PharmaElectrohypnograms from
humans: Biomarkers for Recreational Sleep
Prof. Dr. Wilfried
Dimpfel, Justus-Liebig-University Giessen
c/o NeuroCode AG, D 35578 Wetzlar,
Sportparkstr. 9, Germany
Phone: 0049(0)64412002030 Email: w.dimpfel@neurocode-ag.com
To assess drug effects on sleep, polysomnographic recordings in sleep laboratories are the tool of choice. During this procedure EEG as well as a number of additional parameters like breathing, snoring and muscle activity are recorded continuously during at least two complete nights.
Fig.
1 The sleep laboratory at NeuroCode AG
Due to a newly developed world wide patented index of depth of sleep, which was developed at the end of the nineties new objective assessment of sleep became available (Dimpfel, 1998). It is based on the relationship of theta and beta frequencies of the EEG and depicts depth of sleep between 35 and 100%. Sleep starts at about 80%. This sleep index – also called spectral frequency index (SFX) or “Hypnax” – was validated against the gold standard of Rechtschaffen and Kales. Meanwhile this approach has proven to be more sensitive and better suitable to characterize drug effects in comparison to the historical but still widely used analysis by Rechtschaffen and Kales (Rechtschaffen and Kales, 1968). The time course of sleep also called an Electrohypnogram is depicted according to depth of sleep not longer as a stairway but – more physiologically – as a continuous change of deeper and flat sleep.
Fig. 2 Comparison of Electrohypnograms from a healthy and a sick patient.
From this new Electrohypnogram it is quite easy to determine the amount of time which is spent by a patient beyond a particular depth of sleep (like 68% representative for deeper sleep). One can calculate this new parameter for successive depths of sleep (i.e. 62%-56%-50%) for every night recorded. If the first night is a so-called placebo night and the second one recorded after ingestion of a sleeping aid one determines the difference for each patient and averages the data on a group of i.e. 20 patients.
Fig. 3 Data
from a recent sleep study with red bar representing the placebo group and green
bars representing the verum group. Differences are statistically significant
different at p<0.01.
This kind of sleep analysis is the first one to allow to relate data from EEG to parameters from sleep questionnaires like the SFA, which is used in most clinical studies regarding sleep. It contains information on the recreational aspects of sleep but (like with most questionnaires) needs larger groups of patients to prove significant differences between placebo and verum. Relating now the time spent beyond a particular depth of sleep with data from the questionnaire a correlation can be observed.
In summary the newly developed sleep analysis based on
an objective determination of depth of sleep from continuously recorded EEG
data provides better information on the recreational effects of sleeping aids.
References
Dimpfel W, Hofmann H-C, Schober F, Todorova A (1998).
Validation of an EEG-Derived Spectral Frequency Index (SFx) for continuous
monitoring of sleep depth in humans.
Eur. J. Med. Res. 3: 453-460
Hammer N, Todorova A, Hofmann HC, Schober F, Vonderheid-Guth B, Dimpfel
W (2001) Description of healthy and disturbed
sleep by means of the spectral frequency index (SFx)- a retrospective analysis.
Eur J Med Res 6: 333-44
Rechtschaffen
A, Kales A (1968) A manual
for standard terminology, techniques and scoring system for sleep stages of
human subjects. Public Health