Evidence of Dissociated Arousal States During NREM Parasomnia from an Intracerebral Neurophysiological Study

Study Objectives:

Arousal parasomnias are expressions of sleep/wake state dissociations in which wakefulness and NREM sleep seem to coexist. We describe the results of a neurophysiological (intracerebral EEG) investigation that captured an episode of confusional arousal.

Design:

Observational analysis.

Setting:

Tertiary sleep center.

Subject:

A 20-year-old male with refractory focal epilepsy.

Measurements and Results:

The intracerebral EEG findings documented the presence of a local arousal of the motor and cingulate cortices associated with increased delta activity in the frontoparietal associative cortices; these findings were noted preceding the onset and persisting throughout the episode.

Conclusions:

The presence of dissociated sleep/wake states in confusional arousals is the expression not of a global phenomenon, but rather of the coexistence of different local states of being: arousal of the motor and cingulate cortices and inhibition of the associative ones. Whether this is an exclusive feature of NREM parasomnias, or a common substrate on which other triggering elements act, needs to be clarified.

Citation:

Terzaghi M; Sartori I; Tassi L; Didato G; Rustioni V; LoRusso G; Manni R; Nobili L. Evidence of dissociated arousal states during NREM parasomnia from an intracerebral neurophysiological study. SLEEP 2009;32(3):409–412.     

EEG Spectral Analysis in Primary Insomnia: NREM Period Effects and Sex Differences

Study Objectives:

To compare NREM EEG power in primary insomnia (PI) and good sleeper controls (GSC), examining both sex and NREM period effects; to examine relationships between EEG power, clinical characteristics, and self-reports of sleep.

Design:

Overnight polysomnographic study.

Setting:

Sleep laboratory.

Participants:

PI (n = 48; 29 women) and GSC (n = 25; 15 women).

Interventions:

None.

Measurements:

EEG power from 1–50 Hz was computed for artifactfree sleep epochs across four NREM periods. Repeated measures mixed effect models contrasted differences between groups, EEG frequency bands, and NREM periods. EEG power-frequency curves were modeled using regressions with fixed knot splines.

Results:

Mixed models showed no significant group (PI vs. GSC) differences; marginal sex differences (delta and theta bands); significant differences across NREM periods; and group*sex and group*NREM period interactions, particularly in beta and gamma bands. Modeled power-frequency curves showed no group difference in whole-night NREM, but PI had higher power than GSC from 18–40 Hz in the first NREM period. Among women, PI had higher 16 to 44-Hz power than GSC in the first 3 NREM periods, and higher 3 to 5-Hz power across all NREM periods. PI and GSC men showed no consistent differences in EEG power. High-frequency EEG power was not related to clinical or subjective sleep ratings in PI.

Conclusions:

Women with PI, but not men, showed increased high-frequency and low-frequency EEG activity during NREM sleep compared to GSC, particularly in early NREM periods. Sex and NREM period may moderate quantitative EEG differences between PI and GSC.

Citation:

Buysse DJ; Germain A; Hall ML; Moul DE; Nofzinger EA; Begley A; Ehlers CL; Thompson W; Kupfer DJ. EEG spectral analysis in primary insomnia: NREM period effects and sex differences. SLEEP 2008;31(12):1673–1682.     

Analysis of slow-wave activity and slow-wave oscillations prior to somnambulism

Study Objectivies:

Several studies have investigated slow wave sleep EEG parameters, including slow-wave activity (SWA) in relation to somnambulism, but results have been both inconsistent and contradictory. The first goal of the present study was to conduct a quantitative analysis of sleepwalkers'' sleep EEG by studying fluctuations in spectral power for delta (1-4 Hz) and slow delta (0.5-1 Hz) before the onset of somnambulistic episodes. A secondary aim was to detect slow-wave oscillations to examine changes in their amplitude and density prior to behavioral episodes.

Participants:

Twenty-two adult sleepwalkers were investigated polysomnographically following 25 h of sleep deprivation.

Results:

Analysis of patients'' sleep EEG over the 200 sec prior to the episodes'' onset revealed that the episodes were not preceded by a gradual increase in spectral power for either delta or slow delta over frontal, central, or parietal leads. However, time course comparisons revealed significant changes in the density of slow-wave oscillations as well as in very slow oscillations with significant increases occurring during the final 20 sec immediately preceding episode onset.

Conclusions:

The specificity of these sleep EEG parameters for the occurrence and diagnosis of NREM parasomnias remains to be determined.

Citation:

Jaar O; Pilon M; Carrier J; Montplaisir J; Zadra A. Analysis of slow-wave activity and slow-wave oscillations prior to somnambulism. SLEEP 2010;33(11):1511-1516.     

Clonidine has a paradoxical effect on cyclic arousal and sleep bruxism during NREM sleep

Study Objective:

Clonidine disrupts the NREM/REM sleep cycle and reduces the incidence of rhythmic masticatory muscle activity (RMMA) characteristic of sleep bruxism (SB). RMMA/SB is associated with brief and transient sleep arousals. This study investigates the effect of clonidine on the cyclic alternating pattern (CAP) in order to explore the role of cyclic arousal fluctuation in RMMA/SB.

Design:

Polysomnographic recordings from a pharmacological study.

Setting:

University sleep research laboratory.

Participants and Interventions:

Sixteen SB subjects received a single dose of clonidine or placebo at bedtime in a crossover design.

Measurements and Results:

Sleep variables and RMMA/SB index were evaluated. CAP was scored to assess arousal instability between sleep-maintaining processes (phase A1) and stronger arousal processes (phases A2 and A3). Paired t-tests, ANOVAs, and cross-correlations were performed. Under clonidine, CAP time, and particularly the number of A3 phases, increased (P ≤ 0.01). RMMA/SB onset was time correlated with phases A2 and A3 for both placebo and clonidine nights (P ≤ 0.004). However, under clonidine, this positive correlation began up to 40 min before the RMMA/SB episode.

Conclusions:

CAP phase A3 frequency increased under clonidine, but paradoxically, RMMA/SB decreased. RMMA/SB was associated with and facilitated in CAP phase A2 and A3 rhythms. However, SB generation could be influenced by other factors besides sleep arousal pressure. NREM/REM ultradian cyclic arousal fluctuations may be required for RMMA/SB onset.

Citation:

Carra MC; Macaluso GM; Rompré PH; Huynh N; Parrino L; Terzano MG; Lavigne GJ. Clonidine has a paradoxical effect on cyclic arousal and sleep bruxism during NREM sleep. SLEEP 2010;33(12):1711-1716.     

Effects of Modafinil on the Sleep EEG Depend on Val158Met Genotype of COMT

Study Objectives:

Modafinil may promote wakefulness by increasing cerebral dopaminergic neurotransmission, which importantly depends on activity of catechol-O-methyltransferase (COMT) in prefrontal cortex. The effects of modafinil on sleep homeostasis in humans are unknown. Employing a novel sleep-pharmacogenetic approach, we investigated the interaction of modafinil with sleep deprivation to study dopaminergic mechanisms of sleep homeostasis.

Design:

Placebo-controlled, double-blind, randomized crossover study.

Setting:

Sleep laboratory in temporal isolation unit.

Participants:

22 healthy young men (23.4 ± 0.5 years) prospectively enrolled based on genotype of the functional Val158Met polymorphism of COMT (10 Val/Val and 12 Met/Met homozygotes).

Interventions:

2 × 100 mg modafinil and placebo administered at 11 and 23 hours during 40 hours prolonged wakefulness.

Measurements and Results:

Subjective sleepiness and EEG markers of sleep homeostasis in wakefulness and sleep were equally affected by sleep deprivation in Val/Val and Met/Met allele carriers (placebo condition). Modafinil attenuated the evolution of sleepiness and EEG 5-8 Hz activity during sleep deprivation in both genotypes. In contrast to caffeine, modafinil did not reduce EEG slow wave activity (0.75-4.5 Hz) in recovery sleep, yet specifically increased 3.0-6.75 Hz and > 16.75 Hz activity in NREM sleep in the Val/Val genotype of COMT.

Conclusions:

The Val158Met polymorphism of COMT modulates the effects of modafinil on the NREM sleep EEG in recovery sleep after prolonged wakefulness. The sleep EEG changes induced by modafinil markedly differ from those of caffeine, showing that pharmacological interference with dopaminergic and adenosinergic neurotransmission during sleep deprivation differently affects sleep homeostasis.

Citation:

Bodenmann S; Landolt HP. Effects of modafinil on the sleep EEG depend on Val158Met genotype of COMT. SLEEP 2010;33(8):1027-1035.     

Dream-Enacting Behaviors in a Normal Population

Study Objectives:

Determine the prevalence and gender distributions of behaviors enacted during dreaming (“dream-enacting [DE] behaviors”) in a normal population; the independence of such behaviors from other parasomnias; and the influence of different question wordings, socially desirable responding and personality on prevalence.

Design:

3-group questionnaire study

Setting:

University classrooms

Participants:

Three undergraduate samples (Ns = 443, 201, 496; mean ages = 19.9 ± 3.2 y; 20.1 ± 3.4 y; 19.1 ± 1.6 y)

Interventions:

N/A

Measurements and Results:

Subjects completed questionnaires about DE behaviors and Social Desirability. Study 1 employed a nonspecific question about the behaviors, Study 2 employed the same question with examples, and Study 3 employed 7 questions describing specific behavior subtypes (speaking, crying, smiling/laughing, fear, anger, movement, sexual arousal). Somnambulism, somniloquy, nightmares, dream recall, alexithymia, and absorption were also assessed. Factor analyses were conducted to determine relationships among DE behaviors and their independence from other parasomnias. Prevalence increased with increasing question specificity (35.9%, 76.7%, and 98.2% for the 3 samples). No gender difference obtained for the nonspecific question, but robust differences occurred for more specific questions. Females reported more speaking, crying, fear and smiling/laughing than did males; males reported more sexual arousal. When controlling other parasomnias and dream recall frequency, these differences persisted. Factor solutions revealed that DE behaviors were independent of other parasomnias and of dream recall frequency, except for an association between dream-talking and somniloquy. Sexual arousal was related only to age. Behaviors were independent of alexithymia but moderately related to absorption.

Conclusions:

Dream-enacting behaviors are prevalent in healthy subjects and sensitive to question wording but not social desirability. Subtypes are related, differ with gender and occur independently of other parasomnias.

Citation:

Nielsen T; Svob C; Kuiken D. Dream-enacting behaviors in a normal population. SLEEP 2009;32(12):1629-1636.     

Development of NREM Sleep Instability-Continuity (Cyclic Alternating Pattern) in Healthy Term Infants Aged 1 to 4 months

Study Objectives:

To evaluate non-rapid eye movement (NREM) sleep instability, as measured by the cyclic alternating pattern (CAP), in the first months of life in a group of normal healthy infants, in order to obtain more information on the maturation of arousal mechanisms during NREM sleep and to set normative data of CAP parameters in this age range (from 1 to 4 months of life).

Design:

Retrospective study.

Setting:

Sleep unit of an academic centre.

Participants:

Twenty-three healthy newborns and infants with a mean conceptional age (gestational age plus postnatal age) of 47.6 ± 3.8 weeks, age range 42 to 55 weeks, 10 boys (43.47%), were studied while they slept in the morning between feedings, by means of a 3-hour video-electroencephalographic (EEG)-polygraphic recording. Sleep was visually scored for sleep architecture and CAP in a blinded fashion, using standard criteria.

Measurements and results:

We found 3 different sleep EEG patterns in our infants, according to their age, and we subdivided the entire group into 3 subgroups. Group 1—Tracé alternant mixed with high-voltage slow activity included 9 subjects (3 boys), with a mean conceptional age of 43.9 ± 1.3 weeks; Group 2 (high-voltage slow activity and rudimentary spindles) included 6 subjects (4 boys), with a mean conceptional age of 49.4 ± 3.1 weeks; and Group 3 (slow-wave activity and spindles, scored as NREM sleep) included 8 subjects (3 boys), with a mean conceptional age of 50.4 ± 2.9 weeks. CAP rate was 6.83 ± 3.58 in infants belonging to Group 2 and increased to 12.91 ± 2.21 in Group 3. We found a statistically significant higher A1 index in only Group 3. The relative percentages of the A1, A2, and A3 subtypes showed non significant changes with age. The duration of CAP events and the cortical and subcortical arousal indexes were not statistically different between Groups 2 and 3.

Conclusions:

With this study, we provide the first data on CAP analysis in infants from 1 to 4 months of life, and we found that there is a transitory period when tracè alternant disappears and CAP events begin to occur. Furthermore, we suggest that the more appropriate time of life when CAP analysis can be first performed is related to the appearance of mature stage 2 NREM with spindles and slow delta waves mixed with theta waves, at approximately 3 months of life.

Citation:

Miano S; PiaVilla M; Blanco D; Zamora E; Rodriguez R; Ferri R; Bruni O; Peraita-Adrados R. Development of NREM sleep instability-continuity (cyclic alternating pattern) in healthy term infants aged 1 to 4 months. SLEEP 2009;32(1):83-90.     

Utility of sleep stage transitions in assessing sleep continuity

Study Objectives:

Sleep continuity is commonly assessed with polysomnographic measures such as sleep efficiency, sleep stage percentages, and the arousal index. The aim of this study was to examine whether the transition rate between different sleep stages could be used as an index of sleep continuity to predict self-reported sleep quality independent of other commonly used metrics.

Design and Setting:

Analysis of the Sleep Heart Health Study polysomnographic data.

Participants:

A community cohort.

Measurements and Results:

Sleep recordings on 5,684 participants were deemed to be of sufficient quality to allow visual scoring of NREM and REM sleep. For each participant, we tabulated the frequency of transitions between wake, NREM sleep, and REM sleep. An overall transition rate was determined as the number of all transitions per hour sleep. Stage-specific transition rates between wake, NREM sleep, and REM sleep were also determined. A 5-point Likert scale was used to assess the subjective experience of restless and light sleep the morning after the sleep study. Multivariable regression models showed that a high overall sleep stage transition rate was associated with restless and light sleep independent of several covariates including total sleep time, percentages of sleep stages, wake time after sleep onset, and the arousal index. Compared to the lowest quartile of the overall transition rate (< 7.76 events/h), the odds ratios for restless sleep were 1.27, 1.42, and 1.38, for the second (7.77–10.10 events/h), third (10.11–13.34 events/h), and fourth (≥ 13.35 events/h) quartiles, respectively. Analysis of stage-specific transition rates showed that transitions between wake and NREM sleep were also independently associated with restless and light sleep.

Conclusions:

Assessing overall and stage-specific transition rates provides a complementary approach for assessing sleep continuity. Incorporating such measures, along with conventional metrics, could yield useful insights into the significance of sleep continuity for clinical outcomes.

Citation:

Laffan A; Caffo B; Swihart BJ; Punjabi NM. Utility of sleep stage transitions in assessing sleep continuity. SLEEP 2010;33(12):1681-1686.     

EEG Sleep Spectra in Older Adults Across All Circadian Phases During NREM Sleep

Study Objectives:

Healthy aging is associated with changes in sleep-wake regulation, and those changes often lead to problems sleeping, both during the night and during daytime. We aimed to examine the electroencephalographic (EEG) sleep spectra during non-rapid eye movement (NREM) sleep when sleep was scheduled at all times of day.

Design/Interventions:

After three 24-h baseline (BL) days, participants were scheduled to live on 20-hour “days” consisting of 6.7 hours of bed rest and 13.3 hours of wakefulness for 12 consecutive days (forced desynchrony, FD). The EEG was recorded from a central derivation during all scheduled sleep episodes, with subsequent visual scoring and spectral analysis.

Setting:

Intensive Physiological Monitoring Unit of the Brigham & Women''s Hospital General Clinical Research Center.

Participants:

Twenty-four healthy older subjects (64.2 ± 6.3 yr; 13 women, 11 men)

Measurements and Results:

Compared with BL nights, EEG activity in the slow wave (0.5 to 5.25 Hz), theta (6 to 6.25 and 7 Hz), alpha (10 to 11.25 Hz), and high spindle range (14.5 to 15.5 Hz) was significantly greater during FD, when subjects slept across many times of day and night. During FD, there was a significant interaction between homeostatic and circadian factors, such that EEG delta activity (0.5 to 1.5 Hz) was higher in the biological morning/early afternoon than at other times. EEG activity was significantly increased in almost all frequency ranges (0.5 to 21 Hz) during the biological day, as compared with the biological night, except for the lower EEG spindle range (12.25 to 14 Hz). Overall, EEG beta activity was positively correlated with wakefulness and negatively correlated with total sleep time.

Conclusion:

Our findings provide some new evidence for the underlying mechanisms that contribute to age-related difficulties in sleep consolidation, especially when sleep occurs during the daytime.

Citation:

Münch M; Silva EJ; Ronda JM; Czeisler CA; Duffy JF. EEG sleep spectra in older adults across all circadian phases during NREM sleep. SLEEP 2010;33(3):389-401.     

Does the Circadian Modulation of Dream Recall Modify with Age?

Study objectives:

The ultradian NREM-REM sleep cycle and the circadian modulation of REM sleep sum to generate dreaming. Here we investigated age-related changes in dream recall, number of dreams, and emotional domain characteristics of dreaming during both NREM and REM sleep.

Design:

Analysis of dream recall and sleep EEG (NREM/REM sleep) during a 40-h multiple nap protocol (150 min of wakefulness and 75 min of sleep) under constant routine conditions.

Setting:

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.

Participants:

Seventeen young (20-31 years) and 15 older (57-74 years) healthy volunteers

Interventions:

N/A.

Measurements and Results:

Dream recall and number of dreams varied significantly across the circadian cycle and between age groups, with older subjects exhibiting fewer dreams (P < 0.05), particularly after naps scheduled during the biological day, closely associated with the circadian rhythm of REM sleep. No significant age differences were observed for the emotional domain of dream content.

Conclusions:

Since aging was associated with attenuated amplitude in the circadian modulation of REM sleep, our data suggest that the age-related decrease in dream recall can result from an attenuated circadian modulation of REM sleep.

Citation:

Chellappa SL; Möunch M; Blatter K; Knoblauch V; Cajochen C. Does the circadian modulation of dream recall modify with age? SLEEP 2009;32(9):1201-1209.     

Race and Financial Strain are Independent Correlates of Sleep in Midlife Women: The SWAN Sleep Study

Study Objectives:

To examine racial differences in sleep in a large cohort of midlife women and to evaluate whether indices of socioeconomic status (SES) are associated with racial differences in sleep.

Design:

Cross-sectional study.

Setting:

Participants'' homes.

Participants:

Caucasian (n = 171), African American (n = 138) and Chinese women (n = 59).

Interventions:

None.

Measurements:

Sleep quality was assessed with the Pittsburgh Sleep Quality Index. Polysomnographically assessed sleep duration, continuity, architecture, and NREM electroencephalograhic (EEG) power were calculated over multiple nights. Sleep disordered breathing and periodic leg movements were measured on a separate night. Linear regression analysis was used to model the independent and synergistic effects of race and SES on sleep after adjusting for other factors that impact sleep in midlife women. Indices of SES were self-reported educational attainment and financial strain.

Results:

Sleep was worse in African American women than Caucasian participants as measured by self-report, visual sleep stage scoring, and NREM EEG power. Slow wave sleep differences were also observed between Chinese and Caucasian participants. Racial differences persisted after adjustment for indices of SES. Although educational attainment was unrelated to sleep, financial strain was associated with decreased sleep quality and lower sleep efficiency. Financial strain-by-race interactions were not statistically significant, suggesting that financial strain has additive effects on sleep, independent of race.

Conclusions:

Independent relationships between race and financial strain with sleep were observed despite statistical adjustment for other factors that might account for these relationships. Results do not suggest that assessed indices of SES moderate the race-sleep relationship, perhaps due to too few women of low SES in the study.

Citation:

Hall MH; Matthews KA; Kravitz HM; Gold EB; Buysse DJ; Bromberger JT; Owens JF; Sowers M. Race and financial strain are independent correlates of sleep in midlife women: the SWAN sleep study. SLEEP 2009;32(1):73-82.     

Acute Cardiovascular Changes with Obstructive Events in Children with Sleep Disordered Breathing

Study Objectives:

Obstructive apneas in adults are associated with acute changes in blood pressure (BP) and heart rate (HR) that may contribute to poor cardiovascular outcome. Children with sleep disordered breathing (SDB) are similarly at risk for cardiovascular complications. We aimed to test the hypothesis that BP and HR are augmented during obstructive events in children equivalent to levels reported in adults.

Design:

Beat-by-beat mean arterial pressure (MAP) and HR were analyzed over the course of obstructive events (pre, early, late, and post-event) during NREM and REM sleep and compared using 2-way ANOVA with post hoc analyses.

Setting:

Pediatric sleep laboratory.

Patients or Participants:

30 children (15M/15F) aged 7–12 y referred for investigation of SDB

Interventions:

N/A

Measurements and Results:

All children underwent overnight polysomnography with continuous BP recording. MAP and HR increased significantly from late to post event in both sleep states (mean ± SEM, NREM: MAP, 74 ± 3 to 93 ± 3 mm Hg; HR, 76 ± 2 to 97 ± 2 bpm. REM: MAP, 76 ± 3 to 89 ± 3 mm Hg; HR, 76 ± 2 to 91 ± 2 bpm. P < 0.05 for all). NREM sleep state and arousal from sleep were significant independent predictors of the magnitude of cardiovascular change from late to post event (P < 0.05 for all).

Conclusions:

Children with SDB experience significant changes in HR and BP during obstructive events with magnitudes that are similar to levels reported in adults. These changes are more pronounced during NREM sleep and with arousal. These acute cardiovascular changes may have important implications for poor cardiovascular outcome in children with OSA as repetitive cardiovascular perturbations may contribute to the development of hypertension.

Citation:

O''Driscoll DM; Foster AM; Ng ML; Yang JSC; Bashir F; Nixon GM; Davey MJ; Anderson V; Walker AM; Trinder J; Horne RSC. Acute cardiovascular changes with obstructive events in children with sleep disordered breathing. SLEEP 2009;32(10):1265-1271.     

Sleep Spindle Activity Is Correlated With Reading Abilities in Developmental Dyslexia

Study Objectives:

To analyze sleep architecture of children with dyslexia, by means of conventional parameters and EEG spectral analysis and to correlate sleep parameters and EEG spectra with neuropsychological measures.

Design:

Cross-sectional study involving validated sleep questionnaires, neuropsychological scales, and polysomnographic recordings.

Setting:

Sleep laboratory in academic center.

Participants:

Sixteen subjects with developmental dyslexia (mean age 10.8 years) and 11 normally reading children (mean age 10.1 years). All the subjects underwent overnight polysomnographic recording; EEG power spectra were computed from the Cz derivation and spindle density was calculated during sleep stages N2.

Intervention:

N/A

Measurements and Results:

Dyslexic children showed an increase in power of frequency bands between 0.5–3 Hz and 11–12 Hz in stage N2 and between 0.5–1 Hz in stage N3; they also showed significantly increased spindle density during N2. The power of the sigma band in N2 was positively correlated with the Word reading and MT reading tests; similarly, spindle density was significantly correlated with the Word reading test. The increased spindle activity and EEG sigma power in dyslexic subjects were found to be correlated with the degree of dyslexic impairment.

Conclusions:

The correlation found between sleep spindle activity and reading abilities in developmental dyslexia supports the hypothesis of a role for NREM sleep and spindles in sleep-related neurocognitive processing.

Citation:

Bruni O; Ferri R; Novelli L; Terribili M; Troianiello M; Finotti E; Leuzzi V; Curatolo P. Sleep spindle activity is correlated with reading abilities in developmental dyslexia. SLEEP 2009;32(10):1333-1340.     

Irregular Respiration as a Marker of Wakefulness During Titration of CPAP

Study Objectives:

Regularity of respiration is characteristic of stable sleep without sleep disordered breathing. Appearance of respiratory irregularity may indicate onset of wakefulness. The present study examines whether one can detect transitions from sleep to wakefulness using only the CPAP flow signal and automate this recognition.

Design:

Prospective study with blinded analysis

Setting:

Sleep disorder center, academic institution.

Participants:

74 subjects with obstructive sleep apnea/hypopnea syndrome (OSAHS)

Interventions:

n/a

Measurements and Results:

74 CPAP titration polysomnograms in patients with OSAHS were examined. First we visually identified characteristic patterns of ventilatory irregularity on the airflow signal and tested their relation to conventional detection of EEG defined wake or arousal. To automate recognition of sleep-wake transitions we then developed an artificial neural network (ANN) whose inputs were parameters derived exclusively from the airflow signal. This ANN was trained to identify the visually detected ventilatory irregularities. Finally, we prospectively determined the accuracy of the ANN detection of wake or arousal against EEG sleep/wake transitions. A visually identified irregular respiratory pattern (IrREG) was highly predictive of appearance of EEG wakefulness (Positive Predictive Value [PPV] = 0.89 to 0.98 across subjects). Furthermore, we were able to automate identification of this irregularity with an ANN which was highly predictive for wakefulness by EEG (PPV 0.66 to 0.86).

Conclusions:

Despite not detecting all wakefulness, the high positive predictive value suggests that analysis of the respiration signal alone may be a useful indicator of CNS state with potential utility in the control of CPAP in OSAHS. The present study demonstrates the feasibility of automating the detection of IrREG.

Citation:

Ayappa I; Norman RG; Whiting D; Tsai AHW; Anderson F; Donnely E; Silberstein DJ; Rapoport DM. Irregular respiration as a marker of wakefulness during titration of CPAP. SLEEP 2009;32(1):99-104.     

Inter-individual Differences in the Dynamics of Sleep Homeostasis

Study Objectives:

The two-process model posits that sleep is regulated by 2 independent processes, a circadian Process C and a homeostatic Process S. EEG slow-wave activity (SWA) is a marker of NREM sleep intensity and is used as an indicator of sleep homeostasis. So far, parameters of the two-process model have been derived mainly from average data. Our aim was to quantify inter-individual differences.

Design:

Polysomnographic recordings (analysis of existing data).

Setting:

Sound attenuated sleep laboratory.

Patients or Participants:

Eight healthy young males.

Interventions:

40-h sustained wakefulness.

Measurements and Results:

Process S was modeled by a saturating exponential function during wakefulness and an exponential decline during sleep. Empirical mean SWA (derivation C3A2) per NREM sleep episode at episode midpoint were used for parameter estimation. Parameters were estimated simultaneously by minimizing the mean square error between data and simulations of Process S. This approach was satisfactory for average data and most individual data. We further improved our methodological approach by limiting the time constants to a physiologically meaningful range. This allowed a satisfactory fit also for the one individual whose parameters were beyond a physiological range. The time constants of the buildup of Process S ranged from 14.1 h to 26.4 h and those of the decline from 1.2 h to 2.9 h with similar inter-individual variability of the buildup and decline of Process S.

Conclusions:

We established a robust method for parameter estimation of Process S on an individual basis.

Citation:

Rusterholz T; Dürr R; Achermann P. Inter-individual differences in the dynamics of sleep homeostasis. SLEEP 2010;33(4):491-498.     

Auditory Inhibition of Rapid Eye Movements and Dream Recall from REM Sleep

Study Objectives:

There is debate in dream research as to whether ponto-geniculo-occipital (PGO) waves or cortical arousal during sleep underlie the biological mechanisms of dreaming. This study comprised 2 experiments. As eye movements (EMs) are currently considered the best noninvasive indicator of PGO burst activity in humans, the aim of the first experiment was to investigate the effect of low-intensity repeated auditory stimulation on EMs (and inferred PGO burst activity) during REM sleep. It was predicted that such auditory stimuli during REM sleep would have a suppressive effect on EMs. The aim of the second experiment was to examine the effects of this auditory stimulation on subsequent dream reporting on awakening.

Design:

Repeated measures design with counterbalanced order of experimental and control conditions across participants.

Setting:

Sleep laboratory based polysomnography (PSG)

Participants:

Experiment 1: 5 males and 10 females aged 18-35 years (M = 20.8, SD = 5.4). Experiment 2: 7 males and 13 females aged 18-35 years (M = 23.3, SD = 5.5).

Interventions:

Below-waking threshold tone presentations during REM sleep compared to control REM sleep conditions without tone presentations.

Measurements and Results:

PSG records were manually scored for sleep stages, EEG arousals, and EMs. Auditory stimulation during REM sleep was related to: (a) an increase in EEG arousal, (b) a decrease in the amplitude and frequency of EMs, and (c) a decrease in the frequency of visual imagery reports on awakening.

Conclusions:

The results of this study provide phenomenological support for PGO-based theories of dream reporting on awakening from sleep in humans.

Citation:

Stuart K; Conduit R. Auditory inhibition of rapid eye movements and dream recall from REM sleep. SLEEP 2009;32(3):399–408.     

Benzodiazepine Receptor Agonists Cause Drug-Specific and State-Specific Alterations in EEG Power and Acetylcholine Release in Rat Pontine Reticular Formation

Study Objectives:

Benzodiazepine (BDZ) and non-benzodiazepine (NBDZ) hypnotics enhance GABAergic transmission and are widely used for the treatment of insomnia. In the pontine reticular formation (PRF), GABA inhibits rapid eye movement (REM) sleep and acetylcholine (ACh) release. No previous studies have characterized the effects of BDZ and NBDZ hypnotics on ACh release in the PRF. This study tested 2 hypotheses: (1) that microdialysis delivery of zolpidem, eszopiclone, and diazepam to rat PRF alters ACh release in PRF and electroencephalographic (EEG) delta power and (2) that intravenous (IV) administration of eszopiclone to non-anesthetized rat alters ACh release in the PRF, sleep, and EEG delta power.

Design:

A within- and between-groups experimental design.

Setting:

University of Michigan.

Patients or Participants:

Adult male Crl:CD*(SD) (Sprague-Dawley) rats (n = 57).

Interventions:

In vivo microdialysis of the PRF in rats anesthetized with isoflurane was used to derive the concentration-response effects of zolpidem, eszopiclone, and diazepam on ACh release. Chronically instrumented rats were used to quantify the effects of eszopiclone (3 mg/kg, IV) on ACh release in the PRF, sleep-wake states, and cortical EEG power.

Measurements and Results:

ACh release was significantly increased by microdialysis delivery to the PRF of zolpidem and eszopiclone but not diazepam. EEG delta power was increased by zolpidem and diazepam but not by eszopiclone administered to the PRF. Eszopiclone (IV) decreased ACh release in the PRF of both anesthetized and non-anesthetized rats. Eszopiclone (IV) prevented REM sleep and increased EEG delta power.

Conclusion:

The concentration-response data provide the first functional evidence that multiple GABA_A receptor subtypes are present in rat PRF. Intravenously administered eszopiclone prevented REM sleep, decreased ACh release in the PRF, and increased EEG delta power. The effects of eszopiclone are consistent with evidence that ACh release in the PRF is lower during NREM sleep than during REM sleep, and with data showing that cholinergic stimulation of the PRF activates the cortical EEG.

Citation:

Hambrecht-Wiedbusch VS; Gauthier EA; Baghdoyan HA; Lydic R. Benzodiazepine receptor agonists cause drug-specific and state-specific alterations in EEG power and acetylcholine release in rat pontine reticular formation. SLEEP 2010;33(7):909-918.     

Violent somnambulism: A parasomnia of young men with stereotyped dream-like experiences

Objective

To characterize a subgroup of arousal parasomnias associated with violent behavior in adults.

Design

A pilot study on clinical and polysomnographic data of 13 adult patients seen in a tertiary sleep center for the suspicion of arousal parasomnia associated with violence.

Results

Nine young patients (8 males 1 female) had a common pattern of abnormalities: similar ‘claustrophobic’ dream-like experiences and complex, vehement dream enactments; no REM sleep without atonia on polysomnography. We call this syndrome ‘violent somnambulism’.The rest of the patients had alcoholic delirium, partial epilepsy, possible REM sleep behavior disorder and a single sleep walking episode provoked by a sleeping pill.

Conclusions and hypothesis

Sleep related violence needs thorough diagnostic evaluation for preventing life-threatening consequences. Violent somnambulism appears to be a distinct NREM sleep-related overlap parasomnia.     

Abnormal Sleep/Wake Dynamics in Orexin Knockout Mice

Study Objectives:

Narcolepsy with cataplexy is caused by a loss of orexin (hypocretin) signaling, but the physiologic mechanisms that result in poor maintenance of wakefulness and fragmented sleep remain unknown. Conventional scoring of sleep cannot reveal much about the process of transitioning between states or the variations within states. We developed an EEG spectral analysis technique to determine whether the state instability in a mouse model of narcolepsy reflects abnormal sleep or wake states, faster movements between states, or abnormal transitions between states.

Design:

We analyzed sleep recordings in orexin knockout (OXKO) mice and wild type (WT) littermates using a state space analysis technique. This non-categorical approach allows quantitative and unbiased examination of sleep/wake states and state transitions.

Measurements and Results:

OXKO mice spent less time in deep, delta-rich NREM sleep and in active, theta-rich wake and instead spent more time near the transition zones between states. In addition, while in the midst of what should be stable wake, OXKO mice initiated rapid changes into NREM sleep with high velocities normally seen only in transition regions. Consequently, state transitions were much more frequent and rapid even though the EEG progressions during state transitions were normal.

Conclusions:

State space analysis enables visualization of the boundaries between sleep and wake and shows that narcoleptic mice have less distinct and more labile states of sleep and wakefulness. These observations provide new perspectives on the abnormal state dynamics resulting from disrupted orexin signaling and highlight the usefulness of state space analysis in understanding narcolepsy and other sleep disorders.

Citation:

Diniz Behn CG; Klerman EB; Mochizuki T; Lin S; Scammell TE. Abnormal sleep/wake dynamics in orexin knockout mice. SLEEP 2010;33(3):297-306.     

Discharge Patterns of Human Genioglossus Motor Units during Arousal from Sleep

Study Objectives:

Single motor unit recordings of the human genioglossus muscle reveal motor units with a variety of discharge patterns. Integrated multiunit electromyographic recordings of genioglossus have demonstrated an abrupt increase in the muscle''s activity at arousal from sleep. The aim of the present study was to determine the effect of arousal from sleep on the activity of individual motor units as a function of their particular discharge pattern.

Design:

Genioglossus activity was measured using intramuscular fine-wire electrodes inserted via a percutaneous approach. Arousals from sleep were identified using the ASDA criterion and the genioglossus electromyogram recordings analyzed for single motor unit activity.

Setting:

Sleep research laboratory.

Participants:

Sleep and respiratory data were collected in 8 healthy subjects (6 men).

Measurements and Results:

138 motor units were identified during prearousalarousal sleep: 25% inspiratory phasic, 33% inspiratory tonic, 4% expiratory phasic, 3% expiratory tonic, and 35% tonic. At arousal from sleep inspiratory phasic units significantly increased the proportion of a breath over which they were active, but did not appreciably increase their rate of firing. 80 new units were identified at arousals, 75% were inspiratory, many of which were active for only 1 or 2 breaths. 22% of units active before arousal, particularly expiratory and tonic units, stopped at the arousal.

Conclusions:

Increased genioglossus muscle activity at arousal from sleep is primarily due to recruitment of inspiratory phasic motor units. Further, activity within the genioglossus motoneuron pool is reorganized at arousal as, in addition to recruitment, ∼20% of units active before arousals stopped firing.

Citation:

Wilkinson V; Malhotra A; Nicholas CL; Worsnop C; Jordan AS; Butler JE; Saboisky JP; Gandevia SC; White DP; Trinder J. Discharge patterns of human genioglossus motor units during arousal from sleep. SLEEP 2010;33(3):379-387.