Circadian and homeostatic modulation of sleep spindles in the human electroencephalogram

Sleep spindles are transient EEG oscillations of about 12-16 Hz. Together with slow waves, they hallmark the human non-REM sleep EEG. Sleep spindles originate in the thalamus and are suggested to have a sleep protective function by reducing sensory transmission to the cortex. Other evidence points to an involvement of sleep spindles in brain plasticity processes during sleep. Previous studies have shown that sleep spindles are both under homeostatic (sleep-wake dependent) and circadian (time of day-dependent) control. Furthermore, frequency-specific topographical distribution of power density within the spindle frequency range has been reported. The aim of this thesis was to assess homeostatic and circadian influences on spectral spindle frequency activity (SFA) and spindle parameters in different brain regions. Healthy young volunteers participated in both a 40-h sleep deprivation (SD) and a 40-h multiple nap paradigm. The recovery nights after the SD and the nap protocol served to assess the effect of enhanced and reduced homeostatic sleep pressure, respectively. The multiple nap paradigm revealed the modulation of sleep spindles across the circadian cycle. Two different methodological approaches were used to analyze the EEGs: classical spectral analysis (Fast Fourier Transform, FFT) and a new method for instantaneous spectral analysis (Fast Time Frequency Transform, FTFT), developed as a part of this thesis project in collaboration with Wim Martens from TEMEC, The Netherlands. Slow wave activity (SWA, spectral power density in the 0.75-4.5 Hz range) and spindle frequency activity (SFA, spectral power density in the spindle frequency range) in the high frequency range (13.75-16.5 Hz) were oppositely affected by the differential levels of sleep pressure (Chapter 2). These effects strongly depended on brain location. After SD, the SWA increase compared to the baseline night was most pronounced in the beginning of the night and in the fronto-central region. Power density in the high spindle frequency range was reduced in the centro-parietal brain region. After the nap protocol, when sleep pressure was reduced, power density in the SWA range was decreased at the beginning of the night. SFA was generally increased after the nap protocol. The data indicate that the balance between SWA and high-frequency spindle activity may represent a sensitive marker for the level of homeostatic sleep pressure. The new method of FTFT revealed that spindle density was reduced after SD (Chapter 3). This reduction was particularly apparent in the frontal derivation, and most pronounced in the first half of the night. The reduction of spindle density with its temporal and local specificity confirms the inverse homeostatic regulation of slow waves and sleep spindles. Sleep spindles had a lower frequency and a higher amplitude after SD. Within an individual spindle, frequency variability was reduced, which indicates that sleep spindles were more stable and homogenous after SD. The increase in spindle amplitude and the reduced intra-spindle frequency variability suggests a higher degree of synchronization in thalamocortical neurons under high homeostatic sleep pressure. EEGs during the nap paradigm were analyzed to compare SFA and sleep spindle characteristics during and outside the circadian phase of melatonin secretion (the “biological night” and “biological day”, respectively) (Chapter 4). In naps occurring during the phase of melatonin secretion, lower spindle frequencies were promoted, indexed as a reduction in mean spindle frequency (i.e. slowing of sleep spindles) and an increase in spindle amplitude and SFA in the low-frequency range (up to ~14.25 Hz) paralleled by a reduction in the high-frequency range (~ 14.5-16 Hz). Furthermore, spindle density was increased, and intra-spindle frequency variability reduced during the night. Thus, the circadian pacemaker is likely to promote low-frequency, high amplitude and homogenous sleep spindles during the biological night. The circadian modulation of sleep spindles may be a way by which the circadian system modulates and times sleep consolidation. This circadian modulation clearly depended on brain location such that it was maximal in the parietal and minimal in the frontal derivation. Taken together, the segregated analysis of different spindle parameters by the new high-time and high-frequency resolution spindle analysis provides new insights into sleep spindles and their regulation. Both homeostatic and circadian processes affected sleep spindles characteristics in a topography-specific manner. These statedependent local aspects provide further evidence that sleep is a dynamic phenomenon which reflects use-dependent recovery or reactivation processes

Circadian and homeostatic modulation of sleep spindles in the human electroencephalogram

Sleep spindles are transient EEG oscillations of about 12-16 Hz. Together with slow waves, they hallmark the human non-REM sleep EEG. Sleep spindles originate in the thalamus and are suggested to have a sleep protective function by reducing sensory transmission to the cortex. Other evidence points to an involvement of sleep spindles in brain plasticity processes during sleep. Previous studies have shown that sleep spindles are both under homeostatic (sleep-wake dependent) and circadian (time of day-dependent) control. Furthermore, frequency-specific topographical distribution of power density within the spindle frequency range has been reported. The aim of this thesis was to assess homeostatic and circadian influences on spectral spindle frequency activity (SFA) and spindle parameters in different brain regions. Healthy young volunteers participated in both a 40-h sleep deprivation (SD) and a 40-h multiple nap paradigm. The recovery nights after the SD and the nap protocol served to assess the effect of enhanced and reduced homeostatic sleep pressure, respectively. The multiple nap paradigm revealed the modulation of sleep spindles across the circadian cycle. Two different methodological approaches were used to analyze the EEGs: classical spectral analysis (Fast Fourier Transform, FFT) and a new method for instantaneous spectral analysis (Fast Time Frequency Transform, FTFT), developed as a part of this thesis project in collaboration with Wim Martens from TEMEC, The Netherlands. Slow wave activity (SWA, spectral power density in the 0.75-4.5 Hz range) and spindle frequency activity (SFA, spectral power density in the spindle frequency range) in the high frequency range (13.75-16.5 Hz) were oppositely affected by the differential levels of sleep pressure (Chapter 2). These effects strongly depended on brain location. After SD, the SWA increase compared to the baseline night was most pronounced in the beginning of the night and in the fronto-central region. Power density in the high spindle frequency range was reduced in the centro-parietal brain region. After the nap protocol, when sleep pressure was reduced, power density in the SWA range was decreased at the beginning of the night. SFA was generally increased after the nap protocol. The data indicate that the balance between SWA and high-frequency spindle activity may represent a sensitive marker for the level of homeostatic sleep pressure. The new method of FTFT revealed that spindle density was reduced after SD (Chapter 3). This reduction was particularly apparent in the frontal derivation, and most pronounced in the first half of the night. The reduction of spindle density with its temporal and local specificity confirms the inverse homeostatic regulation of slow waves and sleep spindles. Sleep spindles had a lower frequency and a higher amplitude after SD. Within an individual spindle, frequency variability was reduced, which indicates that sleep spindles were more stable and homogenous after SD. The increase in spindle amplitude and the reduced intra-spindle frequency variability suggests a higher degree of synchronization in thalamocortical neurons under high homeostatic sleep pressure. EEGs during the nap paradigm were analyzed to compare SFA and sleep spindle characteristics during and outside the circadian phase of melatonin secretion (the “biological night” and “biological day”, respectively) (Chapter 4). In naps occurring during the phase of melatonin secretion, lower spindle frequencies were promoted, indexed as a reduction in mean spindle frequency (i.e. slowing of sleep spindles) and an increase in spindle amplitude and SFA in the low-frequency range (up to ~14.25 Hz) paralleled by a reduction in the high-frequency range (~ 14.5-16 Hz). Furthermore, spindle density was increased, and intra-spindle frequency variability reduced during the night. Thus, the circadian pacemaker is likely to promote low-frequency, high amplitude and homogenous sleep spindles during the biological night. The circadian modulation of sleep spindles may be a way by which the circadian system modulates and times sleep consolidation. This circadian modulation clearly depended on brain location such that it was maximal in the parietal and minimal in the frontal derivation. Taken together, the segregated analysis of different spindle parameters by the new high-time and high-frequency resolution spindle analysis provides new insights into sleep spindles and their regulation. Both homeostatic and circadian processes affected sleep spindles characteristics in a topography-specific manner. These statedependent local aspects provide further evidence that sleep is a dynamic phenomenon which reflects use-dependent recovery or reactivation processes

Subjective Mood in Young Unmedicated Depressed Women under High and Low Sleep Pressure Conditions

Diurnal mood variations are one of the core symptoms in depression, and total sleep deprivation (SD) can induce rapid, short-lasting clinical improvement in depressed patients. Here, we investigated if differential sleep pressure conditions impact on subjective mood levels in young women with major depressive disorder (MDD) without sleep disturbances, and in healthy controls. Eight healthy and eight MDD women underwent 40-h SD (high sleep pressure) and 40-h multiple NAP (low sleep pressure) protocols under constant routine conditions during which subjective mood was assessed every 30-min. MDD women rated overall significantly worse mood than controls, with minimal values for both groups during the biological night (ca. 4 a.m.), under high and low sleep pressure conditions. During SD, nighttime mood ratings in MDD women were lower than in controls and partially recovered during the second day of SD, but never attained control levels. The degree of this diurnal time-course in mood under SD correlated positively with sleep quality in MDD women. Our data indicate that MDD women without sleep disturbances did not exhibit a SD-induced antidepressant response, suggesting that the mood enhancement response to sleep deprivation might be related to the co-existence of sleep disturbances, which is an association that remains to be fully established

Age effects on spectral electroencephalogram activity prior to dream recall.

Ageing is associated with marked changes in sleep timing, structure and electroencephalographic (EEG) activity. Older people exhibit less slow-wave and spindle activity during non-rapid eye movement (NREM) sleep, together with attenuated levels of rapid eye movement (REM) sleep as compared to young individuals. However, the extent to which these age-related changes in sleep impact on dream processing remains largely unknown. Here we investigated NREM and REM sleep EEG activity prior to dream recall and no recall in 17 young (20-31 years) and 15 older volunteers (57-74 years) during a 40 h multiple nap protocol. Dream recall was assessed immediately after each nap. During NREM sleep prior to dream recall, older participants displayed higher frontal EEG delta activity (1-3 Hz) and higher centro-parietal sigma activity (12-15 Hz) than the young volunteers. Conversely, before no recall, older participants had less frontal-central delta activity and less sigma activity in frontal, central and parietal derivations than the young participants. REM sleep was associated to age-related changes, such that older participants had less frontal-central alpha (10-12 Hz) and beta (16-19 Hz) activity, irrespective of dream recall and no recall. Our data indicate that age-related differences in dream recall seem to be directly coupled to specific frequency and topography EEG patterns, particularly during NREM sleep. Thus, the spectral correlates of dreaming can help to understand the cortical pathways of dreaming

Age effects on spectral electroencephalogram activity prior to dream recall

Ageing is associated with marked changes in sleep timing, structure and electroencephalographic (EEG) activity. Older people exhibit less slow-wave and spindle activity during non-rapid eye movement (NREM) sleep, together with attenuated levels of rapid eye movement (REM) sleep as compared to young individuals. However, the extent to which these age-related changes in sleep impact on dream processing remains largely unknown. Here we investigated NREM and REM sleep EEG activity prior to dream recall and no recall in 17 young (20-31years) and 15 older volunteers (57-74years) during a 40h multiple nap protocol. Dream recall was assessed immediately after each nap. During NREM sleep prior to dream recall, older participants displayed higher frontal EEG delta activity (1-3Hz) and higher centro-parietal sigma activity (12-15Hz) than the young volunteers. Conversely, before no recall, older participants had less frontal-central delta activity and less sigma activity in frontal, central and parietal derivations than the young participants. REM sleep was associated to age-related changes, such that older participants had less frontal-central alpha (10-12Hz) and beta (16-19Hz) activity, irrespective of dream recall and no recall. Our data indicate that age-related differences in dream recall seem to be directly coupled to specific frequency and topography EEG patterns, particularly during NREM sleep. Thus, the spectral correlates of dreaming can help to understand the cortical pathways of dreaming. © 2011 European Sleep Research Society

Does the Circadian Modulation of Dream Recall Modify with Age?

STUDY OBJECTIVES: The ultradian NREM-REM sleep cycle and the circadian modulation of REM sleep sum to generate dreaming. Here we investigated age-related changes in dream recall, number of dreams, and emotional domain characteristics of dreaming during both NREM and REM sleep. DESIGN: Analysis of dream recall and sleep EEG (NREM/REM sleep) during a 40-h multiple nap protocol (150 min of wakefulness and 75 min of sleep) under constant routine conditions. SETTING: Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland. PARTICIPANTS: Seventeen young (20-31 years) and 15 older (57-74 years) healthy volunteers INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Dream recall and number of dreams varied significantly across the circadian cycle and between age groups, with older subjects exhibiting fewer dreams (P > 0.05), particularly after naps scheduled during the biological day, closely associated with the circadian rhythm of REM sleep. No significant age differences were observed for the emotional domain of dream content. CONCLUSIONS: Since aging was associated with attenuated amplitude in the circadian modulation of REM sleep, our data suggest that the age-related decrease in dream recall can result from an attenuated circadian modulation of REM sleep

Impact of age, sleep pressure and circadian phase on time-of-day estimates

Orientation and self-location within the temporal fabric of the environment involves multiple organismic systems. While temporal self-location on the physiological level has been known for some time to be based on a 'biological clock' located within the hypothalamus, the mechanisms that participate in temporal position finding on the cognitive level are not yet fully understood. In order to probe the mechanisms that underlie this faculty, verbal estimates on time-of-day were collected at 3.75-h intervals from 16 young (7 males, 8 females; 20-31 years) and 16 older (8 males, 8 females; 57-74 years) subjects in a balanced crossover design during 40-h epochs of prolonged wakefulness and 40-h epochs of sleep satiation spent under constant routine conditions. An overestimation of clock time during prolonged wakefulness was found in both age-groups, with significantly larger errors for the older group (young: 0.5+/-0.2h; older: 1.5+/-0.2h, p>0.05). In both age-groups, estimation errors ran roughly parallel to the time course of core body temperature. However a significant interaction between time-of-day and age-group was observed (rANOVA, p>0.05): younger subjects exhibited similar estimation errors as the older subjects after 16 h of prior wakefulness, whereas the latter did not manifest decrements under high sleep pressure. Data collected under conditions of sleep satiation also displayed a diurnal oscillation in estimation errors and a general overestimation (young: 0.8+/-0.2h; older: 1.3+/-0.3h, p>0.05). Here however, the age-groups did not differ significantly nor was there an interactive effect between time-of-day and age-group. The effects of age, duration of wake time and circadian phase on temporal position finding are in line with predictions based on the idea that awareness about current position in time is derived from interval timing processes