Non-rapid Eye Movement Sleep Electroencephalogram Research Articles

0033 Dysregulated sleep and NREM sleep electroencephalogram delta power induced by intermittent hypoxia exposure are attenuated in NLRP3 knockout mice

Abstract Introduction The nucleotide-binding domain leucine rich family pyrin containing 3 (NLRP3) inflammasome protein complex activates caspase-1 to convert the pro-forms of IL-18 and IL-1 beta (IL-1β) into their active forms and is involved in homeostatic sleep and sleep responses to pathogenic stimuli. Intermittent hypoxia (IH) is a hallmark of sleep disordered breathing (SDB) and both IL-18 receptors are associated with SDB in humans. Thus, we hypothesized that NLRP3 inflammasomes are involved in SDB-related sleep disturbances. Methods Sleep architecture was assessed by polysomnography in NLRP3 knockout (KO) and wild-type (WT) mice (N = 8 per group). A gas exchange mixer delivered house air serving as a control or chronic IH that involved 90 second episodic oxygen reductions that consisted of ambient oxygen (21%) with brief hypoxic conditions (~10%) that lasted for 3 seconds for the first 10 h of the light period for 5 consecutive days. Gene expression and protein levels in the brain and lungs were assayed using real-time polymerase chain reaction and enzyme-linked immunosorbent assays, respectively. Results In WT mice, significant increased non-rapid-eye movement (NREM) sleep amounts and NREM sleep electroencephalogram delta power (0.5-4 Hz) were found after 1 day of IH compared to control conditions (p < 0.001). After 5 days of IH, WT mice showed a significant attenuation in NREM sleep amounts and NREM sleep delta power (p < 0.001) and increased wake bout frequency (p = 0.006) when compared to control conditions. However, the IH-induced NREM sleep and NREM sleep delta power enhancements and reductions were attenuated (21-35%) in NLRP3 KO mice compared to WT mice. In WT mice, NLRP3, IL-1β, IL-18 and caspase-1 gene expression, IL-1β and IL-18 protein levels, and caspase-1 activity were significantly increased in the somatosensory cortices, NTS, and lungs after both 1 and 5 days of IH when compared to control conditions (p < 0.05 for all), although NLRP3 KO mice did not exhibit significant differences in molecules downstream of NLRP3 inflammasome activation. Conclusion Our findings indicate that altered NLRP3 inflammasome activation contributes to dysregulated sleep occurring from IH and likely is involved in sleep disturbances in SDB. Support (If Any) VA Career Development Aware IBX002823, VA Merit BX004500, NIH/NIMH 1R21MH125242, NIH/NHLBI R03 HL154284, and NIH/NHLBI R35 HL135818. JTM received partial salary compensation and funding from Merck Investigator Sponsored Programs but has no conflict of interest with this work.

S6. SLEEP ENDOPHENOTYPES OF SCHIZOPHRENIA: A HIGH-DENSITY EEG STUDY IN DRUG-NAïVE, FIRST EPISODE PSYCHOSIS PATIENTS

BackgroundSlow waves, the hallmark of the deep nonrapid eye movement sleep electroencephalogram (EEG), are critical for restorative sleep and brain plasticity. They arise from the synchronous depolarization and hyperpolarization of millions of cortical neurons and their proper generation and propagation relies upon the integrity of widespread cortico-thalamic networks. Slow wave abnormalities have been reported in patient with Schizophrenia, although with partially contradictory results, probably related to antipsychotic and sedative medications. Recently, their presence and delineation, have been convincingly shown in first-episode psychosis patients (FEP). However, clear evidence of this biomarker at the onset of the disease, prior to any psychopharmacological intervention, remains limited. Moreover, no attempt has been made to elucidate the prognostic meaning of this finding.MethodsWe collected whole night sleep high–density electroencephalography recordings (64-channel BrainAmp, Brain Products GmbH, Gilching, Germany) in 20 drug-naive FEP patients and 20 healthy control subjects (HC). Several clinical psychometric scales as well as neurocognitive tests were administered to all subjects in order to better define psychopathological status and vulnerability. EEG slow wave activity (SWA, spectral power between 1 and 4 Hz) and several slow wave parameters were computed at each electrode location, including density and amplitude, at each electrode location. Along with a group analysis between FEP and HC, a subgroup analysis was also computed between patients who showed a progression of symptoms to full-blown Schizophrenia (SCZ, n = 10) over the next 12-month follow-up and those who did not (OTH, n = 10).ResultsSleep macro-architecture was globally preserved in FEP patients. SWA (1–4 Hz) was lower in FEP compared to HC but this difference didn’t reach statistical significance. Slow wave density was decreased in FEP compared to HC, with a significance that survived multiple comparison correction over a large fronto-central cluster. Mean amplitude was preserved. At the subgroup analysis, these results were largely driven by the subgroup of patients with a confirmed diagnosis of SCZ at a 12-month follow-up. Indeed, no difference could be found between OTH and HC, while a strong significance was still evident between SCZ and HC.DiscussionOur data confirm previous findings on reduced slow wave density in FEP, and expand them to acute subjects, before any treatment is prescribed. This is in line with available data on diffuse abnormalities of cortico-cortical and cortico-thalamic networks in these patients. Interestingly, our data also offer preliminary evidence that this deficit is specific for SCZ, as it appears to differentiate patients who developed SCZ from those with other diagnoses at follow-up. Given the traveling properties of slow waves, future research should establish their potential as markers of connectivity in SCZ.

NREM sleep EEG slow waves in autistic and typically developing children: Morphological characteristics and scalp distribution.

Autism is a developmental disorder with a neurobiological aetiology. Studies of the autistic brain identified atypical developmental trajectories that may lead to an impaired capacity to modulate electroencephalogram activity during sleep. We assessed the topography and characteristics of non-rapid eye movement sleep electroencephalogram slow waves in 26 boys aged between 6 and 13 years old: 13 with an autism spectrum disorder and 13 typically developing. None of the participants was medicated, intellectually disabled, reported poor sleep, or suffered from medical co-morbidities. Results are derived from a second consecutive night of polysomnography in a sleep laboratory. Slow waves (0.3-4.0 Hz; >75 µV) were automatically detected on artefact-free sections of non-rapid eye movement sleep along the anteroposterior axis in frontal, central, parietal and occipital derivations. Slow wave density (number per minute), amplitude (µV), slope (µV s-1 ) and duration (s) were computed for the first four non-rapid eye movement periods. Slow wave characteristics comparisons between groups, derivations and non-rapid eye movement periods were assessed with three-way mixed ANOVAs. Slow wave density, amplitude, slope and duration were higher in anterior compared with most posterior derivations in both groups. Children with autism spectrum disorder showed lower differences in slow waves between recording sites along the anteroposterior axis than typically developing children. These group differences in the topography of slow wave characteristics were stable across the night. We propose that slow waves during non-rapid eye movement sleep could be an electrophysiological marker of the deviant cortical maturation in autism linked to an atypical functioning of thalamo-cortical networks.

Traveling Slow Oscillations During Sleep: A Marker of Brain Connectivity in Childhood.

Slow oscillations, a defining characteristic of the nonrapid eye movement sleep electroencephalogram (EEG), proliferate across the scalp in highly reproducible patterns. In adults, the propagation of slow oscillations is a recognized fingerprint of brain connectivity and excitability. In this study, we (1) describe for the first time maturational features of sleep slow oscillation propagation in children (n = 23; 2-13 years) using high-density (hd) EEG and (2) examine associations between sleep slow oscillatory propagation characteristics (ie, distance, traveling speed, cortical involvement) and white matter myelin microstructure as measured with multicomponent Driven Equilibrium Single Pulse Observation of T1 and T2-magnetic resonance imaging (mcDESPOT-MRI). Results showed that with increasing age, slow oscillations propagated across longer distances (average growth of 0.2 cm per year; R(21) = 0.50, p < .05), while traveling speed and cortical involvement (ie, slow oscillation expanse) remained unchanged across childhood. Cortical involvement (R(20) = 0.44) and slow oscillation speed (R(20) = -0.47; both p < .05, corrected for age) were associated with myelin content in the superior longitudinal fascicle, the largest anterior-posterior, intrahemispheric white matter connectivity tract. Furthermore, slow oscillation distance was moderately associated with whole-brain (R(21) = 0.46, p < .05) and interhemispheric myelin content, the latter represented by callosal myelin water fraction (R(21) = 0.54, p < .01, uncorrected). Thus, we demonstrate age-related changes in slow oscillation propagation distance, as well as regional associations between brain activity during sleep and the anatomical connectivity of white matter microstructure. Our findings make an important contribution to knowledge of the brain connectome using a noninvasive and novel analytic approach. These data also have implications for understanding the emergence of neurodevelopmental disorders and the role of sleep in brain maturation trajectories.

Sleep spindles and rapid eye movement sleep as predictors of next morning cognitive performance in healthy middle‐aged and older participants

Spindles and slow waves are hallmarks of non-rapid eye movement sleep. Both these oscillations are markers of neuronal plasticity, and play a role in memory and cognition. Normal ageing is associated with spindle and slow wave decline and cognitive changes. The present study aimed to assess whether spindle and slow wave characteristics during a baseline night predict cognitive performance in healthy older adults the next morning. Specifically, we examined performance on tasks measuring selective and sustained visual attention, declarative verbal memory, working memory and verbal fluency. Fifty-eight healthy middle-aged and older adults (aged 50-91years) without sleep disorders underwent baseline polysomnographic sleep recording followed by neuropsychological assessment the next morning. Spindles and slow waves were detected automatically on artefact-free non-rapid eye movement sleep electroencephalogram. All-night stage N2 spindle density (no./min) and mean frequency (Hz) and all-night non-rapid eye movement sleep slow wave density (no./min) and mean slope (μV/s) were analysed. Pearson's correlations were performed between spindles, slow waves, polysomnography and cognitive performance. Higher spindle density predicted better performance on verbal learning, visual attention and verbal fluency, whereas spindle frequency and slow wave density or slope predicted fewer cognitive performance variables. In addition, rapid eye movement sleep duration was associated with better verbal learning potential. These results suggest that spindle density is a marker of cognitive functioning in older adults and may reflect neuroanatomic integrity. Rapid eye movement sleep may be a marker of age-related changes in acetylcholine transmission, which plays a role in new information encoding.

Slow oscillations in human non-rapid eye movement sleep electroencephalogram: effects of increased sleep pressure

Slow oscillations (< 1 Hz) in the non-rapid eye movement (NREM) sleep electroencephalogram (EEG) result from slow membrane potential fluctuations of cortical neurones, alternating between a depolarized up-state and a hyperpolarized down-state. They are thought to underlie the restorative function of sleep. We investigated the behaviour of slow oscillations in humans under increased sleep pressure to assess their contribution to sleep homeostasis. EEG recordings (C3A2) of baseline and recovery sleep after sleep deprivation (eight healthy males, mean age 23 years; 40 h of prolonged wakefulness) were analysed. Half-waves were defined as positive or negative deflections between consecutive zero crossings in the 0.5-2 Hz range of the band-pass filtered EEG. Increased sleep pressure resulted in a redistribution of half-waves between 0.5 and 2 Hz: the number of half-waves per minute was reduced below 0.9 Hz while it was increased above 1.2 Hz. EEG power was increased above 1 Hz. The increase in frequency was accompanied by increased slope of the half-waves and decreased number of multi-peak waves. In both baseline and recovery sleep, amplitude and slope were correlated highly over a broad frequency range and positive half-waves were characterized by a lower frequency than the negative ones, pointing to a longer duration of up- than down-states. We hypothesize that the higher frequency of slow oscillatory activity after prolonged wakefulness may relate to faster alternations between up- and down-states at the cellular level under increased sleep pressure. This study does not question slow-wave activity as a marker of sleep homeostasis, as the observed changes occurred within the same frequency range.