Enhancing Slow Wave Sleep with Sodium Oxybate Reduces the Behavioral and Physiological Impact of Sleep Loss

Study Objectives:

To investigate whether enhancement of slow wave sleep (SWS) with sodium oxybate reduces the impact of sleep deprivation.

Design:

Double-blind, parallel group, placebo-controlled design

Setting:

Sleep research laboratory

Participants:

Fifty-eight healthy adults (28 placebo, 30 sodium oxybate), ages 18-50 years.

Interventions:

A 5-day protocol included 2 screening/baseline nights and days, 2 sleep deprivation nights, each followed by a 3-h daytime (08:00-11:00) sleep opportunity and a recovery night. Sodium oxybate or placebo was administered prior to each daytime sleep period. Multiple sleep latency test (MSLT), psychomotor vigilance test (PVT), Karolinska Sleepiness Scale (KSS), and Profile of Mood States were administered during waking hours.

Measurements and Results:

During daytime sleep, the sodium oxybate group had more SWS, more EEG spectral power in the 1-9 Hz range, and less REM. Mean MSLT latency was longer for the sodium oxybate group on the night following the first daytime sleep period and on the day following the second day sleep period. Median PVT reaction time was faster in the sodium oxybate group following the second day sleep period. The change from baseline in SWS was positively correlated with the change in MSLT and KSS. During recovery sleep the sodium oxybate group had less TST, SWS, REM, and slow wave activity (SWA) than the placebo group.

Conclusions:

Pharmacological enhancement of SWS with sodium oxybate resulted in a reduced response to sleep loss on measures of alertness and attention. In addition, SWS enhancement during sleep restriction appears to result in a reduced homeostatic response to sleep loss.

Citation:

Walsh JK; Hall-Porter JM; Griffin KS; Dodson ER; Forst EH; Curry DT; Eisenstein RD; Schweitzer PK. Enhancing slow wave sleep with sodium oxybate reduces the behavioral and physiological impact of sleep loss. SLEEP 2010;33(9):1217-1225.     

Changes in Cardiac Variability after REM Sleep Deprivation in Recurrent Nightmares

Study Objectives:

To assess whether dysfunctional autonomic regulation during REM sleep as indexed by heart rate variability (HRV) is a pathophysiological factor in frequent nightmares (NMs).

Design:

Monitoring with polysomnography (PSG) and electrocardiography (ECG) for 3 consecutive nights: Night 1 (N1), adaptation night; N2, administration of partial REM sleep deprivation; N3, recovery night. Differences between NM and control (CTL) groups assessed for ECG measures drawn from wakefulness, REM sleep, and Stage 2 sleep on both N1 and N3.

Setting:

Hospital-based sleep laboratory

Participants:

Sixteen subjects with frequent NMs ( ≥ 1 NM/week; mean age = 26.1 ± 8.7 years) but no other medical or psychiatric disorders and 11 healthy comparison subjects ( < 1 NM/month; mean age = 27.1±5.6 years).

Results:

NM and CTL groups differed on 2 REM sleep measures only on N1; the NM group had longer REM latencies and REM/NREM cycle durations than did the CTL group. No differences were found on time domain and absolute frequency domain ECG measures for either N1 or N3. However, altered HRV for the NM group was suggested by significantly higher LFnu, lower HFnu, and higher LF/HF ratio than for the CTL group.

Conclusions:

Results are consistent with a higher than normal sympathetic drive among NM subjects which is unmasked by high REM sleep propensity. Results also support a growing literature linking anxiety disorders of several types (panic disorder, posttraumatic stress disorder (PTSD), generalized anxiety disorder) to altered HR variability.

Citation:

Nielsen T; Paquette T; Solomonova E; Lara-Carrasco J; Colombo R; Lanfranchi P. Changes in cardiac variability after rem sleep deprivation in recurrent nightmares. SLEEP 2010;33(1):113-122.     

Sleep deprivation and interference by emotional distracters

Study Objectives:

We determined if sleep deprivation would amplify the effect of negative emotional distracters on working memory.

Design:

A crossover design involving 2 functional neuroimaging scans conducted at least one week apart. One scan followed a normal night of sleep and the other followed 24 h of sleep deprivation. Scanning order was counterbalanced across subjects.

Setting:

The study took place in a research laboratory.

Participants:

24 young, healthy volunteers with no history of any sleep, psychiatric, or neurologic disorders.

Interventions:

N/A

Measurements and Results:

Study participants were scanned while performing a delayed-response working memory task. Two distracters were presented during the maintenance phase, and these differed in content: highly arousing, negative emotional scenes; low-arousing, neutral scenes; and digitally scrambled versions of the pictures. Irrespective of whether volunteers were sleep deprived, negative emotional (relative to neutral) distracters elicited greater maintenance-related activity in the amygdala, ventrolateral prefrontal cortex, and fusiform gyri, while concurrently depressing activity in cognitive control regions. Individuals who maintained or increased distracter-related amygdala activation after sleep deprivation showed increased working memory disruptions by negative emotional distracters. These individuals also showed reduced functional connectivity between the amygdala and the ventromedial and dorsolateral prefrontal cortices, regions postulated to mediate cognitive control against emtional distraction.

Conclusions:

Increased distraction by emotional stimuli following sleep deprivation is accompanied by increases in amygdala activation and reduced functional connectivity between the amygdala and prefrontal cognitive control regions. These findings shed light on the neural basis for interindividual variation in how negative emotional stimuli might distract sleep deprived persons.

Citation:

Chuah LYM; Dolcos F; Chen AK; Zheng H; Parimal S; Chee MWL. Sleep deprivation and interference by emotional distracters. SLEEP 2010;33(10):1305-1313.     

Dopamine Transporter Regulation during Four Nights of REM Sleep Deprivation Followed by Recovery – An in vivo Molecular Imaging Study in Humans

Objectives:

To assess the influence of total or selective REM sleep deprivation on the dopamine transporter (DAT) densities and sleep patterns of healthy volunteers.

Design:

Prospective study.

Setting:

Evaluation of polysomnography recordings and DAT density after 4 nights of selective REM sleep deprivation followed by 3 nights of sleep recovery compared to a control group and a group that was subjected to 2 nights of total sleep deprivation. Single positron emission computed tomography and [^99mTc]TRODAT-1 were used to assess the cerebral DAT density in the striatum at baseline, after REM sleep deprivation and total sleep deprivation as well as after sleep recovery. Blood was collected daily to examine prolactin and estradiol levels, which were correlated with dopaminergic activity.

Patients or Participants:

Thirty healthy male volunteers ranging from 19 to 29 years of age were randomly assigned to one of three experimental groups after giving written informed consent (10 non-sleep deprived, 10 total sleep deprived, and 10 REM sleep deprived).

Measurements and Results:

Four nights of REM sleep deprivation and 2 nights of total sleep deprivation induced distinct and heterogeneous patterns of sleep recovery. No significant modulation of DAT availability was observed within groups. In the recovery nights, changes in cortisol, prolactin and estradiol concentrations were significantly correlated with specific sleep stages in the total and REM sleep deprived groups. In addition, DAT density was positively correlated with estradiol concentration and inversely associated with SWS latency only after total sleep deprivation.

Conclusion:

Our study demonstrates that although sleep deprivation did not promote significant alterations in DAT density within the striatum, there were significant correlations among transporter availability, hormonal concentrations and sleep parameters.

Citation:

Martins, RCS; Andersen ML; Garbuio SA; Bittencourt LR: Guindalini C; Shih MC; Hoexter MQ; Bressan RA; Castiglioni MLV; Tufik S. Dopamine transporter regulation during four nights of REM sleep deprivation followed by recovery – an in vivo molecular imaging study in humans. SLEEP 2010;33(2):243-251.     

The Effects of Sleep Deprivation on Information-Integration Categorization Performance

Background:

Sleep deprivation is a serious problem facing individuals in many critical societal roles. One of the most ubiquitous tasks facing individuals is categorization. Sleep deprivation is known to affect rule-based categorization in the classic Wisconsin Card Sorting Task, but, to date, information-integration categorization has not been examined.

Study Objectives:

To investigate the effects of sleep deprivation on information-integration category learning.

Design:

Participants performed an information-integration categorization task twice, separated by a 24-hour period, with or without sleep between testing sessions.

Participants:

Twenty-one West Point cadets participated in the sleep-deprivation group and 28 West Point cadets participated in a control group.

Measurements and Results:

Sleep deprivation led to an overall performance deficit during the second testing session—that is, whereas participants allowed to sleep showed a significant performance increase during the second testing session, Sleepless participants showed a small (but nonsignificant) performance decline during the second testing session. Model-based analyses indicated that a major contributor to the sleep-deprivation effect was the poor second-session performance of a subgroup of sleep-deprived participants who shifted from optimal information-integration strategies at the end of the first session to less-optimal rule-based strategies at the start of the second session. Sleep-deprived participants who used information-integration strategies in both sessions showed no drop in performance in the second session, mirroring the behavior of control participants.

Conclusions:

The findings suggest that the neural systems underlying information-integration strategies are not strongly affected by sleep deprivation but, rather, that the use of an information-integration strategy in a task may require active inhibition of rule-based strategies, with this inhibitory process being vulnerable to the effects of sleep deprivation.

Citation:

Maddox WT; Glass BD; Wolosin SM; Savarie ZR; Bowen C; Matthews MD; Schnyer DM. The effects of sleep deprivation on information-integration categorization performance. SLEEP 2009;32(11):1439-1448.     

Upper Airway Collapsibility During REM Sleep in Children with the Obstructive Sleep Apnea Syndrome

Study Objectives:

In children, most obstructive events occur during rapid eye movement (REM) sleep. We hypothesized that children with the obstructive sleep apnea syndrome (OSAS), in contrast to age-matched control subjects, would not maintain airflow in the face of an upper airway inspiratory pressure drop during REM sleep.

Design:

During slow wave sleep (SWS) and REM sleep, we measured airflow, inspiratory time, inspiratory time/total respiratory cycle time, respiratory rate, tidal volume, and minute ventilation at a holding pressure at which flow limitation occurred and at 5 cm H₂O below the holding pressure in children with OSAS and in control subjects.

Setting:

Sleep laboratory.

Participants:

Fourteen children with OSAS and 23 normal control subjects.

Results:

In both sleep states, control subjects were able to maintain airflow, whereas subjects with OSAS preserved airflow in SWS but had a significant decrease in airflow during REM sleep (change in airflow of 18.58 ± 12.41 mL/s for control subjects vs −44.33 ± 14.09 mL/s for children with OSAS, P = 0.002). Although tidal volume decreased, patients with OSAS were able to maintain minute ventilation by increasing the respiratory rate and also had an increase in inspiratory time and inspiratory time per total respiratory cycle time

Conclusion:

Children with OSAS do not maintain airflow in the face of upper-airway inspiratory-pressure drops during REM sleep, indicating a more collapsible upper airway, compared with that of control subjects during REM sleep. However, compensatory mechanisms exist to maintain minute ventilation. Local reflexes, central control mechanisms, or both reflexes and control mechanisms need to be further explored to better understand the pathophysiology of this abnormality and the compensation mechanism.

Citation:

Huang J; Karamessinis LR; Pepe ME; Glinka SM; Samuel JM; Gallagher PR; Marcus CL. Upper airway collapsibility during REM sleep in children with the obstructive sleep apnea syndrome. SLEEP 2009;32(9):1173-1181.     

Sleep Homeostasis During Repeated Sleep Restriction and Recovery: Support from EEG Dynamics

Study Objectives:

Sleep reduction normally causes a homeostatic response during subsequent recovery sleep, but this does not seem to be true for repeated partial sleep loss. The aim of the present study was to test the response to repeated partial sleep loss through detailed focus on spectral data and parts of sleep.

Design:

The experiment involved 4 h of sleep across 5 days in the laboratory (partial sleep deprivation [PSD]), followed by 3 days of recovery sleep. PSD was achieved through a delayed bedtime. Nine individuals participated. To avoid “laboratory monotony,” subjects were permitted to leave the lab for a few hours each day.

Measurements and results:

All sleep stages and the latencies to sleep and slow wave sleep (SWS) showed a significant reduction during PSD. However, SWS and TST (total sleep time) during the first half of sleep increased gradually across days with PSD. During the first recovery sleep, SWS was significantly increased, while stage 1 and latency to stage 3 were reduced. All were back to baseline on the second night of recovery sleep. Summed spectral power during the first 3.8 h of sleep showed a gradual and robust increase (50% above baseline) in the range 1.25–7.25 Hz across days with PSD up to first recovery sleep and then returned to baseline.

Conclusions:

SWS and summed power density in a broad low-frequency band respond to repeated partial sleep deprivation in a dose-response fashion during the first 4 h sleep, apparently reflecting a robust and stable homeostatic response to sleep loss.

Citation:

Åkerstedt T; Kecklund G; Ingre M; Lekander M; Axelsson J. Sleep homeostasis during repeated sleep restriction and recovery: support from EEG dynamics. SLEEP 2009;32(2):217–222.     

Age-Related Reduction in Daytime Sleep Propensity and Nocturnal Slow Wave Sleep

Objective:

To investigate whether age-related and experimental reductions in SWS and sleep continuity are associated with increased daytime sleep propensity.

Methods:

Assessment of daytime sleep propensity under baseline conditions and following experimental disruption of SWS. Healthy young (20-30 y, n = 44), middle-aged (40-55 y, n = 35) and older (66-83 y, n = 31) men and women, completed a 2-way parallel group study. After an 8-h baseline sleep episode, subjects were randomized to 2 nights with selective SWS disruption by acoustic stimuli, or without disruption, followed by 1 recovery night. Objective and subjective sleep propensity were assessed using the Multiple Sleep Latency Test (MSLT) and the Karolinska Sleepiness Scale (KSS).

Findings:

During baseline sleep, SWS decreased (P < 0.001) and the number of awakenings increased (P < 0.001) across the 3 age groups. During the baseline day, MSLT values increased across the three age groups (P < 0.0001) with mean values of 8.7min (SD: 4.5), 11.7 (5.1) and 14.2 (4.1) in the young, middle-aged, and older adults, respectively. KSS values were 3.7 (1.0), 3.2 (0.9), and 3.4 (0.6) (age-group: P = 0.031). Two nights of SWS disruption led to a reduction in MSLT and increase in KSS in all 3 age groups (SWS disruption vs. control: P < 0.05 in all cases).

Conclusions:

Healthy aging is associated with a reduction in daytime sleep propensity, sleep continuity, and SWS. In contrast, experimental disruption of SWS leads to an increase in daytime sleep propensity. The age-related decline in SWS and reduction in daytime sleep propensity may reflect a lessening in homeostatic sleep requirement. Healthy older adults without sleep disorders can expect to be less sleepy during the daytime than young adults.

Citation:

Dijk DJ; Groeger JA; Stanley N; Deacon S. Age-related reduction in daytime sleep propensity and nocturnal slow wave sleep. SLEEP 2010;33(2):211-223.     

Sleep Deprivation Impairs the Accurate Recognition of Human Emotions

Study Objectives:

Investigate the impact of sleep deprivation on the ability to recognize the intensity of human facial emotions.

Design:

Randomized total sleep-deprivation or sleep-rested conditions, involving between-group and within-group repeated measures analysis.

Setting:

Experimental laboratory study.

Participants:

Thirty-seven healthy participants, (21 females) aged 18–25 y, were randomly assigned to the sleep control (SC: n = 17) or total sleep deprivation group (TSD: n = 20).

Interventions:

Participants performed an emotional face recognition task, in which they evaluated 3 different affective face categories: Sad, Happy, and Angry, each ranging in a gradient from neutral to increasingly emotional. In the TSD group, the task was performed once under conditions of sleep deprivation, and twice under sleep-rested conditions following different durations of sleep recovery. In the SC group, the task was performed twice under sleep-rested conditions, controlling for repeatability.

Measurements and Results:

In the TSD group, when sleep-deprived, there was a marked and significant blunting in the recognition of Angry and Happy affective expressions in the moderate (but not extreme) emotional intensity range; differences that were most reliable and significant in female participants. No change in the recognition of Sad expressions was observed. These recognition deficits were, however, ameliorated following one night of recovery sleep. No changes in task performance were observed in the SC group.

Conclusions:

Sleep deprivation selectively impairs the accurate judgment of human facial emotions, especially threat relevant (Anger) and reward relevant (Happy) categories, an effect observed most significantly in females. Such findings suggest that sleep loss impairs discrete affective neural systems, disrupting the identification of salient affective social cues.

Citation:

van der Helm E; Gujar N; Walker MP. Sleep deprivation impairs the accurate recognition of human emotions. SLEEP 2010;33(3):335-342.     

Determining Sleep Quality in Children with Sleep Disordered Breathing: EEG Spectral Analysis Compared with Conventional Polysomnography

Study Objectives:

To identify the extent of sleep disruption in children with various severities of sleep disordered breathing (SDB) using both conventional visually scored assessment of sleep stages and arousal indices together with EEG power spectral analysis.

Design:

Sleep stages and power spectral analysis of the sleep EEG in children with varying severities of SDB with matched control subjects with no history of snoring were compared across the whole night, across sequential hours from sleep onset, and across sleep stages.

Measurements:

Overnight polysomnography was performed on 90 children (49M/41F) aged 7-12 y with SDB and 30 age-matched healthy controls (13M/17F). Sleep stages were visually scored and the EEG spectra were analyzed in 5-s epochs.

Results:

Conventional visual scoring indicated that, although sleep duration was reduced in severely affected children, sleep quality during the essential stages of SWS and REM was preserved, as evidenced by the lack of any significant decrease in their duration in SDB severity groups. This finding was supported by the lack of substantial differences in EEG spectral power between the groups over the whole night, within specific hours, and in individual sleep stages.

Conclusions:

Both conventional scoring and EEG spectral analysis indicated only minor disruptions to sleep quality in children with SDB when assessed across the night, in any specific hour of the night, or in any specific sleep stage. These results suggest that reduced daytime functioning previously reported in children with SDB may not be due to sleep disruption. We speculate that in children, in contrast to adults, a stronger sleep drive may preserve sleep quality even in severe SDB.

Citation:

Yang JSC; Nicholas CL; Nixon GM; Davey MJ; Anderson V; Walker AM; Trinder JA; Horne RSC. Determining sleep quality in children with sleep disordered breathing: EEG spectral analysis compared with conventional polysomnography. SLEEP 2010;33(9):1165-1172.     

Neurobehavioral Dynamics Following Chronic Sleep Restriction: Dose-Response Effects of One Night for Recovery

Objective:

Establish the dose-response relationship between increasing sleep durations in a single night and recovery of neurobehavioral functions following chronic sleep restriction.

Design:

Intent-to-treat design in which subjects were randomized to 1 of 6 recovery sleep doses (0, 2, 4, 6, 8, or 10 h TIB) for 1 night following 5 nights of sleep restriction to 4 h TIB.

Setting:

Twelve consecutive days in a controlled laboratory environment.

Participants:

N = 159 healthy adults (aged 22-45 y), median = 29 y).

Interventions:

Following a week of home monitoring with actigraphy and 2 baseline nights of 10 h TIB, subjects were randomized to either sleep restriction to 4 h TIB per night for 5 nights followed by randomization to 1 of 6 nocturnal acute recovery sleep conditions (N = 142), or to a control condition involving 10 h TIB on all nights (N = 17).

Measurements and Results:

Primary neurobehavioral outcomes included lapses on the Psychomotor Vigilance Test (PVT), subjective sleepiness from the Karolinska Sleepiness Scale (KSS), and physiological sleepiness from a modified Maintenance of Wakefulness Test (MWT). Secondary outcomes included psychomotor and cognitive speed as measured by PVT fastest RTs and number correct on the Digit Symbol Substitution Task (DSST), respectively, and subjective fatigue from the Profile of Mood States (POMS). The dynamics of neurobehavioral outcomes following acute recovery sleep were statistically modeled across the 0 h-10 h recovery sleep doses. While TST, stage 2, REM sleep and NREM slow wave energy (SWE) increased linearly across recovery sleep doses, best-fitting neurobehavioral recovery functions were exponential across recovery sleep doses for PVT and KSS outcomes, and linear for the MWT. Analyses based on return to baseline and on estimated intersection with control condition means revealed recovery was incomplete at the 10 h TIB (8.96 h TST) for PVT performance, KSS sleepiness, and POMS fatigue. Both TST and SWE were elevated above baseline at the maximum recovery dose of 10 h TIB.

Conclusions:

Neurobehavioral deficits induced by 5 nights of sleep restricted to 4 h improved monotonically as acute recovery sleep dose increased, but some deficits remained after 10 h TIB for recovery. Complete recovery from such sleep restriction may require a longer sleep period during 1 night, and/or multiple nights of recovery sleep. It appears that acute recovery from chronic sleep restriction occurs as a result of elevated sleep pressure evident in both increased SWE and TST.

Citation:

Banks S; Van Dongen HPA; Maislin G; Dinges DF. Neurobehavioral dynamics following chronic sleep restriction: dose-response effects of one night for recovery. SLEEP 2010;33(8):1013–1026.     

Sleep Deprivation Specifically Impairs Short-term Olfactory Memory in Drosophila

Study Objectives:

Sleep is crucial to memory consolidation in humans and other animals; however, the effect of insufficient sleep on subsequent learning and memory remains largely elusive.

Design:

Learning and memory after 1-day sleep deprivation (slpD) was evaluated using Pavlovian olfactory conditioning in Drosophila, and locomotor activity was measured using the Drosophila Activity Monitoring System in a 12:12 light-dark cycle.

Results:

We found that slpD specifically impaired 1-h memory in wild type Canton-S flies, and this effect could persist for at least 2 h. However, alternative stresses (heat stress, oxidative stress, starvation, and rotation stress) did not result in a similar effect and left the flies’ memory intact. Mechanistic studies demonstrated that flies with either silenced transmission of the mushroom body (MB) during slpD or down-regulated cAMP levels in the MB demonstrated no slpD-induced 1-h memory impairment.

Conclusion:

We found that slpD specifically impaired 1-h memory in Drosophila, and either silencing of MB transmission during slpD or down-regulation of the cAMP level in the MB protected the flies from slpD-induced impairment.

Citation:

Li X; Yu F; Guo A. Sleep deprivation specifically impairs short-term olfactory memory in drosophila. SLEEP 2009;32(11):1417-1424.     

Donepezil Improves Episodic Memory in Young Individuals Vulnerable to the Effects of Sleep Deprivation

Study Objectives:

We investigated if donepezil, a long-acting orally administered cholinesterase inhibitor, would reduce episodic memory deficits associated with 24 h of sleep deprivation.

Design:

Double-blind, placebo-controlled, crossover study involving 7 laboratory visits over 2 months. Participants underwent 4 functional MRI scans; 2 sessions (donepezil or placebo) followed a normal night''s sleep, and 2 sessions followed a night of sleep deprivation.

Setting:

The study took place in a research laboratory.

Participants:

26 young, healthy volunteers with no history of any sleep, psychiatric, or neurologic disorders.

Interventions:

5 mg of donepezil was taken once daily for approximately 17 days.

Measurements and Results:

Subjects were scanned while performing a semantic judgment task and tested for word recognition outside the scanner 45 minutes later. Sleep deprivation increased the frequency of non-responses at encoding and impaired delayed recognition. No benefit of donepezil was evident when participants were well rested. When sleep deprived, individuals who showed greater performance decline improved with donepezil, whereas more resistant individuals did not benefit. Accompanying these behavioral effects, there was corresponding modulation of task-related activation in functionally relevant brain regions. Brain regions identified in relation to donepezil-induced alteration in non-response rates could be distinguished from regions relating to improved recognition memory. This suggests that donepezil can improve delayed recognition in sleep-deprived persons by improving attention as well as enhancing memory encoding.

Conclusions:

Donepezil reduced decline in recognition performance in individuals vulnerable to the effects of sleep deprivation. Additionally, our findings demonstrate the utility of combined fMRI–behavior evaluation in psychopharmacological studies.

Citation:

Chuah LYM; Chong DL; Chen AK; Rekshan WR; Tan JC; Zheng H; Chee MWL. Donepezil improves episodic memory in young individuals vulnerable to the effects of sleep deprivation. SLEEP 2009;32(8):999-1010.     

Sleep Contribution to Motor Memory Consolidation: A Motor Imagery Study

Study Objectives:

Sleep is known to enhance performance following physical practice (PP) of a new sequence of movements. Apart from a pilot study, it is still unknown whether a similar sleep-dependent consolidation effect can be observed following motor imagery (MI) and whether this mnemonic process is related to MI speed.

Design:

Counterbalanced within-subject design.

Setting:

The laboratory.

Participants:

Thirty-two participants.

Interventions:

PP, real-time MI, fast MI, and NoSleep (control) groups.

Measurements and Results:

Subjects practiced an explicitly known sequence of finger movements, and were assigned to PP, real-time MI, or fast MI, in which they intentionally imagined the sequence at a faster pace. A NoSleep group subjected to real-time MI, but without any intervening sleep, was also tested. Performance was evaluated before practice, as well as prior to, and after a night of sleep or a similar time interval during the daytime. Compared with the NoSleep group, the results revealed offline gains in performance after sleep in the PP, real-time MI, and fast MI groups. There was no correlation between a measure of underestimation of the time to imagine the motor sequence and the actual speed gains after sleep, neither between the ease/difficulty to form mental images and performance gains.

Conclusions:

These results provide evidence that sleep contributes to the consolidation of motor sequence learning acquired through MI and further suggests that offline delayed gains are not related to the MI content per se. They extend our previous findings and strongly confirm that performance enhancement following MI is sleep dependent.

Citation:

Debarnot U; Creveaux T; Collet C; Doyon J; Guillot A. Sleep contribution to motor memory consolidation: a motor imagery study. SLEEP 2009;32(12):1559-1565.     

Sleep Deprivation in Pigeons and Rats Using Motion Detection

Study Objectives:

Forced sleep deprivation results in substantial behavioral and physiologic effects in mammals. The disk-over-water (DOW) method produces a syndrome characterized by increased energy expenditure and a robust preferentially rapid-eye-movement sleep rebound upon recovery or eventual death after several weeks of sleep deprivation. The DOW has been used successfully only in rats. This paper presents a method to enforce long-term controlled sleep deprivation across species and to compare its effects in rats and pigeons.

Design and Intervention:

A conveyor was substituted for the DOW disk. Behavior rather than electroencephalography was used to trigger arousal stimuli, as in gentle-handling deprivation. Rats and pigeons were deprived using this apparatus, and the were compared with each other and with published reports.

Measurements and Results:

The physiologic consequences and recovery sleep in rats were like those published for DOW rats. Magnitude of sleep loss and recovery patterns in pigeons were similar to those seen in rats, but expected symptoms of the sleep deprivation syndrome were absent in pigeons. The use of a motion trigger allowed us to measure and, thus, to assess the quality and impact of the procedure.

Conclusion:

Prolonged and controlled sleep deprivation can be enforced using automated motion detection and a conveyor-over-water system. Pigeons and rats, deprived of sleep to the same extent, showed similar patterns of recovery sleep, but pigeons did not exhibit the hyperphagia, weight loss, and debilitation seen in rats.

Citation:

Newman SM; Paletz EM; Obermeyer WH; Benca RM. Sleep Deprivation In Pigeons And Rats Using Motion Detection. SLEEP 2009;32(10):1299-1312.     

Effects of Acute 3, 4-Methylenedioxymethamphetamine on Sleep and Daytime Sleepiness in MDMA Users: A Preliminary Study

Study Objective:

3, 4-Methylenedioxymethamphetamine (MDMA) affects monoamine neurotransmitters that play a critical role in sleep and daytime alertness. However, the acute effects of MDMA on sleep and daytime sleepiness have not been studied under placebo-controlled conditions. This study was designed to establish the effects of acute MDMA or placebo administration and sleep restriction on sleep and daytime sleepiness.

Design:

Participants with a history of MDMA use were studied on 3 sessions of 3 nights (baseline, treatment, and recovery) and 2 days (following night 2 and 3) per session. On treatment nights (night 2), participants received placebo or 2 mg/kg of MDMA or underwent a restricted bed schedule with placebo. Sleep restriction was a positive control to compare sleep loss and consequent sleepiness associated with MDMA use. The scheduled sleep period was 8 hours long on nonrestricted nights, and standard sleep recordings and daytime sleepiness tests were conducted. Age-matched controls received 1 night and day of standard sleep and daytime sleepiness testing.

Setting:

Sleep laboratory

Participants:

Seven recreational MDMA-users and 13 matched control subjects.

Measurements and Results:

Acute MDMA shortened sleep primarily by increasing sleep latency, and it reduced stage 3/4 sleep and suppressed rapid eye movement (REM) sleep. The MDMA-reduced sleep time was not associated with increased daytime sleepiness the following day, as was seen in the sleep-restriction condition. Compared with control subjects, the MDMA users on the first night in the laboratory had shorter total sleep times and less stage 3/4 sleep. Average daily sleep latency on daytime sleepiness tests the day after nighttime placebo administration was increased in MDMA users compared with the control subjects, and MDMA users had an elevated number of sleep-onset REM periods on these tests, compared with control subjects.

Conclusions:

Acute MDMA administration disrupts sleep and REM sleep, specifically, without producing daytime sleepiness such as sleep restriction does. Compared with control subjects, recreational MDMA users showed evidence of hyperarousal and impaired REM function. The mechanism behind these effects is likely due to the deleterious effects of MDMA on catecholamines.^1–3

Citation:

Randall S; Johanson CE; Tancer M; Roehrs T. Effects of acute 3, 4-methylenedioxymethamphetamine on sleep and daytime sleepiness in MDMA users: a preliminary study. SLEEP 2009;32(11):1513-1519.     

Banking Sleep: Realization of Benefits During Subsequent Sleep Restriction and Recovery

Objective:

Determine whether sleep extension (a) improves alertness and performance during subsequent sleep restriction and (b) impacts the rate at which alertness and performance are restored by post-restriction recovery sleep.

Design:

Participants were randomly assigned to an Extended (10 h time in bed [TIB]) or Habitual TIB [mean (SD) hours = 7.09 (0.7)] sleep group for one week, followed by 1 Baseline (10 hours or habitual TIB), 7 Sleep Restriction (3 h TIB), and 5 Recovery Sleep nights (8 h TIB). Performance and alertness tests were administered hourly between 08:00–18:00 during all in-laboratory phases of the study.

Setting:

Residential sleep/performance testing facility.

Participants:

Twenty-four healthy adults (ages 18–39) participated in the study.

Interventions:

Extended vs. habitual sleep durations prior to sleep restriction.

Results:

Psychomotor vigilance task (PVT) lapses were more frequent and modified maintenance of wakefulness (MWT) sleep latency was shorter in the Habitual group than in the Extended group across the sleep restriction phase. During the Recovery phase, PVT speed rebounded faster (and PVT lapsing recovered significantly after the first night of recovery sleep) in the Extended group. No group differences in subjective sleepiness were evident during any phase of the study.

Conclusion:

The extent to which sleep restriction impairs objectively measured alertness and performance, and the rate at which these impairments are subsequently reversed by recovery sleep, varies as a function of the amount of nightly sleep obtained prior to the sleep restriction period. This suggests that the physiological mechanism(s) underlying chronic sleep debt undergo long-term (days/weeks) accommodative/adaptive changes.

Citation:

Rupp TL; Wesensten NJ; Bliese PD; Balkin TJ. Banking sleep: realization of benefits during subsequent sleep restriction and recovery. SLEEP 2009;32(3):311–321.     

Paradoxical (REM) Sleep Deprivation Causes a Large and Rapidly Reversible Decrease in Long-Term Potentiation,Synaptic Transmission,Glutamate Receptor Protein Levels,and ERK/MAPK Activation in the Dorsal Hippocampus

Study Objectives:

It has been shown that wake (W) and slow wave sleep (SWS) modulate synaptic transmission in neocortical projections. However the impact of paradoxical sleep (PS) quantities on synaptic transmission remains unknown. We examined whether PS modulated the excitatory transmission and expression of glutamate receptor subtypes and phosphorylated extracellular signal-regulated kinases (p-ERK1/2).

Design:

PS deprivation (PSD) was carried out with the multiple platforms method on adult male Sprague-Dawley rats. LTP, late-LTP, and synaptic transmission were studied in the dorsal and ventral hippocampus of controls, 75-h PSD and 150-min PS rebound (PSR). GluR1 and NR1 protein and mRNA expression were evaluated by western blot and real-time PCR. P-ERK1/2 level was quantified by western blot and immunohistochemistry.

Measurement and Results:

PSD decreased synaptic transmission and LTP selectively in dorsal CA1 and PSR rescued these deficits. PSD-induced synaptic modifications in CA1 were associated with a decrease in GluR1, NR1, and p-ERK1/2 levels in dorsal CA1 without change in GluR1 and NR1 mRNA expression. Regression analysis shows that LTP is positively correlated with both PS quantities and SWS episodes duration, whereas synaptic transmission and late-LTP are positively correlated with PS quantities and negatively correlated with SWS quantities.

Conclusions:

These findings unveil previously unrecognized roles of PSD on synaptic transmission and LTP in the dorsal, but not in the ventral, hippocampus. The fact that the decrease in protein expression of GluR1 and NR1 was not associated with a change in mRNA expression of these receptors suggests that a sleep-induced modulation of translational mechanisms occurs in dorsal CA1.

Citation:

Ravassard P; Pachoud B; Comte JC; Mejia-Perez C; Scoté-Blachon C; Gay N; Claustrat B; Touret M; Luppi PH; Salin PA. Paradoxical (REM) sleep deprivation causes a large and rapidly reversible decrease in long-term potentiation, synaptic transmission, glutamate receptor protein levels, and ERK/MAPK activation in the dorsal hippocampus. SLEEP 2009;32(2):227–240.     

Effects of Modafinil on the Sleep EEG Depend on Val158Met Genotype of COMT

Study Objectives:

Modafinil may promote wakefulness by increasing cerebral dopaminergic neurotransmission, which importantly depends on activity of catechol-O-methyltransferase (COMT) in prefrontal cortex. The effects of modafinil on sleep homeostasis in humans are unknown. Employing a novel sleep-pharmacogenetic approach, we investigated the interaction of modafinil with sleep deprivation to study dopaminergic mechanisms of sleep homeostasis.

Design:

Placebo-controlled, double-blind, randomized crossover study.

Setting:

Sleep laboratory in temporal isolation unit.

Participants:

22 healthy young men (23.4 ± 0.5 years) prospectively enrolled based on genotype of the functional Val158Met polymorphism of COMT (10 Val/Val and 12 Met/Met homozygotes).

Interventions:

2 × 100 mg modafinil and placebo administered at 11 and 23 hours during 40 hours prolonged wakefulness.

Measurements and Results:

Subjective sleepiness and EEG markers of sleep homeostasis in wakefulness and sleep were equally affected by sleep deprivation in Val/Val and Met/Met allele carriers (placebo condition). Modafinil attenuated the evolution of sleepiness and EEG 5-8 Hz activity during sleep deprivation in both genotypes. In contrast to caffeine, modafinil did not reduce EEG slow wave activity (0.75-4.5 Hz) in recovery sleep, yet specifically increased 3.0-6.75 Hz and > 16.75 Hz activity in NREM sleep in the Val/Val genotype of COMT.

Conclusions:

The Val158Met polymorphism of COMT modulates the effects of modafinil on the NREM sleep EEG in recovery sleep after prolonged wakefulness. The sleep EEG changes induced by modafinil markedly differ from those of caffeine, showing that pharmacological interference with dopaminergic and adenosinergic neurotransmission during sleep deprivation differently affects sleep homeostasis.

Citation:

Bodenmann S; Landolt HP. Effects of modafinil on the sleep EEG depend on Val158Met genotype of COMT. SLEEP 2010;33(8):1027-1035.     

A Video Method to Study Drosophila Sleep

Study Objectives:

To use video to determine the accuracy of the infrared beam-splitting method for measuring sleep in Drosophila and to determine the effect of time of day, sex, genotype, and age on sleep measurements.

Design:

A digital image analysis method based on frame subtraction principle was developed to distinguish a quiescent from a moving fly. Data obtained using this method were compared with data obtained using the Drosophila Activity Monitoring System (DAMS). The location of the fly was identified based on its centroid location in the subtracted images.

Measurements and Results:

The error associated with the identification of total sleep using DAMS ranged from 7% to 95% and depended on genotype, sex, age, and time of day. The degree of the total sleep error was dependent on genotype during the daytime (P < 0.001) and was dependent on age during both the daytime and the nighttime (P < 0.001 for both). The DAMS method overestimated sleep bout duration during both the day and night, and the degree of these errors was genotype dependent (P < 0.001). Brief movements that occur during sleep bouts can be accurately identified using video. Both video and DAMS detected a homeostatic response to sleep deprivation.

Conclusions:

Video digital analysis is more accurate than DAMS in fly sleep measurements. In particular, conclusions drawn from DAMS measurements regarding daytime sleep and sleep architecture should be made with caution. Video analysis also permits the assessment of fly position and brief movements during sleep.

Citation:

Zimmerman JE; Raizen DM; Maycock MH; Maislin G; Pack AI. A video method to study drosophila sleep. SLEEP 2008;31(11):1587–1598.