Non-rapid Eye Movement Sleep Period Research Articles

SSAVE: A tool for analysis and visualization of sleep periods using electroencephalography data.

Human sleep architecture is structured with repeated episodes of rapid-eye-movement (REM) and non-rapid-eye-movement (NREM) sleep. An overnight sleep study facilitates identification of macro and micro changes in the pattern and duration of sleep stages associated with sleep disorders and other aspects of human mental and physical health. Overnight sleep studies record, in addition to electroencephalography (EEG) and other electro-physiological signals, a sequence of sleep-stage annotations. SSAVE, introduced here, is open-source software that takes sleep-stage annotations and EEG signals as input, identifies and characterizes periods of NREM and REM sleep, and produces a hypnogram and its time-matched EEG spectrogram. SSAVE fills an important gap for the rapidly growing field of sleep medicine by providing an easy-to-use tool for sleep-period identification and visualization. SSAVE can be used as a Python package, a desktop standalone tool or through a web portal. All versions of the SSAVE tool can be found on: https://manticore.niehs.nih.gov/ssave.

Sleep slow-wave oscillations trigger seizures in a genetic epilepsy model of Dravet syndrome.

Sleep is the preferential period when epileptic spike-wave discharges appear in human epileptic patients, including genetic epileptic seizures such as Dravet syndrome with multiple mutations including SCN1A mutation and GABAA receptor γ2 subunit Gabrg2Q390X mutation in patients, which presents more severe epileptic symptoms in female patients than male patients. However, the seizure onset mechanism during sleep still remains unknown. Our previous work has shown that the sleep-like state-dependent homeostatic synaptic potentiation can trigger epileptic spike-wave discharges in one transgenic heterozygous Gabrg2+/Q390X knock-in mouse model.1 Here, using this heterozygous knock-in mouse model, we hypothesized that slow-wave oscillations themselves in vivo could trigger epileptic seizures. We found that epileptic spike-wave discharges in heterozygous Gabrg2+/Q390X knock-in mice exhibited preferential incidence during non-rapid eye movement sleep period, accompanied by motor immobility/facial myoclonus/vibrissal twitching and more frequent spike-wave discharge incidence appeared in female heterozygous knock-in mice than male heterozygous knock-in mice. Optogenetically induced slow-wave oscillations in vivo significantly increased epileptic spike-wave discharge incidence in heterozygous Gabrg2+/Q390X knock-in mice with longer duration of non-rapid eye movement sleep or quiet-wakeful states. Furthermore, suppression of slow-wave oscillation-related homeostatic synaptic potentiation by 4-(diethylamino)-benzaldehyde injection (i.p.) greatly attenuated spike-wave discharge incidence in heterozygous knock-in mice, suggesting that slow-wave oscillations in vivo did trigger seizure activity in heterozygous knock-in mice. Meanwhile, sleep spindle generation in wild-type littermates and heterozygous Gabrg2+/Q390X knock-in mice involved the slow-wave oscillation-related homeostatic synaptic potentiation that also contributed to epileptic spike-wave discharge generation in heterozygous Gabrg2+/Q390X knock-in mice. In addition, EEG spectral power of delta frequency (0.1-4 Hz) during non-rapid eye movement sleep was significantly larger in female heterozygous Gabrg2+/Q390X knock-in mice than that in male heterozygous Gabrg2+/Q390X knock-in mice, which likely contributes to the gender difference in seizure incidence during non-rapid eye movement sleep/quiet-wake states of human patients. Overall, all these results indicate that slow-wave oscillations in vivo trigger the seizure onset in heterozygous Gabrg2+/Q390X knock-in mice, preferentially during non-rapid eye movement sleep period and likely generate the sex difference in seizure incidence between male and female heterozygous Gabrg2+/Q390X knock-in mice.

Relating Pupil Diameter and Blinking to Cortical Activity and Hemodynamics across Arousal States.

Arousal state affects neural activity and vascular dynamics in the cortex, with sleep associated with large changes in the local field potential and increases in cortical blood flow. We investigated the relationship between pupil diameter and blink rate with neural activity and blood volume in the somatosensory cortex in male and female unanesthetized, head-fixed mice. We monitored these variables while the mice were awake, during periods of rapid eye movement (REM), and non-rapid eye movement (NREM) sleep. Pupil diameter was smaller during sleep than in the awake state. Changes in pupil diameter were coherent with both gamma-band power and blood volume in the somatosensory cortex, but the strength and sign of this relationship varied with arousal state. We observed a strong negative correlation between pupil diameter and both gamma-band power and blood volume during periods of awake rest and NREM sleep, although the correlations between pupil diameter and these signals became positive during periods of alertness, active whisking, and REM. Blinking was associated with increases in arousal and decreases in blood volume when the mouse was asleep. Bilateral coherence in gamma-band power and in blood volume dropped following awake blinking, indicating a reset of neural and vascular activity. Using only eye metrics (pupil diameter and eye motion), we could determine the arousal state of the mouse ('Awake,' 'NREM,' 'REM') with >90% accuracy with a 5 s resolution. There is a strong relationship between pupil diameter and hemodynamics signals in mice, reflecting the pronounced effects of arousal on cerebrovascular dynamics.SIGNIFICANCE STATEMENT Determining arousal state is a critical component of any neuroscience experiment. Pupil diameter and blinking are influenced by arousal state, as are hemodynamics signals in the cortex. We investigated the relationship between cortical hemodynamics and pupil diameter and found that pupil diameter was strongly related to the blood volume in the cortex. Mice were more likely to be awake after blinking than before, and blinking resets neural activity. Pupil diameter and eye motion can be used as a reliable, noninvasive indicator of arousal state. As mice transition from wake to sleep and back again over a timescale of seconds, monitoring pupil diameter and eye motion permits the noninvasive detection of sleep events during behavioral or resting-state experiments.

A deep learning algorithm based on 1D CNN-LSTM for automatic sleep staging.

Sleep staging is an important part of sleep research. Traditional automatic sleep staging based on machine learning requires extensive feature extraction and selection. This paper proposed a deep learning algorithm without feature extraction based on one-dimensional convolutional neural network and long short-term memory. The algorithm can automatically divide sleep into 5 phases including awake period, non-rapid eye movement sleep period (N1 ∼ N3) and rapid eye movement using the electroencephalogram signals. The raw signal was processed by the wavelet transform. Then, the processed signal was directly input into the deep learning algorithm to obtain the staging result. The accuracy of staging is 93.47% using the Fpz-Cz electroencephalogram signal. When using the Fpz-Cz and electroencephalogram signal, the algorithm can obtain the highest accuracy of 94.15%. These results show that this algorithm is suitable for different physiological signals and can realize end-to-end automatic sleep staging without any manual feature extraction.

Sleep in the lesser mouse-deer (Tragulus kanchil).

The mouse-deer or chevrotains are the smallest of the ungulates and ruminants. They are characterized by a number of traits which are considered plesiomorphic for the Artiodactyla order. The objective of this study was to examine sleep in the lesser mouse-deer (Tragulus kanchil), which is the smallest in this group (body mass < 2.2 kg). Electroencephalogram, nuchal electromyogram, electrooculogram, and body acceleration were recorded in four adult mouse-deer females using a telemetry system in Bu Gia Map National Park in Vietnam. The mouse-deer spent on average 49.7 ± 3.0% of 24 h in non-rapid eye movement (NREM) sleep. REM sleep occupied 1.7 ± 0.3% of 24 h or 3.2 ± 0.5% of total sleep time. The average duration of REM sleep episodes was 2.0 ± 0.2 min, the average maximum was 5.1 ± 1.1 min, and the longest episodes lasted 8 min. NREM sleep occurred in sternal recumbency with the head held above the ground while 64.7 ± 6.4% of REM sleep occurred with the head resting on the ground. The eyes were open throughout most of the NREM sleep period. The mouse-deer displayed polyphasic sleep and crepuscular peaks in activity (04:00-06:00 and 18:00-19:00). The largest amounts of NREM occurred in the morning (06:00-09:00) and the smallest before dusk (at 04:00-06:00). REM sleep occurred throughout most of the daylight hours (08:00-16:00) and in the first half of the night (19:00-02:00). We suggest that the pattern and timing of sleep in the lesser mouse-deer is adapted to the survival of a small herbivorous animal, subject to predation, living in high environmental temperatures in the tropical forest undergrowth.

No effect of targeted memory reactivation during sleep on retention of vocabulary in adolescents

Re-exposure of newly acquired vocabulary during sleep improves later memory recall in healthy adults. The success of targeted memory reactivation (TMR) during sleep presumably depends on the presence of slow oscillations (i.e., EEG activity at a frequency of about 0.75 Hz). As slow oscillating activity is at its maximum during adolescence, we hypothesized that TMR is even more beneficial at this developmental stage. In the present study, adolescents aged 11 to 13 learnt Dutch vocabulary in the evening and were tested on recall performance the next morning. Half of the words were presented via loudspeakers during post-learning periods of NREM (Non Rapid Eye Movement) sleep in order to stimulate memory reactivation. Unexpectedly, TMR during sleep did not improve memory on the behavioral level in adolescents. On the oscillatory level, successful reactivation during sleep resulted in the characteristic increase in theta power over frontal brain regions, as reported in adults. However, we observed no increase in spindle power during successful reactivation. Possible factors that may explain the lacking effect of TMR in adolescents in this study such as differences in learning abilities and pre-sleep performance levels are discussed.

Sleep EEG spectral power is correlated with subjective-objective discrepancy of sleep onset latency in major depressive disorder

We aimed to identify the sleep electroencephalography (EEG) spectral power correlates of the subjective-objective discrepancy (SOD) of sleep onset latency (SOL) in major depressive disorder (MDD), primary insomnia (PI), and normal sleeping control (NSC) groups. We examined relative power values in standard frequency bands of the EEG spectra during the first Non-Rapid Eye Movement (NREM) sleep period as correlates of SOD of SOL between sleep diary and polysomnography in MDD (n = 36), PI (n = 19), and NSC (n = 23) groups. We also compared the relative spectral power of sleep EEG among MDD (n = 40), PI (n = 19), and NSC (n = 23) groups. SOD of SOL in MDD patients was positively correlated with relative sigma (r = 0.622, p corrected < 0.001), beta power (r = 0.559, p corrected = 0.002), and alpha power (r = 0.469, p corrected = 0.024) in the first NREM sleep period. There was no significant difference of sleep EEG power spectra among the three groups. SOD was positively correlated with high frequency EEG in MDD. High frequency EEG power is thought to be associated with hyperarousal and memory consolidation, and future larger-scale studies may further elucidate the neurophysiological mechanisms underlying SOD of sleep onset duration.

Role of Somatostatin-Positive Cortical Interneurons in the Generation of Sleep Slow Waves.

During non-rapid eye-movement (NREM) sleep, cortical and thalamic neurons oscillate every second or so between ON periods, characterized by membrane depolarization and wake-like tonic firing, and OFF periods, characterized by membrane hyperpolarization and neuronal silence. Cortical slow waves, the hallmark of NREM sleep, reflect near-synchronous OFF periods in cortical neurons. However, the mechanisms triggering such OFF periods are unclear, as there is little evidence for somatic inhibition. We studied cortical inhibitory interneurons that express somatostatin (SOM), because ∼70% of them are Martinotti cells that target diffusely layer I and can block excitatory transmission presynaptically, at glutamatergic terminals, and postsynaptically, at apical dendrites, without inhibiting the soma. In freely moving male mice, we show that SOM+ cells can fire immediately before slow waves and their optogenetic stimulation during ON periods of NREM sleep triggers long OFF periods. Next, we show that chemogenetic activation of SOM+ cells increases slow-wave activity (SWA), slope of individual slow waves, and NREM sleep duration; whereas their chemogenetic inhibition decreases SWA and slow-wave incidence without changing time spent in NREM sleep. By contrast, activation of parvalbumin+ (PV+) cells, the most numerous population of cortical inhibitory neurons, greatly decreases SWA and cortical firing, triggers short OFF periods in NREM sleep, and increases NREM sleep duration. Thus SOM+ cells, but not PV+ cells, are involved in the generation of sleep slow waves. Whether Martinotti cells are solely responsible for this effect, or are complemented by other classes of inhibitory neurons, remains to be investigated.SIGNIFICANCE STATEMENT Cortical slow waves are a defining feature of non-rapid eye-movement (NREM) sleep and are thought to be important for many of its restorative benefits. Yet, the mechanism by which cortical neurons abruptly and synchronously cease firing, the neuronal basis of the slow wave, remains unknown. Using chemogenetic and optogenetic approaches, we provide the first evidence that links a specific class of inhibitory interneurons-somatostatin-positive cells-to the generation of slow waves during NREM sleep in freely moving mice.

Sleep spindles predict stress-related increases in sleep disturbances.

Background and Aim: Predisposing factors place certain individuals at higher risk for insomnia, especially in the presence of precipitating conditions such as stressful life events. Sleep spindles have been shown to play an important role in the preservation of sleep continuity. Lower spindle density might thus constitute an objective predisposing factor for sleep reactivity to stress. The aim of this study was therefore to evaluate the relationship between baseline sleep spindle density and the prospective change in insomnia symptoms in response to a standardized academic stressor.Methods: Twelve healthy students had a polysomnography recording during a period of lower stress at the beginning of the academic semester, along with an assessment of insomnia complaints using the insomnia severity index (ISI). They completed a second ISI assessment at the end of the semester, a period coinciding with the week prior to final examinations and thus higher stress. Spindle density, amplitude, duration, and frequency, as well as sigma power were computed from C4–O2 electroencephalography derivation during stages N2–N3 of non-rapid-eye-movement (NREM) sleep, across the whole night and for each NREM sleep period. To test for the relationship between spindle density and changes in insomnia symptoms in response to academic stress, spindle measurements at baseline were correlated with changes in ISI across the academic semester.Results: Spindle density (as well as spindle amplitude and sigma power), particularly during the first NREM sleep period, negatively correlated with changes in ISI (p < 0.05).Conclusion: Lower spindle activity, especially at the beginning of the night, prospectively predicted larger increases in insomnia symptoms in response to stress. This result indicates that individual differences in sleep spindle activity contribute to the differential vulnerability to sleep disturbances in the face of precipitating factors.

Time-varying correlations between delta EEG power and heart rate variability in midlife women: the SWAN Sleep Study.

No studies have evaluated the dynamic, time-varying relationship between delta electroencephalographic (EEG) sleep and high frequency heart rate variability (HF-HRV) in women. Delta EEG and HF-HRV were measured during sleep in 197 midlife women (M(age) = 52.1, SD = 2.2). Delta EEG-HF-HRV correlations in nonrapid eye movement (NREM) sleep were modeled as whole-night averages and as continuous functions of time. The whole-night delta EEG-HF-HRV correlation was positive. The strongest correlations were observed during the first NREM sleep period preceding and following peak delta power. Time-varying correlations between delta EEG-HF-HRV were stronger in participants with sleep-disordered breathing and self-reported insomnia compared to healthy controls. The dynamic interplay between sleep and autonomic activity can be modeled across the night to examine within- and between-participant differences including individuals with and without sleep disorders.

Spatial patterns of neuronal activity in rat cerebral cortex during non-rapid eye movement sleep.

It is commonly assumed that cortical activity in non-rapid eye movement sleep (NREMS) is spatially homogeneous on the mesoscopic scale. This is partly due to the limited observational scope of common metabolic or imaging methods in sleep. We used the recently developed technique of thallium-autometallography (TlAMG) to visualize mesoscopic patterns of activity in the sleeping cortex with single-cell resolution. We intravenously injected rats with the lipophilic chelate complex thallium diethyldithiocarbamate (TlDDC) during spontaneously occurring periods of NREMS and mapped the patterns of neuronal uptake of the potassium (K+) probe thallium (Tl+). Using this method, we show that cortical activity patterns are not spatially homogeneous during discrete 5-min episodes of NREMS in unrestrained rats—rather, they are complex and spatially diverse. Along with a relative predominance of infragranular layer activation, we find pronounced differences in metabolic activity of neighboring neuronal assemblies, an observation which lends support to the emerging paradigm that sleep is a distributed process with regulation on the local scale.Electronic supplementary materialThe online version of this article (doi:10.1007/s00429-014-0867-9) contains supplementary material, which is available to authorized users.

Neurobiologic Mechanisms of Sleep and Wakefulness

Neurobiologic Mechanisms of Sleep and Wakefulness

Complex Sleep Apnea

Complex sleep apnea currently refers to the emergence and persistence of central apneas and hypopneas following the application of positive airway pressure therapy in patients with obstructive sleep apnea. However, this narrow definition is an "outcome" and does not capture the spectrum of pathological activation of the respiratory chemoreflex in sleep apnea. The International Classification of Sleep Disorders - 3rd edition recognizes the phenomenon of Treatment-Related Central Sleep Apnea, but the phenotype is usually evident prior to onset of therapy. The key polysomnographic characteristics of chemoreflex modulated and mediated sleep apnea are nonrapid eye movement (NREM) dominance of respiratory events, short (<30seconds) or long (>60seconds) cycle time with a self-similar metronomic timing, and spontaneous improvement during rapid eye movement (REM) sleep. Thus, the majority of chemoreflex effects go unrecognized due to the bias toward obstructive sleep apnea's current scoring criteria. Any treatment of apparently obstructive sleep apnea, including surgery and oral appliances, can expose chemoreflex-driven instabilities. As both sleep fragmentation and a narrow CO2 reserve or increased loop gain drive the disease, sedatives (to induce longer periods of stable NREM sleep and reduce the destabilizing effects of arousals in NREM sleep) and CO2-based stabilization approaches are logical. Adaptive ventilation reduces mean hyperventilation yet can induce ventilator-patient desynchrony, while enhanced expiratory rebreathing space (EERS, dead space during positive pressure therapy) and CO2 manipulation directly stabilize respiratory control by moving CO2 above the apnea threshold. Carbonic anhydrase inhibition can provide further adjunctive benefits. Novel pharmacological approaches may target mediators of carotid body hypoxic sensitization, such as the balance between gas neurotransmitters. In complex apnea patients, single mode therapy is unlikely to be successful, and the power of multi-modality therapy should be harnessed for optimal outcomes.

A Moderate Increase of Physiological CO2 in a Critical Range during Stable NREM Sleep Episode: A Potential Gateway to REM Sleep

Sleep is characterized as rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. Studies suggest that wake-related neurons in the basal forebrain, posterior hypothalamus and brainstem, and NREM sleep-related neurons in the anterior-hypothalamic area inhibit each other, thus alternating sleep–wakefulness. Similarly, pontine REM-ON and REM-OFF neurons reciprocally inhibit each other for REM sleep modulation. It has been proposed that inhibition of locus coeruleus (LC) REM-OFF neurons is pre-requisite for REM sleep genesis, but it remains ambiguous how REM-OFF neurons are hyperpolarized at REM sleep onset. The frequency of breathing pattern remains high during wake, slows down during NREM sleep but further escalates during REM sleep. As a result, brain CO2 level increases during NREM sleep, which may alter REM sleep manifestation. It has been reported that hypocapnia decreases REM sleep while hypercapnia increases REM sleep periods. The groups of brainstem chemosensory neurons, including those present in LC, sense the alteration in CO2 level and respond accordingly. For example, one group of LC neurons depolarize while other hyperpolarize during hypercapnia. In another group, hypercapnia initially depolarizes but later hyperpolarizes LC neurons. Besides chemosensory functions, LC REM-OFF neurons are an integral part of REM sleep executive machinery. We reason that increased CO2 level during a stable NREM sleep period may hyperpolarize LC neurons including REM-OFF, which may help initiate REM sleep. We propose that REM sleep might act as a sentinel to help maintain normal CO2 level for unperturbed sleep.

Ischemic stroke selectively inhibits REM sleep of rats

Sleep disorders are important risk factors for stroke; conversely, stroke patients suffer from sleep disturbances including disruptions of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep and a decrease in total sleep. This study was performed to characterize the effect of stroke on sleep architecture of rats using continuous electroencephalography (EEG) and activity monitoring. Rats were implanted with transmitters which enabled continuous real time recording of EEG, electromyography (EMG), and locomotor activity. Baseline recordings were performed prior to induction of either transient middle cerebral artery (MCA) occlusion or sham surgery. Sleep recordings were obtained for 60h after surgery to identify periods of wakefulness, NREM, and REM sleep before and after stroke. Spectral analysis was performed to assess the effects of stroke on state-dependent EEG. Finally, we quantified the time in wake, NREM, and REM sleep before and after stroke. Delta power, a measure of NREM sleep depth, was increased the day following stroke. At the same time, there was a significant shift in theta rhythms to a lower frequency during REM and wake periods. The awake EEG slowed after stroke over both hemispheres. The EEG of the ischemic hemisphere demonstrated diminished theta power specific to REM in excess of the slowing seen over the contralateral hemisphere. In contrast to rats exposed to sham surgery which had slightly increased total sleep, rats undergoing stroke experienced decreased total sleep. The decrease in total sleep after stroke was the result of dramatic reduction in the amount of REM sleep after ischemia. The suppression of REM after stroke was due to a decrease in the number of REM bouts; the length of the average REM bout did not change. We conclude that after stroke in this experimental model, REM sleep of rats is specifically and profoundly suppressed. Further experiments using this experimental model should be performed to investigate the mechanisms and consequences of REM suppression after stroke.

The effect of electromagnetic fields emitted by mobile phones on human sleep

Previous research has suggested that exposure to radiofrequency electromagnetic fields increases electroencephalogram spectral power in non-rapid eye movement sleep. Other sleep parameters have also been affected following exposure. We examined whether aspects of sleep architecture show sensitivity to electromagnetic fields emitted by digital mobile phone handsets. Fifty participants were exposed to electromagnetic fields for 30 min prior to sleep. Results showed a decrease in rapid eye movement sleep latency and increased electroencephalogram spectral power in the 11.5-12.25 Hz frequency range during the initial part of sleep following exposure. These results are evidence that mobile phone exposure prior to sleep may promote rapid eye movement sleep and modify the sleep electroencephalogram in the first non-rapid eye movement sleep period.

The Effects of Hyperbilirubinemia on Sleep-Spindle Characteristics in Infants

The purpose of this study is to investigate the effect of hyperbilirubinemia on sleep-spindle characteristics. Rhythmic activities, such as sleep spindles, may be abolished by hyperbilirubinemia. Electroencephalogram records were taken from 15 infants with hyperbilirubinemia and 18 healthy infants at the 12th week after birth. Sleep spindles of the 2 groups were compared according to location, density, duration, amplitude, frequency, asynchrony, and asymmetry. In the study and control groups, the density of the spindles was found to be 76.9 +/- 23.7 and 105.2 +/- 33.9, respectively, in a 1-hour non-rapid eye movement sleep period. The mean durations of the sleep spindles in the study and control groups were found to be 4105 +/- 802 milliseconds and 5162 +/- 1075 milliseconds, respectively. There was not any difference between the groups according to the amplitude and asymmetry. However, there was a significant difference between the 2 groups in the frequency of spindles. The mean frequency was found to be 12.5 +/- 0.6 Hz in the study group and 13.2 +/- 0.9 in the control group. The percentage of asynchronous spindles was higher in the study group than in the control group. There was a significant negative correlation between the bilirubin levels during the newborn period and density, duration, and frequency of spindles. However, there was a significantly positive correlation between the bilirubin levels and percentage of asynchronous spindles. There was a significant negative correlation between the duration of hyperbilirubinemia and spindleamplitude. We suggest that studies on the critical maturation periods of sleep-spindle patterns might provide a sensitive tool for early diagnosis of neurophysiologic brain alterations during the first trimester of life in a population of at-risk children, such as jaundiced infants.

Arousal from sleep shortens sympathetic burst latency in humans.

1. Bursts of sympathetic activity in muscle nerves are phase-locked to the cardiac cycle by the sinoaortic baroreflexes. Acoustic arousal from non-rapid eye movement (NREM) sleep reduces the normally invariant interval between the R-wave of the electrocardiogram (ECG) and the peak of the corresponding sympathetic burst; however, the effects of other forms of sleep disruption (i.e. spontaneous arousals and apnoea-induced arousals) on this temporal relationship are unknown. 2. We simultaneously recorded muscle sympathetic nerve activity in the peroneal nerve (intraneural electrodes) and the ECG (surface electrodes) in seven healthy humans and three patients with sleep apnoea syndrome during NREM sleep. 3. In seven subjects, burst latencies were shortened subsequent to spontaneous K complexes (1.297 +/- 0.024 s, mean +/- s. e.m.) and spontaneous arousals (1.268 +/- 0.044 s) compared with latencies during periods of stable NREM sleep (1.369 +/- 0.023 s). In six subjects who demonstrated spontaneous apnoeas during sleep, apnoea per se did not alter burst latency relative to sleep with stable electroencephalogram (EEG) and breathing (1.313 +/- 0.038 vs. 1.342 +/- 0.026 s); however, following apnoea-induced EEG perturbations, burst latencies were reduced (1.214 +/- 0.034 s). 4. Arousal-induced reduction in sympathetic burst latency may reflect a temporary diminution of baroreflex buffering of sympathetic outflow. If so, the magnitude of arterial pressure perturbations during sleep (e.g. those caused by sleep disordered breathing and periodic leg movements) may be augmented by arousal.

Sleep Apnea Syndrome and Cerebral Hemodynamics

The dynamics of cerebral blood flow velocity (CBFV) during sleep were investigated in the right middle cerebral artery of 10 patients with sleep apnea syndrome (SAS) (mean age, 37 years) and 10 healthy control subjects (mean age, 32 years) throughout the entire sleep period. A computer-assisted pulsed (2 MHz) transcranial Doppler ultrasonography system was modified for continuous long-term and on-line recording of cerebral hemodynamics. Concurrently, simultaneous polysomnography, continuous BP recordings, and measurement of the end-expiratory carbon dioxide were undertaken. CBFV showed comparable nocturnal profiles in both groups with decreases during non-rapid eye movement (NREM) sleep and increases during rapid eye movement (REM) sleep, indicating that the general pattern of brain perfusion during normal sleep is maintained in SAS. Sleep stage changes were not regularly accompanied by corresponding changes in CBFV. This reflected a quantitative uncoupling between cerebral electrical activity and cerebral perfusion during sleep and indicated a dissociation in the activity of central regulatory mechanisms. Sleep stage-related analysis showed slightly reduced CBFV in patients with SAS compared with healthy control subjects during wakefulness and the first NREM sleep period, suggesting depressed brain activity in the patient group. The higher CBFV values observed in patients with SAS compared with control subjects during REM sleep and sleep stage 2, both preceding and following REM sleep, underline the influence of dynamically changing sleep patterns on cerebral perfusion in these patients. Reproducible rapid decreases in CBFV were related to EEG arousals. Since apneas are terminated by arousals, these results showed that direct neuronal influences on brain perfusion during apnea are evident.

Abnormal behavioral patterns in the human fetus at term: correlation with lesion sites in the central nervous system after birth.

We describe three fetuses at term that demonstrated abnormal behavioral patterns in utero when observed using real-time ultrasound. The abnormal patterns turned out to have neurologic correlations after birth. In case 1, despite a normal breathing pattern, no movement in any of the four extremities was observed, thus suggesting the existence of a spinal cord lesion at the rostral end, located at C4 or C5. In case 2 a lack of breathing movement was noted repeatedly, together with the abnormal finding that alternation of periods of rapid eye movement (REM) sleep with those of non-rapid eye movement (NREM) sleep was not present. These findings implied a lesion involving the pons and/or medulla oblongata. In case 3 movement of the four extremities, breathing movement, and alternating periods of REM sleep and NREM sleep were found to be within the normal range. The concurrence of regular mouthing and the NREM sleep period was not observed, however, suggesting impairment in the brain function responsible for NREM sleep located from the pons through the thalamocortical connection to the cerebral hemisphere.