The impact of sleep on complex gross‐motor adaptation in adolescents

Sleep has been shown to facilitate the consolidation of newly acquired motor memories in adults. However, the role of sleep in motor memory consolidation is less clear in children and adolescents, especially concerning real‐life gross‐motor skills. Therefore, we investigated the effects of sleep and wakefulness on a complex gross‐motor adaptation task by using a bicycle with an inverse steering device. A total of 29 healthy adolescents aged between 11 and 14 years (five female) were either trained to ride an inverse steering bicycle (learning condition) or a stationary bicycle (control condition). Training took place in the morning (wake, n = 14) or in the evening (sleep, n = 15) followed by a 9‐hr retention interval and a subsequent re‐test session. Slalom cycling performance was assessed by speed (riding time) and accuracy (standard deviation of steering angle) measures. Behavioural results showed no evidence for sleep‐dependent memory consolidation. However, overnight gains in accuracy were associated with an increase in left hemispheric N2 slow sleep spindle activity from control to learning night. Furthermore, decreases in REM and tonic REM duration were related to higher overnight improvements in accuracy. Regarding speed, an increase in REM and tonic REM duration was favourable for higher overnight gains in riding time. Thus, although not yet detectable on a behavioural level, sleep seemed to play a role in the acquisition of gross‐motor skills. A promising direction for future research is to focus on the possibility of delayed performance gains in adolescent populations.     

Slow Wave Sleep and REM Sleep Awakenings Do Not Affect Sleep Dependent Memory Consolidation

Study Objectives:

The effects of REM sleep and slow wave sleep (SWS) deprivation on sleep-dependent motor and declarative memory consolidation.

Design:

Randomized, within-subject, cross-over study

Setting:

Weekly (women: monthly) sleep laboratory visits, with retest 60 hours later

Participants:

Twelve healthy subjects (6 men) aged between 20 and 30 years

Interventions:

REM sleep deprivation, SWS deprivation, or undisturbed sleep

Measurements and Results:

We deprived subjects once each of REM sleep and SWS, and once let them sleep undisturbed through the night. After each night, we tested declarative and procedural memory consolidation. We tested memory performance by a verbal paired associate task and a sequential finger-tapping task at 21:00 on the study night and again 60 hours later. Although REM sleep and SWS awakenings led to a significant reduction of the respective sleep stages, memory consolidation remained unaffected. We also found a significant correlation between the declarative task and sleep spindles in the undisturbed condition, especially the sleep spindles in the first third of the night.

Conclusion:

We suggest that word-pair learning relies on stage 2 sleep spindles and requires little SWS. Their sleep dependent consolidation is not affected by SWS deprivation. Simple motor tasks may either be consolidated in stage 2 sleep or depend on only small amounts of REM sleep. Their sleep dependent consolidation is not influenced by REM sleep deprivation.

Citation:

Genzel L; Dresler M; Wehrle R; Grözinger M; Steiger A. Slow wave sleep and REM sleep awakenings do not affect sleep dependent memory consolidation. SLEEP 2009;32(3):302–310.     

Sleep-dependent motor memory plasticity in the human brain

Growing evidence indicates a role for sleep in off-line memory processing, specifically in post-training consolidation. In humans, sleep has been shown to trigger overnight learning on a motor-sequence memory task, while equivalent waking periods produce no such improvement. But while the behavioral characteristics of sleep-dependent motor learning become increasingly well characterized, the underlying neural basis remains unknown. Here we present functional magnetic resonance imaging data demonstrating a change in the representation of a motor memory after a night of sleep. Subjects trained on a motor-skill memory and 12 hours later, after either sleep or wake, were retested during functional magnetic resonance imaging. Following sleep relative to wake, regions of increased activation were expressed in the right primary motor cortex, medial prefrontal lobe, hippocampus and left cerebellum; changes that can support faster motor output and more precise mapping of key-press movements. In contrast, signal decreases were identified in parietal cortices, the left insular cortex, temporal pole and fronto-polar region, reflecting a reduced need for conscious spatial monitoring and a decreased emotional task burden. This evidence of an overnight, systems-level change in the representation of a motor memory holds important implications for acquiring real-life skills and in clinical rehabilitation following brain trauma, such as stroke.     

Twenty-four hours retention of visuospatial memory correlates with the number of parietal sleep spindles

Recent evidence suggests that the sleep-dependent consolidation of declarative memories relies on the non-rapid eye movement (NREM) rather than the rapid eye movement (REM) phase of sleep. Moreover, a few studies both at the cellular and the behavioural levels have suggested the involvement of sleep spindles, the most synchronous oscillatory waveforms during NREM sleep stage 2, in this process. Our previous study showed that overnight verbal memory retention correlates with the total number of sleep spindles in left frontocentral areas, while spindling in other regions did not correlate with mnemonic retention. In the present study, we show that retention of visuospatial memories over a 24-h period correlates with the total number of sleep spindles detected over parietal regions during the intervening night-time sleep. This result provides further evidence for the association between sleep spindle activity and declarative memory consolidation, and suggests that visuospatial and verbal memory retention differ in the topographic distribution of the NREM spindle activity with which they are associated.     

Consolidation of temporal order in episodic memories

Even though it is known that sleep benefits declarative memory consolidation, the role of sleep in the storage of temporal sequences has rarely been examined. Thus we explored the influence of sleep on temporal order in an episodic memory task followed by sleep or sleep deprivation. Thirty-four healthy subjects (17 men) aged between 19 and 28 years participated in the randomized, counterbalanced, between-subject design. Parameters of interests were NREM/REM cycles, spindle activity and spindle-related EEG power spectra. Participants of both groups (sleep group/sleep deprivation group) performed retrieval in the evening, morning and three days after the learning night. Results revealed that performance in temporal order memory significantly deteriorated over three days only in sleep deprived participants. Furthermore our data showed a positive relationship between the ratios of the (i) first NREM/REM cycle with more REM being associated with delayed temporal order recall. Most interestingly, data additionally indicated that (ii) memory enhancers in the sleep group show more fast spindle related alpha power at frontal electrode sites possibly indicating access to a yet to be consolidated memory trace. We suggest that distinct sleep mechanisms subserve different aspects of episodic memory and are jointly involved in sleep-dependent memory consolidation.     

Sleepiness/alertness on a simulated night shift following sleep at home with triazolam

Physiological sleep tendency during a simulated night shift schedule was examined in 15 middle-aged subjects following daytime sleep after administration of triazolam or placebo. A double-blind, counterbalanced, crossover design involving two tours of five laboratory nights and four daytime home sleep periods was used. Triazolam lengthened daytime sleep as measured by wrist actigraph and improved nighttime alertness as measured by the MSLT. Sleepiness was most profound during the early morning hours (0430 to 0630) but improved significantly across nights for both conditions. Repeated test of sustained wakefulness latencies and simulated assembly line task performance decreased slightly across the night, but there were no significant condition effects. Subjective data tended to support objective measures, although Stanford Sleepiness Scale ratings indicated that subjects did not perceive improved alertness at night after triazolam-aided daytime sleep.     

Sleep modulates word-pair learning but not motor sequence learning in healthy older adults

Sleep benefits memory across a range of tasks for young adults. However, remarkably little is known of the role of sleep on memory for healthy older adults. We used 2 tasks, 1 assaying motor skill learning and the other assaying nonmotor/declarative learning, to examine off-line changes in performance in young (20-34 years), middle-aged (35-50 years), and older (51-70 years) adults without disordered sleep. During an initial session, conducted either in the morning or evening, participants learned a motor sequence and a list of word pairs. Memory tests were given twice, 12 and 24 hours after training, allowing us to analyze off-line consolidation after a break that included sleep or normal wake. Sleep-dependent performance changes were reduced in older adults on the motor sequence learning task. In contrast, sleep-dependent performance changes were similar for all 3 age groups on the word pair learning task. Age-related changes in sleep or networks activated during encoding or during sleep may contribute to age-related declines in motor sequence consolidation. Interestingly, these changes do not affect declarative memory.     

Selective effects of triazolam on memory for emotional,relative to neutral,stimuli: differential effects on gist versus detail

Benzodiazepines are known to reduce learning and memory performance, presumably through their facilitation of GABAergic neurotransmission, but the effects of these drugs specifically on memory for emotional material has not been addressed in humans. The effects of a benzodiazepine (triazolam, 0.25 mg) on nonincidental memory for emotional stimuli were assessed in 20 healthy volunteers (10 female). Triazolam reduced the normally facilitative effect of emotion on memory. The drug specifically affected memory for the gist of stimuli while leaving detail memory relatively unaffected. This pattern of performance is similar to that seen in patients with amygdala damage. Results suggest an effect of GABAergic neurotransmission at the level of the amygdala on memory modulation.     

Pathophysiology of sleep-dependent memory consolidation processes in children

Cognitive impairments are often associated with abnormal sleep activity in developmental disorders and pathologies of childhood. Besides, accumulated evidence indicates that post-training sleep benefits to the consolidation of recently learned information in healthy adults and children. Although sleep-dependent consolidation effects in children are clearly established for declarative memories, they remain more debated in the procedural memory domain. Nowadays, recent experimental data suggest close interactions between the development of sleep-dependent plasticity markers, cortical maturation and cognition in children. In the present review, we propose that studying sleep and memory consolidation processes in developmental disorders and acquired childhood pathologies can provide novel, enlightening clues to understand the pathophysiological mechanisms subtending the disruption of long-term cerebral plasticity processes eventually leading to cognitive and learning deficits in children.     

Neurotoxic lesions of phasic pontine-wave generator cells impair retention of 2-way active avoidance memory

STUDY OBJECTIVES: The aim of this study was to test the hypothesis that the activation of pontine (P)-wave generator is critical for the posttraining rapid eye movement (REM) sleep-dependent memory processing. DESIGN: Ibotenic acid was microinjected (0.5 microg in 0.05 microL) into the functionally identified P-wave generator in order to destroy the cell bodies and thus to study the effects of their destruction upon waking-sleep states, P-waves, and 2-way active avoidance memory. SETTING: Sleep research laboratory at Boston University School of Medicine. PARTICIPANTS: Adult male Sprague-Dawley rats (N = 27). INTERVENTIONS: Chronically implanted for recording polygraphic signs of sleep and bilateral guide tubes for the local microinjections into the P-wave generator. MEASUREMENTS AND RESULTS: The ibotenic acid produced a small spherical area (< or = 0.35 mm in diameter) of nerve cell loss centered on the P-wave generator. Bilateral lesioning of the P-wave generator decreased P-waves during REM sleep by > 95% without significantly changing the amounts of time spent in wake, slow-wave sleep, or REM sleep. In these P-wave generator-lesioned rats, acquisition of avoidance learning and posttraining wake-sleep changes were identical to those of the sham-lesioned rats. However, in the test trials, after 6 hours of undisturbed sleep-wake, P-wave generator-lesioned rats had no retention of avoidance memory. CONCLUSIONS: These findings, for the first time, provide direct evidence that P-wave-generating cells are critical for normal REM sleep-dependent memory processing. This evidence supports our hypothesis that the P-wave generator in the brainstem may act as an on switch to provide activating input to forebrain structures for sleep-dependent memory processing.     

REM-dependent repair of competitive memory suppression

Memories are enhanced during sleep through memory consolidation processes. A recent study reported that sleep increases competitive forgetting in the absence of sleep-dependent consolidation of the target memory (Racsmany et al. in Psychol Sci 21:80–85, 2010). Here, using a modified retrieval-induced forgetting task, we examined whether sleep-dependent modulation of forgetting occurs concurrently with the consolidation of related target memories. Participants encoded a word-pair list and then practiced retrieving a portion of these pairs. Following a break with sleep or wake, recall of all pairs was tested. As expected, recall for practiced pairs was greater following sleep relative to wake. Contrary to Racsmany et al. (Psychol Sci 21:80–85, 2010), competitive forgetting decreased following sleep. Moreover, recall for practiced pairs correlated with slow wave sleep (SWS) while forgetting of competing targets correlated negatively with REM, suggesting a novel function of these sequential brain states on memory processing.     

Effects of the short-acting benzodiazepine triazolam, taken at bedtime, on circadian and sleep-related hormonal profiles in normal men

Studies in rodents have shown that triazolam, a commonly used hypnotic, may shift circadian rhythms, with the direction and magnitude of the phase-shifts being dependent on the time of drug administration. To determine whether benzodiazepine, taken at standard bedtime, modifies the amount and/or temporal organization of hormonal secretion, six normal men were studied during basal conditions and on the first and third days of treatment with 0.5 mg triazolam. In each study, sleep was polygraphically monitored and plasma cortisol, growth hormone (GH), melatonin, and prolactin (PRL) (i.e., hormones influenced by circadian rhythmicity and/or sleep) were measured at 20-min intervals for 24 h. The sleep latency and the number and duration of awakenings were reduced during triazolam treatment as compared to baseline conditions. The only alteration of sleep architecture was a partial suppression of stages III + IV (SW) in late sleep. Triazolam did not affect the mean cortisol and melatonin levels or the total amount of GH secreted over the 24-h span. The circadian timings of the onsets of cortisol and melatonin secretions were essentially unaltered. The nocturnal rise of melatonin was prolonged by 45 to 60 minutes. Sleep-associated GH release was not modified by triazolam. Sleep-associated PRL secretion persisted, but in half of the nights studied was enhanced almost threefold. This effect of the drug on nocturnal PRL secretion was not specific to either the first or the third night of treatment, nor was it specific to certain subjects. Irrespective of the magnitude of the nocturnal elevation, morning PRL levels were slightly but consistently higher after triazolam treatment than under basal conditions. Normal PRL levels resumed around noon. In conclusion, administration of 0.5 mg triazolam at normal bedtime (2230) for three consecutive days may induce a transient hyperprolactinemia, but does not abolish sleep-related hormone secretion and does not affect the timing of endocrine events controlled by the circadian clock. These findings are consistent with studies in hamsters where treatment with triazolam in the early subjective night was also without effect on the rodent circadian clock.     

Effect of gradual withdrawal on the rebound sleep disorder after discontinuation of triazolam

Sixty volunteers with insomnia participated in a randomized, double-blind, controlled clinical trial. After an initial six nights of placebo, 30 subjects (the abrupt-withdrawal group) received 0.5 mg of triazolam nightly for 7 to 10 nights, after which they received placebo. The other 30 subjects (the tapered-dosage group) received the same initial placebo treatment, then triazolam at 0.5 mg for seven nights, at 0.25 mg for two nights, and at 0.125 mg for two nights, and then placebo. As compared with the initial placebo period, the triazolam period significantly reduced the interval before the onset of sleep (sleep latency), and it prolonged sleep duration, reduced the number of awakenings, and improved the self-rated soundness of sleep in all cohorts. In the abrupt-withdrawal group, plasma levels of triazolam were undetectable the morning after the first night of placebo substitution, and subjects reported prolongation of sleep latency (57 minutes longer than base line), reduction in sleep duration (1.4 hours less than base line), and increased awakenings (1.2 per night above base line). The symptoms of rebound sleep disorder lasted one or possibly two nights, and there was a reversion toward base line on subsequent placebo nights. In the tapered-dosage group, however, plasma triazolam levels fell gradually to zero, and rebound symptoms were decreased or eliminated. Thus, rebound sleep disorder following abrupt discontinuation of triazolam can be attenuated by a regimen of tapering.     

Biperiden administration during REM sleep deprivation diminished the frequency of REM sleep attempts.

Sixteen subjects were assigned to a group using either placebo or biperiden, with eight subjects in each group. Both groups were studied for one acclimatization night, one baseline night, four nights of rapid eye movement (REM) sleep deprivation and two recovery nights. All the subjects received either placebo or 4 mg biperiden 1 hour before sleep during the four nights of REM sleep deprivation. During the baseline and the recovery nights both groups received placebo capsules. The results showed that REM sleep time during the REM sleep deprivation was reduced by 70-75% below the baseline night in both groups. The number of attempts to enter REM sleep was significantly reduced by biperiden as compared to placebo for each of the four REM sleep deprivation nights. Because the total sleep time in the biperiden group was reduced, the number of REM sleep attempts was corrected by the total sleep time. The adjusted number of REM sleep attempts was also significantly reduced in the biperiden group. REM sleep latency showed a reduction in the placebo group, whereas in the biperiden group REM sleep latency was unchanged throughout the deprivation nights. In the recovery night REM sleep time was increased in both groups, with no differences between the groups. The REM sleep latency showed a reduction in the first recovery night in both groups that persisted through the second recovery night. The above findings support the role of biperiden as a REM sleep suppressive drug.     

Effect of emotional and neutral declarative memory consolidation on sleep architecture

The relationship between emotional or neutral declarative memory consolidation and sleep architecture was investigated. Thirty university students (21 females) viewed negative, neutral, or positive pictures and rated their valence and arousal in the evening. Participants performed a recognition test 1 h later and then underwent overnight polysomnography. Their post-encoding sleep architecture was compared to a baseline night. Participants returned 6 days following encoding for a second recognition test. Results showed no group (Negative, Neutral, Positive) differences in recognition 1 h or 6 days following encoding. Stage 2 sleep spindle density decreased across all groups following encoding, and recognition after 6 days was positively correlated with Stage 2 sleep spindle density on both nights. There was no change in REM density in any of the groups. This is the first investigation into phasic sleep microarchitecture changes following emotional and neutral declarative learning. Future investigations may benefit from more salient emotional stimuli.     

Short-term triazolam use improves nocturnal sleep of narcoleptics.

This study was undertaken to determine whether the use of triazolam by narcoleptic patients leads to improvement of nighttime sleep or excessive sleepiness. Ten narcoleptic patients, 5 males and 5 females, with complaints of sleep disturbance and aged between 18 and 60 years, were assigned to a single-blind within-subject crossover-designed study comparing placebo with 0.25 mg triazolam. All subjects completed sleep questionnaires and underwent 6 nights of polysomnographic testing. Following an adaptation night, subjects received either triazolam or placebo for 2 nights. Objective tests of sleepiness (multiple sleep latency testing/maintenance of wakefulness test) were performed. Sleep efficiency and overall sleep quality were improved on all triazolam nights. Daytime excessive sleepiness was not reduced objectively after triazolam. This study demonstrates that the short-term use of triazolam improves nocturnal sleep quality in narcoleptics. Studies of long-term administration of triazolam are required to determine if the improvement of nocturnal sleep is maintained.     

Naps reliably estimate nocturnal sleep spindle density in health and schizophrenia

Sleep spindles, defining oscillations of non‐rapid eye movement stage 2 sleep (N2), mediate memory consolidation. Spindle density (spindles/minute) is a stable, heritable feature of the sleep electroencephalogram. In schizophrenia, reduced spindle density correlates with impaired sleep‐dependent memory consolidation and is a promising treatment target. Measuring sleep spindles is also important for basic studies of memory. However, overnight sleep studies are expensive, time consuming and require considerable infrastructure. Here we investigated whether afternoon naps can reliably and accurately estimate nocturnal spindle density in health and schizophrenia. Fourteen schizophrenia patients and eight healthy controls had polysomnography during two overnights and three afternoon naps. Although spindle density was lower during naps than nights, the two measures were highly correlated. For both groups, naps and nights provided highly reliable estimates of spindle density. We conclude that naps provide an accurate, reliable and more scalable alternative to measuring spindle density overnight.     

Effects of body heating during sleep interruption

This study assessed the effects that elevating body temperature had on sleep structure in the third and fourth sleep cycles, cycles typically characterized by a high propensity for REM sleep and diminished levels of delta amplitude and incidence. The sleep of eight women and two men was interrupted for 30 min on each of 3 consecutive nights following an undisturbed adaptation night. The subjects were awakened each night following the end of the second REM sleep period. On 2 nights, subjects were immersed to midthorax in water at either 34 degrees C (TW condition) or 41 degrees C (HW condition) for 20 min. A third interruption without immersion (NW condition) was performed to provide a second type of baseline condition. The HW condition induced a mean tympanic temperature rise of 2.5 degrees C, that returned to baseline levels in approximately 60 min. Analysis of sleep patterns focused on the two sleep cycles following interruption. The mean of the two baseline conditions (TW + NW/2) was compared with the HW condition. Sleep onset latency, REM latency, REM duration, and eye movement activity in REM were unaffected by heating. Heating evoked increases in both total NREM and slow wave sleep, though these increases were delayed until the second cycle following sleep onset (i.e., appearing in the fourth, but not the third, NREM period). These were paralleled by increases in two objective measures of delta activity: integrated slow-wave amplitude (33% increase) and slow-wave density (10% increase).     

Effects of lorazepam on short latency afferent inhibition and short latency intracortical inhibition in humans

Experimental studies have demonstrated that the GABAergic system modulates acetylcholine release and, through GABA_A receptors, tonically inhibits cholinergic activity. Little is known about the effects of GABA on the cholinergic activity in the human central nervous system. In vivo evaluation of some cholinergic circuits of the human brain has recently been introduced using a transcranial magnetic stimulation (TMS) protocol based on coupling peripheral nerve stimulation with TMS of the motor cortex. Peripheral nerve inputs have an inhibitory effect on motor cortex excitability at short intervals (short latency afferent inhibition, SAI). We investigated whether GABA_A activity enhancement by lorazepam modifies SAI. We also evaluated the effects produced by lorazepam on a different TMS protocol of cortical inhibition, the short interval intracortical inhibition (SICI), which is believed to be directly related to GABA_A activity. In 10 healthy volunteers, the effects of lorazepam were compared with those produced by quetiapine, a psychotropic drug with sedative effects with no appreciable affinity at cholinergic muscarinic and benzodiazepine receptors, and with those of a placebo using a randomized double-blind study design. Administration of lorazepam produced a significant increase in SICI  ( F _3,9= 3.19, P = 0.039)  . In contrast to SICI, SAI was significantly reduced by lorazepam  ( F _3,9= 9.39, P = 0.0002)  . Our findings demonstrate that GABA_A activity enhancement determines a suppression of SAI and an increase of SICI.     

Transdermal scopolamine alters phasic REM activity in normal young adults.

Transdermal scopolamine has been widely used for the prevention of motion-sickness by travelers due to its potent anticholinergic effects and the ease of administration. Nevertheless, its effects on sleep physiology are not known, despite the wellknown fact that the administration of scopolamine as an injection or an oral form could influence the sleep architecture, especially prolonging rapid eye movement (REM) sleep latency and shortening duration of REM sleep. This study aimed to measure the influence of transdermal scopolamine on REM sleep in order to examine whether it affects REM sleep as in the previous studies. We studied eight young healthy male adults polysomnographically for three nights including one adaptation night in a double blind crossover design and compared REM sleep-related variables between sleeps with and without scopolamine patch of 1.5 mg. We found no differences in tonic REM sleep measures such as REM duration and REM latency, but phasic REM sleep measures such as total REM activity (p < 0.05) and total REM density (p < 0.05) were significantly suppressed by the transdermal scopolamine; REM densities of the first (p < 0.05) and the second (p < 0.05) REM sleep periods as well as REM activity of the fourth REM sleep period (p < 0.05) were decreased significantly on the scopolamine patch nights compared with placebo patch nights. These results suggest that phasic REM components reflect cholinergic mechanism in the central nervous system (CNS) even at the lowest commercial dose, and could be useful markers of CNS cholinergic activities in the future research.