Sleep Rapid Eye Movement Research Articles

Regulation of REM sleep by inhibitory neurons in the dorsomedial medulla

The two major stages of mammalian sleep-rapid eye movement sleep (REMs) and non-REM sleep (NREMs)-are characterized by distinct brain rhythms ranging from millisecond to minute-long (infraslow) oscillations. Themechanisms controlling transitions between sleep stages and how they are synchronized with infraslow rhythms remain poorly understood. Using opto- and chemogenetic manipulation in mice, we show that GABAergic neurons in the dorsomedial medulla (dmM) promote the initiation and maintenance of REMs, in part through their projections to the dorsal and median raphe nuclei. Fiber photometry revealed that their activity is strongly increased during REMs and fluctuates during NREMs in close synchrony with infraslow oscillations in the sleep spindle band of the electroencephalogram. The phase of this rhythm influenced the latency and probability with which dmM activation induced REMs. Thus, dmM inhibitory neurons strongly promote REMs, and their slow activity fluctuations may coordinate the timing of REMs episodes with infraslow brain rhythms.

Sleep: The Sensory Disconnection of Dreams

It has been known for some time that the brain can react selectively to meaningful sensory stimuli during sleep. A recent study shows that this ability may be selectively suppressed during rapid eye movements of sleep.

The Prevalence and Characteristics of REM Sleep without Atonia (RSWA) in Patients Taking Antidepressants.

The association of REM sleep without atonia (RSWA) as well as REM sleep behavior disorder (RBD) with the intake of selective serotonin reuptake inhibitors (SSRI) and selective norepinephrine reuptake inhibitors (SNRI) is well established. Our study objective was to determine the prevalence of RSWA and RBD among a group of sleep center patients taking SSRI and SNRI. A retrospective chart review was done at our tertiary sleep center, and 10,746 consecutive records from October 1, 2007, through October 31, 2013, were searched for SSRI and SNRI names using the Sleep Cataloguer Software. The search resulted in 1,444 records, which were then reviewed for keywords of RSWA and RBD. The AASM scoring criteria were used to determine RSWA. Reports of 41 patients with known narcolepsy or α-synucleinopathies were excluded. The remaining records were mined for age, sex, presence of obstructive sleep apnea (OSA), type of antidepressant (SSRI or SNRI), and diagnosis for which antidepressant was prescribed. We used logistic regression analysis to adjust for age, OSA, and sex. Of the 1,444 participants on antidepressants, 176 (12.2%) had RSWA (all confirmed by the investigators) compared to 226 of the entire sleep lab population of 10,746 (2.1%), risk ratio (95% CI) 9.978 (8.149, 12.22). Seven of the 176 patients on antidepressants had RBD (0.48%) compared to 108 of 10,746 (1%), p = 0.005. SSRI and SNRI are associated with a higher prevalence of RSWA but not of RBD. This is independent of medication type.

Neurobiologic Mechanisms of Sleep and Wakefulness

Neurobiologic Mechanisms of Sleep and Wakefulness

Sleep in children with high functioning autism: polysomnography, questionnaires and diaries in a non-complaining sample

Sleep disorders in children with autism are frequently reported on questionnaires filled by parents. The aim of this study was to characterize sleep using objective and subjective measures in the same sample of autistic children without comorbidities and no primary complaints of sleep disorders. Eleven autistic children (10.3 ± 2.2 years) diagnosed with ADI-R and ADOS criteria and 13 typically-developing children (10.2 ± 2.0 years) were recruited. Exclusion criteria comprised the use of psychotropic medication, a full IQ lower than 75, a history of epilepsy and spontaneous complaints of sleep disorders from the parents. After their children were recruited, parents filled a sleep diary for 2 weeks and the Child Sleep Habit Questionnaire (CSHQ); children were then recorded for 2 consecutive nights in a sleep laboratory. Sleep stages of night 2 were scored according to Rechtschaffen and Kales (1968) using 20 s. epochs. Stage 2 sleep spindles and K-complexes were visually scored on bilateral prefrontal and central electrodes; REM sleep rapid eye movements were also scored. Variables were log transformed when abnormally distributed. Groups were compared using t -tests for independent samples. Sleep diaries showed a longer sleep latency in autistic children (43.6 ± 39.0 mn vs. 17.2 ± 17.5 mn, p = .037). The CSHQ showed no significant group differences. Polysomnographically recorded sleep latency was longer in autistic children (33.0 ± 8.3 min vs. 14.4 ± 4.6 min, p = .023), the duration of stages 3 and 4 (slow-wave sleep: SWS) was shorter (18.2 ± 3.2% vs 23.6 ± 5.7%; p = .009) but total sleep time was similar (539.7 ± 54.3 vs. 560.8 ± 60.2; p = .94). Sleep spindle density (per hour of Stage 2) was similar in both groups at central electrodes and Fp1 but it was lower at Fp2 (119.2 ± 97.7 vs. 225.5 ± 122.2, p = .03). The density of K-complexes was lower at the four electrodes (.0001 < p < .01). REM sleep parameters (latency, duration, distribution, eye movement density) were not different between groups. These results show that autistic children without subjectively reported sleep difficulties according to the CSHQ show signs of poor sleep on sleep diaries and polysomnography. Sleep diaries disclosed longer sleep latencies. Most polysomnographic differences were in nonREM sleep, raising the hypothesis of a difficulty for autistics to synchronize their cortical activity, possibly leading to impaired cortical sleep protective mechanisms such as sleep spindles and K-complexes. Canadian Institute for Health Research; ”Fonds de recherche du Québec – Santé”.

Rapid eye movements during sleep in mice: High trait-like stability qualifies rapid eye movement density for characterization of phenotypic variation in sleep patterns of rodents

BackgroundIn humans, rapid eye movements (REM) density during REM sleep plays a prominent role in psychiatric diseases. Especially in depression, an increased REM density is a vulnerability marker for depression. In clinical practice and research measurement of REM density is highly standardized. In basic animal research, almost no tools are available to obtain and systematically evaluate eye movement data, although, this would create increased comparability between human and animal sleep studies.MethodsWe obtained standardized electroencephalographic (EEG), electromyographic (EMG) and electrooculographic (EOG) signals from freely behaving mice. EOG electrodes were bilaterally and chronically implanted with placement of the electrodes directly between the musculus rectus superior and musculus rectus lateralis. After recovery, EEG, EMG and EOG signals were obtained for four days. Subsequent to the implantation process, we developed and validated an Eye Movement scoring in Mice Algorithm (EMMA) to detect REM as singularities of the EOG signal, based on wavelet methodology.ResultsThe distribution of wakefulness, non-REM (NREM) sleep and rapid eye movement (REM) sleep was typical of nocturnal rodents with small amounts of wakefulness and large amounts of NREM sleep during the light period and reversed proportions during the dark period. REM sleep was distributed correspondingly. REM density was significantly higher during REM sleep than NREM sleep. REM bursts were detected more often at the end of the dark period than the beginning of the light period. During REM sleep REM density showed an ultradian course, and during NREM sleep REM density peaked at the beginning of the dark period. Concerning individual eye movements, REM duration was longer and amplitude was lower during REM sleep than NREM sleep. The majority of single REM and REM bursts were associated with micro-arousals during NREM sleep, but not during REM sleep.ConclusionsSleep-stage specific distributions of REM in mice correspond to human REM density during sleep. REM density, now also assessable in animal models through our approach, is increased in humans after acute stress, during PTSD and in depression. This relationship can now be exploited to match animal models more closely to clinical situations, especially in animal models of depression.

Developmental changes in the clustering pattern of sleep rapid eye movement activity during the first year of life: a Markov-process approach

Findings are presented in support of the hypothesis that the tendency of sleep rapid eye movement (REM) activity to group into burst structures changes with age during the first year of life in normal infants. Specifically, by assuming a markovian model for the generation of 1 sec long units of REM activity,, it is shown that the propensity of those units to develop a sustained clustering pattern may increase during the first 2 months, possibly reaching a plateau at about 4 months. On the other hand, the overall density of REM activity units may continue to increase beyond that point in time.

EOG-based recording and automated detection of sleep rapid eye movements: a critical review, and some recommendations.

ABSTRACTThis paper presents a critical discussion of methods used for the recording and the automated detection of sleep rapid eye movements (REMs) via electro‐oculographic (EOG) methodologies. Specifically, the paper elaborates on: 1) various EOG montages for sleep eye movement recording, 2) AC vs. DC coupling for EOG signal amplification, 3) artifact presence and elimination thereof via filtering of the EOG signal, and 4) available EOG‐based automated methods for REM detection. Recommendations for the development of an “optimum’ automatic sleep REM detection system based on EOG recordings are presented as well.

Human cerebral potentials associated with REM sleep rapid eye movements: links to PGO waves and waking potentials

Eye movement triggered averaging and topographic display techniques indicate the presence of parieto-occipital potentials that precede the rapid eye movements of human REM sleep. Since these potentials have strong similarities with PGO waves in animals, including lateralization according to eye movement (EM) direction, and with waking EM-antecedent potentials in man, this suggests that PGO-like activity both exists in man, and may be functionally related to EM-antecedent potentials in waking. The ability to detect such central potentials opens the possibility of studying REM sleep central physiological structure in a variety of normal and pathological conditions in humans.

Automatic rem detection: Modifications on an existing system and preliminary normative data

This paper describes hardware changes and additions to a previously reported sleep rapid eye movement (REM) automatic detection system. Specifically, it describes the design philosophy of a new and optimum analogue bandpass prefilter, new detection criteria based on a detailed study of the waveform distortion due to AC coupling and bandpass prefiltering and the implementation of an artifact detection system for a more accurate detection of seemingly REM-related electro-oculographic (EOG) waveforms. Preliminary normative data on phasic REM patterns from young adults, detected by the described system, are also presented.

Semi-automatic analysis of rapid eye movement (REM) patterns: A software package

This paper describes a collection of software programs interfacing a hardware sleep rapid eye movement (REM) automatic detection system with a general purpose digital minicomputer ( PDP- 8 e ) for the collection and further quantitative processing of sleep REM times of occurrence. The software to be described is divided into four categories: (a) acquisition of REM times, (b) REM burst detection and analysis, (c) density measurements, and (d) connectivity measurements.

Activité unitaire corticocérébelleuse et mouvements oculaires: Modifications associées aux saccades du sommeil et de la veille

Single unit activity of vermian oculomotor cortex (Lobules V, VI, VII) and conjugated horizontal rapid eye movements were recorded in the cat, during wakefulness (W) and paradoxical sleep (PS). Correlation between cerebellar and oculomotor events showed the following findings. During PS the units — mostly Purkinje (P) cells — all increased their rate of discharge (mossy fiber activation for P cells) in coincidence with saccadic movements. Two kinds of movement related cells were observed: (i) Most of the units showed an increase of their discharge rate together with occasional bursts. These events were related to magnitude and rate of the saccades without accurate synchronization. (ii) Some cells showed a burst type activation strictly synchronized with the rapid eye movements of sleep. During W, two thirds of the units changed their pattern of discharge (mossy fiber activation for P cells) with waking ocular activity. Modifications of discharge patterns were very different from cells to cells (activation or suppression, increase or decrease in the rate of discharge). Many cells had an accurately synchronized response with the saccades. Some units had a directional reactivity, others gave a similar response for opposite eye movements. P cells showed an increase of their climbing fiber driven activity during PS with eye movements compared with PS without saccades. During PS and W, complex spikes discharges of P cells evidently showed no accurate relation to saccadic eye movements. Functional significations of the above described events are also discussed.

Lateral geniculate spikes and eye movements in sleeping and awake cats following uni- and bilateral labyrinthectomy and cerebellar lesion

The role of the labyrinthine apparatus and the cerebellum in producing sleep rapid eye movements and lateral geniculate nucleus spikes was assessed by performing staged labyrinthectomies and cerebellar lesions in cats with chronically implanted electrodes. Eye movements during fast-wave sleep and lateral geniculate nucleus spikes in the awake and sleeping cat or after reserpine administration were apparently normal in all respects following these procedures. Changes in sleep patterns were noted in all cats after cerebellar lesions. The labyrinthine apparatus and cerebellum make no necessary contribution to the production of lateral geniculate nucleus spikes or fast-wave sleep rapid eye movements.

Lateral geniculate and occipital cortex spikes with eye movements in awake and sleeping cats: Temporal and functional correlations

The temporal relationship between lateral geniculate and occipital cortex spikes and the fast and slow components of nystagmus and of fast-wave sleep rapid eye movements were investigated, using cats bearing chronically implanted electrodes. Computer averaging of the electrical activity from the electrooculogram, from occipital cortex, and from lateral geniculate nucleus (using the latter as the trigger point) demonstrated that the lateral geniculate spike is in all cases initiated at the fixation point of eye movements, i.e., at the inflection from fast to slow eye movement. Since phasic activation of midbrain reticular formation is considered to occur with the lateral geniculate spikes, it appears that the spikes normally function to produce an augmented reactivity at the moment of eye fixation.

Transformation of somatic afferent volleys across the prethalamic and thalamic components of the lemniscal system during the rapid eye movements of sleep

1. 1. The orthodromic lemniscal response recorded from the contralateral medial lemniscus to single shock stimulation of the forelimb nerves is phasically depressed during the bursts of rapid eye movement (REM) typical of desynchronized sleep. On the contrary, the post-synaptic potential evoked from the nucleus ventralis postero-lateralis on single shcok stimulation of the medial lemniscus is greatly facilitated during REM. 2. 2. While the depression of prethalamic lemniscal responses occurs only during large bursts of REM, facilitation of the thalamic responses elicited by lemniscal stimulation appears not only during large but also during small bursts of REM. 3. 3. Comparison of the lemniscal and thalamic responses induced by cutaneous afferent volleys during the same periods of desynchronized sleep indicated that facilitation of thalamic responses generally occurred during small bursts of REM, which were usually not associated with changes in amplitude of the lemniscal responses. 4. 4. On the contrary, during large bursts of REM the post-synaptic facilitation of thalamic responses was unable to compensate for the reduced transmission of the somatic afferent volley through the dorsal column nuclei and the final effect was a reduction of the orthodromic thalamic volley. 5. 5. Previous observations indicate that muscular contractions occur during bursts of REM. It is postulated that some part of the efferent activity giving rise to contractions of the limb musculature during REM is fed into the somatic sensory system, particularly the nucleus ventralis postero-lateralis, where it interacts with the incoming somatic information filtered at dorsal column level.

An analysis of rapid eye movements of sleep in the monkey

Eye movements and the parietal EEG were measured in two Macaca mulatta monkeys during natural sleep. Most of the eye movements during the REM period occurred at velocities less than 50 deg/sec which corresponds to the velocity range of smooth pursuit movements in the awake monkey. Saccades or rapid fixation changes also occur during REM sleep but take up only 0.5% of the total episode time. In addition, the eye often turns at velocities intermediate to the normal saccadic and smooth pursuit velocities, exhibiting a type of movement which is not observed in the awake animal. During one-third of the REM episode the eye undergoes loop-shaped trajectories composed of movements of different velocities and there is a constancy of the velocity histograms among REM episodes. Neither of these phenomena were observed in the awake monkey suggesting that the interpretation that all eye movements during REM sleep are related to dream content should be made with caution.

Effects of vestibular stimulation during sleep

1. 1. The effects of vestibular stimulation upon eye movements were studied in five sleeping children. 2. 2. The production of depressed nystagmus was significantly associated with the occurrence of the rapid eye movements of sleep. 3. 3. Slow conjugate deviation of the eyes was observed predominantly during the non-rapid eye movements phase of sleep.

Discharge patterns of single geniculate neurons during the rapid eye movements of sleep.

Discharge patterns of single geniculate neurons during the rapid eye movements of sleep.

Dream imagery: relationship to rapid eye movements of sleep.

George Trumbull Ladd³⁹suggested in 1892 that the visual elements of dreams were derivations of the "psychical synthesis" of night-time retinal sense data. This hypothesis led him to speculate that the eyeballs move during dreaming. "As we look down the street of a strange city, for example, in a dream we probably focus our eyes somewhat as we should do in making the same observation when awake. . . ." Ladd's ingenious surmise went unverified until 1955 when Aserinsky and Kleitman²reported actual observations of ocular movements during sleep. They described 2 types which appear at separate times during the night in a predictable pattern: (a) slow eye movements (SEM's)—,slow, often asynchronous, gliding excursions of the eyeballs at sleep onset and after every body movement occurring during the night's sleep; (b) rapid eye movements (REM's)—bursts of quick, binocularly synchronous, single and grouped ocular deviations often in clusters