Eye Movements In REM Sleep Research Articles

Characterization of sleep in six patients with pantothenate kinase-associated neurodegeneration

BackgroundPantothenate kinase-associated neurodegeneration (PKAN) is a rare neurologic disorder included in the group of neurodegeneration with brain iron accumulation diseases (NBIA). Information regarding sleep in patients with PKAN is limited. ObjectivesTo describe the clinical and polysomnographic characteristics of sleep in six patients with genetically confirmed PKAN. MethodsThe evaluation included a clinical interview, sleep questionnaires -Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale (HADS)- and a video-polysomnography (VPSG). In addition to standard sleep measures we manually quantified sleep spindle density in stage N2 and rapid eye movements in REM sleep comparing the results with matched controls. Quantification of EMG activity in REM sleep was performed following standard criteria. ResultsAll the patients reported at least one sleep complaint, most commonly sleep fragmentation (4/6) and sleep onset insomnia (3/6). ESS and PSQI were abnormal in 3/6 and 4/6, respectively. VPSG showed in 4/6 decreased ocular movements during REM sleep, an increase in sleep spindles in 3/6 (all of them with deep brain pallidal stimulation), an absence of slow wave sleep in 2 and undifferentiated NREM sleep and delayed sleep phase in one. Three patients had an abnormal sleep apnea/hypopnea index, and 2 periodic limb movements of sleep. REM sleep muscular atonia was preserved in all. ConclusionsSleep disorders are common in patients with PKAN. Although our sample is small and heterogeneous, with different symptomatic treatments possibly influencing the results, it suggests that evaluation of sleep should be considered in their management.

Michel Jouvet and "exotic" sleep

Michel Jouvet directed my medical thesis on paradoxical sleep in cats obtained in 1969, and my research on sleep in extreme environments (Antarctica, Arctic winter cold, physical exercise), which was the subject of my Ph.D. dissertation in 1984. As a military MD and scientist, I was posted in “exotic” (far away) places (Antarctica, Canada, Niger) and participated in several remote field trials (Canada, Côte d’Ivoire, Congo, Angola). Michel Jouvet supervised my research activity, allowing me the use of his laboratory facilities. He co-authored the work on sleep in Antarctica in 1987. In 1988, he was invited to Niamey (Niger) to preside on the international jury of medical doctorate dissertations. He then examined one of my patients with narcolepsy-like sleep attacks, suspect of sleeping sickness. Jouvet also co-authored our work on nitric oxide in the rat model of sleeping sickness. His scientific curiosity led him to study REM sleep eye movements in Bassari people, an isolated ethnic group in Senegal. With Monique Gessain, he co-authored a book on the Bassari oneiric activity. He was convinced that research in electricity-free villages was capital for understanding past mankind story. The present contribution recognizes the tremendous work capacity and scientific curiosity of Michel Jouvet.

Bilateral Eye Movements, Attentional Flexibility and Metaphor Comprehension: The Substrate of REM Dreaming?

Explanations for the effects of the rapid eye movements induced during Eye Movement Desensitization Reprocessing (EMDR; Shapiro, 2001) have drawn upon an analogy with the eye movements of REM sleep (Kuiken, Bears, Miall, and Smith, 2002). An extension of that analogy posits two orienting systems, one involving threat-fear related mnemonic contextualization and another involving loss-pain related monitoring of conflicting response alternatives. In a study involving individuals who had recently experienced significant loss or trauma, we found that experimentally induced saccadic eye movements decreased reaction times to unexpected stimuli among those reporting traumatic distress (characterized by hyperarousal and intrusive thoughts) and increased reaction times among those reporting separation distress (characterized by vivid reminiscences and the sense of a foreshortened future). Also, we found that saccadic eye movements increased the perceived strikingness of metaphoric sentence endings among those reporting amnesia for events related to either loss or trauma. The eye movements of both EMDR and REM sleep may differently affect the attentional and cognitive reorienting activity of those living with the consequences of loss or trauma. These differences may be evident in their waking reflections and in their dreams.

Brain activity and temporal coupling related to eye movements during REM sleep: EEG and MEG results

EEG and MEG REM sleep gamma activity was studied immediately before rapid eye movement onset (PRE-EM), during REM sleep with eye movements away from eye movement onset –phasic-REM (Ph-REM) – and during REM sleep without eye movements, or tonic REM (T-REM). For this purpose, activity was segmented into three different time windows: of 62.5, 250 and 500 ms. Two strategies were used: one a statistical comparison of changes between T-REM, Ph-REM and PRE-EM; the other a descriptive approach using principal component analysis. Significant findings showed that both EEG and MEG gamma activity are higher directly before eye movement onset in PRE-EM periods and during Ph-REM than during T-REM; temporal coupling of electrical activity between the frontal and parietal regions is decreased, while temporal coupling between the right frontal and midline is increased. Just before eye movement onset, larger recording sites become related. For the first time, results showed a close temporal link between power and temporal coupling of fast oscillations andrapid eye movements in REM sleep, indicating increased activation, uncoupling between the left frontal executive areas and posterior sensory association regions and increased coupling between the right frontal attentional and midline alerting systems. Brain activity is reorganized by phasic events.

Don’t Let Your Patients Lose Sleep Over Insomnia

Don’t Let Your Patients Lose Sleep Over Insomnia

Neurodegenerative diseases and sleep disorders

The interest in sleep disorders associated with neurodegenerative diseases is growing. Indeed, they add up to the clinical features of each of these conditions and may bring insight into their mechanisms. Along this line one of the major findings in recent years has been that REM-sleep behaviour disorder (RBD) has a predilection for synucleinopathies including idiopathic Parkinson's disease, multiple system atrophy and dementia with Lewy bodies, though not for tauopathies. We have reviewed neurodegenerative diseases without dementia (with the exception of idiopathic Parkinson's disease reviewed in another article of the same issue) and neurodegenerative diseases with dementia, in considering clinical features, pathologic patterns, associated sleep disorders and their treatments. Multiple system atrophy is characterised by rather severe breathing abnormalities, including obstructive sleep apnoea/hypopnoea syndrome, dysrhythmic breathing and laryngeal stridor, and by REM-sleep behaviour disorder which may precede the onset of clinical features of multiple system atrophy by several years. Insomnia is the most common sleep-related symptom of progressive supranuclear palsy. It is generally more severe than in other neurodegenerative diseases. Polysomnography shows the progressive shortening of sleep. Rapid eye movements of REM sleep are abnormal. Sleep disorders have not been systematically investigated in corticobasal degeneration. The most efficient therapeutic approaches of these conditions include continuous positive airway pressure (CPAP) in the case of sleep breathing abnormalities and clonazepam for REM-sleep behaviour disorder. Alzheimer's disease is the most frequent neurodegenerative disease with dementia. Sleep is both reduced and disorganised. Sleep-related breathing disorders are common. Special features of Alzheimer's disease are sundowning''. an agitation behaviour occurring during the early evening and episodic nocturnal wandering. In frontotemporal dementia sleep disorders are comparable to those of other dementias with aspecific impairment of sleep continuity and architecture. In comparison with other dementias, dementia with Lewy bodies leads to more severe sleep disturbances, including more movement disorders whilst asleep, more excessive daytime sleepiness and REM-sleep behaviour disorder characteristic of a synucleinopathy. Current treatments fall into four categories: identifying and treating any medical factor of impaired sleep, using sedative medications as parcimoniously as possible, environmental and circadian manipulations.

Eye movements in REM sleep could be controlled by the same conjugate system while awake

We describe the impairment of eye movements during REM sleep in a patient with internuclear ophthalmoplegia. A 75-year-old woman, complaining of acute unsteady gait and diplopia, was diagnosed to have right medial longitudinal fasciculus (MLF) syndrome with limited adduction of the right eye. Overnight polysomnography revealed the same impairment of right adductive ocular movement during REM sleep. Our findings suggest that the MLF mediates lateral conjugation of eye movements during REM sleep as well as voluntary lateral conjugate eye movements during wakefulness.

Reflexive and orienting properties of REM sleep dreaming and eye movements

In this manuscript Hobson et al. propose a model exploring qualitative differences between the three states of consciousness, waking, NREM sleep, and REM sleep, in terms of state-related brain activity. The model consists of three factors, each of which varies along a continuum, creating a three-dimensional space: activation (A), information flow (I), and mode of information processing (M). Hobson has described these factors previously (1990; 1992a). Two of the dimensions, activation and modulation, deal directly with subcortical influences upon cortical structures – the reticular activation system, with regard to the activation dimension and the locus coeruleus and the pontine raphe neuclei, with regard to the modulation dimension. The focus of this review is a further exploration of the interaction between dreaming and the cortical and subcortical structures relevant to REM sleep eye movements.[Hobson et al. ]

Effect of a presleep optokinetic stimulation on rapid eye movements during REM sleep

Some evidence supports the view point that phasic motor events of REM sleep show a complementary relation with the corresponding wake motor activities: (a) an inverse relationship between waking saccades and REM sleep eye movements (REMs) has been found with respect to frequency, amplitude, and direction; (b) an increase of middle-ear muscle activity (MEMA) in the 2 h before sleep causes a complementary decrease of MEMA during REM sleep. The present study evaluated this relation with respect to the optokinetic (OKN) system, assessing the role of automatically induced eye movements in affecting direction and frequency of REMs during sleep. Ten subjects were recorded following standard rules in 3 consecutive nights (one adaptation, one baseline, one experimental). In the experimental night subjects underwent 2 h presleep OKN stimulation at 15°/s. The actual mean number of quick phases of nystagmus induced by the OKN stimulation was 12461.4 ± 1.7 quick phases/s). No significant effect was found with regard to direction or frequency of REMs; the hypothesis that differences in REM direction and frequency could be modulated by the rank order of REM episodes (i.e., as a function of time elapsed from presleep stimulation) also failed to show any effect of a complementary relation between OKN and REMs. The results suggest that the complementary relation between wake and sleep eye movements is specific for the saccadic system, allowing us to exclude a peripheral mechanism, that is, an effect due to fatigue of extraocular muscles.

The effects of varying stimulus intensity on P300 during REM sleep.

Event-related potentials (ERPs) are often used to measure the extent of information processing during sleep. Previous studies have indicated that a late positive wave, P300, can be elicited during REM sleep if stimuli are very rare and/or very loud. The present study examined the role of stimulus intensity in eliciting a P300 during REM sleep. Eight subjects were presented with auditory tone pips with an intensity of either 0, 60, 80 or 100 dB SPL. Stimuli were delivered at random with equal probability. Trials were sorted by stage of sleep, stimulus intensity, and presence or absence of rapid eye movements in REM sleep. During the waking state, when subjects read a book, the loud 100 dB stimulus elicited short (P3a) and long latency (P300) positive waves (peaking at 293 and 373 ms respectively). In stage of 2 non-REM sleep, N1 decreased to baseline level while P2 increased in amplitude compared to the waking state. A P300 could not be observed in stage 2 sleep regardless of the level of stimulus intensity. During REM sleep, a late P300 (latency 363 ms) was elicited by the 100 dB stimulus. The earlier positive peak (i.e. P3a) was not apparent. The P300 was reduced in amplitude compared to the waking state. Its amplitude did not differ between phasic and tonic states of REM sleep. A late parietal negative slow wave (SW) was also apparent during REM. Although the SW was larger during phasic compared to tonic REM, the difference was not significant. These data suggest that stimuli which are sufficiently intrusive to elicit a P300 in the waking state continue to do so in REM sleep.

REM sleep eye movement counts correlate with visual imagery in dreaming: a pilot study.

Based on the findings of our previously published positron emission tomography study, we proposed that recorded eye movements during REM sleep are visually targeted saccades. In the present study, we examined the correlation between the number of eye movements in REM sleep (EM) and visual imagery in dreaming (V) and provided further support for our proposal. All the observations (N = 11) were made with one individual to eliminate interindividual variation and were made during the second REM sleep period to control for a time-of-night effect. V, with or without dream report length partialled out, was strongly associated with EM only in the 1-min interval immediately preceding awakening. The time course of the association suggests that the strong EM-V association reflects a phasic, localized activation of the eye-movement-control system in association with REM sleep eye movements.

Sleep disturbance in children with growth hormone deficiency

We examined the effects of growth hormone (GH) deficiency on sleep development by performing all-night polysomnography in three female children with GH deficiency (GHD). The percentage of REM sleep seemed to be reduced before the treatment in 2 cases, and human GH (hGH) compensation slightly increased it. Submental twitch movements (mTMs), i.e., body movements during sleep localized in the submental muscle and lasting less than 0.5 seconds, were commonly disturbed in the three patients. Rapid eye movements in REM sleep (REMs) were reduced before the therapy in one case, this decrease being reversed on hGH compensation. REMs also seemed to increase after hGH treatment in the other two cases. Dopamines and cholinergic muscarinic agonists can cause GH release, while mTMs and REMs might be related to dopaminergic and cholinergic systems in the human brain. It is intriguing that GHD, and the disturbance of mTMs and REMs coexisted in children with GHD. Since a relatively poor social outcome in patients with GHD has been reported, even after hGH compensation, it is important to monitor their neurological development by means of evaluation of their sleep disturbance.

Markovian analysis of biperiden's effect on REM sleep eye movements in schizophrenics and normals : Alan B. Douglass, James E. Shipley, Rajiv Tandon, JoAnn Goodson University of Michigan, Ann Arbor, MI 48105

Markovian analysis of biperiden's effect on REM sleep eye movements in schizophrenics and normals : Alan B. Douglass, James E. Shipley, Rajiv Tandon, JoAnn Goodson University of Michigan, Ann Arbor, MI 48105

Eye movement patterns in REM sleep

Eye movements in 6 healthy men and women were studied for recurrent patterns during REM sleep. The REM periods of noctural polysomnograms, on 2 consecutive nights, were analyzed in each subject. A discrete scale from 1 to 8 was used to record each eye position. The total number of recorded eye positions for the 2 nights of testing varied from 1314 to 3006. The distributions of eye movement were similar for males and females, for both nights of testing for each subject, among individual REM periods, and between subjects. This was in spite of marked differences in the number and length of REM period, and in the number of eye movements per minute of REM sleep. In 5 of 6 subjects there was a marked tendency for the eyes to move between the 2 opposite lateral positions. Regardless of the eye position, the opposite movement was generally most likely, with an underlying tendency to return to the most opposite of the two lateral positions. In the remaining subject the opposite movement was also favored, but in this subject eye movements were more likely to be vertical rather than horizontal. Our data suggest that eye movements in REM sleep are organized in complex recurring patterns, with marked similarities between subjects. The significance of these patterns and the significance of deviations from these patterns require further study.

Quantitative analysis of eye movements during REM‐sleep in developing rats

Development of eye movements in REM-sleep was studied in rats during the second and third week of postnatal life. An increased frequency of eye movements was found after eye opening, which was due only to changes in burst activity. Since pups reared in constant darkness showed an increase in eye movement activity similar to that of those exposed to diurnal light-dark alterations, the change seems to be part of an endogenous developmental timetable rather than due to an increase of visual stimulation by eye opening.

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.

Rapid eye movements in REM sleep — more evidence for a periodic organization

Density scores of horizontal eye movements during 70 REM sleep periods of normal young adults and combat neurotic patients were subjected to spectral analysis. The results showed that in 58% of all REM periods, spectral peaks occurred at either 0.1 c/min or 0.05 c/min. The percentages of spectral peaks at these frequencies were equal in both groups. Since the estimated variance at these frequencies was significantly higher than the estimated variance at the adjacent frequencies and the mean variance at the rest of the spectra, it was concluded that eye movements in REM sleep tend to cluster every 10–20 min. These results and findings on the neural control of REM ocular activity suggest that REMs in sleep are generated by at least 3 generators: a burst generator, an isolated eye movement generator, and a 10–20 min periodic generator.

The Temporal and Periodic Organization of REM Eye Movements in Mental Retardation

Time trends and periodic cycles in REM sleep eye movements were examined in 6 functional and 6 mongoloid adolescent retardates. Both groups of subjects showed approximately equal percentages of linear trends, quadratic trends, linear and quadratic trends, and absence of trend. The eye movement time-series were subject to an orthogonal spectral analysis. In both groups of subjects, peak spectral estimates generally occurred at 10.6- or 21.3-min periods. Following this, the eye movements of the longest REM periods (and one long period of pre-sleep wakefulness) were subject to a least-squares spectral analysis. This analysis yielded estimates ranging from 22 to 44 min. Eye movements lacked the ultradian organization previously reported for eye movements of normal subjects. These results imply that the ultradian organization of REM sleep and the ultradian organization of eye movements may be independent.

Time trends and periodic cycles in rem sleep eye movements

Eye movements during REM sleep episodes were tabulated in 16 young adults. REM episodes were then broken down into four ranges according to length in min: (1) 11.0–21.3; (2) 21.7–29.7; (3) 30.0–42.3; (4) 42.7 or longer. These data were then analyzed for linear and quadratic trends. Eight episodes had a significant linear trend, 10 had a significant quadratic trend, 7 had both linear and quadratic trends, while 12 had no trend. The residuals from the best-fitting polynomial curve were then subject to a spectral analysis. In addition, 2 long periods of pre-sleep wakefulness (approximately 2 h each) were also analyzed. In general, the spectral analysis revealed the dominant presence of a slow cycle (period of 10 min to about 30 min) the exact period of which varied according to the length of the REM episode. A binomial probability test indicated that the presence of slow cycles was significant in REM episodes except for those in the 21–30 min range. For the episodes of wakefulness, a dominant slow cycle was found in both cases. The results give the impression of similarity in the periodic organization of eye movements during REM sleep and waking. The data also indicated that an ultradian (70–150 min) cycle was present in eye movements during sleep and waking. Further, the finding of a decrease in eye movements before sleep onset, coupled with previous reports of an increase in eye movement after sleep onset, indicate the presence of a circadian cycle.

Spontaneous eyelid behavior in the sleeping cat

Recordings of the movements of the cat's eyelids were made to determine the nature of the closure process at sleep onset and whether or not the eye movements of REM sleep were accompanied by associated lid movements as in wakefulness. After 16 hr of treadmill deprivation, cats with chronically implanted electrodes were atraumatically restrained and their head immobilized. Lid movements were recorded by attaching to the lids levers of mechanically operated, variable apertures which controlled the amount of light striking a phototransistor. The results revealed that closure was a complex process consisting of a series of simultaneous downward movements of the upper lid and upward movements of the lower lid and that this closure was necessarily, in part, an active process. At REM onset, the palpebral fissures widened as the lower lid underwent a slow descent to the open position. In REM there were also phasic twitches of the lids, predominantly upward twitches of the lower lids, and there were periods in which the upper lid demonstrated movements similar to the lid movements associated with waking eye movements.