Sleep deprivation increases susceptibility to kindled and penicillin seizure events during all waking and sleep states in cats

The timing of amygdala kindled and penicillin seizures was studied throughout the sleep-wake cycle in eight cats following near total sleep deprivation and a control procedure that did not affect sleep time. Sleep loss was induced by 24-h exposure to a modified "flower pot" procedure employing a small pedestal. The control procedure consisted of 24-h exposure to a larger pedestal. Sleep loss increased susceptibility to generalized kindled and penicillin seizures during all waking and sleep states but did not alter temporal patterns of seizure susceptibility. Both before and after sleep loss, kindled cats showed maximal seizure susceptibility, indexed by lowest seizure thresholds, during slow wave sleep (SWS) and transitions from SWS to REM sleep (REMS). The spike-wave discharges and motor seizures of systemic penicillin epilepsy were always most frequent during SWS and during drowsiness after awakening. Both models were invariably most resistant to seizures during stable REMS. To explain sleep- and sleep loss-activated seizures, we summarized previous work suggesting that sleep abnormalities dictate the timing of seizures and are exacerbated by sleep loss. Abnormal behavioral arousals and pathological somatomotor system excitability occur in both models and are particularly pronounced during seizure-prone intervals. Sleep loss may magnify somatomotor system hyperexcitability patterns in all states, thus allowing abnormal motor arousals and seizures to intrude during seizure-prone and seizure-resistant sleep and waking states.     

Organization of sleeping and waking states in infants: consistency across contexts

The sleep and waking states of infants are described from direct behavioral observations made in the home for a 7-hour period on weeks 2, 3, 4, and 5. States were analyzed separately for two contexts: infant alone and infant with the mother. States analyzed included Alert, Waking (Non-Alert) Activity, Fussing or Crying, Drowse or Sleep-Wake Transition, Active Sleep, Quiet Sleep, and Unclassified Sleep. Individual state profiles for each context were obtained for each week. A quantitative measure of profile consistency over weeks was calculated as an index of stability of state organization. Infants showed considerable range in state stability over weeks. State stability when alone was significantly correlated with state stability when with the mother (r = .67), even though there were differences in sleep-wake distributions and in level of stimulation in these contexts. These findings demonstrate within-individual consistency in CNS control of behavioral states, across sleep and wakefulness and throughout the diverse activities of the caretaking environment.     

Sleep and waking modulate spine turnover in the adolescent mouse cortex

Cortical development involves synaptic formation and elimination. Although synaptogenesis predominates in the early stages and pruning in the later stages, the two processes are thought to happen concurrently. In adults, synaptic strength is modulated by behavioral state, and we asked whether synaptic remodeling may be affected by sleep and waking states. Using two-photon microscopy in adolescent mice, we found that waking results in a net increase in cortical spines, whereas sleep is associated with net spine loss.     

Expert-system classification of sleep/waking states in infants

This work is part of a project to develop an expert system for automated classification of the sleep/waking states in human infants; i.e. active or rapid-eye-movement sleep (REM), quiet or non-REM sleep (NREM), including its four stages, indeterminate sleep (IS) and wakefulness (WA). A model to identify these states, introducing an objective formalisation in terms of the state variables characterising the recorded patterns, is presented. The following digitally recorded physiological events are taken into account to classify the sleep/waking states: predominant background activity and the existence of sleep spindles in the electro-encephalogram; existence of rapid eye movements in the electro-oculogram; and chin muscle tone in the electromyogram. Methods to detect several of these parameters are described. An expert system based on artificial ganglionar lattices is used to classify the sleep/waking states, on an off-line minute-by-minute basis. Algorithms to detect patterns automatically and an expert system to recognise sleep/waking states are introduced, and several adjustments and tests using various real patients are carried out. Results show an overall performance of 96.4% agreement with the expert on validation data without artefacts, and 84.9% agreement on validation data with artefacts. Moreover, results show a significant improvement in the classification agreement due to the application of the expert system, and a discussion is carried out to justify the difficulties of matching the expert's criteria for the interpretation of characterising patterns.     

Expert-system classification of sleep/waking states in infants

This work is part of a project to develop an expert system for automated classification of the sleep/waking states in human infants; i.e. active or rapid-eye-movement sleep (REM), quiet or non-REM sleep (NREM), including its four stages, indeterminate sleep (IS) and wakefulness (WA). A model to identify these states, introducing an objective formalisation in terms of the state variables characterising the recorded patterns, is presented. The following digitally recorded physiological events are taken into account to classify the sleep/waking states: predominant background activity and the existence of sleep spindles in the electro-encephalogram; existence of rapid eye movements in the electro-oculogram; and chin muscle tone in the electromyogram. Methods to detect several of these parameters are described. An expert system based on artificial ganglionar lattices is used to classify the sleep/waking states, on an off-line minute-by-minute basis. Algorithms to detect patterns automatically and an expert system to recognise sleep/waking states are introduced, and several adjustments and tests using various real patients are carried out. Results show an overall performance of 96.4% agreement with the expert on validation data without artefacts, and 84.9% agreement on validation data with artefacts. Moreover, results show a significant improvement in the classification agreement due to the application of the expert system, and a discussion is carried out to justify the difficulties of matching the expert's criteria for the interpretation of characterising patterns.     

Natural waking and sleep states: a view from inside neocortical neurons

In this first intracellular study of neocortical activities during waking and sleep states, we hypothesized that synaptic activities during natural states of vigilance have a decisive impact on the observed electrophysiological properties of neurons that were previously studied under anesthesia or in brain slices. We investigated the incidence of different firing patterns in neocortical neurons of awake cats, the relation between membrane potential fluctuations and firing rates, and the input resistance during all states of vigilance. In awake animals, the neurons displaying fast-spiking firing patterns were more numerous, whereas the incidence of neurons with intrinsically bursting patterns was much lower than in our previous experiments conducted on the intact-cortex or isolated cortical slabs of anesthetized cats. Although cortical neurons displayed prolonged hyperpolarizing phases during slow-wave sleep, the firing rates during the depolarizing phases of the slow sleep oscillation was as high during these epochs as during waking and rapid-eye-movement sleep. Maximum firing rates, exceeding those of regular-spiking neurons, were reached by conventional fast-spiking neurons during both waking and sleep states, and by fast-rhythmic-bursting neurons during waking. The input resistance was more stable and it increased during quiet wakefulness, compared with sleep states. As waking is associated with high synaptic activity, we explain this result by a higher release of activating neuromodulators, which produce an increase in the input resistance of cortical neurons. In view of the high firing rates in the functionally disconnected state of slow-wave sleep, we suggest that neocortical neurons are engaged in processing internally generated signals.     

Sleep deprivation in the rat: XIV. Comparison of waking hypothalamic and peritoneal temperatures

Earlier studies of rats subjected to total sleep deprivation (TSD) by the disk-over-water method had shown an initial increase in waking peritoneal temperature (T(ip)) followed by an even greater decrease as deprivation proceeded. In the present study, hypothalamic temperature (T(hy)), as well as T(ip), were recorded continuously. As in the earlier studies, TSD rats showed an increase in energy expenditure and an initial increase followed by a decrease in T(ip). Waking T(hy) showed a more prolonged initial rise and a smaller late decline than waking T(ip) Assuming that, as the literature suggests, T(hy) is held closer to temperature setpoint (TSET) than is T(ip), the present results suggest an elevated waking TSET during deprivation. T(ip) became progressively lower than T(hy) over the course of deprivation, indicating a decreased ability to maintain the whole body near TSET. This decreased ability could result from insufficient thermogenesis or excessive heat loss. Because thermogenesis rose progressively throughout deprivation, heat loss must have increased even more than heat production. Thus, the results are consistent with other data which indicate that TSD in the rat produces two opposing effects on waking temperature, an elevation of setpoint and excessive heat loss, which together increase the demand for energy expenditure.     

The sleeping and waking states of infants: correlations across time and person

Study of the sleeping and waking states of infants was extended to the time domain by analyzing their temporal covariation over a 4-week interval using the intra-person correlation coefficient. As a methodological question, inter-person and intra-person correlation matrices were compared. Twenty-eight fullterm, normal infants were observed in the home weekly from 2 to 5 weeks of age. Over each 7-hour observation, the following states were recorded every 10 seconds: Alert, Non-Alert Waking Activity, Fussing, Crying, Daze, Drowse, Sleep-Wake Transition, Active Sleep, Quiet Sleep, and Unclassified Sleep (sleep during periods of the day when a mother was holding her baby). Data were obtained in two social contexts: when the baby was with the mother and when alone. Significant individual differences were found for each of the states in both social contexts. When the baby was alone, there were a greater number of intra-person correlations than inter-person correlations. All correlations between the waking states and Active Sleep or Quiet Sleep were negative, suggesting the hypothesis that the underlying neurobiological mechanisms may allow a degree of substitution among coupled sleep and wake states. This is an extension of the original hypothesis by Roffwarg, Muzio, and Dement. There were fewer systematic relationships among the states when the babies were with their mother in comparison with periods when they were alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cytomegalovirus infection in infancy: virological and immunological studies

Immunological and virological studies on 18 infants with cytomegalovirus (CMV) infection were performed. Eleven of these infants were studied on multiple occasions over a period of 1 year. The patients were divided into three clinical groups based on the probable time of infection and the resulting variation in clinical presentation. General parameters of cell-mediated immunity as determined by E-rosette formation and lymphocyte proliferative responses to mitogens and antigens were found to be normal. Quantitation of CMV excretion in urine, CMV-specific immunofluorescent (IF) and complement-fixing (CF) antibody titres and CMV-specific cell-mediated immune responses were done on all patients at approximately monthly intervals. Throughout the study period all patients continued to excrete CMV despite the presence of high antibody titres to the virus. CMV-specific lymphocyte proliferative responses were absent or diminished in 15 of the 18 patients. The immunological and virological status of all patients was similar regardless of the clinical manifestation of infection.     

Transient versus stable behavior problems in a normative sample: infancy to school age.

Identified 3 subgroups of children from a prospective longitudinal study of temperament and development: (a) those with stable, (b) transient, or (c) no-behavior problems, as rated by mothers across the toddler, preschool, and preparatory school grade periods. Children with stable behavior problems were particularly characterized by more difficult temperament, mothers' overall perception of the child as difficult, and aggressive behavior in the 2- to 4-year age period. Group differences were linear rather than categorical with transient behavior problem children showing a lesser degree of difficulty. In a second study where more comprehensive child and family measures were available, temperament was again an important discriminator, with Vineland Adaptive Behavior Composite Score, mothers' overall perception of the child's temperament, and maternal psychological health and stress factors also more adverse for the stable group. However, correct classification of the members of these groups using a combination of the above variables was not impressive.     

Development of sinus arrhythmia during sleeping and waking states in normal infants.

The development of variability in heart rate (HR) due to respiration (sinus arrhythmia; SA) has been examined in normal infants from birth through the first 6 months of life. Two aspects of HR variation were examined: the absolute variation at the median respiratory frequency, or extent of sinus arrhythmia (XSA), and the degree to which HR follows respiration regardless of the absolute amount of variation, or coherence of sinus arrhythmia (CSA). Extent of sinus arrhythmia tended to be highest in quiet sleep (QS), lower in active or REM sleep (AS), and lowest in waking (AW), especially after 2 months of age. Extent declined at 1 month of age in QS, but rose over the first 6-month period in all states. During this same period, CSA was also highest in QS, lower in AS, and lowest in AW. Coherence in QS also declined at 1 month and rose between 1 and 6 months; however, no age effects were found in other states. Heart rate was negatively correlated with XSA, but less so with CSA. Sleep state appears to have a significant effect on cardiorespiratory coupling, and this coupling undergoes dramatic changes at 1 month in QS.     

Sleep states and wakefulness in human infants: profiles from motility monitoring

Wakefulness and sleep states were determined from a single-channel analog recording of motility, including body movements and respiration. The subjects were normal infants ranging from 2 days to 4 months of age. First, one observer recorded behavioral states; at the same time respiration and motility was recorded from a pressure sensor under the baby. Subsequently, 4 judges used only the motility recordings to identify wakefulness and states of active, quiet, and active-quiet transitional sleep, for each successive 30-sec epoch. Inter-judge reliability ranged from a mean of 74.9 to 93.1 percent, assessed separately for each individual subject. Judge-observer validity was assessed over all subjects with agreement of r=0.90 for active sleep and r=0.92 for quiet sleep, and complete agreement on the occurrence and relative amount of wakefulness. Judge-observer validity was also assessed based on exact epoch-by-epoch agreement for each subject. Over the total observation agreement ranged from 70.3 to 89.0 percent, from 67.0 to 87.6 percent for active sleep, and from 59.3 to 93.0 percent for quiet sleep. Motility recording makes it possible to study the sequencing of states in infants during prolonged observational periods without instrumentation of the baby for the purpose of making the observations.     

Dynamic characteristics of cardiac R-R intervals during sleep and waking states.

Traditional assessment of cardiac R-R intervals during sleep-wake states uses summary statistics such as mean and interquartile range. Such summary statistics are less able to provide information about instantaneous or dynamic aspects of beat-to-beat control. We examined state-dependent beat-to-beat patterning by plotting each cardiac R-R interval against the previous interval (Poincaré plots). This procedure provides an indication of the probability of occurrence of one interval from its predecessor and allows assessment of dynamic properties of R-R interval variation. Cardiac R-R intervals were determined over 5-12-minute periods of wakefulness (AW), quiet sleep (QS) and rapid eye movement sleep (REM) from six cats; each interval was plotted on the y-axis against the previous value on the x-axis resulting in an RRn + 1 vs. RRn plot. These plots provided evidence that the correlation between an interval and its successor was greater in REM than in QS, even though the overall range was greater in REM. The results suggest that short-term cardiac control during REM may be influenced by more closely regulated mechanisms than suggested by classic concepts.     

Spontaneous and evoked activities of anterior thalamic neurons during waking and sleep states

Summary In contrast with most dorsal thalamic nuclei, the anterior thalamic (AT) complex is devoid of input from the reticular (RE) thalamic nucleus. Instead, it is interposed in a limbic circuit linking the mammillary bodies (MB) to various allo- and periallocortical fields. To investigate the electrophysiological consequences of this peculiar pattern of connectivity, a sample of 92 AT cells, physiologically identified by their short-latency response to MB stimulation, was recorded in chronically-implanted animals and compared to a group of rostral intralaminar centralis-paracentralis (CL-PC) thalamic neurons receiving a dense innervation from the RE nucleus. Numerous similarities were found between the state-related fluctuations in spontaneous and evoked activities of AT and CL-PC neurons. For instance, both types of cells displayed stereotyped, high-frequency (250–300 Hz) bursts of 2–4 spikes in S and a more tonic discharge pattern in W and D. However, the high-frequency bursts of the S state occurred randomly in AT cells, whereas in CL-PC neurons they appeared rhythmically in clusters closely related to spindle waves. In addition, we found that a period of decreased responsiveness consistently followed the ortho- or antidromic activation of AT an CL-PC cells. This inhibitory period lasted less than 80 ms in AT cells and contrasted with the much longer (120ms) period of decreased excitability observed in CL-PC neurons during S. We suggest that these differences reflect the lack of RE input to the AT group. Since the AT complex is, through the MB, intimately linked to the hippocampal formation, it was expected that such prominent hippocampal activities as the theta rhythm would be channeled to the AT nuclei. Surprisingly, no theta-related modulation of neuronal activity was observed in identified AT cells during D epochs. This finding suggests that dramatic transformations are made on the signals emitted by the hippocampal formation somewhere along the pathway linking the hippocampal formation to the AT complex.     

Effects of eszopiclone and zolpidem on sleep and waking states in the adult guinea pig

STUDY OBJECTIVE: The present study was designed to compare and contrast the effects of eszopiclone and zolpidem on the states of sleep and wakefulness in chronically instrumented, unanesthetized adult guinea pigs. DESIGN: Adult guinea pigs were implanted with electrodes to record sleep and waking states and to perform a frequency analysis of the EEG. Eszopiclone (1 and 3 mg/kg) and zolpidem (1 and 3 mg/kg) were administered intraperitoneally. MEASUREMENTS AND RESULTS: The administration of eszopiclone (1 and 3 mg/kg) resulted in a significant dose-dependent increase in NREM sleep. Zolpidem produced a significant increase in NREM sleep, but only at a dose of 3 mg/kg. The following changes in NREM and REM sleep, as well as in the power spectra, were all significant when the effects of 1 and 3 mg/kg of eszopiclone were compared with responses induced with 1 and 3 mg/kg of zolpidem, respectively: The increase in NREM sleep produced by eszopiclone was greater than that following the administration of zolpidem. The mean latency to NREM sleep following the administration of eszopiclone was significantly shorter than zolpidem. Eszopiclone significantly increased the latency to REM sleep. The mean duration of episodes of NREM sleep was increased by eszopiclone, but not by zolpidem. The EEG power increased in the delta band and decreased in the theta band during NREM sleep following the administration of eszopiclone. No significant changes occurred in any of the frequency bands analyzed following zolpidem administration. CONCLUSIONS: The differences in the effects of eszopiclone and zolpidem on sleep and waking states and the power spectra of the EEG likely reflect the fact that eszopiclone and zolpidem bind to different subunits of the GABAA receptor complex.     

Meta-analysis of P300 normative aging studies

The theoretical and empirical backgrounds for the utility of the P300 event-related potential (ERP) as a measure of cognitive aging are summarized. P300 latency data from 32 different normative aging studies are then reviewed and assessed with meta-analytic procedures. Evaluation of moderator variables indicates that sample characteristics, stimulus factors, and task conditions contribute significantly to the “normal” change in peak latency that occurs with aging. These findings are critiqued in the context of previous reports, and implications are outlined for future applications of ERPs to normative aging. It is concluded that P300 latency can provide useful information about cognitive aging but that specific variables must be considered to obtain more precise results.