Caída abrupta del tono muscular al entrar a sueño MOR en el ser humano / Sudden drop of muscle tone at the onset of REM sleep in humans

Relatively low tonic electromyographic activity of the mentalis or sub-mentalis muscles constitutes one of the three electrophysiological signs for identifying rapid eye movement sleep (REM), described in the standardized manual for scoring sleep stages in human subjects. The other two signs, low voltage mixed frequency EEG activity and episodic rapid eye movements are inadequate for delimiting the start of REM sleep, because EEG activity resembles that of stage 1 and rapid eye movements are not constantly present. The term <> tonic EMG and not <> is used according to the standardized manual because tonic EMG shows considerable variation from subject to subject and from session to session, and more important because low EMG values may be reached during other sleep stages. Therefore, REM sleep scoring is based on <> tonic EMG. Despite the relevance of the loss of muscular tone for scoring the start of REM sleep and for sleep disorders -such as narcolepsy and REM sleep behavioral disorder, where loss of muscle tone or the lack of it is implicated-, very few quantitative studies of EMG activity during REM sleep in humans have been performed. Amplitude analysis of mentalis and orbicularis oris muscles and spectral power analysis of suprahyoid, masseter and temporalis muscles have demonstrated that EMG activity is lower during REM than during NREM sleep. The mentalis muscle maintains tonically the lowest values during REM sleep with very low variability during the same REM sleep episode and across REM episodes, except for very brief phasic activations, whereas during NREM sleep muscle tone shows large variations within the same sleep stage and along the night. Only one study exists which analyzes the time course of the loss of tone during the transition from NREM to REM sleep integrating the EMG amplitude. However, it was done for long time windows of 20 seconds that does not allow identifying the precise moment of EMG activity drop. Given that the fall in EMG activity is one of the main keys for REM sleep scoring, the objective of the present investigation is to describe the EMG activity of the mentalis muscle during the NREM-REM sleep transition by analyzing short time windows of two seconds. Ten healthy, young adult, right-handed subjects (5 men and 5 women) participated in the study after giving informed consent. All had regular sleeping habits, were in good health and were free of drugs, medication or caffeine intake as assessed by interviews and questionnaires on sleeping habits and health. Polysomnography (PSG) was recorded using a Grass model 8-20E polygraph with filters set at .03 and 70 Hz. Additionally to EEG (C3-A2 and C4-A1), electroculogram (EOG) and EMG of the mentalis muscle, nasal-oral air flow and EMG of anterior tibialis muscles were recorded to remove those subjects showing signs of sleep apnea or periodic limb movement disorder. EEG, EMG and EOG were digitized at 1024 Hz through an analog-to-digital converter of 12 bits resolution using the acquisition program Gamma (version 4.4). The initiation of the first three REM sleep episodes of one night for each subject was indicated in the PSG recordings, following the standardized rules of the manual for scoring sleep stages of human subjects. The fourth REM sleep episode was not considered for analysis because not all subjects had a fourth REM episode. EMG activity of the mentalis muscle of three 30-second epochs around the start of REM sleep (the previous one, the REM entrance and the posterior one) was analyzed. EMG activity was submitted to Fast Fourier Transform and absolute power for every 250 msec (256 points) was obtained for two broad bands: one from 24 to 28 Hz and the other from 28 to 32 Hz, as these have demonstrated significant differences between REM and NREM sleep, in previous studies. Absolute power values were log-transformed previous to statistical analysis to approximate them toward normal distribution. The time course of the drop in muscle tone was established in the case of each individual NREM-REM sleep transition for two second time windows, both visually on the EMG signal and also by statistically comparing consecutive 2-second averages of EMG absolute power (8 means of 250 msec). When there was no clear visual or statistical evidence of decreased EMG activity, the 30-second epoch was divided in half. Additionally, the first rapid eye movement was visually identified. EMG signals were visually inspected and absolute power values of two-second epochs containing eye movement or phasic EMG artifacts were substituted by the average of the preceding and following two-second means. This procedure was chosen instead of rejection in order to maintain the time sequence. The average of substituted epochs was lower than 1 for the NREM-REM sleep transitions. Once the significant differences were established for the individual NREM-REM sleep transitions, the absolute power for the 20 seconds prior and the 20 seconds after the turning point was averaged for the group and compared using the Student t test. A level of p <0.05 was required for significance for both individual and group analyses. EMG drop was statistically identified in 15 out of the 30 NREM-REM sleep transitions (p < 0.05). In 14 cases more than one significant difference was found due to phasic increases shorter than two seconds. Thus, EMG drop was established where both visual inspection of EMG signal and statistical differences were matched. It was necessary to divide the 30-second epoch in half just in one individual case. The comparison of EMG power after averaging for the group the 20 seconds before and the twenty seconds after the individual turning point showed that EMG absolute power was significantly different for the two bands (p < 0.0001 for both bands). The first eye movement occurred after the EMG drop in 28 out of the 30 NREM-REM sleep transitions within a range of 2 and 52 seconds. EMG fall was simultaneous to the first eye movement in one case and eye movement preceded EMG drop in just one NREM-REM sleep transition. Present results indicate that the loss of muscle tone of the mental is muscle during the transition from NREM to REM sleep occurs suddenly rather than gradually, within a time window lasting no longer than 2 sec. This could be appreciated in individual as well as in group analysis. It still remains a matter of debate if REM sleep is under the control of a single generator that simultaneously commands the start of all of its physiological changes, or if each of the physiological systems involved in REM sleep is under its own command starting at its own time and are only orchestrated by a common mechanism. The loss of muscle tone occurred before the first rapid eye movement in 29 out of 30 of the REM sleep onset episodes analyzed, upholding the proposition that physiological systems involved in REM sleep follow different time courses in agreement with non-simultaneous onset of the different physiological mechanisms as it happens with ponto-geniculate-occipital waves in cats that begin long before EEG desynchronization and EMG fall and with results observed in two studies in man which report that EMG amplitude decreases before eye movements. The sudden drop in muscle tone during NREM-REM sleep transition may help to understand the physiological mechanisms involved in sleep disorders where loss of muscle tone or the lack of it is implicated, such as narcolepsy and REM sleep behavioral disorder. It can also be used as an objective sign to establish the onset of REM sleep in research where the precise moment of REM sleep onset is needed. The time relationship among muscle tone fall and other physiological signs of REM sleep remains to be investigated.

De acuerdo con el manual estandarizado para la clasificación del sueño en el ser humano, tres variables fisiológicas marcan el inicio del sueño con movimientos oculares rápidos (MOR): la desincronización electroencefalográfica (EEG), los movimientos oculares rápidos y la pérdida de tono muscular. De estos tres indicadores, uno de ellos, los movimientos oculares rápidos, es una manifestación intermitente o fásica que consiste en movimientos que pueden ser aislados o emitirse en salvas de varios movimientos, pero que no está presente de manera continua. Los otros dos, la desincronización EEG y la atonía, aparecen desde el inicio y se mantienen durante todo el episodio de sueño MOR. Sin embargo, la actividad EEG del sueño MOR en el ser humano es muy semejante, bajo inspección visual, al EEG de la etapa 1, por lo que el EEG y los movimientos oculares rápidos no permiten determinar por sí solos el inicio del sueño MOR, por lo que la atonía muscular se hace indispensable para ello. A pesar de que la caída de tono muscular es uno de los principales indicadores del sueño con movimientos oculares rápidos (MOR) y de la importancia que tiene la actividad muscular durante esta etapa del sueño para comprender mejor los trastornos en que se encuentra alterada la pérdida del tono muscular, como la narcolepsia y el trastorno conductual del sueño MOR, son muy escasas las investigaciones sobre el curso temporal de la caída del tono muscular durante la transición del sueño NMOR al MOR en el ser humano. Dado que la caída del tono muscular es uno de los principales indicadores del SMOR y que ni la desincronización electroencefalográfica ni los movimientos oculares rápidos permiten señalar con precisión la entrada al sueño MOR, el principal objetivo de esta investigación es caracterizar el curso temporal de la disminución del tono del músculo mentalis por ventanas de dos segundos y describir en detalle su curso temporal durante la transición del sueño NMOR al MOR. El establecimiento del cambio EMG en el tiempo permitirá contar con un signo objetivo de la entrada al SMOR que contribuirá a comprender mejor los trastornos del sueño. Con este objetivo, se registró el sueño de 10 adultos jóvenes, sanos y diestros (cinco hombres y cinco mujeres). La polisomnografía (PSG) y la clasificación de las etapas del sueño se realizaron de acuerdo con los procedimientos habituales. Se identificaron las tres primeras entradas a sueño MOR de la noche. Se analizó el EMG del mentón de tres épocas de 30 segundos del periodo de inicio del SMOR (IMOR), una antes, una durante y otra después. Para cada sujeto y episodio de SMOR, se calculó el espectro de potencia absoluta (PA) para dos bandas anchas del EMG para épocas de 250 milisegundos. Se determinó individualmente para cada entrada a sueño MOR la evolución temporal de la caída del tono muscular del IMOR, promediando la PA para cada dos segundos, y se excluyeron los segmentos con artefactos. Se estableció la caída del tono muscular al encontrar diferencias significativas entre dos épocas consecutivas, así como visualmente en el trazo EMG. Posteriormente, se promedió la PA de 10 segmentos de dos segundos previos y de 10 segmentos posteriores a la caída del EMG para todo el grupo y se compararon por medio de la prueba t de Student para muestras correlacionadas. La caída del tono muscular en la transición del sueño NMOR al MOR ocurrió de manera abrupta y no paulatina en un intervalo no mayor a dos segundos. Los resultados estadísticos detectaron la caída del tono muscular tanto en los análisis individuales como de grupo. La aparición de la pérdida de tono muscular ocurrió antes del primer movimiento ocular en 29 de las 30 entradas a MOR analizadas. Estos resultados apoyan la observación de que los diversos sistemas fisiológicos involucrados en el sueño MOR entran en acción en diferentes momentos y no simultáneamente. La caída brusca del tono muscular puede constituir un indicador para determinar objetivamente la entrada al sueño MOR que a su vez se puede emplear para estudiar la pérdida del tono muscular en otras alteraciones, como la narcolepsia y el trastorno conductual del sueño MOR, así como en investigaciones que requieran establecer el momento preciso de la entrada al sueño MOR.

La actividad Alfa frontal en insomnes primarios con dificultad para iniciar el sueño / Frontal alpha activity in primary insomniacs with sleep onset difficulties

Difficulty in sleep initiation, with or without objective signs, is one of the most frequent complaints in primary insomniacs. The electroencephalographic (EEG) activity characteristic of waking (beta and alpha oscillations) is gradually replaced by the EEG signs of sleep (sleep spindles and theta/delta waves) during the sleep onset period (SOP) in normal subjects. The decrease in fast oscillations occurs at the first signs of stage 1, whereas theta and delta increase occurs later, indicating that waking promoting mechanisms are turned off before sleep-promoting mechanisms are fully started. It could be therefore hypothesized that difficulty in sleep initiation in insomniacs might be due to either a hyperactivation of waking promoting systems, a weakness of sleep promoting mechanisms or an imbalance between them. Quantitative EEG analysis has revealed higher beta during wakefulness, as well as during sleep and lower slow (delta) activity in insomniacs. The presence of alpha activity during cognitive information processing, especially of slow alpha activity in relation to attention, as well as in some pathologies associated to sleep disturbances, has suggested that alpha activity during sleep is a sign of activation; however, alpha activity during sleep has been less studied in insomniacs. Only broad bands have been considered in all of the aforementioned studies, and in almost all of them the analyses were restricted to central regions. It is therefore important to study the entire frequency spectrum of EEG activity in insomniacs. Sleep initiation does not occur simultaneously over the entire cortex but starts as a local process which gradually invades the rest of the cortex, in which the frontal lobes play a crucial role. Frontal and parietal regions are part of an important network involved in attention and conduction of thought. Thus, quantitative analysis of narrow EEG bands and their distribution in the cerebral cortex may contribute to a better understanding of neural mechanisms compromised in etiology of sleep initiation in primary insomnia. The main objective of the present investigation was, therefore, to analyze the spectral power of narrow EEG bands in the 19 derivations of the 10-20 International System during SOP in primary insomniacs with difficulty in sleep initiation. Given that one of the main complaints of insomniacs is the difficulty to initiate sleep and that hyperarousal is one of the factors proposed to be involved in the etiology of insomnia, EEG activity during SOP of the first night in the laboratory was analyzed to control activating effects of surrounding circumstances and isolate permanent EEG characteristics. Subjects were 19-34 years old, right-handed with primary sleep insomnia, which were thoroughly screened via structured psychiatric, medical and sleep interviews and scales. Subjects were younger and the age range was narrower than in other EEG frequency spectral content studies of primary insomniacs to avoid confounding effects of changes in sleep architecture or in EEG generated by development. All patients met the criteria for primary insomnia with sleep onset difficulty and impaired daytime function on three or more nights per week for at least six months and with no medical, psychiatric or neurological conditions; they were not medicated and had no other sleep disorders. Participants taking sleep medications or other drugs (urine test), respiratory or sleep disorders such as apnea and periodic limb movements (PSG) were excluded. The control group (n = 9) was matched for age and dexterity, but had no complaints of insomnia and reported their sleep as restorative and satisfactory. All participants underwent a single night of standard polysomnography (EEG, EOG and EMG) in the laboratory. In addition, the 19 electrode sites of the 10-20 International System referred to ipsilateral earlobes, oral-nasal airflow and anterior tibialis EMG were recorded. PSG was scored in 30 sec epochs, blind to the subject group according to Rechtschaffen and Kales criteria. EEG from SOP (lights out to consolidate sleep), defined as 3 consecutive minutes of delta sleep, was digitized at 1024 Hz with 12 bits resolution and filter settings of 0.03-70 Hz. EEG was segmented into two-sec non-overlapping epochs and inspected for artifacts. All artifact-free epochs were Fast Fourier Transformed and absolute (AP) and relative power (RP: AP in each Hz bin/total spectrum power × 100) was obtained for 1 Hz bins. AP and RP was log-transformed before statistical analysis, and was averaged over each derivation and sleep stage of SOP. Group differences were compared by means of Student's t tests and probability level was set at p<0.05. In contrast with healthy controls, insomniac patients exhibited higher alpha RP (7 and 8 Hz) over all frontal derivations during stage 2 of SOP and higher RP of isolated beta and gamma frequencies during wakefulness. PSG of both groups showed the <> with decreased total sleep time, decreased sleep efficiency index and REM sleep percentage compared to normal values for the 20-30 age decade; PSG variables were not significantly different between the two groups except for wakefulness percentage during SOP. Insomniacs did differ from controls in subjective estimation of sleep quality and continuity in spite of similar PSG. The absence of significant differences between insomniacs and controls in sleep EEG activity (delta, theta and sigma frequencies) suggests that sleep homeostatic function is preserved in insomniacs, which agrees with results obtained in other studies after partial sleep deprivation. The absence of a stronger promoting effect of insomnia in the insomniac group by the first recording night indicates that EEG characteristics found in this group cannot be attributed to external stimuli nor surrounding circumstances and rather suggests a more stable alteration; however, further studies of larger groups and other age spans are needed to confirm present results. The evidence mentioned above suggests an imbalance between waking and sleep promoting mechanisms in primary insomniacs with difficulty in sleep initiation and sleep perception. Attention depends not only on vigilance level, but also on frontal regions which, together with posterior association areas, conform an essential network for purposive endogenously guided attention. The presence in insomniacs of alpha activity in frontal regions, which is a sign of top-down control of attention, and its absence in posterior regions during stage 2 suggests the persistence of a certain level of endogenous attention during stage 2 of SOP, which contributes in turn to the subjective perception of sleep onset difficulties and bad sleep quality.

La dificultad para conciliar el sueño es uno de los síntomas más frecuentes del insomnio primario. La apreciación subjetiva de un periodo prolongado de latencia al sueño, aun en presencia de signos de sueño, puede deberse a la coexistencia de los mecanismos promotores de la vigilia y del sueño, y la lucha por el predominio de uno de ellos. La red de atención ejecutiva, conformada por las áreas de asociación frontales y parietales, cumple un papel de particular importancia en el control endógeno de la atención y en la regulación del alertamiento por parte de la corteza. Las frecuencias del EEG en el rango de actividad alfa lenta (7 y 8 Hz) participan en los procesos cognoscitivos activos de la vigilia, especialmente en la atención y la memoria, y son indicadoras del control corticofugo, o top-down, de estos procesos. Sin embargo, el análisis cuantitativo del EEG durante el proceso de conciliación del sueño en los insomnes se ha centrado fundamentalmente en la actividad delta, theta y beta, y únicamente en las regiones centrales (C3 y C4), de tal forma que el análisis de banda estrecha del EEG y su distribución en toda la corteza podría contribuir a una mejor comprensión de los mecanismos neurales comprometidos en la etiología del insomnio primario. El objetivo principal de esta investigación es, por lo tanto, analizar el espectro de frecuencias con resolución de 1 Hz en todas las derivaciones del Sistema Internacional 10-20 en insomnes primarios crónicos durante el periodo inicial del sueño (PIS) y comparar a estos últimos con un grupo control. Con el fin de aislar las características del EEG de los insomnes de causas circunstanciales, se analizará la primera noche de PSG igualando en ambos grupos el efecto activador que ejerce el medio circundante sobre el Sistema Nervioso Central, el estado psicológico y la arquitectura del sueño. Se estudiaron nueve pacientes insomnes primarios cuya queja principal era la dificultad para iniciar el sueño y nueve sujetos controles libres de problemas de sueño, diestros y entre 19-34 años de edad. Se realizó la PSG durante la primera noche en el laboratorio siguiendo los procedimientos estándar y adicionalmente se registraron las 19 derivaciones del Sistema Internacional 10-20. Se obtuvieron los espectros de potencia del EEG de todas las derivaciones con resolución de 1 Hz del PIS (tiempo comprendido entre las buenas noches y el sueño consolidado: 3 minutos consecutivos de sueño delta). Los insomnes tuvieron mayor actividad alfa lenta (7 y 8 Hz) en las regiones frontales durante la etapa 2 del PIS y de algunas frecuencias rápidas (beta y gamma) en la vigilia; subestimaron la calidad de sueño; y mostraron el mismo efecto de primera noche que los controles. La ausencia de diferencias entre los dos grupos en el EEG típico del sueño (delta, theta y sigma) sugiere que los insomnes tienen preservada la función homeostásica del sueño. La ausencia de diferencias en la PSG de los insomnes y controles indica que la dificultad para conciliar el sueño del grupo de insomnes no se encuentra en estímulos externos ambientales ni en condiciones circunstanciales y sugiere que se debe a alteraciones más permanentes. El conjunto de estas evidencias apunta hacia una alteración de la vigilia en concordancia con las hipótesis que proponen que el insomnio tiene un componente primordial de activación fisiológica y psicológica. La atención depende, además del nivel de vigilancia, de las regiones frontales que, junto con las áreas posteriores de asociación, conforman una red esencial para la atención dirigida endogenamente. La presencia de ritmo alfa en las regiones frontales y su ausencia en las áreas posteriores durante la etapa 2 en los insomnes podría reflejar la permanencia de cierto nivel de atención endógena durante la etapa 2 del PIS y podría constituir un mecanismo alterado del sistema frontal subyacente a la dificultad para iniciar el sueño.