Spectral analysis of the sleep onset period in primary insomnia.

OBJECTIVE: To compare the EEG power spectra characteristics of the sleep onset period (SOP) in patients with sleep onset insomnia (SOI), sleep maintenance insomnia (SMI) and good sleepers (GS). METHODS: The time course of EEG power density (1-40Hz) during the SOP was examined in thirty subjects (SOI patients: N=10, SMI patients: N=10, GS: N=10). RESULTS: The EEG power of the beta2 frequency band (18-29.75 Hz) was significantly lower in SOI than in SMI in the period preceding sleep onset. The alpha power was significantly higher for the SMI group compared to GS before sleep onset. Despite the lack of statistical significance, several differences in EEG dynamics were observed in SOI compared to two other groups: delta power increased slower after sleep onset; beta2 and 3 (18-29.75 and 30-39.75 Hz) power decrease less abruptly before sleep onset; beta1 (15-17.75 Hz) power increase through the whole SOP. CONCLUSIONS: The lower level of beta2 frequency band in SOI and the differences in dynamics in delta and beta bands may suggest that a mechanism other than hyperarousal participates in etiology of SOI. SIGNIFICANCE: SOI and SMI patients have different spectral characteristics in SOP, thus future studies should avoid the inclusion of mixed insomnia samples.

The neuronal transition probability (NTP) model for the dynamic progression of non-REM sleep EEG: the role of the suprachiasmatic nucleus.

Little attention has gone into linking to its neuronal substrates the dynamic structure of non-rapid-eye-movement (NREM) sleep, defined as the pattern of time-course power in all frequency bands across an entire episode. Using the spectral power time-courses in the sleep electroencephalogram (EEG), we showed in the typical first episode, several moves towards-and-away from deep sleep, each having an identical pattern linking the major frequency bands beta, sigma and delta. The neuronal transition probability model (NTP)--in fitting the data well--successfully explained the pattern as resulting from stochastic transitions of the firing-rates of the thalamically-projecting brainstem-activating neurons, alternating between two steady dynamic-states (towards-and-away from deep sleep) each initiated by a so-far unidentified flip-flop. The aims here are to identify this flip-flop and to demonstrate that the model fits well all NREM episodes, not just the first. Using published data on suprachiasmatic nucleus (SCN) activity we show that the SCN has the information required to provide a threshold-triggered flip-flop for TIMING the towards-and-away alternations, information provided by sleep-relevant feedback to the SCN. NTP then determines the PATTERN of spectral power within each dynamic-state. NTP was fitted to individual NREM episodes 1-4, using data from 30 healthy subjects aged 20-30 years, and the quality of fit for each NREM measured. We show that the model fits well all NREM episodes and the best-fit probability-set is found to be effectively the same in fitting all subject data. The significant model-data agreement, the constant probability parameter and the proposed role of the SCN add considerable strength to the model. With it we link for the first time findings at cellular level and detailed time-course data at EEG level, to give a coherent picture of NREM dynamics over the entire night and over hierarchic brain levels all the way from the SCN to the EEG.

Spectral power time-courses of human sleep EEG reveal a striking discontinuity at approximately 18 Hz marking the division between NREM-specific and wake/REM-specific fast frequency activity.

Spectral power time-courses over the ultradian cycle of the sleep electroencephalogram (EEG) provide a useful window for exploring the temporal correlation between cortical EEG and sub-cortical neuronal activities. Precision in the measurement of these time-courses is thus important, but it is hampered by lacunae in the definition of the frequency band limits that are in the main based on wake EEG conventions. A frequently seen discordance between the shape of the beta power time-course across the ultradian cycle and that reported for the sequential mean firing rate of brainstem-thalamic activating neurons invites a closer examination of these band limits, especially since the sleep EEG literature indicates in several studies an intriguing non-uniformity of time-course comportment across the traditional beta band frequencies. We ascribe this tentatively to the sharp reversal of slope we have seen at approximately 18 Hz in our data and that of others. Here, therefore, using data for the first four ultradian cycles from 18 healthy subjects, we apply several criteria based on changes in time-course comportment in order to examine this non-uniformity as we move in 1 Hz bins through the frequency range 14-30 Hz. The results confirm and describe in detail the striking discontinuity of shape at around 18 Hz, with only the upper range (18-30 Hz) displaying a time-course similar to that of the firing-rate changes measured in brainstem activating neurons and acknowledged to engender states of brain activation. Fast frequencies in the lower range (15-18 Hz), on the other hand, are shown to be specific to non-rapid-eye-movement sleep. Splitting the beta band at approximately 18 Hz therefore permits a significant improvement in EEG measurement and a more precise correlation with cellular activity.

State transitions between wake and sleep, and within the ultradian cycle, with focus on the link to neuronal activity.

The structure of sleep across the night as expressed by the hypnogram, is characterised by repeated transitions between the different states of vigilance: wake, light and deep non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. This review is concerned with current knowledge on these state transitions, focusing primarily on those findings that allow the integration of data at cellular level with spectral time-course data at the encephalographic (EEG) level. At the cellular level it has been proposed that, under the influence of circadian and homeostatic factors, transitions between wake and sleep may be determined by mutually inhibitory interaction between sleep-active neurons in the hypothalamic preoptic area and wake-active neurons in multiple arousal centres. These two fundamentally different behavioural states are separated by the sleep onset and the sleep inertia periods each characterised by gradual changes in which neither true wake nor true sleep patterns are present. The results of sequential spectral analysis of EEG data on moves towards and away from deep sleep are related to findings at the cellular level on the generating mechanisms giving rise to the various NREM oscillatory modes under the neuromodulatory control of brainstem-thalamic activating systems. And there is substantial evidence at cellular level that transition to and from REM sleep is governed by the reciprocal interaction between cholinergic REM-on neurons and aminergic REM-off neurons located in the brainstem. Similarity between the time-course of the REM-on neuronal activity and that of EEG power in the high beta range (approximately 18-30 Hz) allows a tentative parallelism to be drawn between the two. This review emphasises the importance of the thalamically projecting brainstem activating systems in the orchestration of the transitions that give rise to state progression across the sleep-wake cycle.

A unique pattern of sleep structure is found to be identical at all cortical sites: a neurobiological interpretation.

There is substantial evidence both at the cellular and at the electroencephalogram (EEG) level to support the view that the brainstem activating systems control the sleep-state (stage) progression over time that constitutes the overall sleep structure as seen at the EEG. We argue here that the brainstem therefore modulates the time-courses of spectral power in the different EEG frequency bands. These show during non-rapid eye movement (NREM) sleep a very particular interrelationship the origin of which has received little attention and for which the neuronal transition probability model for sleep structure has proposed a physiological explanation. We advance the hypothesis that if the brainstem is modulating these time-courses then they should show a marked similarity in shape and timing at all sites. Using data from 10 healthy subjects, we measure the degree of similarity of the time-courses over each of the first four NREM episodes at the frontal, central and parietal sites, for each of the frequency bands beta, sigma and delta, and also the cortically generated slow oscillation. All the cross- correlation coefficients are high and statistically significant, indicating that the shape and timing of these time-courses are practically identical at different sites despite regional differences in their average power levels. These results tend to suggest that two processes may operate concurrently: the brainstem controls the shape and timing of the power time-courses while cortical-thalamic interaction controls their site-dependent average power.

Beta EEG activity and insomnia.

To date there have been seven studies which find that beta EEG is elevated at around sleep onset and during polysomnographic sleep in patients with insomnia. These findings suggest that insomnia may be characterized by central nervous system (CNS) hyperarousal. In this article, the seven studies are critically reviewed, two theoretical perspectives on beta EEG are presented, and the concept of hyperarousal as a three component process is discussed.

Modificación de la densidad de los movimientos oculares rápidos bajo la administración de los agonistas y los antagonistas de los receptores a las benzodiazepinas / Modification of rapid eye movement density under administration of agonists and antagonists of benezodiazepine receptors

Las benzodiazepinas (BZ) tienen efectos sobre algunas de las variables del sueño en el hombre, pero el mecanismo por el cual modifican los movimeintos oculares rápidos (MOR), que ocurren durante el sueño paradójico (SP), no está suficientemente descrito. El mecanismo de acción de las BZ puede explicarse por su interacción con sitios de unión selectivos localizados en el sistema nervioso central (SNC) y en la periferia, o por su interacción con los receptores descritos para neuromoduladores como la adenosina (AD). El presente estudio se realizó para tratar de distinguir farmacológicamente cuál de los posibles sitios de unión descritos para las BZ participan en las modificaciones observadas con las BZ en el SP y en los MOR. Treinta y dos sujetos voluntarios sanos, de uno y otro sexo, fueron estudiados bajo tres diferentes condiciones experimentales, para determinar la participación del flumazenil (FLU), un antagonista de los receptores centrales a las BZ, el PK 11195 (PK), un antagonista de los receptores post sinápticos a la AD, en las modificaciones del SP que generalmente inducen las BZ. Los resultados que las BZ estudiadas, flunitrazepan y clonazepam, disminuyen el número y la desnidad de MOR (DMOR) y que el FLU, el PK y la CAF no revierten este efecto. Más aún, el FLU tiende a disminuir la DMOR como un efecto intrínseco. Los datos obtenidos muestran que los receptores a la AD probablemente no participan en la regulación de los MOR e indirectamente sugieren que el complejo supramolecular (receptor, a BZ, receptor a GABA y canal de cloro) puede participar en la modulación de los MOR, aunque es necesario realizar otros estudios con ligandos más específicos, para poder confirmar esta interpretación