Sleep onset rapid-eye-movement episodes in narcolepsy: REM sleep pressure or nonREM-REM sleep dysregulation?

Abstract Introduction Agrypnia Excitata (AE) is a syndrome characterized by loss of sleep with permanent motor and autonomic hyper activation. This case describes this peculiar syndrome in a patient with paraneoplastic autoimmune encephalitis. Report of Case DG is a 35 yr old male with a history of anti-Ma2 limbic encephalitis secondary to cystic teratoma of the left testis diagnosed 6 months prior to presenting in Sleep Clinic. His parents described significant sleep disturbances including short sleep and wake periods throughout the day and night with no apparent pattern, acting out dreams, motor activity during sleep including pulling at his clothes or using his hands to manipulate invisible objects. Additionally they described low-grade fevers, and severe hyperphagia. Polysomnogram showed absence of slow-wave sleep and what appeared to be an admixture of stage 1 non-rapid eye movement (NREM) with rapid-eye movement (REM) sleep. Multiple sleep-latency testing (MSLT) demonstrated a mean sleep latency of 5.2 minutes and four sleep-onset REM periods (SOREMPs). Magnetic resonance imaging of the brain revealed persistent inflammation of the mesial temporal lobes and hippocampal region. Cerebral spinal fluid testing showed persistent anti-Ma2 antibodies. Based on this clinical presentation we made a diagnosis of Agrypnia Excitata. Conclusion Agrypnia Excitata is a syndrome characterized by loss of the normal sleep-wake rhythm. Sleep consists of the disappearance of spindle-delta activities, and persistent stage 1 NREM sleep mixed with recurrent episodes of REM sleep. The second hallmark of AE is persistent motor and autonomic hyperactivity observed during wake and sleep. AE has been described in three distinct clinical syndromes: Morvan Syndrome (autoimmune encephalitis), Fatal Familial Insomnia, and Delirium tremens. The pathogenesis of AE consists of intra-limbic disconnection releasing the hypothalamus and brainstem reticular formation from cortico-limbic inhibitory control. In autoimmune encephalitis, antibodies that act on voltage-gated potassium channels within the limbic system have been implicated in the pathophysiology.

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Vesicular GABA-transporter neurons in the zona incerta are maximally active during non rapid-eye movement (NREM) and rapid-eye movement (REM) sleep

10.1101/2020.04.15.043372 ◽

2020 ◽

Author(s):

Carlos Blanco-Centurion ◽

SiWei Luo ◽

Aurelio Vidal-Ortiz ◽

Priyattam J. Shiromani

Keyword(s):

Eye Movement ◽

Lateral Hypothalamus ◽

Rem Sleep ◽

Sleep Onset ◽

Nrem Sleep ◽

Zona Incerta ◽

Imaging Method ◽

Rapid Eye Movement ◽

Gaba Transporter

AbstractSleep and wake are opposing behavioral states controlled by the activity of specific neurons. The neurons responsible for sleep/wake control have not been fully identifed due to the lack of in-vivo high throughput technology. We use the deep-brain calcium (Ca2+) imaging method to identify activity of hypothalamic neurons expressing the vesicular GABA transporter (vGAT), a marker of GABAergic neurons. vGAT-cre mice (n=5) were microinjected with rAAV-FLEX-GCaMP6M into the lateral hypothalamus and 21d later the Ca2+ influx in vGAT neurons (n=372) was recorded in freely-behaving mice during waking (W), NREM and REM sleep. Post-mortem analysis revealed the lens tip located in the zona incerta/lateral hypothalamus (ZI-LH) and the change in fluorescence of neurons in the field of view was as follows: 54.9% of the vGAT neurons had peak fluorescence during REM sleep (REM-max), 17.2% were NREM-max, 22.8% were wake-max while 5.1% were both wake+REM max. Thus, three quarters of the recorded vGAT neurons in the ZI-LH were most active during sleep. In the NREM-max group Ca2+ fluorescence anticipated the initiation of NREM sleep onset and remained high throughout sleep (NREM and REM sleep). In the REM-max neurons Ca2+fluorescence increased before the onset of REM sleep and stayed elevated during the episode. Activation of the vGAT NREM-max neurons in the zona incerta and dorsal lateral hypothalamus would inhibit the arousal neurons to initiate and maintain sleep.

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Validation of Fitbit Charge 2 Sleep and Heart Rate Estimates Against Polysomnographic Measures in Shift Workers: Naturalistic Study (Preprint)

10.2196/preprints.26476 ◽

2020 ◽

Author(s):

Benjamin Stucky ◽

Ian Clark ◽

Yasmine Azza ◽

Walter Karlen ◽

Peter Achermann ◽

...

Keyword(s):

Heart Rate ◽

Eye Movement ◽

Shift Work ◽

Rem Sleep ◽

Sleep Onset ◽

Data Access ◽

Sleep Stages ◽

Rapid Eye Movement ◽

Limits Of Agreement ◽

Shift Workers

BACKGROUND Multisensor fitness trackers offer the ability to longitudinally estimate sleep quality in a home environment with the potential to outperform traditional actigraphy. To benefit from these new tools for objectively assessing sleep for clinical and research purposes, multisensor wearable devices require careful validation against the gold standard of sleep polysomnography (PSG). Naturalistic studies favor validation. OBJECTIVE This study aims to validate the Fitbit Charge 2 against portable home PSG in a shift-work population composed of 59 first responder police officers and paramedics undergoing shift work. METHODS A reliable comparison between the two measurements was ensured through the data-driven alignment of a PSG and Fitbit time series that was recorded at night. Epoch-by-epoch analyses and Bland-Altman plots were used to assess sensitivity, specificity, accuracy, the Matthews correlation coefficient, bias, and limits of agreement. RESULTS Sleep onset and offset, total sleep time, and the durations of rapid eye movement (REM) sleep and non–rapid-eye movement sleep stages N1+N2 and N3 displayed unbiased estimates with nonnegligible limits of agreement. In contrast, the proprietary Fitbit algorithm overestimated REM sleep latency by 29.4 minutes and wakefulness after sleep onset (WASO) by 37.1 minutes. Epoch-by-epoch analyses indicated better specificity than sensitivity, with higher accuracies for WASO (0.82) and REM sleep (0.86) than those for N1+N2 (0.55) and N3 (0.78) sleep. Fitbit heart rate (HR) displayed a small underestimation of 0.9 beats per minute (bpm) and a limited capability to capture sudden HR changes because of the lower time resolution compared to that of PSG. The underestimation was smaller in N2, N3, and REM sleep (0.6-0.7 bpm) than in N1 sleep (1.2 bpm) and wakefulness (1.9 bpm), indicating a state-specific bias. Finally, Fitbit suggested a distribution of all sleep episode durations that was different from that derived from PSG and showed nonbiological discontinuities, indicating the potential limitations of the staging algorithm. CONCLUSIONS We conclude that by following careful data processing processes, the Fitbit Charge 2 can provide reasonably accurate mean values of sleep and HR estimates in shift workers under naturalistic conditions. Nevertheless, the generally wide limits of agreement hamper the precision of quantifying individual sleep episodes. The value of this consumer-grade multisensor wearable in terms of tackling clinical and research questions could be enhanced with open-source algorithms, raw data access, and the ability to blind participants to their own sleep data.

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Selectively driving cholinergic fibers optically in the thalamic reticular nucleus promotes sleep

eLife ◽

10.7554/elife.10382 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 22

Author(s):

Kun-Ming Ni ◽

Xiao-Jun Hou ◽

Ci-Hang Yang ◽

Ping Dong ◽

Yue Li ◽

...

Keyword(s):

Eye Movement ◽

Nicotinic Acetylcholine Receptors ◽

Rem Sleep ◽

Sleep Onset ◽

Cholinergic Neurons ◽

Nrem Sleep ◽

Gabaergic Neurons ◽

Thalamic Reticular Nucleus ◽

Reticular Nucleus ◽

Rapid Eye Movement

Cholinergic projections from the basal forebrain and brainstem are thought to play important roles in rapid eye movement (REM) sleep and arousal. Using transgenic mice in which channelrhdopsin-2 is selectively expressed in cholinergic neurons, we show that optical stimulation of cholinergic inputs to the thalamic reticular nucleus (TRN) activates local GABAergic neurons to promote sleep and protect non-rapid eye movement (NREM) sleep. It does not affect REM sleep. Instead, direct activation of cholinergic input to the TRN shortens the time to sleep onset and generates spindle oscillations that correlate with NREM sleep. It does so by evoking excitatory postsynaptic currents via α7-containing nicotinic acetylcholine receptors and inducing bursts of action potentials in local GABAergic neurons. These findings stand in sharp contrast to previous reports of cholinergic activity driving arousal. Our results provide new insight into the mechanisms controlling sleep.

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Glutamatergic neurons in the preoptic hypothalamus promote wakefulness, destabilize NREM sleep, suppress REM sleep, and regulate cortical dynamics

10.1101/2020.10.20.347260 ◽

2020 ◽

Author(s):

Alejandra Mondino ◽

Viviane Hambrecht-Wiedbusch ◽

Duan Li ◽

A. Kane York ◽

Dinesh Pal ◽

...

Keyword(s):

Eye Movement ◽

Rem Sleep ◽

Preoptic Area ◽

Sleep Onset ◽

Nrem Sleep ◽

State Transitions ◽

Rapid Eye Movement ◽

Cortical Dynamics ◽

Glutamatergic Neurons ◽

Conditional Expression

ABSTRACTClinical and experimental data from the last nine decades indicate that the preoptic area of the hypothalamus is a critical node in a brain network that controls sleep onset and homeostasis. By contrast, we recently reported that a group of glutamatergic neurons in the lateral and medial preoptic area increases wakefulness, challenging the long-standing notion in sleep neurobiology that the preoptic area is exclusively somnogenic. However, the precise role of these subcortical neurons in the control of behavioral state transitions and cortical dynamics remains unknown. Therefore, in this study we used conditional expression of excitatory hM3Dq receptors in these preoptic glutamatergic (Vglut2+) neurons and show that their activation initiates wakefulness, decreases non-rapid eye movement (NREM) sleep, and causes a persistent suppression of rapid eye movement (REM) sleep. Activation of preoptic glutamatergic neurons also causes a high degree of NREM sleep fragmentation, promotes state instability with frequent arousals from sleep, and shifts cortical dynamics (including oscillations, connectivity, and complexity) to a more wake-like state. We conclude that a subset of preoptic glutamatergic neurons may initiate -but not maintain- arousals from sleep, and their inactivation may be required for NREM stability and REM sleep generation. Further, these data provide novel empirical evidence supporting the conclusion that the preoptic area causally contributes to the regulation of both sleep and wakefulness.

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Validation of Fitbit Charge 2 Sleep and Heart Rate Estimates Against Polysomnographic Measures in Shift Workers: Naturalistic Study

Journal of Medical Internet Research ◽

10.2196/26476 ◽

2021 ◽

Vol 23 (10) ◽

pp. e26476

Author(s):

Benjamin Stucky ◽

Ian Clark ◽

Yasmine Azza ◽

Walter Karlen ◽

Peter Achermann ◽

...

Keyword(s):

Heart Rate ◽

Eye Movement ◽

Shift Work ◽

Rem Sleep ◽

Sleep Onset ◽

Data Access ◽

Sleep Stages ◽

Rapid Eye Movement ◽

Limits Of Agreement ◽

Shift Workers

Background Multisensor fitness trackers offer the ability to longitudinally estimate sleep quality in a home environment with the potential to outperform traditional actigraphy. To benefit from these new tools for objectively assessing sleep for clinical and research purposes, multisensor wearable devices require careful validation against the gold standard of sleep polysomnography (PSG). Naturalistic studies favor validation. Objective This study aims to validate the Fitbit Charge 2 against portable home PSG in a shift-work population composed of 59 first responder police officers and paramedics undergoing shift work. Methods A reliable comparison between the two measurements was ensured through the data-driven alignment of a PSG and Fitbit time series that was recorded at night. Epoch-by-epoch analyses and Bland-Altman plots were used to assess sensitivity, specificity, accuracy, the Matthews correlation coefficient, bias, and limits of agreement. Results Sleep onset and offset, total sleep time, and the durations of rapid eye movement (REM) sleep and non–rapid-eye movement sleep stages N1+N2 and N3 displayed unbiased estimates with nonnegligible limits of agreement. In contrast, the proprietary Fitbit algorithm overestimated REM sleep latency by 29.4 minutes and wakefulness after sleep onset (WASO) by 37.1 minutes. Epoch-by-epoch analyses indicated better specificity than sensitivity, with higher accuracies for WASO (0.82) and REM sleep (0.86) than those for N1+N2 (0.55) and N3 (0.78) sleep. Fitbit heart rate (HR) displayed a small underestimation of 0.9 beats per minute (bpm) and a limited capability to capture sudden HR changes because of the lower time resolution compared to that of PSG. The underestimation was smaller in N2, N3, and REM sleep (0.6-0.7 bpm) than in N1 sleep (1.2 bpm) and wakefulness (1.9 bpm), indicating a state-specific bias. Finally, Fitbit suggested a distribution of all sleep episode durations that was different from that derived from PSG and showed nonbiological discontinuities, indicating the potential limitations of the staging algorithm. Conclusions We conclude that by following careful data processing processes, the Fitbit Charge 2 can provide reasonably accurate mean values of sleep and HR estimates in shift workers under naturalistic conditions. Nevertheless, the generally wide limits of agreement hamper the precision of quantifying individual sleep episodes. The value of this consumer-grade multisensor wearable in terms of tackling clinical and research questions could be enhanced with open-source algorithms, raw data access, and the ability to blind participants to their own sleep data.

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Neurophysiological control of sleep with special emphasis on melatonin

Trakia Journal of Sciences ◽

10.15547/tjs.2020.04.011 ◽

2020 ◽

Vol 18 (4) ◽

pp. 355-376

Author(s):

Iv. Penchev Georgiev

Keyword(s):

Sleep Disorders ◽

Eye Movement ◽

Rem Sleep ◽

Sleep Onset ◽

Vascular Diseases ◽

Nrem Sleep ◽

Brain Structures ◽

Rapid Eye Movement ◽

Human Beings ◽

Melatonin Receptor Agonists

Sleep and wakefulness are two main types of human and animal behavior. On the average human beings spend about one-third of their lives asleep. The sleep-wake cycle is the most important circadian rhythms which alternates in a periodic manner lasting for about 24 hours. Sleep is determined as the natural periodic suspension of consciousness characterized by relative immobility and reduced responsiveness to external stimuli. The researchers have found and identified many special brain structures and systems controlling waking, rapid eye movement (REM) sleep and non-rapid eye (NREM) sleep and the transitions among these states. Currently, there is an enhanced interest of researchers toward sleep and its neurophysiological mechanisms of regulation because the number of people suffering from various sleep disturbance such as insomnia, delayed sleep onset, duration and propensity of sleep, worldwide dramatically increases. In addition to the next day drowsiness, nervousness, tiredness and decreased workability, it has been suggested that sleep is important also for the maintaining of mood, memory and cognitive function of the brain and is essential for the normal functioning of the endocrine and immune systems. More recently, new studies show a sustained link between sleep disorders and different serious health problems, including obesity, insulin resistance, type 2 diabetes mellitus, cardio-vascular diseases and depression. Therefore, the purpose of this review is to summarize and analyze the available data about the neurological control of wakefulness, non-rapid-eye-movement (NREM) sleep and rapid- eye-movement (REM) sleep creating a substantial basis for better understanding different sleep disorders. Special attention is paid on the pharmacological aspects and use of some new classes of sleep promoting agents – melatonin, melatonin receptor agonists and orexin receptor antagonists.

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Structural organization of dream experience during daytime sleep-onset rapid eye movement period sleep of patients with narcolepsy type 1

SLEEP ◽

10.1093/sleep/zsaa012 ◽

2020 ◽

Vol 43 (8) ◽

Cited By ~ 1

Author(s):

Carlo Cipolli ◽

Fabio Pizza ◽

Claudia Bellucci ◽

Michela Mazzetti ◽

Giovanni Tuozzi ◽

...

Keyword(s):

Eye Movement ◽

Rem Sleep ◽

Structural Organization ◽

Sleep Onset ◽

Nrem Sleep ◽

Rapid Eye Movement ◽

Story Grammar ◽

Late Night ◽

Grammar Analysis

Abstract Study Objective To assess the frequency of dream experience (DE) developed during naps at Multiple Sleep Latency Test (MSLT) by patients with narcolepsy type 1 (NT1) and establish, using story-grammar analysis, the structural organization of DEs developed during naps with sleep onset rapid eye movement (REM) period (SOREMP) sleep compared with their DEs during early- and late-night REM sleep. Methods Thirty drug-free cognitively intact adult NT1 patients were asked to report DE developed during each MSLT nap. Ten NT1 patients also spent voluntarily a supplementary night being awakened during the first-cycle and third-cycle REM sleep. Patients provided dream reports, white dreams, and no dreams, whose frequencies were matched in naps with SOREMP versus non-REM (NREM) sleep. All dream reports were then analyzed using story-grammar rules. Results DE was recalled in detail (dream report) by NT1 patients after 75% of naps with SOREMP sleep and after 25% of naps with NREM sleep. Dream reports were provided by 8 out of 10 NT1 patients after both awakenings from nighttime REM sleep. Story-grammar analysis of dream reports showed that SOREMP-DEs are organized as hierarchically ordered sequences of events (so-called dream-stories), which are longer and more complex in the first and fourth SOREMP naps and are comparable with nighttime REM-DEs. Conclusions The similar structural organization of SOREMP-DEs with nighttime REM-DEs indicates that their underlying cognitive processes are highly, albeit not uniformly, effective during daytime SOREMP sleep. Given the peculiar neurophysiology of SOREMP sleep, investigating SOREMP-DEs may cast further light on the relationships between the neurophysiological and psychological processes involved in REM-dreaming.

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