Improvements in Cognitive Function and Quantitative Sleep EEG in OSA after Six Months of CPAP Treatment

Study Objectives Untreated obstructive sleep apnea (OSA) is associated with cognitive deficits and altered brain electrophysiology. We evaluated the effect of continuous positive airway pressure (CPAP) treatment on quantitative sleep electroencephalogram (EEG) measures and cognitive function. Methods We studied 162 OSA patients (age 50±13, AHI 35.0±26.8) before and after 6 months of CPAP. Cognitive tests assessed working memory, sustained attention, visuospatial scanning and executive function. All participants underwent overnight polysomnography at baseline and after CPAP. Power spectral analysis was performed on EEG data (C3-M2) in a sub-set of 90 participants. Relative delta EEG power and sigma power in NREM and EEG slowing in REM were calculated. Spindle densities (events p/min) in N2 were also derived using automated spindle event detection. All outcomes were analysed as change from baseline. Results Cognitive function across all cognitive domains improved after six months of CPAP. In our sub-set, increased relative delta power (p<0.0001) and reduced sigma power (p=0.001) during NREM were observed after the 6-month treatment period. Overall, fast and slow sleep spindle densities during N2 were increased after treatment. Conclusions Cognitive performance was improved and sleep EEG features were enhanced when assessing the effects of CPAP. These findings suggest the reversibility of cognitive deficits and altered brain electrophysiology observed in untreated OSA following six months of treatment.

Systematic Review and Meta-analysis of Efficacy and Safety of Melatonin and Triclofos for Inducing Adequate Sedation for Sleep Electroencephalogram in Children

Introduction Triclofos and melatonin are commonly used oral sedatives in children for obtaining a sleep electroencephalogram (EEG) record. There has been no systematic review till now to compare the efficacy and safety of these two medications. Objectives The review intended to compare the efficacy of oral triclofos and melatonin in children <18 years of age for inducing adequate sedation for obtaining a sleep EEG record. We also attempted to compare the adverse effects, impact on EEG record, the yield of epileptiform abnormalities, and sleep onset latency in both groups. Methods A systematic search was conducted on “MEDLINE/PUBMED, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Web of Science, and Google Scholar” till November 30, 2020, with the following keywords/the Medical Subject Headings (MESH) terms while searching: “sleep EEG,” “electroencephalogram,” “triclofos,” “melatonin” OR “ramelteon” AND “epilepsy,” “seizure,” OR “convulsion.” ROB 2.0 and ROBINS-I tool was used to determine the risk of bias. To assess heterogeneity in studies, Higgins and Thompson's I 2 method was utilized. When I 2 was more than 50%, a random effects model was utilized and a fixed-effect model was used for other parameters. To assess the presence of publication bias, Egger's test was used. Results For describing the efficacy of triclofos in 1,284 and melatonin in 1,532 children, we selected 16 articles. The indirect comparison between the pooled estimate of all children receiving individual medications revealed comparable efficacy in obtaining successful sleep EEG record with a single dose (90 vs. 76%, p = 0.058) and repeat dose (p = 0.054), detection of epileptiform abnormalities (p = 0.06), and sleep onset latency (p = 0.06), but more proportion of children receiving triclofos had adverse effects (p = 0.001) and duration of sleep was also higher with triclofos (p = 0.001). Conclusion Efficacy of triclofos and melatonin are comparable in inducing sleep for recording EEG in children, although triclofos is more likely to cause adverse effects. However, the level of evidence is low for this conclusion and the weak strength of recommendation for the results of this review is likely to change in the future after completion of controlled trials exploring these two medications.

The sleep EEG envelope: a novel, neuronal firing-based human biomarker

Sleep EEG reflects instantaneous voltage differences relative to a reference, while its spectrum reflects the degree to which it is comprised of oscillations at various frequencies. In contrast, the envelope of the sleep EEG reflects the instantaneous amplitude of oscillations at specific frequencies, and its spectrum reflects the rhythmicity of the occurrence of these oscillations. The ordinary sleep EEG and its spectrum have been extensively studied and its individual stability and relationship to various demographic characteristics, psychological traits and pathologies is well known. In contrast, the envelope spectrum has not been extensively studied before. In two studies, we explored the generating mechanisms and utility of studying the envelope of the sleep EEG. First, we used human invasive data from cortex-penetrating microelectrodes and subdural grids to demonstrate that the sleep EEG envelope spectrum reflects local neuronal firing. Second, we used a large database of healthy volunteers to demonstrate that the scalp EEG envelope spectrum is highly stable within individuals, especially in NREM sleep, and that it is affected by age and sex. Multivariate models based on a learning algorithm could predict both age (r=0.6) and sex (r=0.5) with considerable accuracy from the EEG envelope spectrum. With age, oscillations characteristically shifted from a 4-5 second rhythm to higher rhythms. The envelope spectrum was not associated with general cognitive ability (IQ). Our results demonstrate that the sleep envelope spectrum is a promising, neuronal firing-based biomarker of various demographic and disease-related phenotypes.

Preliminary Study on Changes of Sleep EEG Power and Plasma Melatonin in Male Patients With Major Depressive Disorder After 8 Weeks Treatment

Objective: To clarify the effects of escitalopram on sleep EEG power in patients with Major depressive disorder (MDD).Method: Polysomnography (PSG) was detected overnight, and blood samples were collected at 4 h intervals over 24 h from 13 male healthy controls and 13 male MDD patients before and after treatment with escitalopram for 8 weeks. The outcome measures included plasma melatonin levels, sleep architecture, and the sleep EEG power ratio.Results: Compared with healthy controls, MDD patients presented abnormalities in the diurnal rhythm of melatonin secretion, including peak phase delayed 3 h and a decrease in plasma melatonin levels at night and an increase at daytime, accompanied by sleep disturbances, a decrease in low-frequency bands and an increase in high-frequency bands, and the dominant right-side brain activity. Several of these abnormalities (abnormalities in the diurnal rhythm of melatonin secretion, partial sleep architecture parameters) persisted for at least the 8-week testing period.Conclusions: Eight weeks of treatment with escitalopram significantly improved subjective sleep perception and depressive symptoms of patients with MDD, and partially improved objective sleep parameters, while the improvement of circadian rhythm of melatonin was limited.

Sources of variation in the spectral slope of the sleep EEG

Building on previous work linking changes in the electroencephalogram (EEG) spectral slope to arousal level, Lendner et al. (2021) reported that wake, non rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep exhibit progressively steeper 30-45 Hz slopes, interpreted in terms of increasing cortical inhibition. Here we sought to replicate Lendner et al.'s scalp EEG findings (based on 20 individuals) in a larger sample of 11,630 individuals from multiple cohorts in the National Sleep Research Resource (NSRR). In a final analytic sample of N = 10,255 distinct recordings, there was unambiguous statistical support for the hypothesis that, within individuals, the mean spectral slope grows steeper going from wake to NREM to REM sleep. We found that the choice of mastoid referencing scheme modulated the extent to which electromyogenic or electrocardiographic artifacts were likely to bias 30-45 Hz slope estimates, as well as other sources of technical, device-specific bias. Nonetheless, within individuals, slope estimates were relatively stable over time. Both cross-sectionally and longitudinal, slopes tended to become shallower with increasing age, particularly for REM sleep; males tended to show flatter slopes than females across all states. Although conceptually distinct, spectral slope did not predict sleep state substantially better than other summaries of the high frequency EEG power spectrum (>20 Hz, in this context) including beta band power, however. Finally, to more fully describe sources of variation in the spectral slope and its relationship to other sleep parameters, we quantified state-dependent differences in the variances (both within and between individuals) of spectral slope, power and interhemispheric coherence, as well as their covariances. In contrast to the common conception of the REM EEG as relatively wake-like (i.e. 'paradoxical' sleep), REM and wake were the most divergent states for multiple metrics, with NREM exhibiting intermediate profiles. Under a simplified modelling framework, changes in spectral slope could not, by themselves, fully account for the observed differences between states, if assuming a strict power law model. Although the spectral slope is an appealing, theoretically inspired parameterization of the sleep EEG, here we underscore some practical considerations that should be borne in mind when applying it in diverse datasets. Future work will be needed to fully characterize state-dependent changes in the aperiodic portions of the EEG power spectra, which appear to be consistent with, albeit not fully explained by, changes in the spectral slope.

Pediatric Sleep Apnea: The Overnight Electroencephalogram as a Phenotypic Biomarker

Pediatric obstructive sleep apnea (OSA) is a prevalent disorder that disrupts sleep and is associated with neurocognitive and behavioral negative consequences, potentially hampering the development of children for years. However, its relationships with sleep electroencephalogram (EEG) have been scarcely investigated. Here, our main objective was to characterize the overnight EEG of OSA-affected children and its putative relationships with polysomnographic measures and cognitive functions. A two-step analysis involving 294 children (176 controls, 57% males, age range: 5–9 years) was conducted for this purpose. First, the activity and irregularity of overnight EEG spectrum were characterized in the typical frequency bands by means of relative spectral power and spectral entropy, respectively: δ1 (0.1–2 Hz), δ2 (2–4 Hz), θ (4–8 Hz), α (8–13 Hz), σ (10–16 Hz), β1 (13–19 Hz), β2 (19–30 Hz), and γ (30–70 Hz). Then, a correlation network analysis was conducted to evaluate relationships between them, six polysomnography variables (apnea–hypopnea index, respiratory arousal index, spontaneous arousal index, overnight minimum blood oxygen saturation, wake time after sleep onset, and sleep efficiency), and six cognitive scores (differential ability scales, Peabody picture vocabulary test, expressive vocabulary test, design copying, phonological processing, and tower test). We found that as the severity of the disease increases, OSA broadly affects sleep EEG to the point that the information from the different frequency bands becomes more similar, regardless of activity or irregularity. EEG activity and irregularity information from the most severely affected children were significantly associated with polysomnographic variables, which were coherent with both micro and macro sleep disruptions. We hypothesize that the EEG changes caused by OSA could be related to the occurrence of respiratory-related arousals, as well as thalamic inhibition in the slow oscillation generation due to increases in arousal levels aimed at recovery from respiratory events. Furthermore, relationships between sleep EEG and cognitive scores emerged regarding language, visual–spatial processing, and executive function with pronounced associations found with EEG irregularity in δ1 (Peabody picture vocabulary test and expressive vocabulary test maximum absolute correlations 0.61 and 0.54) and β2 (phonological processing, 0.74; design copying, 0.65; and Tow 0.52). Our results show that overnight EEG informs both sleep alterations and cognitive effects of pediatric OSA. Moreover, EEG irregularity provides new information that complements and expands the classic EEG activity analysis. These findings lay the foundation for the use of sleep EEG to assess cognitive changes in pediatric OSA.