Angela L. D'Rozario

Adolescent Sleep Patterns and Night-Time Technology Use: Results of the Australian Broadcasting Corporation's Big Sleep Survey

Introduction Electronic devices in the bedroom are broadly linked with poor sleep in adolescents. This study investigated whether there is a dose-response relationship between use of electronic devices (computers, cellphones, televisions and radios) in bed prior to sleep and adolescent sleep patterns. Methods Adolescents aged 11–17 yrs (n = 1,184; 67.6% female) completed an Australia-wide internet survey that examined sleep patterns, sleepiness, sleep disorders, the presence of electronic devices in the bedroom and frequency of use in bed at night. Results Over 70% of adolescents reported 2 or more electronic devices in their bedroom at night. Use of devices in bed a few nights per week or more was 46.8% cellphone, 38.5% computer, 23.2% TV, and 15.8% radio. Device use had dose-dependent associations with later sleep onset on weekdays (highest-dose computer adjOR  = 3.75: 99% CI  = 2.17–6.46; cellphone 2.29: 1.22–4.30) and weekends (computer 3.68: 2.14–6.32; cellphone 3.24: 1.70–6.19; TV 2.32: 1.30–4.14), and later waking on weekdays (computer 2.08: 1.25–3.44; TV 2.31: 1.33–4.02) and weekends (computer 1.99: 1.21–3.26; cellphone 2.33: 1.33–4.08; TV 2.04: 1.18–3.55). Only ‘almost every night’ computer use (: 2.43: 1.45–4.08) was associated with short weekday sleep duration, and only ‘almost every night’ cellphone use (2.23: 1.26–3.94) was associated with wake lag (waking later on weekends). Conclusions Use of computers, cell-phones and televisions at higher doses was associated with delayed sleep/wake schedules and wake lag, potentially impairing health and educational outcomes.

Hypercapnia is a Key Correlate of EEG Activation and Daytime Sleepiness in Hypercapnic Sleep Disordered Breathing Patients

BACKGROUND The key determinants of daytime drowsiness in sleep disordered breathing (SDB) are unclear. Hypercapnia has not been examined as a potential contributor due to the lack of reliable measurement during sleep. To overcome this limitation, we studied predominantly hypercapnic SDB patients to investigate the role of hypercapnia on EEG activation and daytime sleepiness. METHODS We measured overnight polysomnography (PSG), arterial blood gases, and Epworth Sleepiness Scale in 55 severe SDB patients with obesity hypoventilation syndrome or overlap syndrome (COPD+ obstructive sleep apnea) before and ∼3 months after positive airway pressure (PAP) treatment. Quantitative EEG analyses were performed, and the Delta/ Alpha ratio was used as an indicator of EEG activation. RESULTS After the PAP treatment, these patients showed a significant decrease in their waking pCO(2), daytime sleepiness, as well as all key breathing/oxygenation parameters during sleep. Overnight Delta/Alpha ratio of EEG was significantly reduced. There is a significant cross-correlation between a reduced wake pCO(2), a faster (more activated) sleep EEG (reduced Delta/Alpha ratio) and reduced daytime sleepiness (all p < 0.05) with PAP treatment. Multiple regression analyses showed the degree of change in hypercapnia to be the only significant predictor for both ESS and Delta/ Alpha ratio. CONCLUSIONS Hypercapnia is a key correlate of EEG activation and daytime sleepiness in hypercapnic SDB patients. The relationship between hypercapnia and sleepiness may be mediated by reduced neuro-electrical brain activity.

Agreement between simple questions about sleep duration and sleep diaries in a large online survey

INTRODUCTION Self-reported habitual sleep duration has been used widely in epidemiologic research, yet this measure remains to be validated. We evaluated whether simple sleep duration questions concord with sleep diaries in an online sample. METHODS Australian adults aged 18+ years completed an internet survey examining measures of sleep, sociodemographic risk factors, and a 7-day sleep diary. We examined single-question (how many hours of sleep would you normally get?) and 2-question assessments (difference between sleep and wake times) to a 7-day sleep diary estimation of sleep duration. Using Bland-Altman plots and associated statistics, we tested systematic differences, precision, and systematic bias. We also evaluated whether the differences were consistent along the entire range of the measurement and whether they were associated with any sociodemographic risk factors (Spearman rho). RESULTS Data were analyzed from 1662 participants (67.3% female). Bland-Altman plots displayed visual discrepancies between both 1-question and 2-question reports of sleep duration compared with sleep diaries. Both the single- (-17 minutes) and double-question (8 minutes) sleep duration estimates differed significantly (both P < .001). These simple estimates only agreed to within ±2.5-3 hours compared with diary estimates. The measure was also weakly systematically biased (rho = +0.204 and +0.309, P < .001) through the measurement range. There were significant differences and associations between differences in sleep duration estimation and determinants of health. CONCLUSIONS Simple questions estimating habitual sleep duration are imprecise and systematically biased in a large online survey. The amount of difference is correlated with well-known sociodemographic risk factors.

Ethics, consent and blinding: lessons from a placebo/sham controlled CPAP crossover trial

Introduction Performing rigorously designed clinical trials in device-based treatments is challenging. Continuous positive airway pressure (CPAP) is the most effective device-based treatment for obstructive sleep apnoea. We performed a randomised crossover trial of CPAP versus placebo therapy and did not disclose the presence of placebo. We assessed rates of staff unblinding, the likelihood of patient unblinding and obtained patient perceptions on lack of full disclosure. Methods All patients (n=30) underwent a semi-structured exit interview. Prior to full disclosure patients were asked questions to ascertain whether they suspected one therapy was ineffective. The use of placebo was then disclosed and additional questions were administered to indicate the likelihood of unblinding had full disclosure occurred during consent. Staff unblinding was determined by means of a questionnaire that was completed after each patient encounter. Results While the lack of full disclosure prevented patient unblinding during the trial, patients revealed a clear preference for active CPAP. After disclosing the presence of placebo, 73% (n=22) felt they would have been unblinded had they known at the start of the trial. Only one patient described unease about the lack of full disclosure. Staff thought they were unblinded in 6% (n=16/282) of encounters. They correctly identified the treatment device in 69% of cases (n=11/16, p<0.001). Conclusions Successful patient blinding was achieved, however this was probably reliant on the lack of full disclosure. Staff unblinding occurred and highlights the difficulty with investigator blinding in device-based trials. Ethical challenges in this type of study are likely to compromise research feasibility. Trial registration number This clinical trial is registered with the Australian and New Zealand Clinical Trials Registry at http://www.anzctr.org.au (ACTRN 12605000066684).

Quantitative electroencephalogram measures in adult obstructive sleep apnea – Potential biomarkers of neurobehavioural functioning

Obstructive sleep apnea (OSA) results in significantly impaired cognitive functioning and increased daytime sleepiness in some patients leading to increased risk of motor vehicle and workplace accidents and reduced productivity. Clinicians often face difficulty in identifying which patients are at risk of neurobehavioural dysfunction due to wide inter-individual variability, and disparity between symptoms and conventional metrics of disease severity such as the apnea hypopnea index. Quantitative electroencephalogram (EEG) measures are determinants of awake neurobehavioural function in healthy subjects. However, the potential value of quantitative EEG (qEEG) measurements as biomarkers of neurobehavioural function in patients with OSA has not been examined. This review summarises the existing literature examining qEEG in OSA patients including changes in brain activity during wake and sleep states, in relation to daytime sleepiness, cognitive impairment and OSA treatment. It will speculate on the mechanisms which may underlie changes in EEG activity and discuss the potential utility of qEEG as a clinically useful predictor of neurobehavioural function in OSA.

Modafinil Increases Awake EEG Activation and Improves Performance in Obstructive Sleep Apnea during Continuous Positive Airway Pressure Withdrawal.

OBJECTIVES We examined the changes in waking electroencephalography (EEG) biomarkers with modafinil during continuous positive airway pressure (CPAP) withdrawal in patients with obstructive sleep apnea (OSA) to investigate neurophysiological evidence for potential neurocognitive improvements. DESIGN Randomized double-blind placebo-controlled crossover study. CPAP was used for the first night and then withdrawn for 2 subsequent nights. Each morning after the 2 CPAP withdrawal nights, patients received either 200 mg modafinil or placebo. After a 5-w washout, the procedure repeated with the crossover drug. SETTINGS University teaching hospital. PARTICIPANTS Stable CPAP users (n = 23 men with OSA). MEASUREMENT AND RESULTS Karolinska Drowsiness Test (KDT) (awake EEG measurement with eyes open and closed), Psychomotor Vigilance Task (PVT), and driving simulator Performance were assessed bihourly during the 3 testing days following CPAP treatment and CPAP withdrawal nights. Compared to placebo, modafinil significantly increased awake EEG activation (faster EEG frequency) with increased alpha/delta (A/D) ratio (P < 0.0001) and fast ratio = (alpha+beta)/(delta+theta) (P < 0.0001) across the 2 days of CPAP withdrawal. The A/D ratio significantly correlated with the driving simulator response time (P = 0.015), steering variation (P = 0.002), and PVT reaction time (P = 0.006). In contrast, individual EEG band power of alpha, beta, theta, and delta did not correlate with any neurocognitive performance. CONCLUSIONS Modafinil administration during continuous positive airway pressure (CPAP) withdrawal increased awake EEG activation, which correlated to improved performance. This study provides supporting neurophysiological evidence that modafinil is a potential short-term treatment option during acute CPAP withdrawal.

An Objective Short Sleep Insomnia Disorder Subtype Is Associated With Reduced Brain Metabolite Concentrations In Vivo: A Preliminary Magnetic Resonance Spectroscopy Assessment.

Objectives To evaluate brain metabolites in objective insomnia subtypes defined from polysomnography (PSG): insomnia with short sleep duration (I-SSD) and insomnia with normal sleep duration (I-NSD), relative to good sleeping controls (GSCs). Methods PSG empirically grouped insomnia patients into I-SSD (n = 12: mean [SD] total sleep time [TST] = 294.7 minutes [30.5]) or I-NSD (n = 19: TST = 394.4 minutes [34.9]). 1H magnetic resonance spectroscopy (MRS) acquired in the left occipital cortex (LOCC), left prefrontal cortex, and anterior cingulate cortex was used to determine levels of creatine, aspartate, glutamate, and glutamine (referenced to water). Glutathione, glycerophosphocholine, lactate, myoinositol, and N-acetylaspartate measurements were also obtained. Sixteen GSCs were included for comparison. Multivariate analysis of variance was used to evaluate differences in creatine, aspartate, glutamate, and glutamine. Results Aspartate and glutamine concentrations were reduced in the LOCC in I-SSD compared with I-NSD (both p < .05, d = .80-.99). Creatine displayed a nonsignificant mean reduction in I-SSD compared with I-NSD (p = .05, d = .58). Glutamine was reduced in I-SSD compared with controls (p < .05, d = .93). There were no differences in metabolites between all (I-SSD and I-NSD) insomnia patients and controls. In patients with insomnia, LOCC glutamine concentrations were found to be positively correlated with TST (r = .43, p < .05) and negatively correlated with wake-time after sleep onset (r = -.40, p < .05). Conclusions Results indicate that I-SSD is associated with reduced brain metabolites in the LOCC compared with I-NSD and control concentrations of aspartate, glutamine, and creatine. Clinical Trial Registration Insomnia MRS imaging sleep study: Australia New Zealand Clinical Trials Registry (ANZCTR): https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612000050853. Trial Identification Number 12612000050853.

K-complexes, spindles, and ERPs as impulse responses: unification via neural field theory

To interrelate K-complexes, spindles, evoked response potentials (ERPs), and spontaneous electroencephalography (EEG) using neural field theory (NFT), physiology-based NFT of the corticothalamic system is used to model cortical excitatory and inhibitory populations and thalamic relay and reticular nuclei. The impulse response function of the model is used to predict the responses to impulses, which are compared with transient waveforms in sleep studies. Fits to empirical data then allow underlying brain physiology to be inferred and compared with other waves. Spontaneous K-complexes, spindles, and other transient waveforms can be reproduced using NFT by treating them as evoked responses to impulsive stimuli with brain parameters appropriate to spontaneous EEG in sleep stage 2. Using this approach, spontaneous K-complexes and sleep spindles can be analyzed using the same single theory as previously been used to account for waking ERPs and other EEG phenomena. As a result, NFT can explain a wide variety of transient waveforms that have only been phenomenologically classified to date. This enables noninvasive fitting to be used to infer underlying physiological parameters. This physiology-based model reproduces the time series of different transient EEG waveforms; it has previously reproduced experimental EEG spectra, and waking ERPs, and many other observations, thereby unifying transient sleep waveforms with these phenomena.

Effect of 1 month of zopiclone on obstructive sleep apnoea severity and symptoms: a randomised controlled trial

Hypnotic use in obstructive sleep apnoea (OSA) is contraindicated due to safety concerns. Recent studies indicate that single-night hypnotic use worsens hypoxaemia in some and reduces OSA severity in others depending on differences in pathophysiology. However, longer clinical trial data are lacking. This study aimed to determine the effects of 1 month of zopiclone on OSA severity, sleepiness and alertness in patients with low–moderate respiratory arousal thresholds without major overnight hypoxaemia. 69 participants completed a physiology screening night with an epiglottic catheter to quantify arousal threshold. 30 eligible patients (apnoea–hypopnoea index (AHI) 22±11 events·h−1) then completed standard in-laboratory polysomnography (baseline) and returned for two additional overnight sleep studies (nights 1 and 30) after receiving either nightly zopiclone (7.5 mg) or placebo during a 1-month, double-blind, randomised, parallel trial (ANZCTR identifier ANZCTRN12613001106729). The change in AHI from baseline to night 30 was not different between zopiclone versus placebo groups (−5.9±10.2 versus −2.4±5.5 events·h−1; p=0.24). Similarly, hypoxaemia, next-day sleepiness and driving simulator performance were not different. 1 month of zopiclone does not worsen OSA severity, sleepiness or alertness in selected patients without major overnight hypoxaemia. As the first study to assess the effect of a hypnotic on OSA severity and sleepiness beyond single-night studies, these findings provide important safety data and insight into OSA pathophysiology. 1 month of nightly zopiclone does not worsen OSA severity or symptoms in individuals with low–moderate arousal thresholds http://ow.ly/9JD230khJpl

Impaired Neurobehavioural Performance in Untreated Obstructive Sleep Apnea Patients Using a Novel Standardised Test Battery

Objective/Background Although polysomnography (PSG) is the gold-standard measure for assessing disease severity in obstructive sleep apnea (OSA), it has limited value in identifying individuals experiencing significant neurobehavioural dysfunction. This study used a brief and novel computerised test battery to examine neurobehavioural function in adults with and without OSA. Patients/Methods 204 patients with untreated OSA [age 49.3 (12.5) years; body mass index, [BMI] 33.6 (8.0) kg/m2; Epworth sleepiness scale 12 (4.9)/24; apnea hypopnea index 33.6 (25.8)/h] and 50 non-OSA participants [age 39.2 (14.0) years; BMI 25.8 (4.2) kg/m2, ESS 3.6 (2.3)/24]. All participants completed a computerised neurobehavioural battery during the daytime in the sleep clinic. The OSA group subsequently underwent an overnight PSG. The 30 min test battery assessed cognitive domains of visual spatial scanning and selective attention (Letter Cancellation Test), executive function (Stroop task) and working memory (2- and 3-Back tasks), and a validated sustained attention task (psychomotor vigilance task, PVT). Group differences in performance were compared. Associations between disease severity and performance were examined in the OSA group. Results After controlling for age, gender and education, OSA patients demonstrated impaired performance on the Stroop-Text, 2 and 3-Back tasks, and the PVT compared with the non-OSA group. OSA patients had worse performance on the LCT with fewer average hits albeit with better accuracy. Some OSA polysomnographic disease severity measures were weakly correlated with performance. Conclusions This brief test battery may provide a sensitive, standardised method of assessing daytime dysfunction in OSA.