SLEEP

Murillo-Rodriguez, Eric; Blanco-Centurion, Carlos; Sanchez, Cristina; Daniele, Piomelli; Shiromani, Priyattam J.

doi: 10.1093/sleep/26.8.943pmid: 14746372

AbstractStudy Objectives:The principal component of marijuana, delta-9-tetrahydrocannabinol increases sleep in humans. Endogenous cannabinoids, such as N-arachidonoylethanolamine (anandamide), also increase sleep. However, the mechanism by which these molecules promote sleep is not known but might involve a sleep-inducing molecule such as adenosine. Microdialysis samples were collected from the basal forebrain in order to detect levels of adenosine before and after injection of anandamide.Design:Rats were implanted for sleep studies, and a cannula was placed in the basal forebrain to collect microdialysis samples. Samples were analyzed using high-performance liquid chromatography.Settings:Basic neuroscience research laboratory.Participants and Interventions:Three-month-old male F344 rats. At the start of the lights-on period, animals received systemic injections of dimethyl sulfoxide (vehicle), anandamide, SR141716A (cannabinoid receptor 1 [CB1] antagonist), or SR141716A and anandamide. One hour after injections, microdialysis samples were collected (5µL) from the basal forebrain every hour over a 20-minute period for 5 hours. The samples were immediately analyzed via high-performance liquid chromatography for adenosine levels. Sleep was also recorded continuously over the same period.Measurements and Results:Anandamide increased adenosine levels compared to vehicle controls with the peak levels being reached during the third hour after drug injection. There was a significant increase in slow-wave sleep during the third hour. The induction in sleep and the rise in adenosine were blocked by the CB1-receptor antagonist, SR141716A.Conclusions:Anandamide increased adenosine levels in the basal forebrain and also increased sleep. The soporific effects of anandamide were mediated by the CB1 receptor, since the effects were blocked by the CB1-receptor antagonist. These findings identify a potential therapeutic use of endocannabinoids to induce sleep in conditions where sleep may be severely attenuated.

Dewasmes, Gérard; Loos, Nathalie; Delanaud, Stéphane; Ramadan, Wiam; Dewasmes, Danielle

doi: 10.1093/sleep/26.8.948pmid: 14746373

AbstractStudy Objective:The liver, like brown adipose tissue, is an important source of nonshivering thermogenesis. We tested the hypothesis that the thermal state of the liver is preserved during slow wave sleep but deteriorates during paradoxical sleep.Methods:Twelve adult male Wistar rats were equipped with electrodes and thermistor probes—which measured cortical (Tco), interscapular brown adipose tissue (Tibat), and liver (Tl) temperatures—for thermal and sleep studies. Six rats were exposed to thermoneutral (24°C) and 6 to low (9°C) ambient temperature. Isolated paradoxical sleep episodes preceded and followed by more than 3 minutes of wakefulness or slow wave sleep were analyzed. The Tco, Tibat, and Tl levels were also assessed during the slow wave sleep that preceded each isolated paradoxical sleep episode.Results:During slow wave sleep, the Tibat and Tl were clearly higher in rats exposed to the cold than in those exposed to the thermoneutral condition (< 1°C). During paradoxical sleep, however, these 2 temperatures decreased in rats exposed to the cold condition, and the changes observed for Tco were completely inversed.Conclusions:These results support the hypothesis that the thermal state in the liver of rats deteriorates during paradoxical sleep and suggest that nonshivering thermogenesis in the liver contributes to the defense of global thermal homeostasis in the sleeping endothermic organism, especially during slow wave sleep.

Fujiki, Nobuhiro; Yoshida, Yasushi; Ripley, Beth; Mignot, Emmanuel; Nishino, Seiji

doi: 10.1093/sleep/26.8.953pmid: 14746374

AbstractStudy Objectives:Using two different canine models of narcolepsy, we evaluated the therapeutic effects of hypocretin-1 on cataplexy and sleep.Measurements and Results:Intracerebroventricular administration of hypocretin-1 (10 and 30 nmol per dog) but not intravenous administration (up to 6µg/kg) induced significant wakefulness in control dogs. However, hypocretin-1 had no effect on cataplexy or wakefulness in hypocretin receptor-2 gene (Hcrtr2) mutated narcoleptic Dobermans. Only very high intravenously doses of hypocretin-1 (96 – 384 µg/kg) penetrated the brain, to produce a short-lasting anticataplectic effect in a hypocretin-ligand-deficient animal.Conclusions:Hypocretin-1 administration, by central and systemic routes, does not improve narcoleptic symptoms in Hcrtr2 mutated Dobermans. Systemic hypocretin-1 hardly crosses the blood-brain barrier to produce therapeutic effects. The development of more centrally penetrable and longer lasting hypocretin analogs will be needed to further explore this therapeutic pathway in humans.

Lovering, Andrew T.; Fraigne, Jimmy J.; Witali L., Dunin-Barkowski; Vidruk, Edward H.; Orem, John M.

doi: 10.1093/sleep/26.8.961pmid: 14746375

AbstractContext:Sleep is disturbed at high altitudes. Low Po2 levels at high altitude cause hyperventilation, which results in secondary hypocapnia (low Paco2 levels). Thus, although sleep disruption at high altitudes is generally assumed to be caused by hypoxia, it may instead be the result of hypocapnia.Objective:To determine whether hypocapnia disrupts sleep.Methods:Four cats were studied for a total of 345 hours of sleep recordings. Two methods were used to test this idea. First we studied their sleep when the cats breathed oxygen concentrations (15% and 10%) equivalent to those at approximately 12,000 feet and 21,000 feet. Then we studied their sleep again in response to the same hypoxic stimuli but with CO2 added to the inspirate to maintain normal CO2 levels. Second, we used mechanical hyperventilation to vary the levels of CO2 while maintaining normal O2 levels.Results:Hypoxia (10% O2) decreased the amount of rapid eye movement sleep to about 20% of normal, and adding back CO2 restored rapid eye movement sleep to approximately 70% of normal. Periodic breathing and apneas were not observed during hypoxia in sleep. When mechanical hyperventilation lowered the CO2 to 85%, 75%, and 65% of normal, rapid eye movement sleep decreased progressively from a control level of 17% of total recording time to 12%, 7%, and 4%, respectively.Conclusion:We conclude that hypocapnia rather than hypoxia may account for most of the sleep disturbance at high altitudes.

Anderson, Clare; Horne, James A.

doi: 10.1093/sleep/26.8.968pmid: N/A

AbstractStudy Objective:Separate studies have shown for the frontal cortex that: i) sleep electroencephalogram (EEG) activity less than 1 Hz may be linked to waking recovery, and ii) waking frontal theta activity may reflect “cortical workload.” We explored the potential linkage between (i) and (ii) in relation to specific waking theta frequencies and 0.5-Hz to 1.0-Hz activity in sleep.Design:A correlational studySetting:Laboratory-based waking EEGs under different (eyes-closed) contrived “thinking” conditions (mostly localized to the left frontal area), and night sleep EEGs at home.Participants:Twelve right-handed, healthy, good-sleeping, older adults (mean age, 67.3 years)Measurement & Results:EEGs comprised 4 bipolar derivations (Fp1-F3; Fp2-F4; O1-P3; O2-P4). Power in the 7-8-Hz bin was the only waking frequency significantly (positively) correlated with power in the 0.5- to 1.0-Hz bin during the first NREM period and only for the left frontal EEG. Interestingly, 7- to 8-Hz power immediately after lights out at bedtime, and before the appearance of EEG sleepiness, showed an even higher positive correlation with 0.5- to 1.0-Hz power during sleep. This wake-sleep EEG link was confirmed in another sample of 8 similar participants. Waking frontal 7- to 8-Hz EEG may not be typical theta, but “kappa” activity, believed to be associated with thinkingConclusions:Within limits of the EEG, and for the left frontal area, waking thinking may be reflected by putative cortical reorganization during the first NREM period.

Darchia, Nato; Campbell, Ian G.; Feinberg, Irwin

doi: 10.1093/sleep/26.8.973pmid: 14746377

AbstractStudy Objectives:While there is general agreement on the age changes in non-rapid eye movement sleep, there is conflicting evidence on whether eye movement density (EMD) in rapid eye movement sleep is affected by aging. We therefore performed computer measurement of EMD in young and elderly normal subjects.Design:Sleep electroencephalogram and electrooculogram were recorded in each subject on 4 nonconsecutive baseline nights. Eye movement density in the elderly subjects was compared to that in young adults.Setting:A sleep research laboratory with 4 separate bedrooms.Interventions:Not applicable.Participants:Subjects were 19 young normal adults and 19 elderly normal adults.Measurements and Results:Digitized electrooculograms were analyzed with the extensively validated zero-cross period-amplitude module of PASS PLUS software. The EMD was measured as 0.3 to 2 Hz integrated amplitude per 20-second stage of rapid eye movement sleep. Eye-movement incidence was the number of half waves. Eye-movement amplitude was the sum of peak-trough excursions (curve length) in the average half wave. We also counted visually the number of 2-second epochs with eye movements for 1 baseline night in both groups. The EMD in the elderly subjects was substantially and significantly lower than in the young subjects. Visual scoring of EMD on 1 baseline night confirmed the statistically significant difference between age groups. Period-amplitude analysis revealed that a lower eye-movement incidence rather than reduced amplitude caused the lower EMD in the elderly. The EMD was significantly correlated within subjects across the nonconsecutive baseline nights in both groups; in both, subjects’ EMD average across 2 nights provided a correlation greater than .90 with the 4-night mean.Conclusions:The incidence of eye movements during rapid eye movement sleep is substantially reduced in the elderly. We hypothesize that this reduction is due to degenerative (aging) rather than developmental brain changes. The correlation analysis indicates that EMD is a reasonably stable individual trait in both young and elderly adults. These results encourage normative studies of EMD over a wider age span and continued exploration of the relation of EMD to cognitive function in the elderly.

Roehrs, Timothy; Burduvali, Eleni; Bonahoom, Alicia; Drake, Christopher; Roth, Thomas

doi: 10.1093/sleep/26.8.981pmid: 14746378

AbstractStudy Objectives:Studies to assess the risks associated with sleep loss relative to the well-documented risks of alcohol are limited in number and design. This study compared the “dose”-related sedative, performance-impairing, and amnestic effects of sleep loss to those of ethanol ingestion.Design:Mixed-design experiment with random assignment to a sleep loss (n=12) or ethanol (n=20) group, with each participant assessed under 4 conditions.Participants:Thirty-two healthy normal adult volunteers, aged 21 to 35 years.Interventions:In sleep loss, participants had 8, 6, 4, and 0 hours time in bed, producing 0, 2, 4, and 8 hours of sleep loss. For ethanol, participants ingested 0.0 g/kg, 0.3 g/kg, 0.6 g/kg, and 0.9 g/kg ethanol from 8:30 AM to 9:00 AM after 8 hours of time in bed the previous night. Each participant received his or her 4 doses of ethanol or sleep loss in a Latin square design with 3 to 7 days between doses.Measurements:All subjects completed the Multiple Sleep Latency Test (MSLT) at 9:30 AM, 11:30 AM, 1:30 PM, 3:30 PM, and 5:30 PM and a performance battery at 10:00 AM, 12:00 NOON, 2:00 PM, and 4:00 PM consisting of memory, psychomotor vigilance, and divided attention tests.Results:Ethanol and sleep loss reduced the average daily sleep latency on the MSLT, both as a linear function of dose, with sleep loss in hours being 2.7 times more potent than ethanol in grams per kilogram. Ethanol and sleep loss also slowed reaction time on the psychomotor vigilance test in a linear dose-related function with the 2 being equipotent in their impairing effect. On the divided attention test, tracking deviations were increased by both ethanol and sleep loss in an equipotent and linear dose-related function. Memory recall was reduced in a linear dose-related function by both ethanol and sleep loss with ethanol being slightly more potent. Finally, sleep loss doses produced a linear decrease in self-rated quality of performance, while only at the highest ethanol dose was performance rated as poorer.Conclusions:At the studied doses, sleep loss was more potent than ethanol in its sedative effects but comparable in effects on psychomotor performance. Ethanol produced greater memory deficits, and subjects were less aware of their overall performance impairment.

Ogawa, Yuriko; Kanbayashi, Takashi; Saito, Yasushi; Takahashi, Yuji; Kitajima, Tsuyoshi; Takahashi, Kenichi; Hishikawa, Yasuo; Shimizu, Tetsuo

doi: 10.1093/sleep/26.8.986pmid: 14746379

AbstractStudy Objectives:Sleep deprivation has a profound effect on cardiovascular regulation through the autonomic nervous system. This study examined the effect of 24-hour total sleep deprivation on muscle sympathetic nerve activity (MSNA), which is a direct measurement of the postganglionic sympathetic efferent innervating the vascular bed in the skeletal muscle and other circulatory structures.Design:The study was performed on 6 young healthy men. The factors exerting influence on MSNA, such as aging, obesity, body posture, activity, intensity of illumination, and food and beverage consumption were strictly controlled. Burst rate and burst incidence were used as parameters of MSNA. The burst rate, burst incidence, heart rate, and systolic and diastolic blood pressure were measured after total sleep deprivation and control sleep. To perform a linear regression analysis of arterial baroreflex (ABR), the incidence of MSNA bursts corresponding to a given diastolic blood pressure (%MSNA) was examined.Measurement and Results:The diastolic blood pressure was significantly higher after total sleep deprivation than after control sleep (66.5 ± 1.7 vs 57.4 ± 3.3 mm Hg). The burst rate (9.6 ± 1.8 vs 13.3 ± 2.7 bursts/min) and burst incidence (21.6 ± 4.5 vs 30.3 ± 8.9 bursts/100 heart beats) of MSNA were significantly lower after total sleep deprivation than after control sleep (P < .05). Analysis of the ABR disclosed a significant linear regressive relation between %MSNA and diastolic blood pressure in every subject after both total sleep deprivation and control sleep. This result implies that the ABR regulates the occurrence of MSNA bursts under different diastolic blood pressure conditions. The threshold (X-axis intercept) of the blood pressure regression line (ie, an indicator of the ABR set point) shifted by 12 ± 4.3 mm Hg toward a higher blood pressure level after total sleep deprivation (P < .05). The ABR sensitivity, or the slope of the regression line, tended to be less steep after total sleep deprivation than after control sleep, although it was not statistically significant (P = .09).Conclusions:The diastolic blood pressure increased and both burst rate and burst incidence of MSNA decreased after total sleep deprivation. The results show that resetting of the ABR toward a higher blood pressure level occurred after total sleep deprivation. This ABR resetting probably brings about an increase in arterial blood pressure after total sleep deprivation.

Feng, Pingfu; Ma, Yuxian

doi: 10.1093/sleep/26.8.990pmid: 14746380

AbstractStudy Objectives:Previous studies have demonstrated that neonatal suppression of rapid eye movement (REM) sleep by pharmacologic agents, particularly clomipramine, produces adult depressive behavior. These findings suggest the hypothesis that REM sleep deprivation (RSD) mediates the depressogenic behaviors of neonatally administered antidepressant drugs. Drug suppression of RSD, however, was thought to be confounded by the other effects of the drugs. The current study was aimed to show the adult effect of neonatal RSD in rats by instrumental means, ie, a computer-controlled shaking method.Design:Three treatment groups were studied: an instrumental RSD group, a yoked control group, and a nonshaken, maternally separated, control group. All treatments began at the age of 14 days and lasted for 7 days. Adult behavior measurements including tests of sexual activity, locomotor activity, shock-induced fighting, and sleep recording were subsequently performed.Measurements and Results:The major findings of our investigation were that rats subjected to neonatal instrumental RSD demonstrated diminished sexual activity, decreased aggressive behavior, increased percentage of REM sleep, and decreased wake-REM sleep ratio compared with yoked control rats. These data are compatible with the findings from adult rats subjected to neonatal treatment with the REM-sleep suppressant, clomipramine, and supports the hypothesis that neonatal RSD results in adult depressive abnormalities.Conclusion:Neonatal RSD induced by a nondrug method results in adult depression-like changes similar to those induced by a REM-sleep suppressant drug, although the extent of these changes varies.

Friedman, Bat-Chen; Hendeles-Amitai, Ayelet; Kozminsky, Ely; Leiberman, Alberto; Friger, Michael; Tarasiuk, Ariel; Tal, Asher

doi: 10.1093/sleep/26.8.999pmid: 14746381

AbstractObjective:To evaluate neurocognitive functions of children with obstructive sleep apnea syndrome (OSAS), before and after adenotonsillectomy, compared with healthy controls.Design:Prospective study.Patients and Methods:Thirty-nine children with OSAS aged 5 to 9 years (mean age, 6.8 ± 0.2 years) and 20 healthy children (mean age, 7.4 ± 1.4 years) who served as controls, underwent a battery of neurocognitive tests containing process-oriented intelligence scales. Twenty-seven children in the OSAS group underwent follow-up neurocognitive testing 6 to 10 months after adenotonsillectomy. Fourteen children in the control group were also reevaluated 6 to 10 months after the first evaluation.Results:Children with OSAS had lower scores compared with healthy children in some Kaufman Assessment Battery for Children (K-ABC) subtests and in the general scale Mental Processing Composite, indicating impaired neurocognitive function. No correlation was found between neurocognitive performance and OSAS severity. Six to 10 months after adenotonsillectomy, the children with OSAS demonstrated significant improvement in sleep characteristics, as well as in daytime behavior. Their neurocognitive performance improved considerably, reaching the level of the control group in the subtests Gestalt Closure, Triangles, Word Order, and the Matrix analogies, as well as in the K-ABC general scales, Sequential and Simultaneous Processing scales, and the Mental Processing Composite scale. The magnitude of the change expressed as effect sizes showed medium and large improvements in all 3 general scales of the K-ABC tests.Conclusions:Neurocognitive function is impaired in otherwise healthy children with OSAS. Most functions improve to the level of the control group, indicating that the impaired neurocognitive functions are mostly reversible, at least 3 to 10 months following adenotonsillectomy.