Ventilatory Drive Withdrawal Rather Than Reduced Genioglossus Compensation as a Mechanism of Obstructive Sleep Apnea in REM Sleep.

Rationale: REM sleep is associated with reduced ventilation and greater obstructive sleep apnea (OSA) severity than non-REM (nREM) sleep for reasons that have not been fully elucidated. Objectives: Here, we use direct physiological measurements to determine whether the pharyngeal compromise in REM sleep OSA is most consistent with 1) withdrawal of neural ventilatory drive or 2) deficits in pharyngeal pathophysiology per se (i.e., increased collapsibility and decreased muscle responsiveness). Methods: Sixty-three participants with OSA completed sleep studies with gold standard measurements of ventilatory "drive" (calibrated intraesophageal diaphragm EMG), ventilation (oronasal "ventilation"), and genioglossus EMG activity. Drive withdrawal was assessed by examining these measurements at nadir drive (first decile of drive within a stage). Pharyngeal physiology was assessed by examining collapsibility (lowered ventilation at eupneic drive) and responsiveness (ventilation-drive slope). Mixed-model analysis compared REM sleep with nREM sleep; sensitivity analysis examined phasic REM sleep. Measurements and Main Results: REM sleep (⩾10 min) was obtained in 25 patients. Compared with drive in nREM sleep, drive in REM sleep dipped to markedly lower nadir values (first decile, estimate [95% confidence interval], -21.8% [-31.2% to -12.4%] of eupnea; P < 0.0001), with an accompanying reduction in ventilation (-25.8% [-31.8% to -19.8%] of eupnea; P < 0.0001). However, there was no effect of REM sleep on collapsibility (ventilation at eupneic drive), baseline genioglossus EMG activity, or responsiveness. REM sleep was associated with increased OSA severity (+10.1 [1.8 to 19.8] events/h), but this association was not present after adjusting for nadir drive (+4.3 [-4.2 to 14.6] events/h). Drive withdrawal was exacerbated in phasic REM sleep. Conclusions: In patients with OSA, the pharyngeal compromise characteristic of REM sleep appears to be predominantly explained by ventilatory drive withdrawal rather than by preferential decrements in muscle activity or responsiveness. Preventing drive withdrawal may be the leading target for REM sleep OSA.

Suppression of interictal spikes during phasic rapid eye movement sleep: a quantitative stereo-electroencephalography study.

Tonic and phasic rapid eye movement (REM) sleep seem to represent two different brain states exerting different effects on epileptic activity. In particular, interictal spikes are suppressed strongly during phasic REM sleep. The reason for this effect is not understood completely. A different level of synchronization in phasic and tonic REM sleep has been postulated, yet never measured directly. Here we assessed the interictal spike rate across non-REM (NREM) sleep, phasic and tonic REM sleep in nine patients affected by drug resistant focal epilepsy: five with type II focal cortical dysplasia and four with hippocampal sclerosis. Moreover, we applied different quantitative measures to evaluate the level of synchronization at the local and global scale during phasic and tonic REM sleep. We found a lower spike rate in phasic REM sleep, both within and outside the seizure onset zone. This effect seems to be independent from the histopathological substrate and from the brain region, where epileptic activity is produced (temporal versus extra-temporal). A higher level of synchronization was observed during tonic REM sleep both on a large (global) and small (local) spatial scale. Phasic REM sleep appears to be an interesting model for understanding the mechanisms of suppression of epileptic activity.

Senior Vipassana Meditation practitioners exhibit distinct REM sleep organization from that of novice meditators and healthy controls.

The present study is aimed to ascertain whether differences in meditation proficiency alter rapid eye movement sleep (REM sleep) as well as the overall sleep-organization. Whole-night polysomnography was carried out using 32-channel digital EEG system. 20 senior Vipassana meditators, 16 novice Vipassana meditators and 19 non-meditating control subjects participated in the study. The REM sleep characteristics were analyzed from the sleep-architecture of participants with a sleep efficiency index >85%. Senior meditators showed distinct changes in sleep-organization due to enhanced slow wave sleep and REM sleep, reduced number of intermittent awakenings and reduced duration of non-REM stage 2 sleep. The REM sleep-organization was significantly different in senior meditators with more number of REM episodes and increased duration of each episode, distinct changes in rapid eye movement activity (REMA) dynamics due to increased phasic and tonic activity and enhanced burst events (sharp and slow bursts) during the second and fourth REM episodes. No significant differences in REM sleep organization was observed between novice and control groups. Changes in REM sleep-organization among the senior practitioners of meditation could be attributed to the intense brain plasticity events associated with intense meditative practices on brain functions.

Reduction in the propensity of rapid eye movement sleep and phasic-to-tonic ratio in patients with refractory epilepsy.

STUDY OBJECTIVES: Patients with epilepsy exhibit disturbed sleep architecture and shorter rapid eye movement (REM) sleep compared with healthy controls. REM sleep consists of two microstates, phasic and tonic REM. Studies suggest that epileptic activity is suppressed in phasic but not in tonic REM. However, changes in the REM microstructure in patients with epilepsy are still unknown. Therefore, this study evaluated the differences in REM microstructure between patients with refractory and medically controlled epilepsy. METHODS: This retrospective case-control study included patients with refractory and medically controlled epilepsy. Sleep parameters of the patients were recorded by standard polysomnography. In addition, the microstructures of sleep and REM sleep were compared between the two epilepsy groups. RESULTS: Forty-two patients with refractory epilepsy and 106 with medically controlled epilepsy were evaluated. The refractory group showed significantly decreased REM sleep (p = 0.0062), particularly in the first and second sleep cycles (p = 0.0028 and 0.00482, respectively), as well as longer REM latency (p = 0.0056). Eighteen and 28 subjects in the refractory and medically controlled epilepsy groups, respectively, with comparable REM sleep percentages, underwent REM microstructure examination. Phasic REM sleep was significantly lower in the refractory group (4.5% ± 2.1% vs. 8.0% ± 4.1%; p = 0.002). In addition, the phasic-to-tonic ratio was significantly decreased (4.8 ± 2.3 vs. 8.9 ± 4.9; p = 0.002) and negatively associated with refractory epilepsy (coefficient = -0.308, p = 0.0079). CONCLUSION: Patients with refractory epilepsy exhibited REM sleep disturbance at both macro and microstructure levels.

Eye movements during phasic versus tonic rapid eye movement sleep are biomarkers of dissociable electroencephalogram processes for the consolidation of novel problem-solving skills.

The hallmark eye movement (EM) bursts that occur during rapid eye movement (REM) sleep are markers of consolidation for procedural memory involving novel cognitive strategies and problem-solving skills. Examination of the brain activity associated with EMs during REM sleep might elucidate the processes involved in memory consolidation, and may uncover the functional significance of REM sleep and EMs themselves. Participants performed a REM-dependent, novel procedural problem-solving task (i.e. the Tower of Hanoi; ToH) before and after intervals of either overnight sleep (n = 20) or a daytime 8-hour wake period (n = 20). In addition, event-related spectral perturbation of the electroencephalogram (EEG) time-locked to EMs occurring either in bursts (i.e. phasic REM), or in isolation (i.e. tonic REM), were compared to sleep on a non-learning control night. ToH improvement was greater following sleep compared to wakefulness. During sleep, prefrontal theta (~2-8 Hz) and central-parietal-occipital sensorimotor rhythm (SMR) activity (~8-16 Hz) time-locked to EMs, were greater on the ToH night versus control night, and during phasic REM sleep, were both positively correlated with overnight memory improvements. Furthermore, SMR power during tonic REM increased significantly from the control night to ToH night, but was relatively stable from night to night during phasic REM. These results suggest that EMs are markers of learning-related increases in theta and SMR during phasic and tonic REM sleep. Phasic and tonic REM sleep may be functionally distinct in terms of their contribution to procedural memory consolidation.

On the role of REM sleep microstructure in suppressing interictal spikes in Electrical Status Epilepticus during Sleep.

OBJECTIVE: Non-Rapid Eye Movement (NREM) sleep promotes the spread and propagation of Interictal Epileptiform Discharges (IEDs), while IEDs are suppressed during REM. Recently, it has been shown that the inhibitory effect on epileptic activity is mostly exerted by the phasic REM (PREM) microstate. This study aims at assessing if this holds true even in the extreme condition of IEDs activation during sleep represented by Electrical Status Epilepticus during Sleep (ESES). METHODS: eight patients affected by ESES, who underwent long-term EEG were included. REM was subdivided into phasic and tonic microstates along with the sleep scoring. IEDs count was carried out using a semi-automatic method and a Spike Index (SI) was calculated. RESULTS: The SI was significantly higher in NREM sleep than in REM. Within REM, the SI was significantly lower in PREM than in tonic REM (TREM). The SI was reduced by 84% in TREM with respect to NREM and by 97% in PREM with respect to NREM. Moreover, the SI was reduced by 87% in PREM with respect to TREM. CONCLUSIONS: PREM has a greater suppressive effect on epileptic activity even in the extreme IEDs activation during sleep typical of ESES. SIGNIFICANCE: Understanding the protective effect of PREM sleep on epileptic activity might be relevant for future therapeutic approaches.

Tracking Eye Movements During Sleep in Mice.

Eye movement is not only for adjusting the visual field and maintaining the stability of visual information on the retina, but also provides an external manifestation of the cognitive status of the brain. Recent studies showed similarity in eye movement patterns between wakefulness and rapid eye movement (REM) sleep, indicating that the brain status of REM sleep likely resembles that of awake status. REM sleep in humans could be divided into phasic REM and tonic REM sleep according to the difference in eye movement frequencies. Mice are the most commonly used animal model for studying neuronal and molecular mechanisms underlying sleep. However, there was a lack of details for eye movement patterns during REM sleep, hence it remains unknown whether REM sleep can be further divided into different stages in mice. Here we developed a device combining electroencephalogram (EEG), electromyogram (EMG) as well as eye movements recording in mice to study the eye movement patterns during sleep. We implanted a magnet beneath the conjunctiva of eye and tracked eye movements using a magnetic sensor. The magnetic signals showed strong correlation with video-oculography in head-fixed mice, indicating that the magnetic signals reflect the direction and magnitude of eye movement. We also found that the magnet implanted beneath the conjunctiva exhibited good biocompatibility. Finally, we examined eye movement in sleep-wake cycle, and discriminated tonic REM and phasic REM according to the frequency of eye movements, finding that compared to tonic REM, phasic REM exhibited higher oscillation power at 0.50 Hz, and lower oscillation power at 1.50-7.25 Hz and 9.50-12.00 Hz. Our device allowed to simultaneously record EEG, EMG, and eye movements during sleep and wakefulness, providing a convenient and high temporal-spatial resolution tool for studying eye movements in sleep and other researches in mice.

Unaltered EEG spectral power and functional connectivity in REM microstates in frequent nightmare recallers: are nightmares really a REM parasomnia?

BACKGROUND: Frequent nightmares show signs of hyperarousal in NREM sleep. Nevertheless, idiopathic nightmare disorder is considered a REM parasomnia, but the pathophysiology of REM sleep in relation to frequent nightmares is controversial. Cortical oscillatory activity in REM sleep is largely modulated by phasic and tonic REM periods and seems to be linked to different functions and dysfunctions of REM sleep. Here, we examined cortical activity and functional synchronization in frequent nightmare recallers and healthy controls, during phasic and tonic REM. METHODS: Frequent nightmare recallers (N = 22) and healthy controls (N = 22) matched for high dream recall spent two nights in the laboratory. Phasic and tonic REM periods from the second nights' recordings were selected to examine differences in EEG spectral power and weighted phase lag index (WPLI) across groups and REM states. RESULTS: Phasic REM showed increased power and synchronization in delta and gamma frequency bands, whereas tonic REM featured increased power and synchronization in the alpha and beta bands. In the theta band, power was higher during tonic, and synchronization was higher during phasic REM sleep. No differences across nightmare and control participants or patterns representing interactions between the groups and REM microstates emerged. CONCLUSIONS: Our findings do not support the idea that abnormal REM sleep power and synchronization play a role in the pathophysiology of frequent nightmares. Altered REM sleep in nightmare disorder could have been confounded with comorbid pathologies and increased dream recall, or might be linked to more specific state factors (nightmare episodes).