Quantitative electroencephalography during rapid eye movement (REM) and non‐REM sleep in combat‐exposed veterans with and without post‐traumatic stress disorder

Sleep disturbances are a hallmark feature of post‐traumatic stress disorder (PTSD), and associated with poor clinical outcomes. Few studies have examined sleep quantitative electroencephalography (qEEG), a technique able to detect subtle differences that polysomnography does not capture. We hypothesized that greater high‐frequency qEEG would reflect ‘hyperarousal’ in combat veterans with PTSD (n = 16) compared to veterans without PTSD (n = 13). EEG power in traditional EEG frequency bands was computed for artifact‐free sleep epochs across an entire night. Correlations were performed between qEEG and ratings of PTSD symptoms and combat exposure. The groups did not differ significantly in whole‐night qEEG measures for either rapid eye movement (REM) or non‐REM (NREM) sleep. Non‐significant medium effect sizes suggest less REM beta (opposite to our hypothesis), less REM and NREM sigma and more NREM gamma in combat veterans with PTSD. Positive correlations were found between combat exposure and NREM beta (PTSD group only), and REM and NREM sigma (non‐PTSD group only). Results did not support global hyperarousal in PTSD as indexed by increased beta qEEG activity. The correlation of sigma activity with combat exposure in those without PTSD and the non‐significant trend towards less sigma activity during both REM and NREM sleep in combat veterans with PTSD suggests that differential information processing during sleep may characterize combat‐exposed military veterans with and without PTSD.     

Changes in EEG power density of NREM sleep in depressed patients during treatment with citalopram

According to a recent hypothesis the therapeutic effects of antidepressants might be related to acute or cumulative suppression of NREM sleep intensity. This intensity has been proposed to be expressed in the EEG power density in NREM sleep. In the present study the relationship was examined between the changes of EEG power density in NREM sleep and the changes in clinical state in 16 depressed patients during treatment with citalopram, a highly specific serotonin uptake inhibitor. A one-week wash-out period was followed by 1 week of placebo administration, a medication period of 5 weeks, and a one-week placebo period. In order to minimize systematic influences of sleep duration and NREM-REM sleep alterations, EEG power was measured over the longest common amount of NREM sleep stages 2, 3 and 4 (91.5 min). During the last treatment week and the week after withdrawal, a significant decrease of EEG power as compared to baseline was found in the 8-9 Hz frequency range. No clear-cut change, however, was observed in the EEG power of the delta frequency range (1-4 Hz), which is considered to be the principle manifestation of NREMS intensity. Furthermore, no relationship between changes in EEG power density and changes in clinical state could be demonstrated.     

EEG predictors of dreaming outside of REM sleep

The stream of human consciousness persists during sleep, albeit in altered form. Disconnected from external input, the mind and brain remain active, at times creating the bizarre sequences of thought and imagery that comprise “dreaming.” Yet despite substantial effort toward understanding this unique state of consciousness, no reliable neurophysiological indicator of dreaming has been discovered. Here, we identified electroencephalographic (EEG) correlates of dreaming using a within‐subjects design to characterize the EEG preceding awakenings from sleep onset, REM (rapid eye movement) sleep, and N2 (NREM Stage 2) sleep from which participants were asked to report their mental experience. During the transition into sleep, compared to periods during which participants reported thinking, emergence of dream imagery was associated with increased absolute power below 7 Hz. During later N2, dreaming conversely occurred during periods of decreased relative power below 1 Hz, accompanied by an increase in relative power above 4 Hz. No EEG predictors of dreaming were identified during REM. These observations suggest an inverted‐U relationship between dreaming and the prevalence of low‐frequency EEG rhythms, such that dreaming first emerges in concert with EEG slowing during the sleep‐wake transition, but then disappears as high‐amplitude slow oscillations come to dominate the recording during later N2 sleep.     

Quantitative description of EEG periodicities during stationary sleep stages

SUMMARY  A quantitative method was applied in order to assess variations in EEG activities during sleep. Three classes of variations were distinguished: variations connected with sleep-stage changes (class 1), higher-frequency variations described by the envelope of frequency-band activities (class 2), intermediate-frequency variations, corresponding to periods from 4 to 120 s (class 3). For each class, parameters characterizing the frequency spectra were computed. These parameters were mathematically simple and clear in their meaning, since they measured power, modulation index and mean squared frequency. A statistical comparison of the mean values of the parameters during different sleep stages evidenced a certain number of significant shifts in each of the three classes. The most important class-1 and class-2 variations were described by our parameters with high levels of significance. The results obtained for class 3 were in agreement with visual observations reported in the literature, such as the progressive increase in the interval between successive arousals from sleep onset to Stage 4 and the frequent occurrence of cyclic alternating patterns during Stage 2 epochs immediately preceding REM sleep.     

Regional differences of the sleep electroencephalogram in adolescents

The sleep electroencephalogram (EEG) was recorded from anterior (Fz/Cz) and posterior (Pz/Oz) bipolar derivations in two developmental groups: 20 pre- or early pubertal (Tanner 1/2, mean age 11.4 +/- 1.1 years, 11 boys) and 20 late pubertal or mature adolescents (Tanner 4/5, 14.1 +/- 1.3 years, 8 boys). A sleep-state independent reduction of EEG power over almost the entire frequency range was present in Tanner 4/5 compared with Tanner 1/2 adolescents. Spectral characteristics of the sleep EEG yielded state- and frequency-dependent regional differences that were similar in both developmental groups. Anterior predominance of power in delta and sigma ranges occurred in non-rapid eye movement sleep. Rapid eye movement sleep EEG power was greater in low delta, alpha, and sigma ranges for the posterior derivation and in theta and beta ranges for the anterior derivation. The decay rate of the sleep homeostatic process--reflected by the exponential decline of the 2-Hz EEG power band across the sleep episode--did not differ for derivations or groups. These results indicate that the nocturnal dynamics of sleep homeostasis are independent of derivation and remain stable across puberty.     

Automatic recognition of rapid eye movement (REM) sleep by artificial neural networks

SUMMARY  Artificial neural networks are well known for their good performance in pattern recognition. Their suitability for detecting REM sleep periods on the basis of preprocessed EEG data in humans under clinical conditions was tested and their performance compared with the manual evaluation. A single channel of the EEG signal was analysed in time periods of 20s and preprocessed into a vector of six real numbers, which served as input to the network. EOG and EMG information was ignored. Backpropagation was used as a learning rule for the network, which consisted of 12 neurons and 39 synapses. Training datasets were put together from the input vectors and the corresponding sleep stages were scored manually. In working mode different networks were compared in terms of the rate of misclassified time periods for data not belonging to the training sets. The indicator function of REM sleep was well approximated by the network output in the course of the night, which was especially true for REM onsets. The average rate of correctly classified time periods was 89%. The errors were analysed and suggestions for improvements developed.     

Topographic mapping of EEG during sleep

Summary Topographic aspects of all night sleep EEG were investigated in 10 healthy volunteers (age 20–35 years). EEG brain maps showed an increase of delta power from stage 1 to 4, a decrease of alpha power most pronounced parieto-occipitally and a slowing of the dominant alpha frequency. Differences of EEG power in different sleep stages (as compared to wakefulness) are displayed topographically. Analysis of the course of stage 2 showed an increase of delta power and a decrease of theta power in the first sections of the night, and an increase of beta power later in the night.     

Regional differences in NREM sleep slow-wave activity in mice with congenital callosal dysgenesis

Topographic differences in the sleep EEG have been repeatedly found in humans and rodents. A frontal predominance of EEG slow-wave activity (0.75-4 Hz; delta band) during non-rapid eye movement (NREM) sleep is particularly evident under conditions of increased sleep propensity. Local aspects of neuronal connectivity in the neocortex that are modified by specific neuronal stimulation may underlie these differences. To investigate the role of altered neuronal connectivity on anterior-posterior EEG topography, sleep was recorded in mice with congenital dysgenesis of the corpus callosum (B1 strain) during baseline and after 6 h sleep deprivation (SD). In these mice neuronal connections within a hemisphere are increased due to the longitudinal Probst bundle, a structure of re-routed callosal fibers. After SD the frequencies above 1.5 Hz within the delta band in NREM sleep were reduced in B1 mice compared with control C57BL/6 mice, a strain that has a normal corpus callosum, while power in the lowest frequency band (0.75-1.0 Hz) was enhanced in B1 mice. The differences between the strains subsided in the course of recovery. The redistribution of EEG power within the delta band in the frontal region in mice with a well developed Probst bundle, suggests a role of intracortical connectivity in local sleep regulation.     

Renin as a biological marker of the NREM-REM sleep cycle: effect of REM sleep suppression

SUMMARY  We have previously described that, in normal man, the nocturnal oscillations of plasma renin activity (PRA) exactly reflect the rapid eye movement (REM)–non(N)REM sleep cycles, with increasing PRA levels during NREM sleep and decreasing levels during REM sleep. This study was carried out to determine whether REM sleep suppression affects nocturnal renin profiles and to define which sleep stage is essential for renin release.
In a first experimental series, REM sleep was suppressed by using clomipramine, a tricyclic antidepressant. Seven healthy young men were studied once during a night when a placebo was given and once during a night following a single dose of 50 mg clomipramine. Blood was collected every 10 min from 23.00 hours to 07.00 hours. PRA was measured by radio-immunoassay and the nocturnal profiles were analysed using the pulse detection program ULTRA. Clomipramine suppressed REM sleep in all subjects but one, but did not affect the number of SWS episodes nor their duration. Similar PRA profiles were observed in both experimental conditions. Neither the mean levels, nor the number and the amplitude of the oscillations were modified and the normal relationship between slow wave sleep and increasing PRA levels was preserved.
In a second experimental series, REM sleep was prevented by rapidly awakening the subjects as soon as they fell into REM sleep. The four subjects studied attempted several times to go into REM sleep, but only when PRA levels were decreasing. The interruption of REM sleep by short waking periods did not disturb PRA for which the oscillations remained unaffected. Again, the relationship between SWS and increasing PRA levels was preserved.
These results provide evidence that mechanisms increasing slow-wave activity are principally involved in increasing PRA levels and that replacing REM sleep by waking periods and light sleep does not modify nocturnal PRA oscillations.     

Unilateral vibrissae stimulation during waking induces interhemispheric EEG asymmetry during subsequent sleep in the rat

To test the theory that sleep is a regional, use-dependent process, rats were subjected to unilateral sensory stimulation during waking. This was achieved by cutting the whiskers on one side, in order to reduce the sensory input to the contralateral cortex. The animals were kept awake for 6 h in an enriched environment to activate the cortex contralateral to the intact side. Whiskers are known to be represented in the barrel field of the contralateral somatosensory cortex and their stimulation during exploratory behavior results in a specific activation of the projection area. In the 6 h recovery period following sleep deprivation, spectral power of the nonrapid eye-movement (NREM) sleep EEG in the 0.75-6.0 Hz range exhibited an interhemispheric shift towards the cortex that was contralateral to the intact whiskers. The results support the theory that sleep has a regional, use-dependent facet.     

Temporal analysis of REM sleep after nest-building behavior in nulliparous albino rat

EEG recording was performed, during nest-building behavior (NBB), from the hippocampus and sensorimotor cortex of nulliparous albino rats with simultaneous recordings of EMGs of neck-muscle and eye movements. The duration of NBB varied with a period of 4–5 days. However, the relative durations of behavioral transitions in NBB, i.e., nest-building, grooming, and sleeping, were regular in both long lasting and early terminated NBB. REM sleep was identified, in every instance, immediately after NBB. The latency of REM sleep was significantly tied to the termination of NBB without regard to the druation of NBB. Differences in the duration of NBB, however, affected REM-propensity: the longer the NBB was, the shorter the latency of REM sleep tended to be. NBB might accelerate the induction of the physiological condition responsible for REM sleep generation.     

Cortical activation patterns herald successful dream recall after NREM and REM sleep

Dreaming pertains to both REM and NREM sleep. However, frequency and regional specific differences in EEG activity remains controversial. We investigated NREM and REM sleep EEG power density associated with and without dream recall in 17 young subjects during a 40-h multiple nap protocol under constant routine conditions. NREM sleep was associated with lower EEG power density for dream recall in the delta range, particularly in frontal derivations, and in the spindle range in centro-parietal derivations. REM sleep was associated with low frontal alpha activity and with high alpha and beta activity in occipital derivations. Our data indicate that specific EEG frequency- and topography changes underlie differences between dream recall and no recall after both NREM and REM sleep awakening. This dual NREM-REM sleep modulation holds strong implications for the mechanistic understanding of this complex ongoing cognitive process.     

Muscle artifacts in the sleep EEG: Automated detection and effect on all-night EEG power spectra

Owing to the use of scalp electrodes in human sleep recordings, cortical EEG signals are inevitably intermingled with the electrical activity of the muscle tissue on the skull. Muscle artifacts are characterized by surges in high frequency activity and are readily identified because of their outlying high values relative to the local background activity. To detect bursts of myogenic activity a simple algorithm is introduced that compares high frequency activity (26.25–32.0 Hz) in each 4-s epoch with the activity level in a local 3-min window. A 4-s value was considered artifactual if it exceeded the local background activity by a certain factor. Sensitivity and specificity of the artifact detection algorithm were empirically adjusted by applying different factors as artifact thresholds. In an analysis of sleep EEG signals recorded from 25 healthy young adults 2.3% (SEM: 0.16) of all 4-s epochs during sleep were identified as artifacts when a threshold factor of four was applied. Contamination of the EEG by muscle activity was more frequent towards the end of non-REM sleep episodes when EEG slow wave activity declined. Within and across REM sleep episodes muscle artifacts were evenly distributed. When the EEG signal was cleared of muscle artifacts, the all-night EEG power spectrum showed significant reductions in power density for all frequencies from 0.25–32.0 Hz. Between 15 and 32 Hz, muscle artifacts made up a substantial part (20–70%) of all-night EEG power density. It is concluded that elimination of short-lasting muscle artifacts reduces the confound between cortical and myogenic activity and is important in interpreting quantitative EEG data. Quantitative approaches in defining and detecting transient events in the EEG signal may help to determine which EEG phenomena constitute clinically significant arousals.     

Story-like organization of dream experience in different periods of REM sleep

Four dream reports, collected from each of 16 subjects in an experimental night, were analysed using the criteria of Mandler and Johnson's story grammar. The experimental night was the first of the four nights where subjects had spontaneously given a dream report after each of the four awakenings planned in REM sleep. A multivariate analysis of covariance, taking the order of the nights where the experimental night occurred and the order of reports as factors, the number of stories per report as covariate and the number of statements in the setting, the number of statements in the event structure and number of episodes per story as dependent variables, showed that the greater length and complexity of reports collected in the second half of the night depends on a greater effectiveness of the dream production system rather than on a greater accuracy of recall. This increase concerns the organization of individual stories rather than the number of stories developed in a given time. These findings raise the issue of how dream production is re-triggered during REM sleep. To cast light on this issue, it seems important to establish whether and how the themes of the various stories developed in a given dream experience are interrelated.     

Period-amplitude analysis and power spectral analysis: a comparison based on all-night sleep EEG recordings

Both period-amplitude analysis (PAA) and power spectral analysis (PSA) were performed on all-night human sleep EEG recordings obtained from 11 subjects. The comparison of the two methods was based on the PAA variables time in band (a wave incidence measure) and rectified amplitude, and on the PSA variables spectral power density and spectral amplitude (the square root of power). The mean time course of these variables was determined for the first 4 nonREM-REM sleep cycles. Spectral power density and spectral amplitude in the delta range were high in nonREM sleep and low in REM sleep, and showed a declining trend over consecutive nonREM sleep episodes. In the frequency range below 2 Hz, rectified amplitude was highly correlated with both time in band and spectral amplitude, and there was no evidence for a dissociation between wave amplitude and wave incidence measures. However, in frequencies above 2 Hz, the modulation of time in band was a mirror image of that below 2 Hz. This result does not reflect a property of the data, but is inherent to the methodology applied. The reversal point of modulation was merely shifted when the high-pass filter settings were changed. It is concluded that band-pass filtering is necessary prior to PAA even for the analysis of the lowest frequency range, and that the indiscriminate use of PAA may give rise to spurious results.     

Circadian and homeostatic sleep regulation in morningness-eveningness

Morningness-eveningness has been associated with the entrained circadian phase. However, we recently identified morning and evening types having similar circadian phases. In this paper, we compared parameters of slow-wave activity (SWA) decay in non-rapid-eye-movement (NREM) sleep between these two subgroups to test the hypothesis that differences in the dynamics of nocturnal homeostatic sleep pressure could explain differences in sleep timing preference. Twelve morning-type subjects and 12 evening-type subjects with evening types (aged 19-34 years) selected using the Morningness-Eveningness Questionnaire were further classified according to the phase of their dim light melatonin onset (DLMO). The six morning types with the earliest DLMO were compared to the six evening types with the latest DLMO ('extreme' phases), and the six morning types with the latest DLMO were compared to the six evening types with the earliest DLMO ('intermediate' phases). Subjects slept according to their preferred sleep schedule. Spectral activity in four midline derivations (Fz, Cz, Pz, Oz) was calculated in NREM sleep and an exponential decay function was applied on SWA data averaged per sleep cycle. In the subjects with intermediate circadian phases, both initial level and decay rate of SWA in Fz were significantly higher in morning than in evening types. No difference appeared between chronotypes of extreme circadian phases. There was no correlation between individual estimates of SWA decay and DLMO. These results support the hypothesis that chronotype can originate from differences in the dissipation of sleep pressure and that homeostatic and circadian processes influence the sleep schedule preference independently.     

Challenging sleep in aging: the effects of 200 mg of caffeine during the evening in young and middle-aged moderate caffeine consumers

The aim of this study was to evaluate the effects of a 200-mg administration of caffeine on polysomnographic sleep variables and quantitative sleep electroencephalography (EEG) in 12 young (20-30 years) and 12 middle-aged (40-60 years) moderate caffeine consumers (one to three cups of coffee per day). All subjects were submitted to both a caffeine (200 mg) and placebo (lactose) condition in a double-blind cross-over design. The conditions were separated by 1 week. Compared with the placebo condition, the evening ingestion of caffeine lengthened sleep latency, reduced sleep efficiency, and decreased sleep duration and amount of stage 2 sleep in both age groups. Caffeine also reduced spectral power in delta frequencies in frontal, central and parietal brain areas, but not in prefrontal (PF) and occipital regions. Moreover, caffeine increased spectral power in beta frequencies in frontal and central brain areas in both age groups. A suppression of spectral power in the PF area in low delta frequencies (0.5-1.00 Hz) and a rise in spectral power in the parietal region in high alpha (10.00-12.00 Hz) and beta frequencies (17.00-21.00, 23.00-25.00, 27.00-29.00 Hz) occurred solely in middle-aged subjects. No such changes were noticeable in young subjects. Generally, caffeine produced similar effects in young and middle-aged subjects. Only a few frequency bins showed more effects of caffeine in middle-aged subjects compared with young subjects. Furthermore, sleep EEG results do not entirely support the hypothesis that caffeine fully mimics the effects of a reduction of homeostatic sleep propensity when following a normal sleep-wake cycle.     

Optimization of sigma amplitude threshold in sleep spindle detection

Sleep spindles are transient EEG waveforms of non-rapid eye movement sleep. There is considerable intersubject variability in spindle amplitudes. The problem in automatic spindle detection has been that, despite this fact, a fixed amplitude threshold has been used. Selection of the spindle detection threshold value is critical with respect to the sensitivity of spindle detection. In this study a method was developed to estimate the optimal recording-specific threshold value for each all-night recording without any visual scorings. The performance of the proposed method was validated using four test recordings each having a very different number of visually scored spindles. The optimal threshold values for the test recordings could be estimated well. The presented method seems very promising in providing information about sleep spindle amplitudes of individual all-night recordings.     

Reduced Alpha power associated with the recall of mentation from Stage 2 and Stage REM sleep

Relationships between Alpha (8-12 Hz) activity and cognitive processes during wakefulness raise the possibility of similar relationships between Alpha and cognitive activity during sleep. We hypothesized that Alpha power decreases during both Stage 2 and REM sleep would index the presence of sleep mentation in these stages. Absolute power for six classical EEG bands and three Alpha subbands was calculated for Stage 2 and REM sleep awakenings both with and without mentation recall. In both stages, recall was associated with lower Alpha power, especially with middle Alpha power (9.5-11.5 Hz). Unexpectedly, a similar effect for Delta power (0.5-4.0 Hz) was also observed. The Alpha effect may reflect cognitive elaboration active in the minutes preceding awakening; however, attention and memory processes cannot be excluded. The Delta effect is consistent with prior observations of regular linkages between Alpha and Delta power during sleep.     

Normal sleep homeostasis and lack of epilepsy phenotype in GABA A receptor alpha3 subunit-knockout mice

Thalamo-cortical networks generate specific patterns of oscillations during distinct vigilance states and epilepsy, well characterized by electroencephalography (EEG). Oscillations depend on recurrent synaptic loops, which are controlled by GABAergic transmission. In particular, GABA A receptors containing the alpha3 subunit are expressed predominantly in cortical layer VI and thalamic reticular nucleus (nRT) and regulate the activity and firing pattern of neurons in relay nuclei. Therefore, ablation of these receptors by gene targeting might profoundly affect thalamo-cortical oscillations. Here, we investigated the role of alpha3-GABA A receptors in regulating vigilance states and seizure activity by analyzing chronic EEG recordings in alpha3 subunit-knockout (alpha3-KO) mice. The presence of postsynaptic alpha3-GABA A receptors/gephyrin clusters in the nRT and GABA A-mediated synaptic currents in acute thalamic slices was also examined. EEG spectral analysis showed no difference between genotypes during non rapid-eye movement (NREM) sleep or at waking-NREM sleep transitions. EEG power in the spindle frequency range (10-15 Hz) was significantly lower at NREM-REM sleep transitions in mutant compared with wild-type mice. Enhancement of sleep pressure by 6 h sleep deprivation did not reveal any differences in the regulation of EEG activities between genotypes. Finally, the waking EEG showed a slightly larger power in the 11-13-Hz band in alpha3-KO mice. However, neither behavior nor the waking EEG showed alterations suggestive of absence seizures. Furthermore, alpha3-KO mice did not differ in seizure susceptibility in a model of temporal lobe epilepsy. Strikingly, despite the disruption of postsynaptic gephyrin clusters, whole-cell patch clamp recordings revealed intact inhibitory synaptic transmission in the nRT of alpha3-KO mice. These findings show that the lack of alpha3-GABA(A) receptors is extensively compensated for to preserve the integrity of thalamo-cortical function in physiological and pathophysiological situations.