Dominik P. J. Heib

The Fate of Incoming Stimuli during NREM Sleep is Determined by Spindles and the Phase of the Slow Oscillation

The present study aimed at identifying the neurophysiological responses associated with auditory stimulation during non-rapid eye movement (NREM) sleep using simultaneous electroencephalography (EEG)/functional magnetic resonance imaging (fMRI) recordings. It was reported earlier that auditory stimuli produce bilateral activation in auditory cortex, thalamus, and caudate during both wakefulness and NREM sleep. However, due to the spontaneous membrane potential fluctuations cortical responses may be highly variable during NREM. Here we now examine the modulation of cerebral responses to tones depending on the presence or absence of sleep spindles and the phase of the slow oscillation. Thirteen healthy young subjects were scanned successfully during stage 2–4 NREM sleep in the first half of the night in a 3 T scanner. Subjects were not sleep-deprived and sounds were post hoc classified according to (i) the presence of sleep spindles or (ii) the phase of the slow oscillation during (±300 ms) tone delivery. These detected sounds were then entered as regressors of interest in fMRI analyses. Interestingly wake-like responses – although somewhat altered in size and location – persisted during NREM sleep, except during present spindles (as previously published in Dang-Vu et al., 2011) and the negative going phase of the slow oscillation during which responses became less consistent or even absent. While the phase of the slow oscillation did not alter brain responses in primary sensory cortex, it did modulate responses at higher cortical levels. In addition EEG analyses show a distinct N550 response to tones during the presence of light sleep spindles and suggest that in deep NREM sleep the brain is more responsive during the positive going slope of the slow oscillation. The presence of short temporal windows during which the brain is open to external stimuli is consistent with the fact that even during deep sleep meaningful events can be detected. Altogether, our results emphasize the notion that spontaneous fluctuations of brain activity profoundly modify brain responses to external information across all behavioral states, including deep NREM sleep.

Slow sleep spindle activity, declarative memory, and general cognitive abilities in children.

STUDY OBJECTIVES Functional interactions between sleep spindle activity, declarative memory consolidation, and general cognitive abilities in school-aged children. DESIGN Healthy, prepubertal children (n = 63; mean age 9.56 ± 0.76 y); ambulatory all-night polysomnography (2 nights); investigating the effect of prior learning (word pair association task; experimental night) versus nonlearning (baseline night) on sleep spindle activity; general cognitive abilities assessed using the Wechsler Intelligence Scale for Children-IV (WISC-IV). MEASUREMENTS AND RESULTS Analysis of spindle activity during nonrapid eye movement sleep (N2 and N3) evidenced predominant peaks in the slow (11-13 Hz) but not in the fast (13-15 Hz) sleep spindle frequency range (baseline and experimental night). Analyses were restricted to slow sleep spindles. Changes in spindle activity from the baseline to the experimental night were not associated with the overnight change in the number of recalled words reflecting declarative memory consolidation. Children with higher sleep spindle activity as measured at frontal, central, parietal, and occipital sites during both baseline and experimental nights exhibited higher general cognitive abilities (WISC-IV) and declarative learning efficiency (i.e., number of recalled words before and after sleep). CONCLUSIONS Slow sleep spindles (11-13 Hz) in children age 8-11 y are associated with inter-individual differences in general cognitive abilities and learning efficiency.

Heartbeat-related EEG amplitude and phase modulations from wakefulness to deep sleep: Interactions with sleep spindles and slow oscillations.

Based on physiological models of neurovisceral integration, different studies have shown how cognitive processes modulate heart rate and how the heartbeat, on the other hand, modulates brain activity. We tried to further determine interactions between cardiac and electrical brain activity by means of EEG. We investigated how the heartbeat modulates EEG in 23 healthy controls from wakefulness to deep sleep and showed that frontocentral heartbeat evoked EEG amplitude and phase locking (as measured by intertrial phase locking), at about 300-400 ms after the R peak, decreased with increasing sleep depth with a renewed increase during REM sleep, which underpins the assumption that the heartbeat evoked positivity constitutes an active frontocortical response to the heartbeat. Additionally, we found that individual heart rate was correlated with the frequency of the EEGs spectral peak (i.e., alpha peak frequency during wakefulness). This correlation was strongest during wakefulness and declined linearly with increasing sleep depth. Furthermore, we show that the QRS complex modulates spindle phase possibly related to the correspondence between the frequency of the QRS complex and the spindle frequency of about 12-15 Hz. Finally, during deep sleep stages, a loose temporal coupling between heartbeats and slow oscillation (0.8 Hz) could be observed. These findings indicate that cardiac activity such as heart rate or individual heartbeats can modulate or be modulated by ongoing oscillatory brain activity.

Susceptibility to declarative memory interference is pronounced in primary insomnia.

Sleep has been shown to stabilize memory traces and to protect against competing interference in both the procedural and declarative memory domain. Here, we focused on an interference learning paradigm by testing patients with primary insomnia (N = 27) and healthy control subjects (N = 21). In two separate experimental nights with full polysomnography it was revealed that after morning interference procedural memory performance (using a finger tapping task) was not impaired in insomnia patients while declarative memory (word pair association) was decreased following interference. More specifically, we demonstrate robust associations of central sleep spindles (in N3) with motor memory susceptibility to interference as well as (cortically more widespread) fast spindle associations with declarative memory susceptibility. In general the results suggest that insufficient sleep quality does not necessarily show up in worse overnight consolidation in insomnia but may only become evident (in the declarative memory domain) when interference is imposed.

Oscillatory brain responses to own names uttered by unfamiliar and familiar voices

Among auditory stimuli, the own name is one of the most powerful and it is able to automatically capture attention and elicit a robust electrophysiological response. The subject’s own name (SON) is preferentially processed in the right hemisphere, mainly because of its self-relevance and emotional content, together with other personally relevant information such as the voice of a familiar person. Whether emotional and self-relevant information are able to attract attention and can be, in future, introduced in clinical studies remains unclear. In the present study we used EEG and asked participants to count a target name (active condition) or to just listen to the SON or other unfamiliar names uttered by a familiar or unfamiliar voice (passive condition). Data reveals that the target name elicits a strong alpha event related desynchronization with respect to non-target names and triggers in addition a left lateralized theta synchronization as well as delta synchronization. In the passive condition alpha desynchronization was observed for familiar voice and SON stimuli in the right hemisphere. Altogether we speculate that participants engage additional attentional resources when counting a target name or when listening to personally relevant stimuli which is indexed by alpha desynchronization whereas left lateralized theta synchronization may be related to verbal working memory load. After validating the present protocol in healthy volunteers it is suggested to move one step further and apply the protocol to patients with disorders of consciousness in which the degree of residual cognitive processing and self-awareness is still insufficiently understood.

Better than sham? A double-blind placebo-controlled neurofeedback study in primary insomnia

See Thibault et al. (doi:10.1093/awx033) for a scientific commentary on this article. Neurofeedback has been claimed to have therapeutic efficacy in multiple disorders. In a double-blind, placebo-controlled trial in insomnia, Schabus et al. report that sensorimotor rhythm neurofeedback (12–15 Hz) neither changes the EEG nor objectively improves sleep. While patients do report subjective improvements, these do not differ from those seen with placebo feedback.

Slow Oscillation Amplitudes and Up-State Lengths Relate to Memory Improvement

There is growing evidence of the active involvement of sleep in memory consolidation. Besides hippocampal sharp wave-ripple complexes and sleep spindles, slow oscillations appear to play a key role in the process of sleep-associated memory consolidation. Furthermore, slow oscillation amplitude and spectral power increase during the night after learning declarative and procedural memory tasks. However, it is unresolved whether learning-induced changes specifically alter characteristics of individual slow oscillations, such as the slow oscillation up-state length and amplitude, which are believed to be important for neuronal replay. 24 subjects (12 men) aged between 20 and 30 years participated in a randomized, within-subject, multicenter study. Subjects slept on three occasions for a whole night in the sleep laboratory with full polysomnography. Whereas the first night only served for adaptation purposes, the two remaining nights were preceded by a declarative word-pair task or by a non-learning control task. Slow oscillations were detected in non-rapid eye movement sleep over electrode Fz. Results indicate positive correlations between the length of the up-state as well as the amplitude of both slow oscillation phases and changes in memory performance from pre to post sleep. We speculate that the prolonged slow oscillation up-state length might extend the timeframe for the transfer of initial hippocampal to long-term cortical memory representations, whereas the increase in slow oscillation amplitudes possibly reflects changes in the net synaptic strength of cortical networks.

Oscillatory theta activity during memory formation and its impact on overnight consolidation: A missing link?

Sleep has been shown to promote memory consolidation driven by certain oscillatory patterns, such as sleep spindles. However, sleep does not consolidate all newly encoded information uniformly but rather “selects” certain memories for consolidation. It is assumed that such selection depends on salience tags attached to the new memories before sleep. However, little is known about the underlying neuronal processes reflecting presleep memory tagging. The current study sought to address the question of whether event-related changes in spectral theta power (theta ERSP) during presleep memory formation could reflect memory tagging that influences subsequent consolidation during sleep. Twenty-four participants memorized 160 word pairs before sleep; in a separate laboratory visit, they performed a nonlearning control task. Memory performance was tested twice, directly before and after 8 hr of sleep. Results indicate that participants who improved their memory performance overnight displayed stronger theta ERSP during the memory task in comparison with the control task. They also displayed stronger memory task-related increases in fast sleep spindle activity. Furthermore, presleep theta activity was directly linked to fast sleep spindle activity, indicating that processes during memory formation might indeed reflect memory tagging that influences subsequent consolidation during sleep. Interestingly, our results further indicate that the suggested relation between sleep spindles and overnight performance change is not as direct as once believed. Rather, it appears to be mediated by processes beginning during presleep memory formation. We conclude that theta ERSP during presleep memory formation reflects cortico-hippocampal interactions that lead to a better long-term accessibility by tagging memories for sleep spindle-related reprocessing.

Night and day variations of sleep in patients with disorders of consciousness

Brain injuries substantially change the entire landscape of oscillatory dynamics and render detection of typical sleep patterns difficult. Yet, sleep is characterized not only by specific EEG waveforms, but also by its circadian organization. In the present study we investigated whether brain dynamics of patients with disorders of consciousness systematically change between day and night. We recorded ~24 h EEG at the bedside of 18 patients diagnosed to be vigilant but unaware (Unresponsive Wakefulness Syndrome) and 17 patients revealing signs of fluctuating consciousness (Minimally Conscious State). The day-to-night changes in (i) spectral power, (ii) sleep-specific oscillatory patterns and (iii) signal complexity were analyzed and compared to 26 healthy control subjects. Surprisingly, the prevalence of sleep spindles and slow waves did not systematically vary between day and night in patients, whereas day-night changes in EEG power spectra and signal complexity were revealed in minimally conscious but not unaware patients.

Preferential processing of emotionally and self-relevant stimuli persists in unconscious N2 sleep

HighlightsOwn names (SONs) and angry voice (AV) stimuli are salient during wakefulness.Intriguingly, SONs and AV stimuli remain salient during unconscious N2 sleep.Results suggest a ‘sentinel processing mode’ of the brain during unconscious sleep.A K‐complex‐like response indicates preferential processing of salient stimuli.Presumably, delta, theta and sigma ERS reflect the subsequent sleep‐protecting mechanism. Abstract Information processing has been suggested to depend on the current state of the brain as well as stimulus characteristics (e.g. salience). We compared processing of salient stimuli (subject’s own names [SONs] and angry voice [AV] stimuli) to processing of unfamiliar names (UNs) and neutral voice (NV) stimuli across different vigilance stages (i.e. wakefulness as well as sleep stages N1 and N2) by means of event‐related oscillatory responses during wakefulness and a subsequent afternoon nap. Our findings suggest that emotional prosody and self‐relevance drew more attentional resources during wakefulness with specifically AV stimuli being processed more strongly. During N1, SONs were more arousing than UNs irrespective of prosody. Moreover, emotional and self‐relevant stimuli evoked stronger responses also during N2 sleep suggesting a ‘sentinel processing mode’ of the brain during this state of naturally occurring unconsciousness. Finally, this initial preferential processing of salient stimuli during N2 sleep seems to be followed by an inhibitory sleep‐protecting process, which is reflected by a K‐complex‐like response.