The Future of Sleep Staging, Revisited.

In 1996, I published a paper entitled "The Future of Sleep Staging". At this time, paper and ink records were the standard way of recording sleep records. Computerised systems had only recently become commercially available. The original article was a response to those initial computer-based systems, pointing out the potential limitations of the systems. Now, digital sleep recording is ubiquitous and software and hardware capabilities have improved immeasurably. However, I will argue that despite 50 years of progress, there has not been an increase in the accuracy of sleep staging. I will propose that this is due to the limitations of the task that we have set the automatic analysis methods.

Standard procedures for adults in accredited sleep medicine centres in Europe.

The present paper describes standardized procedures within clinical sleep medicine. As such, it is a continuation of the previously published European guidelines for the accreditation of sleep medicine centres and European guidelines for the certification of professionals in sleep medicine, aimed at creating standards of practice in European sleep medicine. It is also part of a broader action plan of the European Sleep Research Society, including the process of accreditation of sleep medicine centres and certification of sleep medicine experts, as well as publishing the Catalogue of Knowledge and Skills for sleep medicine experts (physicians, non-medical health care providers, nurses and technologists), which will be a basis for the development of relevant educational curricula. In the current paper, the standard operational procedures sleep medicine centres regarding the diagnostic and therapeutic management of patients evaluated at sleep medicine centres, accredited according to the European Guidelines, are based primarily on prevailing evidence-based medicine principles. In addition, parts of the standard operational procedures are based on a formalized consensus procedure applied by a group of Sleep Medicine Experts from the European National Sleep Societies. The final recommendations for standard operational procedures are categorized either as 'standard practice', 'procedure that could be useful', 'procedure that is not useful' or 'procedure with insufficient information available'. Standard operational procedures described here include both subjective and objective testing, as well as recommendations for follow-up visits and for ensuring patients' safety in sleep medicine. The overall goal of the actual standard operational procedures is to further develop excellence in the practice and quality assurance of sleep medicine in Europe.

Age-related reduction in daytime sleep propensity and nocturnal slow wave sleep.

OBJECTIVE: To investigate whether age-related and experimental reductions in SWS and sleep continuity are associated with increased daytime sleep propensity. METHODS: Assessment of daytime sleep propensity under baseline conditions and following experimental disruption of SWS. Healthy young (20-30 y, n = 44), middle-aged (40-55 y, n = 35) and older (66-83 y, n = 31) men and women, completed a 2-way parallel group study. After an 8-h baseline sleep episode, subjects were randomized to 2 nights with selective SWS disruption by acoustic stimuli, or without disruption, followed by 1 recovery night. Objective and subjective sleep propensity were assessed using the Multiple Sleep Latency Test (MSLT) and the Karolinska Sleepiness Scale (KSS). FINDINGS: During baseline sleep, SWS decreased (P < 0.001) and the number of awakenings increased (P < 0.001) across the 3 age groups. During the baseline day, MSLT values increased across the three age groups (P < 0.0001) with mean values of 8.7 min (SD: 4.5), 11.7 (5.1) and 14.2 (4.1) in the young, middle-aged, and older adults, respectively. KSS values were 3.7 (1.0), 3.2 (0.9), and 3.4 (0.6) (age-group: P = 0.031). Two nights of SWS disruption led to a reduction in MSLT and increase in KSS in all 3 age groups (SWS disruption vs. control: P < 0.05 in all cases). CONCLUSIONS: Healthy aging is associated with a reduction in daytime sleep propensity, sleep continuity, and SWS. In contrast, experimental disruption of SWS leads to an increase in daytime sleep propensity. The age-related decline in SWS and reduction in daytime sleep propensity may reflect a lessening in homeostatic sleep requirement. Healthy older adults without sleep disorders can expect to be less sleepy during the daytime than young adults.

European guidelines for the certification of professionals in sleep medicine: report of the task force of the European Sleep Research Society.

In recent years, sleep medicine has evolved into a full-grown discipline, featuring a multidisciplinary approach to diagnosis and treatment of patients with sleep disorders. Sleep medicine cuts across the boundaries of different conventional disciplines and is therefore open to medical and non-medical professionals with different specialty backgrounds. The aim of the current paper is to introduce a qualification for those professionals whose main occupation is to practice sleep medicine in the setting of a sleep medicine centre. The drafting of guidelines dealing with requirements for such qualification was entrusted to a task force by the European Sleep Research Society. The guidelines are the result of a progressive consensus procedure in which standards were defined for education, training, and evaluation. The final step along this pathway is a theoretical and practical examination, providing proof of proficiency in the field of sleep medicine. This paper describes the object of specific competences, the scope of sleep medicine, and the qualification procedures that pertain to three professional categories: medical specialists, non-medical professionals with a university master degree (such as psychologists and biologists), and nurses and technologists. Indices of preceding practical experience and theoretical knowledge are presented in Appendices 1 and 2. These guidelines are a European standard. They may be adapted in the future according to new scientific insights. National certification programs that comply with these guidelines may be subject to homologation by the ESRS.

Benzodiazepine-induced reduction in activity mirrors decrements in cognitive and psychomotor performance.

OBJECTIVE: To assess whether actigraphy is sensitive to benzodiazepine-induced changes in cognitive and psychomotor performance and sleep. METHODS: Healthy young volunteers (n = 23; 11 males), were randomised to a double-blind, placebo-controlled, crossover trial. Actigraphy was used to record motor activity continuously. Following dosing at 18.00 h with 2.5 mg lorazepam (LZP), psychomotor and cognitive assessments were made at hourly intervals post-dose for 4 h and after sleep at 14.5 h post-dose. RESULTS: Activity levels were significantly reduced after LZP for 5 h post-dose (p = 0.0104), during sleep (5-13 h) (p < 0.02) and the following morning, 13-14.5 h post-dose (p < 0.02). At the same time cognitive and psychomotor performance was also significantly impaired (p < 0.05). LZP also significantly increased actigraphic sleep efficiency and sleep per cent (p < 0.02). CONCLUSION: This study showed that activity levels were significantly reduced following dosing with a benzodiazepine and these changes coincided with impairment of cognitive and psychomotor performance. Actigraphy, therefore, appears to be able to reflect the psychopharmacological effects of a benzodiazepine in changes in daytime function and nocturnal behaviour, which, without waking the subject, is beyond the power of conventional psychometrics.

Allergy medication in Japanese volunteers: treatment effect of single doses on nocturnal sleep architecture and next day residual effects.

OBJECTIVES: To evaluate the acute effects of two histamine H(1)-receptor antagonists on nocturnal sleep architecture and on next day cognitive function and psychomotor performance. METHODS: This was a single-site, randomized, double-blind, 3-way crossover study, comparing the effects of a single dose of chlorpheniramine (6 mg), fexofenadine (120 mg) and placebo in 18 healthy (male and female) Japanese volunteers aged 20-55 years. Volunteers were resident for 3 days and each period was separated by a minimum 5-day washout period. The three treatments were administered at 23.00 h. Overnight sleep was measured from 23.00 h to 07.00 h using polysomnography. Residual effects were studied at 07.00 h and 9.00 h the next morning, with the latency to sleep (sleep latency test) measured at 09.30 h. RESULTS: Compared with placebo, chlorpheniramine increased the latencies to sleep onset and rapid eye movement (REM) sleep (p < or = 0.05 for both), and reduced the duration of REM sleep (p

A double-blind study in healthy volunteers to assess the effects on sleep of pregabalin compared with alprazolam and placebo.

STUDY OBJECTIVES: To assess the effects of pregabalin compared with alprazolam and placebo on aspects of sleep in healthy volunteers. DESIGN: Randomized, double-blind, placebo- and active-controlled, 3-way crossover. SETTING: Single research center. PARTICIPANTS AND INTERVENTIONS: Healthy adult (12 men) volunteers (N=24) received oral pregabalin 150 mg t.i.d., alprazolam 1 mg t.i.d., and placebo t.i.d. for 3 days. MEASUREMENTS AND RESULTS: Objective sleep was measured by an 8-channel polysomnograph; subjective sleep was measured using the Leeds Sleep Evaluation Questionnaire. Compared with placebo, pregabalin significantly increased slow-wave sleep both as a proportion of the total sleep period and the duration of stage 4 sleep. Alprazolam significantly reduced slow-wave sleep. Pregabalin and alprazolam produced modest, but significant, reductions in sleep-onset latency compared with placebo. Rapid eye movement sleep latency after pregabalin was no different than placebo but was significantly shorter than that found with alprazolam. Although there were no differences between the active treatments, both pregabalin and alprazolam reduced rapid eye movement sleep as a proportion of the total sleep period compared with placebo. Pregabalin also significantly reduced the number of awakenings of more than 1 minute in duration. Leeds Sleep Evaluation Questionnaire ratings of the ease of getting to sleep and the perceived quality of sleep were significantly improved following both active treatments, and ratings of behavior following awakening were significantly impaired by both drug treatments. CONCLUSIONS: Pregabalin appears to have an effect on sleep and sleep architecture that distinguishes it from benzodiazepines. Enhancement of slow-wave sleep is intriguing, since reductions in slow-wave sleep have frequently been reported in fibromyalgia and general anxiety disorder.

Acute sleep responses in a normobaric hypoxic tent.

PURPOSE: Sleeping in a hypoxic environment is becoming increasingly popular among athletes attempting to simulate a "live high, train low" training regime. The purpose of this study was to investigate the acute effects (one night) of sleeping in a normobaric hypoxic tent (NH) (PO(2) = 110 mm Hg approximately 2500 m) upon markers of sleep physiology and quality, compared with sleep in a normal ambient environment (BL) (PO(2) = 159 mm Hg approximately sea level) and sleep in a normobaric normoxic tent (NN) (PO(2) = 159 mm Hg). METHODS: Eight male recreational athletes (age 34.5 +/- 6.9 yr; stature 169.1 +/- 8.7 cm; mass 69.3 +/- 8.2 kg; VO(2max) 56.4 +/- 8.3 mL.kg(-1).min(-1)) participated in the study using a randomized, double-blind crossover design. Polysomnographic studies were undertaken to measure sleep stages, arterial oxygen saturation (SpO(2)), heart rate (HR), and the Respiratory Disturbance Index (RDI). The Leeds Sleep Evaluation Questionnaire (LSEQ) was used to measure subjective sleep quality. RESULTS: NH (89.9 +/- 4.8%) resulted in a significantly lower (P < 0.05) SpO(2) compared with both BL (95.7 +/- 1.5%) and NN (93.5 +/- 4.0%). Heart rate was significantly higher (P < 0.05) in NH (51.5 +/- 7.6 beats.min(-1)) compared with NN (48.3 +/- 6.9 beats.min(-1)) but was similar versus BL (50.3 +/- 4.3 beats.min(-1)). RDI (counts.h) and RDI (total counts) were lowest in BL (3.5 +/- 2.5; 18.1 +/- 7.9) and highest in NH (36.8 +/- 42.7; 221.9 +/- 254.5). The difference in RDI (counts.h(-1) and total counts) between NH and BL was significant (P < 0.05). The LSEQ revealed that subjects' "behavior following waking" score was significantly (P < 0.05) lower in NH (40.9 +/- 9.2) compared with BL (52.3 +/- 8.3). CONCLUSION: This study presents evidence that sleep in a normobaric hypoxic tent at a simulated altitude of 2500 m may affect sleep parameters in some individuals. This type of analysis may be useful in the early identification of poorly responding individuals to simulated altitude environments.

A double-blind, randomized, 26-week study comparing the cognitive and psychomotor effects and efficacy of 75 mg (37.5 mg b.i.d.) venlafaxine and 75 mg (25 mg mane, 50 mg nocte) dothiepin in elderly patients with moderate major depression being treated in general practice.

To investigate the efficacy and cognitive and psychomotor effects of venlafaxine and dothiepin in elderly patients with moderate major depression. A prospective, randomized, double-blind, parallel-group, active comparator controlled study was conducted. Eighty-eight patients (aged > or = 60 years) were enrolled. Each patient received either venlafaxine (immediate release formulation) 37.5 mg twice per day or dothiepin 25 mg mane followed by 50 mg nocte for 26 weeks. Efficacy was assessed with the Montgomery-Asberg Depression Rating Scale and the Hamilton Depression Rating Scale. A psychometric test battery to assess cognitive function, activities of daily living and sleep consisted of Critical Flicker Fusion (CFF), Short-term Memory--Kim's Game, Cognitive Failures Questionnaire, Milford Epworth Sleepiness Scale, Leeds Sleep Evaluation Questionnaire, and an Accident Scoring Questionnaire. Quality of Life Questionnaires (Short Form 36 and Quality of Life in Depression Scale) were also administered. Venlafaxine significantly (p < 0.05) raised CFF scores compared to baseline but had no effect on any other measure. Dothiepin significantly (p < 0.05) lowered CFF threshold, and increased ratings of both sedation and difficulty in waking. The results showed that venlafaxine at doses of 37.5 mg b.i.d. in elderly depressed patients is free from disruptive effects on cognitive function and psychomotor performance.

Residual effects of zaleplon and zolpidem following middle of the night administration five hours to one hour before awakening.

The objective was to assess residual effects of zaleplon and zolpidem after a middle of the night administration. This was a randomized, double-blind, placebo-controlled, crossover study, conducted in 40 healthy young male and female subjects. Subjects were awakened in the middle of the night and administered either placebo or zaleplon 10 or 20 mg or zolpidem 10 mg. A battery of objective tests exploring psychomotor and cognitive functions such as critical flicker fusion (CFF), choice reáction time (CRT), digit symbol substitution test (DSST), and memory tests (Sternberg memory scanning and a word list) were administered immediately after morning waking. Zaleplon 10 mg was devoid of residual effects whatever - the time of dosing - except a minimal but significant decrease in DSST scores when administered 1 h before awakening. Zaleplon 20 mg produced significant residual effects on performance (increase in CRT, and decrease in CFF threshold and in DSST scores) and memory (decrease in immediate and delayed free recall of words) only when administered 1 h before awakening. In contrast, zolpidem 10 mg produced significant detrimental residual effects on CRT and delayed free recall of words, when administered up to 5 h before waking, on DSST and Sternberg when administered up to 3 h before awakening and on CFF when administered 1 h before awakening. The residual effects of zolpidem 10 mg were more marked than those observed after zaleplon 20 mg. The present results demonstrate that zaleplon 10 mg has no or minimal residual effects when administered in the middle of the night as little as 1 h before waking. The lack of clinically significant residual effects with zaleplon may be explained by its unique pharmacokinetic (rapid elimination half-life) and pharmacodynamic (selective binding for GABA(A) receptors with the alpha(1) subunit, dissociation between sleep inducing properties and impairment of cognitive functions) profiles. Copyright 2001 John Wiley & Sons, Ltd.

Dissociating effects of global SWS disruption and healthy aging on waking performance and daytime sleepiness.

STUDY OBJECTIVE: To contrast the effects of slow wave sleep (SWS) disruption and age on daytime functioning. DESIGN: Daytime functioning was contrasted in three age cohorts, across two parallel 4-night randomized groups (baseline, two nights of SWS disruption or control, recovery sleep). SETTING: Sleep research laboratory. PARTICIPANTS: 44 healthy young (20-30 y), 35 middle-aged (40-55 y), and 31 older (66-83 y) men and women. INTERVENTIONS: Acoustic stimulation contingent on appearance of slow waves. MEASUREMENTS AND RESULTS: Cognitive performance was assessed before sleep latency tests at five daily time-points. SWS disruption resulted in less positive affect, slower or impaired information processing and sustained attention, less precise motor control, and erroneous implementation, rather than inhibition, of well-practiced actions. These performance impairments had far smaller effect sizes than the increase in daytime sleepiness and differed from baseline to the same extent for each age group. At baseline, younger participants performed better than older participants across many cognitive domains, with largest effects on executive function, response time, sustained attention, and motor control. At baseline, the young were sleepier than other age groups. CONCLUSIONS: SWS has been considered a potential mediator of age-related decline in performance, although the effects of SWS disruption on daytime functioning have not been quantified across different cognitive domains nor directly compared to age-related changes in performance. The data imply that two nights of SWS disruption primarily leads to an increase in sleepiness with minor effects on other aspects of daytime functioning, which are different from the substantial effects of age.

Acute sleep deprivation: the effects of the AMPAKINE compound CX717 on human cognitive performance, alertness and recovery sleep.

AMPA receptor modulation is a potential novel approach to enhance cognitive performance. CX717 is a positive allosteric modulator of the AMPA receptor that has shown efficacy in rodent and primate cognition models. CX717 (100 mg, 300 mg and 1000 mg) and placebo were studied in 16 healthy male volunteers (18-45 years) in a randomized, crossover study. Cognitive function, arousal and recovery sleep (by polysomnography) were assessed during the extended wakefulness protocol. Placebo condition was associated with significant decrements in cognition, particularly at the circadian nadir (between 03:00 and 05:00). Pre-specified primary and secondary analyses (general linear mixed modelling, GLMM) at each separate time point did not reveal consistent improvements in performance or objective alertness with any dose of CX717. Exploratory repeated measures analysis, a method used to take into account the influence of individual differences, demonstrated an improvement in attention-based task performance following the 1000 mg dose. Analysis of the recovery sleep showed that CX717 1000 mg significantly reduced stage 4 and slow-wave sleep (p ≤ 0.05) with evidence of reduced electroencephalogram (EEG) slow-wave and spindle activity. The study suggests that CX717 only at the 1000 mg dose may counteract effects of sleep deprivation on attention-based tasks and that it may interfere with subsequent recovery sleep.

Exploring the interdependence of couples' rest-wake cycles: an actigraphic study.

Within western societies, it is commonplace for couples to share a bed. Yet there has been remarkably little research carried out on couples' sleep. This paper draws upon actigraphy, audio diary, and questionnaire data from both partners of 36 heterosexual couples (age 20-59 yrs) and aims to quantify the extent to which it is important to take into account the dyadic nature of sleep-wake cycles. It achieves this through two interrelated aims: to use hierarchical linear models to measure dyadic interdependence in actigraphically recorded variables, and to investigate how much of this dyadic interdependence truly results from couple dynamics. The variables with the most significant couple interdependency were actual bed time, sleep latency, light/dark ratio, and wake bouts. The paper concludes by suggesting that interdependence may be the defining feature of couples' sleep, and that we need to employ analytic approaches that both acknowledge this and are sensitive to the possibilities that not all aspects of sleep will behave in the same way.

Sleep profiles and mood states during an expedition to the South Pole.

OBJECTIVE: To study sleep parameters and mood profiles of a female explorer traveling solo and unaided to the South Pole during the winter. METHODS: During the 44-day expedition, global activity and sleep were assessed using a wrist actigraph (AW) worn on the nondominant wrist. Mood was assessed using an adapted Profile of Mood States questionnaire. Pre- and post expedition physiologic profiles were conducted to assess body composition, strength and power, and aerobic capacity. RESULTS: The AW data revealed decreasing sleep duration throughout the expedition, with an average sleep time of 5 hours (range, 8 hours and 14 minutes to 1 hour and 42 minutes), with sleep times consistently <3 hours during the final third of the expedition. Mood responses indicated a progressive reduction in vigor and increase in fatigue. Sleep time was positively related to vigor and inversely related to depression and fatigue, a finding that is consistent with the notion that positive feelings (high vigor and low fatigue) are linked with sleep. CONCLUSIONS: This account provides insight to help understand the limits of human tolerance and may be directly applicable when planning future expeditions of this nature.

A double-blind, placebo-controlled investigation of the residual psychomotor and cognitive effects of zolpidem-MR in healthy elderly volunteers.

AIM: To assess residual psychomotor and cognitive effects of a modified-release formulation of zolpidem (zolpidem-MR), developed to provide sustained hypnotic efficacy during the whole night, compared with placebo and flurazepam. METHODS: Twenty-four healthy elderly volunteers received four study treatments (zolpidem-MR 6.25 mg and 12.5 mg, placebo and flurazepam 30 mg) using a randomized, cross-over, double-blind design. Residual psychomotor and cognitive effects were assessed with a psychometric test battery. Quality of sleep and residual effects were evaluated subjectively with the Leeds Sleep Evaluation Questionnaire. RESULTS: Psychometric performance was significantly impaired with flurazepam but not with zolpidem-MR at either dose. Ease of falling asleep and sleep quality were significantly improved with both doses of zolpidem-MR and with flurazepam. Neither active drug modified perception of well-being on awakening. CONCLUSION: In elderly subjects, zolpidem-MR showed no residual functional impairment in psychometric or cognitive tests sensitive to flurazepam.

Actigraphy in human psychopharmacology: a review.

Over the last 25 years wrist actigraphy has predominantly been used in sleep research and chronobiology where the technique has proved useful in the measurement of sleep and the characterisation of the sleep/wake cycle. Whilst there are a large number of studies published that have used actigraphy, there have only been relatively few studies that have shown that the technique is capable of measuring drug-induced changes in nocturnal and/or diurnal behaviour. Thus the use of actigraphy to measure drug effects in clinical trials has up till now remained on the periphery of psychopharmacology. However this may be because of the disparate nature of the studies published rather than lack of usefulness. This paper reviews the relevant literature and in doing so concludes that there is a convincing body of evidence for the utility of actigraphy as a technique in human psychopharmacology.