Corticospinal excitability and sleep: a motor threshold assessment by transcranial magnetic stimulation after awakenings from REM and NREM sleep

Transcranial magnetic stimulation (TMS) is a recently established technique in the neurosciences that allows the non-invasive assessment, among other parameters, of the excitability of motor cortex. Up to now, its application to sleep research has been very scarce and because of technical problems it provided contrasting results. In fact delivering one single suprathreshold magnetic stimulus easily awakes subjects, or lightens their sleep. For this reason, in the present study we assessed motor thresholds (MTs) upon rapid eye movement (REM) and non-rapid eye movement (NREM) sleep awakenings, both in the first and in the last part of the night. Taking into account that a full re-establishment of wake regional brain activity patterns upon awakening from sleep needs up to 20-30 min, it is possible to make inferences about the neurophysiological characteristics of the different sleep stages by analyzing the variables of interest immediately after provoked awakenings. Ten female volunteers slept in the lab for four consecutive nights. During the first night the MTs were collected, following a standardized procedure: 5 min before lights off, upon stage 2 awakening (second NREM period), upon REM sleep awakening (second REM period), upon the final morning awakening (always from stage 2). Results showed that MTs increased linearly from presleep wakefulness to REM sleep awakenings, and from the latter to stage 2 awakenings. There was also a time-of-night effect on MTs upon awakening from stage 2, indicating that MTs decreased from the first to the second part of the night. The increase in corticospinal excitability across the night, which parallels the fulfillment of sleep need, is consistent with the linear decrease of auditory arousal thresholds during the night. The maximal reduction of corticospinal excitability during early NREM sleep can be related to the hyperpolarization of thalamocortical neurons, and is in line with the decreased metabolic activity of motor cortices during this sleep stage. On the contrary, the increase of MTs upon REM sleep awakenings should reflect peripheral factors. We conclude that our findings legitimate the introduction of the TMS technique as a new proper tool in sleep research.     

Cortico-motoneurone excitability in patients with obstructive sleep apnoea

A disordered neuromotor control of pharynx muscles may play a role in the genesis of obstructive sleep apnoea syndrome (OSAS). This raises the possibility of a dysfunction of projections descending from the cortex to segmental nuclei. With single pulse transcranial magnetic stimulation (TMS) we studied the physiology of the corticospinal projection to hand muscles in seven OSAS patients. At first, we compared them with nine age- and sex-matched normal controls in the wake state. The only abnormality was a lengthening of the central silent period (P < 0.001). This supports a steady imbalance of motor cortical interneurone activities towards a state of enhanced inhibition. Then we looked at changes of the motor-evoked potential (MEP) size and latency, according to whether patients were awake, or in a non-rapid eye movement (REM) 2 sleep stage, or during a typical apnoea. During non-REM 2 sleep, the average MEP amplitude was significantly (P < 0.05) smaller than in the awake state. The MEP latency was, in turn, significantly longer (P < 0.05). During apnoeas, the MEP size decreased, and the latency increased further (P < 0.05), indicating an extra depression of the cortico-motoneuronal activity. All TMS changes were detected outside the pharyngeal district, suggesting a widespread dysfunction of the cortico-motoneuronal system in the OSAS, which is more evident during apnoeas.     

The effect of time of day on apnoea index in the sleeping rat

This study tested the hypothesis that apnoea index would be greater during daytime sleep than nighttime sleep in the rat. Electroencephalogram and electromyogram were monitored via biotelemetry implant and respiration was measured using whole body plethysmography in six male rats in two separate 34h recording sessions per animal. Apnoeas were classified as "spontaneous" or "post-sigh". Daily average spontaneous apnoea index was 35 times greater (p<0.0001) during rapid eye movement (REM) sleep than in non-REM (NREM) sleep. In contrast, daily average post-sigh apnoea index was not significantly greater in REM sleep than in non-REM (NREM) sleep (p=0.39). There was a greater post-sigh apnoea index during daytime REM than during nighttime REM (p=0.043) but REM-related spontaneous apnoea index was unaffected by time of day. There was no day to night difference in spontaneous apnoea index or post-sigh apnoea index during NREM sleep. Respiratory variability (coefficient of variation for breath duration and tidal volume) was not affected by time of day in REM or NREM sleep. We conclude that the circadian timing system has no effect on apnoea index during NREM sleep in the rat, but it may influence the propensity for post-sigh apnoea during REM sleep.     

SPONTANEOUS ELECTRODERMAL ACTIVITY DURING WAKING AND SLEEPING

Spontaneous electrodermal activity (EDA) (galvanic skin response [GSR] and skin potential response [SPR]) was recorded during daytime sleep and nighttime sleep. During all sleep, spontaneous EDA occurred most frequently during stages 3 and 4 (slow wave sleep) and least frequently during stage 1 (rapid eye movement [REM] and non-REM). This pattern was consistent over 3 nights of sleep. There was no relation between waking and sleeping spontaneous EDA. The spontaneous EDA during slow wave sleep significantly exceeded that during waking. During sleep, spontaneous SPRs often occurred without spontaneous GSRs.     

Effects of nighttime nap and age on sleep patterns of shift workers

The effects of nighttime nap and age on sleep patterns of shift workers were examined for two groups of young and older guards working a 24-h shift with a nighttime nap of approximately 3.2 h. For both groups, day sleep was reduced by approximately 4.1 h, mainly affecting stage 2 sleep, slow wave sleep (SWS), and REM sleep. The totals of the different sleep stages of the nighttime nap plus day sleep were shorter than those of the control night only in stage 2 sleep. The nighttime nap appears to compensate for the sleep loss caused by night duty. During day sleep, the older subjects had relatively more awakenings and stage shifts. In the older group, the acrophase of oral temperature exhibited a significant phase advance of circadian rhythm, with reductions of means in the mesor and amplitude. Morningness-eveningness questionnaires tended to show higher scores (morningness) for the older group. From these results, it was determined that for older workers, an aberration in the phase of the circadian rhythm would slightly increase the difficulty of day sleep following night duty.     

Effects of sleep fragmentation on the arousability to resistive loading in NREM and REM sleep in normal men

STUDY OBJECTIVE: In healthy subjects, arousability to inspiratory resistive loading is greater during rapid eye movement (REM) sleep compared with non-REM (NREM) sleep but is poorest in REM sleep in patients with sleep apnea. We therefore examined the hypothesis that sleep fragmentation impairs arousability, especially from REM sleep. DESIGN: Two blocks of 3 polysomnographies (separated by at least 1 week) were performed randomly. An inspiratory-loaded night followed either 2 undisturbed control nights (LN(C)) or 2 acoustically fragmented nights (LN(F)) SETTING: Sleep laboratory. PARTICIPANTS: Sixteen healthy men aged 20 to 29 years. INTERVENTIONS: In both loaded nights, an inspiratory resistive load was added via a valved facemask every 2 minutes during sleep and turned off either when arousal occurred or after 2 minutes. MEASUREMENTS AND RESULTS: During LN(F), arousability remained significantly greater in REM sleep (71% aroused within 2 minutes) compared with stage 2 (29%) or stage 3/4 (16%) sleep. After sleep fragmentation, arousability was decreased in stage 2 sleep (LN(F): 29%; LN(C): 38%; p < .05) and low in early REM sleep, increasing across the night (p < .01). In stage 3/4 sleep, neither an attenuation nor a change across the night was seen after sleep fragmentation. CONCLUSIONS: Mild sleep fragmentation is already sufficient to attenuate arousability in stage 2 sleep and to decrease arousability in early, compared with late, REM sleep. This means that sleep fragmentation affects the arousal response to increasing resistance and that the effects are different in stage 2 and REM sleep. The biologic reason for this increase in the arousal response in REM sleep across the night is not clear.     

Spontaneous eyelid movements (ELMS) during sleep are related to dream recall on awakening

The present study aimed to test whether spontaneous eyelid movements (ELMs) during stage 2 and rapid eye movement (REM) sleep are related to more frequent and vivid reports of visual mentation on awakening. Participants were awakened 15 s after an ELM was observed during ongoing REM and stage 2 sleep and immediately asked for a mentation report and to rate the visual vividness of any imagery they could remember. These reports were compared with control reports collected after a period of ELM quiescence before awakening (noELM). Significantly greater frequencies of imagery reports were collected after ELM awakenings compared with noELM awakenings from stage 2, but not REM sleep. When imagery was reported, imagery ratings were not significantly different between ELM and noELM conditions, regardless of sleep stage. The average amount of electroencephalogram (EEG) arousal 15 s after stage 2 awakenings was significantly higher in the ELM compared with noELM conditions. In addition, within the stage 2 ELM condition, EEG arousal was significantly higher when visual imagery was reported compared with reports without imagery; suggesting that the observed increase in imagery reporting from the stage 2 ELM condition could have been mediated by the level of brain arousal. Such arousal possibly provides better conditions to attend and recall previous mental activity from NREM sleep. However, there was no ELM/arousal effect within REM sleep, possibly because this state is already at maximum sleeping levels of arousal, attention and resulting dream recall.     

Sleepiness and REM Sleep Recurrence: The Effects of Stage 2 and REM Sleep Awakenings

Determinants of daytime sleepiness include sleep length, sleep continuity, and circadian factors. Sleep stage composition has not been seen as influencing subsequent daytime functioning; however, earlier studies did not focus explicitly on sleepiness. The present experiment studied the effects of selective sleep-stage restriction on an objective measure of sleep tendency, and explored the relationship between sleepiness and subsequent REM recurrence during REM deprivation. Daytime sleep latency was measured by a modified Multiple Sleep Latency Test prior to and following two nights of awakenings from either REM or Stage 2 sleep in 16 normal young adults. Sleep latency following these awakenings was also measured. REM sleep and Stage 2 awakenings produced comparable levels of sleepiness, both during the Awakening Nights and subsequent daytime Multiple Sleep Latency Testing. Pooling the groups, daytime and nocturnal sleepiness measures were correlated within individuals. In the REM-Awakening Group, Pre-Awakening daytime sleepiness was associated with the tendency for REM sleep to recur following experimental awakenings. Comparable levels of sleepiness may result from nonspecific processes such as sleep curtailment and fragmentation, or alternatively from separate REM and Stage 2 mechanisms. The relationship between REM sleep and sleepiness is discussed in the context of both state and trait models.     

Administration of the protein synthesis inhibitor, anisomycin, has distinct sleep-promoting effects in lateral preoptic and perifornical hypothalamic sites in rats

Although a robust relationship between sleep and increased brain protein synthesis is well-documented, there have been few reports of the effects of local application of a protein synthesis inhibitor (PSI) on sleep. In this study, we compared the effects of local microdialytic administration of the protein synthesis inhibitor, anisomycin (ANI) into the lateral preoptic area (LPOA), a sleep promoting area vs. the perifornical/lateral hypothalamus (PF/LH), a wake and rapid eye movement (REM) sleep-promoting area. ANI administered to the LPOA at night resulted in an increase in stage 2 of rat non-REM sleep, whereas ANI delivered into the PF/LH during the daytime increased REM sleep. ANI microdialysis into hippocampus did not affect sleep or waking. These differential effects of local protein synthesis inhibition on sleep support a hypothesis that mechanisms controlling protein synthesis are critically involved in the regulation of both NREM sleep and REM sleep.     

Corticospinal excitability in human subjects during nonrapid eye movement sleep: single and paired-pulse transcranial magnetic stimulation study

The mechanisms responsible for changes in brain function during normal sleep are poorly understood. In this study, we aimed to investigate the effects of sleep on human corticospinal excitability by estimating resting motor threshold (RMT), and latency and amplitude of motor-evoked potentials (MEPs) after delivering transcranial magnetic stimulation (TMS) in ten healthy subjects. We also aimed to study short-interval intracortical inhibition (SICI) during sleep with paired-pulse TMS (pp-TMS). Ten healthy volunteers were studied. They were monitored immediately before, during and after a 3-h sleep (from 1 p.m. to 4 p.m., immediately after the mid-day meal). EEG was continuously recorded during sleep and the various sleep stages were identified off line. Every 10 min, subjects received ten single stimuli (to estimate RMT, MEP latency and amplitude) and six paired stimuli (to estimate SICI). MEP amplitude decreased and latency and RMT increased during the various sleep stages and returned to baseline values on awakening. Post hoc comparisons showed a significant difference in pp-TMS MEP amplitudes between the sleep and all the other conditions. The changes in TMS evoked variables during the different sleep stages indicate that during nonrapid eye movement sleep, cortical pyramidal neuron excitability (as measured by RMT, MEP latency and amplitude) progressively diminishes and the efficiency of the intracortical GABA-ergic network (as assessed by three pp-TMS) increases. On awakening, these sleep-induced changes in corticospinal excitability return rapidly to values observed during wakefulness.     

Sleep inertia varies with circadian phase and sleep stage in older adults

The purpose of our analysis was to determine if older adults show sleep inertia effects on performance at scheduled wake time, and whether these effects depend on circadian phase or sleep stage at awakening. Using the Digit Symbol Substitution Test, effects of sleep inertia on performance were assessed over the first 30 min after wake time on baseline days and when sleep was scheduled at different circadian phases. Mixed model analyses revealed that performance improved as time awake increased; that beginning levels of performance were poorest when wake time was scheduled to occur during the biological night; and that effects of sleep inertia on performance during the biological night were greater when awaking from non-REM (NREM) sleep than from REM sleep. Based on our current understanding of sleep inertia effects in young subjects, and previous reports that older subjects awaken at an earlier circadian phase and are more likely to have their final awakening from NREM sleep than younger adults, our findings suggest older adults may be more vulnerable to sleep inertia effects than young adults.     

The effects of slow-wave sleep (SWS) deprivation and time of night on behavioral performance upon awakening

The aim of the present study is to evaluate the effects of selective SWS deprivation on the motor and sensory motor performance impairment immediately after awakening from nocturnal sleep at different times of the night. Ten normal males slept for 6 consecutive nights in the laboratory: one adaptation, two baseline, two selective SWS deprivation, and one recovery night. During the last 4 nights performance was assessed four times: (a) before sleep, as a baseline measure; (b) within 30 s from the first nighttime awakening, after 2 h of sleep; (c) within 30 s from the second nighttime awakening, after 5 h of sleep; (d) within 30 s from the final morning awakening. After each awakening, following a 3-min cognitive test, a simple Auditory Reaction Time task (ART, about 5 min) and a Finger Tapping Task (FTT, 3 min) were administered. Median of Reaction Times (RT) and of Intertapping Intervals (ITI), 10% fastest RT, 10% slowest RT, and number of misses were considered as dependent variables. The selective SWS deprivation was very effective: SWS percentage during both the deprivation nights was close to zero. This strong manipulation of SWS amount interacted with time-of-night factors in influencing sleep inertia. The SWS deprivation procedure caused a worsening of behavioral performance during the deprivation nights. as well as upon the final awakening of the recovery night. Behavioral performance slowing upon awakening is accounted for by: (1) a general decrement in overall response speed (median of RT); (2) an "optimum response shift", i.e., a decrease in speed of the fastest responses; (3) an increase of lapsing, with more marked response delays resulting in a further decrease in response speed in the "lapse domain". Finally, our results do not support the existence of a circadian rhythm of sleep inertia linked to body temperature rhythm.     

Survival analysis indicates that age-related decline in sleep continuity occurs exclusively during NREM sleep

A common complaint of older persons is disturbed sleep, typically characterized as an inability to return to sleep after waking. As every sleep episode (i.e., time in bed) includes multiple transitions between wakefulness and sleep (which can be subdivided into rapid eye movement [REM] sleep and non-REM [NREM] sleep), we applied survival analysis to sleep data to determine whether changes in the “hazard” (duration-dependent probability) of awakening from sleep and/or returning to sleep underlie age-related sleep disturbances. The hazard of awakening from sleep—specifically NREM sleep—was much greater in older than in young adults. We found, however, that when an individual had spontaneously awakened, the probability of falling back asleep was not greater in young persons. Independent of bout length, the number of transitions between NREM and REM sleep stages relative to number of transitions to wake was approximately 6 times higher in young than older persons, highlighting the difficulty in maintaining sleep in older persons. Interventions to improve age-related sleep complaints should thus target this change in awakenings.     

Ontogenetic variations in auditory arousal threshold during sleep

Developmental variations in auditory arousal thresholds during sleep were investigated in four groups of normal male subjects - children, preadolescents, adolescents, and young adults. Arousal thresholds were determined during NREM and REM sleep for tones presented via earphone insert on a single night following two adaptation nights of undisturbed sleep. Age-related relationships were observed for both awakening frequency and stimulus intensity required to effect awakening, with awakenings occurring more frequently in response to lower stimulus intensities with increasing age. Although stimulus intensities required for awakening were high and statistically equivalent across sleep stages in nonadults, higher intensity stimuli were required in Stage 4 relative to Stage 2 and REM sleep in adults. These results confirm previous observations of marked resistance to awakening during sleep in preadolescent children and suggest that processes underlying awakening from sleep undergo systematic modification during ontogenetic development.     

Heart rate-based nighttime awakening detection

Sleep fragmentation is a cause of impaired daytime performance. We have developed an algorithm for detection of nighttime awakenings based on heart rate. As much as 15 healthy normal sleepers, 23 ± 3 years, participated in this study. The dataset contains 33 nights of polysomnographic (PSG) and electrocardiographic (ECG) measurements. After a habituation night, the subjects underwent a reference night without interventions, followed by some nights with interventions. These included noise, light, physical and cognitive interventions. Nighttime awakenings were subdivided in to awakenings (>15 s) and short awakenings (<15 s). The overall number of awakenings was 18.5 (±10.5) and short awakenings 13.2 (±10.5). The number of nighttime awakenings did not differ significantly between the reference and intervention nights; a repeated measures ANOVA resulted in a p value of 0.66 for awakenings and 0.57 for short awakenings. As much as 5 reference nights were used as training set, 28 as validation set. The algorithm detects the awakening periods with a sensitivity of 80.5% (confidence interval 77.9–82.9%). Heart rate is an adequate measure that allows for detection of nighttime awakenings and hence sleep quality.     

The relationship between subjective sleep estimation and objective sleep variables in depressed patients.

INTRODUCTION: To our knowledge there is no evidence in the literature about the relationship between subjective sleep estimation and objective sleep variables in depression. It is not known whether the subjective estimation of sleep quality and sleep duration is directly related to any objective sleep variable in depressed patients. METHODS: Thirty patients with major depression and 10 healthy subjects have been investigated in our sleep laboratory during 1 or 2 consecutive nights after 1 night for adaptation. Every subject, after final awakening in the laboratory, answered questions concerning the subjective feelings about sleep duration, number of awakenings and sleep depth. We compared the sleep estimation in both groups and calculated the correlation between objective and subjective sleep variables in depressed patients. RESULTS: The degree of a wrong sleep estimation in depressed patients is larger than in healthy subjects. Slow wave sleep (SWS) in depressed patients correlates positively with the subjective estimation of sleep duration. Eye movement density in REM sleep correlates with the subjective estimation of the number of awakenings. CONCLUSION: SWS in depression has a positive influence on the subjective feeling of sleep duration while phasic REM sleep activity has a negative influence.     

Enhanced synchronization of gamma activity between frontal lobes during REM sleep as a function of REM sleep deprivation in man

Studies have shown that synchrony or temporal coupling of gamma activity is involved in processing and integrating information in the brain. Comparing rapid eye movement (REM) sleep to waking and non-REM (NREM) sleep, interhemispheric temporal coupling is higher, but lower between the frontal and posterior association areas of the same hemisphere. However, the homeostatic response of REM sleep temporal coupling after selective REM sleep deprivation (REMD) has not been studied. This study proposed exploring the effect of one night of selective REMD on the temporal coupling of cortical gamma activity during recovery REM sleep. Two groups of healthy subjects were subjected to either REMD by awakening them at each REM sleep onset, or to NREM sleep interruptions. Subjects slept four consecutive nights in the laboratory: first for adaptation, second as baseline, third for sleep manipulation, and fourth for recovery. Interhemispheric and intrahemispheric EEG correlations were analyzed during tonic REM (no eye movements) for the first three REM sleep episodes during baseline sleep, and recovery sleep after one night of selective REMD. Temporal coupling between frontal lobes showed a significant homeostatic rebound that increased during recovery REM sleep relative to baseline and controls. Results showed a rebound in temporal coupling between the two frontal lobes after REM sleep deprivation, indicating that the enhanced gamma temporal coupling that occurs normally during REM sleep has functional consequences. Conclusion: results suggest that synchronized activity during REM sleep may play an important role in integrating and reprocessing information.     

Chronic Sleep Reduction: Daytime Vigilance Performance and EEG Measures of Sleepiness, With Particular Reference to "Practice" Effects

Six pairs of young adult 8-hr sleepers were divided equally into two groups, Reduction (R) and Control (C). They adhered to strict bed and arising times for six weeks. Additionally, R subjects reduced their sleep systematically to an average of 6 hrs per night. Following a baseline week, and on a weekly basis, “yoked” pairs of subjects, one from each group, were assessed for daytime sleepiness during prolonged vigilance performance, and by EEG measurement. All-night sleep EEGs were taken on R subjects before and at the end of the reduction. There were no significant differences between the groups for any of the daytime sleepiness measures, but both groups displayed significant “practice” effects over the weeks. R subjects experienced no major difficulties, except for some tiredness around awakening and lunchtime. Overall daytime sleepiness was not increased. Reduction was at the expense of REM and stage 2 sleep, and led to significant declines in sleep onset latency and in stages W + 1 at nighttime. SWS was not affected. This level of reduction in young adults seems to be achieved relatively easily.     

SLEEP MENTATION AND AUDITORY AWAKENING THRESHOLDS

Auditory awakening thresholds (AATs) were assessed in 53 Ss during all stages of sleep and at various times of night. Sixteen of these Ss met previously devised criteria for an AAT light-sleep group (LSG) and 16 for an AAT deep-sleep group (DSG). Reports of mental activity were collected during awakenings from REM and NREM sleep and rated on a standard questionnaire by Ss and independent judges. The REM mentation of the LSG and DSG did not differ. However, LSG Ss reported dreaming after 71% of their NREM awakenings, while DSG Ss claimed to have been dreaming after only 21% of their NREM awakenings. This difference was supported by other rating scales and by the independent judges. An hypothesis was offered which suggests that dreaming is a function of the level of cerebral arousal in the absence of reality contact, regardless of the stage of sleep, and that LSG Ss, as evidenced by several criteria, were more cerebrally aroused during NREM sleep than DSG Ss.     

Night-time right hemisphere superiority and daytime left hemisphere superiority: a repatterning of laterality across wake-sleep-wake states

During the sleep onset period (SOP), there is a state-specific relative advantage of the right hemisphere (RH). This superiority could either be due to the ability of the RH when operating at levels of reduced arousal, as suggested by its superiority in sustaining vigilance, or it could depend on a more pronounced homeostatic deactivation of the left hemisphere (LH). To evaluate whether variations of lateralization from wake to sleep are consistent with one of these two hypotheses, we considered a finger tapping task (FTT) bimanually performed during two wakeful conditions, during the SOP, upon experimental awakenings from stage 2 and REM sleep in the first and in the second part of the night, and upon morning awakening. The RH advantage in sustaining vigilance would be supported if the relative RH advantage was present throughout the sleep period. Finding that the repatterning of hemispheric asymmetry is present and/or prominent in the first part of the night would support the homeostatic hypothesis, i.e. when the homeostatic process is more pronounced. Results from 16 subjects revealed a significant superiority of the LH during the two wakeful conditions. At sleep onset, a clear reversal of dominance was observed and it was followed by a steady RH superiority upon both REM and NREM sleep awakenings, and upon the morning sleep-wake transition. Therefore, performance in a FTT reveals a repatterning of laterality across wake-sleep-wake states. These results are interpreted as consistent with the hypothesis concerning an advantage of the RH in sustaining vigilance.