Cortical locations of maximal spindle activity: magnetoencephalography (MEG) study

The aim of this study was to determine the main cortical regions related to maximal spindle activity of sleep stage 2 in healthy individual subjects during a brief morning nap using magnetoencephalography (MEG). Eight volunteers (mean age: 26.1 ± 8.7, six women) all right handed, free of any medical psychiatric or sleep disorders were studied. Whole-head 148-channel MEG and a conventional polysomnography montage (EEG; C3, C4, O1 and O2 scalp electrodes and EOG, EMG and ECG electrodes) were used for data collection. Sleep MEG/EEG spindles were visually identified during 15 min of stage 2 sleep for each participant. The distribution of brain activity corresponding to each spindle was calculated using a combination of independent component analysis and a current source density technique superimposed upon individual MRIs. The absolute maximum of spindle activation was localized to frontal, temporal and parietal lobes. However, the most common cortical regions for maximal source spindle activity were precentral and/or postcentral areas across all individuals. The present study suggests that maximal spindle activity localized to these two regions may represent a single event for two types of spindle frequency: slow (at 12 Hz) and fast (at 14 Hz) within global thalamocortical coherence.     

Topographic distribution of sleep spindles in young healthy subjects

The application of an automatic sleep spindle detection procedure allowed the documentation of the topographic distribution of spindle characteristics, such as number, amplitude, frequency and duration, as a function of sleep depth and of recording time. Multichannel all-night EEG recordings were performed in 10 normal healthy subjects aged 20–35 years. Although the interindividual variability in the number of sleep spindles was very high (2.7±2.1 spindles per minute stage 2 sleep), all but two subjects showed maximal spindle activity in centro-parietal midline leads. Moreover, this topography was seen in all sleep stages and changed only slightly – to a more central distribution – towards the end of the night. On the other hand, slow (11.5–14 Hz) and fast (14–16 Hz) spindles showed a completely different topography, with slow spindles distributed anteriorly and fast spindles centro-parietally. The number of sleep spindles per min was significant depending on sleep stages, with the expected highest occurrence in stage 2, and on recording time, with a decrease in spindle density from the beginning towards the end of the night. However, spindle amplitude, frequency and individual duration was not influenced by sleep depth or time of the night.     

The role of the spindle in human information processing of high-intensity stimuli during sleep

Sleep spindles are 12-14 Hz oscillations in EEG, which are thought to inhibit or 'gate' information processing. Event-related potentials may be employed to probe the extent of information processing during sleep. Previous research indicates that event-related potentials elicited by moderate intensity stimuli show increased positivity (or further removal of negativity) when stimuli are presented concurrent with spindles. However, the effectiveness of spindles to inhibit the processing of much louder stimuli remains unknown. The purpose of the present study was to investigate the extent of this gating, by using a range of stimuli including those that are loud and intrusive. Eight good sleepers were recorded during a single night. Auditory stimuli were delivered randomly at 0, 60, 80 or 100 dB SPL. Trials were sorted off-line by sleep stage, stimulus intensity and spindle characteristic (i.e. spindle absent, spindle present). During the sleep-onset period, the often-reported changes in event-related potentials were observed - N1 decreased and P2 increased in amplitude. In Stage 2 sleep, P2 was affected by the presence of spindles, particularly when stimulus intensity was loud. Its amplitude was greatest when spindles occurred following the onset of the stimulus. Scalp-recorded spindles might, therefore, be a consequence of the prior thalamic inhibition of information processing, especially when confronted by loud, intrusive external stimuli.     

Sound‐induced perturbations of the brain network in non‐REM sleep,and network oscillations in wake

During sleep, the brain network processes sensory stimuli without awareness. Stimulation must affect differently brain networks in sleep versus wake, but these differences have yet to be quantified. We recorded cortical activity in stage 2 (SII) sleep and wake using EEG while a tone was intermittently played. Zero‐lag correlation measured input to pairs of sensors in the network; cross‐correlation and phase‐lag index measured pairwise corticocortical connectivity. Our analysis revealed that under baseline conditions, the cortical network, in particular the central regions of the frontoparietal cortex, interact at a characteristic latency of 50 ms, but only during wake, not sleep. Nonsalient auditory stimulation causes far greater perturbation of connectivity from baseline in sleep than wake, both in the response to common input and corticocortical connectivity. The findings have key implications for sensory processing.     

多分辨率小波信号分解用于大鼠睡眠纺锤波的分析

本研究首先设计了慢波睡眠期脑电信号的合成仿真信号 ,对小波基函数进行了选择 ,结果证明Coiflet 5阶小波变换对大鼠慢波睡眠期EEG信号具有较好的分解结果。据此 ,应用多分辨率小波分析法设计了提取睡眠纺锤波的算法 ,并利用该算法对安定用药后和睡眠剥夺后大鼠慢波睡眠期纺锤波的持续时间和能量变化进行了分析 ,结果表明 :安定具有延长慢波睡眠期纺锤波持续时间的作用 ,而睡眠剥夺可以增加慢波睡眠期纺锤波的能量。这些结果说明 ,小波分析算法可以提供功率谱分析无法表现的时频信息。     

Modulation of somatosensory evoked potentials during wake-sleep states and spike-wave discharges in the rat

STUDY OBJECTIVE: To clarify the cortical evoked responses in the primary somatosensory cortex of the rat under states of waking, slow-wave sleep (SWS), paradoxical sleep (PS), and spike-wave discharges (SWDs), which are associated with absence seizure. DESIGN: Somatosensory evoked potentials (SEPs) in response to single- and paired-pulse stimulations under waking, SWS, PS, and SWDs were compared. SEPs to a single-pulse stimulus with regard to cortical spikes of sleep spindles and SWDs were also evaluated. PARTICIPANTS: Twenty Long Evans rats. INTERVENTIONS: Single- and paired-pulse innocuous electrical stimulations were applied to the tail of rats with chronically implanted electrodes in the primary somatosensory cortex and neck muscle under waking, SWS, PS, and SWDs. MEASUREMENTS AND RESULTS: SEPs displayed distinct patterns under waking/PS and SWS/SWDs. The short-latency P1-N1 wave of the SEP was severely impeded during SWDs but not in other states. Reduction of the P1-N1 magnitude to the second stimulus of the paired-pulse stimulus for interstimulus intervals of < or = 300 milliseconds appeared in waking and PS states, but the decrease occurred only at particular interstimulus intervals under SWS. Interestingly, augmentation was found under SWDs. Moreover, cyclic augmentation of the P1-N1 magnitude was associated with spindle spikes, but cyclic reduction was observed with SWD spikes. CONCLUSION: Changes in SEPs are not only behavior dependent, but also phase locked onto ongoing brain activity. Distinct short-term plasticity of SEPs during sleep spindles or SWDs may merit further studies for seizure control and tactile information processing.     

Spindles are highly heritable as identified by different spindle detectors

Study ObjectivesSleep spindles, a defining feature of stage N2 sleep, are maximal at central electrodes and are found in the frequency range of the electroencephalogram (EEG) (sigma 11–16 Hz) that is known to be heritable. However, relatively little is known about the heritability of spindles. Two recent studies investigating the heritability of spindles reported moderate heritability, but with conflicting results depending on scalp location and spindle type. The present study aimed to definitively assess the heritability of sleep spindle characteristics.MethodsWe utilized the polysomnography data of 58 monozygotic and 40 dizygotic same-sex twin pairs to identify heritable characteristics of spindles at C3/C4 in stage N2 sleep including density, duration, peak-to-peak amplitude, and oscillation frequency. We implemented and tested a variety of spindle detection algorithms and used two complementary methods of estimating trait heritability.ResultsWe found robust evidence to support strong heritability of spindles regardless of detector method (h² > 0.8). However not all spindle characteristics were equally heritable, and each spindle detection method produced a different pattern of results.ConclusionsThe sleep spindle in stage N2 sleep is highly heritable, but the heritability differs for individual spindle characteristics and depends on the spindle detector used for analysis.     

Sleep spindles in human prefrontal cortex: an electrocorticographic study

To investigate the sleep spindle activity of the human prefrontal cortex (PFC), we simultaneously recorded whole nights of polysomnographic and electrocorticographic (ECoG) activities during the natural sleep of epileptic patients. Subjects were nine patients with intractable epilepsy who had subdural electrodes surgically attached to the orbital (seven cases), medial (three cases), or dorsolateral (two cases) PFC, and in one case to the frontal pole. To examine spindle frequencies, fast Fourier transformation (FFT) and auto-correlation analyses were performed on the PFC ECoG and Cz EEG data, primarily on epochs of stage 2 sleep. Lower sigma band ECoG oscillations of about 12 Hz were widely distributed across all prefrontal cortical areas including the frontal limbic regions, but none of the PFC sigma frequency peaks coincided with the faster (about 14 Hz) Cz EEG sleep spindles. Combining our results with anatomical and electrophysiological facts, it is suggested that the thalamofrontal circuit involving the rostral reticular and the mediodorsal nucleus of the thalamus is responsible for the generation of 12 Hz frontal spindles in humans.     

Functional features of crossmodal mismatch responses

Research on brain mechanisms of deviance detection and sensory memory trace formation, best indexed by the mismatch negativity, mainly relied on the investigation of responses elicited by auditory stimuli. However, comparable less research reported the mismatch negativity elicited by somatosensory stimuli. More importantly, little is known on the functional features of mismatch deviant and standard responses across different sensory modalities. To directly compare different sensory modalities, we adopted a crossmodal roving paradigm and collected event-related potentials elicited by auditory, non-nociceptive somatosensory, and nociceptive trains of stimuli, during Active and Passive attentional conditions. We applied a topographical segmentation analysis to cluster successive scalp topographies with quasi-stable landscape of significant differences to extract crossmodal mismatch responses. We obtained three main findings. First, across different sensory modalities and attentional conditions, the formation of a standard sensory trace became robust mainly after the second stimulus repetition. Second, the neural representation of a modality deviant stimulus was influenced by the preceding sensory modality. Third, the mismatch negativity significantly covaried between Active and Passive attentional conditions within the same sensory modality, but not between different sensory modalities. These findings provide robust evidence that, while different modalities share a similar process of standard trace formation, the process of deviance detection is largely modality dependent.     

The characteristics of the nogo-N140 component in somatosensory go/nogo tasks

Nogo-related brain potentials may not be dependent on sensory modalities but reflect common neural activities specific to the inhibitory process. Recent studies reported that nogo potentials were elicited by not only visual and auditory but also somatosensory stimulation. However, the characteristics of this nogo potential evoked by somatosensory stimulation have been unclear because of the small number of reports. In the present study, therefore, to determine the characteristics of this potential, the effects of stimulus site and response hand were investigated. Electrical stimulation was delivered to the second and fifth digit of one hand, and the subjects had to respond to a go stimulus by pushing a button with the thumb contralateral to the stimulated side as quickly as possible. The amplitudes of the nogo-N140 component (N140 evoked by the nogo stimuli), which is very similar to the nogo-N2 components following visual and auditory stimulation, were unrelated to the stimulated digits, the second and fifth digit of the left and right hand. However, differences between go and nogo ERPs were significantly larger in the hemisphere contralateral to the response hand than the ipsilateral hemisphere. This result was inconsistent with visual and auditory go/nogo studies showing a right-hemisphere dominance or bilateral activities in nogo trials. Therefore, nogo-N140 should be considered to reflect the inhibitory process especially in the hemisphere contralateral to the response hand and the sensory modality dependency of nogo potentials.     

Spindle frequencies in sleep EEG show U-shape within first four NREM sleep episodes

It has been shown in previous studies on sleep electroencephalogram (EEG) that spindles are slower in the beginning of the night fastening towards the end of the night. Corresponding findings have been obtained by spectral analysis. The present study was based on our preliminary observation that slower spindles are found in the middle of the non-rapid eye movement (NREM) sleep episodes as compared with the beginning or the end of the episodes. Eight healthy female and six male subjects were studied. Sleep spindles were visually selected and spindle frequencies calculated for 11 analysis points in each NREM sleep episode. The median spindle frequencies formed a clear U-shape within NREM sleep episodes with an initial decrease and final increase. The decrease was statistically significant within the first four NREM sleep episodes. It is possible that the spindle frequency pattern could be used to reveal variations in sleep depth within sleep stage 2. In animal studies the spindle frequency has been found to be associated to the duration of the hyperpolarization-rebound sequences of the thalamocortical cells. If it is assumed that the same cellular mechanisms are responsible for spindle frequencies in humans then the study of variations in spindle frequency could be used to examine the NREM sleep process in humans.     

The N550 component of the evoked K-complex: A modality non-specific response?

A large amplitude late negative deflection peaking between 500 and 650 ms is observable in the averaged K-complex wave-form. This peak is thus often labelled the N550. 'N550' appears during stage 2 and is maintained into slow wave sleep but is not apparent during REM. Most studies have employed auditory stimuli to elicit the K-complex. Two experiments were run to examine the effects of stimulus modality on the topographical distribution of the N550. In the first experiment, the K-complexes were elicited in an auditory oddball procedure. In the second experiment, K-complexes were elicited by respiratory occlusions. Twenty-nine channel recordings were used to increase spatial resolution. N550 was substantially larger in the average of trials containing K-complexes than in trials in which a K-complex could not be identified. N550 varied inversely in amplitude with the probability of accordance of the stimulus. The topographic distribution of the N550 was consistent between experiments. It was bilaterally symmetrical and was maximal over fronto-central regions of the scalp. The results indicate that the N550 reflects the activity of a modality non-specific, sleep dependent generator that responds to both interoceptive and external stimulation.     

Development and comparison of four sleep spindle detection methods

OBJECTIVE: The objective of the present work was to develop and compare methods for automatic detection of bilateral sleep spindles. METHODS AND MATERIALS: All-night sleep electroencephalographic (EEG) recordings of 12 healthy subjects with a median age of 40 years were studied. The data contained 6043 visually scored bilateral spindles occurring in frontopolar or central brain location. In the present work a new sigma index for spindle detection was developed, based on the fast Fourier transform (FFT) spectrum, aiming at approximating our previous fuzzy spindle detector. The sigma index was complemented with spindle amplitude analysis, based on finite impulse response (FIR) filtering, to form of a combination detector of bilateral spindles. In this combination detector, the spindle amplitude distribution of each recording was estimated and used to tune two different amplitude thresholds. This combination detector was compared to bilaterally extracted sigma indexes and fuzzy detections, which aim to be independent of absolute spindle amplitudes. As a fourth method a fixed spindle amplitude detector was included. RESULTS: The combination detector provided the best overall performance; in S2 sleep a 70% true positive rate was reached with a specificity of 98.6%, and a false-positive rate of 32%. The bilateral sigma indexes provided the second best results, followed by fuzzy detector, while the fixed amplitude detector provided the poorest results so that in S2 sleep a 70% true positive rate was reached with a specificity of 97.7% and false-positive rate of 46%. The spindle amplitude distributions automatically determined for each recording by the combination detector were compared to amplitudes of visually scored spindles and they proved to correspond well. Inter-hemispheric amplitude variation of visually scored bilateral spindles is also presented. CONCLUSION: Flexibility is beneficial in the detection of bilateral spindles. The present work advances automated spindle detection and increases the knowledge of bilateral sleep spindle characteristics.     

Newborn Responses to Nonsignal Auditory Stimuli: I. Electroencephalographic Desynchronization

There are suggestions in the literature that the electroencephalographic (EEG) desynchronization response is in the newborn's repertoire. The present investigation was designed to examine that possibility under stringent experimental conditions. Sixteen normal neonates were presented with a 1-Sec pure tone or white noise during one episode of quiet sleep and one episode of active sleep. Flat activity during stimulated quiet sleep was compared with spontaneous periods of low voltage activity during a nonstimulated quiet sleep episode. Comparisons were also made between responses in quiet sleep with and without prior stimulation in active sleep. Habituation and dishabituation were studied by presenting the nonfamiliar stimulus after repetition of the original stimulus. Increased EEG desynchronization to stimulation was found but the response appears to be a complex function of the type of stimulus, recording location, stimulus repetition, and the prior experience variable. The results have implications for differential maturation of the brain, the perceptual capacities of the neonate, and the controversy over orientation in the newborn.     

Scalp topography of the spontaneous K-complex and of delta-waves in human sleep

Objective: Together with spindles, K-complexes are well known hallmarks of stage 2 sleep (S2). However, little is known about their topographical distribution in comparison to delta-waves and to K-complexes superimposed by spindles. Patients and methods: In this study, the topographical distribution of spontaneous K-complexes and delta-waves in S2 and delta-waves in stage 4 sleep (S4) in 10 healthy young adults (aged 20 to 35 years, 7 female) was investigated. K-complexes with and without spindles in S2, delta-waves with and without spindles in S2, and delta-waves in S4 distributed all over the night were visually selected. EEG power maps and statistical parametric maps were calculated. Results: Absolute delta power of S2 K-complexes appeared to be significantly higher than of S2 delta-waves and delta power of S4 delta-waves was higher than of S2 delta-waves. In K-complexes and delta-waves, power was found to be highest over medio-frontal regions in the delta frequency band (0.5 - 4.0 Hz) with a second maximum occipitally in delta-waves, no matter whether superimposed by a spindle or not. Conclusion: K-complexes and delta-waves in S2 differ in topographical distribution. Even though in S2 delta-waves have less power, they have a similar topographical distribution in S2 and S4, supporting the hypothesis that delta-waves in S2 further develop towards delta-waves in slow wave sleep. The delta frequency components of K-complexes and delta-waves are unaffected by spindles.     

The space-time profiles of sleep spindles and their coordination with slow oscillations on the electrode manifold

Sleep spindles are important for sleep quality and cognitive functions, with their coordination with slow oscillations (SOs) potentially organizing cross-region reactivation of memory traces. Here, we describe the organization of spindles on the electrode manifold and their relation to SOs. We analyzed the sleep night EEG of 34 subjects and detected spindles and SOs separately at each electrode. We compared spindle properties (frequency, duration, and amplitude) in slow wave sleep (SWS) and Stage 2 sleep (S2); and in spindles that coordinate with SOs or are uncoupled. We identified different topographical spindle types using clustering analysis that grouped together spindles co-detected across electrodes within a short delay (±300 ms). We then analyzed the properties of spindles of each type, and coordination to SOs. We found that SWS spindles are shorter than S2 spindles, and spindles at frontal electrodes have higher frequencies in S2 compared to SWS. Furthermore, S2 spindles closely following an SO (about 10% of all spindles) show faster frequency, shorter duration, and larger amplitude than uncoupled ones. Clustering identified Global, Local, Posterior, Frontal-Right and Left spindle types. At centro-parietal locations, Posterior spindles show faster frequencies compared to other types. Furthermore, the infrequent SO-spindle complexes are preferentially recruiting Global SO waves coupled with fast Posterior spindles. Our results suggest a non-uniform participation of spindles to complexes, especially evident in S2. This suggests the possibility that different mechanisms could initiate an SO-spindle complex compared to SOs and spindles separately. This has implications for understanding the role of SOs-spindle complexes in memory reactivation.     

Effects of systemic atropine sulfate administration on the frequency content of the cat sensorimotor EEG during sleep and waking

Sensorimotor electroencephalogram (EEG) frequencies in cats were evaluated with power spectral analysis before and after 3 doses of atropine sulfate. All doses of atropine tested caused enhanced EEG slow waves (0-7 Hz) and spindles (8-15 Hz) during waking immobility, and postdrug frequency profiles during slow-wave sleep and waking immobility were identical. With 0.75 mg/kg atropine, movement (head movement, locomotion) resulted in EEG desynchronization and reduced power in all frequencies less than 24 Hz. After 1.5 or 3.0 mg/kg atropine, power in low frequencies remained elevated during movement, but power in spindle frequencies was significantly reduced compared with other states. During active REM sleep after 1.5 mg/kg atropine, power in spindle frequencies was significantly lower than that during quiet REM sleep. These results indicate that the sensorimotor cortical EEG in cats is under the control of multiple systems. At least 1 of these systems is active during movement, and its actions are resistant to muscarinic receptor blockade.     

Sleep spindle activity changes in patients with affective disorders

Various polysomnographic sleep patterns are associated with affective disorders, but very little is known about sleep spindle characteristics in adult depression. In primary endogenous depressive male patients (unipolar, UP, and bipolar, BP) with comparable depression scores and in normal control subjects recorded during 3 consecutive nights, no night effect was observed on the sleep variables investigated except for REM latencies of stages 1 and 2. Stage 2 duration and variables related to sleep spindle characteristics (the number and the density of spindles of 1/2 s; the number and the density of full spindles of stage 2 over the 3 nights) were significantly lower in depressed patients than in control subjects, the mean number of spindles being lower in UP than in BP patients. Sleep spindle measures were clearly negatively correlated with age in the overall group (i.e., depressed plus control subjects). They were also negatively correlated with the REM latencies of stages 1 and 2 in BP depressed patients, whereas this relation was not observed in UP patients.