Correlation between ventilation and brain blood flow during hypoxic sleep

Ventilation and brain blood flow (BBF) were simultaneously measured during carbon monoxide (CO) inhalation in awake and sleeping goats up to HbCO levels of 40%. Unilateral BBF, which was continuously measured with an electromagnetic flow probe placed around the internal maxillary artery, progressively increased with CO inhalation in the awake and both sleep stages. The increase in BBF with CO inhalation during rapid-eye-movement (REM) sleep (delta BBF/delta arterial O2 saturation = 1.34 +/- 0.27 ml X min-1 X %-1) was significantly greater than that manifested during wakefulness (0.87 +/- 0.14) or slow-wave sleep (0.92 +/- 0.13). Ventilation was depressed by CO inhalation during both sleep stages but was unchanged from base-line values in awake goats. In contrast to slow-wave (non-REM) sleep, the ventilatory depression of REM sleep was primarily due to a reduction in tidal volume. Since tidal volume is more closely linked to central chemoreceptor function, we believe that these data suggest a possible role of the increased cerebral perfusion during hypoxic REM sleep. Induction of relative tissue alkalosis at the vicinity of the medullary chemoreceptor may contribute to the ventilatory depression exhibited during this sleep period.     

Assessing the dream-lag effect for REM and NREM stage 2 dreams

This study investigates evidence, from dream reports, for memory consolidation during sleep. It is well-known that events and memories from waking life can be incorporated into dreams. These incorporations can be a literal replication of what occurred in waking life, or, more often, they can be partial or indirect. Two types of temporal relationship have been found to characterize the time of occurrence of a daytime event and the reappearance or incorporation of its features in a dream. These temporal relationships are referred to as the day-residue or immediate incorporation effect, where there is the reappearance of features from events occurring on the immediately preceding day, and the dream-lag effect, where there is the reappearance of features from events occurring 5-7 days prior to the dream. Previous work on the dream-lag effect has used spontaneous home recalled dream reports, which can be from Rapid Eye Movement Sleep (REM) and from non-Rapid Eye Movement Sleep (NREM). This study addresses whether the dream-lag effect occurs only for REM sleep dreams, or for both REM and NREM stage 2 (N2) dreams. 20 participants kept a daily diary for over a week before sleeping in the sleep laboratory for 2 nights. REM and N2 dreams collected in the laboratory were transcribed and each participant rated the level of correspondence between every dream report and every diary record. The dream-lag effect was found for REM but not N2 dreams. Further analysis indicated that this result was not due to N2 dream reports being shorter, in terms of number of words, than the REM dream reports. These results provide evidence for a 7-day sleep-dependent non-linear memory consolidation process that is specific to REM sleep, and accord with proposals for the importance of REM sleep to emotional memory consolidation.     

Rapid eye movement (rem) sleep deprivation: effect on acid mucopolysaccharides in rat brain.

The effect of rapid eye movement (REM) sleep deprivation on the total content and proportion of different mucopolysaccharides (AMPS) containing uronic acid in rat brain was studied. REM sleep deprivation was induced by the water tank methods. Five experimental groups of animals were used: control, stressed, REM sleep deprived, post-stress sleeping and post-deprivation sleeping rats. No changes of AMPS were observed in any of the experimental groups when the whole brain was analysed. A significant increase of AMPS was found in the cerebral hemispheres of stressed and REM deprived rats. A significant decrease of AMPS was observed in the cerebellum and brain stem. A further increase of AMPS was found in the cerebral hemispheres after the rebound of REM sleep following its deprivation, and after the recovery sleep following the stress. A significant increase of AMPS was found in the brain stem of rats allowed to recuperate after REM deprivation or stress as compared with the stressed and REM deprived animals. Recovery sleep induced a significant increase of AMPS in the cerebellum in previously stressed rats, while previously REM deprived rats exhibited a further decrease of AMPS from control values. The possible functional meaning of these results is discussed in relation to the role of REM sleep in protein synthesis and learning and memory processes. Intriguing, well-controlled positive findings and the fact that no experimental design is known where stress is minimal while REM deprivation is 100 per cent, justify and encourage continued efforts in studying the biochemical state of the brain during sleep and/or its alterations.     

Alpha Reactivity to Complex Sounds Differs during REM Sleep and Wakefulness

We aimed at better understanding the brain mechanisms involved in the processing of alerting meaningful sounds during sleep, investigating alpha activity. During EEG acquisition, subjects were presented with a passive auditory oddball paradigm including rare complex sounds called Novels (the own first name - OWN, and an unfamiliar first name - OTHER) while they were watching a silent movie in the evening or sleeping at night. During the experimental night, the subjects’ quality of sleep was generally preserved. During wakefulness, the decrease in alpha power (8–12 Hz) induced by Novels was significantly larger for OWN than for OTHER at parietal electrodes, between 600 and 900 ms after stimulus onset. Conversely, during REM sleep, Novels induced an increase in alpha power (from 0 to 1200 ms at all electrodes), significantly larger for OWN than for OTHER at several parietal electrodes between 700 and 1200 ms after stimulus onset. These results show that complex sounds have a different effect on the alpha power during wakefulness (decrease) and during REM sleep (increase) and that OWN induce a specific effect in these two states. The increased alpha power induced by Novels during REM sleep may 1) correspond to a short and transient increase in arousal; in this case, our study provides an objective measure of the greater arousing power of OWN over OTHER, 2) indicate a cortical inhibition associated with sleep protection. These results suggest that alpha modulation could participate in the selection of stimuli to be further processed during sleep.     

The maturational trajectories of NREM and REM sleep durations differ across adolescence on both school-night and extended sleep

We recorded sleep electroencephalogram longitudinally across ages 9-18 yr in subjects sleeping at home. Recordings were made twice yearly on 4 consecutive nights: 2 nights with the subjects maintaining their ongoing school-night schedules, and 2 nights with time in bed extended to 12 h. As expected, school-night total sleep time declined with age. This decline was entirely produced by decreasing non-rapid eye movement (NREM) sleep. Rapid eye movement (REM) sleep durations increased slightly but significantly. NREM and REM sleep durations also exhibited different age trajectories when sleep was extended. Both durations exceeded those on school-night schedules. However, the elevated NREM duration did not change with age, whereas REM durations increased significantly. We interpret the adolescent decline in school-night NREM duration in relation to our hypothesis that NREM sleep reverses changes produced in plastic brain systems during waking. The "substrate" produced during waking declines across adolescence, because synaptic elimination decreases the intensity (metabolic rate) of waking brain activity. Declining substrate reduces both NREM intensity (i.e., delta power) and NREM duration. The absence of a decline in REM sleep duration on school-night sleep and its age-dependent increase in extended sleep pose new challenges to understanding its physiological role. Whatever their ultimate explanation, these robust findings demonstrate that the two physiological states of human sleep respond differently to the maturational brain changes of adolescence. Understanding these differences should shed new light on both brain development and the functions of sleep.     

Development of REM sleep drive and clinical implications.

Rapid eye movement (REM) sleep in the human declines from approximately 50% of total sleep time ( approximately 8 h) in the newborn to approximately 15% of total sleep time (approximately 1 h) in the adult, and this decrease takes place mainly between birth and the end of puberty. We hypothesize that without this developmental decrease in REM sleep drive, lifelong increases in REM sleep drive may ensue. In the rat, the developmental decrease in REM sleep occurs 10-30 days after birth, declining from >70% of total sleep time in the newborn to the adult level of approximately 15% of sleep time during this period. Rats at 12-21 days of age were anesthetized with ketamine and decapitated, and brain stem slices were cut for intracellular recordings. We found that excitatory responses of pedunculopontine nucleus (PPN) neurons to N-methyl-D-aspartic acid decrease, while responses to kainic acid increase, over this critical period. During this developmental period, inhibitory responses to serotonergic type 1 agonists increase but responses to serotonergic type 2 agonists do not change. The results suggest that as PPN neurons develop, they are increasingly activated by kainic acid and increasingly inhibited by serotonergic type 1 receptors. These processes may be related to the developmental decrease in REM sleep. Developmental disturbances in each of these systems could induce differential increases in REM sleep drive, accounting for the postpubertal onset of a number of different disorders manifesting increases in REM sleep drive. Examination of modulation by PPN projections to ascending and descending targets revealed the presence of common signals modulating ascending arousal-related functions and descending postural/locomotor-related functions.     

Waking and genioglossus muscle responses to upper airway pressure oscillation in sleeping dogs

We studied waking and genioglossus electromyographic (EMGgg) responses to oscillating pressure waves applied to the upper airways of three sleeping dogs. The dogs were previously prepared with a permanent side-hole tracheal stoma and were trained to sleep with a tight-fitting snout mask, hermetically sealed in place, while breathing through a cuffed endotracheal tube inserted through the tracheostomy. Sleep state was determined by behavioral, electroencephalographic, and electromyographic criteria, and EMGgg activity was measured using fine bipolar electrodes inserted directly into the muscle. Oscillatory pressure waves of 30 Hz and +/- 3 cmH2O (tested at atmospheric and subatmospheric upper airway pressures) were applied at the dog's nostrils or larynx, either constantly for a period of 1 min or in 0.5-s bursts. We found that the pressure stimulus had two major effects. First, it was a potentially powerful arousal-promoting stimulus. Arousal occurred in 78% of tests in slow-wave sleep (SWS) and 55% of tests in rapid-eye-movement (REM) sleep, with swallowing and sighing accompanying many of the arousals. Second, it produced an immediate and sustained augmentation of EMGgg, in wakefulness, SWS, and REM sleep. We conclude that oscillatory pressure waves in the upper airway, as found in snoring, produce reflex responses that help maintain upper airway patency during sleep. Loss of this type of reflex might contribute to the onset of obstructive sleep apnea in chronic snorers.     

Upper airway dilating forces during wakefulness and sleep in dogs

We measured the pressure within an isolated segment of the upper airway in three dogs during wakefulness (W), slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. Measurements were taken from a segment of the upper airway between the nares and midtrachea while the dog breathed through a tracheostoma. These pressure changes represented the sum of respiratory-related forces generated by all muscles of the upper airway. The mean base-line level of upper airway pressure (Pua) was -0.5 +/- 0.03 cmH2O during W, increased by a mean of 2.1 +/- 0.2 cmH2O during SWS, and was variable during REM sleep. The mean inspiratory-related phasic change in Pua was -1.2 +/- 0.1 cmH2O during wakefulness. During SWS, this phasic change in Pua decreased significantly to a mean of -0.9 +/- 0.1 cmH2O (P less than 0.05). During REM sleep, the phasic activity was extremely variable with periods in which there were no fluctuations in Pua and others with high swings in Pua. These data indicate that in dogs the sum of forces which dilate the upper airway during W decreases during SWS and REM sleep. The consistent coupling between inspiratory drive and upper airway dilatation during wakefulness persists in SWS, but is frequently uncoupled during REM sleep.     

Light-Dark Difference in Arterial Pressure Variability During REM Sleep in the Rat

We have observed mean arterial pressure (MAP) variability during rapid eye movement (REM) sleep and brain temperature (Tb) in the rat during both light and dark periods over 24 h. MAP was measured using a telemetric device with a computer data capture and analysis system. As markers of MAP variability, the maximum and coefficient of variation (CV%) of MAP during REM sleep were determined. The following results were obtained: (a) there was a light-dark difference in MAP during non-REM (NREM) sleep and Tb during both NREM and REM sleep; (b) the increase of MAP in going from NREM to REM sleep in the light period was greater than that in the dark period, whereas the increase of Tb in the light period was not different from that in the dark period; (c) the maximum and CV% for MAP during REM sleep in the light period were greater than those in the dark period; (d) there was a negative correlation between the average Tb and MAP CV% during REM sleep. We suggest that phasic fluctuation of MAP during REM sleep may be influenced, in part, by a factor independent of sleep mechanisms.     

Light-Dark Difference in Arterial Pressure Variability During REM Sleep in the Rat

We have observed mean arterial pressure (MAP) variability during rapid eye movement (REM) sleep and brain temperature (Tb) in the rat during both light and dark periods over 24 h. MAP was measured using a telemetric device with a computer data capture and analysis system. As markers of MAP variability, the maximum and coefficient of variation (CV%) of MAP during REM sleep were determined. The following results were obtained: (a) there was a light-dark difference in MAP during non-REM (NREM) sleep and Tb during both NREM and REM sleep; (b) the increase of MAP in going from NREM to REM sleep in the light period was greater than that in the dark period, whereas the increase of Tb in the light period was not different from that in the dark period; (c) the maximum and CV% for MAP during REM sleep in the light period were greater than those in the dark period; (d) there was a negative correlation between the average Tb and MAP CV% during REM sleep. We suggest that phasic fluctuation of MAP during REM sleep may be influenced, in part, by a factor independent of sleep mechanisms.     

Changes in upper airway muscle activation and ventilation during phasic REM sleep in normal men

Several investigators have observed that irregular breathing occurs during rapid-eye-movement (REM) sleep in healthy subjects, with ventilatory suppression being prominent during active eye movements [phasic REM (PREM) sleep] as opposed to tonic REM (TREM) sleep, when ocular activity is absent and ventilation more regular. Inasmuch as considerable data suggest that rapid eye movements are a manifestation of sleep-induced neural events that may importantly influence respiratory neurons, we hypothesized that upper airway dilator muscle activation may also be suppressed during periods of active eye movements in REM sleep. We studied six normal men during single nocturnal sleep studies. Standard sleep-staging parameters, ventilation, and genioglossus and alae nasi electromyograms (EMG) were continuously recorded during the study. There were no significant differences in minute ventilation, tidal volume, or any index of genioglossus or alae nasi EMG amplitude between non-REM (NREM) and REM sleep, when REM was analyzed as a single sleep stage. Each breath during REM sleep was scored as "phasic" or "tonic," depending on its proximity to REM deflections on the electrooculogram. Comparison of all three sleep states (NREM, PREM, and TREM) revealed that peak inspiratory genioglossus and alae nasi EMG activities were significantly decreased during PREM sleep compared with TREM sleep [genioglossus (arbitrary units): NREM 49 +/- 12 (mean +/- SE), TREM 49 +/- 5, PREM 20 +/- 5 (P less than 0.05, PREM different from TREM and NREM); alae nasi: NREM 16 +/- 4, TREM 38 +/- 7, PREM 10 +/- 4 (P less than 0.05, PREM different from TREM)]. We also observed, as have others, that ventilation, tidal volume, and mean inspiratory airflow were significantly decreased and respiratory frequency was increased during PREM sleep compared with both TREM and NREM sleep. We conclude that hypoventilation occurs in concert with reduced upper airway dilator muscle activation during PREM sleep by mechanisms that remain to be established.     

Respiratory events and periodic breathing in cyclists sleeping at 2,650-m simulated altitude.

We examined the initial effect of sleeping at a simulated moderate altitude of 2,650 m on the frequency of apneas and hypopneas, as well as on the heart rate and blood oxygen saturation from pulse oximetry (SpO2) during rapid eye movement (REM) and non-rapid eye movement (NREM) sleep of 17 trained cyclists. Pulse oximetry revealed that sleeping at simulated altitude significantly increased heart rate (3 +/- 1 beats/min; means +/- SE) and decreased SpO2 (-6 +/- 1%) compared with baseline data collected near sea level. In response to simulated altitude, 15 of the 17 subjects increased the combined frequency of apneas plus hypopneas from baseline levels. On exposure to simulated altitude, the increase in apnea was significant from baseline for both sleep states (2.0 +/- 1.3 events/h for REM, 9.9 +/- 6.2 events/h for NREM), but the difference between the two states was not significantly different. Hypopnea frequency was significantly elevated from baseline to simulated altitude exposure in both sleep states, and under hypoxic conditions it was greater in REM than in NREM sleep (7.9 +/- 1.8 vs. 4.2 +/- 1.3 events/h, respectively). Periodic breathing episodes during sleep were identified in four subjects, making this the first study to show periodic breathing in healthy adults at a level of hypoxia equivalent to 2,650-m altitude. These results indicate that simulated moderate hypoxia of a level typically chosen by coaches and elite athletes for simulated altitude programs can cause substantial respiratory events during sleep.     

Arousal responses to airway occlusion in sleeping dogs: comparison of nasal and tracheal occlusions

Previous studies have shown that the arousal threshold to hypoxia, hypercapnia, and tracheal occlusions is greatly depressed in rapid-eye-movement (REM) sleep compared with slow-wave sleep (SWS). The aim of this study was to compare the arousal thresholds in SWS and REM sleep in response to an upper airway pressure stimulus. We compared the waking responses to tracheal (T) vs. nasal (N) occlusion in four unanesthetized, naturally sleeping dogs. The dogs either breathed through a tracheal fistula or through the snout using a fiberglass mask. A total of 295 T and 160 N occlusion tests were performed in SWS and REM sleep. The mean time to arousal during N and T tests was variable in the same dog and among the dogs. The mean time to arousal in SWS-tracheal occlusion was longer than that in N tests in only two of the four dogs. The total number of tests inducing arousal within the first 15 s of SWS-nasal occlusion tests was significantly more than that of T tests (N: 47%; T: 27%). There was a marked depression of arousal within the initial 15 s of REM sleep in T tests compared with N tests (N: 21%; T: 0%). The frequency of early arousals in REM tests was less than that of SWS for both N and T tests. The early arousal in N occlusion is in sharp contrast to the well-described depressed arousal responses to hypoxia, hypercapnia, and asphyxia. This pattern of arousal suggests that the upper airway mechanoreceptors may play an important role in the induction of an early arousal from nasal occlusion.     

Relationship between sleep stages and short‐term changes in rectal temperature in humans

Abstract

Sixteen volunteers have been studied during 3–4 control nights and eight of these subjects again during four successive sleeps on 30‐h “days”;. The experiments took place in a comfortable environment provided by an isolation chamber. Rectal temperature and the sleep EEG were measured throughout. The relationship between sleep stages, particularly SWS and REM sleep, and short‐term changes in rectal temperature has been investigated during both protocols. Care was taken to correct for or remove those temperature changes that could be attributed to circadian rhythmicity or the effects of loss of masking due to being awake. Results showed that there was a small but significant effect of sleep stages, with SWS producing a fall and REM sleep a rise in rectal temperature after a delay of about 30–48 minutes. It is concluded that such spontaneous changes in sleeping subjects accord with the results of other studies which indicate that thermoregulatory reflexes to hot or cold stimuli alter in different sleep stages.     

Brain state and plasticity: an integration of the reciprocal interaction model of sleep cycle oscillation with attentional models of hippocampal function

The present paper relates the reciprocal interaction model for sleep cycle oscillation (McCarley and Hobson, ref. 29) to an attentional model of hippocampal function (Schmajuk and Moore, ref. 44). We consider mechanisms by which the interaction between gigantocellular tegmental field (FTG) cells and locus coeruleus (LC) activity proposed by the sleep cycle model may differentially modulate the information processing carried out in the hippocampus as described by the attentional model. Our fundamental assumption is that learning about the relevancy of different stimuli is proportional to the level of LC activation. If the environment becomes unpredictable during waking, the FTG and LC are activated and the LC facilitates hippocampal learning about stimulus relevancy. In a predictable situation during waking, FTG cells discharge rarely because no novelty is detected, and LC neurons are moderately active. If the predictable situation lasts, LC cells also decrease their activity, and a sleep period might start. At sleep onset, LC inhibition decreases and FTG activity is low leading to slow sleep. As FTG activity increases and LC activity reaches its low point, REM sleep starts. Because LC activity is low during REM sleep, values of stimulus relevancy remain unchanged. Since during sleep the threshold for external stimuli is high, only internally generated novel stimuli (subjectively perceived as dream mentation) may activate the LC. LC renewed inhibitory influence on the FTG ends REM sleep.     

A probabilistic model for the ultradian timing of REM sleep in mice

A salient feature of mammalian sleep is the alternation between rapid eye movement (REM) and non-REM (NREM) sleep. However, how these two sleep stages influence each other and thereby regulate the timing of REM sleep episodes is still largely unresolved. Here, we developed a statistical model that specifies the relationship between REM and subsequent NREM sleep to quantify how REM sleep affects the following NREM sleep duration and its electrophysiological features in mice. We show that a lognormal mixture model well describes how the preceding REM sleep duration influences the amount of NREM sleep till the next REM sleep episode. The model supports the existence of two different types of sleep cycles: Short cycles form closely interspaced sequences of REM sleep episodes, whereas during long cycles, REM sleep is first followed by an interval of NREM sleep during which transitions to REM sleep are extremely unlikely. This refractory period is characterized by low power in the theta and sigma range of the electroencephalogram (EEG), low spindle rate and frequent microarousals, and its duration proportionally increases with the preceding REM sleep duration. Using our model, we estimated the propensity for REM sleep at the transition from NREM to REM sleep and found that entering REM sleep with higher propensity resulted in longer REM sleep episodes with reduced EEG power. Compared with the light phase, the buildup of REM sleep propensity was slower during the dark phase. Our data-driven modeling approach uncovered basic principles underlying the timing and duration of REM sleep episodes in mice and provides a flexible framework to describe the ultradian regulation of REM sleep in health and disease.     

Effects of delta sleep-inducing peptide on electrophysiological parameters of sleep during alcohol withdrawal in rats

In rats with the persistent alcohol motivation the electrophysiological sleep pattern was studied during ethanol intake, after 24 and 48 hours of alcohol withdrawal. It was established that during the voluntary ethanol intake rats may be divided into two groups: with comparative deficit (1st group) and comparative abundance (2nd group) of REM sleep. Alcohol withdrawal caused differential alterations of sleep-wakefulness cycle: in the 1st group of rats REM sleep was more suppressed while in the 2nd group--more increased in comparison to those during ethanol intake. In all animals the SWS depression, increase of awakenings, the aggravation of falling asleep and decrease of sleep depth were observed. DSIP (0.1 mg/kg, i.p. 1 hour before sleep recording) was found to regulate sleep disorders caused by ethanol withdrawal. It makes the neuropeptide possible to be recommended for ethanol withdrawal syndrome treatment in clinical practice.     

Association between Poor Glycemic Control,Impaired Sleep Quality,and Increased Arterial Thickening in Type 2 Diabetic Patients

Objective

Poor sleep quality is an independent predictor of cardiovascular events. However, little is known about the association between glycemic control and objective sleep architecture and its influence on arteriosclerosis in patients with type-2 diabetes mellitus (DM). The present study examined the association of objective sleep architecture with both glycemic control and arteriosclerosis in type-2 DM patients.

Design

Cross-sectional study in vascular laboratory.

Methods

The subjects were 63 type-2 DM inpatients (M/F, 32/31; age, 57.5±13.1) without taking any sleeping promoting drug and chronic kidney disease. We examined objective sleep architecture by single-channel electroencephalography and arteriosclerosis by carotid-artery intima-media thickness (CA-IMT).

Results

HbA1c was associated significantly in a negative manner with REM sleep latency (interval between sleep-onset and the first REM period) (β=-0.280, p=0.033), but not with other measurements of sleep quality. REM sleep latency associated significantly in a positive manner with log delta power (the marker of deep sleep) during that period (β=0.544, p=0.001). In the model including variables univariately correlated with CA-IMT (REM sleep latency, age, DM duration, systolic blood pressure, and HbA1c) as independent variables, REM sleep latency (β=-0.232, p=0.038), but not HbA1c were significantly associated with CA-IMT. When log delta power was included in place of REM sleep latency, log delta power (β=-0.257, p=0.023) emerged as a significant factor associated with CA-IMT.

Conclusions

In type-2 DM patients, poor glycemic control was independently associated with poor quality of sleep as represented by decrease of REM sleep latency which might be responsible for increased CA-IMT, a relevant marker for arterial wall thickening.     

Cutaneous vasomotion during REM sleep in the rabbit's ear, after alpha-receptor blockade

Cutaneous vasoconstriction in the rabbit's ear during REM sleep in a warm environment is not abolished by alpha-receptor blockade (phenoxybenzamine 6 mg/kg i.v.), thus confirming that the vasomotor response during REM sleep is independent of the activity of circulating catecholamines. The decrease in cardiac output during REM sleep may be responsible for the slight fall in transmural pressure which underlies cutaneous ear vasoconstriction during REM sleep.