Hartmut Schulz

Topographical Analysis of Sleep Spindle Activity

There is evidence for two types of sleep spindle activity, one with a frequency of about 12 cycles/s (cps) and the other of about 14 cps. Visual examination indicates that both spindle types occur independently, whereby the 12-cps spindles are more pronounced in the frontal and the 14-cps spindles in the parietal region. The purpose of this paper is to provide more information about the exact topography of these patterns. First the occurrence of distinct signals in anterior and posterior brain regions was verified using pattern recognition techniques based on matched filtering. Thus the existence of two distinct sources of activity located in the frontal and parietal region of the brain, respectively, was demonstrated using EEG frequency mapping. Evaluation of sleep recordings showed high stability both in the frequency and location of the presumed spindle generators across sleep. Pharmacological effects of lormetazepam and zopiclone on both spindle types were investigated. Both substances enhanced the sleep spindle activity recorded from the frontal and parietal electrodes, but this increase was more pronounced in the parietal brain region.

Fatigue, sleepiness, and physical activity in patients with multiple sclerosis

Fatigue is a frequent and disabling symptom in patients with multiple sclerosis (MS). The objective of the study was to compare fatigue and sleepiness in MS, and their relationship to physical activity. Eighty patients with MS rated the extent of experienced fatigue (Fatigue Severity Scale, FSS) and sleepiness (Epworth Sleepiness Scale, ESS). The relationship between the scales was analysed for the scales as a whole and for single items. The clinical status of the patients was measured with the Extended Disability Status Scale (EDSS). In addition, physical activity was recorded continuously for 1xa0week by wrist actigraphy. The mean scores of fatigue and sleepiness were significantly correlated (FSS vs. ESS rxa0=xa00.42). Single item analysis suggests that fatigue and sleepiness converge for situations that demand self-paced activation, while they differ for situations in which external cues contribute to the level of activation. While fatigue correlated significantly with age (rxa0=xa00.40), disease severity (EDSS, rxa0=xa00.38), and disease duration (rxa0=xa00.25), this was not the case for sleepiness. Single patient analysis showed a larger scatter of sleepiness scores in fatigued patients (FSSxa0>xa04) than in non-fatigued patients. Probably, there is a subgroup of MS patients with sleep disturbances that rate high on ESS and FSS. The amount of physical activity, which was measured actigraphically, decreased with disease severity (EDSS) while it did not correlate with fatigue or sleepiness.

A review of sleep EEG patterns. Part I: A compilation of amended rules for their visual recognition according to Rechtschaffen and Kales

ZusammenfassungFragestellungAus polysomnographischen Labor- und Feldstudien leitete das DLR-Institut für Luft- und Raumfahrtmedizin Kriterien zum Schutz vor nächtlichen Fluglärm für den Flughafen Leipzig/Halle ab, der zu einem Frachtdrehkreuz ausgebaut werden soll. Mit den hier vorgestellten Analysen sollte untersucht werden, ob die prognostizierte dichte Flugabfolge in der Nacht bei Einhaltung der empfohlenen Kriterien zu gravierenden makrostrukturellen Änderungen des schlafes führt oder nicht.MethodikAls Datengrundlage diente eine Feldstudie, in der am Flughafen Köln/Bonn 64 Anwohner polysomnographisch untersucht wurden. Markov-Prozesse wurden für die Modellierung einer achtstündigen Bettzeit verwendet. Es wurde nur zwischen den beiden Zuständen Wach und Schlaf (S1-S4, REM) unterschieden. Übergangswahrscheinlichkeiten zwischen den beiden Zuständen wurden mit logistischen Regressionsmodellen in Abhängigkeit vom aktuellen Zustand, von der in diesem Zustand bereits verbrachten Dauer, von der verstrichenen Schlafzeit und vom Maximalpegel des Fluggeräusches bestimmt. 3 Flugbetriebsszenarien wurden simuliert: Ruhe, Fluglärm vorwiegend am Anfang der Nacht (Modell A) und Fluglärm vorwiegend am Ende der Nacht (Modell E).ErgebnisseBezogen auf eine Bettzeit von 8 Stunden war der Wachanteil im Vergleich zum Ruhemodell (81,1 min) im Modell A um 3,8 min (+4,7%) und im Modell E um 5,9 min (+7,3%) erhöht. Fluglärm am Ende der Nacht führte jedoch zu größeren Schlafstörungen als Fluglärm am Anfang der Nacht, weshalb empfohlen wird, Fluggeräusche in der zweiten Nachthälfte mit einem Malus von 1,4 dB zu belegen.SchlussfolgerungIm Zusammenhang mit Fluglärmwirkungen auf den Schlaf erlauben Markov-Prozesse die flexible Modellierung abhängiger Ereignisse und unterschiedlicher Betriebsszenarien. Bei einhaltung der vom DLR vorgeschlagenen Schutzkriterien ermitteln die vorgestellten Modelle nur geringfügige fluglärmbedingte Erhöhungen von Wachanteil und der Anzahl zusätzlicher erinnerbarer Aufwachreaktionen.SummaryQuestion of the studyOn the basis of polysomnographic laboratory and field studies, the DLR Institute of Aerospace Medicine has developed a concept to protect against adverse effects of nocturnal aircraft noise at Airport Leipzig/Halle, which will be extended to a freight hub. We investigated whether or not the expected high traffic densities during the night will relevantly interfere with sleep macrostructure, if the criteria suggested by DLR are met.MethodsModels were based on data sampled in a polysomnographic field study on 64 residents living in the vicinity of Airport Cologne/Bonn. Markov processes wer used to model a time in bed (TIB) of 8 h. Only two states were differentiated: wake and sleep, the latter consisting of S1-S4 and REM. Transition probabilities were estimated with logistic regression including current state (wake/sleep), duration of current state, elapsed sleep time, and maximum sound pressure level (SPL) of the aircraft noise event (ANE) as covariates. Three traffic scenarios were simulated: (i) no noise, (ii) aircraft noise at the beginning of the night (model A), and (iii) aircraft noise at the end of the night (model E).ResultsOn the basis of 8 hours TIB and compared to the scenario without aireraft noise (81.1 min), time spent awake increased by 3.8 min (+4.7%) in model A and by 5.9 min (+7.3%) in model E. However, aircraft noise at the end of the night caused more pronounced changes in sleep structure than aircraft noise at the beginning of the night. Therefore, we propose to levy a malus of 1.4 dB on aircraft noise events occurring in the second half of the night.ConclusionIn the context of noise effects on sleep, Markov processes allow for a flexible modelling of dependent events and variable traffic scenarios. If the criteria of the DLR protection concept are met, the models predict only minor noise-induced changes in time spent awake and in the number of awakenings recalled in the morning.

The use of diurnal vigilance changes in the EEG to verify vigilance-enhancing effects of memantine in a clinical pharmacological study

In elderly subjects there is a vigilance decrease from morning to noon which was used in a clinical pharmacological model as a state condition to verify vigilance-enhancing effects of an antidementia drug. In this model the effects of Memantine (20 mg, single-dose application) on the quantified EEG were investigated in 16 elderly (mean age: 65 +/- 5 years), healthy subjects (10 females, 6 males) in a randomised, twofold cross-over design vs. placebo under double-blind conditions. EEG was recorded before medication, and 2 and 4 h after medication under reaction time (RT) and resting (RS) conditions. EEG data were subjected to spectral analysis and the topographic distribution of the amplitude values was mapped. The results show that a time-dependent decrease (from morning to noon) in vigilance (indicated by an increase in average EEG amplitudes caused by increased synchronisation in the alpha and beta range and an increase in delta) occurred under placebo which was counteracted by Memantine. The diurnal variations of the EEG and their compensation by a pharmacological agent represent an effective model for investigating the vigilance-enhancing effects of antidementia drugs.

The disturbance of cognitive processes in narcolepsy

SUMMARYu2002 Neuropsychological methods have been applied by different authors to investigate cognitive processes such as attention, information processing, memory and psychomotor performance in narcoleptic patients. A review of the results strongly suggests that cognitive processes in narcoleptic patients are not impaired on a functional but only on a temporal level. Providing that short and challenging tasks were used, the performance of narcoleptic patient did not differ significantly from that of healthy subjects. Performance was impaired mainly when a low and monotonous information input had to be processed, a situation which is typical for tests of vigilance. This was supported by this study measuring critical flicker fusion (CFF) at 15‐min intervals for 10 hours in 10 narcoleptic patients and matched healthy controls. While peak performance did not differ between groups, narcoleptic patients were unable to perform at a steady level through the day. Tiredness and episodes of sleepiness seem to be the main reason for cognitive impairments in narcolepsy.

What have fatigue and sleepiness in common

Hossain et al. (2005) have recently suggested that fatigue and sleepiness can be independent consequences of sleep disorders. They found that a majority (64%) of referred patients with sleep disorders had pathological fatigue scores without overlap of sleepiness, while only 4% had pathological sleepiness without overlapping fatigue. To clarify the relationship between fatigue and sleepiness is of general interest since fatigue is a frequently encountered symptom also in other diseases such as multiple sclerosis (MS), where fatigue is one of the most disabling symptoms. Here we present data on the relationship of fatigue and sleepiness in a sample of 53 patients (39 females, 14 males) with relapsing-remitting or secondary progressive MS from an ongoing study on fatigue and actimetry in MS patients. Patients had a mean age of 42 ± 11 years. Mean duration of the disease was 7.3 ± 6.7 years and the mean score on the Expanded Disability Status Scale (EDSS) was 2.8 ± 1.5. All patients were under treatment with Interferon-beta 1b (Betaferon). Exclusion criteria were psychoactive medication or treatment with corticosteroids during the last 3 months. The patients completed different questionnaires, two of them addressing fatigue and sleepiness. As in the study by Hossain et al. (2005) fatigue was assessed by the Fatigue Severity Scale (FSS; Krupp et al., 1989) and sleepiness by the Epworth Sleepiness Scale (ESS; Johns, 1991). Mean (±SD) scores were 4.2 ± 1.6 for the FSS, and 8.3 ± 3.7 for the ESS. We adopted from Hossain et al. an FSS cut-off scores >3 for increased fatigue and an ESS cut-off score >10 for pathological sleepiness. As in the Hossain et al. analysis we classified the MS patients into four groups according to their FSS and ESS scores. Twenty-five patients (47.2%) were fatigued but not sleepy, 12 patients (22.6%) were both fatigued and sleepy while only three patients (5.7%) were not fatigued but sleepy. The remaining 13 patients (24.5%) were neither fatigued nor sleepy (Fig. 1). The observed proportions are close to those reported by Hossain et al. for patients with sleep disorders, 63.9% scored high on fatigue only, 19.1% on fatigue and sleepiness, 3.9% on sleepiness only and 13.1% neither on fatigue nor on sleepiness. The data from both samples suggest that self-rated fatigue and sleepiness are two dimensions, which vary independently to a large degree. However, while Hossain et al. reported a low correlation (r 1⁄4 0.18) between FSS and ESS total scores, this correlation was higher and significant (r 1⁄4 0.52, P < 0.001) for our sample of MS patients. To further explore the relationship between the two scales, we have performed a single-item analysis (chi-squared tests). Taking multiple testing into account, only P-values £ 0.01 were accepted as statistically significant. Four of eight ESS items were significantly related to one or more FSS items, namely the items ESS 1 (sitting and reading), ESS 2 (watching TV), ESS 3 (sitting, inactive in a public place, e.g. a theatre or a meeting) and ESS 4 (as a passenger in a car for an hour without a break). From the nine FSS items, only three (FSS 1, FSS 3 and FSS 4) were significantly related to single ESS items. The single-item analysis showed that there is limited overlap between both scales, and that the correlation between the FSS and ESS total scores depends essentially on a subset of items. The four ESS items, which were significantly related to FSS items describe situations where patients tend to fall asleep unintentionally while sitting more or less inactive. The four remaining ESS items, which did not correlate significantly with FSS items, describe situations where sleepiness is either intended or at least not clearly avoided, as in item 5 ( Lying down to rest in the afternoon when circumstances permit ) and item 7 ( Sitting quietly after a lunch without alcohol ), or situations, where sleepiness would be absolutely inappropriate as in items 6 ( Sitting and talking to someone ) and 8 ( In a car, while stopped for a few minutes in traffic ). It would be of interest to see whether patients with sleep disorders show a Correspondence to: Stefan Merkelbach, Department of Neurology, HELIOS-Klinikum Erfurt, Nordhäuser Str. 74, 99089 Erfurt, Germany. Tel.: +49 361 781 2131; fax: +49 361 781 2132; e-mail: smerkelbach@erfurt.helios-kliniken.de 24.5

Pattern Recognition by Matched Filtering: An Analysis of Sleep Spindle and K-Complex Density under the Influence of Lormetazepam and Zopiclone

The evaluation of sleep EEG patterns is mostly accomplished by visual analysis. With modern personal computers however, it is possible to perform signal detection within a reasonable length of time automatically. This paper presents a method for signal processing based on matched filtering. This allows the detection of sleep spindles and K-complexes in a sleep EEG recording with a high degree of accuracy. First the technique is described, and the results of a validation study based on the comparison of visual evaluations and computer analysis are presented. Thereafter, results of an application study are presented. Sleep spindle and K-complex density under the influence of lormetazepam and zopiclone were examined. Under both medications sleep spindle density increased while K-complex density decreased. Computation of Pearsons correlation coefficients demonstrated that the interindividual sleep spindle and K-complex variations under both treatments are highly correlated. The data suggest that lormetazepam and zopiclone, although chemically different, have a similar mode of action and display comparable effects on the sleep EEG.

When sleep is perceived as wakefulness: an experimental study on state perception during physiological sleep.

While electrophysiologically measured sleep and perception of sleep generally concur, various studies have shown this is not always the case. The objective of the present study was to assess the perception of actual state during sleep by the technique of planned awakenings and interviewing subjects on the preawakening state. Sixty‐eight (43 females, 25 males) young (mean age: 24.1, SD 5.1u2003years) normal sleeping subjects were deliberately awakened out of consolidated sleep, either stage 2 (S2), or REM sleep, during the first night in a non‐clinical sleep laboratory. While the preawakening state was experienced as sleep in 48 cases (70.6%), it was experienced as wakefulness in 20 cases (29.4%). The percentage of awake judgements was somewhat, but not significantly, higher for awakenings out of S2 (38.2%), to REM sleep (20.6%). The proportion of mismatches between electrophysiologically defined sleep and state judgements was time‐dependent with more awake judgements for REM sleep in the second half of the sleep period (41.7%) than in the first one (17.4%). Those subjects who made an awake judgement more frequently had a feeling of being aware of the situation and their surroundings than those who made a sleep judgement (80% versus 33%). Awareness during sleep may be a cognitive style, which favours mismatches between state perception and electrophysiologically defined sleep. Sleep periods with concordant or discordant state judgements did not differ in electrophysiologically defined sleep onset latency, sleep efficiency, or sleep state distribution.

Lunar cycle effects on sleep and the file drawer problem

Summary Popular beliefs about the influence of the full moon on humans exist, although no solid evidence has so far confirmed these ideas [1]. Cajochen et al. [2] recently presented fascinating data on lunar cycle effects on human sleep. However, in a re-analysis of sleep electroencephalography (EEG) data in three large samples, we were unable to replicate their findings. In addition, we identified further mostly unpublished null findings, suggesting that the conflicting results might be an example of a publication bias (i.e., the file drawer problem).

Do the B-vitamins exhibit antinociceptive efficacy in men ? Results of a placebo-controlled repeated-measures double-blind study

Additive analgesic effects of long-term application of a combination of the vitamins B1, B6, B12 (thiamine diphosphate 100 mg, pyridoxsine-HCl 200 mg, cyanocobalamin 20 micrograms, p.o.) on a single dose of the nonsteroidal anti-inflammatory drug (NSAID) diclofenac (diclofenac-Na, 50 mg, p.o.) were investigated with a noninflammatory experimental pain model in 38 healthy volunteers. B-vitamins were given with 3 dosages/day for 1 week. Then experimental sessions of 3 h followed to test the analgesic efficacy of the NSAID. In these sessions, phasic pain was induced by intracutaneously applied brief electrical pulses (20 ms). Measured were the pain ratings, the cerebral potentials and the EEG delta power in responses to the stimuli as target variables for the analgesic test. Unspecific effects upon the vigilance system were evaluated by spontaneous EEG, auditory-evoked potentials and reaction times. The investigation was performed as a placebo-controlled, double-blind cross-over study. Blood samples were taken to monitor the plasma concentrations of the active agents. Whereas in the first block of stimuli (40-60 min after diclofenac medication) no analgesic effects of diclofenac could be observed, either given alone or after pretreatment with the B-vitamins, in the second stimulus block (100-120 min after medication) significant effects appeared in all target variables describing analgesia. Pain ratings were decreased by about 5%, late cerebral potentials by about 9% and stimulus-induced delta power of the EEG by about 14%. These effects were significant (p < 0.05, p < 0.01) against those under placebo, but came out to be independent of the B-vitamin pretreatment. No B-vitamin effects of the B-vitamins could be detected, either additive analgesic effects on diclofenac analgesia or on the concomitant variables describing unspecific sedative effects. Clearly the B-vitamin pretreatment for 1 week enlarged the plasma levels for vitamin B6 by 700%, for vitamin B1 by 70% and for vitamin B12 by 50%. All B-vitamin concentrations were independent of each other.