Increased Delta Power Research Articles

Optogenetic targeting of cortical astrocytes selectively improves NREM sleep in an Alzheimer’s disease mouse model

Alzheimer’s disease (AD) is a progressive neurodegenerative condition marked by memory impairments and distinct histopathological features such as amyloid-beta (Aβ) accumulations. Alzheimer’s patients experience sleep disturbances at early stages of the disease. APPswe/PS1dE9 (APP) mice exhibit sleep disruptions, including reductions in non-rapid eye movement (NREM) sleep, that contribute to their disease progression. In addition, astrocytic calcium transients associated with a sleep-dependent brain rhythm, slow oscillations prevalent during NREM sleep, are disrupted in APP mice. However, at present it is unclear whether restoration of circuit function by targeting astrocytic activity could improve sleep in APP mice. To that end, APP mice expressing channelrhodopsin-2 (ChR2) targeted to astrocytes underwent optogenetic stimulation at the slow oscillation frequency. Optogenetic stimulation of astrocytes significantly increased NREM sleep duration but not duration of rapid eye movement (REM) sleep. Optogenetic treatment increased delta power and reduced sleep fragmentation in APP mice. Thus, optogenetic activation of astrocytes increased sleep quantity and improved sleep quality in an AD mouse model. Astrocytic activity provides a novel therapeutic avenue to pursue for enhancing sleep and slowing AD progression.

Emotion perception through the nose: how olfactory emotional cues modulate the perception of neutral facial expressions in affective disorders

Humans can decode emotional states from the body odors of the conspecifics and this type of emotional communication is particularly relevant in conditions in which social interactions are impaired, as in depression and social anxiety. The present study aimed to explore how body odors collected in happiness and fearful conditions modulate the subjective ratings, the psychophysiological response and the neural processing of neutral faces in individuals with depressive symptoms, social anxiety symptoms, and healthy controls (N = 22 per group). To this aim, electrocardiogram (ECG) and HD-EEG were recorded continuously. Heart Rate Variability (HRV) was extracted from the ECG as a measure of vagal tone, event-related potentials (ERPs) and event-related spectral perturbations (ERPSs) were extracted from the EEG. The results revealed that the HRV increased during the fear and happiness body odors conditions compared to clean air, but no group differences emerged. For ERPs data, repeated measure ANOVA did not show any significant effects. However, the ERPSs analyses revealed a late increase in delta power and a reduced beta power both at an early and a late stage of stimulus processing in response to the neutral faces presented with the emotional body odors, regardless of the presence of depressive or social anxiety symptoms. The current research offers new insights, demonstrating that emotional chemosignals serve as potent environmental cues. This represents a substantial advancement in comprehending the impact of emotional chemosignals in both individuals with and without affective disorders.

Sleep-wake behavior and responses to sleep deprivation and immune challenge of protein kinase RNA-activated knockout mice

Protein Kinase RNA-activated (PKR) is an enzyme that plays a role in many systemic processes, including modulation of inflammation, and is implicated in neurodegenerative diseases, such as Alzheimer’s disease (AD). PKR phosphorylation results in the production of several cytokines involved in the regulation / modulation of sleep, including interleukin-1β, tumor necrosis factor-α and interferon-γ. We hypothesized targeting PKR would alter spontaneous sleep of mice, attenuate responses to sleep deprivation, and inhibit responses to immune challenge. To test these hypotheses, we determined the sleep-wake phenotype of mice lacking PKR (knockout; PKR-/-) during undisturbed baseline conditions; in responses to six hours of sleep deprivation; and after immune challenge with lipopolysaccharide (LPS). Adult male mice (C57BL/6J, n = 7; PKR-/-, n = 7) were surgically instrumented with EEG recording electrodes and an intraperitoneal microchip to record core body temperature. During undisturbed baseline conditions, PKR -/- mice spent more time in non-rapid eye movement sleep (NREMS) and rapid-eye movement sleep (REMS), and less time awake at the beginning of the dark period of the light:dark cycle. Delta power during NREMS, a measure of sleep depth, was less in PKR-/- mice during the dark period, and core body temperatures were lower during the light period. Both mouse strains responded to sleep deprivation with increased NREMS and REMS, although these changes did not differ substantively between strains. The initial increase in delta power during NREMS after sleep deprivation was greater in PKR-/- mice, suggesting a faster buildup of sleep pressure with prolonged waking. Immune challenge with LPS increased NREMS and inhibited REMS to the same extent in both mouse strains, whereas the initial LPS-induced suppression of delta power during NREMS was greater in PKR-/- mice. Because sleep regulatory and immune responsive systems in brain are redundant and overlapping, other mediators and signaling pathways in addition to PKR are involved in the responses to acute sleep deprivation and LPS immune challenge.

Functional changes in sleep-related arousal after ketamine administration in individuals with treatment-resistant depression

The glutamatergic modulator ketamine is associated with changes in sleep, depression, and suicidal ideation (SI). This study sought to evaluate differences in arousal-related sleep metrics between 36 individuals with treatment-resistant major depression (TRD) and 25 healthy volunteers (HVs). It also sought to determine whether ketamine normalizes arousal in individuals with TRD and whether ketamine’s effects on arousal mediate its antidepressant and anti-SI effects. This was a secondary analysis of a biomarker-focused, randomized, double-blind, crossover trial of ketamine (0.5 mg/kg) compared to saline placebo. Polysomnography (PSG) studies were conducted one day before and one day after ketamine/placebo infusions. Sleep arousal was measured using spectral power functions over time including alpha (quiet wakefulness), beta (alert wakefulness), and delta (deep sleep) power, as well as macroarchitecture variables, including wakefulness after sleep onset (WASO), total sleep time (TST), rapid eye movement (REM) latency, and Post-Sleep Onset Sleep Efficiency (PSOSE). At baseline, diagnostic differences in sleep macroarchitecture included lower TST (p = 0.006) and shorter REM latency (p = 0.04) in the TRD versus HV group. Ketamine’s temporal dynamic effects (relative to placebo) in TRD included increased delta power earlier in the night and increased alpha and delta power later in the night. However, there were no significant diagnostic differences in temporal patterns of alpha, beta, or delta power, no ketamine effects on sleep macroarchitecture arousal metrics, and no mediation effects of sleep variables on ketamine’s antidepressant or anti-SI effects. These results highlight the role of sleep-related variables as part of the systemic neurobiological changes initiated after ketamine administration. Clinical Trials Identifier: NCT00088699.

5-MeO-DMT induces sleep-like LFP spectral signatures in the hippocampus and prefrontal cortex of awake rats

5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a potent classical psychedelic known to induce changes in locomotion, behaviour, and sleep in rodents. However, there is limited knowledge regarding its acute neurophysiological effects. Local field potentials (LFPs) are commonly used as a proxy for neural activity, but previous studies investigating psychedelics have been hindered by confounding effects of behavioural changes and anaesthesia, which alter these signals. To address this gap, we investigated acute LFP changes in the hippocampus (HP) and medial prefrontal cortex (mPFC) of freely behaving rats, following 5-MeO-DMT administration. 5-MeO-DMT led to an increase of delta power and a decrease of theta power in the HP LFPs, which could not be accounted for by changes in locomotion. Furthermore, we observed a dose-dependent reduction in slow (20–50 Hz) and mid (50–100 Hz) gamma power, as well as in theta phase modulation, even after controlling for the effects of speed and theta power. State map analysis of the spectral profile of waking behaviour induced by 5-MeO-DMT revealed similarities to electrophysiological states observed during slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. Our findings suggest that the psychoactive effects of classical psychedelics are associated with the integration of waking behaviours with sleep-like spectral patterns in LFPs.

Slow wave activity disruptions and memory impairments in a mouse model of aging

The aging population suffers from memory impairments. Slow-wave activity (SWA) is composed of slow (0.5–1 Hz) and delta (1–4 Hz) oscillations, which play important roles in long-term memory and working memory function respectively. SWA disruptions might lead to memory disturbances often experienced by older adults. We conducted behavioral tests in young and older C57BL/6 J mice. SWA was monitored using wide-field imaging with voltage sensors. Cell-specific calcium imaging was used to monitor the activity of excitatory and inhibitory neurons in these mice. Older mice exhibited impairments in working memory but not memory consolidation. Voltage-sensor imaging revealed aberrant synchronization of neuronal activity in older mice. Notably, we found older mice exhibited no significant alterations in slow oscillations, whereas there was a significant increase in delta power compared to young mice. Calcium imaging revealed hypoactivity in inhibitory neurons of older mice. Combined, these results suggest that neural activity disruptions might correlate with aberrant memory performance in older mice.

Association Between EEG Power During Sleep and Attention Levels in Patients with Major Depressive Disorder.

Major depressive disorder (MDD) is associated with cognitive impairment through unclear mechanisms. We examined the relationship between sleep electroencephalogram (EEG) power and attention level in MDD. Forty-seven untreated patients with MDD and forty-seven age- and sex-matched controls were included. We examined relative EEG power during non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep by fast Fourier transform. The Attention Network Test (ANT) was performed to evaluate attention levels. Compared to controls, patients with MDD had lower theta power during NREM (P = 0.018) and REM (P = 0.002) sleep, while higher beta power (P = 0.050) during NREM sleep and delta power (P = 0.018) during REM sleep. Regarding attention level, patients with MDD had lower levels of accuracy (P = 0.021), longer mean reaction time (P < 0.001), poorer manifestations of the alerting effect (P = 0.038) and worse executive control (P = 0.048). Moreover, decreased theta power during NREM sleep was correlated with worsened accuracy (β = 0.329, P = 0.040), decreased theta power during REM sleep was correlated with worsened alerting effect (β = 0.355, P = 0.020), and increased delta power during REM sleep was correlated with longer mean reaction time (β = 0.325, P = 0.022) in patients with MDD. No association between ANT performance and other frequency bands was observed in patients with MDD. Our findings suggest that patients with MDD manifest impaired selective attention function that is associated with decreased theta power during NREM/REM sleep and increased delta power during REM sleep.

Effects of head alignment devices on working memory and postural support during computer work.

The most common risk factor of computer workers is poor head and neck posture. Therefore, upright seated posture has been recommended repeatedly. However, maintaining an upright seated posture is challenging during computer work and induces various complaints, such as fatigue and discomfort, which can interfere working performance. Therefore, it is necessary to maintain an upright posture without complaints or intentional efforts during long-term computer work. Alignment devices are an appropriate maneuver to support postural control for maintaining head-neck orientation and reduce head weight. This study aimed to demonstrate the effects of workstations combined with alignment device on head-neck alignment, muscle properties, comfort and working memory ability in computer workers. Computer workers (n = 37) participated in a total of three sessions (upright computer (CPT_U), upright support computer (CPT_US), traction computer (CPT_T) workstations). The craniovertebral angle, muscles tone and stiffness, visual analog discomfort scale score, 2-back working memory performance, and electroencephalogram signals were measured. All three workstations had a substantial effect on maintaining head-neck alignment (p< 0.001), but only CPT_US showed significant improvement on psychological comfort (p = 0.04) and working memory performance (p = 0.024), which is consistent with an increase in delta power. CPT_U showed the increased beta 2 activity, discomfort, and false rates compared to CPT_US. CPT_T showed increased alpha and beta 2 activity and decreased delta activity, which are not conductive to working memory performance. In conclusion, CPT_US can effectively induce efficient neural oscillations without causing any discomfort by increasing delta and decreasing beta 2 activity for working memory tasks.

Exercise-with-melatonin therapy improves sleep disorder and motor dysfunction in a rat model of ischemic stroke.

Abstract JOURNAL/nrgr/04.03/01300535-202406000-00038/inline-graphic1/v/2023-10-30T152229Z/r/image-tiff Exercise-with-melatonin therapy has complementary and synergistic effects on spinal cord injury and Alzheimer’s disease, but its effect on stroke is still poorly understood. In this study, we established a rat model of ischemic stroke by occluding the middle cerebral artery for 60 minutes. We treated the rats with exercise and melatonin therapy for 7 consecutive days. Results showed that exercise-with-melatonin therapy significantly prolonged sleep duration in the model rats, increased delta power values, and regularized delta power rhythm. Additionally, exercise-with-melatonin therapy improved coordination, endurance, and grip strength, as well as learning and memory abilities. At the same time, it led to higher hippocampal CA1 neuron activity and postsynaptic density thickness and lower expression of glutamate receptor 2 than did exercise or melatonin therapy alone. These findings suggest that exercise-with-melatonin therapy can alleviate sleep disorder and motor dysfunction by increasing glutamate receptor 2 protein expression and regulating hippocampal CA1 synaptic plasticity.

Exploring neurophysiological correlates of visually induced motion sickness using electroencephalography (EEG).

Visually induced motion sickness (VIMS) is a common phenomenon when using visual devices such as smartphones and virtual reality applications, with symptoms including nausea, fatigue, and headache. To date, the neuro-cognitive processes underlying VIMS are not fully understood. Previous studies using electroencephalography (EEG) delivered mixed findings, with some reporting an increase in delta and theta power, and others reporting increases in alpha and beta frequencies. The goal of the study was to gain further insight into EEG correlates for VIMS. Participants viewed a VIMS-inducing visual stimulus, composed of moving black-and-white vertical bars presented on an array of three adjacent monitors. The EEG was recorded during visual stimulation and VIMS ratings were recorded after each trial using the Fast Motion Sickness Scale. Time-frequency analyses were conducted comparing neural activity of participants reporting minimal VIMS (n = 21) and mild-moderate VIMS (n = 12). Results suggested a potential increase in delta power in the centro-parietal regions (CP2) and a decrease in alpha power in the central regions (Cz) for participants experiencing mild-moderate VIMS compared to those with minimal VIMS. Event-related spectral perturbations (ERSPs) suggested that group differences in EEG activity developed with increasing duration of a trial. These results support the hypothesis that the EEG might be sensitive to differences in information processing in VIMS and minimal VIMS contexts, and indicate that it may be possible to identify neurophysiological correlate of VIMS. Differences in EEG activity related to VIMS may reflect differential processing of conflicting visual and vestibular sensory information.

EEG response to a high volume (1.5 mL/kg) caudal block in infants less than 3 months

IntroductionThe substantial compression of the dural sac and the subsequent cranial shift of cerebrospinal fluid caused by a high-volume caudal block has been shown to significantly but transiently reduce cerebral...

Deep brain stimulation of the anterior nucleus of the thalamus increases slow wave activity in NREM sleep.

Previous studies suggest that intermittent deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) affects physiological sleep architecture. Here, we investigated the impact of continuous ANT-DBS on sleep in epilepsy patients in a multicenter cross-over study in ten patients. We assessed sleep stage distribution, delta power, delta energy, and total sleep time (TST) in standardized 10/20 polysomnography (PSG) investigations before and 12 months after DBS lead implantation. In contrast to previous studies, we found no disruption of sleep architecture or alterations of sleep stage distribution under active ANT-DBS (P = 0.76). On the contrary, we observed more consolidated and deeper slow wave sleep (SWS) under continuous high frequency DBS as compared to baseline sleep prior to DBS lead implantation. In particular, biomarkers of deep sleep (delta power and delta energy) showed a significant increase post-DBS as compared to baseline (36.67 ± 13.68 μV2 and 799.86 ± 407.56 μV2 *s, P < 0.001). Furthermore, the observed increase in delta power was related to the location of the active stimulation contact within the ANT: we found higher delta power and higher delta energy in patients with active stimulation in more superior contacts as compared to inferior ANT stimulation. We also observed significantly less nocturnal EEG discharges in DBS ON condition. In conclusion, our findings suggest that continuous ANT-DBS in the most cranial part of the target region leads to more consolidated SWS. From a clinical perspective, these findings suggest that patients with sleep disruption under cyclic ANT-DBS could benefit from an adaptation of stimulation parameters to more superior contacts and continuous mode stimulation.

What a single electroencephalographic (EEG) channel can tell us about Alzheimer's disease patients with mild cognitive impairment

AbstractBackgroundAbnormalities in the neurophysiological oscillatory mechanisms generating dominant resting‐state eyes closed electroencephalographic (rsEEG) rhythms portray the Alzheimer’s disease (AD) continuum, from the preclinical to the dementia stage. Here, we tested whether these abnormalities may be reproducible by analyzing the rsEEG signals acquired in bipolar configuration with a montage consisting of only four centro‐parietal and parieto‐occipital channels (C3‐P3, C4‐P4, P3‐O1, and P4‐O2) in patients with mild cognitive impairment (MCI) due to AD (ADMCI).MethodTo evaluate the study hypotheses, clinical, neuropsychological, anthropometric, genetic, cerebrospinal fluid (CSF), MRI, and rsEEG data in 70 Nold and 75 ADMCI subjects from an international archive were used in the present study. The subgroups were matched for age, gender, and education. In all subjects, rsEEG recordings lasted about 3‐5 minutes. The rsEEG data were recorded with a sampling frequency of 128‐512 Hz and related antialiasing bandpass between 0.01 Hz and 60‐100 Hz. Electrode montage included 19 scalp monopolar sensors placed following 10‐20 System. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands as well as fixed beta (14‐30 Hz) and gamma (30‐40 Hz) bands.ResultResults confirmed previous evidence about the abnormalities of the delta, theta, and alpha rhythms in ADMCI patients compared to Nold subjects. Moreover, as compared to the Nold group, the ADMCI group showed increased delta power density and decreased alpha power density at the C3‐P3, C4‐P4, P3‐O1, and P4‐O2 bipolar channels. Increased theta power density for ADMCI patients was observed only at the C3‐P3 bipolar channel. Best classification accuracy between the ADMCI and Nold individuals reached 81% (area under the receiver operating characteristic curve) using Alpha2/Theta power density computed at the C3‐P3 bipolar channel.ConclusionThe current findings provide evidence in the potential use of rsEEG low‐channel portable devices as a topographic biomarker of cognitive decline within the extensive screening of in elderly population at risk of developing AD‐ or other dementia‐related disorders. Moreover, the confirmation of this hypothesis would have exciting applications in the framework of telehealth home monitoring of global brain functions.

Progressive inflammation reduces high-frequency EEG activity and cortical dendritic arborisation in late gestation fetal sheep

BackgroundAntenatal infection/inflammation is associated with disturbances in neuronal connectivity, impaired cortical growth and poor neurodevelopmental outcomes. The pathophysiological substrate that underpins these changes is poorly understood. We tested the hypothesis that progressive inflammation in late gestation fetal sheep would alter cortical neuronal microstructure and neural function assessed using electroencephalogram band power analysis.MethodsFetal sheep (0.85 of gestation) were surgically instrumented for continuous electroencephalogram (EEG) recording and randomly assigned to repeated saline (control; n = 9) or LPS (0 h = 300 ng, 24 h = 600 ng, 48 h = 1200 ng; n = 8) infusions to induce inflammation. Sheep were euthanised 4 days after the first LPS infusion for assessment of inflammatory gene expression, histopathology and neuronal dendritic morphology in the somatosensory cortex.ResultsLPS infusions increased delta power between 8 and 50 h, with reduced beta power from 18 to 96 h (P < 0.05 vs. control). Basal dendritic length, numbers of dendritic terminals, dendritic arborisation and numbers of dendritic spines were reduced in LPS-exposed fetuses (P < 0.05 vs. control) within the somatosensory cortex. Numbers of microglia and interleukin (IL)-1β immunoreactivity were increased in LPS-exposed fetuses compared with controls (P < 0.05). There were no differences in total numbers of cortical NeuN + neurons or cortical area between the groups.ConclusionsExposure to antenatal infection/inflammation was associated with impaired dendritic arborisation, spine number and loss of high-frequency EEG activity, despite normal numbers of neurons, that may contribute to disturbed cortical development and connectivity.

Effects of medial prefrontal transcranial alternating current stimulation on neural activity and connectivity in people with Huntington’s disease and neurotypical controls

We investigated the effects of transcranial alternating current stimulation (tACS) targeted to the medial prefrontal cortex (mPFC) on resting electroencephalographic (EEG) indices of oscillatory power, aperiodic exponent and offset, and functional connectivity in 22 late premanifest and early manifest stage individuals with HD and 20 neurotypical controls. Participants underwent three 20-minute sessions of tACS at least 72 hours apart; one session at alpha frequency (either each participant’s Individualised Alpha Frequency (IAF), or 10 Hz when an IAF was not detected); one session at delta frequency (2 Hz); and a session of sham tACS. Session order was randomised and counterbalanced across participants. EEG recordings revealed a reduction of the spectral exponent (‘flattening’ of the 1/f slope) of the eyes-open aperiodic signal in participants with HD following alpha-tACS, suggestive of an enhancement in excitatory tone. Contrary to expectation, there were no changes in oscillatory power or functional connectivity in response to any of the tACS conditions in the participants with HD. By contrast, alpha-tACS increased delta power in neurotypical controls, who further demonstrated significant increases in theta power and theta functional connectivity in response to delta-tACS. This study contributes to the rapidly growing literature on the potential experimental and therapeutic applications of tACS by examining neurophysiological outcome measures in people with HD as well as neurotypical controls.

Different oscillatory rhythms anticipate failures in executive and arousal vigilance

IntroductionVigilance is the challenging ability to maintain attention during long periods. When performing prolonged tasks, vigilance failures are often observed, reflecting a decrease in performance. Previous research has shown that changes in oscillatory rhythms are associated with states of vigilance loss. The present study aimed to investigate whether changes in different oscillatory rhythms anticipate failures in two vigilance components: (a) executive vigilance –necessary to detect infrequent critical signals– and (b) arousal vigilance –necessary to maintain a fast reaction to environmental stimuli without much control–.Methods37 young adults (age: M = 25.86; SD = 4.99) completed two experimental sessions in which high-density electroencephalography signal was recorded while they performed the Attentional Networks Test for Interactions and Vigilance – executive and arousal components, a task that simultaneously measures executive and arousal vigilance along with others attentional functions. Changes in delta, theta, alpha, beta, and gamma power before target onset were analyzed at the trial level in the executive and the arousal vigilance subtasks and as a function of the behavioral response.ResultsChanges in different oscillatory rhythms were observed prior to failures in executive and arousal vigilance. While increased alpha power in left occipital regions anticipated misses in the executive vigilance subtask, increased delta power in frontal-central regions anticipated very slow responses in the arousal vigilance subtask.DiscussionThe present results further support an empirical dissociation at the neural level between executive and arousal vigilance. Changes in alpha –in left occipital regions– and delta –in frontal-central regions– power might be identified as different brain states associated with loss in vigilance components when performing prolonged tasks.

Source Localization and Spectrum Analyzing of EEG in Stuttering State upon Dysfluent Utterances.

Purpose: The present study which addressed adults who stutter (AWS) attempted to investigate power spectral dynamics in the stuttering state by answering the questions using quantitative electroencephalography (qEEG). Method: A 64-channel electroencephalography (EEG) setup was used for data acquisition at 20 AWS. Since the speech, especially stuttering, causes significant noise in the EEG, 2 conditions of speech preparation (SP) and imagined speech (IS) were considered. EEG signals were decomposed into 6 bands. The corresponding sources were localized using the standard low-resolution electromagnetic tomography (sLORETA) tool in both fluent and dysfluent states. Results: Significant differences were noted after analyzing the time-locked EEG signals in fluent and dysfluent utterances. Consistent with previous studies, poor alpha and beta suppression in SP and IS conditions were localized in the left frontotemporal areas in a dysfluent state. This was partly true for the right frontal regions. In the theta range, disfluency was concurrence with increased activation in the left and right motor areas. Increased delta power in the left and right motor areas as well as increased beta2 power over left parietal regions was notable EEG features upon fluent speech. Conclusion: Based on the present findings and those of earlier studies, explaining the neural circuitries involved in stuttering probably requires an examination of the entire frequency spectrum involved in speech.

The M1 Muscarinic Acetylcholine Receptor Positive Allosteric Modulator (PAM) VU0453595 and M4 PAM VU0467154 Normalize Sleep‐Wake Architecture Deficits in Aged Mice

AbstractBackgroundDeclining basal forebrain cholinergic integrity has been associated with disturbances in sleep‐wake architecture in Alzheimer’s Disease (AD). Acetylcholinesterase inhibitors (AChEIs) provide symptomatic treatment for the cognitive deficits in AD through nonselective enhancement of cholinergic signaling. Additionally, AChEIs promote wakefulness, but reduce NREM sleep quality and produce dose limiting side effects through nonselective activation of peripheral muscarinic acetylcholine receptors (mAChR). Selectively targeting different mAChRs with positive allosteric modulators (PAMs) provides an alternate approach. In the current study, we assessed the effects of the M1 PAM VU0453595 and the M4 PAM VU0467154 on sleep‐wake architecture and arousal following dosing across the circadian cycle in aged mice.MethodsYoung (3‐4 month‐old, n = 13‐14 per group) and aged (19‐21 month‐old, n = 14 per group) C57/BL6 mice were implanted with HD‐X02 telemetry devices (DSI) for electroencephalography (EEG) recording. The M1 PAM VU0453595 (3‐30mg/kg IP) or the M4 PAM VU0467154 (1‐30mg/kg IP) were dosed 2‐hours into the active or inactive phases of the circadian cycle. EEG was recorded for 24‐hours, with sleep stages scored in 5‐second epochs. Arousal was assessed through changes in gamma power during wake, and sleep quality was measured through changes in delta power during NREM sleep. Statistical comparisons involved repeated measures one‐ or two‐way ANOVAs as appropriate, with Dunnett’s or Sidak’s multiple comparisons applied in all cases.ResultsThe M1 PAM VU0453595 increased wakefulness and arousal with inactive phase dosing in young and aged mice. During the active phase, VU0453595 increased wakefulness and arousal only in aged mice. The M4 PAM VU0467154 increased NREM sleep in young and aged mice when dosed in both phases. In the inactive phase, suppression of REM sleep in young and aged mice is also observed. During NREM sleep, VU0467154 increased delta power in young and aged mice.ConclusionThese findings suggest that M1 and M4 PAMs may be valuable as treatments in AD at different phases of the circadian cycle. M1 PAMs could be beneficial with morning dosing in clinical populations as they enhanced wakefulness and arousal. M4 PAMs could be advantageous with evening dosing in clinical population as they enhanced NREM sleep quantity and quality.

Alternating hemiplegia of childhood: An electroclinical study of sleep and hemiplegia.

Alternating Hemiplegia of Childhood (AHC) is characterised by paroxysmal hemiplegic episodes and seizures. Remission of hemiplegia upon sleep is a clinical diagnostic feature of AHC. We investigated whether: 1) Hemiplegic events are associated with spectral EEG changes 2) Sleep in AHC is associated with clinical or EEG spectral features that may explain its restorative effect. We retrospectively performed EEG spectral analysis in five adults with AHC and twelve age-/gender-matched epilepsy controls. Five-minute epochs of hemiplegic episodes and ten-minute epochs of four sleep stages were selected from video-EEGs. Arousals were counted per hour of sleep. We found 1) hemispheric differences in pre-ictal and ictal spectral power (p = 0.034), during AHC hemiplegic episodes 2) 22% reduced beta power (p = 0.017) and 26% increased delta power (p = 0.025) during wakefulness in AHC versus controls. There were 98% more arousals in the AHC group versus controls (p = 0.0003). There are hemispheric differences in spectral power preceding hemiplegic episodes in adults with AHC, and sleep is disrupted. Spectral EEG changes may be a potential predictive tool for AHC hemiplegic episodes. Significantly disrupted sleep is a feature of AHC.

MEG measured delta waves increase in adolescents after concussion.

IntroductionThe purpose of this study is to determine if delta waves, measured by magnetoencephalography (MEG), increase in adolescents due to a sports concussion.MethodsTwenty‐four adolescents (age 14–17) completed pre‐ and postseason MRI and MEG scanning. MEG whole‐brain delta power was calculated for each subject and normalized by the subject's total power. In eight high school football players diagnosed with a concussion during the season (mean age = 15.8), preseason delta power was subtracted from their postseason scan. In eight high school football players without a concussion (mean age = 15.7), preseason delta power was subtracted from postseason delta power and in eight age‐matched noncontact controls (mean age = 15.9), baseline delta power was subtracted from a 4‐month follow‐up scan.ANOVA was used to compare the mean differences between preseason and postseason scans for the three groups of players, with pairwise comparisons based on Student's t‐test method.ResultsPlayers with concussions had significantly increased delta wave power at their postseason scans than nonconcussed players (p = .018) and controls (p = .027).ConclusionWe demonstrate that a single concussion during the season in adolescent subjects can increase MEG measured delta frequency power at their postseason scan. This adds to the growing body of literature indicating increased delta power following a concussion.