Slow Oscillation Power Research Articles

O017 Investigating the role of amyloid burden on sleep microarchitecture and associations with cognitive functioning in individuals with OSA

Abstract Background Emerging evidence suggests obstructive sleep apnoea (OSA) is a risk factor for increased amyloid aggregation, a biomarker of Alzheimer’s disease, with disrupted sleep architecture hypothesised as a potential mechanism. Moreover, sleep architecture abnormalities observed in (OSA) may explain impaired cognition. However, the relationships between sleep microarchitecture, amyloid burden and cognition in OSA are unclear. Methods Thirty-four participants with OSA (age=57.7, 19 males), and 12 controls (age=57.1, 6 males) underwent diagnostic polysomnography (PSG), 11C-PiB positron emission tomography (PET) scan to quantify amyloid burden, and a cognitive assessment battery. All-night EEG recordings were processed and spectral power in slow oscillation (SO) and delta frequency ranges were calculated. Results Higher global amyloid burden was associated with lower delta power at O2 during slow wave sleep (SWS) in the OSA group (ß=-0.443, R2=0.142, p=0.048, controlled for age and non-REM AHI) and in the entire sample (ß=-.497, R2=.161, p=.019). Delta power and SO power in the OSA group was in turn associated with verbal memory (frontal regions - delta: ß=-0.811, p<0.001 and SO: ß=-0.661, p=0.008; central - delta: ß=0.537, p=0.026; occipital - delta: ß=0.586, p=0.014 and SO: ß=0.526, p =0.043). Discussion Greater amyloid burden was associated with slow wave deficits in older people with and without OSA. Worse memory performance was associated with lower slow frequency activity in central and occipital brain regions but higher activity in frontal regions. It is possible that pathological EEG slowing in some brain regions may explain the differential associations between sleep neurophysiological measures and memory.

Memory Consolidation during Ultra-short Offline States.

Traditionally, neuroscience and psychology have studied the human brain during periods of "online" attention to the environment, while participants actively engage in processing sensory stimuli. However, emerging evidence shows that the waking brain also intermittently enters an "offline" state, during which sensory processing is inhibited and our attention shifts inward. In fact, humans may spend up to half of their waking hours offline [Wamsley, E. J., & Summer, T. Spontaneous entry into an "offline" state during wakefulness: A mechanism of memory consolidation? Journal of Cognitive Neuroscience, 32, 1714-1734, 2020; Killingsworth, M. A., & Gilbert, D. T. A wandering mind is an unhappy mind. Science, 330, 932, 2010]. The function of alternating between online and offline forms of wakefulness remains unknown. We hypothesized that rapidly switching between online and offline states enables the brain to alternate between the competing demands of encoding new information and consolidating already-encoded information. A total of 46 participants (34 female) trained on a memory task just before a 30-min retention interval, during which they completed a simple attention task while undergoing simultaneous high-density EEG and pupillometry recording. We used a data-driven method to parse this retention interval into a sequence of discrete online and offline states, with a 5-sec temporal resolution. We found evidence for three distinct states, one of which was an offline state with features well-suited to support memory consolidation, including increased EEG slow oscillation power, reduced attention to the external environment, and increased pupil diameter (a proxy for increased norepinephrine). Participants who spent more time in this offline state following encoding showed improved memory at delayed test. These observations are consistent with the hypothesis that even brief, seconds-long entry into an offline state may support the early stages of memory consolidation.

Multiple cross-frequency coupling analysis of resting-state EEG in patients with mild cognitive impairment and Alzheimer's disease.

Electroencephalographic (EEG) abnormalities are seen in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) with characteristic features of cognitive impairment. The most common findings of EEG features in AD and MCI patients are increased relative power of slow oscillations (delta and theta rhythms) and decreased relative power of fast oscillations (alpha, beta and gamma rhythms). However, impairments in cognitive processes in AD and MCI are not sufficiently reflected by brain oscillatory activity in a particular frequency band. MCI patients are at high risk of progressing to AD. Cross-frequency coupling (CFC), which refers to coupling between different frequency bands, is a crucial tool for comprehending changes in brain oscillations and cognitive performance. CFC features exhibit some specificity in patients with AD and MCI, but a comparison between CFC features in individuals with these disorders is still lacking. The aim of this study was to explore changes in CFC properties in MCI and AD and to explore the relationship between CFC properties and multiple types of cognitive functional performance. We recorded resting-state EEG (rsEEG) signals in 46 MCI patients, 43 AD patients, and 43 cognitively healthy controls (HCs) and analyzed the changes in CFC as well as the relationship between CFC and scores on clinical tests of cognitive function. Multiple couplings between low-frequency oscillations and high-frequency oscillations were found to be significantly enhanced in AD patients compared to those of HCs and MCI, while delta-gamma as well as theta-gamma couplings in the right temporal and parietal lobes were significantly enhanced in MCI patients compared to HCs. Moreover, theta-gamma coupling in the right temporal lobe tended to be stronger in MCI patients than in HCs, and it was stronger in AD than in MCI. Multiple CFC properties were found to correlate significantly with various cognitive domains, especially the memory function domain. Overall, these findings suggest that AD and MCI patients must use more neural resources to maintain a resting brain state and that alterations in theta-gamma coupling in the temporal lobe become progressively obvious during disease progression and are likely to be a valuable indicator of MCI and AD pathology.

Asymmetry of sleep electrophysiological markers in patients with focal epilepsy.

Sleep can modulate epileptic activities, but our knowledge of sleep perturbation by epilepsy remains sparse. Interestingly, epilepsy and sleep both present with defining electrophysiological features in the form of specific graphoelements on EEG. This raises the possibility to identify, within ongoing EEG activity, how epilepsy impacts and disrupts sleep. Here, we asked whether the presence of a lateralized epileptic focus interferes with the expression of the dominant electrophysiological hallmarks of sleep: slow oscillations, slow waves and spindles. To this aim, we conducted a cross-sectional study and analysed sleep recordings with surface EEG from 69 patients with focal epilepsy (age range at EEG: 17-61 years, 29 females, 34 left focal epilepsy). Comparing patients with left and right focal epilepsy, we assessed inter-hemispheric asymmetry of sleep slow oscillations power (delta range, 0.5-4 Hz); sleep slow wave density; amplitude, duration and slope; and spindle density, amplitude, duration as well as locking to slow oscillations. We found significantly different asymmetries in slow oscillation power (P < 0.01); slow wave amplitude (P < 0.05) and slope (P < 0.01); and spindle density (P < 0.0001) and amplitude (P < 0.05). To confirm that these population-based differences reflect actual patient-by-patient differences, we then tested whether asymmetry of sleep features can classify laterality of the epileptic focus using a decision tree and a 5-fold cross-validation. We show that classification accuracy is above chance level (accuracy of 65%, standard deviation: 5%) and significantly outperforms a classification based on a randomization of epileptic lateralization (randomization data accuracy: 50%, standard deviation 7%, unpaired t-test, P < 0.0001). Importantly, we show that classification of epileptic lateralization by the canonical epileptic biomarker, i.e. interictal epileptiform discharges, improves slightly but significantly when combined with electrophysiological hallmarks of physiological sleep (from 75% to 77%, P < 0.0001, one-way ANOVA + Sidak's multiple comparisons test). Together, we establish that epilepsy is associated with inter-hemispheric perturbation of sleep-related activities and provide an in-depth multi-dimensional profile of the main sleep electrophysiological signatures in a large cohort of patients with focal epilepsy. We provide converging evidence that the underlying epileptic process interacts with the expression of sleep markers, in addition to triggering well-known pathological activities, such as interictal epileptiform discharges.

Post-cardiac arrest Sedation Promotes Electroencephalographic Slow-wave Activity and Improves Survival in a Mouse Model of Cardiac Arrest.

Patients resuscitated from cardiac arrest are routinely sedated during targeted temperature management, while the effects of sedation on cerebral physiology and outcomes after cardiac arrest remain to be determined. The authors hypothesized that sedation would improve survival and neurologic outcomes in mice after cardiac arrest. Adult C57BL/6J mice of both sexes were subjected to potassium chloride-induced cardiac arrest and cardiopulmonary resuscitation. Starting at the return of spontaneous circulation or at 60 min after return of spontaneous circulation, mice received intravenous infusion of propofol at 40 mg · kg-1 · h-1, dexmedetomidine at 1 µg · kg-1 · h-1, or normal saline for 2 h. Body temperature was lowered and maintained at 33°C during sedation. Cerebral blood flow was measured for 4 h postresuscitation. Telemetric electroencephalogram (EEG) was recorded in freely moving mice from 3 days before up to 7 days after cardiac arrest. Sedation with propofol or dexmedetomidine starting at return of spontaneous circulation improved survival in hypothermia-treated mice (propofol [13 of 16, 81%] vs. no sedation [4 of 16, 25%], P = 0.008; dexmedetomidine [14 of 16, 88%] vs. no sedation [4 of 16, 25%], P = 0.002). Mice receiving no sedation exhibited cerebral hyperemia immediately after resuscitation and EEG power remained less than 30% of the baseline in the first 6 h postresuscitation. Administration of propofol or dexmedetomidine starting at return of spontaneous circulation attenuated cerebral hyperemia and increased EEG slow oscillation power during and early after sedation (40 to 80% of the baseline). In contrast, delayed sedation failed to improve outcomes, without attenuating cerebral hyperemia and inducing slow-wave activity. Early administration of sedation with propofol or dexmedetomidine improved survival and neurologic outcomes in mice resuscitated from cardiac arrest and treated with hypothermia. The beneficial effects of sedation were accompanied by attenuation of the cerebral hyperemic response and enhancement of electroencephalographic slow-wave activity.

Transient oscillation dynamics during sleep provide a robust basis for electroencephalographic phenotyping and biomarker identification.

Transient oscillatory events in the sleep electroencephalogram represent short-term coordinated network activity. Of particular importance, sleep spindles are transient oscillatory events associated with memory consolidation, which are altered in aging and in several psychiatric and neurodegenerative disorders. Spindle identification, however, currently contains implicit assumptions derived from what waveforms were historically easiest to discern by eye, and has recently been shown to select only a high-amplitude subset of transient events. Moreover, spindle activity is typically averaged across a sleep stage, collapsing continuous dynamics into discrete states. What information can be gained by expanding our view of transient oscillatory events and their dynamics? In this paper, we develop a novel approach to electroencephalographic phenotyping, characterizing a generalized class of transient time-frequency events across a wide frequency range using continuous dynamics. We demonstrate that the complex temporal evolution of transient events during sleep is highly stereotyped when viewed as a function of slow oscillation power (an objective, continuous metric of depth-of-sleep) and phase (a correlate of cortical up/down states). This two-fold power-phase representation has large intersubject variability-even within healthy controls-yet strong night-to-night stability for individuals, suggesting a robust basis for phenotyping. As a clinical application, we then analyze patients with schizophrenia, confirming established spindle (12-15 Hz) deficits as well as identifying novel differences in transient non-rapid eye movement events in low-alpha (7-10 Hz) and theta (4-6 Hz) ranges. Overall, these results offer an expanded view of transient activity, describing a broad class of events with properties varying continuously across spatial, temporal, and phase-coupling dimensions.

Effects of continuous positive airway pressure treatment on sleep architecture in adults with obstructive sleep apnea and type 2 diabetes.

Obstructive sleep apnea (OSA) severely impacts sleep and has long-term health consequences. Treating sleep apnea with continuous positive airway pressure (CPAP) not only relieves obstructed breathing, but also improves sleep. CPAP improves sleep by reducing apnea-induced awakenings. CPAP may also improve sleep by enhancing features of sleep architecture assessed with electroencephalography (EEG) that maximize sleep depth and neuronal homeostasis, such as the slow oscillation and spindle EEG activity, and by reducing neurophysiological arousal during sleep (i.e., beta EEG activity). We examined cross-sectional differences in quantitative EEG characteristics of sleep, assessed with power spectral analysis, in 29 adults with type 2 diabetes treated with CPAP and 24 adults undergoing SHAM CPAP treatment (total n = 53). We then examined changes in spectral characteristics of sleep as the SHAM group crossed over to active CPAP treatment (n = 19). Polysomnography (PSG) from the CPAP titration night was used for the current analyses. Analyses focused on EEG frequencies associated with sleep maintenance and arousal. These included the slow oscillation (0.5–1 Hz), sigma activity (12–16 Hz, spindle activity), and beta activity (16–20 Hz) in F3, F4, C3, and C4 EEG channels. Whole night non-rapid eye movement (NREM) sleep and the first period of NREM spectral activity were examined. Age and sex were included as covariates. There were no group differences between CPAP and SHAM in spectral characteristics of sleep architecture. However, SHAM cross-over to active CPAP was associated with an increase in relative 12–16 Hz sigma activity across the whole night and a decrease in average beta activity across the whole night. Relative slow oscillation power within the first NREM period decreased with CPAP, particularly for frontal channels. Sigma and beta activity effects did not differ by channel. These findings suggest that CPAP may preferentially enhance spindle activity and mitigate neurophysiological arousal. These findings inform the neurophysiological mechanisms of improved sleep with CPAP and the utility of quantitative EEG measures of sleep as a treatment probe of improvements in neurological and physical health with CPAP.

0170 Slow Oscillation Power and Heart Rate Variability During Sleep Predicts Next-day Subjective Sleepiness in Healthy, Young Adults

Abstract Introduction High amplitude, slow oscillations in the electroencephalogram (EEG) often characterize the central nervous system’s homeostatic drive for sleep. Slow oscillations dominate the first part of the night and often dissipate as sleep need is satiated. These physiological changes are also reflected in next day subjective measures of sleepiness. Fluctuations in the autonomic nervous system, particularly parasympathetic activity, also coincide with slow wave sleep and are understood to represent bodily homeostasis. However, it is unclear if autonomic indicators effectively predict next-day sleepiness. Here, we investigated whether slow oscillatory (SO) power and cardiac autonomic activity during a night of sleep can predict next day subjective sleepiness. Methods 88 young (aged 18-35), healthy participants spent the night in a University sleep lab. Before and after sleep, participants completed the Karolinska Sleepiness Scale (KSS) to measure subjective sleepiness. Each participant slept with polysomnography, including electroencephalography and electrocardiography. From these measures, we assessed slow oscillation power (0.5-1Hz) and high frequency heart rate variability (HRV; 0.15-0.45 Hz) --an indicator of parasympathetic, vagally-mediated cardiac tone-- during the first quartile of slow wave sleep. Paired T-tests compared the differences in KSS scores pre- and post-sleep. Pearson’s correlations assessed bivariate associations between slow oscillatory power, high frequency HRV, and KSS scores. Mixed linear models assessed the ability of SO power and high frequency HRV to predict next day subjective sleepiness. Results No significant differences were found in KSS ratings pre- (M±SD = 4.23±1.92) and post-sleep (4.38±1.80). No bivariate correlations were present between pre-sleep KSS, SO, or high frequency HRV. A significant correlation between KSS-post sleep and SO power emerged (r=0.286, p=0.001). In Model 1, we found that SO power was a predictor of subjective sleepiness (p&amp;lt;0.001; AIC: 777.469). In Model 2, we included high frequency HRV and reduced the AIC to 515.588. Both slow oscillatory power (p&amp;lt;0.001) and high frequency HRV (p&amp;lt;0.001) were significant predictors of KSS after sleep in Model 2. Conclusion We found evidence that both central and autonomic indicators of sleep predict psychological measures of sleepiness. Using autonomic indicators to characterize physiological sleepiness, compared to in-lab polysomnography, may be a more generalizable and cost-effective approach. Support (If Any)

Spindle-targeted acoustic stimulation may stabilize an ongoing nap.

There have been numerous attempts over the decades to introduce closed-loop feedback to induce sleep oscillations. Recently, our group also introduced closed-loop acoustic feedback to the sleep spindle and reported improved procedural memory consolidation during a nap with spindle-targeted pink noise stimulation. In this study, we replicated our previous work with a control condition in an attempt to investigate the effect of closed-loop feedback on procedural memory. The results demonstrated a significant improvement in the subjects' procedural learning and reduced wake time during the nap with closed-loop acoustic stimulation compared with the control condition. Further, we found that randomized acoustic stimuli lead to more frequent spindle activity and a faster decrement in slow oscillation power compared with the sham condition. There were strong correlations between slow oscillation and measures related to sleep efficiency as well. Interestingly, we found a marginal enhancement in procedural learning during the nap with the closed-loop acoustic stimulation compared with the sham nap. We also found a marginal decrement in theta power during the nap with closed-loop feedback compared with the sham nap, and a negative correlation between slow oscillation and theta power. We speculate that the marginal improvement in procedural learning may be related to closed-loop acoustic feedback's stabilization of non-rapid eye movement sleep. Taken together, this study shows that the closed-loop feedback method has the potential to stabilize sleep and improve procedural memory.

Human NREM Sleep Promotes Brain-Wide Vasomotor and Respiratory Pulsations.

The physiological underpinnings of the necessity of sleep remain uncertain. Recent evidence suggests that sleep increases the convection of cerebrospinal fluid (CSF) and promotes the export of interstitial solutes, thus providing a framework to explain why all vertebrate species require sleep. Cardiovascular, respiratory and vasomotor brain pulsations have each been shown to drive CSF flow along perivascular spaces, yet it is unknown how such pulsations may change during sleep in humans. To investigate these pulsation phenomena in relation to sleep, we simultaneously recorded fast fMRI, magnetic resonance encephalography (MREG), and electroencephalography (EEG) signals in a group of healthy volunteers. We quantified sleep-related changes in the signal frequency distributions by spectral entropy analysis and calculated the strength of the physiological (vasomotor, respiratory, and cardiac) brain pulsations by power sum analysis in 15 subjects (age 26.5 ± 4.2 years, 6 females). Finally, we identified spatial similarities between EEG slow oscillation (0.2–2 Hz) power and MREG pulsations. Compared with wakefulness, nonrapid eye movement (NREM) sleep was characterized by reduced spectral entropy and increased brain pulsation intensity. These effects were most pronounced in posterior brain areas for very low-frequency (≤0.1 Hz) vasomotor pulsations but were also evident brain-wide for respiratory pulsations, and to a lesser extent for cardiac brain pulsations. There was increased EEG slow oscillation power in brain regions spatially overlapping with those showing sleep-related MREG pulsation changes. We suggest that reduced spectral entropy and enhanced pulsation intensity are characteristic of NREM sleep. With our findings of increased power of slow oscillation, the present results support the proposition that sleep promotes fluid transport in human brain.SIGNIFICANCE STATEMENT We report that the spectral power of physiological brain pulsation mechanisms driven by vasomotor, respiration, and cardiac rhythms in human brain increase during sleep, extending previous observations of their association with glymphatic brain clearance during sleep in rodents. The magnitudes of increased pulsations follow the rank order of vasomotor greater than respiratory greater than cardiac pulsations, with correspondingly declining spatial extents. Spectral entropy, previously known as vigilance and as an anesthesia metric, decreased during NREM sleep compared with the awake state in very low and respiratory frequencies, indicating reduced signal complexity. An EEG slow oscillation power increase occurring in the early sleep phase (NREM 1–2) spatially overlapped with pulsation changes, indicating reciprocal mechanisms between those measures.

Accelerated Aging Characterizes the Early Stage of Alzheimer's Disease.

For Alzheimer’s disease (AD), aging is the main risk factor, but whether cognitive impairments due to aging resemble early AD deficits is not yet defined. When working with mouse models of AD, the situation is just as complicated, because only a few studies track the progression of the disease at different ages, and most ignore how the aging process affects control mice. In this work, we addressed this problem by comparing the aging process of PS2APP (AD) and wild-type (WT) mice at the level of spontaneous brain electrical activity under anesthesia. Using local field potential recordings, obtained with a linear probe that traverses the posterior parietal cortex and the entire hippocampus, we analyzed how multiple electrical parameters are modified by aging in AD and WT mice. With this approach, we highlighted AD specific features that appear in young AD mice prior to plaque deposition or that are delayed at 12 and 16 months of age. Furthermore, we identified aging characteristics present in WT mice but also occurring prematurely in young AD mice. In short, we found that reduction in the relative power of slow oscillations (SO) and Low/High power imbalance are linked to an AD phenotype at its onset. The loss of SO connectivity and cortico-hippocampal coupling between SO and higher frequencies as well as the increase in UP-state and burst durations are found in young AD and old WT mice. We show evidence that the aging process is accelerated by the mutant PS2 itself and discuss such changes in relation to amyloidosis and gliosis.

Disruptions in sleep‐dependent brain rhythms contribute to Alzheimer’s pathogenesis

Sleep-dependent brain rhythms are important for memory consolidation during sleep, and Alzheimer's disease (AD) patients experience memory disturbances. We sought to examine sleep-dependent brain rhythms, slow oscillations, in an animal model of AD (APP mice). The power of slow oscillations was decreased early in the disease progression. Soluble amyloid-beta was sufficient to disrupt the slow waves. Cortical GABA levels were low in APP mice and application of exogenous GABA restored the slow oscillations, indicating that aberrant excitatory activity within the cortical circuit was responsible for slow oscillation dysfunction. Next we sought to manipulate slow waves in APP mice with optogenetics. Driving slow oscillations at normal frequency with light activation of channelrhodopsin-2 (ChR2) expressed in cortical neurons restored slow wave power by synchronizing neuronal activity. Using multiphoton microscopy, we performed longitudinal imaging of senile plaques and monitored intracellular calcium. Cytosolic calcium is a surrogate marker of neuronal activity and is normally tightly regulated. We had previously demonstrated that resting calcium levels measured with the genetically encoded calcium sensor YellowCameleon 3.6 were elevated in a subset of neurons in APP transgenics, and hypothesized that an effective treatment would restore calcium to control levels. Driving slow oscillation activity with optogenetics halted amyloid plaque deposition and prevented calcium overload associated with this pathology. On the other hand, driving slow oscillation activity at twice the normal frequency resulted in increased amyloid production, increased amyloid plaque deposition, disruptions in neuronal calcium homeostasis, and loss of synaptic spines. Therefore, while restoration of physiological circuit dynamics is sufficient to abrogate the progression of Alzheimer's disease pathology and should be considered an avenue for clinical treatment of patients with sleep disorders, pathophysiological stimulation of neuronal circuits leads to activity dependent acceleration of amyloid production, aggregation and downstream neuronal dysfunction.

Relationship between the Spectral Power Density of Sleep Electroencephalography and Psychiatric Symptoms in Patients with Breathing-related Sleep Disorder

ObjectivePatients with breathing-related sleep disorder (BRSD) often complain of psychiatric symptoms such as depression in addition to snoring, excessive sleepiness, and disturbed sleep. However, the relationship between psychiatric symptoms and severity of sleep apnea in BRSD is controversial. We conducted this study to investigate the relationship between psychiatric symptoms and sleep electroencephalography (EEG) findings in BRSD patients using spectral analysis.MethodsAll participants underwent polysomnography and evaluation using Symptom Checklist-90-Revised (SCL-90-R) scale. We analyzed the absolute spectral power density values of standard EEG frequency bands in the participants (n = 169) with BRSD during the non-rapid eye movement (NREM) sleep period. We performed correlation analysis between the domain scores of SCL-90-R scale and the absolute values of the EEG frequency bands.ResultsSignificant positive correlation was observed between the absolute spectral power density values in the slow oscillation band and the degree of paranoid ideation (r = 0.226, p = 0.028) and depression (r = 0.216, p = 0.044) in SCL-90-R. The multiple linear regression model showed that higher paranoid ideation domain score (B = 0.007, p = 0.020), younger age (B = −0.011, p < 0.001), and female sex (B = 0.213, p = 0.004) were associated with higher slow oscillation power during NREM sleep.ConclusionThe results of the present study suggested a relationship between sleep EEG and psychiatric symptoms in patients with BRSD. This relationship needs to be validated with further studies.

No benefit of auditory closed-loop stimulation on memory for semantically-incongruent associations

Auditory closed-loop stimulation has gained traction in recent years as a means of enhancing slow oscillatory activity and, consequently, sleep-associated memory consolidation. Previous studies on this topic have primarily focused on the consolidation of semantically-congruent associations. In this study, we investigated the effect of auditory closed-loop stimulation on the overnight retention of semantically-incongruent associations. Twelve healthy males (age: M = 20.06, SD = 2.02 years) participated in two experimental conditions (simulation and sham). In the stimulation condition, clicks were delivered in phase with slow oscillation up-states, whereas in the sham condition no auditory stimuli were applied. Corroborating earlier work, stimulation (vs. sham) enhanced the slow oscillation rhythm, phase-coupled spindle activity and slow oscillation power. However, there was no benefit of stimulation on overnight memory retention. These findings suggest that closed-loop stimulation does not benefit semantically-incongruent associations.

0350 Characterizing Continuous Changes in Spectral Dynamics of Sleep EEG as a Function of Age

Abstract Introduction Sleep is a continuous and dynamic physiological process. Current research practice, however, limits our ability to observe electroencephalography (EEG) oscillation dynamics by breaking sleep into discrete stages. In this study, we propose a novel quantitative framework that represents population-level changes in sleep EEG spectral dynamics as a function of age, preserving the information-rich spectral dynamics of sleep data. Rather than relying on sleep stages, our approach uses slow-oscillation power (SO-power) as an objective, continuous-valued correlate of sleep depth. Methods We analyzed the EEG signal (Fz-Cz, 256 Hz sampling rate) from a subset of the Multi-Ethnic Study of Atherosclerosis (MESA) study participants (n = 2056, 53.6% female, age: mean 69.37 ± 9.12, range 54 - 94) who underwent polysomnography. For each subject, we computed the sleep EEG multitaper spectrogram and extracted the total baseline-normalized SO-power (0.1 - 1.5 Hz). We next computed mean EEG spectral power as a function of SO-power, which we then tracked across all subjects as a function of age in sliding windows. Results The population analysis shows apparent, continuous changes in time-frequency domain features of the EEG as a function of a sleep depth along with age, that would be otherwise lost in traditional analyses. Moreover, by analyzing the directionality of the SO-power, we show that there is no apparent difference in neural activity during deepening sleep and lightening sleep; thus EEG sleep state is likely non-directional. Conclusion Our results show that state-based sleep dynamics of the EEG power spectrum can comprehensively be represented using SO-power as a surrogate of sleep depth. This representation identifies state-based activity independent of the temporal evolution of sleep architecture. As such, it is a powerful tool for analysis and phenotyping of EEG activity in large cohorts. Support The Biomedical Global Talent Nurturing Program through the Korea Health Industry Development Institute, funded by the Ministry of Health &amp; Welfare, Republic of Korea (HI19C1065) to HK, National Institute of Neurological Disorders and Stroke (NINDS, R01 NS-096177) to MP.

A daytime nap restores hippocampal function and improves declarative learning.

Study ObjectivesDaytime naps can confer benefits on subsequent declarative learning, but the physiological correlates of this improvement are less well studied. We examined learning following a daytime nap compared with an equivalent waking period using fMRI and polysomnography. MethodsForty healthy young adults who slept normally the previous night encoded word pair lists in an MRI scanner at 13:00 and 16:30. Between sessions, participants either stayed awake and watched a documentary (Wake Group; N = 20) or had a 90-minute nap opportunity (Nap Group; N = 20) monitored by polysomnography. Approximately 40 minutes after completing each encoding session, memory for learned words was assessed using cued-recall.ResultsA significant Session × Group interaction effect (p < 0.001) was observed in which memory was significantly improved in the Nap but not in the Wake group (p < 0.001). There was also a Session × Run × Group interaction effect in the left hippocampus (p = 0.001), whereby activation during word pair encoding increased only following the nap. Both performance improvement (rs = 0.46, p = 0.04) and nap-related increase in hippocampal activation (rs = 0.46, p = 0.04) were correlated with nap spindle count (12–15 Hz) but not with slow oscillation power (p’s ≥ 0.18).ConclusionsAfter a habitual nocturnal sleep, participants who had a 90-minute afternoon nap encoded word pairs better than a comparable group who stayed awake. Increases in hippocampal activation following the nap suggest restored hippocampal function. Naptime spindles may contribute to improved memory.

A Glial-Silicon Nanowire Electrode Junction Enabling Differentiation and Noninvasive Recording of Slow Oscillations from Primary Astrocytes.

The correct human brain function is dependent on the activity of non-neuronal cells called astrocytes. The bioelectrical properties of astrocytes in vitro do not closely resemble those displayed in vivo and the former are incapable of generating action potential; thus, reliable approaches in vitro for noninvasive electrophysiological recording of astrocytes remain challenging for biomedical engineering. Here it is found that primary astrocytes grown on a device formed by a forest of randomly oriented gold coated-silicon nanowires, resembling the complex structural and functional phenotype expressed by astrocytes in vivo. The device enables noninvasive extracellular recording of the slow-frequency oscillations generated by differentiated astrocytes, while flat electrodes failed on recording signals from undifferentiated cells. Pathophysiological concentrations of extracellular potassium, occurring during epilepsy and spreading depression, modulate the power of slow oscillations generated by astrocytes. A reliable approach to study the role of astrocytes function in brain physiology and pathologies is presented.

The spectral fingerprint of sleep problems in post-traumatic stress disorder.

Study ObjectivesSleep problems are a core feature of post-traumatic stress disorder (PTSD). The aim of this study was to find a robust objective measure for the sleep disturbance in patients having PTSD.MethodsThe current study assessed EEG power across a wide frequency range and multiple scalp locations, in matched trauma-exposed individuals with and without PTSD, during rapid eye movement (REM) and non-REM (NREM) sleep. In addition, a full polysomnographical evaluation was performed, including sleep staging and assessment of respiratory function, limb movements, and heart rate. The occurrence of sleep disorders was also assessed.ResultsIn patients having PTSD, NREM sleep shows a substantial loss of slow oscillation power and increased higher frequency activity compared with controls. The change is most pronounced over right-frontal sensors and correlates with insomnia. PTSD REM sleep shows a large power shift in the opposite direction, with increased slow oscillation power over occipital areas, which is strongly related to nightmare activity and to a lesser extent with insomnia. These pronounced spectral changes occur in the context of severe subjective sleep problems, increased occurrence of various sleep disorders and modest changes in sleep macrostructure.ConclusionsThis is the first study to show pronounced changes in EEG spectral topologies during both NREM and REM sleep in PTSD. Importantly, the observed power changes reflect the hallmarks of PTSD sleep problems: insomnia and nightmares and may thus be specific for PTSD. A spectral index derived from these data distinguishes patients from controls with high effect size, bearing promise as a candidate biomarker.

Does working memory improvement benefit from sleep in older adults?

Working Memory (WM), is an important factor influencing many higher-order cognitive functions that decline with age. Repetitive training appears to increase WM, yet the mechanisms underlying this improvement are not understood. Sleep has been shown to benefit long-term memory formation and may also play a role in WM enhancement in young adults. However, considering age-related decline in sleep, it is uninvestigated whether sleep will facilitate WM in older adults. In the present work, we investigated the impact of a nap, quiet wakefulness (QW) and active wakefulness (AW) on within-day training on the Operation Span (OSPAN) task in older adults. Improvement in WM was found following a nap and QW, but not active wake. Furthermore, better WM was associated with shared electrophysiological features, including slow oscillation (SO, 0.5–1 Hz) power in both the nap and QW, and greater coupling between SO and sigma (12–15 Hz) in the nap. In summary, our data suggest that WM improvement in older adults occurs opportunistically during offline periods that afford enhancement in slow oscillation power, and that further benefits may come with cross-frequency coupling of neural oscillations during sleep.

Age-Dependent Changes in the Propofol-Induced Electroencephalogram in Children With Autism Spectrum Disorder.

Patients with autism spectrum disorder (ASD) often require sedation or general anesthesia. ASD is thought to arise from deficits in GABAergic signaling leading to abnormal neurodevelopment. We sought to investigate differences in how ASD patients respond to the GABAergic drug propofol by comparing the propofol-induced electroencephalogram (EEG) of ASD and neurotypical (NT) patients. This investigation was a prospective observational study. Continuous 4-channel frontal EEG was recorded during routine anesthetic care of patients undergoing endoscopic procedures between July 1, 2014 and May 1, 2016. Study patients were defined as those with previously diagnosed ASD by DSM-V criteria, aged 2–30 years old. NT patients were defined as those lacking neurological or psychiatric abnormalities, aged 2–30 years old. The primary outcome was changes in propofol-induced alpha (8–13 Hz) and slow (0.1–1 Hz) oscillation power by age. A post hoc analysis was performed to characterize incidence of burst suppression during propofol anesthesia. The primary risk factor of interest was a prior diagnosis of ASD. Outcomes were compared between ASD and NT patients using Bayesian methods. Compared to NT patients, slow oscillation power was initially higher in ASD patients (17.05 vs. 14.20 dB at 2.33 years), but progressively declined with age (11.56 vs. 13.95 dB at 22.5 years). Frontal alpha power was initially lower in ASD patients (17.65 vs. 18.86 dB at 5.42 years) and continued to decline with age (6.37 vs. 11.89 dB at 22.5 years). The incidence of burst suppression was significantly higher in ASD vs. NT patients (23.0% vs. 12.2%, p < 0.01) despite reduced total propofol dosing in ASD patients. Ultimately, we found that ASD patients respond differently to propofol compared to NT patients. A similar pattern of decreased alpha power and increased sensitivity to burst suppression develops in older NT adults; one interpretation of our data could be that ASD patients undergo a form of accelerated neuronal aging in adolescence. Our results suggest that investigations of the propofol-induced EEG in ASD patients may enable insights into the underlying differences in neural circuitry of ASD and yield safer practices for managing patients with ASD.