EEG Alterations Research Articles

Non-REM sleep in major depressive disorder

Disturbed sleep is a key symptom in major depressive disorder (MDD). REM sleep alterations are well described in the current literature, but little is known about non-REM sleep alterations. Additionally, sleep disturbances relate to a variety of cognitive symptoms in MDD, but which features of non-REM sleep EEG contribute to this, remains unknown. We comprehensively analyzed non-REM sleep EEG features in two central channels in three independently collected datasets (N = 284 recordings of 216 participants). This exploratory and descriptive study included MDD patients with a broad age range, varying duration and severity of depression, unmedicated or medicated, age- and gender-matched to healthy controls. We explored changes in sleep architecture including sleep stages and cycles, spectral power, sleep spindles, slow waves (SW), and SW-spindle coupling. Next, we analyzed the association of these sleep features with acute measures of depression severity and overnight consolidation of procedural memory. Overall, no major systematic alterations in non-REM sleep architecture were found in patients compared to controls. For the microstructure of non-REM sleep, we observed a higher spindle amplitude in unmedicated patients compared to controls, and after the start of antidepressant medication longer SWs with lower amplitude and a more dispersed SW-spindle coupling. In addition, long-term, but not short-term medication seemed to lower spindle density. Overnight procedural memory consolidation was impaired in medicated patients and associated with lower sleep spindle density. Our results suggest that alterations of non-REM sleep EEG in MDD might be more subtle than previously reported. We discuss these findings in the context of antidepressant medication intake and age.

Alterations in Patients With First-Episode Depression in the Eyes-Open and Eyes-Closed Conditions: A Resting-State EEG Study.

Altered resting-state EEG activity has been repeatedly reported in major depressive disorder (MDD), but no robust biomarkers have been identified until now. The poor consistency of EEG alterations may be due to inconsistent resting conditions; that is, the eyes-open (EO) and eyes-closed (EC) conditions. Here, we explored the effect of the EO and EC conditions on EEG biomarkers for discriminating MDD subjects and healthy control (HC) subjects. EEG data were recorded from 30 first-episode MDD and 26 HC subjects during an 8-min resting-state session. The features were extracted using spectral power, Lempel-Ziv complexity, and detrended fluctuation analysis. Significant features were further selected via the sequential backward feature selection algorithm. Support vector machine (SVM), logistic regression, and linear discriminate analysis were used to determine a better resting condition to provide more reliable estimates for identifying MDD. Compared with the HC group, we found that the MDD group exhibited widespread increased β and γ powers ( ) in both conditions. In the EO condition, the MDD group showed increased complexity and scaling exponents in the α band relative to HC subjects ( ). The best classification performance of the combined feature sets was found in the EO condition, with the leave-one-out classification accuracy of 89.29%, sensitivity of 90.00%, and specificity of 88.46% using SVM with the linear kernel classifier when the threshold was set to 0.7, followed by the β and γ spectral features with an average accuracy of 83.93%. Overall, EO and EC conditions indeed affected the between-group variance, and the EO condition is suggested as the more separable resting condition to identify depression. Specially, the β and γ powers are suggested as potential biomarkers for first-episode MDD.

Relationship between Cortical Thickness and EEG Alterations during Sleep in the Alzheimer's Disease.

Recent evidence showed that EEG activity alterations that occur during sleep are associated with structural, age-related, changes in healthy aging brains, and predict age-related decline in memory performance. Alzheimer’s disease (AD) patients show specific EEG alterations during sleep associated with cognitive decline, including reduced sleep spindles during NREM sleep and EEG slowing during REM sleep. We investigated the relationship between these EEG sleep alterations and brain structure changes in a study of 23 AD patients who underwent polysomnographic recording of their undisturbed sleep and 1.5T MRI scans. Cortical thickness measures were correlated with EEG power in the sigma band during NREM sleep and with delta- and beta-power during REM sleep. Thinning in the right precuneus correlated with all the EEG indexes considered in this study. Frontal–central NREM sigma power showed an inverse correlation with thinning of the left entorhinal cortex. Increased delta activity at the frontopolar and temporal regions was significantly associated with atrophy in some temporal, parietal, and frontal cortices, and with mean thickness of the right hemisphere. Our findings revealed an association between sleep EEG alterations and the changes to AD patients’ brain structures. Findings also highlight possible compensatory processes involving the sources of frontal–central sleep spindles.

NREM Sleep EEG Characteristics Correlate to the Mild Cognitive Impairment in Patients with Parkinsonism.

Early identification and diagnosis of mild cognitive impairment (MCI) in patients with parkinsonism (PDS) are critical. The aim of this study was to identify biomarkers of MCI in PDS using conventional electroencephalogram (EEG) power spectral analysis and detrended fluctuation analysis (DFA). In this retrospective study, patients with PDS who underwent an overnight polysomnography (PSG) study in our hospital from 2019 to 2020 were enrolled. Patients with PDS assessed by clinical examination and questionnaires were divided into two groups: the PDS with normal cognitive function (PDS-NC) group and the PDS with MCI (PDS-MCI) group. Sleep EEG signals were extracted and purified from the PSG and subjected to a conventional power spectral analysis, as well as detrended fluctuation analysis (DFA) during wakefulness, nonrapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Forty patients with PDS were enrolled, including 25 with PDS-NC and 15 with PDS-MCI. Results revealed that compared with PDS-NC patients, patients with PDS-MCI had a reduced fast ratio ((alpha + beta)/(delta + theta)) and increased DFA during NREM sleep. DFA during NREM was diagnostic of PDS-MCI, with an area under the receiver operating characteristic curve of 0.753 (95% CI: 0.592–0.914) (p < 0.05). Mild cognitive dysfunction was positively correlated with NREM-DFA (r = 0.426, p = 0.007) and negatively correlated with an NREM-fast ratio (r = −0.524, p = 0.001). This suggested that altered EEG activity during NREM sleep is associated with MCI in patients with PDS. NREM sleep EEG characteristics of the power spectral analysis and DFA correlate to MCI. Slowing of EEG activity during NREM sleep may reflect contribution to the decline in NREM physiological function and is therefore a marker in patients with PDS-MCI.

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

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

EEG alterations during wake and sleep in mild cognitive impairment and Alzheimer's disease

SummaryPatients with Alzheimer's disease (AD) undergo a slowing of waking electroencephalographic (EEG) rhythms since prodromal stages, which could be ascribed to poor sleep quality. We examined the relationship between wake and sleep alterations by assessing EEG activity during sleep and (pre-sleep/post-sleep) wakefulness in AD, mild cognitive impairment (MCI) and healthy controls. AD and MCI show high sleep latency and less slow-wave sleep. Reduced sigma activity characterizes non-rapid eye movement (NREM) sleep, reflecting sleep spindles loss. The EEG slowing characterizes REM sleep and wakefulness of AD and MCI, with strong correlations among the two phenomena suggesting common neuropathological mechanisms. Evening-to-morning variations in waking EEG revealed the gradual disappearance in MCI and AD of overnight changes in delta activity, indicating a progressive decay of sleep restorative functions on diurnal activity that correlates with the impairment of sleep high-frequency activity in AD. Our findings support a linkage between wake and sleep alterations, and the importance of sleep-related processes in Alzheimer's disease progression.

Early EEG Alterations Correlate with CTP Hypoperfused Volumes and Neurological Deficit: A Wireless EEG Study in Hyper-Acute Ischemic Stroke

Brain electrical activity in acute ischemic stroke is related to the hypoperfusion of cerebral tissue as manifestation of neurovascular coupling. EEG could be applicable for bedside functional monitoring in emergency settings. We aimed to investigate the relation between hyper-acute ischemic stroke EEG changes, measured with bedside wireless-EEG, and hypoperfused core-penumbra CT-perfusion (CTP) volumes. In addition, we investigated the association of EEG and CTP parameters with neurological deficit measured by NIHSS. We analyzed and processed EEG, CTP and clinical data of 31 anterior acute ischemic stroke patients registered within 4.5 h from symptom onset. Delta/alpha ratio (DAR), (delta + theta)/(alpha + beta) ratio (DTABR) and relative delta power correlated directly (ρ = 0.72; 0.63; 0.65, respectively), while alpha correlated inversely (ρ = − 0.66) with total hypoperfused volume. DAR, DTBAR and relative delta and alpha parameters also correlated with ischemic core volume (ρ = 0.55; 0.50; 0.59; − 0.51, respectively). The same EEG parameters and CTP volumes showed significant relation with NIHSS at admission. The multivariate stepwise regression showed that DAR was the strongest predictor of NIHSS at admission (p < 0.001). The results of this study showed that hyper-acute alterations of EEG parameters are highly related to the extent of hypoperfused tissue highlighting the value of quantitative EEG as a possible complementary tool in the evaluation of stroke severity and its potential role in acute ischemic stroke monitoring.

An mtDNA mutant mouse demonstrates that mitochondrial deficiency can result in autism endophenotypes

Autism spectrum disorders (ASDs) are characterized by a deficit in social communication, pathologic repetitive behaviors, restricted interests, and electroencephalogram (EEG) aberrations. While exhaustive analysis of nuclear DNA (nDNA) variation has revealed hundreds of copy number variants (CNVs) and loss-of-function (LOF) mutations, no unifying hypothesis as to the pathophysiology of ASD has yet emerged. Based on biochemical and physiological analyses, it has been hypothesized that ASD may be the result of a systemic mitochondrial deficiency with brain-specific manifestations. This proposal has been supported by recent mitochondrial DNA (mtDNA) analyses identifying both germline and somatic mtDNA variants in ASD. If mitochondrial defects do predispose to ASD, then mice with certain mtDNA mutations should present with autism endophenotypes. To test this prediction, we examined a mouse strain harboring an mtDNA ND6 gene missense mutation (P25L). This mouse manifests impaired social interactions, increased repetitive behaviors and anxiety, EEG alterations, and a decreased seizure threshold, in the absence of reduced hippocampal interneuron numbers. EEG aberrations were most pronounced in the cortex followed by the hippocampus. Aberrations in mitochondrial respiratory function and reactive oxygen species (ROS) levels were also most pronounced in the cortex followed by the hippocampus, but absent in the olfactory bulb. These data demonstrate that mild systemic mitochondrial defects can result in ASD without apparent neuroanatomical defects and that systemic mitochondrial mutations can cause tissue-specific brain defects accompanied by regional neurophysiological alterations.

Sleep-Related Declarative Memory Consolidation in Children and Adolescents with Developmental Dyslexia.

Sleep has a crucial role in memory processes, and maturational changes in sleep electrophysiology are involved in cognitive development. Albeit both sleep and memory alterations have been observed in Developmental Dyslexia (DD), their relation in this population has been scarcely investigated, particularly concerning topographical aspects. The study aimed to compare sleep topography and associated sleep-related declarative memory consolidation in participants with DD and normal readers (NR). Eleven participants with DD and 18 NR (9–14 years old) underwent a whole-night polysomnography. They were administered a word pair task before and after sleep to assess for declarative memory consolidation. Memory performance and sleep features (macro and microstructural) were compared between the groups, and the intercorrelations between consolidation rate and sleep measures were assessed. DD showed a deeper worsening in memory after sleep compared to NR and reduced slow spindles in occipito-parietal and left fronto-central areas. Our results suggest specific alterations in local sleep EEG (i.e., sleep spindles) and in sleep-dependent memory consolidation processes in DD. We highlight the importance of a topographical approach, which might shed light on potential alteration in regional cortical oscillation dynamics in DD. The latter might represent a target for therapeutic interventions aimed at enhancing cognitive functioning in DD.

EEG changes and motor deficits in Parkinson’s disease patients: Correlation of motor scales and EEG power bands

Over the years motor deficit in Parkinson’s Disease (PD) patients was largely studied, however, no consistent pattern of relations between quantitative electroencephalography (qEEG) and motor scales emerged. There is a general lack of information on the relation between EEG changes and scales related to specific motor deficits. Therefore, the study aimed to investigate the relation between brain oscillatory activity alterations (EEG power bands) and most used PD-related motor deficit scales. A positive correlation was found between the freezing of the gait questionnaire (FOGQ) and delta spectral power band (rho=0.67; p=0.008), while a negative correlation with the same scale was observed in the alpha spectral power band (rho=-0.59, p=0.027). Additionally, motor scores measure by motor part of Unified Parkinson’s Disease Rating Scale (UPDRS) correlated directly with theta (rho=0.55, p=0.040) and inversely with beta EEG power band (rho=-0.77, p=0.001). No significant correlation was found between spectral powers and Hoehn and Yahr (H&Y), BERG (Berg K. et. al. 1995), Modified Parkinson Activity Scale (MPAS), Six-Minute Walk Test (6MWT) and Timed Up and Go Test (TUG). In conclusion, our study supports the earlier findings suggesting a link between EEG slowing and motor decline, providing more insight into the relation between EEG alteration and deficits in different motor domains. These findings indicate that EEG assessment may be a useful biomarker for objective monitoring of progression and neurophysiological effect of rehabilitation approaches in PD’s.

Cognitive Dysfunctions And&amp;nbsp;Spontaneous EEG Alterations Induced by Hippocampal Amyloid Pathology in Rats

Cognitive Dysfunctions And&amp;nbsp;Spontaneous EEG Alterations Induced by Hippocampal Amyloid Pathology in Rats

Clinical Characteristics and Treatment Outcomes of De Novo Nonconvulsive Status Epilepticus: A Retrospective Study.

Background and PurposeNonconvulsive status epilepticus (NCSE) is challenging to diagnose. This study aimed to describe and classify the clinical features and electroencephalography (EEG) findings of patients with de novo NCSE and to correlate them with clinical outcomes.MethodsWe retrospectively reviewed the medical and EEG records of patients admitted to our institution with altered mentation and EEG abnormalities from January 1, 2013 to December 31, 2018. We evaluated premorbid modified Rankin Scale (mRS) scores, underlying disorders, precipitating factors, clinical manifestations, laboratory tests, and outcomes after a 3-month follow-up. Patients who met the Salzburg Consensus Criteria for NCSE were categorized into good-outcome and poor-outcome groups. A good outcome was defined as 1) clinical and electrographic seizures ceasing after treatment, and 2) an mRS score of ≤2 or remaining unchanged during the 3-month follow-up. A poor outcome was defined as 1) death, 2) seizures continuing despite treatment, or 3) a follow-up mRS score of ≥3 in a patient with a premorbid mRS score of ≤2, or a follow-up mRS score that increased in a patient with a premorbid mRS score of ≥3.ResultsThe 48 included patients comprised 37 categorized into the good-outcome group and 11 into the poor-outcome group. The presence of acute metabolic disturbances was significantly correlated with poor outcome (p=0.036), while the other analyzed variables were not significantly correlated with outcomes.ConclusionsAcute metabolic disturbances in NCSE are associated with poor outcomes. Adequate treatment of underlying reversible disorders alongside controlling seizures is critical for patients with NCSE.

Epileptic seizures in multiple sclerosis: prevalence, competing causes and diagnostic accuracy

BackgroundMultiple sclerosis (MS) is accompanied by an increased risk of epileptic seizures, but data with a detailed description of the competing causes are lacking.MethodsWe aimed to describe a cohort of patients with both MS and epileptic seizures in a retrospective, population-based study.ResultsWe included 59 out of 2285 MS patients who had at least one epileptic seizure. Out of them, 22 had seizures before the diagnosis of MS, whereas epileptic seizures occurred after MS diagnosis in 37 patients, resulting in a total prevalence of epileptic seizures in MS of 2.6%. Competing causes could be found in 50.8% (30/59) of all patients, with 40.9% (9/22) compared to 56.8% (21/37) of the MS patients with seizures before vs after MS diagnosis. The main alternative causes were traumatic brain injury and cerebral ischemia accounting for more than 30% of the patients, with no difference between the subgroups. 33.3% and 55.6% of MS patients with seizures before/after MS diagnosis had documented pathological EEG alterations. ConclusionA remarkable percentage of MS patients with epileptic seizures do have alternative competing causes at the time of the first seizure. A detailed diagnostic setup including patient history, EEG and MRI is recommended in the evaluation and choice for the best treatment.

Hyper-acute EEG alterations predict functional and morphological outcomes in thrombolysis-treated ischemic stroke: a wireless EEG study

Owing to the large inter-subject variability, early post-stroke prognosis is challenging, and objective biomarkers that can provide further prognostic information are still needed. The relation between quantitative EEG parameters in pre-thrombolysis hyper-acute phase and outcomes has still to be investigated. Hence, possible correlations between early EEG biomarkers, measured on bedside wireless EEG, and short-term/long-term functional and morphological outcomes were investigated in thrombolysis-treated strokes. EEG with a wireless device was performed in 20 patients with hyper-acute (< 4.5 h from onset) anterior ischemic stroke before reperfusion treatment. The correlations between outcome parameters (i.e., 7-day/12-month National Institutes of Health Stroke Scale NIHSS, 12-month modified Rankin Scale mRS, final infarct volume) and the pre-treatment EEG parameters were studied. Relative delta power and alpha power, delta/alpha (DAR), and (delta+theta)/(alpha+beta) (DTABR) ratios significantly correlated with NIHSS 7-day (rho = 0.80, − 0.81, 0.76, 0.75, respectively) and NIHSS 12-month (0.73, − 0.78, 0.74, 0.73, respectively), as well as with final infarct volume (0.75, − 0.70, 0.78, 0.62, respectively). A good outcome in terms of mRS ≤ 2 at 12 months was associated with DAR parameter (p = 0.008). The neurophysiological biomarkers obtained by non-invasive and portable technique as wireless EEG in the early pre-treatment phase may contribute as objective parameters to the short/long-term outcome prediction pivotal to better establish the treatment strategies.Graphical abstractBlock diagram of study protocol and main findings. Assessment at admission including wireless EEG acquisition in emergency setting (< 4.5 from stroke onset), extracted EEG features before reperfusion thrombolytic treatment. The main findings in our study sample are summarized in two different exemplificative stroke patients with different pre-thrombolysis alterations of EEG parameters resulting in different final infarct volume extensions and short/long-term clinical outcomes (NIHSS, mRS).

Regional Disconnection in Alzheimer Dementia and Amyloid-Positive Mild Cognitive Impairment: Association Between EEG Functional Connectivity and Brain Glucose Metabolism.

Introduction: The disconnection hypothesis of Alzheimer's disease (AD) is supported by growing neuroimaging and neurophysiological evidence of altered brain functional connectivity in cognitively impaired individuals. Brain functional modalities such as [18F]fluorodeoxyglucose positron-emission tomography ([18F]FDG-PET) and electroencephalography (EEG) measure different aspects of synaptic functioning, and can contribute to understanding brain connectivity disruptions in AD.Aim: This study investigated the relationship between cortical glucose metabolism and topographical EEG measures of brain functional connectivity in subjects along AD continuum.Methods: Patients diagnosed with mild cognitive impairment (MCI) and AD (n = 67), and stratified into amyloid-positive (n = 32) and negative (n = 10) groups according to cerebrospinal fluid Aβ42/40 ratio, were assessed with [18F]FDG-PET and resting-state EEG recordings. EEG-based neuroimaging analysis involved standardized low-resolution electromagnetic tomography (sLORETA), which estimates functional connectivity from cortical sources of electrical activity in a 3D head model.Results: Glucose hypometabolism in temporoparietal lobes was significantly associated with altered EEG functional connectivity of the same regions of interest in clinically diagnosed MCI and AD patients and in patients with biomarker-verified AD pathology. The correlative pattern of disrupted connectivity in temporoparietal lobes, as detected by EEG sLORETA analysis, included decreased instantaneous linear connectivity in fast frequencies and increased lagged linear connectivity in slow frequencies in relation to the activity of remaining cortex.Conclusions: Topographical EEG measures of functional connectivity detect regional dysfunction of AD-vulnerable brain areas as evidenced by association and spatial overlap with the cortical glucose hypometabolism in MCI and AD patients.Impact statementThe association between glucose hypometabolism, as evidenced by [18F]FDG-PET ([18F]fluorodeoxyglucose positron-emission tomography), and altered electroencephalography (EEG) functional connectivity metrics within temporoparietal lobes provides link between synaptic, neurophysiological, and metabolic impairment in mild cognitive impairment and Alzheimer's disease patients. This study reported alterations in EEG measures of both instantaneous and lagged linear connectivity across distinct frequency bands, both of which were shown to be important for inter- and intrahemispheric communication and function of memory systems in general. EEG-based imaging of brain functional connectivity has a potential to serve as a noninvasive, low-cost, and widely available alternative in assessing synaptic and network dysfunction in cognitively impaired patients.

Altered phase and nonphase EEG activity expose impaired maintenance of a spatial-object attentional focus in multiple sclerosis patients

Some of the anatomical and functional basis of cognitive impairment in multiple sclerosis (MS) currently remains unknown. In particular, there is scarce knowledge about modulations in induced EEG (nonphase activity) for diverse frequency bands related to attentional deficits in this pathology. The present study analyzes phase and nonphase alpha and gamma modulations in 26 remitting-relapsing multiple sclerosis patients during their participation in the attention network test compared with twenty-six healthy controls (HCs) matched in sociodemographic variables. Behavioral results showed that the MS group exhibited general slowing, suggesting impairment in alerting and orienting networks, as has been previously described in other studies. Time–frequency analysis of EEG revealed that the gamma band was related to the spatial translation of the attentional focus, and the alpha band seemed to be related to the expectancy mechanisms and cognitive processing of the target. Moreover, phase and nonphase modulations differed in their psychophysiological roles and were affected differently in the MS and HC groups. In summary, nonphase modulations can unveil hidden cognitive mechanisms for phase analysis and complete our knowledge of the neural basis of cognitive impairment in multiple sclerosis pathology.

Altered circadian activity and sleep/wake rhythms in the stable tubule only polypeptide (STOP) null mouse model of schizophrenia.

Sleep and circadian rhythm disruptions commonly occur in individuals with schizophrenia. Stable tubule only polypeptide (STOP) knockout (KO) mice show behavioral impairments resembling symptoms of schizophrenia. We previously reported that STOP KO mice slept less and had more fragmented sleep and waking than wild-type littermates under a light/dark (LD) cycle. Here, we assessed the circadian phenotype of male STOP KO mice by examining wheel-running activity rhythms and EEG/EMG-defined sleep/wake states under both LD and constant darkness (DD) conditions. Wheel-running activity rhythms in KO and wild-type mice were similarly entrained in LD, and had similar free-running periods in DD. The phase delay shift in response to a light pulse given early in the active phase under DD was preserved in KO mice. KO mice had markedly lower activity levels, lower amplitude activity rhythms, less stable activity onsets, and more fragmented activity than wild-type mice in both lighting conditions. KO mice also spent more time awake and less time in rapid eye movement sleep (REMS) and non-REMS (NREMS) in both LD and DD conditions, with the decrease in NREMS concentrated in the active phase. KO mice also showed altered EEG features and higher amplitude rhythms in wake and NREMS (but not REMS) amounts in both lighting conditions, with a longer free-running period in DD, compared to wild-type mice. These results indicate that the STOP null mutation in mice altered the regulation of sleep/wake physiology and activity rhythm expression, but did not grossly disrupt circadian mechanisms.

Alterations of Resting EEG in Hallucinating and Nonhallucinating Schizophrenia Patients.

Auditory hallucinations (AHs) are a common symptom of schizophrenia and contribute significantly to disease burden. Research on schizophrenia and AHs is limited and fails to adequately address the effect of AHs on resting EEG in patients with schizophrenia. This study assessed changes in frequency bands (delta, theta, alpha, beta) of resting EEG taken from hallucinating patients (n = 12), nonhallucinating patients (n = 11), and healthy controls (n = 12). Delta and theta activity were unaffected by AHs but differed between patients with schizophrenia and healthy controls. Alpha activity was affected by AHs: nonhallucinators had more alpha activity than hallucinators and healthy controls. Additionally, beta activity was inversely related to trait measures of AHs. These findings contribute to the literature of resting eyes closed EEG recordings of schizophrenia and AHs, and indicate the role of delta, theta, alpha, and beta as markers for schizophrenia and auditory hallucinations.

Melatonin ameliorates the sleep disorder induced by surgery under sevoflurane anaesthesia in aged mice.

Post-operative sleep disorders induce adverse effects on patients, especially the elderly, which may be associated with surgery and inhalational anaesthetics. Melatonin is a neuroendocrine regulator of the sleep-wake cycle. In this study, we analysed the alterations of post-operative sleep in aged melatonin-deficient (C57BL/6J) mice, and investigated if exogenous melatonin could facilitate entrainment of circadian rhythm after laparotomy under sevoflurane anaesthesia. The results showed that laparotomy under sevoflurane anaesthesia had a greater influence on post-operative sleep than sevoflurane alone. Laparotomy under anaesthesia led to circadian rhythm shifting forward, altered EEG power density and delta power of NREM sleep, and lengthened REM and NREM sleep latencies. In the light phase, the number of waking episodes tended to decline, and wake episode duration elevated. However, these indicators presented the opposite tendency during the dark phase. Melatonin showed significant efficacy for ameliorating the sleep disorder and restoring physiological sleep, and most of the beneficial effect of melatonin was antagonized by luzindole, a melatonin receptor antagonist.

Inter-band Bispectral Analysis of EEG Background Activity to Characterize Alzheimer's Disease Continuum.

The aim of this study was to characterize the EEG alterations in inter-band interactions along the Alzheimer's disease (AD) continuum. For this purpose, EEG background activity from 51 healthy control subjects, 51 mild cognitive impairment patients, 50 mild AD patients, 50 moderate AD patients, and 50 severe AD patients was analyzed by means of bispectrum. Three inter-band features were extracted from bispectrum matrices: bispectral relative power (BispRP), cubic bispectral entropy (BispEn), and bispectral median frequency (BispMF). BispRP results showed an increase of delta and theta interactions with other frequency bands and the opposite behavior for alpha, beta-1, and beta-2. Delta and theta interactions, along with the rest of the spectrum, also experimented a decrease of BispEn with disease progression, suggesting these bands interact with a reduced variety of components in advanced stages of dementia. Finally, BispMF showed a consistent reduction along the AD continuum in all bands, which is reflective of an interaction of the global spectrum with lower frequency bands as the disease develops. Our results indicate a progressive decrease in inter-band interactions with the severity of the disease, especially those involving high frequency components. Since inter-band coupling oscillations are related to complex and multi-scaled brain processes, these alterations likely reflect the neurodegeneration associated with the AD continuum.