Melinda L. Jackson

Magnetic resonance spectroscopy and neurocognitive dysfunction in obstructive sleep apnea before and after CPAP treatment

STUDY OBJECTIVES To determine whether cerebral metabolite changes may underlie abnormalities of neurocognitive function and respiratory control in OSA. DESIGN Observational, before and after CPAP treatment. SETTING Two tertiary hospital research institutes. PARTICIPANTS 30 untreated severe OSA patients, and 25 age-matched healthy controls, all males free of comorbidities, and all having had detailed structural brain analysis using voxel-based morphometry (VBM). MEASUREMENTS AND RESULTS Single voxel bilateral hippocampal and brainstem, and multivoxel frontal metabolite concentrations were measured using magnetic resonance spectroscopy (MRS) in a high resolution (3T) scanner. Subjects also completed a battery of neurocognitive tests. Patients had repeat testing after 6 months of CPAP. There were significant differences at baseline in frontal N-acetylaspartate/choline (NAA/Cho) ratios (patients [mean (SD)] 4.56 [0.41], controls 4.92 [0.44], P = 0.001), and in hippocampal choline/creatine (Cho/Cr) ratios (0.38 [0.04] vs 0.41 [0.04], P = 0.006), (both ANCOVA, with age and premorbid IQ as covariates). No longitudinal changes were seen with treatment (n = 27, paired t tests), however the hippocampal differences were no longer significant at 6 months, and frontal NAA/Cr ratios were now also significantly different (patients 1.55 [0.13] vs control 1.65 [0.18] P = 0.01). No significant correlations were found between spectroscopy results and neurocognitive test results, but significant negative correlations were seen between arousal index and frontal NAA/Cho (r = -0.39, corrected P = 0.033) and between % total sleep time at SpO(2) < 90% and hippocampal Cho/Cr (r = -0.40, corrected P = 0.01). CONCLUSIONS OSA patients have brain metabolite changes detected by MRS, suggestive of decreased frontal lobe neuronal viability and integrity, and decreased hippocampal membrane turnover. These regions have previously been shown to have no gross structural lesions using VBM. Little change was seen with treatment with CPAP for 6 months. No correlation of metabolite concentrations was seen with results on neurocognitive tests, but there were significant negative correlations with OSA severity as measured by severity of nocturnal hypoxemia.

Feedback blunting: total sleep deprivation impairs decision making that requires updating based on feedback

STUDY OBJECTIVES To better understand the sometimes catastrophic effects of sleep loss on naturalistic decision making, we investigated effects of sleep deprivation on decision making in a reversal learning paradigm requiring acquisition and updating of information based on outcome feedback. DESIGN Subjects were randomized to a sleep deprivation or control condition, with performance testing at baseline, after 2 nights of total sleep deprivation (or rested control), and following 2 nights of recovery sleep. Subjects performed a decision task involving initial learning of go and no go response sets followed by unannounced reversal of contingencies, requiring use of outcome feedback for decisions. A working memory scanning task and psychomotor vigilance test were also administered. SETTING Six consecutive days and nights in a controlled laboratory environment with continuous behavioral monitoring. SUBJECTS Twenty-six subjects (22-40 y of age; 10 women). INTERVENTIONS Thirteen subjects were randomized to a 62-h total sleep deprivation condition; the others were controls. MEASUREMENTS AND RESULTS Unlike controls, sleep deprived subjects had difficulty with initial learning of go and no go stimuli sets and had profound impairment adapting to reversal. Skin conductance responses to outcome feedback were diminished, indicating blunted affective reactions to feedback accompanying sleep deprivation. Working memory scanning performance was not significantly affected by sleep deprivation. And although sleep deprived subjects showed expected attentional lapses, these could not account for impairments in reversal learning decision making. CONCLUSIONS Sleep deprivation is particularly problematic for decision making involving uncertainty and unexpected change. Blunted reactions to feedback while sleep deprived underlie failures to adapt to uncertainty and changing contingencies. Thus, an error may register, but with diminished effect because of reduced affective valence of the feedback or because the feedback is not cognitively bound with the choice. This has important implications for understanding and managing sleep loss-induced cognitive impairment in emergency response, disaster management, military operations, and other dynamic real-world settings with uncertain outcomes and imperfect information.

Sleep Abnormalities in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Review

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a chronic, disabling illness that affects approximately 0.2% of the population. Non-restorative sleep despite sufficient or extended total sleep time is one of the major clinical diagnostic criteria; however, the underlying cause of this symptom is unknown. This review aims to provide a comprehensive overview of the literature examining sleep in CFS/ME and the issues surrounding the current research findings. Polysomnographic and other objective measures of sleep have observed few differences in sleep parameters between CFS/ME patients and healthy controls, although some discrepancies do exist. This lack of significant objective differences contrasts with the common subjective complaints of disturbed and unrefreshed sleep by CFS/ME patients. The emergence of new, more sensitive techniques that examine the microstructure of sleep are showing promise for detecting differences in sleep between patients and healthy individuals. There is preliminary evidence that alterations in sleep stage transitions and sleep instability, and other physiological mechanisms, such as heart rate variability and altered cortisol profiles, may be evident. Future research investigating the etiology of non-restorative sleep in CFS/ME may also help us to undercover the causes of non-restorative sleep and fatigue in other medical conditions.

Investigation of the effectiveness of a split sleep schedule in sustaining sleep and maintaining performance

Shift work is common in today’s society, and is associated with negative health outcomes, and accidents and incidents. These detrimental effects can be primarily attributed to sleeping and working at an adverse circadian time. The aim of this study was to examine whether a split sleep schedule is as effective as a consolidated day shift or night shift schedule for maintaining performance and sustaining sleep. Fifty-three healthy male volunteers (mean ± SD age = 26.51 ± 4.07 years) underwent a randomized three condition study design. A split sleep condition involving two 5-h sleeping opportunities in 24 h [time in bed (TIB) 0300 h–0800 h and 1500 h–2000 h] was compared to a 10-h consolidated nighttime sleep (TIB 2200 h–0800 h) and 10-h consolidated daytime sleep (TIB 1000 h–2000 h). All participants underwent a baseline period of 10 h of nocturnal time in bed (TIB) followed by a 5-d simulated workweek spent in one of the three conditions. Polysomnography, psychomotor vigilance task, digit-symbol substitution task and subjective state were assessed. During the 5-d simulated workweek, participants in the nighttime sleep condition slept the most (total sleep time per day (TST) 8.4 h ± 13.4 min), followed by the split sleep condition (TST 7.16 h ± 14.2 min) and the daytime sleep condition (TST 6.4 h ± 15.3 min). Subjective sleepiness was highest in the daytime sleep condition and lowest in the nighttime sleep condition. No significant differences in performance were observed between the conditions. Compared to a nighttime consolidated sleep opportunity or split sleep, placement of a consolidated sleep opportunity during the day yielded truncated sleep and increased sleepiness. Further research in real-world situations is warranted to fully assess the efficacy of alternative split sleep schedules for improving safety and productivity.

A systematic review of acupuncture for sleep quality in people with insomnia.

OBJECTIVE Acupuncture is widely used in Asia and increasingly in Western countries. We performed a systematic review and meta-analysis to examine the effects of acupuncture for insomnia. METHODS We identified randomized controlled trials from English and Chinese databases. Data were extracted using a predefined form and analysed using RevMan 5.2. We included studies that compared acupuncture to sham/placebo, standard pharmacotherapy or cognitive behavioral therapy. Risk of bias was assessed using the Cochrane risk of bias tool. The primary outcome was sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI). RESULTS A total of 30 studies involving 2363 participants were included. Acupuncture point combinations included the use of at least one of the recommended points for insomnia, HT7, GV20, SP6. Pharmacotherapy control was used in 27 studies and sham/placebo in three studies. Cognitive behavioral therapy was not used in any of the studies. Pharmacotherapies in all studies were benzodiazepine receptor agonists, except for one that used an antidepressant. Acupuncture was superior to sham/placebo in terms of PSQI (MD -0.79, 95% CI -1.38, -0.19, I(2)=49%). Acupuncture was also more effective than pharmacotherapy (MD -2.76, 95% CI -3.67, -1.85, I(2)=94%). Most studies were at risk of bias. Some mild adverse events were reported but they were not causally related to the acupuncture treatments. CONCLUSIONS Acupuncture compared to sham/placebo and pharmacotherapy showed statistically significant results. However, the evidence is limited by bias in the included studies and heterogeneity. Well-designed studies are needed to confirm the results identified in this review.

The utility of automated measures of ocular metrics for detecting driver drowsiness during extended wakefulness.

Slowed eyelid closure coupled with increased duration and frequency of closure is associated with drowsiness. This study assessed the utility of two devices for automated measurement of slow eyelid closure in a standard poor performance condition (alcohol) and following 12-h sleep deprivation. Twenty-two healthy participants (mean age=20.8 (SD 1.9) years) with no history of sleep disorders participated in the study. Participants underwent one baseline and one counterbalanced session each over two weeks; one 24-hour period of sleep deprivation, and one daytime session during which alcohol was consumed after a normal night of sleep. Participants completed a test battery consisting of a 30-min simulated driving task, a 10-min Psychomotor Vigilance Task (PVT) and the Karolinska Sleepiness Scale (KSS) each in two baseline sessions, and in two randomised, counterbalanced experimental sessions; following sleep deprivation and following alcohol consumption. Eyelid closure was measured during both tasks using two automated devices (Copilot and Optalert™). There was an increase in the proportion of time with eyelids closed and the Johns Drowsiness Score (incorporating relative velocity of eyelid movements) following sleep deprivation using Optalert (p<0.05 for both). These measures correlated significantly with crashes, PVT lapses and subjective sleepiness (r-values 0.46-0.69, p<0.05). No difference between the two sessions for PERCLOS recorded during the PVT or the driving task as measured by the Copilot. The duration of eyelid closure predicted frequent lapses following sleep deprivation (which were equivalent to the average lapses at a blood alcohol concentration of 0.05% - area under curve for ROC curve 0.87, p<0.01). The duration of time with slow eyelid closure, assessed by the automated devices, increased following sleep deprivation and was associated with deterioration in psychomotor performance and subjective sleepiness. Comprehensive algorithms inclusive of ocular parameters may be a better indicator of performance impairment following sleep loss.

Efficacy of sleep position modification to treat positional obstructive sleep apnea

OBJECTIVE/BACKGROUND To assess the feasibility and efficacy of sleep position modification in preventing supine sleep and improving sleep-disordered breathing and relevant clinical outcomes in positional obstructive sleep apnea (OSA) patients. PATIENTS/METHODS Eighty-six consecutive participants with moderate positional OSA on routine diagnostic polysomnography underwent a randomized controlled parallel group design trial of 4-weeks treatment using a sleep position modification device (active) or sleep hygiene advice (control). Outcomes were measured at baseline and following a 4-week treatment period. RESULTS There was a significant reduction in the amount of supine sleep in the active group (mean ± SD change from baseline, active group 99.5 ± 85.2 minutes, control group 68.6 ± 103.2 minutes, p = 0.002), and an improvement in apnea-hypopnea index (AHI) (active group reduced by 9.9 ± 11.6, control group reduced by 5.3 ± 13.9, p = 0.013). Post-hoc analyses indicated that positional therapy was most effective for patients with baseline AHI cut-off above 20 (p = 0.02). Logistic regression showed that a treatment response (AHI < 10) was more likely in the active group (OR = 5.57), and those with higher baseline nadir oxygen desaturation (OR = 1.95) and non-supine AHI (OR = 0.55). There were no significant improvements in quality of life, daytime sleepiness, mood, symptoms, neuropsychological measures or blood pressure in the active group. CONCLUSIONS The position device utilized in this study was effective in reducing supine sleep and AHI, which was significant in those with baseline AHI ≥20. Longer duration studies of physical treatments that modify sleep position are needed to explore further whether additional clinical benefits in are achievable.

The accuracy of eyelid movement parameters for drowsiness detection

STUDY OBJECTIVES Drowsiness is a major risk factor for motor vehicle and occupational accidents. Real-time objective indicators of drowsiness could potentially identify drowsy individuals with the goal of intervening before an accident occurs. Several ocular measures are promising objective indicators of drowsiness; however, there is a lack of studies evaluating their accuracy for detecting behavioral impairment due to drowsiness in real time. METHODS In this study, eye movement parameters were measured during vigilance tasks following restricted sleep and in a rested state (n = 33 participants) at three testing points (n = 71 data points) to compare ocular measures to a gold standard measure of drowsiness (OSLER). The utility of these parameters for detecting drowsiness-related errors was evaluated using receiver operating characteristic curves (ROC) (adjusted by clustering for participant) and identification of optimal cutoff levels for identifying frequent drowsiness-related errors (4 missed signals in a minute using OSLER). Their accuracy was tested for detecting increasing frequencies of behavioral lapses on a different task (psychomotor vigilance task [PVT]). RESULTS Ocular variables which measured the average duration of eyelid closure (inter-event duration [IED]) and the ratio of the amplitude to velocity of eyelid closure were reliable indicators of frequent errors (area under the curve for ROC of 0.73 to 0.83, p < 0.05). IED produced a sensitivity and specificity of 71% and 88% for detecting ≥ 3 lapses (PVT) in a minute and 100% and 86% for ≥ 5 lapses. A composite measure of several eye movement characteristics (Johns Drowsiness Scale) provided sensitivities of 77% and 100% for detecting 3 and ≥ 5 lapses in a minute, with specificities of 85% and 83%, respectively. CONCLUSIONS Ocular measures, particularly those measuring the average duration of episodes of eye closure are promising real-time indicators of drowsiness.

The effects of a 30-minute napping opportunity during an actual night shift on performance and sleepiness in shift workers∗∗

Sleepiness due to sleep loss and circadian factors can have a detrimental effect on performance, and contribute to road and workplace accidents. A brief nap taken during or immediately before a night shift may alleviate sleepiness both at work and on the road after work. This study investigated the effects of a 30-minute napping opportunity before or during an actual night shift. Performance was evaluated in three repeated-measures, crossover conditions; a nap prior to night shift (20:15 h), a nap during night shift (04:00 h) and no nap. Eight healthy nightshift workers completed a simulated driving task, the Psychomotor Vigilance Task and the Karolinska Sleepiness Scale at the start, end, and during an actual night shift. No significant improvement in performance was observed at the end of the night shift in either nap condition. A 30-minute napping opportunity was not sufficient to overcome the deleterious effects of sleep loss and circadian effects on performance during a first night shift, with no prior daytime sleep.

Slow eyelid closure as a measure of driver drowsiness and its relationship to performance

ABSTRACT Objective: Slow eyelid closure is recognized as an indicator of sleepiness in sleep-deprived individuals, although automated ocular devices are not well validated. This study aimed to determine whether changes in eyelid closure are evident following acute sleep deprivation as assessed by an automated device and how ocular parameters relate to performance after sleep deprivation. Methods: Twelve healthy professional drivers (45.58 ± 10.93 years) completed 2 randomized sessions: After a normal night of sleep and after 24 h of total sleep deprivation. Slow eye closure (PERCLOS) was measured while drivers performed a simulated driving task. Results: Following sleep deprivation, drivers displayed significantly more eyelid closure (P < .05), greater variation in lane position (P < .01) and more attentional lapses (P < .05) compared to after normal sleep. PERCLOS was moderately associated with variability in both vigilance performance (r = 0.68, P < .05) and variation in lane position on the driving task (r = 0.61, P < .05). Conclusions: Automated ocular measurement appears to be an effective means of detecting impairment due to sleep loss in the laboratory.