[Executive functions in patients with obstructive sleep apnea: exploring the prefrontal model]. / Funciones ejecutivas en pacientes con apnea obstructiva del sueño: explorando el modelo prefrontal.

INTRODUCTION: According to the prefrontal model, individuals with obstructive sleep apnea (OSA) manifest behaviours mimicking dysexecutive syndrome as a result of blood gas abnormalities and sleep fragmentation. OBJECTIVE: To compare executive functions in OSA patients with normative values and explore their relationship with blood gas abnormalities and sleep fragmentation. PATIENTS AND METHODS: Patients were recruited from the wider community and from a tertiary care hospital. The score obtained in the neuropsychological assessment was compared with Student's t-test for a sample. A multiple linear regression analysis was subsequently estimated, using polysomnographic parameters of hypercapnia, hypoxemia and sleep fragmentation as the predictor variables, and the executive function score as the variable to be predicted. RESULTS: Although the neuropsychological assessment performance of 26% of this sample was classified as executive impairment, indicators of sleep fragmentation and gas abnormalities failed to predict the performance of executive functions. CONCLUSION: A proportion of the patients with OSA presented performance similar to a dysexecutive syndrome; however, the factors underlying and fostering this type of cognitive manifestation remain unclear. Early treatment for this public health problem could be the best tool available for improving quality of life and preventing health risks.

TITLE: Funciones ejecutivas en pacientes con apnea obstructiva del sueño: explorando el modelo prefrontal.Introducción. El modelo prefrontal propone que los individuos con apnea obstructiva del sueño (AOS) manifiestan conductas similares a un síndrome disejecutivo como resultado de las alteraciones de gases en la sangre y la fragmentación del sueño. Objetivo. Comparar las funciones ejecutivas en pacientes con AOS con valores normativos y explorar su relación con las alteraciones de gases en la sangre y la fragmentación del sueño. Pacientes y métodos. Se reclutó a pacientes de la comunidad general y de un hospital de tercer nivel. La puntuación obtenida en la evaluación neuropsicológica se contrastó con la t de Student para una muestra. Posteriormente, se estimó un análisis de regresión lineal múltiple mediante parámetros polisomnográficos de hipercapnia, hipoxemia y fragmentación del sueño como variables predictoras, y la puntuación de funciones ejecutivas como variable que se debe predecir. Resultados. Pese a que el desempeño en la evaluación neuropsicológica del 26% de esta muestra se clasificó como alteración ejecutiva, los indicadores de fragmentación del sueño y alteraciones de gases no predijeron el desempeño ejecutivo. Conclusión. Una fracción de los pacientes con AOS mostró un desempeño similar a un síndrome disejecutivo; no obstante, permanecen indefinidos los factores que subyacen y favorecen este tipo de manifestaciones cognitivas. La atención temprana de este problema de salud pública podría ser la mejor herramienta disponible en aras de mejorar la calidad de vida y prevenir riesgos a la salud.

Effects of selective REM sleep deprivation on prefrontal gamma activity and executive functions.

Given that the dorsolateral prefrontal cortex is involved in executive functions and is deactivated and decoupled from posterior associative regions during REM sleep, that Gamma temporal coupling involved in information processing is enhanced during REM sleep, and that adult humans spend about 90 min of every 24h in REM sleep, it might be expected that REM sleep deprivation would modify Gamma temporal coupling and have a deteriorating effect on executive functions. We analyzed EEG Gamma activity and temporal coupling during implementation of a rule-guided task before and after REM sleep deprivation and its effect on verbal fluency, flexible thinking and selective attention. After two nights in the laboratory for adaptation, on the third night subjects (n=18) were randomly assigned to either selective REM sleep deprivation effectuated by awakening them at each REM sleep onset or, the same number of NREM sleep awakenings as a control for unspecific effects of sleep interruptions. Implementation of abstract rules to guide behavior required greater activation and synchronization of Gamma activity in the frontopolar regions after REM sleep reduction from 20.6% at baseline to just 3.93% of total sleep time. However, contrary to our hypothesis, both groups showed an overall improvement in executive task performance and no effect on their capacity to sustain selective attention. These results suggest that after one night of selective REM sleep deprivation executive functions can be compensated by increasing frontal activation and they still require the participation of supervisory control by frontopolar regions.

Enhanced synchronization of gamma activity between frontal lobes during REM sleep as a function of REM sleep deprivation in man.

UNLABELLED: Studies have shown that synchrony or temporal coupling of gamma activity is involved in processing and integrating information in the brain. Comparing rapid eye movement (REM) sleep to waking and non-REM (NREM) sleep, interhemispheric temporal coupling is higher, but lower between the frontal and posterior association areas of the same hemisphere. However, the homeostatic response of REM sleep temporal coupling after selective REM sleep deprivation (REMD) has not been studied. This study proposed exploring the effect of one night of selective REMD on the temporal coupling of cortical gamma activity during recovery REM sleep. Two groups of healthy subjects were subjected to either REMD by awakening them at each REM sleep onset, or to NREM sleep interruptions. Subjects slept four consecutive nights in the laboratory: first for adaptation, second as baseline, third for sleep manipulation, and fourth for recovery. Interhemispheric and intrahemispheric EEG correlations were analyzed during tonic REM (no eye movements) for the first three REM sleep episodes during baseline sleep, and recovery sleep after one night of selective REMD. Temporal coupling between frontal lobes showed a significant homeostatic rebound that increased during recovery REM sleep relative to baseline and controls. Results showed a rebound in temporal coupling between the two frontal lobes after REM sleep deprivation, indicating that the enhanced gamma temporal coupling that occurs normally during REM sleep has functional consequences. CONCLUSION: results suggest that synchronized activity during REM sleep may play an important role in integrating and reprocessing information.

Acute effect of callosotomy on cortical temporal coupling in humans: intraoperative electrocorticographic recording.

OBJECTIVE: To investigate the acute role of the corpus callosum in inter- and intrahemispheric temporal coupling. METHODS: Intraoperative electrocorticography (ECoG) makes it possible to investigate the acute role of the corpus callosum in cortical temporal coupling, or synchrony, without additional surgical intervention, thus avoiding the confounding effects of scalp recordings and the long-term reorganization of functional connectivity. ECoGs were recorded in three patients during callosotomies. Bilateral electrode grids were placed over the frontal cortex. ECoGs were recorded immediately before and after performing the anterior two-thirds callosal transection, were digitalized at a sampling rate of 512Hz, inspected for artifacts, and later analyzed offline. Cross-correlation between inter- and intrahemispheric electrode pairs were obtained for 1Hz bins and special broad bands obtained by principal component analysis for each patient pre- and post-callosotomy. RESULTS: A statistically significant change was observed in intrahemispheric temporal coupling between electrode pairs that exceeded the confidence limit of correlation. CONCLUSIONS: Present results show that interrupting the influence of the corpus callosum has an acute effect on intrahemispheric activity by decreasing temporal coupling between cortical areas. SIGNIFICANCE: Intrahemispheric temporal coupling does not depend exclusively on ipsilateral cortico-cortical pathways or on subcortical influences, but also on callosal pathways.

Within-subject reliability and inter-session stability of EEG power and coherent activity in women evaluated monthly over nine months.

OBJECTIVE: Quantitative EEG parameters during resting conditions are used as baseline in research on cognition and in serial-EEG recordings. Despite its increasing use in cognitive research and the numerous evidences of the existence of sex differences in EEG, EEG stability has been mainly investigated in men. Particularly, studies on stability of coherent activity are scarce. The aim of this study was to investigate within-subject reliability and inter-session stability of resting EEG over a nine-month period in women. METHODS: Within-subject reliability and inter-session stability were analyzed for absolute power and inter- and intrahemispheric coherent activity at central and posterior regions, once a month, in resting conditions, with eyes open and closed. RESULTS: Within-subject reliability was very high (r>0.89) for all subjects and EEG parameters. Inter-session stability was higher with eyes closed and for interhemispheric coherent activity, and poorer with eyes open especially in the alpha band. CONCLUSIONS: Present results indicate high reliability of the pattern of power and coherent activity of each individual woman during rest, and group stability of EEG activity with eyes closed at least over a nine-month period. SIGNIFICANCE: These results provide information on EEG stability in women over a long period.

Role of corpus callosum in interhemispheric coherent activity during sleep.

OBJECTIVE: To investigate to what extent the increase in interhemispheric coherent activity observed from wakefulness to sleep depends on the integrity of the corpus callosum (CC). METHODS: Interhemispheric coherent activity was analyzed in two epileptic patients selected for callosotomy because of multifocal refractory epilepsy, before and 4 months after callosotomy. One patient underwent complete callosotomy and another was subjected to callosotomy of the anterior 2/3, which offered the possibility of comparing the role of the CC in the coherent activity increase from wakefulness to sleep, between anterior regions with interrupted CC communication (in the two patients) and posterior regions with intact communication (in one of them). Results were compared with a group of normal subjects. RESULTS: Both patients showed increased coherent activity from wakefulness to sleep after surgery. CONCLUSIONS: Results demonstrate that interhemispheric coherent activity, despite an attenuation after surgery, is higher during SWS than during wakefulness after sectioning the CC; however, they have to be taken with caution because they come from two patients only. SIGNIFICANCE: Present results show that the increase in coherent activity during sleep does not depend exclusively on callosal integrity but also on state-dependent influences from sleep-promoting mechanisms, probably spread throughout the thalamo-cortical network.

Power and coherent oscillations distinguish REM sleep, stage 1 and wakefulness.

The objective of this work is to determine differences in spectral power and coherent activity between stage 1 (S1) and REM sleep. The EEG activity of the two sleep stages is almost indistinguishable by visual inspection. Although many efforts have been directed toward understanding the process of falling asleep, little is known about differences in EEG activity between stage 1 (S1) and REM sleep. Polysomnography of 8 healthy young adults from S1, REM sleep and wakefulness was recorded. Spectral power and spectral correlation were obtained for 1-50 Hz. Stage 1 was distinguished (ANOVAs) from REM sleep by lower power in 1-9 Hz, higher power in alpha, beta and gamma, lower interhemispheric correlation in 1-8 Hz and gamma, and higher right correlation in 30-50 Hz. It differed from wakefulness by lower power in 9-50 Hz, but not in 1-8 Hz, or in inter- and intrahemispheric correlation. EEG differences between S1 and REM sleep reside not only in changes in power but also in coherent activity. The different behavior of slow and fast frequencies suggests two different mechanisms involved in the gate into sleep, one implicated in promoting sleep, the thalamo-cortical oscillator mode and the other in reducing alertness involving activation mechanisms. Stage 1 is a mixed state, alertness is already reduced but sleep-promoting mechanisms are not yet fully installed. The EEG differences between these two sleep stages contribute to the understanding of REM sleep and S1 physiology and may be relevant for understanding disorders in falling asleep.

Rapid eye movement sleep dreaming is characterized by uncoupled EEG activity between frontal and perceptual cortical regions.

EEG coherent activity is involved in the binding of spatially separated but temporally correlated stimuli into whole events. Cognitive features of rapid eye movement sleep (REM) dreaming resemble frontal lobe dysfunction. Therefore, temporal coupling of EEG activity between frontal and perceptual regions was analyzed from 10 min prior to dream reports (8 adults) from stage-2 and REM sleep. EEG correlation between frontal and perceptual regions decreased and, among perceptual regions increased during REM. The temporal dissociation of EEG activity between executive and perceptual regions supplies an inadequate mechanism for the binding and interpretation of ongoing perceptual activity resulting in dream bizarreness.

Effect of diazepam on EEG power and coherent activity: sex differences.

Benzodiazepine-steroid interactions and sex differences in brain and circulating levels of gonadal steroids, lead to hypothesized differential effects of DZ on EEG in women and men. Coherent activity has been shown to be relevant for binding information into global percepts therefore diazepam effects on EEG correlation and sex differences were assessed in a double-blind crossover study. Healthy males (9) and females (9) received a single-dose (5 mg) of diazepam or placebo. EEG was recorded with eyes open (FP1, FP2, F3, F4, C3, C4, P3, P4, O1, O2) before and 2 h after drug administration in two counterbalanced sessions. DZ selectively increased delta and theta EEG correlation among frontal regions and decreased it between right parieto-occipital (theta) and fronto-central regions (alpha2) in addition to an increase in beta2 interhemispheric correlation in men and women. Men showed increased beta1 interhemispheric correlation, decreased alpha1 and increased beta power; women showed in addition, decreased theta and alpha2 power. theta rhythm was more sensitive to DZ in women, whereas interhemispheric correlation was more affected in men. DZ had a sexually dimorphic effect on waking EEG and a disrupting effect on coherent activity, increasing balance among frontal regions and decreasing temporal coupling between anterior-posterior regions. These sex differences might be related to differences in brain organization and activational effects of female gonadal steroids which are higher in women than in men.

Effect of asymmetry on the electronic delocalization in diiron and iron-cobalt mixed valence metallocenic compounds.

In this work, we report the synthesis and a study on the degree of electronic delocalization in the asymmetric mixed valence complexes [CpFe(C(8)H(6))Fe(C(8)H(7))](+), 3a(+), and [CpCo(C(8)H(6))Fe(C(8)H(7))](+), 3b(+), (Cp = C(5)Me(5), C(8)H(6) = pentalenyde, C(8)H(7) = hydropentalenyde, and = ((3,5(CF(3))(2)C(6)H(3))(4)B(-))). Electrochemical methods, (57)Fe Mössbauer spectroscopy, electronic spectroscopy, and electron paramagnetic resonance were used for this purpose. Although the anti conformation of the complexes precludes any metal-metal interaction, all the techniques employed show that 3a(+) is a electronic delocalized system, while 3b(+) behaves as two individual metallic centers with localized electron density.

EEG bands during wakefulness, slow-wave, and paradoxical sleep as a result of principal component analysis in the rat.

Rat EEG has been empirically divided in bands that frequently do not correspond with EEG generators nor with the functional meaning of EEG rhythms. Power spectra from wakefulness (W), slow-wave sleep (SWS), and paradoxical sleep (PS) of Wistar rats were submitted to Principal Component Analyses (PCA) to investigate which frequencies are covariant. Three independent eigenvectors were identified for SWS: a band between 1-6, an intermediate band between 7-15, and a fast band between 16-32 Hz (90.74% of the variance); two independent eigenvectors were extracted for PS: slow frequencies between 1-6 covarying together with frequencies between 11-16 Hz, and activity between 6-10 covarying together with fast frequencies between 17-32 Hz (80.38% of the variance); four eigen-vectors were obtained for W: 3-7, 8-9, 10-21 and 21-32 Hz (81.47% of the variance). Vigilance states showed significant differences in AP from 1 to 22 Hz. PCA extracted broad bands different for each vigilance state, which included the most representative EEG activities characteristic of them. These results indicate that during SWS, slow oscillations include frequencies up to 6 Hz, and spindle oscillations frequencies down to 7 Hz. No alpha frequencies were identified as an independent band. Frequencies within theta and beta were gathered in the same eigenvector during PS and in different eigenvectors during W suggesting coordinated activation of hippocampal and cortical systems during PS. These bands are consistent with the underlying neurophysiological mechanisms of sleep and wakefulness and with firing frequencies of generators of rhythmic activity obtained in cellular studies in animals.

Paradoxical sleep is characterized by uncoupled gamma activity between frontal and perceptual cortical regions.

STUDY OBJECTIVES: Coherent activity of fast activity has been postulated to be a common language of the brain involved in the processing of information and in integration of spatially separated but temporally correlated stimuli into whole events. Any disruption affecting temporality would result in distortion of cognitive activity. Dreaming during paradoxical sleep (PS) shows cognitive alterations that mimic frontal lobe dysfunction. Decreased temporal coupling of EEG between frontal and perceptual regions was hypothesized. The main objective was to explore temporal relationships of fast activity among these regions. DESIGN: N/A. SETTING: N/A. PARTICIPANTS: 8 young adults. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Interhemispheric (INTERr) and intrahemispheric (INTRAr) EEG correlation spectra (1-50 Hz) were obtained for wakefulness, stage 2, stage 4, and PS during the second night spent at the laboratory. INTERr showed a significant overall increase during sleep in comparison to wakefulness, whereas INTRAr of fast activity (27-48 Hz) between frontal-perceptual regions (F-P, F-O, F-T, Fp-P, Fp-T) decreased exclusively during PS while INTRAr among perceptual regions (P-O, P-T, O-T) maintained wakefulness values. CONCLUSIONS: Present results demonstrate state- and frequency-dependent shifts on temporal coupling. The hypothesized decrease in correlation of fast activity between frontal and perceptual regions during PS was confirmed. This decrease of temporal coupling might underlie the loss of voluntary direction of thinking and congruence with social and temporal context and the lack of judgment and passive acceptance of bizarreness during PS dreaming. The wakefulness levels in correlation of fast activity among perceptual regions might explain perceptual acuity during PS dreaming.

Organizational and activational effects of gonadal steroid hormones on the EEG of male and female rats.

To analyze organizational and activational effects of sex steroids on adult rat electroencephalographic activity (recorded at postnatal day 100), seven groups were included: males (48)-intact, neonatally or adult castrated; females (64)-intact, ovariectomized and exposed pre- or neonatally to testosterone propionate. In males, neonatal orchidectomy increased beta relative power, whereas both neonatal and adult castration reduced interparietal correlation. In females, prenatal testosterone administration produced higher theta absolute power; theta relative power was higher in all experimental groups, whereas beta1 and beta2 were decreased by prenatal and increased by neonatal virilization; prenatal virilization enhanced, while neonatal virilization and adult ovariectomy decreased interparietal correlation. These data indicate that females are more sensitive to early prenatal than to neonatal organizational effects of sex steroids, and some electroencephalographic features are feminized in castrated males and virilized in perinatally androgenized females.

EEG bands during wakefulness, slow-wave and paradoxical sleep as a result of principal component analysis in man.

Human electroencephalogram (EEG) has been divided in bands established by visual inspection that frequently do not correspond with EEG generators nor with functional meaning of EEG rhythms. Power spectra from wakefulness, stage 2, stage 4 and paradoxical sleep of 8 young adults were submitted to Principal Component Analyses to investigate which frequencies covaried together. Two identical eigenvectors were identified for stage 2 and stage 4: 1 to 8 Hz and 5 to 15 Hz (87.95 and 84.62 % of the total variance respectively). Two eigenvectors were extracted for PS: 1 to 9 Hz and 10 to 15 Hz (81.62% of the total variance). Three eigenvectors were obtained for W: with frequencies between 1 to 7 Hz, 7 to 11 Hz, and 12 to 15 Hz (78.32% of the total variance). Power for all frequencies showed significant differences among vigilance states. These results indicate that slow wave activity can oscillate at higher frequencies, up to 8 Hz, and that spindle oscillations have a wider range down to 5 Hz. No theta band was independently identified, suggesting either that delta and theta oscillations are two rhythms under the same global influence, or that the traditional division of theta band in the human cortical EEG is artificial. Alpha as a band was identified only during wakefulness. Principal component analysis upon spectral densities extracted broad bands different for each vigilance state and from traditional bands, consistent with functional significance of EEG and with frequencies of generators of rhythmic activity obtained in cellular studies in animals.