Tonic inhibition and ponto-geniculo-occipital-related activities shape abducens motoneuron discharge during REM sleep

Eye movements, ponto-geniculo-occipital (PGO) waves, muscular atonia and desynchronized cortical activity are the main characteristics of rapid eye movement (REM) sleep. Although eye movements designate this phase, little is known about the activity of the oculomotor system during REM sleep. In this work, we recorded binocular eye movements by the scleral search-coil technique and the activity of identified abducens (ABD) motoneurons along the sleep–wake cycle in behaving cats. The activity of ABD motoneurons during REM sleep was characterized by a tonic decrease of their mean firing rate throughout this period, and short bursts and pauses coinciding with the occurrence of PGO waves. We demonstrate that the decrease in the mean firing discharge was due to an active inhibition of ABD motoneurons, and that the occurrence of primary and secondary PGO waves induced a pattern of simultaneous but opposed phasic activation and inhibition on each ABD nucleus. With regard to eye movements, during REM sleep ABD motoneurons failed to codify eye position as during alertness, but continued to codify eye velocity. The pattern of tonic inhibition and the phasic activations and inhibitions shown by ABD motoneurons coincide with those reported in other non-oculomotor motoneurons, indicating that the oculomotor system – contrary to what has been accepted until now – is not different from other motor systems during REM sleep, and that all motor systems are receiving similar command signals during this period.     

The rate and depth of breathing in new-born infants in different sleep states

1. Ventilation was recorded on ten male and ten female healthy full-term infants during the first week after delivery, using a trunk plethysmograph. Tidal volume (V(T)), respiration rate (f) and pulmonary ventilation (V) for each respiratory cycle were measured during periods of rapid eye movement sleep (REM) and during quiet sleep when eye movements were absent (NREM).2. It was found that mean instantaneous V and f were significantly higher in all infants during REM than during NREM sleep, while mean V(T) was either unchanged or showed a decrease. In addition, there was significantly greater variation in instantaneous V, V(T) and f during REM as compared with NREM sleep.3. Positive correlations were found in most infants in both sleep states between individual values of V(T) and the duration of the respiratory cycle (T).4. Periodic changes in T were found in all infants during both sleep states; these periodicities may reflect the behaviour of respiratory control mechanisms operating over a longer time span than the individual respiratory cycle.     

Are the Eye Movements of Dreaming Sleep Related to the Visual Images of the Dreams?

As a result of recording eye movements during Stage REM sleep by AC electrooculography (EOG) previous investigators concluded that each eye movement is the response to the visual action in each dream. When we repeated the study using DC EOG it was discovered that only a minority of eye movements during Stage REM are in the direction of the visual action in the dream. If only single, large amplitude, prominent eye movements are considered then most such movements are related to colorful, compelling visual action occurring as a prominent single visual action against a quiet background. The AC recording method used in past studies emphasizes these isolated movements; perhaps this explains the disparity in results. At any rate, most eye movements during REM sleep are unrelated to the action in the dream. When these eye movements were analyzed in regard to the direction of movements, sequential order of movements, and randomness in time, we found that similar patterns of oculomotor output were found in all subjects. Thus, the nervous system executes a patterned output of oculomotor activity during dreaming sleep which is fairly consistent in all subjects. At times, however, a link is established between the visual and oculomotor systems and the eyes respond to visual action.     

Respiratory and body movements as indicators of sleep stage and wakefulness in infants and young children

Conventional polysomnographic (PSG) sleep staging to sleep staging based on a static-charge-sensitive bed (SCSB) recording in infants and young children was compared. The study consisted of whole-night clinical sleep studies in 22 children at 24 weeks (SD 24, range 1–79 weeks) of age. Most of the children presented with respiratory disturbances during sleep. From the SCSB record, sleep stages were differentiated according to regularity of breathing, presence of body movements, and most important, presence of high-frequency components of breathing (SCSB spikes). With both methods, three sleep/wake stages were distinguished: rapid eye movement (REM) sleep, non-rapid eye movement (NREM) sleep and wakefulness. The average inter-scorer reliability of the PSG sleep staging controlled in nine subjects was 88%. The average concordance between the two methods ranged from 82 to 85%, depending on the criteria used for scoring the SCSB. The mean sensitivity of the SCSB to detect NREM sleep ranged from 77 to 90% and the mean sensitivity to detect REM sleep ranged from 61 to 86%. The mean positive predictive value was 89–96% for NREM sleep and 54–67% for REM sleep. In conclusion, REM sleep is characterized by irregular breathing with superimposed fast respiratory movements. These changes are specific enough to allow distinction between episodes of NREM sleep, REM sleep and wakefulness with the non-invasive SCSB method in infants and young children. Incomplete concordance between PSG and SCSB score was most frequently observed during sleep stage transition periods, where the behavioural state and electrophysiological criteria disagreed. When combined with the PSG, the SCSB provides complementary information about the behavioural state of child.     

Dreaming during non-rapid eye movement sleep in the absence of prior rapid eye movement sleep

STUDY OBJECTIVES: There is a long-standing controversy surrounding the existence of dream experiences during non-rapid eye movement (NREM) sleep. Previous studies have not answered the question whether this "NREM dream" originates from the NREM sleep mechanism because the subject might simply be recalling experiences from the preceding rapid eye movement (REM) sleep. METHODS: We scheduled 11 healthy men to repeat 20-minute nap trials separated by 40-minute periods of enforced wakefulness across a period of 3 days. At the end of the nap trial, each participant answered questions regarding the formal aspects of his dream experiences during the nap trial, using the structured interviews. RESULTS: We obtained a total of 172 dream reports after naps containing REM sleep (REM naps) and 563 after naps consisting of only NREM sleep (NREM naps). Dream reports from NREM naps were less remarkable in quantity, vividness, and emotion than those from REM naps and were obtained more frequently during the morning hours when the occurrences of REM sleep were highest. CONCLUSIONS: These results suggest that the polysomnographic manifestations of REM sleep are not required for dream experiences but that the mechanisms driving REM sleep alter experiences during NREM sleep in the morning. A subcortical activation similar to REM sleep may occur in human NREM sleep during the morning when REM sleep is most likely to occur, resulting in dream experiences during NREM sleep.     

High frequency activities in the human orbitofrontal cortex in sleep-wake cycle

We recorded human orbitofrontal electrocorticogram during wakefulness and sleep in epileptic patients using subdural electrodes. During wakefulness and rapid eye movement (REM) sleep, we observed beta activity in the raw orbitofrontal signals. Power spectral analysis demonstrated beta enhancement during wakefulness and REM sleep when compared to slow wave sleep (SWS). During the phasic REM periods, the beta power was significantly lower than during the tonic REM periods. Gamma enhancement manifested itself in four out of six subjects during the phasic periods. This study is the first that has focused on electrical activity in the human orbitofrontal cortex. Although the role of the orbitofrontal cortex during sleep still remains unclear, high frequency activities give us important suggestions in elucidating the human sleep mechanism.     

A complementary relationship between wake and REM sleep in the auditory system: a pre-sleep increase of middle-ear muscle activity (MEMA) causes a decrease of MEMA during sleep

Since some evidence has supported a complementary relationship between waking and REM-sleep eye movement (variations in frequency, amplitude, or direction of waking saccades have been found to inversely affect the corresponding parameters of rapid eye movements), the present study assessed whether this relationship can also be shown for other phasic components of REM sleep, such as middle-ear muscle activity (MEMA), as a consequence of an increase of middle-ear reflex frequency during pre-sleep wake. Ten subjects were studied in three consecutive nights (one adaptation, one baseline, one experimental). In the experimental night, subjects underwent a 2-h pure-tone (1000 Hz, 90 dB SPL) auditory stimulation and MEMA was monitored every 15 min; noise exposure during daytime was also controlled. Results show that MEMA frequency during REM sleep significantly decreased during the experimental nights compared with baseline nights, while each sleep variable as well as mean daily auditory input did not present any significant difference between baseline and experimental nights. Results suggest that the complementary relationship between wake and REM sleep is not bounded to oculomotor activity, but it may also be extended at least to middle-ear muscle phasic activity. Received: 30 April 1999 / Accepted: 14 September 1999     

Autonomic control of the cardiovascular system during sleep in normal subjects

The autonomic control of heart rate and blood pressure during sleep is controversial: although it has been reported that vagal activity is more often lower in rapid eye movement sleep (REM) than in other stages of sleep (non-REM, NREM), the opposite has also been described. Initially, it was reported that baroreflex sensitivity (BRS) increases during sleep (REM and NREM), but in later studies, this was only partially confirmed. We therefore studied autonomic control of the cardiovascular (CV) system during sleep in 12 normal adults. The spectral components of the heart rate R-R interval, blood pressure (BP), and BRS were computed at low (LF) and actual breathing frequency (high frequency, HF). Analysis of sleep stage and a cycle-by-cycle stage II analysis were performed. CV variability is affected largely by sleep-stage and sleep-cycle organisation: NREM and the last cycle exhibit the greatest vagal activity and the lowest sympathetic activity. BRS estimation for both the LF and HF bands confirmed previous results obtained by pharmacological and spontaneous slope methods: BRS is greater during sleep than during nocturnal wake periods, and further increased in REM. BRS is frequency dependent: in NREM, the higher value of HF BRS compared to LF BRS favours the HF control of BP variability, whereas higher BRS HF and LF components contribute to the strongest control in REM. BRS variability exhibits no significant pattern during the night. Our results suggest that both sleep-cycle organisation and BRS estimation in the LF and HF bands should be considered in sleep studies of autonomic CV control. Electronic Publication     

Sleep deprivation suppresses the increase of rapid eye movement density across sleep cycles

We investigated the association between rapid eye movement (REM) density (REMd) and electroencephalogram (EEG) activity during non‐rapid eye movement (NREM) and REM sleep, within the re‐assessment, in a large sample of normal subjects, of the reduction of oculomotor activity in REM sleep after total sleep deprivation (SD). Coherently with the hypothesis of a role of homeostatic sleep pressure in influencing REMd, a negative correlation between changes in REMd and slow‐wave activity (SWA) was expected. A further aim of the study was to evaluate if the decreased REMd after SD affects ultradian changes across sleep periods. Fifty normal subjects (29 male and 21 female; mean age = 24.3 ± 2.2 years) were studied for four consecutive days and nights. Sleep recordings were scheduled in the first (adaptation), second (baseline) and fourth night (recovery). After awakening from baseline sleep, a protocol of 40 h SD started at 10:00 hours. Polysomnographic measures, REMd and quantitative EEG activity during NREM and REM sleep of baseline and recovery nights were compared. We found a clear reduction of REMd in the recovery after SD, due to the lack of REMd changes across cycles. Oculomotor changes positively correlated with a decreased power in a specific range of fast sigma activity (14.75–15.25 Hz) in NREM, but not with SWA. REMd changes were also related to EEG power in the 12.75–13.00 Hz range in REM sleep. The present results confirm the oculomotor depression after SD, clarifying that it is explained by the lack of changes in REMd across sleep cycles. The depression of REMd can not simply be related to homeostatic mechanisms, as REMd changes were associated with EEG power changes in a specific range of spindle frequency activity, but not with SWA.     

Intrinsic dreams are not produced without REM sleep mechanisms: evidence through elicitation of sleep onset REM periods

The hypothesis that there is a strict relationship between dreams and a specific rapid eye movement (REM) sleep mechanism is controversial. Many researchers have recently denied this relationship, yet none of their studies have simultaneously controlled both sleep length and depth prior to non-REM (NREM) and REM sleep awakenings, due to the natural rigid order of the NREM--REM sleep cycle. The failure to control sleep length and depth prior to arousal has confounded interpretations of the REM-dreams relationship. We have hypothesised that different physiological mechanisms underlie dreaming during REM and NREM sleep, based on recent findings concerning the specificity of REM sleep for cognitive function. Using the Sleep Interruption Technique, we elicited sleep onset REM periods (SOREMP) from 13 normal subjects to collect SOREMP and sleep onset NREM (NREMP) dreams without the confounds described above. Regression analyses showed that SOREMP dream occurrences were significantly related to the amount of REM sleep, while NREMP dream occurrences were related to arousals from NREM sleep. Dream properties evaluated using the Dream Property Scale showed qualitative differences between SOREMP and NREMP dream reports. These results support our hypothesis and we have concluded that although 'dreaming' may occur during both REM and NREM periods as previous researchers have suggested, the dreams obtained from these distinct periods differ significantly in their quantitative and qualitative aspects and are likely to be produced by different mechanisms.     

Sleep deprivation and phasic activity of REM sleep: independence of middle-ear muscle activity from rapid eye movements

In the recovery nights after total and partial sleep deprivation there is a reduction of rapid eye movements during REM sleep as compared to baseline nights; recent evidence provided by a selective SWS deprivation study also shows that the highest percentage of variance of this reduction is explained by SWS rebound. The present study assesses whether the reduction of rapid eye movements (REMs) during the recovery night after total sleep deprivation is paralleled by a decrease of middle-ear muscle activity (MEMA), another phasic muscle activity of REM sleep. Standard polysomnography, MEMA and REMs of nine subjects were recorded for three nights (one adaptation, one baseline, one recovery); baseline and recovery night were separated by a period of 40 hours of continuous wake. Results show that, in the recovery night, sleep deprivation was effective in determining an increase of SWS amount and of the sleep efficiency index, and a decrease of stage 1, stage 2, intra-sleep wake, and NREM latencies, without affecting REM duration and latency. However, MEMA frequency during REM sleep did not diminish during these nights as compared to baseline ones, while there was a clear effect of REM frequency reduction. Results indicate an independence of phasic events of REM sleep, suggesting that the inverse relation between recovery sleep after sleep deprivation and REM frequency is not paralleled by a concomitant variation in MEMA frequency.     

Sleep disturbances in men with asymptomatic human immunodeficiency (HIV) infection.

During the clinical latency phase of human immunodeficiency virus (HIV) disease the central nervous system may be infected and begin to manifest subtle dysfunction. Our early investigations demonstrated persistent alterations in the sleep architecture of HIV-infected asymptomatic men. The major aims of this study were to delineate alterations of sleep architecture in asymptomatic HIV-infected men, to identify and describe sleep behavior complaints and to seek a correlation between objective sleep parameters and subjective complaints of sleep behavior. The study sample consisted of 24 men, 14 HIV-infected and 10 HIV-negative, age-matched controls. The protocol included a comprehensive history and physical, two polysomnograms, urine toxicity, detailed written sleep questionnaire, the Pittsburgh Sleep Quality Index, the Spielberger State-Trait Anxiety Test and the Beck Depression Inventory. Our results indicated that sleep architecture differed from controls in that wakefulness, slow-wave sleep [SWS-stage 3 and 4 nonrapid eye movement (NREM) sleep] and stage rapid eye movement (REM) sleep were more evenly dispersed throughout the night. In particular, SWS was prevalent during the second half of recorded sleep. The observed changes in the NREM/REM cycle could not be explained on the basis of underlying psychopathology. Just as the course of individuals with HIV infection varies, it is expected that sleep abnormalities will vary. Considering the known relationships between NREM stage 3 and 4 and immune system function, it is possible that the observed alterations in the NREM/REM cycle are related to coincident changes in immunologic function. Quantitative measures of NREM sleep, especially SWS and REM sleep, are perhaps of greater significance than relative measures of sleep stages.(ABSTRACT TRUNCATED AT 250 WORDS)     

Arousal thresholds during human tonic and phasic REM sleep

The goal of the present study was to investigate arousal thresholds (ATs) in tonic and phasic episodes of rapid eye movement (REM) sleep, and to compare the frequency spectrum of these sub‐states of REM to non‐REM (NREM) stages of sleep. We found the two REM stages to differ with regard to behavioural responses to external acoustic stimuli. The AT in tonic REM was indifferent from that in sleep stage 2, and ATs in phasic REM were similar to those in slow‐wave sleep (stage 4). NREM and REM stages of similar behavioural thresholds were distinctly different with regard to their frequency pattern. These data provide further evidence that REM sleep should not be regarded a uniform state. Regarding electroencephalogram frequency spectra, we found that the two REM stages were more similar to each other than to NREM stages with similar responsivity. Ocular activity such as ponto‐geniculo‐occipital‐like waves and microsaccades are discussed as likely modulators of behavioural responsiveness and cortical processing of auditory information in the two REM sub‐states.     

Eye movements and abducens motoneuron behavior after cholinergic activation of the nucleus reticularis pontis caudalis

Study Objectives:

The aim of this work was to characterize eye movements and abducens (ABD) motoneuron behavior after cholinergic activation of the nucleus reticularis pontis caudalis (NRPC).

Methods:

Six female adult cats were prepared for chronic recording of eye movements (using the scleral search-coil technique), electroencephalography, electromyography, ponto-geniculo-occipital (PGO) waves in the lateral geniculate nucleus, and ABD motoneuron activities after microinjections of the cholinergic agonist carbachol into the NRPC.

Results:

Unilateral microinjections of carbachol in the NRPC induced tonic and phasic phenomena in the oculomotor system. Tonic effects consisted of ipsiversive rotation to the injected side, convergence, and downward rotation of the eyes. Phasic effects consisted of bursts of rhythmic rapid eye movements directed contralaterally to the injected side along with PGO-like waves in the lateral geniculate and ABD nuclei. Although tonic effects were dependent on the level of drowsiness, phasic effects were always present and appeared along with normal saccades when the animal was vigilant. ABD motoneurons showed phasic activities associated with ABD PGO-like waves during bursts of rapid eye movements, and tonic and phasic activities related to eye position and velocity during alertness.

Conclusion

The cholinergic activation of the NRPC induces oculomotor phenomena that are somewhat similar to those described during REM sleep. A precise comparison of the dynamics and timing of the eye movements further suggests that a temporal organization of both NRPCs is needed to reproduce the complexity of the oculomotor behavior during REM sleep.

Citation:

Márquez-Ruiz J; Escudero M. Eye movements and abducens motoneuron behavior after cholinergic activation of the nucleus reticularis pontis caudalis. SLEEP 2010;33(11):1517-1527.     

Plasma renin activity and sleep-wake structure of narcoleptic patients and control subjects under continuous bedrest.

In order to determine if renin release would be affected by a dysfunction of the circadian and ultradian organization of sleep, 24-hour profiles of plasma renin activity (PRA) concomitant with sleep stages were established in 10 normal subjects and nine narcoleptic patients, with 10-minute blood sampling intervals. Mean PRA levels were similar in control subjects and narcoleptic patients. Individual 24-hour profiles revealed that the previously described association between renin oscillations and sleep stage alternations was preserved. Increased PRA release was observed during the transition from rapid eye movement (REM) sleep or waking periods to nonrapid eye movement (NREM) sleep, and REM sleep occurred as PRA levels were decreasing. Thus, PRA curves exactly reflected the irregularities and disturbances in the sleep structure of the narcoleptic patients. The 24-hour PRA profiles of the patients did not show the general upward trend during nighttime sleep, which is probably induced in the control subjects by the repetitive recurrence of longer episodes of undisturbed NREM sleep. Because of marked sleep fragmentation in the patients, the duration of NREM sleep was often insufficient to allow for the occurrence of a significant PRA increase. Because sleep onset REM (SOREM) episodes, characteristic of narcolepsy, are not preceded by NREM sleep and its associated increase in PRA, no relative PRA decline occurred during this type of REM sleep. In conclusion, the 24-hour PRA profiles of the narcoleptic patients reflected exactly their sleep stage distribution, confirming previous findings that PRA oscillations appear to be inseparable from the NREM-REM sleep cycle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Facial Muscle Tonus During REM and NREM Sleep

Equipment and procedures were devised for quantifying relatively noise-free recordings of low amplitude chin and lip electromyograms (EMGs) during sleep. A total of 28 REM periods were recorded from 5 young adult female Ss. Tonic EMG levels tended to decline toward their lowest level of the night beginning 5 min in advance of REM periods. With very rare exceptions, the lowest EMG levels of the night were maintained throughout REM sleep. During the 20 min of NREM sleep which followed REM periods, mean EMG levels increased over the REM levels but were lower than those recorded during the 20 min of NREM sleep which preceded the REM periods. This pattern of tonic EMG variation obtained for each of the first 3 REM periods of the night.     

Spectral analysis of all-night human sleep EEG in narcoleptic patients and normal subjects

To investigate the pathophysiology of narcoleptic patients' sleep in detail, we analysed and compared the whole-night polysomnograms of narcoleptic patients and normal human subjects. Eight drug-naive narcoleptic patients and eight age-matched normal volunteers underwent polysomnography (PSG) on two consecutive nights. In addition to conventional visual scoring of the polysomnograms, rapid eye movement (REM)-density and electroencephalograph (EEG) power spectra analyses were also performed. Sleep onset REM periods and fragmented nocturnal sleep were observed as expected in our narcoleptic patients. In the narcoleptic patients, REM period duration across the night did not show the significant increasing trend that is usually observed in normal subjects. In all narcoleptic patient REM periods, eye movement densities were significantly increased. The power spectra of narcoleptic REM sleep significantly increased between 0.3 and 0.9 Hz and decreased between 1.0 and 5.4 Hz. Further analysis revealed that non-rapid eye movement (NREM) period duration and the declining trend of delta power density in the narcoleptic patients were not significantly different from the normal subjects. Compared with normal subjects, the power spectra of narcoleptic NREM sleep increased in the 1.0-1.4 Hz and 11.0-11.9 Hz frequency bands, and decreased in a 24.0-26.9 Hz frequency band. Thus, increased EEG delta and decreased beta power densities were commonly observed in both the NREM and REM sleep of the narcoleptic patients, although the decrease in beta power during REM sleep was not statistically significant. Our visual analysis revealed fragmented nocturnal sleep and increased phasic REM components in the narcoleptic patients, which suggest the disturbance of sleep maintenance mechanism(s) and excessive effects of the mechanism(s) underlying eye movement activities during REM sleep in narcolepsy. Spectral analysis revealed significant increases in delta components and decreases in beta components, which suggest decreased activity in central arousal mechanisms. These characteristics lead us to hypothesize that two countervailing mechanisms underlie narcoleptic sleep pathology.     

Excitation of medullary respiratory neurons in REM sleep

STUDY OBJECTIVE: To study tonic inputs to medullary respiratory neurons during rapid eye movement (REM) sleep. DESIGN: Single medullary-respiratory-neuron recordings during sleep with spontaneous breathing and during apnea caused by mechanical hyperventilation. SETTING: Academic laboratory. SUBJECTS: Three tracheostomized adult cats implanted for polysomnography and extracellular microelectrode recordings. Intervention: Single medullary-respiratory-neuron recordings during spontaneous breathing and mechanical hyperventilation to apnea during non-REM (NREM) and REM sleep. RESULTS: Most but not all respiratory cells of all types (pre-inspiratory, decrementing, augmenting and late inspiratory, phase-spanning, and expiratory) were more active in REM sleep than in NREM sleep during both spontaneous breathing and apnea induced by mechanical hyperventilation. The mean discharge rate of the cells during spontaneous breathing in NREM sleep was 16.7 impulses per second and in REM sleep was 26.5 impulses per second. During ventilator-induced apnea, the mean rates were 10 impulses per second in NREM sleep and 17.5 per second during REM sleep. The increase in activity in REM sleep occurred after a delay of several seconds from the onset of REM sleep. Respiratory cells were excited at times individually and at other times simultaneously in either a reciprocal or nonreciprocal pattern. The degree of excitation of a neuron in REM sleep during ventilator-induced apnea was proportional to the degree of excitation of the neuron in REM sleep during spontaneous breathing. CONCLUSION: Medullary respiratory neurons are excited individually and collectively in REM sleep. The excitation occurs with a delay after the onset of the state and can stimulate and/or disorganize breathing.     

Binocular Depth Perception Following REM Deprivation or Awake State Visual Deprivation

Based upon the demonstration by Wallach and Karsh (1963) that stereoacuity is easily disruptable in the awake state, we postulated that central visual excitation, which is a feature of rapid eye movement sleep, operates to prevent deterioration of depth perception capacity nightly during sleep. Three awake state and four REM sleep conditions, each consisting of an 8-hr period, were tested as follows: Awake: 1) baseline testing, 2) monocular patching, 3) binocular patching; Sleeping: 4) REM sleep deprivation, 5) NREM control (Stage 2 awakenings), 6) eye movement control (Condition 4 with substitution of awake eye movements), 7) uninterrupted sleep. A new device was developed and is described which measures stereoacuity as free as possible from other binocular or monocular cues in an actual depth situation. We replicated Wallach and Karsh's (1963) finding of awake state disruption of stereopsis following monocular patching. However, our results indicate that REM sleep deprivation by awakenings is not detrimental to binocular depth perception the next morning. In a second experiment, we found that binocular depth perception at the end of REM periods is not significantly different from depth perception at the beginning of REM periods. We have concluded that REM sleep does not have the function of enhancement of stereoacuity processing.