Differential Effects of Non-REM and REM Sleep on Memory Consolidation?

Sleep benefits memory consolidation. Previous theoretical accounts have proposed a differential role of slow-wave sleep (SWS), rapid-eye-movement (REM) sleep, and stage N2 sleep for different types of memories. For example the dual process hypothesis proposes that SWS is beneficial for declarative memories, whereas REM sleep is important for consolidation of non-declarative, procedural and emotional memories. In fact, numerous recent studies do provide further support for the crucial role of SWS (or non-REM sleep) in declarative memory consolidation. However, recent evidence for the benefit of REM sleep for non-declarative memories is rather scarce. In contrast, several recent studies have related consolidation of procedural memories (and some also emotional memories) to SWS (or non-REM sleep)-dependent consolidation processes. We will review this recent evidence, and propose future research questions to advance our understanding of the role of different sleep stages for memory consolidation.     

Theta activity of septal neurons during different epileptic phases: The same frequency but different significance?

The multiunit activity in the medial septal–diagonal band complex (MSDB) and field potentials of the hippocampus were simultaneously recorded in waking healthy rabbits (control) and in the same animals that were then exposed to kindling stimulation of the perforant path. In the control, the bursts of spikes in one group of rhythmic MSDB neurons phase-locked to the top of theta waves in the hippocampus, and in the second group, to the trough of these waves. The stimulation evoked seizure afterdischarges in the hippocampus and seizure bursts of spikes separated by periods of inhibition in MSDB neurons. In the first group of septal cells, seizure bursts coincided with inhibitory periods between afterdischarges in the hippocampus; in the second group, these bursts were observed during seizure afterdischarges, suggesting that different MSDB cells play opposite roles in the development of seizures. Evoked afterdischarges were spontaneously followed by recurrent ictal events; neuronal oscillations at the theta (6–7 Hz) or “twice-theta” frequency (12–14 Hz) preceded these secondary epileptic discharges. As a result of kindling, interictal spikes were recorded in the hippocampus; at the same time, synchronous bursts of many cells appeared in the MSDB. In the epileptic brain, the frequency of both the hippocampal theta rhythm and MSDB neuronal theta bursts increased; in the septum, an augmentation of neuronal rhythmicity was also observed. Theta oscillations, either spontaneous or evoked by sensory stimulation, abolished the epileptiform events. Evidently, the activities within the theta range during preictal and interictal periods are of different significance in the generation of seizures.     

Quantitative analysis of the EEG during tonic REM sleep — methodology

Frequency and amplitude characteristics of the clinical (waking) electroencephalogram (EEG) can be diagnostically be limited by neuronal degenerative disorders such as Alzheimer's or other cortical dementias. However, interpretation of the clinical EEG may be limited by many factors, including movement and muscle artifacts and uncontrolled variations along the alert/drowsy continuum. Moreover, the clinical EEG involves subjective judgment by experts whose opinions often differ. In an effort to address these problems, we have developed a computer-automated technology that examines the digitized, all-night sleep EEG for frequency and amplitude characteristics of potential diagnostic relevance to Alzheimer's dementia. Robust time series analysis techniques and a modified power spectral analysis (Z-spectra) are used to suppress artifactual information and to automatically select samples of tonic REM sleep EEG. The spectra (amplitude vs. frequency relationship) of this specific EEG state is then assessed for diagnostically relevant information.     

The Sleep Side of Aging and Alzheimer’s Disease

As we age, sleep patterns undergo significant modifications in micro and macrostructure, worsening cognition and quality of life. These are associated with remarkable brain changes, like deterioration in synaptic plasticity, gray and white matter, and significant modifications in hormone levels. Sleep alterations are also a core component of mild cognitive impairment (MCI) and Alzheimer’s Disease (AD). AD night time is characterized by a gradual decrease in slow-wave activity and a substantial reduction of REM sleep. Sleep abnormalities can accelerate AD pathophysiology, promoting the accumulation of amyloid-β (Aβ) and phosphorylated tau. Thus, interventions that target sleep disturbances in elderly people and MCI patients have been suggested as a possible strategy to prevent or decelerate conversion to dementia. Although cognitive-behavioral therapy and pharmacological medications are still first-line treatments, despite being scarcely effective, new interventions have been proposed, such as sensory stimulation and Noninvasive Brain Stimulation (NiBS). The present review outlines the current state of the art of the relationship between sleep modifications in healthy aging and the neurobiological mechanisms underlying age-related changes. Furthermore, we provide a critical analysis showing how sleep abnormalities influence the prognosis of AD pathology by intensifying Aβ and tau protein accumulation. We discuss potential therapeutic strategies to target sleep disruptions and conclude that there is an urgent need for testing new therapeutic sleep interventions.     

Validation study of REM Sleep Behavior Disorder Questionnaire – Hong Kong (RBDQ-HK) in East China

ObjectiveTo validate the REM Sleep Behavior Disorder (RBD) Questionnaire – Hong Kong (RBDQ-HK) in polysomnography (PSG)-confirmed RBD and non-RBD subjects, and to evaluate its usefulness in different clinical populations.MethodsIn total, 325 subjects (115 RBD and 210 controls) from East China were enrolled. After patients had finished the structured interview, and completed the RBDQ-HK and video-PSG test, we evaluated the reliability of RBDQ-HK (areas under the curves (AUC), the best cut-off values, factor 2 of RBDQ-HK, and overall scale) and validated the usefulness of RBDQ-HK between the Parkinson disease (PD) and obstructive sleep apnea (OSA) groups.ResultsThe best cut-off values for factor 2 of RBDQ-HK were located at 7/8 with a sensitivity of 90% and specificity of 82% (AUC = 0.911), and for RBDQ-HK overall scale were located at 17 with a sensitivity of 85% and specificity of 81% (AUC = 0.892) in all subjects. Both factor 2 and overall scale of RBDQ-HK are valid in all subjects (PD and OSA patients), with a higher accuracy given by factor 2 of RBDQ-HK.ConclusionsRBDQ-HK and its factor 2 are useful and validated RBD screening instruments, and could be used as a tool for screening RBD in patients with PD and OSA.     

The influence of intrapersonal sensorimotor experiences on the corticospinal responses during action–observation

The coupling of perception and action has been strongly indicated by evidence that the observation of an action primes a response in the observer. It has been proposed that these primed responses may be inhibited when the observer is able to more closely distinguish between self- and other-generated actions – the greater the distinction, then the greater the inhibition of the primed response. This self–other distinction is shown to be enhanced following a period of visual feedback of self-generated action. The present study was designed to examine how sensorimotor experiences pertaining to self-generated action affect primed responses from observed actions. Single-pulse transcranial magnetic stimulation was used to investigate corticospinal activity elicited during the observation of index- and little-finger actions before and after training (self-generated action). For sensorimotor training, participants executed finger movements with or without visual feedback of their own movement. Results showed that the increases in muscle-specific corticospinal activity elicited from action–observation persisted after training without visual feedback, but did not emerge following training with visual feedback. This inhibition in corticospinal activity during action–observation following training with vision could have resulted from the refining of internal models of self-generated action, which then led to a greater distinction between “self” and “other” actions.     

A Comparison of the Sleep–Wake Patterns of Cosleeping and Solitary-Sleeping Infants

This study examined whether 3–15, month-old cosleeping infants displayed differences in time spent in active versus quiet sleep, and in the number/duration of nighttime awakenings when compared with solitary-sleeping infants; and also whether they spent the majority of the night sleeping face-to-face, as previously reported. Nine cosleeping and nine solitary-sleeping infants were matched on age, gender, ethnicity, maternal age, and family SES. Video recordings of nighttime sleep yielded percentage of time in active sleep, quiet sleep, and awake, number of wakenings, and the percentage of time cosleeping infants and mothers spent face-to-face. Across age, cosleeping infants had more awakenings per night mean 5.8(1.50) versus 3.2(1.95); t=3.16, p =.006). The percent of the nighttime spent awake did not differ between groups, suggesting that cosleeping infants had shorter awakenings. Cosleeping infants spent 40% of the night face-to-face with their mothers.This work was supported in part by NIMH R01-MH50741 (TFA).     

Theta power responses in mild Alzheimer’s disease during an auditory oddball paradigm: lack of theta enhancement during stimulus processing

There is evidence that theta responses reflect cognitive performance: good performances are associated with a decrease in tonic theta power as well as an increase in phasic theta power. In the present study, both tonic and phasic theta activity were analysed in 22 patients with mild Alzheimer’s disease (AD), and 16 healthy elderly controls. Single-trial theta power responses were evaluated by an active auditory oddball paradigm along an early poststimulus window (0–250 ms) and a late time window (250–500 ms), and then compared to prestimulus theta power during both target tone and standard tone processing. The main findings were: (1) in AD patients, there was an increased prestimulus theta power, as well as no significant poststimulus theta power increase upon both target and non-target stimulus processing; (2) in healthy aged controls, only during target tone processing, an enhancement of both early and late theta responses relative to the prestimulus baseline was found. Moreover, healthy controls had a frontal dominance of theta power. The results might indicate that, during target processing, theta response is not functionally sensitive in AD and cannot be involved in processing demands as efficiently as in healthy controls. From a psychophysiological point of view, this might suggest an impairment of attentional allocation resources. The psychological implications might be related to selective attention/working-memory impairment from the early stage of the disease. Our data confirm that both tonic and phasic theta are relevant indicators of cognitive performance: the lack of a phasic theta and an increase in tonic theta are congruous findings in cognitive decline. Another factor worth noting is that in AD patients theta response is not dominant at the frontal site (as observed in healthy controls), indicating a weaker frontal lobe network reactivity during stimulus processing.     

A Cost Analysis of the Innovation–Decision Process of an Evidence-Based Practice in Schools

School Mental Health - The translation of evidence-based practices (EBPs) to improve students’ social, emotional, behavioral, and academic outcomes into authentic school settings has posed...     

Sleep duration and risk of stroke: a dose–response meta-analysis of prospective cohort studies

ObjectivesSuboptimal sleep duration has been considered to increase the risk of stroke incidence. Thus we aimed to conduct a dose–response meta-analysis to examine the association between sleep duration and stroke incidence.MethodsWe searched PubMed, Web of science and the Cochrane Library to identify all prospective studies evaluating the association of sleep duration and nonfatal and/or fatal stroke incidence. Then, restricted cubic spline functions and piecewise linear functions were used to evaluate the nonlinear and linear dose–response association between them.ResultsWe included a total of 16 prospective studies enrolling 528,653 participants with 12,193 stroke events. Nonlinear dose–response meta-analysis showed a J-shaped association between sleep duration and total stroke with the lowest risk observed with sleeping for 7 h. Considering people sleeping for 7 h as reference, long sleepers had a higher predicted risk of total stroke than short sleepers [the pooled risk ratios (95% confidence intervals): 4 h: 1.17 (0.99–1.38); 5 h: 1.17 (1.00–1.37); 6 h: 1.10 (1.00–1.21); 8 h: 1.17 (1.07–1.28); 9 h: 1.45 (1.23–1.70); 10 h: 1.64 (1.4–1.92); p_nonlinearity<0.001]. Short sleep durations were only significantly associated with nonfatal stroke and with total stroke in the subgroups of structured interview and non-Asian countries. Additionally, we found a slightly decreased risk of ischemic stroke among short sleepers. For piecewise linear trends, compared to 7 h, every 1-h increment of sleep duration led to an increase of 13% [the pooled risk ratios (95% confidence intervals): 1.13 (1.07–1.20); p < 0.001] in risk of total stroke.ConclusionBoth in nonlinear and piecewise linear dose–response meta-analyses, long sleep duration significantly increased the risk of stroke incidence.     

Nurses’ Sleep Quality of “Fangcang” Hospital in China during the COVID-19 Pandemic

International Journal of Mental Health and Addiction -     

Effect of Valproic Acid Through Regulation of NMDA Receptor–ERK Signaling in Sleep Deprivation Rats

Although the effect of mood stabilizer valproic acid (VPA) through multiple signaling pathways has been shown, its therapeutic mechanism is still largely unknown. We investigated the effect of VPA (200 mg/kg, every 12 h) in sleep deprivation (SD) rats (72 h), the manic-like animal model, focusing on the N-methyl-D: -aspartic acid (NMDA) receptor and signaling mediators of synaptic plasticity such as extracellular signal-regulated protein kinase (ERK), cAMP response element-binding protein (CREB), B cell chronic lymphocytic leukemia/lymphoma 2 (BCL2), and brain-derived neurotrophic factor (BDNF). SD reduced the expression of the NR2B subunit of the NMDA receptor in the frontal cortex and hippocampus but did not affect the expression of NR1 and NR2A subunits. In comparison, VPA inhibited the SD-induced reduction of NR2B expression in both brain regions. In addition, SD attenuated ERK phosphorylation in the frontal cortex and hippocampus, whereas VPA prevented the attenuation. VPA also protected the SD-induced decrease of CREB phosphorylation, BCL2 expression, and BDNF expression in the frontal cortex but not in the hippocampus. These results indicate that VPA could regulate NMDA receptor-ERK signaling in SD rats, preventing the SD-induced decrease of the expression of NR2B subunit and the activation of ERK signaling mediators such as ERK, CREB, BCL2, and BDNF.     

The Emerging Relationship Between Interstitial Fluid–Cerebrospinal Fluid Exchange,Amyloid-β, and Sleep

Amyloid-β (Aβ) plaques are a key histopathological hallmark of Alzheimer’s disease (AD), and soluble Aβ species are believed to play an important role in the clinical development of this disease. Emerging biomarker data demonstrate that Aβ plaque deposition begins decades before the onset of clinical symptoms, suggesting that understanding the biological determinants of the earliest steps in the development of AD pathology may provide key opportunities for AD treatment and prevention. Although a clinical association between sleep disruption and AD has long been appreciated, emerging clinical studies and insights from the basic neurosciences have shed important new light on how sleep and Aβ homeostasis may be connected in the setting of AD. Aβ, like many interstitial solutes, is cleared in part through the exchange of brain interstitial fluid and cerebrospinal fluid along a brain-wide network of perivascular pathways recently termed the glymphatic system. Glymphatic function is primarily a feature of the sleeping brain, rather than the waking brain, and is slowed in the aging and posttraumatic brain. These changes may underlie the diurnal fluctuations in interstitial and cerebrospinal fluid Aβ levels observed in both the rodent and the human. These and other emerging studies suggest that age-related sleep disruption may be one key factor that renders the aging brain vulnerable to Aβ deposition and the development of AD. If this is true, sleep may represent a key modifiable risk factor or therapeutic target in the preclinical phases of AD.     

The dynamics of β1 integrin expression during peripheral nerve regeneration

The aim of the present study was to examine the expression of 1 integrin subunit after peripheral nerve transection. After sciatic nerve transection two experimental procedures were used; changes in the freely regenerating rat sciatic nerve were compared to a situation in which spontaneous regeneration was prevented by suturing both ends of the nerve to the muscle next to the point of transection. Specimens for morphological analysis were collected 6 h, 1, 3, 5, 7 days and 2, 4, 6 and 8 weeks after the axotomy. Sections from the proximal (two zones) and distal (three zones) stumps next to the point of transection were stained with antibodies against 1 integrin subunit, macrophages, collagen types I and III, and S-100 protein. The control nerves showed 1 integrin-stained cells in the perineurium and vasa nervorum but the endoncurium was negative. Positively stained endoneurial fibroblast-like cells could be seen in the proximal part of the nerve already at 24 h after transection. The number of these positively stained cells increased steadily; they were most numerous 4 weeks after transection in the distal zone 2. Subsequently, the number of positively stained endoneural cells declined sharply and 8 weeks after transection no positively stained cells could be found. The morphological appearance and the immunohistochemical properties of the cells suggest that the majority of 1 integrin-positive cells are endoneurial fibroblast-like cells. Thus, the process appeared to be dynamic, starting from the proximal part and continuing to the distal parts, and was similar in both experimental groups. The positive staining in perineurial cells indicate that 1 integrin, which is an important mediator of the cell-matrix interaction, may have an essential role in the formation and strengthening of the normal peripheral nerve structures. Furthermore, 1 integrin seems to have an active role in reactions which occur during the early phases of peripheral nerve regeneration.     

Consolidation of vocabulary during sleep: The rich get richer?

Sleep plays a role in strengthening new words and integrating them with existing vocabulary knowledge, consistent with neural models of learning in which sleep supports hippocampal transfer to neocortical memory. Such models are based on adult research, yet neural maturation may mean that the mechanisms supporting word learning vary across development. Here, we propose a model in which children may capitalise on larger amounts of slow-wave sleep to support a greater demand on learning and neural reorganisation, whereas adults may benefit from a richer knowledge base to support consolidation. Such an argument is reinforced by the well-reported “Matthew effect”, whereby rich vocabulary knowledge is associated with better acquisition of new vocabulary. We present a meta-analysis that supports this association between children’s existing vocabulary knowledge and their integration of new words overnight. Whilst multiple mechanisms likely contribute to vocabulary consolidation and neural reorganisation across the lifespan, we propose that contributions of existing knowledge should be rigorously examined in developmental studies. Such research has potential to greatly enhance neural models of learning.     

The Children’s Sleep Comic: Psychometrics of a Self-rating Instrument for Childhood Insomnia

The Children’s Sleep Comic is a standardized self-report questionnaire for assessing insomnia in children ages 5–11 years. The goal of the present study is to introduce a revised version of this measure and to present psychometrics and a cut-off score. Therefore, the revised Children’s Sleep Comic, the Sleep Self Report, the Children’s Sleep Habits Questionnaire, and the Child Behavior Checklist were applied to a sample of 393 children and their parents. Of the parents who participated voluntarily, a subsample (n = 176) was interviewed on the phone to diagnose their children with sleep disorders according to the International Classification of Sleep Disorders, if applicable. The results indicated that the Children’s Sleep Comic is a reliable self-rating instrument for diagnosing childhood insomnia. Internal consistency was α = 0.83; and convergent and divergent validity were adequate. The child-friendly format can foster a good therapeutic relationship, and thus establish the basis for successful intervention.     

The state of systemic oxidative stress during Parkinson’s disease

The development of oxidative stress is considered as one of the key molecular mechanisms that lead to the death of dopamine-producing neurons in Parkinson’s disease (PD). Here, we characterized the oxidative status (OS) of patients depending on the severity of the disease, the time course of the disease, and treatment with antiparkinsonian drugs. The OS was evaluated using Fe²⁺-induced chemiluminescence of serum lipoproteins (LPs) on the basis of informative parameters, including preformed lipid hydroperoxides, the maximum intensity of lipid peroxidation (LPO) and LP resistance to oxidation, due to the activity of the endogenous antioxidant system. In all patients, regardless of the disease stage (second, third, or fourth), we observed a comparable unidirectional increase in the level of lipid hydroperoxides and maximum intensity of (LPO). However, the activity of the endogenous antioxidant system decreased proportionally to the disease severity: second stage > third stage > fourth stage. In patients at the second and third stages of the disease who were treated with antiparkinsonian drugs we found a disruption of the OS in comparison with untreated patients of the same stage. In general, the deterioration of the OS in patients at the second and third stages of the disease, which included an increase in the level of lipid hydroperoxides and the maximum intensity of LPO, was detected in both patients receiving levodopa at a daily dose of more than 300 mg and in patients treated with drugs that did not contain levodopa. The decrease in the activity of the endogenous antioxidant system in these patients did not depend on the method of treatment and the dose of levodopa. The duration of treatment (up to 5 years) did not influence the OS of patients at the second and third stages of the disease. These data confirm the concept of the significance of oxidative stress in the pathogenesis of PD and indicate the advisability of using antioxidant drugs in complex therapy of PD.