EEG Slow Waves Research Articles

Lavender improves sleep through olfactory perception and GABAergic neurons of the central amygdala

Ethnopharmacological relevanceThe use of lavender as sleep aid or hypnotic agent can be traced back as early as ancient Romans and Greeks. Yet, objective experimental data on whether and how lavender enhances sleep duration or/and sleep quality remain lacking. Aim of the studyWe aimed to characterize the sleep-wake regulating effects of lavender in the mouse and to demonstrate the brain targets and neural circuits involved. Materials and methodsA self-made precise odor delivery system combined with chronic polysomnographic recordings was employed to assess the sleep-wake effects of inhalation with lavender essential oil (LEO, extracted from lavender) and its different constituents during the light and dark phases in free-moving C57BL/6J mice. Neuroviral labeling, in situ hybridization and pharmacogenetics were combined to identify the neural circuits and targets involved. Finally, an insomniac model of DL-4-Chlorophenylalanine (PCPA)-treated mice was established to examine the sleep-inducing potential of LEO. ResultsWe found that inhalation of LEO with a concentration at 25.0% during the light (inactive) phase significantly shortened the latency to non-rapid eye movement (NREM) sleep, increased the total amount of NREM sleep at the expense of wakefulness (W), and enhanced cortical EEG slow wave activities, notably delta power spectra density. We further identified linalool, d-limonene, 1,8-cineole, linalyl acetate and terpinene-4-ol as the major effective sleep-promoting monomer components. Importantly, we found that LEO no longer produced any of the above sleep-promoting effect following either nasal injection of zinc sulfate which interrupts the olfactory pathway, or pharmacogenetics silencing of central amygdala GABAergic neurons. Finally, LEO reestablished NREM sleep with short latency in PCPA-treated insomniac mice, effects comparable with those induced by a potent sedative diazepam. ConclusionsWe have characterized the quantitative and qualitative sleep-promoting effects of LEO and its effective components via the olfactory pathway and central amygdala GABA neuronal targets. The hypnotic property of LEO is reinforced by its ability to restore sleep in insomnia. Our study thus establishes a neurobiological basis for aromatherapy of sleep disorders using lavender.

The stability of slow-wave sleep and EEG oscillations across two consecutive nights of laboratory polysomnography in cognitively normal older adults.

Laboratory polysomnography provides gold-standard measures of sleep physiology, but multi-night investigations are resource intensive. We assessed the night-to-night stability via reproducibility metrics for sleep macrostructure and electroencephalography oscillations in a group of cognitively normal adults attending two consecutive polysomnographies. Electroencephalographies were analysed using an automatic algorithm for detection of slow-wave activity, spindle and K-complex densities. Average differences between nights for sleep macrostructure, electroencephalography oscillations and sleep apnea severity were assessed, and test-retest reliability was determined using two-way intraclass correlations. Agreement was calculated using the smallest real differences between nights for all measures. Night 2 polysomnographies showed significantly greater time in bed, total sleep time (6.3 hr versus 6.8 hr, p < 0.001) and percentage of rapid eye movement sleep (17.5 versus 19.7, p < 0.001). Intraclass correlations were low for total sleep time, percentage of rapid eye movement sleep and sleep efficiency, moderate for percentage of slow-wave sleep and percentage of non-rapid eye movement 2 sleep, good for slow-wave activity and K-complex densities, and excellent for spindles and apnea-hypopnea index with hypopneas defined according to 4% oxygen desaturation criteria only. The smallest real difference values were proportionally high for most sleep macrostructure measures, indicating moderate agreement, and proportionally lower for most electroencephalography microstructure variables. Slow waves, K-complexes, spindles and apnea severity indices are highly reproducible across two consecutive nights of polysomnography. In contrast, sleep macrostructure measures all demonstrated poor reproducibility as indicated by low intraclass correlation values and moderate agreement. Although there were average differences in percentage of rapid eye movement sleep and total sleep time, these were numerically small and perhaps functionally or clinically less significant. One night of in-laboratory polysomnography is enough to provide stable, reproducible estimates of an individual's sleep concerning measures of slow-wave activity, spindles, K-complex densities and apnea severity.

Propofol enhancement of slow wave sleep to target the nexus of geriatric depression and cognitive dysfunction: protocol for a phase I open label trial

IntroductionLate-life treatment-resistant depression (LL-TRD) is common and increases risk for accelerated ageing and cognitive decline. Impaired sleep is common in LL-TRD and is a risk factor for cognitive decline. Slow...

Daytime dexmedetomidine sedation with closed-loop acoustic stimulation alters slow wave sleep homeostasis in healthy adults

BackgroundThe alpha-2 adrenergic agonist dexmedetomidine induces EEG patterns resembling those of non-rapid eye movement (NREM) sleep. Fulfilment of slow wave sleep (SWS) homeostatic needs would address the assumption that dexmedetomidine induces functional biomimetic sleep states. MethodsIn-home sleep EEG recordings were obtained from 13 healthy participants before and after dexmedetomidine sedation. Dexmedetomidine target-controlled infusions and closed-loop acoustic stimulation were implemented to induce and enhance EEG slow waves, respectively. EEG recordings during sedation and sleep were staged using modified American Academy of Sleep Medicine criteria. Slow wave activity (EEG power from 0.5 to 4 Hz) was computed for NREM stage 2 (N2) and NREM stage 3 (N3/SWS) epochs, with the aggregate partitioned into quintiles by time. The first slow wave activity quintile served as a surrogate for slow wave pressure, and the difference between the first and fifth quintiles as a measure of slow wave pressure dissipation. ResultsCompared with pre-sedation sleep, post-sedation sleep showed reduced N3 duration (mean difference of −17.1 min, 95% confidence interval −30.0 to −8.2, P=0.015). Dissipation of slow wave pressure was reduced (P=0.02). Changes in combined durations of N2 and N3 between pre- and post-sedation sleep correlated with total dexmedetomidine dose, (r=−0.61, P=0.03). ConclusionsDaytime dexmedetomidine sedation and closed-loop acoustic stimulation targeting EEG slow waves reduced N3/SWS duration and measures of slow wave pressure dissipation on the post-sedation night in healthy young adults. Thus, the paired intervention induces sleep-like states that fulfil certain homeostatic NREM sleep needs in healthy young adults. Clinical trial registrationClinicalTrials.gov NCT04206059.

Thermoneutral temperature exposure enhances slow-wave sleep with a correlated improvement in amyloid pathology in a triple-transgenic mouse model of Alzheimer's disease.

Accumulation of amyloid-β (Aβ) plays an important role in Alzheimer's disease (AD) pathology. There is growing evidence that disordered sleep may accelerate AD pathology by impeding the physiological clearance of Aβ from the brain that occurs in normal sleep. Therapeutic strategies for improving sleep quality may therefore help slow disease progression. It is well documented that the composition and dynamics of sleep are sensitive to ambient temperature. We therefore compared Aβ pathology and sleep metrics derived from polysomnography in 12-month-old female 3xTg-AD mice (n = 8) exposed to thermoneutral temperatures during the light period over 4 weeks to those of age- and sex-matched controls (n = 8) that remained at normal housing temperature (22°C) during the same period. The treated group experienced greater proportions of slow wave sleep (SWS)-i.e. epochs of elevated 0.5-2 Hz EEG slow wave activity during non-rapid eye movement (NREM) sleep-compared to controls. Assays performed on mouse brain tissue harvested at the end of the experiment showed that exposure to thermoneutral temperatures significantly reduced levels of DEA-soluble (but not RIPA- or formic acid-soluble) Aβ40 and Aβ42 in the hippocampus, though not in the cortex. With both groups pooled together and without regard to treatment condition, NREM sleep continuity and any measure of SWS within NREM at the end of the treatment period were inversely correlated with DEA-soluble Aβ40 and Aβ42 levels, again in the hippocampus but not in the cortex. These findings suggest that experimental manipulation of SWS could offer useful clues into the mechanisms and treatment of AD.

Cortical miR-709 links glutamatergic signaling to NREM sleep EEG slow waves in an activity-dependent manner.

MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression that have been implicated in a plethora of neuronal processes. Nevertheless, their role in regulating brain activity in the context of sleep has so far received little attention. To test their involvement, we deleted mature miRNAs in post-mitotic neurons at two developmental ages, i.e., in early adulthood using conditional Dicer knockout (cKO) mice and in adult mice using an inducible conditional Dicer cKO (icKO) line. In both models, electroencephalographic (EEG) activity was affected and the response to sleep deprivation (SD) altered; while the rapid-eye-movement sleep (REMS) rebound was compromised in both, the increase in EEG delta (1 to 4 Hz) power during non-REMS (NREMS) was smaller in cKO mice and larger in icKO mice compared to controls. We subsequently investigated the effects of SD on the forebrain miRNA transcriptome and found that the expression of 48 miRNAs was affected, and in particular that of the activity-dependent miR-709. In vivo inhibition of miR-709 in the brain increased EEG power during NREMS in the slow-delta (0.75 to 1.75 Hz) range, particularly after periods of prolonged wakefulness. Transcriptome analysis of primary cortical neurons in vitro revealed that miR-709 regulates genes involved in glutamatergic neurotransmission. A subset of these genes was also affected in the cortices of sleep-deprived, miR-709-inhibited mice. Our data implicate miRNAs in the regulation of EEG activity and indicate that miR-709 links neuronal activity during wakefulness to brain synchrony during sleep through the regulation of glutamatergic signaling.

Effects of CPAP treatment on electroencephalographic activity in patients with obstructive sleep apnea syndrome during deep sleep: Preliminary findings of a cross-sectional study.

Study objectives: To investigate whether electroencephalographic (EEG) activities during non-rapid eye movement sleep stage 3 (N3) in obstructive sleep apnea syndrome (OSAS) patients were changed with continuous positive airway pressure (CPAP) treatment.Methods: A cross-sectional study of EEG activity during N3 sleep was conducted in 15 patients with moderate to severe OSAS without and with CPAP treatment compared to 15 normal controls. The amplitude, and absolute and relative power of delta, theta, alpha and beta waves as well as the absolute power ratio of slow to fast EEG waves (i.e., absolute power of delta and theta waves/absolute power of alpha and beta waves) and the spectral power density of 0-30Hz EEG activities were analyzed.Results: CPAP significantly increased N3 sleep, the absolute and relative powers, amplitudes of delta and theta waves, and absolute power ratio of slow to fast EEG waves, but decreased relative alpha and beta powers during N3 sleep. However, there were no significant differences in those parameters between the OSAS patients with CPAP treatment and normal controls.Conclusions: CPAP prolongs N3 sleep and increases the power and amplitude of slow EEG waves during N3 sleep, which indicates an improvement in sleep quality and further provides evidence for recommendation of CPAP treatment for OSAS patients.

Detection of interictal epileptiform discharge in focal seizures

Introduction: Many factors underlying basic epileptic conditions determine the characteristics of epileptic seizures and the therapeutic outcome. Visual obvious abnormalities in resting baseline EEG are cardinal but incompletely understood like feature of seizure onset zone in focal epilepsy and interictal epileptiform discharge. Present study is an attempt to diagnose that evidence of epileptic discharge in temporal lobe epilepsy (TLE), would persist during interictal period in absence of abnormalities in baseline EEG, which could increase the impact of automatic analysis of EEG waves for clinical relevance.&#x0D; Material and Methods: By using 10-20 system, functional connectivity was estimated in the 20 channels of delta, theta, alpha, beta and gamma frequency bands of EEG, from 16 diagnosed focal epileptic seizure patients and 16 age and sex matched controls. To observe the dynamics of the healthy brain, differ from the brain of dynamically focal epileptic patients during interictal period treated with anti-epileptic drugs in the context of resting state during eye close session of EEG. Such differences can be observed by using absolute spectral power from BESS ((Brain Electro Scan Software) of the Axxonet System and statistically measure by applied unpaired student t -test.&#x0D; Result: The high significance results in slow frequency EEG waves (delta and theta) in power spectral analysis were observed that demonstrates the potential epileptic discharge occurring during interictal period without visible pathological activity for helping in the diagnosis and lateralization of TLE.&#x0D; Conclusion: The detailed spectral analysis of EEG waves offers novel insight into focal epileptic patients when visually EEG findings were normal. This linear analysis helpful in extracting information from EEG signals in diagnosing specific neuronal correlates for TLE. Present findings concluded that epileptic discharges occur at different topographical regions of brain during interictal period and power spectral analysis plays a new insight in diagnosis of focal discharge.

Sleep and the sleep electroencephalogram in C57BL/6 and C3H/HeN mice.

Different mouse strains used in biomedical research show different phenotypes associated with their genotypes. Two mouse strains commonly used in biomedical sleep research are C57Bl/6 and C3H/He, the strains differ in numerous aspects, including their ability to secrete melatonin as well as the expression of several sleep-related genes. However, sleep regulation has only limitedly been compared between C3H/HeN and C57Bl/6 mice. We therefore compared sleep-wake behaviour and EEG-measured spectral brain activity for C57bl/6 and C3H/HeN mice during a 12:12 h light: dark baseline and during and after a 6 h sleep deprivation. The C3H mice spent more time in NREM sleep around the light-dark transition and more time in REM sleep during the dark phase compared with C57bl/6 mice. The C3H mice also showed more EEG activity in the 4.5-7.5 Hz range during all stages and a stronger 24 h modulation of EEG power density in almost all EEG frequencies during NREM sleep. After the sleep deprivation, C3H mice showed a stronger recovery response, which was expressed in both a larger increase in EEG slow wave activity (SWA) and more time spent in NREM sleep. We show large differences regarding sleep architecture and EEG activity between C3H and C57bl/6 mice. These differences include the amount of waking during the late dark phase, the 24 h amplitude in EEG power density, and the amount of REM sleep during the dark phase. We conclude that differences between mouse strains should be considered when selecting a model strain to improve the generalisability of studies investigating biomedical parameters related to sleep and circadian rhythms.

Maturational trend of daytime sleep propensity in adolescents.

The teenage increase in sleepiness is not simply a response to decreasing nighttime sleep duration. Daytime sleepiness increases across adolescence even when prior sleep duration is held constant. Here we determine the maturational trend in daytime sleep propensity assessed with the multiple sleep latency test (MSLT) and assess the trend's relation to pubertal maturation and changes in the sleep electroencephalogram. We also evaluate whether the relation of daytime sleep propensity to prior sleep duration changes between ages 10 and 23 years. Participants (n = 159) entered the study between ages 9.8 and 22.8 years and were studied annually for up to 3 years. Annually, participants kept each of three sleep schedules in their homes: 7, 8.5, and 10 hours in bed for 4 consecutive nights with polysomnography on nights 2 and 4. MSLT-measured daytime sleep propensity was assessed in the laboratory on the day following the fourth night. A two-part linear spline model described the maturation of daytime sleep propensity. MSLT sleep likelihood increased steeply until age 14.3 years, after which it did not change significantly. The maturational trend was strongly associated with the adolescent decline in slow-wave (delta, 1-4 Hz) EEG power during NREM sleep and with pubertal maturation assessed with Tanner stage measurement of breast/genital development. The effect of prior sleep duration on sleep likelihood decreased with age. Adolescent brain changes related to pubertal maturation and those reflected in the delta decline contribute to the adolescent increase in daytime sleep propensity.

Selected Acoustic Frequencies Have a Positive Impact on Behavioural and Physiological Welfare Indicators in Thoroughbred Racehorses.

(1) Background: Since antiquity, it is considered that sounds influence human emotional states and health. Acoustic enrichment has also been proposed for domestic animals. However, in both humans and animals, effects vary according to the type of sound. Human studies suggest that frequencies, more than melodies, play a key role. Low and high frequencies, music tuning frequency and even EEG slow waves used for 'neurofeedback' produce effects. (2) Methods: We tested the possible impact of such pure frequencies on racehorses' behavior and physiology. A commercial non-audible acoustic stimulus, composed of an array of the above-mentioned frequencies, was broadcasted twice daily and for three weeks to 12 thoroughbred horses in their home stall. (3) Results: The results show a decrease in stereotypic behaviors and other indicators such as yawning or vacuum chewing, an increase in the time spent in recumbent resting and foraging, and better hematological measures during and after the playback phase for 4 of the 10 physiological parameters measured. (4) Conclusions: These results open new lines of research on possible ways of alleviating the stress related to housing and training conditions in racehorses and of improving physical recovery.

Universal System of Tripling Periods for the Eye Is the Way to the “Logarithmic” Treatment of Neurological Diseases with Modern Lighting Technologies

Previously, the pattern of evolutionary adjustment of photodetectors of the human retina to the frequencies of the UPTS (the so-called universal period-tripling system) was phenomenologically established. The period tripling effect is a new direction in the study of complex systems. In these papers, it was established that the UPTS is a characteristic of a wide class of natural fractal systems described, in particular, by complex cubic mappings. In this work, taking into account the fact that both vision and the processing of visual information by the brain work based on the principles of UPTS, a fundamental frequency, dynamic model of the mechanism of the eye-vision system is constructed, generalizing experimental and theoretical data on the fractal dynamics of the brain in normal and neurological diseases. Data on the Luscher test, on MRI and slow EEG waves, neuro-hormones, photooxy-therapy of brain diseases allow us to establish a new paradigm of lighting technology for health-friendly lighting and ways of a new successful therapeutic effect on Pacrkinson’s disease, effects of traumatic brain injury, stroke, schizophrenia, psychopathy, neurosis. In this case, the lighting scheme requires the simultaneous observance of five rows of rankings of lighting parameters: by frequencies (1), according to the combination of frequencies, and the dynamics of the presentation of combinations (2), by colour perception errors (3), according to the patient’s refusals determine the colours (4), according to the fractal laws of the frequencies of vision and the brain (5). The universality of period-tripling system gives new ways to the principles of lighting engineering and photo-medicine.

Forma esporádica de enfermedad de Creutzfeldt-Jakob: reporte de dos casos

La enfermedad de Creutzfeldt-Jakob es la encefalopatía espongiforme más común en el ser humano y prototipo de las patologías causadas por priones. Se caracteriza histológicamente por astrogliosis y degeneración de la sustancia gris. Típicamente inicia con síntomas prodrómicos no específicos progresando a demencia con mioclonias y ataxia. Presentamos dos casos de mujeres en edad media con deterioro cognitivo progresivo, dificultades motrices, alteraciones del lenguaje y mioclonias que conducen a la muerte. En electroencefalogramas de ondas trifásicas lentas periódicas así como elevación de proteínas tau y 14-3-3 en LCR por apoyo del The National Prion Disease Pathology Surveillance Center - Cleveland, todos estos hallazgos definen las condiciones para el diagnóstico clínico de enfermedad por priones. El diagnóstico diferencial en el contexto de demencia rápidamente progresiva es amplio, incluyendo infecciones, intoxicaciones, trastornos metabólicos, autoinmunidad, vasculopatías y neoplasias que podrían explicar un posible subregistro en las estadísticas regionales. Existe una posible asociación de riesgo entre enfermedad por priones y médicos patólogos que, aunque discutida, podría limitar el estudio de los especímenes histológicos que son la clave del diagnóstico definitivo. A pesar de la importancia en salud pública de estas condiciones, el actual modelo de salud limita el manejo integral de los pacientes.

0723 Slow wave activity surrounding K-complexes is associated with long-term all-cause mortality in a large community-dwelling cohort

Abstract Introduction Sleep fragmentation is thought to be associated with adverse long-term consequences including mortality. However, conventional metrics of sleep fragmentation such as time spent in non-REM, REM sleep stages have been inconsistently associated with long-term consequences of sleep fragmentation. Recent studies suggest that morphological features of K-complexes might better describe sleep fragmentation as they are sensitive to effects of sleep disruption and better correlate with short-term outcomes such as daytime sleepiness. We previously demonstrated that the slow wave activity (SWA) surrounding K-complexes (∆SWAK) was a strong predictor of sleepiness in a cohort of sleep apnea subjects, mediated in part by its association with sleep fragmentation, however its association with long-term consequences of sleep fragmentation is not well known. Methods We analyzed nocturnal polysomnography (NPSG) data from Sleep Heart Health Study (1995-1998), a well-characterized cohort examining the cardiovascular consequences of sleep-disordered breathing. The primary quantitative EEG (C3-A2) metrics were: SWA (%relative power in 0.5-4 Hz), K-complex density (number/min of N2), and ∆SWAK. K-complexes were detected automatically using previously published open-source method (DETOKS, Parekh et. al., 2015) during stage N2 of sleep only. All EEG metrics were divided into quartiles to explore potential non-linear associations. Death from any cause up until 2011 (mean follow up of 11 years) was the primary outcome. Cox-regression models were used to assess the relationship between EEG metrics and all-cause mortality. Results After accounting for missing data, 3,909 NPSG’s with at least 6h of usable EEG were available for analysis (age=64±11 yrs., 53.4% female). In multivariate Cox-regression models adjusted for age, gender, race, severity of sleep apnea, total sleep time, time spent in stage N2, and smoking, all-cause mortality was significantly associated with the highest quartile of SWA (HR_q4=0.77 [0.6-0.9], p=0.01), highest two quartiles of ∆SWAK (HR_q3=0.8 [0.6-0.9], p=0.04; HR_q4=0.6 [0.5-0.8], p&amp;lt; 0.001). Conclusion Quantitative EEG measures predict mortality in a large community-dwelling cohort. Specifically, slow-wave activity surrounding K-complexes appear to be strongly associated with all-cause mortality beyond the effect of known covariates. Combined with our previous studies, our data suggest that slow-wave specific EEG measures are predictive of short- and long-term consequences of sleep fragmentation. Support (if any) AASM Foundation BS-233-20, NIH-K25HL151912, R21HL165320

Interrelations of Clinical, Neurophysiological and Neuroimmunological Parameters in Depressive Patients after COVID-19

The aim of the study was to assess the impact of the coronavirus infection on clinical, neurophysiological and neuroimmunological parameters, as well as on their interrelations in young female depressive patients. Patients: a comparative analysis of quantitative clinical (according to the HDRS-17 scale), neurophysiological (EEG) and neuroimmunological (according to the “Neuro-immuno-test” technology) parameters was carried out in two groups of female depressive patients aged 16–25 years. The first group included 46 patients who recovered from a mild or asymptomatic coronavirus infection (“COVID” group). The second group included 40 patients who were studied and treated before the start of the pandemic (i.e., those who did not have COVID — the “pre-COVID” group) and corresponding to patients of the first group by gender, age, diagnoses, and syndrome structure of disorders. In all patients, prior to the start of the course of therapy, a multichannel EEG was recorded with the measurement of absolute spectral power and neuroimmunological parameters in blood plasma were determined. Methods: clinicalpsychopathological, psychometric, neurophysiological, neuroimmunological, statistical. Results: significantly greater scores of somatic disorders cluster of HDRS-17 scale, and increased amount of slow-wave EEG activity (of delta, theta1 and theta2 subbands) were revealed in the “COVID” group in comparison to patients of “pre-COVID” group. Mean values of neuroimmunological parameters were not differed statistically between two groups, but the values of neuroplasticity markers (levels of autoantibodies to the S100b protein and to the basic myelin protein) in the “pre-COVID” group correlated positively with the spectral power values of the main EEG rhythm (alpha2 and alpha3 sub-bands), and in “COVID” group — with the values of the spectral power of slow-wave EEG activity, reflecting a reduced brain functional state. Conclusion: the results obtained indicate that coronavirus infection, even in mild or asymptomatic forms, affects the clinical, neurophysiological and neuroimmunological parameters, as well as their interrelations in young female depressive patients.

0218 Changes in sleep architecture and topography of sleep EEG slow wave activity following acute wake extension in early adolescence

Abstract Introduction A progression of peak sleep EEG slow wave activity (SWA; EEG power 0.5-4Hz) from posterior to anterior expression reflects brain development. Further, increased EEG SWA after extended wakefulness is a marker of sleep pressure. However, it is unclear whether recovery sleep SWA in later youth is expressed in a similar scalp topography as typical sleep. Using experimental wake-extension, we investigated homeostatic changes in sleep architecture and SWA topography in early adolescence. Methods Twenty-two young adolescents (M±SD: 12.03±1.14y, 12F) participated in two consecutive laboratory stays after at least a week of at-home actigraphy-monitored stabilization (9.5h in bed). A baseline night (BSL; 9.5h 21:00-06:30) was followed by wake-extension (WE) to 02:30 and a 4h recovery sleep opportunity (RS; 02:30-06:30), each monitored by polysomnography including a 25-channel EEG array. The current analyses examined R&amp;K sleep architecture at BSL and RS. SWA in RS was compared to the first 4h of BSL in two ways: (1) absolute NREM power (µV2); (2) an index (TI) of the topographical distribution of midline SWA (FPz-AFz-Fz-FCz-Cz-CPz-Pz-POz-Oz) providing a score of 1 to 9 indicating frontal to occipital peak distribution. Results WE significantly altered RS sleep architecture, including an increase in slow-wave sleep (%TST) versus BSL (M±SD BSL: 26.76±5.69%, RS: 51.65±7.83%, t(21)=-17.09, p&amp;lt;.001, d=-3.65). SWA was also significantly greater in RS (channel-averaged SWA BSL: 11883.50±5142.17 µV2, RS: 18955.82±7451.20 µV2, t(21)=-8.67, p&amp;lt;.001) with 22/25 individual electrodes meeting Bonferroni-corrected significance (ps&amp;lt;.001). Finally, we observed a small frontal shift (t(21)=2.39, p=.027, d=.51) of maximal SWA in RS (TI: 4.46±2.58; i.e., FCz/Cz) compared to BSL (5.32±2.78, i.e., Cz/CPz). Conclusion These data indicate robust sleep homeostasis in young adolescents after wake extension, expressed as increased SWA across the scalp. The findings also add to existing literature by indicating that SWA topography may also be sensitive to homeostatic challenge. Specifically, a baseline centroparietal locus of maximal SWA typical to this age became more frontocentral in recovery sleep. This anterior shift may reflect a homeostatic need over developmentally sensitive prefrontal cortex. Next steps will assess how individual responses may reflect a child’s neurodevelopment (e.g., inattention symptoms) or manifested behavior after wake extension and recovery sleep. Support (if any) K01MH109854, P20GM139743, R01HD103655

Sleep waves in a large-scale corticothalamic model constrained by activities intrinsic to neocortical networks and single thalamic neurons.

Many biophysical and non-biophysical models have been able to reproduce the corticothalamic activities underlying different EEG sleep rhythms but none of them included the known ability of neocortical networks and single thalamic neurons to generate some of these waves intrinsically. We built a large-scale corticothalamic model with a high fidelity in anatomical connectivity consisting of a single cortical column and first- and higher-order thalamic nuclei. The model is constrained by different neocortical excitatory and inhibitory neuronal populations eliciting slow (<1 Hz) oscillations and by thalamic neurons generating sleep waves when isolated from the neocortex. Our model faithfully reproduces all EEG sleep waves and the transition from a desynchronized EEG to spindles, slow (<1 Hz) oscillations, and delta waves by progressively increasing neuronal membrane hyperpolarization as it occurs in the intact brain. Moreover, our model shows that slow (<1 Hz) waves most often start in a small assembly of thalamocortical neurons though they can also originate in cortical layer 5. Moreover, the input of thalamocortical neurons increases the frequency of EEG slow (<1 Hz) waves compared to those generated by isolated cortical networks. Our simulations challenge current mechanistic understanding of the temporal dynamics of sleep wave generation and suggest testable predictions.

Effects of emerging alcohol use on developmental trajectories of functional sleep measures in adolescents.

Adolescence is characterized by significant brain development, accompanied by changes in sleep timing and architecture. It also is a period of profound psychosocial changes, including the initiation of alcohol use; however, it is unknown how alcohol use affects sleep architecture in the context of adolescent development. We tracked developmental changes in polysomnographic (PSG) and electroencephalographic (EEG) sleep measures and their relationship with emergent alcohol use in adolescents considering confounding effects (e.g. cannabis use). Adolescents (n = 94, 43% female, age: 12-21 years) in the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study had annual laboratory PSG recordings across 4-years. Participants were no/low drinkers at baseline. Linear mixed effect models showed developmental changes in sleep macrostructure and EEG, including a decrease in slow wave sleep and slow wave (delta) EEG activity with advancing age. Emergent moderate/heavy alcohol use across three follow-up years was associated with a decline in percentage rapid eye movement (REM) sleep over time, a longer sleep onset latency (SOL) and shorter total sleep time (TST) in older adolescents, and lower non-REM delta and theta power in males. These longitudinal data show substantial developmental changes in sleep architecture. Emergent alcohol use during this period was associated with altered sleep continuity, architecture, and EEG measures, with some effects dependent on age and sex. These effects, in part, could be attributed to the effects of alcohol on underlying brain maturation processes involved in sleep-wake regulation.

EEG-LLAMAS: A low-latency neurofeedback platform for artifact reduction in EEG-fMRI

Simultaneous EEG-fMRI is a powerful multimodal technique for imaging the brain, but its use in neurofeedback experiments has been limited by EEG noise caused by the MRI environment. Neurofeedback studies typically require analysis of EEG in real time, but EEG acquired inside the scanner is heavily contaminated with ballistocardiogram (BCG) artifact, a high-amplitude artifact locked to the cardiac cycle. Although techniques for removing BCG artifacts do exist, they are either not suited to real-time, low-latency applications, such as neurofeedback, or have limited efficacy. We propose and validate a new open-source artifact removal software called EEG-LLAMAS (Low Latency Artifact Mitigation Acquisition Software), which adapts and advances existing artifact removal techniques for low-latency experiments. We first used simulations to validate LLAMAS in data with known ground truth. We found that LLAMAS performed better than the best publicly-available real-time BCG removal technique, optimal basis sets (OBS), in terms of its ability to recover EEG waveforms, power spectra, and slow wave phase. To determine whether LLAMAS would be effective in practice, we then used it to conduct real-time EEG-fMRI recordings in healthy adults, using a steady state visual evoked potential (SSVEP) task. We found that LLAMAS was able to recover the SSVEP in real time, and recovered the power spectra collected outside the scanner better than OBS. We also measured the latency of LLAMAS during live recordings, and found that it introduced a lag of less than 50 ms on average. The low latency of LLAMAS, coupled with its improved artifact reduction, can thus be effectively used for EEG-fMRI neurofeedback. A limitation of the method is its use of a reference layer, a piece of EEG equipment which is not commercially available, but can be assembled in-house. This platform enables closed-loop experiments which previously would have been prohibitively difficult, such as those that target short-duration EEG events, and is shared openly with the neuroscience community.

Activation of the nociceptin/orphanin-FQ receptor promotes NREM sleep and EEG slow wave activity

Sleep/wake control involves several neurotransmitter and neuromodulatory systems yet the coordination of the behavioral and physiological processes underlying sleep is incompletely understood. Previous studies have suggested that activation of the Nociceptin/orphanin FQ (N/OFQ) receptor (NOPR) reduces locomotor activity and produces a sedation-like effect in rodents. In the present study, we systematically evaluated the efficacy of two NOPR agonists, Ro64-6198 and SR16835, on sleep/wake in rats, mice, and Cynomolgus macaques. We found a profound, dose-related increase in non-Rapid Eye Movement (NREM) sleep and electroencephalogram (EEG) slow wave activity (SWA) and suppression of Rapid Eye Movement sleep (REM) sleep in all three species. At the highest dose tested in rats, the increase in NREM sleep and EEG SWA was accompanied by a prolonged inhibition of REM sleep, hypothermia, and reduced locomotor activity. However, even at the highest dose tested, rats were immediately arousable upon sensory stimulation, suggesting sleep rather than an anesthetic state. NOPR agonism also resulted in increased expression of c-Fos in the anterodorsal preoptic and parastrial nuclei, two GABAergic nuclei that are highly interconnected with brain regions involved in physiological regulation. These results suggest that the N/OFQ-NOPR system may have a previously unrecognized role in sleep/wake control and potential promise as a therapeutic target for the treatment of insomnia.