Spindle Oscillations in Sleep Disorders: A Systematic Review

Measurement of sleep microarchitecture and neural oscillations is an increasingly popular technique for quantifying EEG sleep activity. Many studies have examined sleep spindle oscillations in sleep-disordered adults; however reviews of this literature are scarce. As such, our overarching aim was to critically review experimental studies examining sleep spindle activity between adults with and without different sleep disorders. Articles were obtained using a systematic methodology with a priori criteria. Thirty-seven studies meeting final inclusion criteria were reviewed, with studies grouped across three categories: insomnia, hypersomnias, and sleep-related movement disorders (including parasomnias). Studies of patients with insomnia and sleep-disordered breathing were more abundant relative to other diagnoses. All studies were cross-sectional. Studies were largely inconsistent regarding spindle activity differences between clinical and nonclinical groups, with some reporting greater or less activity, while many others reported no group differences. Stark inconsistencies in sample characteristics (e.g., age range and diagnostic criteria) and methods of analysis (e.g., spindle bandwidth selection, visual detection versus digital filtering, absolute versus relative spectral power, and NREM2 versus NREM3) suggest a need for greater use of event-based detection methods and increased research standardization. Hypotheses regarding the clinical and empirical implications of these findings, and suggestions for potential future studies, are also discussed

Spindle Oscillations in Sleep Disorders: A Systematic Review

Measurement of sleep microarchitecture and neural oscillations is an increasingly popular technique for quantifying EEG sleep activity. Many studies have examined sleep spindle oscillations in sleep-disordered adults; however reviews of this literature are scarce. As such, our overarching aim was to critically review experimental studies examining sleep spindle activity between adults with and without different sleep disorders. Articles were obtained using a systematic methodology with a priori criteria. Thirty-seven studies meeting final inclusion criteria were reviewed, with studies grouped across three categories: insomnia, hypersomnias, and sleep-related movement disorders (including parasomnias). Studies of patients with insomnia and sleep-disordered breathing were more abundant relative to other diagnoses. All studies were cross-sectional. Studies were largely inconsistent regarding spindle activity differences between clinical and nonclinical groups, with some reporting greater or less activity, while many others reported no group differences. Stark inconsistencies in sample characteristics (e.g., age range and diagnostic criteria) and methods of analysis (e.g., spindle bandwidth selection, visual detection versus digital filtering, absolute versus relative spectral power, and NREM2 versus NREM3) suggest a need for greater use of event-based detection methods and increased research standardization. Hypotheses regarding the clinical and empirical implications of these findings, and suggestions for potential future studies, are also discussed

Sleep deprivation reveals altered brain perfusion patterns in somnambulism

BACKGROUND: Despite its high prevalence, relatively little is known about the pathophysiology of somnambulism. Increasing evidence indicates that somnambulism is associated with functional abnormalities during wakefulness and that sleep deprivation constitutes an important drive that facilitates sleepwalking in predisposed patients. Here, we studied the neural mechanisms associated with somnambulism using Single Photon Emission Computed Tomography (SPECT) with 99mTc-Ethylene Cysteinate Dimer (ECD), during wakefulness and after sleep deprivation. METHODS: Ten adult sleepwalkers and twelve controls with normal sleep were scanned using 99mTc-ECD SPECT in morning wakefulness after a full night of sleep. Eight of the sleepwalkers and nine of the controls were also scanned during wakefulness after a night of total sleep deprivation. Between-group comparisons of regional cerebral blood flow (rCBF) were performed to characterize brain activity patterns during wakefulness in sleepwalkers. RESULTS: During wakefulness following a night of total sleep deprivation, rCBF was decreased bilaterally in the inferior temporal gyrus in sleepwalkers compared to controls. CONCLUSIONS: Functional neural abnormalities can be observed during wakefulness in somnambulism, particularly after sleep deprivation and in the inferior temporal cortex. Sleep deprivation thus not only facilitates the occurrence of sleepwalking episodes, but also uncovers patterns of neural dysfunction that characterize sleepwalkers during wakefulness

Structural Brain Alterations Associated with Rapid Eye Movement Sleep Behavior Disorder in Parkinson’s Disease

Characterized by dream-enactment motor manifestations arising from rapid eye movement (REM) sleep, REM sleep behavior disorder (RBD) is frequently encountered in Parkinson’s disease (PD). Yet the specific neurostructural changes associated with RBD in PD patients remain to be revealed by neuroimaging. Here we identified such neurostructural alterations by comparing large samples of magnetic resonance imaging (MRI) scans in 69 PD patients with probable RBD, 240 patients without RBD and 138 healthy controls, using deformation-based morphometry (p < 0.05 corrected for multiple comparisons). All data were extracted from the Parkinson’s Progression Markers Initiative. PD patients with probable RBD showed smaller volumes than patients without RBD and than healthy controls in the pontomesencephalic tegmentum, medullary reticular formation, hypothalamus, thalamus, putamen, amygdala and anterior cingulate cortex. These results demonstrate that RBD is associated with a prominent loss of volume in the pontomesencephalic tegmentum, where cholinergic, GABAergic and glutamatergic neurons are located and implicated in the promotion of REM sleep and muscle atonia. It is additionally associated with more widespread atrophy in other subcortical and cortical regions whose loss also likely contributes to the altered regulation of sleep-wake states and motor activity underlying RBD in PD patients

Altered regional cerebral blood flow in idiopathic hypersomnia

Objectives Idiopathic hypersomnia is characterized by excessive daytime sleepiness despite normal or long sleep time. Its pathophysiological mechanisms remain unclear. This pilot study aims at characterizing the neural correlates of idiopathic hypersomnia using single photon emission computed tomography. Methods Thirteen participants with idiopathic hypersomnia and sixteen healthy controls were scanned during resting wakefulness using a high-resolution single photon emission computed tomography scanner with 99mTc-ethyl cysteinate dimer to assess cerebral blood flow. The main analysis compared regional cerebral blood flow distribution between the two groups. Exploratory correlations between regional cerebral blood flow and clinical characteristics evaluated the functional correlates of those brain perfusion patterns. Significance was set at p <0.05 after correction for multiple comparisons. Results Idiopathic hypersomnia participants showed regional cerebral blood flow decreases in medial prefrontal cortex, posterior cingulate cortex and putamen, as well as increases in amygdala and temporo-occipital cortices. Lower regional cerebral blood flow in the medial prefrontal cortex was associated with higher daytime sleepiness. Conclusions These preliminary findings suggest that idiopathic hypersomnia is characterized by functional alterations in brain areas involved in the modulation of vigilance states, which may contribute to the daytime symptoms of this condition. The distribution of regional cerebral blood flow changes was reminiscent of the patterns associated with normal non-rapid-eye-movement sleep, suggesting the possible presence of incomplete sleep-wake transitions. These abnormalities were strikingly distinct from those induced by acute sleep deprivation, suggesting that the patterns seen here might reflect a trait associated with idiopathic hypersomnia rather than a non-specific state of sleepiness

Some chalcones derived from thio-phene-3-carbaldehyde: synthesis and crystal structures.

The synthesis, spectroscopic data and crystal and mol-ecular structures of four 3-(3-phenyl-prop-1-ene-3-one-1-yl)thio-phene derivatives, namely 1-(4-hydroxy-phen-yl)-3-(thio-phen-3-yl)prop-1-en-3-one, C13H10O2S, (1), 1-(4-meth-oxy-phen-yl)-3-(thio-phen-3-yl)prop-1-en-3-one, C14H12O2S, (2), 1-(4-eth-oxy-phen-yl)-3-(thio-phen-3-yl)prop-1-en-3-one, C15H14O2S, (3), and 1-(4--bromophen-yl)-3-(thio-phen-3-yl)prop-1-en-3-one, C13H9BrOS, (4), are described. The four chalcones have been synthesized by reaction of thio-phene-3-carbaldehyde with an aceto-phenone derivative in an absolute ethanol solution containing potassium hydroxide, and differ in the substituent at the para position of the phenyl ring: -OH for 1, -OCH3 for 2, -OCH2CH3 for 3 and -Br for 4. The thio-phene ring in 4 was found to be disordered over two orientations with occupancies 0.702 (4) and 0.298 (4). The configuration about the C=C bond is E. The thio-phene and phenyl rings are inclined by 4.73 (12) for 1, 12.36 (11) for 2, 17.44 (11) for 3 and 46.1 (6) and 48.6 (6)° for 4, indicating that the -OH derivative is almost planar and the -Br derivative deviates the most from planarity. However, the substituent has no real influence on the bond distances in the α,β-unsaturated carbonyl moiety. The mol-ecular packing of 1 features chain formation in the a-axis direction by O-H⋯O contacts. In the case of 2 and 3, the packing is characterized by dimer formation through C-H⋯O inter-actions. In addition, C-H⋯π(thio-phene) inter-actions in 2 and C-H⋯S(thio-phene) inter-actions in 3 contribute to the three-dimensional architecture. The presence of C-H⋯π(thio-phene) contacts in the crystal of 4 results in chain formation in the c-axis direction. The Hirshfeld surface analysis shows that for all four derivatives, the highest contribution to surface contacts arises from contacts in which H atoms are involved

A Randomized Trial of Exercise Training Versus Relaxation for the Treatment of Chronic Insomnia in Obstructive Sleep Apnea

Background: Obstructive Sleep Apnea Syndrome (OSA) is a common sleep disorder characterized by partial or complete blockage of the pharyngeal airway during sleep, posing as a significant public health concern. OSA is often comorbid with chronic insomnia (COMISA). Insomnia disorder involves a difficulty initiating sleep, maintaining sleep and/or early awakenings, despite time and opportunity for sleep, causing impairments in daytime functioning and significant distress. Individuals with COMISA suffer from worse sleep and daytime functioning, compared to individuals presenting with either disorder in isolation. Due to their insomnia complaints, these individuals tend to be less compliant with continuous positive airway pressure (CPAP) therapy, the gold standard treatment for OSA. Cognitive behavioural therapy for insomnia (CBTi) has shown promising results in this population but can be difficult for individuals to access, and alone, cannot improve OSA severity. This unique group requires a therapy targeted to both disorders, which would potentially improve apnea-hypopnea index (AHI) and/or insomnia symptomology for a better sleep. Currently, no effective therapy tailored to these individuals has been found. Exercise is a potential non-pharmacological therapy that would simultaneously improve symptoms of both disorders. Studies examining the effects of exercise as a therapy for COMISA are lacking, and research examining exercise as a therapy for either of the two disorders alone yield mixed results likely due to variation in methodology and treatment approach. Objectives: (1) To determine if an 8-week exercise intervention would improve insomnia severity in patients with comorbid OSA and insomnia when compared to an 8-week active control condition of relaxation therapy. (2) To examine the effects of the exercise and relaxation interventions on cardiorespiratory fitness both within-groups and between-groups. (3) To examine if improvements in cardiorespiratory fitness would be associated with improved changes in objective and subjective sleep quality. Methods: Sixteen participants (10 female, 54.9 13.4 years of age) were randomised to 3 weekly sessions of exercise training or self-guided relaxation. The exercise sessions consisted of 60 minutes of moderate-intensity aerobic and resistance exercise, with 1 weekly session supervised and the remaining two unsupervised at home or in the community. The protocol included a screening polysomnography (PSG) night, a cardiopulmonary exercise test, and an overnight PSG, as well as questionnaires (including the Insomnia Severity Index (ISI)) before and after the 8 weeks. All PSG recordings were sampled at 512 Hz (Somnomedics, Germany) and sleep stages were scored offline according to AASM guidelines. ISI and sleep efficiency (SE) (extracted from PSG) were assessed as primary outcomes. VO2peak (ml/kg/min), VO2 at the ventilatory threshold (VT), heart rate (HR) at 50% isotime (ISO) pre- and post- intervention were assessed as secondary outcomes. Bivariate correlations were also performed to examine any potential relationships between change in cardiorespiratory fitness and change in subjective and objective sleep parameters. Results: Results revealed a significant effect of time (pre, post 8-weeks) on ISI score (F(1,14)= 12.315; p=.003), but no significant effect of condition (exercise, relaxation) or time*condition interaction. Both exercise and relaxation had large effects on ISI, with exercise showing a larger effect size (Cohen’s d= 3.88) than relaxation (Cohen’s d= 0.184). No significant effects were found for SE. A significant time*condition interaction was found for VO2peak (ml/kg/min) (F(1,15)= 10.724; p=.006), with the exercise condition showing improvements. Spearman correlations indicated a non-significant association for change in ISI and change in VO2peak (ml/kg/min) (r=0.59; p>.05). Conclusions: Both exercise and relaxation reduced insomnia severity in people with COMISA, with exercise having a larger effect. Objective measures of sleep efficiency did not improve significantly in either group. Cardiorespiratory fitness improved with the partly home-based, moderate-intensity aerobic and resistance training intervention used in this study. Larger trials are warranted to confirm these findings. Significance: This is the first randomized controlled trial (RCT) to examine the effects of an exercise intervention on sleep in this specific COMISA population

Sleep spindles may predict response to cognitive behavioral therapy for chronic insomnia

Background While cognitive-behavioral therapy for insomnia constitutes the first-line treatment for chronic insomnia, only few reports have investigated how sleep architecture relates to response to this treatment. In this pilot study, we aimed at determining whether sleep spindle density at pre-treatment predicts treatment response to cognitive behavioral therapy for insomnia. Methods Twenty-four participants with chronic primary insomnia took part in a 6-week cognitive behavioral therapy for insomnia performed in groups of 4 to 6 participants. Treatment response was assessed using the Pittsburgh Sleep Quality Index and the Insomnia Severity Index measured at pre- and post-treatment and at 3- and 12-months follow-up assessments. Secondary outcome measures were extracted from sleep diaries over seven days and one overnight polysomnography, obtained at pre- and post-treatment. Spindle density during stages N2-N3 sleep was extracted from polysomnography at pre-treatment. Hierarchical linear modeling analysis assessed whether sleep spindle density predicted response to cognitive behavioral therapy. Results After adjusting for age, sex and education level, lower spindle density at pre-treatment predicted poorer response over the 12-months follow-up, as reflected by smaller reduction in Pittsburgh Sleep Quality Index over time. Reduced spindle density also predicted lower improvements in sleep diary sleep efficiency and wake after sleep onset immediately after treatment. There were no significant associations between spindle density and changes in the Insomnia Severity Index or polysomnography variables over time. Conclusion These preliminary results suggest that inter-individual differences in sleep spindle density in insomnia may represent an endogenous biomarker predicting responsiveness to cognitive behavioral therapy. Insomnia with altered spindle activity might constitute an insomnia subtype characterized by a neurophysiological vulnerability to sleep disruption associated with impaired responsiveness to cognitive behavioral therapy

Web-Based Physical Activity Interventions Are Feasible and Beneficial Solutions to Prevent Physical and Mental Health Declines in Community-Dwelling Older Adults During Isolation Periods.

peer reviewed[en] BACKGROUND: Periods of prolonged lockdown increase the risk of physical inactivity, which can contribute to physical decline among older adults. Online technology could be an innovative solution to promote physical activity (PA) habits in this context. The goal of this study was to examine and compare the acceptability, feasibility, and potential benefits of 2 modalities of web-based PA interventions in older adults during the coronavirus disease 2019 lockdown. METHODS: Eighty-three nonphysically active community-dwelling older adults (aged 60 and older) were randomized to a 12-week web-based PA intervention delivered either in a live group (LG; n = 38) or a recorded group (RG; n = 45). Acceptability, feasibility as well as functional capacities, physical performance, quality of life, and PA level were assessed pre and postintervention. RESULTS: There were fewer dropouts in the LG than RG (LG: 16% vs RG: 46%). However, adherence rate (LG: 89%; RG: 81%), level of satisfaction (LG: 77% vs RG: 64%), and enjoyment (LG: 68% vs RG: 62%) were similar across groups, even if the participants found the intervention slightly difficult (LG: 58% vs RG: 63%). Both groups significantly improved on functional capacities, physical performance, and quality of life. Only the LG showed significant improvements in perceived health and PA level. The LG showed greater improvements in physical performance and quality of life than the RG. CONCLUSION: Web-based PA interventions are feasible, acceptable, and beneficial for improving functional capacities and physical performance during periods of lockdown. However, the interactive web and live modalities appear to be more effective for promoting some of these outcomes than recorded and individual modalities

Covert Waking Brain Activity Reveals Instantaneous Sleep Depth

The neural correlates of the wake-sleep continuum remain incompletely understood, limiting the development of adaptive drug delivery systems for promoting sleep maintenance. The most useful measure for resolving early positions along this continuum is the alpha oscillation, an 8–13 Hz electroencephalographic rhythm prominent over posterior scalp locations. The brain activation signature of wakefulness, alpha expression discloses immediate levels of alertness and dissipates in concert with fading awareness as sleep begins. This brain activity pattern, however, is largely ignored once sleep begins. Here we show that the intensity of spectral power in the alpha band actually continues to disclose instantaneous responsiveness to noise—a measure of sleep depth—throughout a night of sleep. By systematically challenging sleep with realistic and varied acoustic disruption, we found that sleepers exhibited markedly greater sensitivity to sounds during moments of elevated alpha expression. This result demonstrates that alpha power is not a binary marker of the transition between sleep and wakefulness, but carries rich information about immediate sleep stability. Further, it shows that an empirical and ecologically relevant form of sleep depth is revealed in real-time by EEG spectral content in the alpha band, a measure that affords prediction on the order of minutes. This signal, which transcends the boundaries of classical sleep stages, could potentially be used for real-time feedback to novel, adaptive drug delivery systems for inducing sleep