Search

Rationale The mechanisms underlying impaired sleep quality in insomnia are not fully known, but an important role for sleep fragmentation has been proposed. Objectives The aim of this study is to explore potential mechanisms of sleep fragmentation influencing alterations of perceived sleep quality. Methods We analyzed polysomnography (PSG) recordings from a double-blind crossover study with zopiclone 7.5 mg and placebo, in elderly participants with insomnia complaints and age-matched healthy controls. We compared survival dynamics of sleep and wake across group and treatment. Subsequently, we used a previously proposed model to estimate the amount of sleep onset latency (SOL) misperception from PSG-defined sleep fragmentation. Self-reported and model-estimated amount of SOL misperception were compared across group and treatment, as well as model prediction errors. Results In the zopiclone night, the average segment length of NREM sleep was increased (group F = 1.16, p = 0.32; treatment F = 8.89, p< 0.01; group x treatment F = 0.44, p = 0.65), while the segment length of wake was decreased (group F = 1.48, p = 0.23; treatment F = 11.49, p< 0.01; group x treatment F = 0.36, p = 0.70). The self-reported and model-estimated amount of SOL misperception were lower during the zopiclone night (self-reported group F = 6.08, p< 0.01, treatment F = 10.8, p< 0.01, group x treatment F = 2.49, p = 0.09; model-estimated F = 1.70, p = 0.19, treatment F = 16.1, p< 0.001, group x treatment F = 0.60, p = 0.55). The prediction error was not altered (group F = 1.62, p = 0.20; treatment F = 0.20, p = 0.65; group x treatment F = 1.01, p = 0.37). Conclusions Impaired subjective sleep quality is associated with decreased NREM stability, together with increased stability of wake. Furthermore, we conclude that zopiclone-induced changes in SOL misperception can be largely attributed to predictable changes of sleep architecture.

Lieke WA Hermans,1 Marta Regis,2 Pedro Fonseca,1,3 Bertram Hoondert,4 Tim RM Leufkens,3 Sebastiaan Overeem,1,4 Merel M van Gilst1,4 1Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; 2Department of Mathematics and Computer Science, Eindhoven University of Technology, Eindhoven, the Netherlands; 3Philips Research, Eindhoven, the Netherlands; 4Sleep Medicine Center Kempenhaeghe, Heeze, the NetherlandsCorrespondence: Lieke WA HermansDepartment of Electrical Engineering, Eindhoven University of Technology, De Zaale, 5600, MB Eindhoven, the NetherlandsEmail l.w.a.hermans@tue.nlIntroduction: Assessing objective measures of sleep fragmentation could yield important features reflecting impaired sleep quality in people with insomnia. Survival analysis allows the specific examination of the stability of NREM sleep, REM sleep and wake. The objective of this study was to assess the differences between survival dynamics of NREM sleep, REM sleep and wake between people with insomnia and healthy controls.Methods: We analyzed retrospective polysomnography recordings from 86 people with insomnia and 94 healthy controls. For each participant, survival dynamics of REM sleep, NREM sleep and wake were represented using Weibull distributions. We used lasso penalized parameter selection in combination with linear regression to analyze the difference between participant groups with respect to the Weibull scale and shape parameters, while correcting for age, sex, total sleep time and relevant interaction effects.Results: Significant effects of group were found for the NREM scale parameter, and for the wake scale and shape parameters. Results indicated that people with insomnia had less stable NREM sleep and more stable wake after sleep onset compared to healthy controls. Additionally, the altered distribution of wake segment lengths indicated an increased difficulty to fall asleep after longer awakenings in the insomnia group. However, these differences were mainly observed in younger participants. Significant effects of group for the survival parameters of REM sleep were not found.Conclusion: As illustrated by our results, survival analysis can be very useful for disentangling different types of sleep fragmentation in people with insomnia. For instance, the current findings suggest that people with insomnia have an increased fragmentation of NREM sleep, but not necessarily of REM sleep. Additional research into the underlying mechanisms of NREM sleep fragmentation could possibly lead to a better understanding of impaired sleep quality in people with insomnia, and consequently to improved treatment.Keywords: insomnia, survival analysis, sleep fragmentation

Study objective To elucidate the contribution of time estimation and pre sleep arousal to the component of sleep onset misperception not explained by sleep fragmentation. Methods At-home ambulatory polysomnograms (PSGs) of 31 people with insomnia were recorded. Participants performed a time estimation task and completed the Pre Sleep Arousal Scale (PSAS). Based on previous modelling of the relationship between objectively measured sleep fragmentation and sleep onset misperception, the subjective sleep onset was estimated for each participant as the start of the first uninterrupted sleep bout longer than 30 min. Subsequently, the component of misperception not explained by sleep fragmentation was calculated as the residual error between estimated sleep onset and perceived sleep onset. This residual error was correlated with individual time estimation task results and PSAS scores. Results A negative correlation between time estimation task results and the residual error of the sleep onset model was found, indicating that participants who overestimated a time interval during the day also overestimated their sleep onset latency (SOL). No correlation was found between PSAS scores and residual error. Conclusions Interindividual variations of sleep architecture possibly obscure the correlation of sleep onset misperception with time estimation and pre sleep arousal, especially in small groups. Therefore, we used a previously proposed model to account for the influence of sleep fragmentation. Results indicate that time estimation is associated with sleep onset misperception. Since sleep onset misperception appears to be a general characteristic of insomnia, understanding the underlying mechanisms is probably important for understanding and treating insomnia., Highlights • Sleep onset misperception is probably a multifactorial process. • We identify the part of misperception not explained by fragmentation. • This metric was correlated with the time estimation and pre sleep arousal. • Results indicate that time estimation is involved in sleep onset misperception.

Objectives To extend and validate a previously suggested model of the influence of uninterrupted sleep bouts on sleep onset misperception in a large independent data set. Methods Polysomnograms and sleep diaries of 139 insomnia patients and 92 controls were included. We modeled subjective sleep onset as the start of the first uninterrupted sleep fragment longer than Ls minutes, where parameter Ls reflects the minimum length of a sleep fragment required to be perceived as sleep. We compared the so-defined sleep onset latency (SOL) for various values of Ls. Model parameters were compared between groups, and across insomnia subgroups with respect to sleep onset misperception, medication use, age, and sex. Next, we extended the model to incorporate the length of wake fragments. Model performance was assessed by calculating root mean square errors (RMSEs) of the difference between estimated and perceived SOL. Results Participants with insomnia needed a median of 34 minutes of undisturbed sleep to perceive sleep onset, while healthy controls needed 22 minutes (Mann–Whitney U = 4426, p < 0.001). Similar statistically significant differences were found between sleep onset misperceivers and non-misperceivers (median 40 vs. 20 minutes, Mann–Whitney U = 984.5, p < 0.001). Model outcomes were similar across other subgroups. Extended models including wake bout lengths resulted in only marginal improvements of model outcome. Conclusions Patients with insomnia, particularly sleep misperceivers, need larger continuous sleep bouts to perceive sleep onset. The modeling approach yields a parameter for which we coin the term Sleep Fragment Perception Index, providing a useful measure to further characterize sleep state misperception.

Most HCI work on the exploration and support of mental wellbeing involves mobiles, sensors, and various on-line systems which focus on tracking users. However, adoption of, and adherence to such systems is not ideal. Are there innovative ways to better design for mental wellbeing? A promising novel approach is to encourage changes to behavior through the use of tailored feedback informed by machine learning algorithms applied to large sets of use data. This one day workshop aims to explore novel ways to actively engage participants through interactive systems, with an overall aim to shape the research agenda of future HCI work on mental wellbeing. The workshop is designed in an innovative format offering a mixture of traditional presentation, hands-on design and future-thinking activities. The workshop brings together both practitioners and HCI researchers from across a range areas addressing mental wellbeing.

In the last decades, Emotion Regulation (ER) represented one of the most studied constructs within the psychological field. Most research, however, has been conducted in laboratory settings; consequently, there are still questions that need to be addressed concerning the deployment and consequences of ER in everyday life. Beyond traditional methods, ecological momentary assessment (EMA) via mobile devices (e.g. smartphones) has the potential to capture ER dynamics during the flow of daily experiences and in real-life settings. Compared to retrospective surveys and laboratory experiments, this approach allows to ecologically and repeatedly investigate the deployment of ER, as well as understand the direct consequences of this process on different aspects of daily life, including behaviors and affect. We will discuss what we currently know about the deployment and consequences of ER in real-life settings focusing on studies that investigated this process by means of EMA. In doing so, we will point out the potentialities of this approach both from a theoretical and clinical point of view.

Introduction Assessing objective measures of sleep fragmentation could yield important features reflecting impaired sleep quality in people with insomnia. Survival analysis allows the specific examination of the stability of NREM sleep, REM sleep and wake. The objective of this study was to assess the differences between survival dynamics of NREM sleep, REM sleep and wake between people with insomnia and healthy controls. Methods We analyzed polysomnography recordings from 88 people with insomnia and 92 healthy controls. For each participant, survival dynamics of REM sleep, NREM sleep and wake were represented using Weibull distributions. We used lasso penalized linear regression to analyze the difference between participant groups with respect to the Weibull scale and shape parameters, while correcting for age, sex, total sleep time and relevant interaction effects. Because comparisons were done for scale and shape parameters of REM sleep, NREM sleep and wake, a Bonferroni correction was applied, resulting in an alpha value of 0.05/6 = 0.0083. Results Significant effects of group were found for the NREM scale parameter (unstandardized model coefficient B=-0.79, t=-3.0, p=0.0035), and for the scale and shape parameters of wake (scale parameter B=7.6, t=2.8, p=0.0065; shape parameter B=0.20, t=2.9, p=0.0048). Results indicated that people with insomnia had less stable NREM sleep and more stable wake after sleep onset compared to healthy controls. Additionally, the altered distribution of wake segment lengths indicated an increased difficulty to fall asleep after longer awakenings in the insomnia group. However, these differences were mainly observed in younger participants. Significant effects of group for the survival parameters of REM sleep were not found. Conclusion As illustrated by our results, survival analysis can be very useful for disentangling different types of sleep fragmentation in people with insomnia. For instance, the current findings suggest that people with insomnia have an increased fragmentation of NREM sleep, but not necessarily of REM sleep. Additional research into the underlying mechanisms of NREM sleep fragmentation could possibly lead to a better understanding of impaired sleep quality in people with insomnia, and consequently to improved treatment. Support (if any)

International audience; Insomniacs report decreased performance in daily routines, which may have detrimental consequences for car driving. We compared changes over time in driving performance (measured as Standard Deviation of Lateral Position – SDLP) and background EEG between 20 untreated insomnia patients (52–70 years old) and 21 normal sleepers (54–73 years old) during a 1 h on-the-road driving test after a normal night of sleep, in the morning. SDLP did not differ between groups and increased slightly over time to similar degrees in both groups. EEG alpha and beta power were lower in insomniacs as compared to normal sleepers. Alpha and beta power slightly reduced during driving in normal sleepers but remained at a constant low level in insomniacs. Changes in EEG power and SDLP were not related. It is concluded that on-the-road driving performance does not differ between older insomniacs and older normal sleepers and that changes in spectral EEG measures of cortical arousal and in driving performance are not related.

Autonomic cardiorespiratory activity changes across sleep stages. However, it is unknown to what extent it is affected by between- and within-subject variability during sleep. As it is hypothesized that the variability is caused by differences in subject demographics (age, gender, and body mass index), time, and physiology, we quantified these effects and investigated how they limit reliable cardiorespiratory-based sleep staging. Six representative parameters obtained from 165 overnight heartbeat and respiration recordings were analyzed. Multilevel models were used to evaluate the effects evoked by differences in sleep stages, demographics, time, and physiology between and within subjects. Results show that the between- and within-subject effects were found to be significant for each parameter. When adjusted by sleep stages, the effects in physiology between and within subjects explained more than 80% of total variance but the time and demographic effects explained less. If these effects are corrected, profound improvements in sleep staging can be observed. These results indicate that the differences in subject demographics, time, and physiology present significant effects on cardiorespiratory activity during sleep. The primary effects come from the physiological variability between and within subjects, markedly limiting the sleep staging performance. Efforts to diminish these effects will be the main challenge.

Rationale Residual effects of hypnotics on driving performance have been mainly determined in studies using a standardized driving test with healthy good sleepers. Responses to effects may differ, however, between insomniacs and healthy volunteers due to the underlying sleep disorder. In addition, a majority of insomniacs uses hypnotics chronically resulting in the development of tolerance to impairing effects. Impaired driving performance in healthy volunteers may then be an overestimation of the actual effects in insomniacs. Objectives The present study aims to compare the residual effects of zopiclone 7.5 mg on on-the-road driving performance of 16 middle-aged insomniacs chronically using hypnotics (chronic users), 16 middle-aged insomniacs not or infrequently using hypnotics (infrequent users), and 16 healthy, age matched, good sleepers (controls). Methods The study was conducted according to a 3 × 2 double-blind, placebo controlled crossover design, with three groups and two treatment conditions. Treatments were single oral doses of zopiclone 7.5 mg and placebo administered at bedtime (2330 hours). Between 10 and 11 h after administration subjects performed a standardized highway driving test. Results Zopiclone 7.5 mg significantly impaired on-the-road driving performance in both insomnia groups and healthy controls. The magnitude of impairment was significantly less in the chronic users group as compared with the controls. Conclusions The smaller magnitude of effects suggests that investigating residual effects of hypnotics in healthy volunteers may yield a minor overestimation of the actual effects in insomnia patients

STUDY OBJECTIVE: To evaluate next-morning driving performance after middle-of-the-night use of zolpidem 3.5 mg in a buffered sublingual formulation (ZST). DESIGN: Single-center, four-period, randomized, double-blind, placebo-controlled, crossover study. SETTING: Maastricht University, The Netherlands. PARTICIPANTS: Forty healthy volunteers (20 females). INTERVENTIONS: Single dose of ZST administered in the middle of the night at 3 and 4 h before driving, zopiclone 7.5 mg at bedtime 9 h before driving, and placebo. MEASUREMENTS: Performance in a 100-km standardized highway driving test in normal traffic measuring standard deviation of lateral position (SDLP) - an index of weaving. Drug-placebo changes in SDLP > 2.5 cm were considered to reflect clinically relevant driving impairment. RESULT: For ZST, Max McNemar symmetry analyses showed that the proportion of drivers classified as impaired was increased 3 h after dosing (P < 0.012), but not 4 h after dosing. Mean increases in SDLP from placebo, although statistically significant, were small (1.46 cm [P < 0.0001] at 3 h and 0.83 cm [P = 0.0174] at 4 h). The morning after zopiclone, 45% of the drivers were classified as impaired with a mean increase in SDLP of 2.46 cm (P < 0.0001). There were no significant sex differences in effects of ZST and zopiclone. CONCLUSION: Zolpidem 3.5 mg in a buffered sublingual formulation has a minimal risk of impairing driving performance in the morning >/= 4 hours after middle-of-the night use. When taken 3 hours before driving, the drug may have impairing effects so caution should be exercised if medication is taken other than as indicated. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov Identifier: NCT01106859; Trial Name: Driving Performance After Middle of the Night Administration of 3.5 mg Zolpidem Tartrate Sublingual Tablet; http://clinicaltrials.gov/ct2/show/NCT01106859. CITATION: Vermeeren A; Vuurman EF; Leufkens TR; Van Leeuwen CJ; Van Oers AC; Laska E; Rico S; Steinberg F; Roth T. Residual effects of low-dose sublingual zolpidem on highway driving performance the morning after middle-of-the-night use. SLEEP 2014;37(3):489-496.

Gaboxadol is a selective extrasynaptic GABA(A) receptor agonist previously in development for the treatment of insomnia. Due to its short half-life (1.5-2 h) it is expected to be free from residual effects the next morning. The present study assessed the residual effects of evening and middle-of-the-night administration of 15 mg of gaboxadol on cognitive, psychomotor and driving performance. Twenty-eight healthy volunteers entered the study with 25 (12 women; mean age 31.4 years) completing a double-blind, placebo-controlled, active-referenced five-way cross-over study. Each treatment night subjects ingested one capsule at 23:00 hours and one at 04:00 hours. Treatments were placebo at both times, 15 mg gaboxadol or 7.5 mg zopiclone followed by placebo, and placebo followed by 15 mg gaboxadol or 10 mg zolpidem. Effects on cognition and psychomotor performance were assessed between 07:30 and 08:30 hours and on driving between 09:00 and 10:00 hours. Driving, as measured by standard deviation of lateral position in an on-the-road driving test, was almost significantly (P

Rationale Alprazolam extended-release (XR) is approved for the treatment of panic disorder. This sustained formulation is absorbed in a delayed manner and is therefore expected to produce fewer and less severe side effects than its immediate release equivalent (alprazolam IR). The effect of alprazolam XR on potentially dangerous daily activities, such as driving a car, is expected to be less as compared to alprazolam IR. Objectives The present study was designed to compare the effects of alprazolam XR (1 mg) and alprazolam IR (1 mg) on actual driving ability and cognitive function. Method Eighteen healthy volunteers (aged 20-45 years) participated in a double-blind, placebo-controlled, three-way crossover study. At 4 h post-dose, subjects performed a standardized driving test on a primary highway in normal traffic. Cognitive and psychomotor tests were assessed 1, 2.5, and 5.5 h post-dose. Memory functioning was measured only 1 h after administration. Results Both formulations severely impaired driving performance between 4 and 5 h after administration. The magnitude of impairment in the driving test observed with alprazolam XR was about half that observed with alprazolam IR. Laboratory test results were in line with the driving data. Conclusions The acute impairing effects of alprazolam XR 1 mg on driving and psychomotor functions were generally less, as compared to its immediate-release equivalent, but still of sufficient magnitude to increase the risk of becoming involved in traffic accidents.

Many older adults report sleep problems and use of hypnotics. Several studies have shown that hypnotics can have acute adverse effects on driving the next morning. It is unclear however whether driving of chronic hypnotic users is impaired. Therapeutic effects on insomnia and development of tolerance may reduce the residual effects on driving.The present study aimed to compare actual driving performance and driving-related skills of chronic hypnotic users to good sleepers. To determine whether insomnia itself affects driving performance, driving and driving-related skills were compared between insomnia patients who do not or infrequently use hypnotics and good sleepers.Twenty-two frequent users of hypnotics (using hypnotics a parts per thousand yen4 nights per week for more than 3 months), 20 infrequent users (using hypnotics a parts per thousand currency sign3 nights per week), and 21 healthy, age-matched controls participated in this study. On the night before testing, all subjects were hospitalized for an 8-h sleep recorded by polysomnography. Frequent hypnotic users used their regular medication at bedtime (2330 hours), while infrequent users and controls received no medication. Cognitive performance (word learning, digit span, tracking, divided attention, vigilance, and inhibitory control) was assessed 8.5 h and driving performance between 10 and 11 h after bedtime and dosing.Polysomnographic recordings did not significantly differ between the groups, but the insomnia patients, treated or untreated, still reported subjective sleep complaints. Results show no differences in driving performance and driving-related skills between both groups of insomnia patients and controls.Driving performance in chronic users of hypnotics and untreated insomnia patients is not impaired. For chronic users, this may be due to prescription of relatively safe drugs and low doses. For untreated insomniacs, this corroborates previous findings showing an absence of neuropsychological deficits in this group of patients.

A major problem related to hypnotic drug use is residual sedation the morning after bedtime administration. This constitutes a particular safety hazard for patients who have to drive a car the next morning. Information on the severity of residual effects is mainly derived from studies conducted with young healthy volunteers. However, most users of hypnotics are older people who may be more sensitive to drug effects. The aim of this study was to evaluate the residual effects the morning after evening doses of temazepam 20 mg and zopiclone 7.5 mg on driving performance in healthy elderly drivers. Eighteen healthy elderly drivers (10 females and 8 males; mean age, 64.3 years) participated in a double-blind, 3-way crossover study. Treatments were single oral doses of temazepam 20 mg, zopiclone 7.5 mg, and placebo administered at bedtime. Subjects performed a standardized highway driving test between 10 and 11 hours after hypnotic intake. Before and after the driving test, cognitive performance was assessed. Driving performance did not differ between temazepam and placebo but was significantly impaired after zopiclone 7.5 mg (P

Introduction Insomnia patients consistently self-reported daytime fatigue and cognitive impairments which could contribute to traffic crashes. However, the model of hyperarousal was proposed to explain the lack of objective evidence of cognitive dysfunction in patients with primary insomnia because of the contribution of psychological and physiological arousal to daytime functioning. In this case it is not clear that insomnia patients could suffer from sleepiness which could contribute to traffic crashes. Electroencephalography recordings during driving were previously used to assess sleepiness and fatigue during a driving task. It appeared that an increase in the theta, alpha and beta band is linked to a higher fatigue. We expected that insomnia patients will not have a decrement in their driving performance associated with EEG correlates of less fatigue. The purpose of the present study was thus to compare the electroencephalographic correlates of sleepiness and fatigue during a driving task in insomniac patients and in good sleepers. Materials and methods Nineteen older insomniacs and nineteen older good sleepers were included in the study (aged between 55–75 years). After a sleep recording night in the sleep unit, the participants performed an on-the-road highway driving task in the morning. The vehicle’s speed and lateral position were continuously recorded. Electroencephalography was also recorded during the driving task. The main driving parameter was the standard deviation of the lateral position (SDLP), which is an index of weaving; the standard deviation of speed (SDS) was also quantified. The fatigue EEG correlates were assessed by quantification of the absolute power spectra in the theta, alpha and beta bands. Results Results for the SDLP and the SDS reveal that driving performance was not impaired in the insomnia group in comparison to the good sleepers group. Preliminary analysis of EEG recordings reveal that good sleepers had a higher power spectrum in the theta, alpha and beta bands. Conclusion It is concluded that older chronic insomnia patients appear to be able to successfully perform a one hour highway driving task in real traffic. EEG results suggested that insomniacs were less fatigued than good sleepers which could explain the lack of difference in the driving performance. This could be in line with the hyperarousal model proposed to explain to lack of cognitive dysfunction in insomnia patients. Acknowledgements We want to thanks Anita Van Oers for the driving data analyses, Henk Brauers and Jo Gorissen as driving instructors and student assistants for the help in the data collection.