REM Density Research Articles

Rapid eye movement density shows trends across REM periods but is uncorrelated with NREM delta in young and elderly human subjects

Rapid eye movement density shows trends across REM periods but is uncorrelated with NREM delta in young and elderly human subjects

Functional neuroanatomical correlates of eye movements during rapid eye movement sleep in depressed patients

In depressed patients, REM density, or the number of rapid eye movements (REMs) per minute of REM sleep, is a correlate of depression severity and clinical outcomes. We investigated the functional neuroanatomical correlates of average REM counts (RC), an automated analog of REM density, in depression. Thirteen medication-free depressed patients underwent all night polysomnography and positron emission tomography (PET) scans using [ 18F]fluoro-2-deoxy- d-glucose ([ 18F] FDG) during REM sleep. Regression analyses were conducted with Statistical Parametric Mapping (SPM-99). Average RC significantly and positively correlated with relative regional cerebral metabolic rate of glucose (rCMRglc) bilaterally in the striate cortex, the posterior parietal cortices, and in the medial and ventrolateral prefrontal cortices. Average RC were negatively correlated with rCMRglc in areas corresponding bilaterally to the lateral occipital cortex, cuneus, temporal cortices, and parahippocampal gyri. The areas where average RC was positively correlated with rCMRglc appear to constitute a diffuse cortical system involved in the regulation of emotion-induced arousal. The observed pattern of correlations suggests that average RC may be a marker of hypofrontality during REM sleep in depressed patients.

Electroencephalographic sleep profiles in treatment course and long-term outcome of major depression: association with DEX/CRH-test response

Altered electroencephalographic (EEG) sleep patterns are among the most prominent neurobiological findings in depression. Several of these alterations have been suggested to be associated with an unfavorable long-term outcome. However, the impact of pathological sleep parameters on a more recurrent course of illness or vice versa still warrants clarification. Underlying mechanisms may involve systems known to be related to both sleep regulation and long-term course of depression such as the hypothalamic-pituitary-adrenocortical (HPA) axis. Thus, EEG sleep profiles of patients with depression were examined to determine whether (1) the retrospective clinical course of depression, and (2) the prospective long-term outcome in follow-up are associated with EEG sleep parameters. To elucidate related mechanisms HPA system functioning was evaluated by using the combined DEX/CRH test. Fifteen patients with affective disorders who participated in an earlier controlled antidepressant treatment study over 6 weeks were consecutively enrolled in an exploratory follow-up study. The retrospective analysis revealed that during the acute state of depression predominantly sleep continuity measures were associated with the number of previously experienced episodes. While this relation disappeared during treatment and did not correlate with the prospective course, decreased slow wave sleep variables especially in the first sleep period and increased rapid eye movement density were predictive for the occurrence of recurrences in follow-up and, hence, probably reflect more trait-like markers. Additionally, EEG sleep variables unfavorable for long-term outcome were related to excessive stress hormone response in the DEX/CRH-test. These disturbances may reflect important mechanisms responsible of causing and maintaining the disease process of depression.

Sleep characteristics of menopausal insomnia: a polysomnographic study.

Although menopausal insomnia is of clinical significance, the essential features of this form of disrupted sleep are poorly understood. The aim of the present study was to identify the sleep characteristics of menopausal insomnia by using overnight polysomnography (PSG). Twenty-one subjects with menopausal insomnia (MI) and 13 sex- and age-matched normal control (NC) subjects without sleep complaints took part in the present study. All MI and NC subjects underwent PSG on two consecutive nights. In comparison with NC, MI subjects had non-specific findings such as significantly shorter total sleep time, longer sleep latency, higher wake time after sleep onset, and lower sleep efficiency. As for rapid eye movement (REM) sleep variables, MI subjects had significantly shorter total REM sleep time, fewer numbers of REM sleep periods, longer REM latency, and higher REM density than did the NC subjects. As for the time course of REM density, REM density during the first 3 h period of nocturnal sleep was significantly higher for MI than for NC subjects. Unlike NC subjects, REM density for MI subjects did not tend to rise progressively during nocturnal sleep. The MI subjects had objective evidence of disrupted sleep and the most striking characteristics of this dysfunction were observed in REM sleep variables. The sleep characteristics of MI subjects were found to differ in REM sleep variables from those of patients with major depression (except for REM density). Menopausal insomnia patients appear to be similar to patients with generalized anxiety disorder accompanied by severe sleep disruption. These data lend support to the clinical distinction between menopausal insomnia and insomnia associated with major psychiatric disorders.

Rapid eye movement activity before spontaneous awakening in elderly subjects.

Previous research in young subjects found that rapid eye movement (REM) density is higher in those REM phases which are followed by an awakening (REM-W) than in those preceding NREM (REM-N), suggesting a 'gating role' of REM sleep toward the awakening. It is not yet known whether this evidence is maintained in elderly subjects, who display, relative to young subjects, more awakenings, different sleep states from which the awakenings come (NREM in a high proportion of cases) and a general impairment of rapid eye movement activity (REMA). To investigate this issue, we have compared in three different age groups (young, old and 'old old' subjects) the features of REMA, including REM density and the amount and duration of REM bursts, between REM-W and REM-N. Whereas in the young REM density is higher in REM-W than in REM-N, this difference is already reduced in the old group and fully cancelled in the old old subjects. The evidence that old individuals spontaneously wake up despite the absence of an increase of REMA could imply that in the aged awakening is not preceded by an increase of the arousal level (expressed in REM sleep by the REMA). The similar duration of REM bursts for REM-W and REM-N in both groups of old subjects suggests that with age a marked impairment occurs in the organizational aspects of REMs, independently from the following state.

Two-minute rapid eye movement (REM) density fluctuations in human REM sleep

Rapid eye movement (REM) density fluctuations during REM sleep were studied in five healthy young adults (23–26 years of age). Appropriate electro-oculographic (EOG) montage and automated EOG analysis enabled the detection of horizontal, vertical, and oblique REMs. REM density time series based on these REMs were formed for all the REM periods of the subjects. Autoregressive (AR) spectral analysis of the REM density time series estimated periodicities in the range of 1.7–2.4 min for 14 of the 16 REM periods analyzed, regardless of duration or number of REMs. Four subjects had such periodicities in each of their REM periods and the fifth subject had such periodicities in half the REM periods. This REM density fluctuation at a periodicity of about 2 min may relate to an important ‘rhythmic’ component of the REM generating mechanism(s).

Understanding Emotion Regulation in Borderline Personality Disorder: Contributions of Neuroimaging

Understanding Emotion Regulation in Borderline Personality Disorder: Contributions of Neuroimaging

Treatment with the CRH 1-receptor-antagonist R121919 improves sleep-EEG in patients with depression

Well documented changes of sleep electroencephalogram (EEG) in patients with depression include rapid eye movement (REM) sleep disinhibition, decreases of slow-wave-sleep (SWS) and increase in wakefulness. Twenty-seven inpatients with major depression were admitted subsequently to a clinical trial with the CRH 1-receptor-antagonist R121919 administered in two different dose escalation panels. A random subgroup of 10 patients underwent three sleep-EEG recordings (baseline before treatment, at the end of the first week and at the end of the fourth week of active treatment). SWS time increased significantly compared with baseline after 1 week and after 4 weeks. The number of awakenings and REM density showed a trend toward a decrease during the same time period. Separate evaluation of these changes for both panels showed no significant effect at lower doses, whereas in the higher doses after R121919 REM density decreased and SWS increased significantly between baseline and week 4. Furthermore positive associations between HAMD scores and SWS at the end of active treatment were found. Although these data might indicate that R121919 has a normalizing influence on the sleep EEG, the design of the study does not allow to differentiate genuine drug effects from those of clinical improvement and habituation to the clinical setting.

Polysomnographic evaluation of clinical patients suffering from mood disturbance

The sleep patterns of sixty patients suffering from mood disturbance, were studied, with mean age of 36.1 +/- 11.3 years ( 12 males, 48 females). These patients were submitted to two nights of nocturnal polysomnographic evaluation; the second night acquired data was employed in the statistics. The following parameters were analyzed: parameters of sleep continuity, parameters of sleep architecture, REM and non-REM sleep parameters. The patients were analyzed in accordance to depression severity, presence of sleep disorders and relevant mood disturbances. The most common diagnosis was dysthymia in 25 cases (41.6%). Descriptive analysis was used to delineate the study. The statistics evaluation used the Fisher exact test and the Kruskal-Wallis statistics heterogeneity test. There was reduction in sleep continuity and increase in REM density, both not statistic significant. Stage 4 sleep showed significant reduction in severely depressed patients (p=0.0253).

The Munich Vulnerability Study on Affective Disorders: risk factors for unipolarity versus bipolarity

Background: An individual with a high genetic load for psychiatric disorders is subject to a considerable risk factor for an affective illness. Family studies usually try to distinguish between bipolar and unipolar disorders since it was suggested that they might show different modes of inheritance. The aim of this study was to differentiate between healthy members of unipolar and bipolar families without a previous history of any psychiatric disorder according to the neurobiological and psychometric findings. Methods: We first analysed the results obtained from neurobiological and psychometric measurements taken from 75 healthy subjects who had at least two close relatives with a unipolar and a bipolar disorder. In a second step we examined the subjects with a parental affective disorder; finally, we compared the members of ‘pure’ unipolar, bipolar and of mixed families to each other. Results: The first-degree relatives of unipolar patients showed a significantly higher REM density and scored higher on scales of ‘neuroticism’ and ‘vegetative lability’ than the controls. No significant differences could be noticed between the relatives of unipolar and bipolar patients, either when considering the degree of relationship, or the parental type of affective disorder and the ‘purity’ of the respective families. Conclusions: We found some distinct neurobiological and psychometric differences between the relatives of unipolar patients and the control probands. No obvious differences, however, were ascertained between relatives of unipolar and bipolar patients. Therefore, we consider it to be possible that these findings represent potential vulnerability markers for affective disorders in general.

Depression-like changes of the sleep-EEG during high dose corticosteroid treatment in patients with multiple sclerosis

Acute exacerbations of multiple sclerosis (MS) are commonly treated with high doses of corticosteroids that can influence sleep regulation and hypothalamo-pituitary-adrenal (HPA) activity. We examined the sleep-EEG (including conventional and spectral EEG analysis) in 9 female patients with relapsing–remitting MS (and no psychiatric disorder) just prior to and on days 2 and 10 of high dose corticosteroid treatment (500 mg/day methylprednisolone given IV for 5 days, then PO taper down) and age-matched healthy female controls. Before treatment with corticosteroids, MS patients compared to controls showed few changes of the sleep EEG, namely a significant increase in slow wave sleep (SWS) and a decrease in stage 2 sleep. In contrast, on day 10, but not day 2 of treatment, MS patients showed a number of sleep-EEG changes typically observed in patients with depression, including a reduction in REM latency, an increase in REM density, a decrease in the SWS and delta sleep ratio and a decrease in sigma EEG activity. However, no concomitant effect of treatment on mood was noted. In summary, unlike acute treatment with methylprednisolone, prolonged treatment induces several changes of the sleep-EEG in MS patients, that are also observed in patients with an acute depressive episode. Further prospective studies with longer-term follow-up are needed to examine the clinical relevance of our preliminary data.

Ingestion of Ethanol Just Prior to Sleep Onset Impairs Memory for Procedural but not Declarative Tasks

The aim of Experiment 1 was to determine if moderate ethanol consumption at bedtime would result in memory loss for recently learned cognitive procedural and declarative tasks. The aim of Experiment 2 was to establish that the memory loss due to alcohol consumption at bedtime was due to the effect of alcohol on sleep states. In Experiment 1, participants were asked to learn a cognitive procedural task and a declarative task in the evening. Then, either the same evening or 2 nights later, they were asked to drink ethanol (0.7g/kg). Sleep was monitored for 3 days and re-testing of the tasks was done on the eighth day after training at the same time of day. In Experiment 2, subjects were asked to learn a cognitive procedural task (Tower of Hanoi) and a motor procedural task (Pursuit Rotor) in the late afternoon. Then one group was asked to drink ethanol (0.9 g/kg) right after task acquisition (5 hours before bed), while the other was asked to drink the same dose of ethanol just prior to bedtime. Re-testing was done 8 days later at the same time of day. Subjects in Experiment 1 were 15 college students between the ages of 19 and 24 that appeared to be in good health and were relatively naive in terms of drinking alcohol. Subjects in Experiment 2 were 13 college students in the same age range. These subjects were considered to be more experienced drinkers than subjects in Experiment 1 but were not judged to be heavy drinkers. In Experiment 1, the alcohol ingestion resulted in memory loss for the cognitive procedural task but not the declarative task. Further, the effect was seen when alcohol ingestion occurred the same day or 2 days after the end of acquisition. In Experiment 2, alcohol ingestion at bedtime impaired memory for the cognitive procedural and motor procedural tasks. By contrast, alcohol ingestion in the afternoon, immediately after the acquisition of these two tasks, did not impair memory. There were clear changes in the nature of rapid eye movement (REM) sleep as a result of evening alcohol ingestion. In Experiment 1, the number of REMs and number of minutes of REM in the first half of the night were reduced. In Experiment 2, the reduction was in REM densities in the first half of the night. Moderate doses of ethanol can modify the REM sleep architecture by reducing the number of REMs and/or REM densities as well as minutes of REM sleep, particularly in the first half of the night. These modifications result in memory impairment for recently learned cognitive procedural material. Alcohol may also have a subtle effect on Stage 2 sleep as well, since memory for a Stage 2 sensitive motor procedural task was also impaired.

Alterations in pattern of rapid eye movement activity during REM sleep in depression

The aim of the study was to evaluate REM sleep parameters, especially the temporal characteristics of rapid eye movement activity, in depressed patients, and to compare three different methods for scoring of REM density. The sleep of 15 nonmedicated depressed patients and 13 healthy controls was recorded during two consecutive nights. Sleep recordings were scored by raters blinded to the diagnosis. In comparison to healthy controls depressed patients showed an increased REM density and increased REM activity. Both groups differed also regarding the pattern of REM density changes between REM sleep periods (REMPs). Whereas in healthy controls REM density in the first REMP was significantly lower than in the successive REMPs, no such difference was found in depressed patients. On visual inspection we failed to find any significant differences in the time course of REM activity within the first REMP in depressed patients. All applied methods for scoring of REM density distinguished depressed patients from healthy controls with comparable accuracy.

Are polysomnographic measures of sleep correlated to alexithymia?: A study on laboratory-adapted sleepers

Objective: Since recent findings have pointed to a correlation between alexithymia and measures of poor sleep quality during the first night of adaptation to a sleep laboratory, the aim of the current study was to assess the same relation in healthy laboratory-adapted sleepers. As a further measure of rapid eye movement (REM) sleep characteristics, REM density was also measured. Methods: Twenty-seven male subjects, without sleep or psychiatric disorders, filled out the 20-item Toronto Alexithymia Scale (TAS-20) and slept for two consecutive undisturbed nights. Polysomnography and REM density were measured in the postadaptation night. Results: Alexithymia scores did not correlate significantly with any polysomnographic variable or with REM density. Only the Externally Oriented Thinking (EOT) subscale showed a negative association with REM latency. Multiple regression on selected sleep measures as predictors confirmed these results. Conclusion: Results do not extend to normal sleep the association previously found between alexithymia and a poor quality of sleep during the adaptation night in the sleep laboratory. The only polysomnographic measure showing an association, albeit little, with one facet of alexithymia was REM latency.

Mid-morning Tryptophan Depletion Delays REM Sleep Onset in Healthy Subjects

Because serotonin is involved in the diachronic regulation of sleep, we tested the effect of a midmorning rapid deficiency in the serotonin precursor tryptophan on the next night's sleep. After a 48-h low-protein diet, 17 healthy volunteers received either a tryptophan-free mixture of amino acids or a placebo at 10:30 a.m., in a randomized double-blind cross-over design, resulting in a 77% decrease and 41% decrease of serum tryptophan at 3:30 p.m. and 9:30 p.m., respectively. Urinary sulfatoxy-melatonin excretion and mood were unaffected by the rapid tryptophan depletion (RTD), but rapid eye movement (REM) sleep latency increased by 21 min (from 91.5 ± 4.5 min to 112.2 ± 6.9 min), sleep fragmentation 58%, and REM density of the first REM sleep period doubled. The results show that midmorning RTD delays REM sleep latency during following night-time sleep, whereas evening RTD shortens REM sleep latency in previous studies, and suggest that the serotonin control of REM sleep latency is upregulated.

The Munich vulnerability study on affective disorders: stability of polysomnographic findings over time

Background Some of the sleep abnormalities found in depression also persist in remission, suggesting that these parameters could represent trait or vulnerability markers. In a previous study, we found that about one third of a group of high-risk probands (HRPs) showed sleep patterns that were comparable to those of depressed patients. In the present study, we re-investigated a subsample of these HRPs to evaluate the stability of these findings over time. Methods We investigated the sleep-electroencephalograms of 82 healthy subjects with a high genetic load of affective disorders. We were able to re-investigate 26 of these HRPs after a mean interval of 3.5 years. Thirty-five unrelated control probands and 33 unrelated depressed inpatients that were recruited at the first investigation served as reference groups. Results At index investigation, we found that the HRPs showed a significantly increased rapid eye movement (REM) sleep density compared to control subjects. At the second examination, no changes of the polysomnographic observations over time could be observed; in particular, the REM density remained elevated. Conclusions The increased REM density in high-risk subjects for an affective disorder at index investigation was stable over time, so that one of the requirements for a true vulnerability marker is fulfilled.

Heterogeneity in EEG sleep findings in adolescent depression: unipolar versus bipolar clinical course

Background: EEG sleep measures in child and adolescent subjects with depression have shown considerable variability regarding group differences between depressed and control subjects. This investigation was designed to assess whether some of the observed variability is related to undifferentiated unipolar and bipolar disorders in a sample that was reported previously. Methods: Twenty-eight adolescents who met criteria for unipolar major depression and 35 controls with no lifetime psychiatric disorder participated in a cross-sectional sleep polysomnography study. Approximately 7 years later, follow-up clinical evaluations were conducted in 94% of the original cohort. Clinical course during the interval period was assessed without knowledge of subjects’ initial diagnostic and psychobiological status. Re-analysis of the original sleep data were performed with the added information of longitudinal clinical course. Results: Depressed subjects who had a unipolar course showed reduced REM latency, higher REM density, and more REM sleep (specifically in the early part of the night) compared with depressed adolescents who converted to bipolar disorder and controls who remained free from psychopathology at follow-up. In contrast to the unipolar group, depressed subjects who would later switch to bipolar disorder had demonstrated more stage 1 sleep and diminished stage 4 sleep. Conclusions: These preliminary results indicate that some of the observed variability in EEG sleep measures in adolescent depression appear to be confounded by latent bipolar illness. The findings also suggest that sleep regulatory changes associated with unipolar versus bipolar mood disorders may be different.

On the role of menopause for sleep-endocrine alterations associated with major depression

Aging and menopause are associated with alterations of the sleep EEG, while age-related changes of the hypothalamo-pituitary-adrenal (HPA) axis remain controversial. Major depression is also associated with typical sleep-endocrine changes, including enhanced activity of the HPA axis, while an influence of age and gender on these alterations is less clear. To test the hypothesis that after menopause sleep-endocrine alterations associated with major depression are accentuated, we examined the sleep EEG and nocturnal hormone secretion (ACTH, cortisol, GH, estradiol, LH, FSH, and leptin) in 16 drug-free female patients, mostly with the first episode of a major depressive disorder (seven pre- and nine postmenopausal subjects) and 19 female controls (10 subjects in the early follicular phase and nine postmenopausal subjects). Nocturnal cortisol secretion was increased in postmenopausal patients with depression, while a decrease was noted in postmenopausal controls. Sleep alterations typically associated with depression, namely a reduction in sleep continuity and slow wave sleep (SWS) and an increase in REM density, were prominent in post- but not in premenopausal patients. An inverse correlation was noted between the decline in SWS and sleep continuity and FSH secretion in patients with depression, suggesting a role of menopause for these sleep-endocrine alterations typically associated with major depression. In contrast, in premenopausal patients we noted primarily a shift in SWS and delta-EEG activity from the first to the second non-REM period, which was not related to age or hormone secretion. Though the relatively small number of subjects per group precludes a definitive conclusion, our data open up the possibility that the sleep-endocrine changes typically associated with major depression are most prominent in postmenopausal patients. Whether the predominant alteration of the distribution of SWS and delta EEG activity in younger patients with a first episode of major depression has a predictive value for the future course of the disease remains to be investigated.

Spontaneous sleep interruptions during extended nights. Relationships with NREM and REM sleep phases and effects on REM sleep regulation.

There is no agreement in the literature as to whether sleep interruption causes rapid eye movement (REM) pressure to increase, and if so, whether this increase is expressed as shortened REM latency, increased REM density, or increased duration of REM sleep. The purpose of the present study was to examine the effect of different durations of spontaneous sleep interruptions on the regulation of REM sleep that occurs after return to sleep. The occurrence of spontaneous periods of wakefulness and their effects on subsequent REM sleep periods were analysed in a total sample of 1189 sleep interruptions which occurred across 364 extended nights in 13 normal subjects. Compared with sleep interruptions that last less than 10 min, sleep interruptions that last longer than 10 min occur preferentially out of REM sleep. In both the short and long types of sleep interruptions, the duration of REM periods that ended in wakefulness were shorter than the duration of those that were not interrupted by wakefulness. REM densities of the REM periods that terminated in periods of wakefulness were higher than those of uninterrupted REM periods. The proportion of episodes of wakefulness following REM sleep that were long-lasting progressively increased over the course of the extended night period. The sleep episodes that followed the periods of wakefulness were characterised by a short REM latency. REM duration was increased in episodes that followed long sleep interruptions compared to those that followed short sleep interruptions. REM density did not appear to change significantly in the episodes that followed sleep interruption. REM sleep mechanisms appear to be the main force controlling sleep after a spontaneous sleep interruption, presumably because during the second half of the night, where more sleep interruptions occur, the pressure for non-rapid eye movement sleep is reduced and the circadian rhythm in REM sleep propensity reaches its peak. Processes promoting REM sleep at the end of the night are consistent with the Pittendrigh and Daan dual oscillator model of the circadian pacemaker.

Sleep- and circadian-dependent modulation of REM density.

Rapid eye movement (REM) density, a measure of the frequency of rapid eye movements during REM sleep, is known to increase over the course of the sleep episode. However, the circadian modulation of REM density has not been thoroughly evaluated. Data from a forced desynchrony protocol, in which 20 consecutive sleep opportunities were systematically scheduled over the entire circadian cycle, were analysed. The REM density was evaluated from polysomnographically recorded REM sleep episodes, and analyzed as a function of time in the sleep opportunity and as a function of phase in the circadian cycle. The REM density showed a robust increase over the course of the sleep episode. This sleep-dependent increase was observed regardless of circadian phase, because data analyzed from different thirds of the circadian cycle exhibited a similar pattern. The REM density did not show a significant circadian-dependent modulation for data from the entire sleep opportunity. However, analysis of circadian modulation from separate thirds of the sleep opportunity revealed a significant circadian modulation in the last third of the sleep episode. Maximum REM densities were observed when the last third of the sleep episode coincided with the wake-maintenance zone, i.e.;8-10 h before the crest of the circadian rhythm of REM sleep propensity. These results confirm the dominant sleep-dependent modulation of REM density, and indicate that the density of REMs is greatest when sleep pressure is low, such as in the latter part of the sleep episode, at which time the circadian modulation of REM density is also appreciable.