Sleep EEG Data Research Articles

Acute, subchronic and discontinuation effects of zopiclone on sleep EEG and nocturnal melatonin secretion

Zopiclone is a new short half-life cyclopyrrolone hypnotic agent acting at the GABA-benzodiazepine receptor complex. In order to characterize its pharmacological profile, the effects of 7.5 mg zopiclone on nocturnal melatonin secretion were investigated under polysomnographic control in 11 healthy subjects following acute and subchronic administration as well as after abrupt discontinuation of the drug. No effect of zopiclone on the melatonin plasma levels could be observed. Regarding both total melatonin production and the temporal pattern of melatonin secretion during the night, there was no difference between placebo baseline condition, acute and subchronic administration, and discontinuation. In contrast, the sleep EEG data demonstrated the hypnotic efficacy of zopiclone under acute administration and indicated a rebound insomnia after abrupt discontinuation. Moreover, alterations of sleep architecture were found under treatment as well as after discontinuation. Whereas, with regard to sleep EEG parameters, zopiclone appears to be comparable with some short-acting benzodiazepines, a discrepancy between the missing effect of zopiclone on pineal function and the suppressing influence of benzodiazepines known from the literature becomes obvious. The fact that zopiclone does not interfere with nocturnal melatonin secretion at pharmacologically active doses as indicated by alterations in sleep EEG parameters might possibly point to a pharmacodynamic difference between the two drug classes.

Sustained facial muscle activity during REM sleep and its correlation with depression

Recently, we proposed that the coupling of cognitive activation and diminished arousal during REM sleep may have a mood regulating effect. Conversely, increased arousal during REM sleep may be associated with mood dysregulation. In this paper, the desensitization model is described, and data are presented on the association between motor activity during REM sleep, wakefulness and severity of depression. Motor activity sleep EEG data and two measures of depressive severity (BDI and HRSD) were obtained from 23 depressed patients. BDI scores were significantly correlated with motor activity only during REM sleep. HRSD scores were correlated with motor activity only during quiet wakefulness. These findings are consistent with the theoretical perspective that dysregulation in arousal mechanisms during REM sleep may promote mood disturbance during the depressive episode.

Effects of race on EEG sleep in major depression

The constellation of EEG sleep changes observed in unipolar depression includes reduced REM latency, increased REM time, increased phasic REM activity, and slow-wave sleep deficits. Effects of depressive severity, medication, family history, episode history, sleep schedules, season, reproductive phase, age, and sex on these measures have been characterized with varying precision. One influence that is virtually uneharacterized is race. Data from an epidemiologically representative sample indicate that races differ with regard to prevalence of affective disorders, with African-Americans at reduced risk relative to Euro-Americans. Studies implicating EEG sleep abnormalities in vulnerability for onset and recurrence of depression indicate that effects of race must be understood. To evaluate the effects of race on sleep, we have conducted a retrospective study of unipolar depressed patients who had participated in research protocols at Western Psychiatric Institute and Clinic from 1981-1994. Groups were based on self-described race (black/white) and were matched blind to EEG sleep data within research protocol to control for diagnostic practices, age, and sex. Patients with histories of substance abuse, alcohol abuse, psychotic disorders, and bipolar disorders were excluded. Only patients with at least two consecutive nights of EEG sleep were included. To date, 46 African-American unipolar depressed patients have been matched to 90 age-, sex-, and protocol-matched Euro-Americans. A double-matched control group was generated to reduce error variance and increase power to detect differences. Results will be discussed with regard to an array of vulnerability factors for unipolar depression.

Nonlinear analysis of sleep EEG data in schizophrenia: calculation of the principal Lyapunov exponent

The generating mechanism of the electroencephalogram (EEG) points to the hypothesis that EEG signals derive from a nonlinear dynamic system. Hence, the unpredictability of the EEG might be considered as a phenomenon exhibiting its chaotic character. The essential property of chaotic dynamics is the so-called sensitive dependence on initial conditions. This property can be quantified by calculating the system's first positive Lyapunov exponent, L 1. We calculated L 1 for sleep EEG segments of 13 schizophrenic patients and 13 control subjects that corresponded to sleep stages I, II, III, IV and REM (rapid eye movement), as defined by Rechtschaffen and Kales, for the lead positions C z and P z. During REM sleep, for both electrode positions, the principal Lyapunov exponent L 1 was significantly increased in schizophrenic patients compared with control subjects. This finding points to altered nonlinear brain dynamics during REM sleep in schizophrenia.

EEG Sleep Characteristics in Dysthymia and Major Depressive Disorder

All night EEG sleep recordings were compared in patients with dysthymia and major depressive disorder. Subjects were selected according to DSM-IV and underwent 2 weeks of treatment with placebo before the sleep evaluations. All patients with major depressive disorder were classified as nonmelancholic and belonged to the recurrent subtype, without full interepisode recovery. Patients with major depressive disorder have a shorter duration of total sleep time, a longer sleep latency and a lower sleep efficiency. However, similar sleep architecture and REM sleep characteristics were found in the two groups. These EEG sleep data seem to favor the existence of a biological overlap between the two forms of nonmelancholic unipolar depression. The validity of dysthymia is still unclear and therefore the nosological implications of our observations are discussed.

On the Dimensionality of Sleep-EEG Data

Sleep-EEG data of 16 healthy subjects, classified according to the Rechtschaffen and Kales criteria, were taken to determine the correlation exponent (CE) or dimensionality (D2) of the data using the Corex program. We tested the applicability of this program to the analysis of sleep-EEG data changing systematically the embedding dimension (ED), the time lag (tau), the number of involved pairs of vectors and the EEG segment by split half. We could confirm the results of other authors according to which the complexity of the EEG signal decreases from stage 'awake, eyes closed' to sleep stages 1, 2, 3 and 4. The differences between the various sleep stages were significant. Stage REM could be differentiated from every stage but stage 1. The most important finding of our study was that the absolute value of the dimensionality depends on almost all the parameters tested: with increasing tau up to tau = 200 the CE increases, which means a 1.56-second shift. A higher number of pairs is needed when the signal is more complex. The ED is selected well between 6 and 11, that means reasonably higher or close to the dimensionalities for that purpose as presented in the literature. Different segments of one sleep stage in 1 subject led to different CE values, thus demonstrating that the EEG signal is not stationary over a segment of 2 min time. Although using chaos mathematics seems to be a useful tool in analyzing EEG data to explore their complexity, we could demonstrate the urgent need of calibrations and conventions to be able to interpret the absolute values.

Persistent effects of antidepressants: EEG sleep studies in depressed patients during maintenance treatment

Electroencephalographic (EEG) sleep studies represent a research tool that can be used to examine depressed patients over different phases of their illness. We examined the long-term effects of imipramine on EEG sleep in 27 subjects who completed 3 years of maintenance treatment on imipramine without experiencing a recurrence. The analyses were performed on EEG sleep data collected prior to acute treatment, after 3 months in maintenance, and every 3 months thereafter. The major aim was to examine specific changes in rapid eye movement (REM) and slow-wave sleep (3WS) as they unfolded over the course of illness and recovery during long-term drug maintenance. The acute changes in the sleep profile produced by antidepressants remained essentially the same throughout the entire period of drug administration. The REM sleep parameters, which were affected immediately, remained essentially unchanged therefter, even as long as 3 years into maintenance treatment. A rapid redistribution of slow-wave sleep in the first part of the night was also observed without an increase in the total amount of slow-wave sleep throughout the night. The application of spectral analysis confirmed that the sleep changes following drug administration remained stable throughout all phases of drug treatment. Thus, it appears that sustained clinical improvement is accompanied by persistent sleep alterations on tricyclic antidepressant medication.

Functional properties of the brain during sleep under subchronic zopiclone administration in man

Zopiclone, a non-benzodiazepine, has been shown to be efficient in the treatment of transient, short-term or chronic sleep disorders. Apart from its hypnotic effects zopiclone has anxiolytic, anticonvulsant and myorelaxant properties and is therefore hardly distinguishable from benzodiazepines. Dependence liability and discontinuation effects have been reported to be less pronounced. Therefore zopiclone seems to be a hypnotic drug which may cause fewer side effects than conventional benzodiazepines. From the electrophysiological point of view one requires from a hypnotic drug the induction of a physiological sleep pattern as well as no alterations of information processing by the brain. The aim of the present study was to investigate the subchronic effect of zopiclone medication on some functional properties of the sleep EEG in healthy subjects. In order to get better insight into the principles of information processing by the brain during sleep and its alterations under the influence of zopiclone we applied some tools from linear system theory to sleep EEG data. For this purpose we investigated late components of auditory and visual evoked potentials during different sleep stages and calculated from these the so-called amplitude-frequency characteristic of the brain. This function describes the relationship between an input and the output of the investigated system. The main advantage of this kind of analysis is that it enables one to detect functional differences during sleep stages. This information can hardly be obtained from conventional spectral analysis. As a result we could demonstrate that under subchronic zopiclone medication no quantitative or qualitative alterations of the functional sleep EEG properties concerning the transfer properties of the brain under auditory and visual stimulation were detectable.

Nonlinear dynamical aspects of the human sleep EEG.

This article deals with the application of methods from the theory of nonlinear dynamical systems to EEG signals. Theoretical background, mathematical concepts and algorithms for the calculation of "non-linear parameters" are reviewed and influences of the structure of reconstructed data sets on the calculations are pointed out. We present results for the estimation of the correlation dimension D2 and the principal Lyapunov-exponent lambda 1 for sleep EEG data respectively from 10 and 15 healthy subjects corresponding to different sleep stages. Essentially, we found a statistically significant decrease of both D2 and lambda 1 as sleep moves towards slow wave stages. The values for REM sleep lie between the values of stage I and II. Moreover, for one subject as an example we present calculations of the principal Lyapunov-exponent lambda 1 and the sum of the two largest Lyapunov-exponents lambda 1 + lambda 2 for EEG segments following subsequently during the night. Finally, we compare our results with investigations of other groups and discuss difficulties and opportunities of the nonlinear approach to human EEG signals.

Nonlinear EEG dynamics during sleep in depression and schizophrenia.

The article deals with the question, whether nonlinear analysis of the sleep EEG may give clues to understanding of disturbed information processing in psychiatric diseases. We point out how the nonlinear approach to EEG dynamics is motivated and review recent investigations concerning nonlinear dynamical properties of physiological systems. We present calculations of the correlation dimension D2 and the principal Lyapunov-exponent lambda 1 for sleep EEG data from 9 depressive and 11 schizophrenic inpatients compared to healthy controls. Combining the findings for D2 and lambda 1 our results point to altered nonlinear brain dynamics mainly during slow wave sleep in depression and during REM sleep in schizophrenia. Finally, possible interpretations of altered nonlinear EEG dynamics during sleep concerning disturbed information processing in depression and schizophrenia are discussed.

Deterministic chaos and the first positive Lyapunov exponent: a nonlinear analysis of the human electroencephalogram during sleep.

Under selected conditions, nonlinear dynamical systems, which can be described by deterministic models, are able to generate so-called deterministic chaos. In this case the dynamics show a sensitive dependence on initial conditions, which means that different states of a system, being arbitrarily close initially, will become macroscopically separated for sufficiently long times. In this sense, the unpredictability of the EEG might be a basic phenomenon of its chaotic character. Recent investigations of the dimensionality of EEG attractors in phase space have led to the assumption that the EEG can be regarded as a deterministic process which should not be mistaken for simple noise. The calculation of dimensionality estimates the degrees of freedom of a signal. Nevertheless, it is difficult to decide from this kind of analysis whether a process is quasiperiodic or chaotic. Therefore, we performed a new analysis by calculating the first positive Lyapunov exponent L1 from sleep EEG data. Lyapunov exponents measure the mean exponential expansion or contraction of a flow in phase space. L1 is zero for periodic as well as quasiperiodic processes, but positive in the case of chaotic processes expressing the sensitive dependence on initial conditions. We calculated L1 for sleep EEG segments of 15 healthy men corresponding to the sleep stages I, II, III, IV, and REM (according to Rechtschaffen and Kales). Our investigations support the assumption that EEG signals are neither quasiperiodic waves nor a simple noise. Moreover, we found statistically significant differences between the values of L1 for different sleep stages.(ABSTRACT TRUNCATED AT 250 WORDS)

The calculation of the first positive Lyapunov exponent in sleep EEG data

To help determine if the EEG is quasiperiodic or chaotic we performed a new analysis by calculating the first positive Lyapunov exponent L 1 from sleep EEG data. Lyapunov exponents measure the mean exponential expansion or contraction of a flow in phase space. L 1 is zero for periodic as well as quasiperiodic processes, but positive in case of chaotic processes expressing the sensitive dependence on initial conditions. We calculated L 1 for sleep EEG segments of 15 healthy male subjects corresponding to sleep stages I, II, III, IV and REM (according to Rechtschaffen and Kales). Our investigations support the assumption that EEG signals are neither quasiperiodic waves nor simple noise. Moreover, we found statistically significant differences between the values of L 1 for different sleep stages.

The influence of lorazepam medication upon the transfer properties of the brain during sleep in man

In order to get better insight into the principles of information processing by the brain during sleep and its alterations under the influence of drugs we applied some tools from linear system theory to sleep EEG data. We investigated late components of auditory and visually evoked potentials (AEPs and VEPs) during different sleep stages and calculated from these the so-called amplitude-frequency characteristics (AFC). The main advantage of this analysis is that it enables one to detect functional differences during different sleep stages. This information can hardly be obtained by conventional spectral analysis. The result of our investigation was that the transfer properties of the brain during sleep were extremely different and that lorazepam medication not only resulted in quantitative alterations of the sleep profile but mainly in highly significant alterations of the functional properties of sleep.

Estimation of the dimensionality of sleep-EEG data in schizophrenics.

Deterministic chaos could be regarded as a healthy flexibility of the human brain necessary for correct neuronal operations. Several investigations have demonstrated that in healthy subjects the dimensionality of REM sleep is much higher than that of slow wave sleep (SWS). We investigated the sleep-EEG of schizophrenic patients with methods from nonlinear system theory in order to estimate the dynamic properties of CNS. We hypothesized that schizophrenics would reveal alterations of their dynamic EEG features indicating impaired information processing. In 11 schizophrenic patients, the EEG's dimensionality during sleep stages II and REM was reduced. We suggest that such lower dimensional chaotic processes might be associated with an overloading of neuronal networks during sleep and therefore the psychopathology of schizophrenics might be due to impaired complexity of their EEG's dynamics.

Are there predictors for sleep deprivation response in depressed patients?

Since Pflug and T611e' s initial report ( 1971), total sleep deprivation (TSD), despite its short-lived, transient effects, has established itself as an antidepressant treatment having positive effects on mood in approximately 60% of dep~ssed patients (for overview see Roy-Burne et al 1984). Hypotheses ascribe the antidepr~ssive properties of TSD to a resynchronization of disturbed biological rhythms (Papousek 1975) or to the prevention of a sleep-associated depressiogenic process (Wu and Bunney 1990). Studies describing the prominent circadian abnormality, diurnal variation of mood (DV), found in many depressives as predictive of a positive response to TSD therapy (for overview see Reinink et al 1990), favor TSD's hypothesized influence on circadian process as the source of its antidepressive action. The present article reexamines DV as a predictor of response to TSD. Sleep-EEG data are

CNS side effects of centrally-active antihypertensive agents: A prospective, placebo-controlled study of sleep, mood state, and cognitive and sexual function in hypertensive males

A prospective, placebo-controlled, comparative evaluation was conducted on two widely prescribed, sympatholytic antihypertensive agents with known CNS effects. In order to separately assess these effects in younger and older male hypertensives, patients were assigned to either of two treatment studies based on age. For study I, 24 males aged 31-59 (mean = 49.8; SD = 7.4) with mild hypertension (mean DBP = 100.2 mm Hg; SD = 8.0) received 3 months of treatment with propranolol (20-80 mg bid), clonidine (0.1-0.3 mg bid), or double-blind placebo in a counterbalanced, crossover design. For study II, 23 elderly hypertensive males (mean DBP = 102.6 mm Hg; SD = 8.2) aged 60-78 years (mean = 65.1; SD = 4.6) were randomized to propranolol (20-40 mg bid) or double-blind placebo therapy. Patients received cognitive testing, mood assessments, and all-night polysomnographic evaluations before and after each treatment period. Multivariate analysis of EEG sleep data was statistically significant for study I, with significant univariate effects on four of the six primary sleep variables: total sleep time was reduced, sleep maintenance decreased, REM latency increased, and percent total REM time was reduced. A similar MANOVA analysis for the effects of treatment on the sleep of older patients (study II) was not significant. However, propranolol administration was found to be associated with a significant decline in cognitive performance in these patients. Significant mood effects were observed with each of the study drugs, and nocturnal penile tumescence (NPT) was significantly decreased in both younger and older patients. Overall, this research suggests that distinct patterns of CNS effects are associated with each of the antihypertensive agents studied.

The effect of in or outpatient status on EEG sleep data and postdex controls levels in depressed patients

In a sample of inpatients with major depressive disorder (MDD), we reported that patients with short REM latency (RL) had higher postdexamethasone (postdex) plasma cortisol levels. We now report on the general association of EEG sleep measures and postdex cortisol levels in the above sample, with comparison to a group of 36 outpatients. EEG sleep data averaged over two nights were compared to data for the 1 .O mg DST. After a two-week drug wash-out period, all patients had a SADS/RDC diagnosis of definite MDD and had a HRS > 14. Clinical and demographic data showed the 52 inpatients did not differ from the 36 outpatients with respect to mean age or HRS. Concerning a comparison of EEG sleep measures, however, the inpatient group showed significantly more impaired sleep efficiency (77.4 ? 14.0% vs 83.0 & 11.77%, p < .05) and other measures of sleep continuity, and had greater abnormalities of REM sleep, including a shorter RL (35.0 ? 25.3 minutes vs 56.3 + 27.5 minutes, p < .OOl), and greater REM time (25.1 ? 13.8 vs 18.5 ? 9.3, p < .05) and REM activity (55.2 + 47.5 vs 29.9 + 24.0, p < .Ol) in the first REM period. A significant correlation between sleep measures and cortisol existed only within the inpatient group, in which the maximum postdex cortisol level was correlated positively with%awake(+0.40,p<.01),%stage1(+0.36,pC.01)andnumberof~ousals (+0.32, p < .05), and negatively with time spent asleep (-0.28, p < .05) and sleep efficiency (-0.44, p < .Ol). Cortisol was negatively correlated with REM latency minus awake (-0.44, p C .OOl) but not with REM activity or REM density. These data suggest that the relationship between sleep and postdex cortisol secretion may hold only in a more severely ill (i.e. inpatient) group.

Depression in borderline patients: A prospective EEG sleep study

The relationship between borderline personality disorder and primary major depression was studied prospectively using Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) interviews and electroencephalographic (EEG) sleep studies. Ten consecutively admitted borderline patients (a prospective sample), defined by Gunderson's Diagnostic Interview for Borderlines (DIB), underwent EEG sleep studies on two consecutive nights and were compared to previously reported samples of nonborderline depressed patients (defined by Research Diagnostic Criteria; RDC), normal controls, and DIB-defined borderline patients who had been referred “to rule out major depression” (a retrospective sample). EEG sleep data were analyzed visually and by automated techniques. Rapid eye movement (REM) latency values were similar in depressed and both borderline groups but significantly different from controls. Eighty-five percent of REM latency values in RDC major depressives were ≤ 65 minutes, compared to similar rates of 75% in the prospective sample of borderline patients and 65% in the retrospective sample, versus 35% for controls ( χ 2 = 10.7, p < 0.005). The REM latency in borderline patients did not vary with the severity of depression as measured by the Hamilton Rating Scale for Depression. In the prospective borderline sample, the major SADS-L diagnoses were chronic intermittent depression (five), current major depression (four) (two unipolar, two bipolar II), and liable personality (one). A convergence of nosologic and EEG sleep data is suggested, and supports the concept of a close relationship between criteria-defined borderline personality disorder and affective illness.

Daytime noise and subsequent night sleep in man.

The effects of daytime noise on recovery processes during subsequent undisturbed night sleep were studied in six healthy men (21-27 years), exposed to 80 dB (A) pink noise 8 h per day for 2 days. Sleep EEG, ECG, and respiration were recorded in the laboratory for five consecutive nights: two baseline nights, two nights following noise stimulation, and again one baseline night. Additionally questionnaire data were collected, reflecting a subjective impairment of the recovery function of sleep after noise exposure. EEG sleep data of the first post-noise night showed an increase in slow wave sleep with a simultaneous decrease in stage 2 sleep. During the second post-noise night these changes were less prominent. Three subjects additionally showed an instability in the sleep course coinciding with elevated heart and respiration rates. However, altogether the autonomic parameters were not clearly affected by the noise exposure. The findings support the assumption that strong daytime noise may interfere with subsequent sleep processes.

Disturbances of sleep and cognitive functioning in patients with dementia

—The relationship of sleep, circadian rhythms, and cognitive impairment in dementia patients is briefly reviewed. All-night sleep EEG data were collected in relatively young and relatively unimpaired patients with presumptive Alzheimer's disease and eight age-matched controls. Delta sleep time and Delta sleep % (Stages 3 and 4)—but not REM sleep measures-were significantly reduced in the patients. Implications of these findings are discussed.