EEG Slow Waves Research Articles

Spike-wave seizures, slow-wave sleep EEG and morphology of substantia nigra pars compacta in WAG/Rij rats with genetic predisposition to absence epilepsy

Spike-wave discharges (SWDs) are EEG hallmarks of absence epilepsy, and they spontaneously appear in adult WAG/Rij rats. SWDs are known to be vigilance-dependent and are modulated by monoaminergic mechanisms. It is also known that loss of neurons in the center of the nigrostriatal dopamine system, substantia nigra pars compacta (SNc), is associated with a variety of sleep disorders. We hypothesized that a disorder of the nigrostriatal dopamine system described for WAG/Rij rats might facilitate generation of SWDs through changes in vigilance state and the quality of sleep. Our study was conducted in ‘epileptic’ and ‘non-epileptic’ phenotype (less than 1 SWDs per h). Analysis included (1) EEG examination, i.e., analysis of SWDs, rudimentary SWDs and slow wave sleep EEG and (2) microstructural examination of SNc, i.e., measuring its size and the number of neurons and glial cells. No differences in size and cellular content of SNc were found between ‘epileptic’ and ‘non-epileptic’ phenotypes. Meanwhile in ‘epileptic’ subjects, the number of SWDs correlated with the number of neurons in SNc (SWDs more frequently occurred in subjects with fewer neurons in SNc). Rudimentary SWDs were found in both phenotypes. No differences in number and duration of rudimentary SWDs were found between ‘epileptic’ and ‘non-epileptic’ phenotypes. Spike-wave EEG activity showed strong association with the number of neurons in SNc: subjects with fewer neurons in SNc were characterized by higher number of SWDs and longer rudimentary SWDs. In sum, our data suggested that intense epileptic EEG activity (in the form of SWDs and rudimentary SWDs) might lead to sleep disruption. However, the lack of direct correlations between sleep parameters and SWDs number indicated that the link between sleep features, SNc cellularity and spike-wave EEG activity could be more complex than we had expected.

069 Chronic pain in Veterans with TBI is associated with decreased EEG slow wave coherence during NREM sleep

Abstract Introduction Chronic pain and sleep disturbances are intricately linked to one another, especially in individuals with a history of traumatic brain injury (TBI) who are at greater risk for both symptoms. Although prior studies have analyzed differences in sleep electroencephalogram (EEG) in these clinical populations, the association between sleep EEG slow wave coherence and pain complaints is not fully examined or known. Our novel slow wave coherence approach may provide new insights into the relationship between TBI, chronic pain, and sleep Methods Ninety-six veterans were recruited and enrolled under a VA IRB-approved protocol. Participants completed a semi-structured clinical interview to determine their history of TBI, Symptom Impact Questionnaire Revised (SIQR), a measure of chronic pain complaints, and underwent an attended overnight in-lab polysomnogram (PSG). We developed a novel computational signal processing algorithm to identify and quantify EEG slow waves within 100 ms bins across the 6 standard PSG EEG channels. When a slow wave was simultaneously observed in 4 or more of the 6 leads, slow wave coherence was inferred, and a percentage of slow wave coherence across each of the sleep stages was then calculated for each subject. Results In our sample, 65 participants (67.7%) endorsed experiencing chronic pain lasting 3 months or longer, and 54 had a history of TBI (56.3%). Participants endorsing chronic pain had a significantly lowered percent of EEG slow wave coherence during NREM sleep than subjects without chronic pain (p = 0.01). NREM EEG slow wave coherence did not correlate with SIQR scores in subjects without TBI (r = -0.03, p = 0.90), but was significantly negatively correlated in subjects with TBI (r = -0.32, p = 0.02). Conclusion EEG slow wave coherence during NREM sleep is correlated with chronic pain complaints in Veterans with a history of TBI, and could be indicative of neuronal dysfunction during sleep. Further research on slow wave coherence is warranted to understand the underlying mechanisms for the association between chronic pain and poor sleep following TBI. Support (if any) D01 W81XWH-17-1-0423

799 Automated Detection of Slow Wave Coherence in Sleep EEG: A potential neurophysiological correlate of cognitive decline

Abstract Introduction A bidirectional relationship exists between sleep disruption and neuropathology in Alzheimer’s disease (AD). The sleep electroencephalogram (EEG) is a highly stereotyped, direct neurophysiological window into brain function; prior studies have identified abnormalities in EEG slow waves in early AD. EEG coherence across channels during sleep, a normally highly coherent brain state, could be an indicator of network coordination across brain regions. Accordingly, altered slow wave coherence during sleep may be an early indicator of cognitive decline. Methods EEG was collected during an attended overnight polysomnogram (PSG) from a community-based cohort of older subjects (n=44, average age = 71), approximately 25% of whom met criteria for mild cognitive impairment or early AD. Files were exported to EDF and a slow wave peak detector was implemented in MATLAB to count the number of slow wave oscillations, with automated artifact rejection, across 6 EEG leads standard for PSG (C3, C4, F3, F4, O1, and O2). Slow wave coherence was inferred when slow waves occurred in temporal synchrony across channels within 100 ms. Results Subjects with cognitive impairment showed significantly reduced total sleep time and time spent in rapid eye movement (REM) sleep compared to age-matched controls. EEG slow wave coherence was reliably quantified during wake, non-REM stages N1, N2, N3, and REM vigilance states as well as during transition periods between sleep stages. Using this algorithm, specific signatures of slow wave propagation during sleep were identified, including increased variability in slow wave activity and coherence, that appeared more prominent in subjects with impaired cognition. Conclusion EEG slow wave coherence during sleep and wake states can be calculated by applying automated algorithms to PSG data, and may be associated with cognitive impairment. Support (if any) NIH R01 AG059507

Fentanyl, but not Morphine, Increases Cortical Electroencephalographic (EEG) Delta Power during Wakefulness in C57BL/6J (B6) Mice

Cortical EEG signals comprise differing oscillations that represent lower-level traits characteristic of higher-level behavioral phenotypes such as sleep and wakefulness (Physiology 32:60, 2017). Opioid-induced changes in neurobehavioral function also are reflected in altered EEG frequency and amplitude. These EEG features have the potential to provide insights regarding the desired actions and undesired side effects of opioids. In rat, morphine (Anesthesiology 103:779, 2005) and fentanyl (Sci Rep 9:14122, 2019) increase EEG slow waves. Studies of mice provide the additional opportunity to use mutated or transgenic animals with features potentially relevant to respiratory depression or addiction. This study is testing the hypothesis that subcutaneous injection of fentanyl and morphine causes dose-dependent EEG changes in wild-type mice. Experiments were conducted in accordance with the FASEB Statement of Principles for the use of Animals in Research and Education. Adult male B6 mice (n = 4) were implanted with telemeters (DSI HD-X02) for wireless recording of cortical EEG and neck muscle electromyogram. The recordings were used to quantify the effects of opioids on sleep and wakefulness. These studies demonstrated dose-dependent sleep disruption by both opioids (see companion abstract by Zebadua Unzaga et al.). EEG data were digitized by DSI Ponemah software and analyzed using public domain software for creating multi-tapered EEG spectrograms (J Vis Exp 153:e60333, 2019). Analyses were based on EEG data from the first 30 min after opioid injection, when all mice were awake. EEG power was expressed as percent change relative to saline (vehicle control) for six frequency bands: delta (0.5 to 4 Hz), theta (4 to 8 Hz), alpha (8 to 13 Hz), sigma (12 to 15 Hz), beta (13 to 30 Hz), and gamma (30 to 60 Hz). Increasing half log doses (mg/kg) ranged from 0.001 to 3 for fentanyl and 0.01 to 30 for morphine. Repeated measures ANOVA with the Geisser-Greenhouse correction showed a significant dose main-effect of fentanyl on EEG delta power (F(1.857, 5.571) = 7.454, p = 0.0276) and alpha power (F(1.705, 5.116) = 6.316, p = 0.0439). For fentanyl (3 mg/kg) compared to saline, Cohen's d = 2.9 for delta power. By contrast, for morphine there was a significant main effect of dose only for EEG sigma power (F(2.162, 6.486) = 6.557, p = 0.0265). Comparing morphine (30 mg/kg) to saline, the Cohen's d = 1.1 for sigma power. Although both fentanyl and morphine are full mu-opioid receptor agonists, they significantly altered EEG power at different frequency bands. Fentanyl, but not morphine, blocks alpha-1 adrenergic receptor subtypes and vesicular reuptake of several monoamine transmitters (J Pharmacol Exp Ther 343:376, 2020). These results support the interpretation that the differential effects of fentanyl and morphine on EEG power may be due, in part, to non-mu-opioid receptor of fentanyl.

Cortical and subcortical hemodynamic changes during sleep slow waves in human light sleep

EEG slow waves, the hallmarks of NREM sleep are thought to be crucial for the regulation of several important processes, including learning, sensory disconnection and the removal of brain metabolic wastes. Animal research indicates that slow waves may involve complex interactions within and between cortical and subcortical structures. Conventional EEG in humans, however, has a low spatial resolution and is unable to accurately describe changes in the activity of subcortical and deep cortical structures. To overcome these limitations, here we took advantage of simultaneous EEG-fMRI recordings to map cortical and subcortical hemodynamic (BOLD) fluctuations time-locked to slow waves of light sleep. Recordings were performed in twenty healthy adults during an afternoon nap. Slow waves were associated with BOLD-signal increases in the posterior brainstem and in portions of thalamus and cerebellum characterized by preferential functional connectivity with limbic and somatomotor areas, respectively. At the cortical level, significant BOLD-signal decreases were instead found in several areas, including insula and somatomotor cortex. Specifically, a slow signal increase preceded slow-wave onset and was followed by a delayed, stronger signal decrease. Similar hemodynamic changes were found to occur at different delays across most cortical brain areas, mirroring the propagation of electrophysiological slow waves, from centro-frontal to inferior temporo-occipital cortices. Finally, we found that the amplitude of electrophysiological slow waves was positively related to the magnitude and inversely related to the delay of cortical and subcortical BOLD-signal changes. These regional patterns of brain activity are consistent with theoretical accounts of the functions of sleep slow waves.

Advanced Dementia: Brain-State Characteristics and Clinical Indicators of Early Mortality.

There is an urgent need in advanced dementia for evidence-based clinical prognostic predictors that could positively influence ethical decisions allowing health provider and family preparation for early mortality. Accordingly, the authors review and discuss the prognostic utility of clinical assessments and objective measures of pathological brain states in advanced dementia patients associated with accelerated mortality. Overall, due to the paucity of brain-activity and clinical-comorbidity predictors of survival in advanced dementia, authors outline the potential prognostic value of brain-state electroencephalography (EEG) measures and reliable clinical indicators for forecasting early mortality in advanced dementia patients. In conclusion, two consistent risk-factors for predicting accelerated mortality in terminal-stage patients with advanced dementia were identified: pressure ulcers and paroxysmal slow-wave EEG parameters associated with cognitive impairment severity and organic disease progression. In parallel, immobility, malnutrition, and co-morbid systemic diseases are highly associated with the risk for early mortality in advanced dementia patients. Importantly, the authors' conclusions suggest utilizing reliable quantitative-parameters of disease progression for estimating accelerated mortality in dementia patients entering the terminal disease-stages characterized by severe intellectual deficits and functional disability.

Diazepam effects on local cortical neural activity during sleep in mice

GABA-ergic neurotransmission plays a key role in sleep regulatory mechanisms and in brain oscillations during sleep. Benzodiazepines such as diazepam are known to induce sedation and promote sleep, however, EEG spectral power in slow frequencies is typically reduced after the administration of benzodiazepines or similar compounds. EEG slow waves arise from a synchronous alternation between periods of cortical network activity (ON) and silence (OFF), and represent a sensitive marker of preceding sleep-wake history. Yet it remains unclear how benzodiazepines act on cortical neural activity during sleep. To address this, we obtained chronic recordings of local field potentials and multiunit activity (MUA) from deep cortical layers of the primary motor cortex in freely behaving mice after diazepam injection. We found that the amplitude of individual LFP slow waves was significantly reduced after diazepam injection and was accompanied by a lower incidence and duration of the corresponding neuronal OFF periods. Further investigation suggested that this is due to a disruption in the synchronisation of cortical neurons. Our data suggest that the state of global sleep and local cortical synchrony can be dissociated, and that the brain state induced by benzodiazepines is qualitatively different from spontaneous physiological sleep.

Closed-Loop Acoustic Stimulation During Sedation with Dexmedetomidine (CLASS-D): Protocol for a Within-Subject, Crossover, Controlled, Interventional Trial with Healthy Volunteers.

IntroductionThe relative power of slow-delta oscillations in the electroencephalogram (EEG), termed slow-wave activity (SWA), correlates with level of unconsciousness. Acoustic enhancement of SWA has been reported for sleep states, but it remains unknown if pharmacologically induced SWA can be enhanced using sound. Dexmedetomidine is a sedative whose EEG oscillations resemble those of natural sleep. This pilot study was designed to investigate whether SWA can be enhanced using closed-loop acoustic stimulation during sedation (CLASS) with dexmedetomidine.MethodsClosed-Loop Acoustic Stimulation during Sedation with Dexmedetomidine (CLASS-D) is a within-subject, crossover, controlled, interventional trial with healthy volunteers. Each participant will be sedated with a dexmedetomidine target-controlled infusion (TCI). Participants will undergo three CLASS conditions in a multiple crossover design: in-phase (phase-locked to slow-wave upslopes), anti-phase (phase-locked to slow-wave downslopes) and sham (silence). High-density EEG recordings will assess the effects of CLASS across the scalp. A volitional behavioral task and sequential thermal arousals will assess the anesthetic effects of CLASS. Ambulatory sleep studies will be performed on nights immediately preceding and following the sedation session. EEG effects of CLASS will be assessed using linear mixed-effects models. The impacts of CLASS on behavior and arousal thresholds will be assessed using logistic regression modeling. Parametric modeling will determine differences in sleepiness and measures of sleep homeostasis before and after sedation.ResultsThe primary outcome of this pilot study is the effect of CLASS on EEG slow waves. Secondary outcomes include the effects of CLASS on the following: performance of a volitional task, arousal thresholds, and subsequent sleep.DiscussionThis investigation will elucidate 1) the potential of exogenous sensory stimulation to potentiate SWA during sedation; 2) the physiologic significance of this intervention; and 3) the connection between EEG slow-waves observed during sleep and sedation.

A pilot study on essential oil aroma stimulation for enhancing slow-wave EEG in sleeping brain

Sleep quality is important to health and life quality. Lack of sleep can lead to a variety of health issues and reduce in daytime function. Recent study by Fultz et al. also indicated that sleep is crucial to brain metabolism. Delta power in sleep EEG often indicates good sleep quality while alpha power usually indicates sleep interruptions and poor sleep quality. Essential oil has been speculated to improve sleep quality. Previous studies also suggest essential oil aroma may affect human brain activity when applied awake. However, those studies were often not blinded, which makes the effectiveness and mechanism of aroma a heavily debated topic. In this study, we aim to explore the effect of essential oil aroma on human sleep quality and sleep EEG in a single-blinded setup. The aroma was released when the participants are asleep, which kept the influence of psychological expectation to the minimum. We recruited nine young, healthy participants with regular lifestyle and no sleep problem. All participants reported better sleep quality and more daytime vigorous after exposing to lavender aroma in sleep. We also observed that upon lavender aroma releases, alpha wave in wake stage was reduced while delta wave in slow-wave sleep (SWS) was increased. Lastly, we found that lavender oil promote occurrence of SWS. Overall, our study results show that essential oil aroma can be used to promote both subjective and objective sleep quality in healthy human subjects. This makes aroma intervention a potential solution for poor sleep quality and insomnia.

High-Resolution Spectral Sleep Analysis Reveals a Novel Association Between Slow Oscillations and Memory Retention in Elderly Adults.

Objective: In recognition of the mixed associations between traditionally scored slow wave sleep and memory, we sought to explore the relationships between slow wave sleep, electroencephalographic (EEG) power spectra during sleep and overnight verbal memory retention in older adults.Design, Setting, Participants, and Measurements: Participants were 101 adults without dementia (52% female, mean age 70.3 years). Delayed verbal memory was first tested in the evening prior to overnight polysomnography (PSG). The following morning, subjects were asked to recall as many items as possible from the same List (overnight memory retention; OMR). Partial correlation analyses examined the associations of delayed verbal memory and OMR with slow wave sleep (SWS) and two physiologic EEG slow wave activity (SWA) power spectral bands (0.5–1 Hz slow oscillations vs. 1–4 Hz delta activity).Results: In subjects displaying SWS, SWS was associated with enhanced delayed verbal memory, but not with OMR. Interestingly, among participants that did not show SWS, OMR was significantly associated with a higher slow oscillation relative power, during NREM sleep in the first ultradian cycle, with medium effect size.Conclusions: These findings suggest a complex relationship between SWS and memory and illustrate that even in the absence of scorable SWS, older adults demonstrate substantial slow wave activity. Further, these slow oscillations (0.5–1 Hz), in the first ultradian cycle, are positively associated with OMR, but only in those without SWS. Our findings raise the possibility that precise features of slow wave activity play key roles in maintaining memory function in healthy aging. Further, our results underscore that conventional methods of sleep evaluation may not be sufficiently sensitive to detect associations between SWA and memory in older adults.

The Study of Electroencephalographic Changes in Patients Diagnosed with Dementia

Dementia refers to a group of disorders caused by the gradual dysfunction and death of brain cells. This disorder can be described clinically as a syndrome that causes a decline in cognitive domain (i.e., attention, memory, executive function, visual-spatial ability, and language)EEG may play an important role in detecting and classifying dementia because of its significant influence on dementia abnormalities in terms of rhythm activity .An increase in EEG slow wave activity (theta and delta frequencies) together with decreased activity in the alpha frequency band are considered to be typical findings in the various types of dementia. Aim and Objective: An analysis of electroencephalographic changes in patients diagnosed with dementia and trying to find significance in diagnosis. Methods and Materials: This study is an observational cross sectional study carried out in 30 patients diagnosed with dementia attending outpatient department in a tertiary care Hospital over a period of 6 months. Subjects are enquired about their history of diagnosis, family history, Treatment history and diagnostic tests such as EEG. Additionally MMSE scoring was also performed for all patients. Results: Out of the 30 patients dementia incidence was higher in males (56.66 %) compared to females (43.33 %). EEG was found to be normal in 9 patients and abnormal in 21 patients. The study also shows a statistically significant correlation between MMSE Scoring and EEG Findings in patients with dementia. Conclusion: There is a definite EEG abnormality found in majority of the patients. Combined MMSE scoring and EEG in evaluation of dementia patients in larger study group will reveal more insight.

Frontal functional connectivity and disease duration interactively predict cognitive decline in Parkinson's disease

ObjectiveCognitive decline does not always follow a predictable course in Parkinson’s disease (PD), with some patients remaining stable while others meet criteria for dementia from early stages. Functional connectivity has been proposed as a good correlate of cognitive decline in PD, although it has not been explored whether the association between this connectivity and cognitive ability is influenced by disease duration, which was our objective. MethodsWe included 30 patients with PD and 15 healthy controls (HC). Six cognitive domains were estimated based on neuropsychological assessment. Phase-based connectivity at frontal and posterior cortical regions was estimated from a resting EEG. ResultsThe PD group showed significant impairment for the executive, visuospatial, and language domains compared with HC. Increased connectivity at frontal regions was also found in the PD group. Frontal delta and theta connectivity negatively influenced general cognition and visuospatial performance, but this association was moderated by disease duration, with increased connectivity predicting worse performance after 8 years of disease duration. ConclusionSubtle neurophysiological changes underlie cognitive decline along PD progression, especially around a decade after motor symptoms onset. SignificanceConnectivity of EEG slow waves at frontal regions might be used as a predictor of cognitive decline in PD.

Slow Wave Sleep and EEG Delta Spectral Power are Associated with Cognitive Function in Parkinson's Disease.

Cognitive and sleep dysfunction are common non-motor symptoms in Parkinson's disease (PD). Determine the relationship between slow wave sleep (SWS) and cognitive performance in PD. Thirty-two PD participants were evaluated with polysomnography and a comprehensive level II neurocognitive battery, as defined by the Movement Disorders Society Task Force for diagnosis of PD-mild cognitive impairment. Raw scores for each test were transformed into z-scores using normative data. Z-scores were averaged to obtain domain scores, and domain scores were averaged to determine the Composite Cognitive Score (CCS), the primary outcome. Participants were grouped by percent of SWS into High SWS and Low SWS groups and compared on CCS and other outcomes using 2-sided t-tests or Mann-Whitney U. Correlations of cognitive outcomes with sleep architecture and EEG spectral power were performed. Participants in the High SWS group demonstrated better global cognitive function (CCS) (p = 0.01, effect size: r = 0.45). In exploratory analyses, the High SWS group showed better performance in domains of executive function (effect size: Cohen's d = 1.05), language (d = 0.95), and processing speed (d = 1.12). Percentage of SWS was correlated with global cognition and executive function, language, and processing speed. Frontal EEG delta power during N3 was correlated with the CCS and executive function. Cognition was not correlated with subjective sleep quality. Increased SWS and higher delta spectral power are associated with better cognitive performance in PD. This demonstrates the significant relationship between sleep and cognitive function and suggests that interventions to improve sleep might improve cognition in individuals with PD.

Stretch syncope or epileptic seizure? A pathologic hypothesis for self-induced stretch syncope

We report on a 7-year-old female who presented paroxysmal episodes of loss of consciousness with clonic movements. The electroencephalogram (EEG) evidenced diffuse slow wave activations, with no symptoms. Epilepsy was suspected but antiepileptic drugs were ineffective. Video-EEG monitoring revealed that the syncope was triggered by stretching with a tachycardia that started during the stretch maneuver and diffuse slow waves on the EEG 2s before the symptoms. Stretch syncope can result in striking manifestations with subcortically driven clonic movements that can be mistaken for signs of epilepsy. Stretching might lead to transient hypoxia of the brainstem; in turn, this might activate the thalamocortical loop and thus generate cardiovascular changes, EEG slow waves, and physical manifestations.

Lack of antidepressant effects of burst-suppressing isoflurane anesthesia in adult male Wistar outbred rats subjected to chronic mild stress.

Post-ictal emergence of slow wave EEG (electroencephalogram) activity and burst-suppression has been associated with the therapeutic effects of the electroconvulsive therapy (ECT), indicating that mere “cerebral silence” may elicit antidepressant actions. Indeed, brief exposures to burst-suppressing anesthesia has been reported to elicit antidepressant effects in a subset of patients, and produce behavioral and molecular alterations, such as increased expression of brain-derived neurotrophic factor (BDNF), connected with antidepressant responses in rodents. Here, we have further tested the cerebral silence hypothesis by determining whether repeated exposures to isoflurane anesthesia reduce depressive-like symptoms or influence BDNF expression in male Wistar outbred rats (Crl:WI(Han)) subjected to chronic mild stress (CMS), a model which is responsive to repeated electroconvulsive shocks (ECS, a model of ECT). Stress-susceptible, stress-resilient, and unstressed rats were exposed to 5 doses of isoflurane over a 15-day time period, with administrations occurring every third day. Isoflurane dosing is known to reliably produce rapid EEG burst-suppression (4% induction, 2% maintenance; 15 min). Antidepressant and anxiolytic effects of isoflurane were assessed after the first, third, and fifth drug exposure by measuring sucrose consumption, as well as performance on the open field and the elevated plus maze tasks. Tissue samples from the medial prefrontal cortex and hippocampus were collected, and levels of BDNF (brain-derived neurotrophic factor) protein were assessed. We find that isoflurane anesthesia had no impact on the behavior of stress-resilient or anhedonic rats in selected tests; findings which were consistent—perhaps inherently related—with unchanged levels of BDNF.

0392 The Effect of Benzodiazepine Use on Non-REM Sleep Instability in Community-Dwelling Older Men

Abstract Introduction Previous studies on the implications of benzodiazepine (BZD), a widely prescribed pharmacotherapeutic treatment method for sleep insomnia, on sleep architecture demonstrated significantly reduced EEG activity in low-frequency bands. In this study, we explore the effect of BZD on NREM sleep instability also known as cyclic alternating pattern (CAP) in community-dwelling older men. Methods CAP was scored in overnight EEG recordings from 30 older men on long-acting BZD (LBZD), 35 older men on short-acting BZD (SBZD), and 50 age-matched men who did not use BZD (NBZD), participating in the Osteoporotic Fractures in Men Sleep Study (MrOS sleep). A high performance automated detection system determined the ratio between CAP time and NREM sleep time (CAP rate), the number of A1-phases per hour of NREM sleep (A1 index), and the number of A2+A3-phases per hour of NREM sleep (A2+A3 index). The relationship between CAP parameters and BZD use was determined using the Kruskal-Wallis test by ranks with Bonferroni correction for post-hoc analysis. Results CAP rate was significantly decreased in older men using long-acting BZD (NBZD: 59.6±18.0%, LBZD: 46.9±13.1%, SBZD: 53.0±20.1%) as compared to non-BZD user (p < 0.01). All BZD users demonstrated significantly lower frequencies of A1-phases (NBZD: 19.9±23.0 no./h, LBZD: 6.9±13.3 no./h, SBZD: 4.5±9.9 no./h) as compared to non-BZD users (LBZD: p < 0.01, SBZD: p < 0.001). The A2+A3 index did not show any variations between the three groups. Conclusion Older men using long-acting BZD demonstrate a significantly reduced CAP rate during sleep, particularly less frequent A1-phases, compared to the control group. Moreover, short-acting BZD user show significantly less frequent A1-phases but no difference in CAP rate and A2+A3-phases than older men using no BZD. Hence, BZD usage has a major adverse effect on the occurrence of EEG slow waves. Support The National Heart, Lung, and Blood Institute (NHLBI) provides funding for the MrOS Sleep ancillary study “Outcomes of Sleep Disorders in Older Men” under the following grant numbers: R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839.

0327 NREM Sleep EEG in Typically Developing and Drug-Naïve ADHD Adolescents: Data from a Longitudinal Study

Abstract Introduction Structural MRI studies suggest delayed brain maturation in children with attention deficit hyperactivity disorder (ADHD). The steep adolescent decline in sleep slow wave EEG activity provides an opportunity to investigate brain electrophysiological evidence for this maturational delay. Most ADHD sleep EEG studies have been cross-sectional. Here we present data from an ongoing longitudinal study of the maturational trajectories of sleep EEG in drug-naïve ADHD and typically developing adolescents. Methods Nine children diagnosed with ADHD (combined subtype, DSM-V criteria, mean age 12.39±0.61 years), and nine typically developing controls (12.07±0.35 years) were recruited. Subjects underwent an adaptation night and all night polysomnography twice yearly at the Laboratory. Sleep EEG was analyzed using fast Fourier transform. NREM delta and theta EEG activity were compared across first two recordings. Results Group effects (ADHD vs. control) on all night delta and theta energy, and delta power were not significant (p>0.2 for all). All night theta power was lower (p=0.035) for the ADHD group, and all night NREM sleep duration trended (p=0.060) toward being lower for the ADHD group. Controlling for sleep duration differences by examining only the first 5 h of NREM sleep showed no group effect on delta power (p=0.77) and a trend toward lower theta power (p=0.057) for the ADHD group. Conclusion At age 12 to 13 years, NREM sleep delta EEG did not differ between ADHD and control subjects. Theta power, which declines at a younger age than delta, was lower in control subjects. The two recordings thus far differ only by 6 months. The entire study will provide 5 semiannual recordings and allow us to determine if the higher theta power in the ADHD group will hold and if delta power will be greater as well, and thus provide electrophysiological support for the delayed brain maturation suggested by MRI findings. Support Shota Rustaveli National Science Foundation Grant FR17_94; Subjects Recruitment Support - Mental Health Service in Tbilisi “Kamara”.

Effectiveness of Visual vs. Acoustic Closed-Loop Stimulation on EEG Power Density during NREM Sleep in Humans.

The aim of the study was to investigate whether visual stimuli have the same potency to increase electroencephalography (EEG) delta wave power density during non-rapid eye movement (NREM) sleep as do auditory stimuli that may be practical in the treatment of some sleep disturbances. Nine healthy subjects underwent two polysomnography sessions—adaptation and experimental—with EEG electrodes positioned at Fz–Cz. Individually adjusted auditory (pink noise) and visual (light-emitting diode (LED) red light) paired 50-ms signals were automatically presented via headphones/eye mask during NREM sleep, shortly (0.75–0.90 s) after the EEG wave descended below a preset amplitude threshold (closed-loop in-phase stimulation). The alternately repeated 30-s epochs with stimuli of a given modality (light, sound, or light and sound simultaneously) were preceded and followed by 30-s epochs without stimulation. The number of artifact-free 1.5-min cycles taken in the analysis was such that the cycles with stimuli of different modalities were matched by number of stimuli presented. Acoustic stimuli caused an increase (p < 0.01) of EEG power density in the frequency band 0.5–3.0 Hz (slow waves); the values reverted to baseline at post-stimuli epochs. Light stimuli did not influence EEG slow wave power density (p > 0.01) and did not add to the acoustic stimuli effects. Thus, dim red light presented in a closed-loop in-phase fashion did not influence EEG power density during nocturnal sleep.

Sleep- and time of day-linked RNA transcript expression in wild-type and IL1 receptor accessory protein-null mice.

Sleep regulation involves interleukin-1β (IL1) family members, TNF, and circadian clock genes. Previously, we characterized spontaneous sleep and sleep after 8 h of sleep deprivation (SD) ending at zeitgeber time (ZT)4 and ZT16 in wild-type (WT) and IL1 receptor accessory protein (AcP)- and brain-specific AcP (AcPb)-knockout (KO) mice. Here, we applied quantitative reverse transcriptase polymerase chain reaction and Spearman gene pair expression correlation methods to characterize IL1, IL1 receptor 1 (IL1R1), AcP, AcPb, Period 1 (Per1), Clock, adenosine deaminase (Ada), peptidoglycan recognition protein 1 (Pglyrp1), and TNF mRNA expressions under conditions with distinct sleep phenotypes. In WT mice, IL1, IL1R1, AcP, Ada, and Clock mRNAs were higher at ZT4 (mid-sleep period) than at ZT16. mRNA expressions differed substantially in AcP and AcPb KO mice at those times. After SD ending at ZT4, only WT mice had a non-rapid eye movement sleep (NREMS) rebound, and AcPb and IL1R1 mRNA increases were unique to WT mice. In AcPb KO mice, which have spontaneous high EEG slow wave power, AcP and Pglyrp1 mRNAs were elevated relative to WT mice at ZT4. At ZT4, the AcPb KO - WT Spearman correlation difference networks showed high positive correlations between IL1R1 and IL1, Per1, and Clock and high negative correlations between TNF and Pglyrp1 and Ada. At ZT16, the WT mice gene pair expression network was mostly negative, whereas in AcP KO mice, which have substantially more rapid eye movement sleep than WT mice, it was all positive. We conclude that gene pair expression correlations depend on the presence of AcP and AcPb.NEW & NOTEWORTHY Spearman gene pair expression correlations depend upon the presence or absence of interleukin-1 receptor accessory protein and upon sleep phenotype.

Effects of sleep on a high-heat capacity mattress on sleep stages, EEG power spectra, cardiac interbeat intervals and body temperatures in healthy middle-aged men‡.

This study deals with the question whether a slow (non-disturbing) reduction of core body temperature (CBT) during sleep increases sleep stage N3 and EEG slow wave energy (SWE) and leads to a slowing of heart rate in humans. Thirty-two healthy male subjects with a mean ± SD age 46 ± 4 years and body mass index 25.2 ± 1.8 kg/m2. A high-heat capacity mattress (HM) was used to lower body temperatures in sleep and was compared to a conventional low-heat capacity mattress (LM) in a double-blinded fashion. Polysomnography was performed accompanied by measurements of skin-, core body- and mattress surface-temperatures, and heart rate. EEG power spectral analyses were carried out using Fast Fourier Transform. Interbeat intervals were derived from the electrocardiogram. The HM led to a larger decline in CBT, mediated through higher heat conduction from the core via the proximal back skin onto the mattress together with reduced heart rate. These effects occurred together with a significant increase in sleep stage N3 and standardized slow wave energy (sSWE, 0.791-4.297 Hz) accumulated in NREM sleep. In the 2nd half of the night sSWE increase was significantly correlated with body temperature changes, for example with CBT decline in the same phase. A HM subtly decreases CBT, leading to an increased amount of sleep stage N3 and of sSWE, as well as a slowing of heart rate.