Abnormal Sleep Delta Rhythm and Interregional Phase Synchrony in Patients with Restless Legs Syndrome and Their Reversal by Dopamine Agonist Treatment

BACKGROUND AND PURPOSE: The purpose of this study was to characterize abnormal cortical activity during sleep in restless legs syndrome (RLS) patients and to determine the effects of treatment with a dopamine agonist. Based on whole-brain electroencephalograms, we attempted to verify alterations in the functional network as well as the spectral power of neural activities during sleep in RLS patients and to determine whether the changes are reversed by treatment with pramipexole. METHODS: Twelve drug-naïve RLS patients participated in the study. Overnight polysomnography was performed before and after treatment: the first recording was made immediately prior to administering the first dose of pramipexole, and the second recording was made 12–16 weeks after commencing pramipexole administration. Sixteen age-matched healthy participants served as a control group. The spectral power and interregional phase synchrony were analyzed in 30-s epochs. The functional characteristics of the cortical network were quantified using graph-theory measures. RESULTS: The delta-band power was significantly increased and the small-world network characteristics in the delta band were disrupted in RLS patients compared to the healthy controls. These abnormalities were successfully treated by dopaminergic medication. The delta-band power was significantly correlated with the RLS severity score in the RLS patients prior to treatment. CONCLUSIONS: Our findings suggest that the spectral and functional network characteristics of neural activities during sleep become abnormal in RLS patients, and these abnormalities can be successfully treated by a dopamine agonist.

Schneiderian First Rank Symptoms and Gamma Oscillatory Activity in Neuroleptic Naive First Episode Schizophrenia: A 192 Channel EEG Study

OBJECTIVE: Schneiderian first-rank symptoms (FRS) and abnormal EEG gamma activity in schizophrenia have been reported independently to have a neurodevelopmental basis. We aimed to investigate spontaneous gamma power in two groups of first episode schizophrenia patients (those who experience FRS and those who do not). METHODS: A comparative hospital based study having 37neuroleptic naive male patients with schizophrenia divided into two groups-FRS(+) and FRS(-) groups based on the presence of FRS. Thirty age, sex, education and handedness matched individuals served as controls (N). All participants underwent a 192-channel resting Electroencephalography (EEG) recording. Gamma spectral power was calculated for low- (30-50 Hz) and high-gamma 1 & 2 (51-70 and 71-100 Hz) bands. Spectral power was compared between three groups using MANOVA and supplementary one-way ANOVA with Bonferroni test controlling for multiple comparisons. Linear regression was used to identifying predictor variables for FRS. Pearson correlation coefficient was computed between spectral power parameters and various clinical variables. RESULTS: Significantly higher high gamma band-1 power was observed over right frontal (p<0.05), parietal (p<0.05) and temporal (p<0.05) regions in FRS(+) than FRS(-) group and normal controls. Right parietal high gamma-1 power and paranoid cluster on PANSS significantly predicted number of FRS in total schizophrenia patients; paranoid cluster on PANSS showed significant correlation with number of FRS in FRS(+) group. CONCLUSION: Findings of our study add to the evidence that areas contained within the hetero modal association cortex are associated with FRS. The study findings also strengthen the neurodevelopmental basis of FRS in schizophrenia.

Influence of deep breathing exercise on spontaneous respiratory rate and heart rate variability: a randomised controlled trial in healthy subjects.

Studies show that yogic type of breathing exercises reduces the spontaneous respiratory rate. However, there are no conclusive studies on the effects of breathing exercise on heart rate variability. We investigated the effects of non-yogic breathing exercise on respiratory rate and heart rate variability. Healthy subjects (21-33 years, both genders) were randomized into the intervention group (n=18), which performed daily deep breathing exercise at 6 breaths/min (0.1 Hz) for one month, and a control group (n=18) which did not perform any breathing exercise. Baseline respiratory rate and short-term heart rate variability indices were assessed in both groups. Reassessment was done after one month and the change in the parameters from baseline was computed for each group. Comparison of the absolute changes [median (inter-quartile ranges)] of the parameters between the intervention and control group showed a significant difference in the spontaneous respiratory rate [intervention group –2.50 (–4.00, –1.00), control group 0.00 (–1.00, 1.00), cycles/min, P<0.001], mean arterial pressure [intervention group –0.67 (–6.67, 1.33), control group 0.67 (0.00, 6.67), mmHg, (P<0.05)], high frequency power [intervention group 278.50 (17.00, 496.00), control group –1.00 (–341.00, 196.00), ms2 P<0.05] and sum of low and high frequency powers [intervention group 512.00 (–73.00, 999.00), control group 51.00 (–449.00, 324.00), ms2, P<0.05]. Neither the mean of the RR intervals nor the parameters reflecting sympatho-vagal balance were significantly different across the groups. In conclusion, the changes produced by simple deep slow breathing exercise in the respiratory rate and cardiac autonomic modulation of the intervention group were significant, when compared to the changes in the control group. Thus practice of deep slow breathing exercise improves heart rate variability in healthy subjects, without altering their cardiac autonomic balance. These findings have implications in the use of deep breathing exercises to improve cardiac autonomic control in subjects known to have reduced heart rate variability.

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.

Quantitative EEG findings in different stage of Alzheimer's Disease

BACKGROUND: Although quantitative-electroencephalography (q-EEG) has been used for many years to differentiate Alzheimer's disease (AD) from the healthy aging process, the electrophysiological changes of AD has not been well established due to progressive nature of AD. The aim of this study was to compare q-EEG parameters among elderly controls, patients with mild cognitive impairment group (MCI), and patients with four different stages of AD. Moreover, we tried to identify the variables that are correlated with the degree of cognitive impairment. METHODS: After logarithmic transformation of relative spectral power, we analyzed the topographical relative spectral power and occipital peak frequency in each group. Multiple regression analysis was applied to these variables to identify parameters related with K-MMSE. RESULTS: (1) In AD patients with less than CDR 0.5, peak frequency in occipital lead was significantly lower than that of elderly controls. (2) Compared with elderly controls, AD patients showed significantly reduced left anterior alpha spectral power in CDR 0.5, increased bilateral posterior theta spectral power and reduced generalized alpha spectral power in CDR 1, generalized reduced alpha, beta spectral power and increased theta spectral power in CDR2, generalized reduced alpha and beta spectral power, increased delta and theta spectral power in CDR 3. (3) Korean Mini-Mental State Examination (K-MMSE) score was closely related to left occipital peak frequency, right posterior delta and left anterior theta spectral power. CONCLUSIONS: This study suggests that q-EEG shows different findings in different stages of AD and the left occipital peak frequency is closely correlated with the severity of cognitive dysfunction.