumatic stress disorder and controlling dropout rate: A meta‐analytic review

Prolonged exposure (PE) has been proved as an efficacious psychological treatment for post‐traumatic stress disorder (PTSD). There are mainly two changed formats of PE: the modified PE (mPE) and the PE combined with drug (PE/d). Symptom reduction following these two PE training formats has been reported in the patients with PTSD. However, very little is focusing on the direct comparison of mPE + PE/d and PE. Therefore, this paper aims to compare the mPE + PE/d with PE on the PTSD treatment effect and the dropout rate directly through the meta‐analysis. Eighteen studies with total sample size of 1,397 met the final inclusion criteria. The results showed that mPE + PE/d had significantly lower posttreatment PTSD severity than control group (relaxation, wait list, etc.). There was no significant difference between mPE + PE/d and PE on the posttreatment, the follow‐up PTSD score, and the posttreatment dropout rate. Compared with PE, lower PTSD symptoms and marginally lower dropout rate following the treatment were observed in the PE/d group. PE/d yielded a significantly larger effect size than mPE when compared with PE on the posttreatment PTSD symptom severity. The significance of the above results would not be changed even if studies causing high heterogeneity were removed. Although PE/d enhanced treatment effect and lowered dropout rate when compared with PE, it was still insufficient to draw the conclusion that formats of adjustments would specifically improve the implementation of PE. Further studies are warranted to develop an easily accomplished and efficacy‐guaranteeing PE programme for PTSD patients.