Increase In Slow Wave Activity Research Articles

Temporal dynamics of awakenings from slow-wave sleep in non-rapid eye movement parasomnia.

Non-rapid eye movement parasomnia disorders, also called disorders of arousal, are characterized by abnormal nocturnal behaviours, such as confusional arousals or sleep walking. Their pathophysiology is not yet fully understood, and objective diagnostic criteria are lacking. It is known, however, that behavioural episodes occur mostly in the beginning of the night, after an increase in slow-wave activity during slow-wave sleep. A better understanding of the prospect of such episodes may lead to new insights in the underlying mechanisms and eventually facilitate objective diagnosis. We investigated temporal dynamics of transitions from slow-wave sleep of 52 patients and 79 controls. Within the patient group, behavioural and non-behavioural N3 awakenings were distinguished. Patients showed a higher probability to wake up after an N3 bout ended than controls, and this probability increased with N3 bout duration. Bouts longer than 15 min resulted in an awakening in 73% and 34% of the time in patients and controls, respectively. Behavioural episodes reduced over sleep cycles due to a reduction in N3 sleep and a reducing ratio between behavioural and non-behavioural awakenings. In the first two cycles, N3 bouts prior to non-behavioural awakenings were significantly shorter than N3 bouts advancing behavioural awakenings in patients, and N3 awakenings in controls. Our findings provide insights in the timing and prospect of both behavioural and non-behavioural awakenings from N3, which may result in prediction and potentially prevention of behavioural episodes. This work, moreover, leads to a more complete characterization of a prototypical hypnogram of parasomnias, which could facilitate diagnosis.

SLEEP MICROARCHITECTURE IN MILD COGNITIVE IMPAIRMENT: A HIGH‐DENSITY EEG STUDY

AbstractBackgroundSleep disturbance and sleep disorders are potential risk factors for dementia. Adults with mild cognitive impairment (MCI) are at increased risk of developing dementia and many report disturbed sleep. Altered sleep neurophysiology including deficits in sleep spindles and slow wave activity (SWA) during NREM sleep have been reported in MCI, though studies are sparse. These NREM EEG oscillations are crucial for overnight memory consolidation and optimal daytime functioning. Abnormal EEG activity during sleep in MCI may adversely impact sleep‐dependent memory processes and cognitive trajectory. This study is the first to examine sleep microarchitecture using high‐density EEG technology in MCI.MethodOlder adults with multi‐domain MCI (n = 19, mean age 68.5 years) and cognitively‐intact controls (n = 22, 69 years) had 256‐channel high‐density EEG recordings during overnight polysomnography and resting wakefulness. Declarative (word paired associates) and procedural (finger tapping) memory tasks were administered before and after sleep. Neuropsychological testing and brain MRI scans were also performed. After artefact processing, spectral analysis was performed for high‐density EEG recordings. Topographical power maps were calculated for standard frequency ranges for NREM sleep (N2 and N3 (slow wave sleep)). Maps were compared between groups using normalized power (z‐scores computed for each subject).ResultThe MCI group had worse declarative (% retention, MCI vs Controls: 84.2 ± 16.6 vs. 94.5 ± 7.8, p = 0.024) and procedural (% early improvement: 92.9 ± 11.0 vs. 103.0 ± 12.0%, p = 0.017) overnight memory consolidation than the controls. Topographic analysis of high‐density EEG data revealed a regional increase in SWA (1‐4.5Hz) EEG power during N3 in a cluster of 18 electrodes overlying the centroparietal cortex in the MCI group (cluster mean t‐value = 3.11, p = 0.0036, uncorrected) and a regional reduction in SWA in the left frontal (5 channels, t = ‐3.75, p<0.001) and right temporal areas (5 channels, t = ‐3.46, p = 0.001), Figure 1.ConclusionOvernight memory consolidation was impaired in this MCI population. Regional differences in SWA during deep sleep were present in distinct brain regions and may indicate pathology. Future analysis exploring associations between EEG abnormalities with underlying brain structures may provide mechanistic insights into the impact of altered sleep neurophysiology on cognitive outcomes in MCI.

Homeostatic NREM sleep and salience network function in adult mice exposed to ethanol during development.

Developmental exposure to ethanol is a leading cause of cognitive, emotional and behavioral problems, with fetal alcohol spectrum disorder (FASD) affecting more than 1:100 children. Recently, comorbid sleep deficits have been highlighted in these disorders, with sleep repair a potential therapeutic target. Animal models of FASD have shown non-REM (NREM) sleep fragmentation and slow-wave oscillation impairments that predict cognitive performance. Here we use a mouse model of perinatal ethanol exposure to explore whether reduced sleep pressure may contribute to impaired NREM sleep, and compare the function of a brain network reported to be impacted by insomnia-the Salience network-in developmental ethanol-exposed mice with sleep-deprived, saline controls. Mice were exposed to ethanol or saline on postnatal day 7 (P7) and allowed to mature to adulthood for testing. At P90, telemetered cortical recordings were made for assessment of NREM sleep in home cage before and after 4 h of sleep deprivation to assess basal NREM sleep and homeostatic NREM sleep response. To assess Salience network functional connectivity, mice were exposed to the 4 h sleep deprivation period or left alone, then immediately sacrificed for immunohistochemical analysis of c-Fos expression. The results show that developmental ethanol severely impairs both normal rebound NREM sleep and sleep deprivation induced increases in slow-wave activity, consistent with reduced sleep pressure. Furthermore, the Salience network connectome in rested, ethanol-exposed mice was most similar to that of sleep-deprived, saline control mice, suggesting a sleep deprivation-like state of Salience network function after developmental ethanol even without sleep deprivation.

Effects of daily exposure to peat smoke on the reproductive and nervous systems in male white rats

Introduction. The regular occurrence of large-scale peat fires is an urgent medical and environmental problem of the modern scientific community. The peat smoke is a complex mixture of pollutants that have a serious impact on air quality and public health. 
 Materials and methods. Adult male rats were exposed to peat smoke for 24 hours, the concentrations of PM2.5 and CO were 0.92±0.08 mg/m3 and 40.8±1.9 mg/m3, respectively. After exposure an open field examination, EEG examination and histological analysis of the testes and brain were performed, after which they were mated with intact females. Postnatal death of offspring in the first week of life, body weight, behaviour and electroencephalography indicators during puberty were evaluated.
 Results. There was showed an increase in motor activity, anxiety, and violation of EEG indicators in rat males exposed to peat smoke. Both an increase in shadow cells and degeneratively altered neurons in the nervous tissue were found. No changes were detected in the testes. Exposure to peat smoke during conception increased stillbirth and mortality of offspring during the first week of life, but did not affect weight gain. Violation of behaviour structure was recorded only in females offspring. An increase in slow-wave activity of the brain in males offspring was revealed.
 Limitations. The study was limited to studying the effects of a single 24-hour exposure to peat smoke on outbred white rats.
 Conclusion. A single peat smoke exposure for 24 hours at a concentration of PM2.5=0.92±0.08 mg/m3 and CO=40.8±1.9 mg/m3 leads to significant morphological and functional changes in the CNS. In the absence of a gonadotoxic effect, peat smoke exposure on males before mating causes specific changes in the behavior and bioelectrical activity of the brain of their offspring.

0095 Magnitude of Temperature Drop Prior to Sleep Onset May Predict Increase in Slow Wave Sleep

Abstract Introduction Neural circuitry implicated in thermoregulation is known to be interdependent with that implicated in regulation of sleep-wake state. In addition, previous studies in both rodent and human have shown that the sleep-associated decline in core body temperature (CBT) is associated with subsequent slow wave sleep. We sought to replicate this association in cognitively normal older adults, and extend upon previous studies by using automated telemetric methods to measure CBT. Methods Thirty-one cognitively normal and mildly cognitively impaired (MCI) older adults (age 68 ± 6 years, 18 female, 3 MCI) underwent measurement of CBT for two consecutive nights with a telemetric sensor, during which lab nocturnal polysomnography was simultaneously performed. Data from the second night were used. A validated algorithm was used to preprocess CBT to exclude and fill artifactual data outliers and small gaps, respectively. The sleep-associated CBT was calculated with an automated procedure by identifying the CBT decrease between the first peak in CBT identified prior to ‘Lights Out’ and the lowest value following Lights Out. Slow wave activity (SWA) increase was calculated as increase relative to baseline in the relative spectral power (0.5-4.0 Hz, F3-M2) in the first 5 second epoch following lights out. Results Of the 31 participants, 21 had both good quality EEG and CBT data, with an average total sleep time of 7.5 ± 1.5 hours, and an average duration 46.6 ± 18.5 hours of CBT data collected. There was a strong positive correlation between the magnitude of CBT decline and subsequent SWA (rho = 0.70, p < 0.001 Spearman’s Rank correlation), supporting previous results. Conclusion This is one of the first studies to obtain simultaneous CBT and NPSG data in older adults using an ingestible telemetric sensor. Our results support the previous research that there is a significant relationship between sleep-associated body cooling prior to sleep onset and increase in SWA. This highlights the potential for future therapeutic thermal intervention in older adults to improve sleep and sleep mediated health conditions. Further research with a bigger sample size will be necessary to control for variables such as obstructive sleep apnea and cognition status. Support (if any) NIH R01AG070866, R21AG055002, K25HL151912,

0128 Muscle injury induces an increase in total and NREM sleep time

Abstract Introduction This study describes macro- and micro- sleep responses to a myotoxic skeletal muscle injury and investigates possible mechanisms. Methods We recorded the electroencephalogram(EEG)/electromyogram(EMG) of 24 wistar rats before and after induction of Tibialis Anterior muscle injury (n=8 per group: control, control +buprenorphine and injured). A top-down analysis of sleep characteristics was processed from total sleep time (TST), sleep stages, sleep stability, spectral-analysis, and spindles. To further investigate the mechanisms involved, we analyzed the protein level of sleep regulatory molecules including TNF-α, IL-1β, IGF-1, BMAL1 in plasma, frontal cortex, hippocampus, and tibialis anterior, collected at Day +2 after injury from non-EEG/EMG implanted rats. Results Muscle injury induces a significant increase in total sleep time at 48 and 72h post-injury, specific to NREM sleep. These increases occur during the dark period and are associated with higher stability of sleep over 24h, without change in the different power/frequency spectral bands of NREM/REM sleep. There was no corresponding sleep increase in slow-wave activity or spindle density, nor were there changes in brain levels of the sleep-regulating proinflammatory cytokine IL-1β, which is otherwise involved in the local response to injury. Conversely, decreased protein levels of brain IGF-1 and muscle BMAL1, a core circadian clock gene, after injury may play a role in increased sleep time. Conclusion Muscle injury induces an increase in total sleep time at 48- and 72-hours post-injury, specific to NREM sleep during the dark period in rats and is associated with higher sleep stability over 24 hours. Support (if any)

Muscle injury induces an increase in total and non-rapid eye movement sleep time.

This study describes macro- and micro-sleep responses to a myotoxic skeletal muscle injury and investigates possible mechanisms. We recorded the electroencephalogram (EEG)/electromyogram (EMG) of 24 Wistar rats before and after induction of tibialis anterior muscle injury (n = 8 per group: control, control + buprenorphine and injured). A top-down analysis of sleep characteristics was processed from total sleep time (TST), sleep stages, sleep stability, spectral analysis, and spindles. To further investigate the mechanisms involved, we analyzed the protein level of sleep regulatory molecules including tumor necrosis factor- α (TNF-α), interleukin-1β (IL-1β), insulin-like growth factor-1 (IGF-1), and brain and muscle ARNT-like 1 (BMAL1) in plasma, frontal cortex, hippocampus, and tibialis anterior, collected at day +2 after injury from non-EEG/EMG implanted rats. Muscle injury induces a significant increase in TST at 48 and 72 h post-injury, specific to non-rapid eye movement (NREM) sleep. These increases occur during the dark period and are associated with the higher stability of sleep over 24 h, without change in the different power/frequency spectral bands of NREM/REM sleep. There was no corresponding sleep increase in slow-wave activity or spindle density, nor were there changes in brain levels of the sleep-regulating proinflammatory cytokine IL-1β, which is otherwise involved in the local response to injury. Conversely, decreased protein levels of brain IGF-1 and muscle BMAL1, a core circadian clock gene, after injury may play a role in increased sleep time. Muscle injury induces an increase in total sleep time at 48- and 72-h post-injury, specific to NREM sleep during the dark period in rats and is associated with higher sleep stability over 24 h.

Chronic sleep restriction in rats leads to a weakening of compensatory reactions in response to acute sleep deprivation

To identify features in the compensatory mechanisms of sleep regulation in response to acute sleep deprivation after chronic sleep restriction in rats. Male Wistar rats 7-8 months old underwent 5-day sleep restriction: 3 h of sleep deprivation and 1 h of sleep opportunity repeating throughout each day. Six-hour acute total sleep deprivation was performed at the beginning of daylight hours on the 3rd day after sleep restriction. Polysomnogramms were recorded throughout the day before chronic sleep restriction, on the 2nd recovery day after chronic sleep restriction and after acute sleep deprivation. The control group was not subjected to chronic sleep restriction. The animals after chronic sleep restriction had the compensatory increase in total sleep time in response to acute sleep deprivation weaker than in control animals. Animals after sleep restriction had the compensatory increase in the time of slow-wave sleep (SWS) only in the first 6 hours after acute sleep deprivation, whereas in control animals the period of compensation of SWS lasted 12 hours. A compensatory increase in slow-wave activity (SWA) was observed in both groups of animals, but in animals experiencing chronic sleep restriction the amplitude of SWA after acute sleep deprivation was less than in control animals. A compensatory increase in REM sleep in sleep restricted animals occurred immediately after acute sleep deprivation and coincides with a compensatory increase in SWS and SWA, whereas in control conditions these processes are spaced in time. Compensatory reactions in response to acute sleep deprivation (sleep homeostasis) are weakened in animals subjected to chronic sleep restriction, as the reaction time and amplitude are reduced.

Distinct signatures of loss of consciousness in focal impaired awareness versus tonic-clonic seizures.

Loss of consciousness is a hallmark of many epileptic seizures and carries risks of serious injury and sudden death. While cortical sleep-like activities accompany loss of consciousness during focal impaired awareness seizures, the mechanisms of loss of consciousness during focal to bilateral tonic-clonic seizures remain unclear. Quantifying differences in markers of cortical activation and ictal recruitment between focal impaired awareness and focal to bilateral tonic-clonic seizures may also help us to understand their different consequences for clinical outcomes and to optimize neuromodulation therapies. We quantified clinical signs of loss of consciousness and intracranial EEG activity during 129 focal impaired awareness and 50 focal to bilateral tonic-clonic from 41 patients. We characterized intracranial EEG changes both in the seizure onset zone and in areas remote from the seizure onset zone with a total of 3386 electrodes distributed across brain areas. First, we compared the dynamics of intracranial EEG sleep-like activities: slow-wave activity (1-4 Hz) and beta/delta ratio (a validated marker of cortical activation) during focal impaired awareness versus focal to bilateral tonic-clonic. Second, we quantified differences between focal to bilateral tonic-clonic and focal impaired awareness for a marker validated to detect ictal cross-frequency coupling: phase-locked high gamma (high-gamma phased-locked to low frequencies) and a marker of ictal recruitment: the epileptogenicity index. Third, we assessed changes in intracranial EEG activity preceding and accompanying behavioural generalization onset and their correlation with electromyogram channels. In addition, we analysed human cortical multi-unit activity recorded with Utah arrays during three focal to bilateral tonic-clonic seizures. Compared to focal impaired awareness, focal to bilateral tonic-clonic seizures were characterized by deeper loss of consciousness, even before generalization occurred. Unlike during focal impaired awareness, early loss of consciousness before generalization was accompanied by paradoxical decreases in slow-wave activity and by increases in high-gamma activity in parieto-occipital and temporal cortex. After generalization, when all patients displayed loss of consciousness, stronger increases in slow-wave activity were observed in parieto-occipital cortex, while more widespread increases in cortical activation (beta/delta ratio), ictal cross-frequency coupling (phase-locked high gamma) and ictal recruitment (epileptogenicity index). Behavioural generalization coincided with a whole-brain increase in high-gamma activity, which was especially synchronous in deep sources and could not be explained by EMG. Similarly, multi-unit activity analysis of focal to bilateral tonic-clonic revealed sustained increases in cortical firing rates during and after generalization onset in areas remote from the seizure onset zone. Overall, these results indicate that unlike during focal impaired awareness, the neural signatures of loss of consciousness during focal to bilateral tonic-clonic consist of paradoxical increases in cortical activation and neuronal firing found most consistently in posterior brain regions. These findings suggest differences in the mechanisms of ictal loss of consciousness between focal impaired awareness and focal to bilateral tonic-clonic and may account for the more negative prognostic consequences of focal to bilateral tonic-clonic.

Characterising the relationship between sleep stages and associated spectral power in diabetes

Sleep disturbances are prevalent in the UK and globally, with sleep data from across 13 countries suggesting that only 55% of adults are satisfied with their sleep. Disturbed sleep is found in diabetes which is one of the most serious diseases worldwide. Specifically, relationships have been found between glycaemic control and sleep duration and quality. It is currently unclear how diabetes specifically affects sleep stages, and their associated spectral power. This study aims to characterise the relationship between polysomnography-measured specific sleep stages and associated spectral power in adults with diabetes and control participants. This study involved a secondary data analysis of multi-cohort Sleep Heart Health (SHH) data using a matched-pairs design. The sample included 414 participants (211 males, 203 females, mean age (years) 70.0, 95% CI [69.1, 70.9]) 207 with diabetes and 207 matched controls. The results suggest an increase in light sleep in diabetes, specifically NREM stage 2 sleep duration (p = 0.05) and percentage (p = 0.04), with an increase in slow-wave activity (p = 0.03) and delta power (p = 0.04) during NREM stage 1 sleep. Slow-wave sleep duration marginally reduced in diabetes, (p = 0.09), whilst delta power (p < 0.01), slow-wave activity (p = 0.02) and theta power (p < 0.01) in slow-wave sleep also significantly reduced in diabetes compared to control participants. No other changes to sleep stages or associated spectral power were observed. These results suggest a potential homoeostatic influence of sleep on glycaemic control, which should be further explored in future research.

Effects of auditory sleep modulation approaches on brain oscillatory and cardiovascular dynamics.

Slow waves, the hallmark feature of deep nonrapid eye movement sleep, do potentially drive restorative effects of sleep on brain and body functions. Sleep modulation techniques to elucidate the functional role of slow waves thus have gained large interest. Auditory slow wave stimulation is a promising tool; however, directly comparing auditory stimulation approaches within a night and analyzing induced dynamic brain and cardiovascular effects are yet missing. Here, we tested various auditory stimulation approaches in a windowed, 10 s ON (stimulations) followed by 10 s OFF (no stimulations), within-night stimulation design and compared them to a SHAM control condition. We report the results of three studies and a total of 51 included nights and found a large and global increase in slow-wave activity (SWA) in the stimulation window compared to SHAM. Furthermore, slow-wave dynamics were most pronouncedly increased at the start of the stimulation and declined across the stimulation window. Beyond the changes in brain oscillations, we observed, for some conditions, a significant increase in the mean interval between two heartbeats within a stimulation window, indicating a slowing of the heart rate, and increased heart rate variability derived parasympathetic activity. Those cardiovascular changes were positively correlated with the change in SWA, and thus, our findings provide insight into the potential of auditory slow wave enhancement to modulate cardiovascular restorative conditions during sleep. However, future studies need to investigate whether the potentially increased restorative capacity through slow-wave enhancements translates into a more rested cardiovascular system on a subsequent day.

Functional changes in brain oscillations in dementia: a review.

A growing body of evidence indicates that several characteristics of electroencephalography (EEG) and magnetoencephalography (MEG) play a functional role in cognition and could be linked to the progression of cognitive decline in some neurological diseases such as dementia. The present paper reviews previous studies investigating changes in brain oscillations associated to the most common types of dementia, namely Alzheimer's disease (AD), frontotemporal degeneration (FTD), and vascular dementia (VaD), with the aim of identifying pathology-specific patterns of alterations and supporting differential diagnosis in clinical practice. The included studies analysed changes in frequency power, functional connectivity, and event-related potentials, as well as therelationship between electrophysiological changes andcognitive deficits. Current evidence suggests that an increase in slow wave activity (i.e.,theta and delta) as well as a general reduction in the power of faster frequency bands (i.e.,alpha and beta) characterizes AD, VaD, and FTD. Additionally, compared to healthy controls, AD exhibits alteration in latencies and amplitudes of the most common event related potentials. In the reviewed studies, these changes generally correlate with performances in many cognitive tests. In conclusion, particularly in AD, neurophysiological changes can be reliable early markers of dementia.

Heart rate variability increases following automated acoustic slow wave sleep enhancement.

Acoustic stimulation has been shown to enhance slow wave sleep and in turn, cognition, and now cardiac outcomes in young adults. With the emergence of commercial acoustic devices in the home, we sought to examine the impact of an acoustic, slow wave enhancing device on heart rate variability in healthy, middle-aged males (n=24, 39.92±4.15years). Under highly controlled conditions, the participants were randomised to receive closed-loop brain state-dependent stimulation in the form of auditory tones (STIM), or no tones (SHAM), in a crossover design, separated by a 1 week washout period. STIM and SHAM were compared on measures of heart rate variability for the whole night and over the first three sleep cycles. We found an increase in slow wave activity following STIM compared with SHAM. There was a significant increase in high frequency power and standard deviation of the normalised RR-intervals (SDNN) during the STIM condition compared with SHAM (p&lt;0.05), due to changes observed specifically during N3. In conclusion, heart rate variability appears to improve following acoustic slow wave sleep enhancement.

P030 The effects of continuous positive airway pressure (CPAP) therapy in moderate to severe obstructive sleep apnea (OSA): A high-density electroencephalography (EEG) study

Abstract Introduction A previous high-density EEG investigation in OSA showed regional sleep EEG deficits particularly slow wave activity (SWA) in the parietal region. It is unclear whether CPAP treatment can reverse local sleep EEG abnormalities, and whether any recovery is related to improved cognitive function. Methods Fifteen males with moderate-severe OSA (age 50.4±6.5yrs, AHI 51.7±23.5/h) underwent polysomnography with 256-channel high-density EEG at baseline and following 3 months of CPAP. Tasks assessing cognitive performance and sleep-dependent memory were administered. Topographical spectral power maps were calculated for standard frequency ranges for sleep stages. Differences in normalized power between baseline and treatment were determined by statistical nonparametric mapping. Results In 11 CPAP compliant patients (data loss: intolerant of CPAP[n=3]/high-density EEG [n=1]), total sleep time did not change after CPAP but N1 (baseline vs. treatment: 66.9 vs. 39.5 mins, p=0.008) and N2 (195.0 vs. 150.6 mins, p=0.002) sleep was lower and N3 (89.8 vs. 128.7 mins, p=0.003) was higher. Topographic high-density EEG analysis revealed a regional increase in SWA (1–4.5Hz) during N3 sleep in a cluster of 22 electrodes overlying the parietal cortex (paired t-test, t(10)=-3.9, p=0.0029). The change in N3 SWA in the parietal cluster after CPAP was correlated with improved overnight procedural memory on the motor sequence task (rho=0.79, p=0.03) and better executive functioning (Stroop accuracy, rho=0.73, p=0.01). Conclusion CPAP treatment reduces localised deficits in sleep EEG, and specific regional recovery relates to short-term improvements in memory and executive function. These data also highlight the potential for long-term therapeutic effects on cognitive outcomes.

Neural Correlates of Aging-Related Differences in Pro-active Control in a Dual Task.

Background: Multi-tasking is usually impaired in older people. In multi-tasking, a fixed order of sub-tasks can improve performance by promoting a time-structured preparation of sub-tasks. How proactive control prioritizes the pre-activation or inhibition of complex tasks in older people has received no sufficient clarification so far.Objective: To explore the effects of aging on neural proactive control mechanisms in a dual task.Methodology: To address this question, the psychological refractory period (PRP) paradigm was used. Two 2-alternative-forced-choice reaction tasks with a predefined order (T1 and T2) signaled by a cue had to be executed simultaneously or consecutively by young (mean age 25.1 years, n = 36) and old subjects (mean age 70.4 years, n = 118). Performance indices of dual-task preparation were used to assess the focused preparation of T1 and T2. To compare preparatory mechanisms at the neurophysiologic level, multi-channel electroencephalogram (EEG) was recorded and negative slow cortical potentials (SCPs) were analyzed as objective markers of the amount and localization of cortical pre-activation before sub-task presentation.Results: Dual-task performance was significantly slower in old adults. T1 performance was facilitated in both age groups, but T2 processing in old adults was not optimized by the temporal structure as efficiently as in young adults. Also, only young adults manifested a stable pattern of focused of negative slow-wave activity increase at medial frontal and right-hemisphere posterior regions, which was associated with a coordinated preparatory T1 pre-activation and T2 deferment, while old adults manifested a broad topographic distribution of negative SCPs associated with a pre-activation of sensory and motor processes.Conclusions: These observations demonstrate that the proactive preparation for dual tasking is altered with aging. It is suggested that in young adults, attention-based pre-activation of working memory and inhibitory networks in the right hemisphere synchronizes the simultaneous preparation of the two sub-tasks, whereas in old adults, sensory and motor networks appear to be non-specifically pre-activated for subsequent deferred mode of processing.

Quantitative Electroencephalographic Markers of Delirium in the Pediatric Intensive Care Unit: Insights From a Heterogenous Convenience Sample.

Little is known about the underlying neurophysiology of pediatric delirium. In adult patients, the sensitivity of EEG to clinical symptoms of delirium has been noted, with a slowing of background activity (alpha) and an increase in slow-wave activity (delta-theta). In this pilot study, the authors extended this investigation to a pediatric cohort. In a convenience sample, 23 critically ill children were screened for delirium, using the Cornell Assessment for Pediatric Delirium (CAPD), every 12 hours throughout their pediatric intensive care unit stay as part of standard intensive care unit procedure, and EEGs were performed as part of their clinical care. After hospital discharge, EEGs were reviewed using quantitative analysis, and the maximum delta-alpha ratio (DAR; eyes closed) was derived for each 12-hour period. DAR values were compared between delirious and nondelirious episodes, and the linear relationship between DAR and CAPD was assessed. Higher DARs were associated with episodes of delirium. The DAR also positively correlated with CAPD assessments, with higher DARs relating to higher delirium scores. Future prospective studies may further investigate this relationship in a more homogeneous and larger sample, and the DAR should be considered to track delirium and assess the effectiveness of therapeutic interventions.

Lateral Habenula Glutamatergic Neurons Modulate Isoflurane Anesthesia in Mice.

Since their introduction in the 1840s, one of the largest mysteries of modern anesthesia are how general anesthetics create the state of reversible loss of consciousness. Increasing researchers have shown that neural pathways that regulate endogenous sleep–wake systems are also involved in general anesthesia. Recently, the Lateral Habenula (LHb) was considered as a hot spot for both natural sleep–wake and propofol-induced sedation; however, the role of the LHb and related pathways in the isoflurane-induced unconsciousness has yet to be identified. Here, using real-time calcium fiber photometry recordings in vivo, we found that isoflurane reversibly increased the activity of LHb glutamatergic neurons. Then, we selectively ablated LHb glutamatergic neurons in Vglut2-cre mice, which caused a longer induction time and less recovery time along with a decrease in delta-band power in mice under isoflurane anesthesia. Furthermore, using a chemogenetic approach to specifically activate LHb glutamatergic neurons shortened the induction time and prolonged the recovery time in mice under isoflurane anesthesia with an increase in delta-band power. In contrast, chemogenetic inhibition of LHb glutamatergic neurons was very similar to the effects of selective lesions of LHb glutamatergic neurons. Finally, optogenetic activation of LHb glutamatergic neurons or the synaptic terminals of LHb glutamatergic neurons in the rostromedial tegmental nucleus (RMTg) produced a hypnosis-promoting effect in isoflurane anesthesia with an increase in slow wave activity. Our results suggest that LHb glutamatergic neurons and pathway are vital in modulating isoflurane anesthesia.

Electrophysiological signatures of acute systemic lipopolysaccharide-induced inflammation: potential implications for delirium science

BackgroundNovel preventive therapies are needed for postoperative delirium, which especially affects older patients. A mouse model is presented that captures inflammation-associated cortical slow wave activity (SWA) observed in patients, allowing exploration of the mechanistic role of prostaglandin-adenosine signalling. MethodsEEG and cortical cytokine measurements (interleukin 6, monocyte chemoattractant protein-1) were obtained from adult and aged mice. Behaviour, SWA, and functional connectivity were assayed before and after systemic administration of lipopolysaccharide (LPS)+piroxicam (cyclooxygenase inhibitor) or LPS+caffeine (adenosine receptor antagonist). To avoid the confounder of inflammation-driven changes in movement which alter SWA and connectivity, electrophysiological recordings were classified as occurring during quiescence or movement, and propensity score matching was used to match distributions of movement magnitude between baseline and post-LPS administration. ResultsLPS produces increases in cortical cytokines and behavioural quiescence. In movement-matched data, LPS produces increases in SWA (likelihood-ratio test: χ2(4)=21.51, P<0.001), but not connectivity (χ2(4)=6.39, P=0.17). Increases in SWA associate with interleukin 6 (P<0.001) and monocyte chemoattractant protein-1 (P=0.001) and are suppressed by piroxicam (P<0.001) and caffeine (P=0.046). Aged animals compared with adult animals show similar LPS-induced SWA during movement, but exaggerated cytokine response and increased SWA during quiescence. ConclusionsCytokine-SWA correlations during wakefulness are consistent with observations in patients with delirium. Absence of connectivity effects after accounting for movement changes suggests decreased connectivity in patients is a biomarker of hypoactivity. Exaggerated effects in quiescent aged animals are consistent with increased hypoactive delirium in older patients. Prostaglandin-adenosine signalling may link inflammation to neural changes and hence delirium.

Acoustic enhancement of slow wave sleep on consecutive nights improves alertness and attention in chronically short sleepers

IntroductionChronic sleep restriction has been linked to occupational errors and motor vehicle crashes. Enhancing slow wave sleep may alleviate some of the cognitive deficits associated with chronic sleep restriction. However, the extent to which acoustic stimulation of slow wave activity (SWA) may improve alertness and attention is not well established, particularly with respect to consecutive nights of exposure. MethodsTwenty-five healthy adults (32.9 ± 8.2 years; 16 female) who self-restricted their sleep during workdays participated in a randomized, double-blind, cross-over study. Participants wore an automated acoustic stimulation device for two consecutive nights. Acoustic tones (50 ms long) were delivered on the up-phase of the slow wave first and then at constant 1-s inter-tone-intervals once N3 was identified (STIM), until an arousal or shift to another sleep stage occurred, or at inaudible decibels during equivalent stimulation periods (SHAM). Subjective alertness/fatigue (KSS, Samn-Perelli) was assessed across both days, and objective measures of alertness (MSLT) and attention (PVT) were assessed after two nights of stimulation. ResultsAfter one night of acoustic stimulation, increased slow wave energy was observed in 68% of participants, with an average significant increase of 17.7% (p = 0.01), while Night 2 was associated with a 22.2% increase in SWA (p = 0.08). SWE was highly stable across the two nights of STIM (ICC 0.93, p < 0.001), and around half (56%) of participants were consistently classified as responders (11/25) or non-responders (3/25). Daytime testing showed that participants felt more alert and awake following each night of acoustic stimulation (p < 0.05), with improved objective attention across the day following two nights of acoustic stimulation. DiscussionConsecutive nights of acoustic stimulation enhanced SWA on both nights, and improved next day alertness and attention. Given large individual differences, we highlight the need to examine both the long-term effects of stimulation, and to identify inter-individual differences in acoustic stimulation response. Our findings suggest that the use of an acoustic device to enhance slow wave sleep may alleviate some of the deficits in alertness and attention typically associated with sleep restriction.

Modulating overnight memory consolidation by acoustic stimulation during slow-wave sleep: a systematic review and meta-analysis.

The low-frequency high-amplitude oscillations of slow-wave sleep (SWS) are considered to promote the consolidation of episodic memory. Previous research suggests that sleep slow waves can be entrained and enhanced by presenting short acoustic stimuli to the up-states of endogenous waves. Several studies have investigated the effects of these increases in slow-wave activity on overnight memory consolidation, with inconsistent results. The aim of this meta-analysis was to evaluate the accumulated evidence connecting acoustic stimulation during sleep to episodic memory consolidation. A systematic literature search was conducted in October 2020 using PubMed, Web of Science, and PsycInfo. The main study inclusion criteria were the application of acoustic slow wave enhancement in healthy participants and an assessment of pre- and post-sleep episodic memory performance. Effect sizes were pooled using a random-effects model. A total of 10 primary studies with 11 experiments and 177 participants were included. Results showed a combined effect size (Hedges' g) of 0.25 (p = 0.07). Subgroup models based on young adults (n = 8), phase-locked stimulation approaches (n = 8), and their combination (n = 6) showed combined effect sizes of 0.31 (p = 0.051), 0.36 (p = 0.047), and 0.44 (p = 0.01), respectively. There was no indication of publication bias or bias in individual studies. Acoustic enhancement of SWS tends to increase the overnight consolidation of episodic memory but effects remain small and-with the exception of subgroup models-at trend levels. Currently, the evidence is not sufficient to recommend the use of commercially available devices.