Circadian and homeostatic sleep regulation in humans : effects of age and monochromatic light

The first part of this thesis deals with age-related modifications in the circadian and
homeostatic sleep regulation, whereas in the second part, the effects of an evening
exposure to monochromatic light on subsequent sleep architecture and sleep
electroencephalographic power spectra are described.
Age and sleep
Sleep in humans undergoes several age-related changes, resulting in less
consolidated sleep, reduced slow wave sleep, advanced sleep-wake timing and
shorter nocturnal sleep episodes. The first aim of this thesis was to gain
comprehensive information about the influence of age on circadian and homeostatic
aspects of sleep regulation. We compared the sleep electroencephalogram (EEG) of
healthy young with older volunteers under high and low sleep pressure conditions.
The study design consisted of two different protocols, both started with a baseline
and ended up with a recovery night. The 40-h episode between these two nights
comprised either an episode of total sleep deprivation (SD; high sleep pressure) or
10 sleep/wake cycles with 75 min of sleep followed by 150 min of wakefulness (low
sleep pressure). The recovery nights served to investigate the age-related influence
during enhanced and reduced sleep pressure conditions. The sleep episodes during
the nap protocol allowed comparing circadian modulation of sleep characteristics
between young and older subjects.
The response to high sleep pressure (i.e. after 40 hours of sleep deprivation)
revealed a significantly attenuated frontal predominance of spectral EEG delta power
in the sleep EEG of older participants, most pronounced at the beginning of the night
(Chapter 2). In addition, the dissipation of homeostatic sleep pressure, as indexed by
EEG delta power density, was shallower in the older than in the young group. This
implies either an age-related weaker homeostatic response to sleep deprivation,
predominantly in frontal brain areas, and/or altered cortical functions with an agerelated
higher vulnerability to sleep deprivation.
Under low sleep pressure (i.e. after multiple naps), older participants exhibited
an attenuated occipital decline in delta frequencies in the all-night EEG during
recovery sleep. This arose from an altered time course of EEG delta power density.
The reduction of EEG delta activity after sleep satiation was similar in both age
groups during the first sleep cycle. However, the EEG delta decrease to low sleep
pressure was not longer present during the second sleep cycle in the older study
group compared with the young (Chapter 4).
During the 40-h nap protocol (Chapter 3), we have quantitative evidence for a
weaker circadian arousal signal in the older volunteers. This is reflected in higher
subjective sleepiness levels during the late afternoon and evening (‘wake
maintenance zone’), with more sleep in the elderly during the naps at this time of day
(Chapter 3). The day-night differences in the EEG lower alpha and spindle range
were less pronounced in the older group. Furthermore, the amplitude of the circadian
modulation of REM sleep was attenuated in the elderly and the nocturnal melatonin
secretion was significantly reduced.
Taken together, our study revealed different responses to high and low sleep
pressure, as assessed by the sleep EEG, subjective sleepiness levels and melatonin
secretion, in older subjects when compared to the younger group. These results
emphasize both the attenuation of circadian amplitude and alterations in homeostatic
sleep regulation with age. We also gained insight into age-related differences in
responsiveness of regional and time-dependent aspects of sleep. These age-related
modifications are not uniformly spread over the brain and thus are likely to reflect
differences in recovery or reactivation processes during sleep.
Light and sleep
Beside rods and cones, there is an additional so-called non-image-forming
visual system (NIF) in the human retinal ganglion cells, with highest sensitivity in the
‘blue’ portion of visible light. The NIF is mediated by the photopigment melanopsin
and projects to the circadian pacemaker, located in the suprachiasmatic nuclei
(SCN). With efferents from the SCN to sleep- and wake-promoting brain regions, the
NIF influences the circadian regulation of sleep and wakefulness. We compared
sleep architecture and EEG spectra in young healthy men after evening exposure to
two different wavelengths of light (blue; 460 nm vs. green; 550 nm) or no light. The
time course of EEG slow-wave activity (SWA; 0.75-4.5 Hz) after blue light was
altered, with slightly lower SWA during the first and significantly higher SWA during
the third sleep cycle in parietal and occipital brain regions. These findings could be
interpreted either as the immediate induction of a circadian phase delay, or that the
acute alerting effects of blue light continue into the sleep episode and are followed by
an intra-sleep SWA rebound. Concomitantly, shorter REM sleep cycles after blue
light exposure were observed during these two cycles. Our results show that the
effects of light on human physiology including sleep not only depend on the duration
and intensity of light but also on its wavelength, and thus further emphasize the
critical role of the NIF in the regulation of sleep and circadian rhythms.