Wake Epochs Research Articles

The acute effect of music on interictal epileptiform discharges

This study was a prospective, randomized, single-blinded, crossover, placebo-controlled, pilot clinical trial investigating the effect of Mozart’s Sonata for Two Pianos (K448) on the frequency of interictal epileptiform discharges (IEDs) from the EEGs of children with benign childhood epilepsy with centrotemporal spikes, or “rolandic” epilepsy. The goal was to demonstrate decreased frequency of IEDs with exposure to K448. Four subjects were recruited and 4-hour awake EEG recordings performed. IED frequency per minute was averaged over each of three epochs per hour. Mean IED count per epoch, standard deviations, and variance were calculated. Only complete waking epochs were analyzed. Two subjects demonstrated sufficient waking IEDs for statistical analysis, consisting of three epochs of K448-related effects. Significant decreases in IEDs per minute (33.7, 50.6, and 33.9%) were demonstrated comparing baseline with exposure to K448, but not to control music (Beethoven’s Fü r Elise).

Temporal correlations between heart rate, medullary units and hippocampal theta rhythm in anesthetized, sleeping and awake guinea pigs

The aim of the present report was to determine whether or not the heart rate could show any relation to a central electrographic rhythm such as hippocampus theta. Our experimental design included anesthetized as well as chronically implanted guinea pigs. The cross-correlation, spike trigger averaging, between the medullary neurons firing, or the R-wave of the electrocardiogram, or hippocampal units, and theta rhythm revealed phase-locking during epochs of wakefulness, slow wave sleep and paradoxical sleep, and under anesthesia. A special case was paradoxical sleep, an epoch known to lack autonomic function control (open-loop), in which a great majority of the recorded units (83%) exhibited theta phase-locking. The experimental control was a flat cross-correlation after unit firing shuffling. A brain-stem autonomic oscillator, together with a hypothalamic and a cortico-frontal centers entrained by baroreceptor input, have been proposed as the heart rhythm control system. The present report suggests that hippocampal theta waves may participate, in coordination with the hypothalamic center, as a heart rate modulator.

Temporal and stagewise distribution of high frequency EEG activity in patients with primary and secondary insomnia and in good sleeper controls.

In the present study, we evaluate the temporal and stagewise distribution of high frequency EEG activity (HFA) in primary and secondary insomnia. Three groups (n=9 per group) were compared: primary insomnia (PI), Insomnia secondary to major depression (MDD), and good sleeper controls (GS). Groups were matched for age, sex and body mass. Average spectral profiles were created for each sleep epoch. Grand averages were created for each NREM cycle and each stage of sleep after removing waking and movement epochs and epochs containing micro or miniarousals. It was found that HFA (in terms of relative power) tends to increase across NREM cycles, occurs maximally during stage 1 and during REM sleep, and that both these effects are exaggerated in patients with PI. In addition, HFA was found to be inversely associated with Delta activity and the three groups in our study appear to exhibit characteristic Delta/Beta patterns. Our data are consistent with the perspective that HFA is related to CNS arousal to the extent that Beta/Gamma activity occurs maximally during shallow stages of sleep and maximally in subjects with PI.

Lipopolysaccharide effects on neuronal activity in rat basal forebrain and hypothalamus during sleep and waking.

Peripheral administration of lipopolysaccharide (LPS) is associated with alterations in sleep and the electroencephalogram. To evaluate potential neuronal mechanisms for the somnogenic effects of LPS administration, we used unanesthetized rats to survey the firing patterns of neurons in various regions of rat basal forebrain (BF) and hypothalamus during spontaneous sleep and waking and during the epochs of sleep and waking that occurred after the intraperitoneal administration of LPS. In the brain regions studied, LPS administration was associated with altered firing rates in 39% of the neurons examined. A larger proportion of LPS-responsive units showed vigilance-related alterations in firing rates compared with nonresponsive units. Approximately equal proportions of LPS-responsive neurons showed increased and decreased firing rates after LPS administration, with some units in the lateral preoptic area of the hypothalamus showing particularly robust increases. These findings are consistent with other studies showing vigilance-related changes in neuronal activity in various regions of BF and hypothalamus and further demonstrate that peripheral LPS administration alters neuronal firing rates in these structures during both sleep and waking.

Effect of frequent brief awakenings from nonREM sleep on the nonREM-REM sleep cycle.

In the framework of a selective sleep deprivation study, eight young men were repeatedly awakened during 3 nights from nonREM sleep (nonREMS). The mean number of awakenings per night was 27.4, 29.5 and 32.8. In order to avoid excessive suppression of slow wave sleep, no awakening occurred in the first nonREMS episode. Compared to baseline, cycle 2 was significantly prolonged in all 3 nights, and cycle 3 in night 3 only. However, after subtracting the waking intervals, the differences from baseline was eliminated. The results show that the mechanisms underlying sleep cycle control keep track of sleep time and disregard epochs of waking.

Polysomnography: a systematic review*

Polysomnography refers to the continuous monitoring of multiple neurophysiological and cardiorespiratory variables, usually over the course of a night, to study normal and disturbed sleep. Electroencephalographic, electrooculographic and electromyographic channels provide the basis for staging the recording into successive epochs of wakefulness and various non-Rapid-Eye-Movement (REM) and REM sleep. Detection of airflow at the nose and mouth by means of thermistors, and analysis of breathing patterns recorded from sensors placed around the ribcage and abdomen, sound recordings, the electrocardiogram and the combined application of several other measurement techniques allow the assessment of normal and abnormal physiological events in relation to sleep structure. Polysomnography has an important role in the diagnosis of disorders of sleep and wakefulness as well as in the assessment of treatment effects and in scientific investigations. Developments in digital signal processing have contributed to its widespread application in clinical practice and research.

Sleep studies and supportive ventilatory treatment in patients with congenital muscle disorders.

Eight ambulant children aged 6-13 years, four with congenital myopathy, two with congenital muscular dystrophy and two with the rigid spine syndrome, presented with recurrent chest infections, morning headaches, shallow breathing at night, or respiratory failure. Polysomnography confirmed the presence of nocturnal hypoxaemia with oxygen saturation on average less than 90% for 49% of sleep and less than 80% for 19% of sleep accompanied with severe hypoventilation. Additionally there was sleep disturbance characterised by an increased number of wake epochs from deep sleep (in comparison to 10 non-hypoxaemic subjects). The severity of sleep hypoxaemia did not correlate with symptoms. Treatment with night time nasal ventilation was started and repeat polysomnography showed normal overnight oxygen saturation and a reduced number of wake epochs during deep sleep. It is important to be vigilant for sleep hypoventilation in these patients and sleep studies should be part of the routine respiratory evaluation. Treatment with nasal ventilation is effective in reversing the nocturnal respiratory failure without significant disturbance to life style.

Changes in hypothalamic prostaglandin E 2 may predict the occurrence of sleep or wakefulness as assessed by parallel EEG and microdialysis in the rat

Prostaglandin (PG) E 2 is produced by mammalian hypothalamus and when administered exogenously prolongs wakefulness. In order to study the relation of endogenous hypothalamic PGE 2 to sleep and wakefulness, we have used microdialysis in freely moving rats associated with EEG recording. Male Wistar rats were implanted with three cortical electrodes and with a guide cannula for microdialysis in the space between the paraventricular nucleus (PVN) and the ventromedial hypothalamus (VMH). PGE 2 was measured by RIA in 3-or 6-min dialysates 15 days after surgery, when sleep patterns were normal again and PGE 2 production stabilised. PGE 2 levels were significantly higher during wakefulness (601 ± 35 pg/ml, 5 experiments, 35 samples) than during slow-wave sleep (487 ± 24 pg/ml, 5 experiments, 49 samples). Samples corresponding to paradoxical sleep showed a tendency towards higher PGE 2 values compared to slow-wave sleep but lower compared to wakefulness. In epochs of wakefulness or sleep lasting at least 12 min, high PGE 2 levels in the middle of wakefulness regularly dropped, thus announcing the occurrence of sleep. During sleep, PGE 2 first went on dropping and then reincreased towards the values that characterize early periods of wakefulness. In its turn, this reincrease in PGE 2 announced the end of sleep and the imminent occurence of wakefulness. It is the first study to our knowledge showing that the evolvement in endogenous PG profile may predict the occurrence of sleep or wakefulness.

Behavioural and electrophysiological studies of entorhinal cortex lesions in the rat

Bilateral ibotenic acid injections aimed at the entorhinal cortex (EC) lesioned the EC and subiculum in 30% of animals (group EC/S) and caused additional hippocampal damage in 50% (group RH). Both lesions increased acetylcholinesterase (AChE) staining in the intermediate molecular layer of the dentate gyrus. EC/S lesions increased diurnal deep sleep and the incidence of spindles but decreased REM sleep. RH lesions increased nocturnal deep sleep and decreased nocturnal quiet sleep. Both lesions reduced power over the theta frequency range from 6–10 Hz for epochs of REM sleep and quiet waking but not deep sleep. Peak frequency was unaffected. The RH group and a subset of the EC/S group were nocturnally, but not diurnally, hyperactive. Six weeks after the lesion there was no evidence for hyperactivity in a novel open field. The EC/S lesion impaired exploration as indicated by reduced motility and rearing in an open field and by the failure of EC/S-lesioned rats to increase contact time in response to a novel olfactory cue. Place navigation learning in a Morris maze was not affected by EC/S or RH lesions. However, when the spatial location of the hidden platform was shifted EC/S-lesioned rats were impaired. The sprouting response, reduced theta power and exploration deficits resemble those reported following electrolytic lesions, but the lack of effect on place navigation learning contrasts with reports of impaired spatial learning following electrolytic lesions. The data prompt a reexamination of the role which the EC projection to the hippocampus plays in spatial learning.

Sleep homeostasis in the rat: Simulation of the time course of EEG slow-wave activity

According to the two-process model of sleep regulation, a homeostatic Process S increases during waking and declines during sleep. For humans, the time course of S has been derived from the changes in EEG slow-wave activity (SWA; spectral power density in the 0.75–4.0 Hz range) during sleep. We tested the applicability of the model to sleep in the rat. The simulation was based on the vigilance states for consecutive 8-s epochs of a 96-h experiment in 9 animals. The level of S was made to decrease in epochs of non-REM sleep (NREMS), and to increase in epochs of waking or REM sleep according to exponential functions. By optimizing the initial value and the time constants of S, a close fit between the hourly values of SWA in NREMS and of S was obtained. The biphasic time course of SWA during baseline, its enhancement in the initial recovery period after 24-h sleep deprivation, and its subsequent prolonged undershoot were present in the simulation. We conclude that sleep homeostasis as conceptualized in the two-process model may be a general property of mammalian sleep.

Sleep suppression following kainic acid-induced lesions of the basal forebrain

We have described elsewhere neurons in the ventral basal forebrain of cats that have elevated discharge rates during sleep and during transitions from waking to sleep, yet have comparatively low discharge rates during waking. These sleep-active neurons may mediate the hypnogenic properties of the basal forebrain. To further evaluate their role in the control of sleep, we examined the effects of basal forebrain lesions produced by microinjections of the relatively cell-selective neurotoxin, kainic acid, on sleep. Lesions were made bilaterally in two regions that contain high densities of sleep-active neurons: the horizontal limb of the diagonal bands of Broca and the lateral preoptic area-substantia innominata. Twelve-hour polygraph recordings were made before and at various intervals after basal forebrain damage in a total of eight cats. The lesions resulted in reduced time spent in deep, nonrapid eye-movement sleep and REM sleep, and increased time spent awake. These abnormalities persisted through 6 to 7 weeks postlesion. Reductions in deep non-REM sleep were due to decreases in bout number, particularly in the number of extended deep non-REM episodes (i.e., those >5 min in duration). The number of REM sleep episodes was also significantly reduced. The average duration of epochs of waking was elevated throughout the postlesion period. Thus, in the postlesion period, cats exhibited an impaired ability to initiate and maintain consolidated periods of sleep, particularly of deeper sleep stages. Lesions were also associated with reduced EEG spindling during sleep. These results are consistent with our hypothesis that sleep-active neurons are a component of a basal forebrain sleep- and EEG-regulating mechanism.

Effect of valproic acid treatment on spike-wave discharge patterns during sleep and wakefulness.

7 patients suffering from absences were recorded before antiepileptic treatment, in the early phase of valproate monotherapy and after having reached steady state. Recordings made with the Oxford-Medilog 4-channel cassette recorder were analyzed visually as well as by a computerized s-w pattern recognition approach, the latter facilitating quantification of pattern characteristics (number, amplitudes and duration of spikes and waves). Measurements were made separately for epochs of wakefulness and sleep. Compared to the premedication phase the amount of s-w discharges in 24 h showed an average reduction of more than 90%. For the majority of the patients, 24-hour discharge profiles showed a maximum in the early morning. Duration and amplitude of both spike and wave elements was higher during sleep. For the waking state, the ratio wave amplitude/spike amplitude was found to be increased under medication.

Zona incerta and lateral hypothalamic afferents to the midbrain reticular core of cat — An HRP and electrophysiological study

The zona incerta (ZI) and lateral hypothalamic afferents to the midbrain reticular formation (MRF) of cat were investigated with the horseradish peroxidase (HRP) technique and by using antidromic identification in experiments on chronically implanted, behaving preparations. Following HRP injections restricted to the MRF territory (nucleus cuneiformis and central tegmental field), the largest number of retrogradely labeled cells appeared in the medial third of the ipsilateral ZI. Labeling extended medially to the adjacent lateral hypothalamus. The number of positive elements gradually diminished towards the lateral extremity of the ZI and continuing reticularis thalamic nucleus. Ventral lateral geniculate neurons were consistently labeled. No positive elements were found in ventrobasal, pulvinar-lateralis posterior and ventralis lateralis thalamic nuclei. The MRF-evoked antidromic invasion of ZI cells occurred with a sharp mode between 0.5 and 0.75 ms (median latency of the whole sample: 0.6 ms). The conduction velocity of the ZI leads to MRF axons is twice as high as the values found in the reciprocal MRF leads to ZI projection. In addition to the antidromically elicited discharges, MRF stimulated resulted in short-latency synaptic excitation, sometimes following the antidromic invasion of the same neuron. The difference between the discharge rates of ZI neurons during EEG-desynchronized and EEG-synchronized behavioral states was not significant. A statistically significant increase in firing rates was found in ZI neurons during waking periods with movements compared to quiet, motionless epochs of waking. The possible involvement of caudally projecting ZI cells in the preparation of postural and/or phasic motor functions is discussed.

Effects of maternal drinking on neonate state regulation.

Sleep-awake state distribution during inter-feed intervals over a 24-hour period on the third day of life was investigated by means of a continuous non-intrusive bassinet sleep monitor. 31 infants were studied: 14 born to mothers who drank heavily throughout pregnancy (group A), eight whose mothers modified their heavy drinking (group B) and nine whose mothers never were heavy drinkers (group C). Over the 24-hour period, group A infants slept less than those in group B. In comparison with group C, group A infants had a larger proportion of quiet sleep episodes interrupted by awake or unclassified epochs, and were more restless, with more frequent major body movements. These pilot observations suggest that heavy maternal consumption of alcohol, when continued throughout pregnancy, is associated with a disturbance of sleep-awake state distribution. Successful therapy of heavy drinking during pregnancy may improve the physiological competence of the newborn to regulate sleep-awake states and facilitate interaction between mother and infant.

Thresholds to arousing stimulation in the developing infant rhesus monkey

Thresholds of vocalization to electroshock were determined in infant and juvenile monkeys during random epochs of wakefulness, during high-voltage, slow-wave sleep, and during low-voltage, fast-wave sleep. These thresholds increased in all states over the first days of postnatal life and then decreased differentially for each of the states thereafter.