Hippocampal slow EEG frequencies during NREM sleep are involved in spatial memory consolidation in humans

The hypothesis that sleep is instrumental in the process of memory consolidation is currently largely accepted. Hippocampal formation is involved in the acquisition of declarative memories and particularly of spatial memories. Nevertheless, although largely investigated in rodents, the relations between spatial memory and hippocampal EEG activity have been scarcely studied in humans. Aimed to evaluate the effects of spatial learning on human hippocampal sleep EEG activity, we recorded hippocampal Stereo‐EEG (SEEG) in a group of refractory epilepsy patients undergoing presurgical clinical evaluation, after a training on a spatial navigation task. We observed that hippocampal high‐delta (2–4 Hz range) activity increases during the first NREM episode after learning compared to the baseline night. Moreover, the amount of hippocampal NREM high‐delta power was correlated with task performance at retest. The effect involved only the hippocampal EEG frequencies inasmuch no differences were observed at the neocortical electrodes and in the traditional polysomnographic measures. The present findings support the crucial role of hippocampal slow EEG frequencies during sleep in the memory consolidation processes. More generally, together with previous results, they suggest that slow frequency rhythms are a fundamental characteristic of human hippocampal EEG during both sleep and wakefulness, and are related to the consolidation of different types of memories. © 2014 Wiley Periodicals, Inc.     

Disruption of ripple‐associated hippocampal activity during rest impairs spatial learning in the rat

The hippocampus plays a key role in the acquisition of new memories for places and events. Evidence suggests that the consolidation of these memories is enhanced during sleep. At the neuronal level, reactivation of awake experience in the hippocampus during sharp‐wave ripple events, characteristic of slow‐wave sleep, has been proposed as a neural mechanism for sleep‐dependent memory consolidation. However, a causal relation between sleep reactivation and memory consolidation has not been established. Here we show that disrupting neuronal activity during ripple events impairs spatial learning. We trained rats daily in two identical spatial navigation tasks followed each by a 1‐hour rest period. After one of the tasks, stimulation of hippocampal afferents selectively disrupted neuronal activity associated with ripple events without changing the sleep‐wake structure. Rats learned the control task significantly faster than the task followed by rest stimulation, indicating that interfering with hippocampal processing during sleep led to decreased learning. © 2009 Wiley‐Liss, Inc.     

Validating the theoretical bases of sleep reactivation during sharp‐wave ripples and their association with emotional valence

Sleep is important for memory consolidation, and an abundant literature suggests that reactivation in the hippocampus during sleep is instrumental to this process. Yet, the current interpretation of activity during sharp‐waves ripples (SWRs), as replay of wake experiences, relies on hypotheses that, while widely accepted, have only recently begun to be tested directly. Moreover, this theory has been mainly studied in the context of pure spatial learning, and it is still not clear how emotional valence can fit into this conceptual framework when considering reward‐ or punishment‐based learning. In this review, we will present recent experimental arguments validating the interpretation of sleep replay as reactivation of awake experiences and examine the evidence showing that the emotional valence is also replayed during sleep in a coordinated fashion with hippocampal SWRs. Finally, we will detail recent experiments showing that brain–computer interfaces can be used to modify the emotional valence associated with sleep replay.     

Transition between encoding and consolidation/replay dynamics via cholinergic modulation of CAN current: A modeling study

Hippocampal place cells that are activated sequentially during active waking get reactivated in a temporally compressed (5–20 times) manner during slow‐wave‐sleep and quiet waking. The two‐stage model of the hippocampus suggests that neural activity during awaking supports encoding function while temporally compressed reactivation (replay) supports consolidation. However, the mechanisms supporting different neural activity with different temporal scales during encoding and consolidation remain unclear. Based on the idea that acetylcholine modulates functional transition between encoding and consolidation, we tested whether the cholinergic modulation may adjust intrinsic network dynamics to support different temporal scales for these two modes of operation. Simulations demonstrate that cholinergic modulation of the calcium activated non‐specific cationic (CAN) current and the synaptic transmission may be sufficient to switch the network dynamics between encoding and consolidation modes. When the CAN current is active and the synaptic transmission is suppressed, mimicking the high acetylcholine condition during active waking, a slow propagation of multiple spikes is evident. This activity resembles the firing pattern of place cells and time cells during active waking. On the other hand, when CAN current is suppressed and the synaptic transmission is intact, mimicking the low acetylcholine condition during slow‐wave‐sleep, a time compressed fast (～10 times) activity propagation of the same set of cells is evident. This activity resembles the time compressed firing pattern of place cells during replay and pre‐play, achieving a temporal compression factor in the range observed in vivo (5–20 times). These observations suggest that cholinergic system could adjust intrinsic network dynamics suitable for encoding and consolidation through the modulation of the CAN current and synaptic conductance in the hippocampus. © 2015 Wiley Periodicals, Inc.     

Sleep spindle activity correlates with implicit statistical learning consolidation in untreated obstructive sleep apnea patients

Objective/BackgroundThe aim of this study was to examine the relationship between overnight consolidation of implicit statistical learning with spindle frequency EEG activity and slow frequency delta power during non-rapid eye movement (NREM) sleep in obstructive sleep apnea (OSA).Patients/MethodsForty-seven OSA participants completed the experiment. Prior to sleep, participants performed a reaction time cover task containing hidden patterns of pictures, about which participants were not informed. After the familiarisation phase, participants underwent overnight polysomnography. 24 h after the familiarisation phase, participants performed a test phase to assess their learning of the hidden patterns, expressed as a percentage of the number of correctly identified patterns. Spindle frequency activity (SFA) and delta power (0.5–4.5 Hz), were quantified from NREM electroencephalography. Associations between statistical learning and sleep EEG, and OSA severity measures were examined.ResultsSFA in NREM sleep in frontal and central brain regions was positively correlated with statistical learning scores (r = 0.41 to 0.31, p = 0.006 to 0.044). In multiple regression, greater SFA and longer sleep onset latency were significant predictors of better statistical learning performance. Delta power and OSA severity were not significantly correlated with statistical learning.ConclusionsThese findings suggest spindle activity may serve as a marker of statistical learning capability in OSA. This work provides novel insight into how altered sleep physiology relates to consolidation of implicitly learnt information in patients with moderate to severe OSA.     

Coherence of the electroencephalogram during the first sleep cycle.

OBJECTIVE: The increasing amplitude of the electroencephalogram (EEG) during non-rapid eye movement sleep implies a progressive synchronization of neuronal activity. We sought to characterize the spatial relationship of cortical activity at different frequencies during the first sleep cycle, focusing on sleep stages 3 and 4 (slow wave sleep). METHODS: Sleep EEGs were obtained at home from six adults using a portable recorder. Signal power and magnitude squared coherence were measured during the first sleep cycle. Spectra obtained from bipolar and common reference derivations were compared. RESULTS: During slow wave sleep, signal power is highest in the delta frequency band and regional coherence below 5 Hz is broadly distributed. Although signal power in the alpha and sigma frequency bands is lower, peaks of regional coherence in those bands are similar to or higher than delta-band coherence. Regional coherence during slow wave sleep is differentially distributed with a 14 Hz component in central and posterior regions and a 10 Hz component in frontal and central regions. CONCLUSIONS: Ten and 14 Hz rhythms are an essential component of slow wave sleep. SIGNIFICANCE: The interpretation of scalp EEG power and coherence spectra is limited by the lack of a satisfactory recording reference. However, conclusions can be made by comparing and contrasting results from both bipolar and common reference recordings.     

Electroencephalographic slow waves prior to sleepwalking episodes

ObjectiveRecent studies have suggested that the onset of sleepwalking episodes may be preceded by fluctuations in slow-wave sleep electroencephalographic characteristics. However, whether or not such fluctuations are specific to sleepwalking episodes or generalized to all sleep–wake transitions in sleepwalkers remains unknown. The goal of this study was to compare spectral power for delta (1–4 Hz) and slow delta (0.5–1 Hz) as well as slow oscillation density before the onset of somnambulistic episodes versus non-behavioral awakenings recorded from the same group of sleepwalkers. A secondary aim was to describe the time course of observed changes in slow-wave activity and slow oscillations during the 3 min immediately preceding the occurrence of somnambulistic episodes.MethodsTwelve adult sleepwalkers were investigated polysomnographically during the course of one night.ResultsSlow-wave activity and slow oscillation density were significantly greater prior to patients' somnambulistic episodes as compared with non-behavioral awakenings. However, there was no evidence for a gradual increase over the 3 min preceding the episodes.ConclusionsIncreased slow-wave activity and slow oscillation density appear to be specific to sleepwalking episodes rather than generalized to all sleep–wake transitions in sleepwalkers.     

Sleep EEG in mice that are deficient in the potassium channel subunit K.v.3.2

Voltage-gated potassium channels containing the K.v.3.2 subunit are expressed in specific neuronal populations such as thalamocortical neurons and fast spiking GABAergic interneurons of the neocortex and hippocampus. These K(+)-channels play a major role in the regulation of firing properties in these neurons. We investigated whether the K.v.3.2 subunit contributes to the generation of the sleep electroencephalogram (EEG). The EEG of a frontal and occipital derivation of K.v.3.2-deficient mice and littermate controls was recorded during a 24-h baseline, 6-h sleep deprivation (SD) and subsequent 18-h recovery to assess also the effects of the K.v.3.2 subunit deficiency under physiological sleep pressure. The K.v.3.2-deficient mice had lower EEG power density in the frequencies between 3.25 and 6 Hz in nonREM (NREM) sleep and 3.25-5 Hz in REM sleep. These differences were more prominent in the frontal derivation than in the occipital derivation. The waking EEG spectrum was not affected by the deletion. In both genotypes SD induced a prominent increase in slow-wave activity in NREM sleep (mean EEG power density between 0.75 and 4.0 Hz), and a concomitant decrease in sleep fragmentation. The effects of SD did not differ significantly between the genotypes. The results indicate that K.v.3.2 channels may be involved in the generation of EEG oscillations in the high delta and low theta range in sleep. They support the notion that GABA-mediated synchronization of cortical activity contributes to the electroencephalogram.     

Memory formation by neuronal synchronization

Cognitive functions not only depend on the localization of neural activity, but also on the precise temporal pattern of activity in neural assemblies. Synchronization of action potential discharges provides a link between large-scale EEG recordings and cellular plasticity mechanisms. Here, we focus on the role of neuronal synchronization in different frequency domains for the subsequent stages of memory formation. Recent EEG studies suggest that synchronized neural activity in the gamma frequency range (around 30–100 Hz) plays a functional role for the formation of declarative long-term memories in humans. On the cellular level, gamma synchronization between hippocampal and parahippocampal regions may induce LTP in the CA3 region of the hippocampus. In order to encode spatial locations or sequences of multiple items and to guarantee a defined temporal order of memory processing, synchronization in the gamma frequency range has to be accompanied by a stimulus-locked phase reset of ongoing theta oscillations. Simultaneous gamma- and theta-dependent plasticity leads to complex learning rules required for realistic declarative memory formation. Subsequently, consolidation of declarative memories may occur via replay of newly acquired patterns in so-called sharp wave–ripple complexes, predominantly during slow-wave sleep. These irregular bursts induce longer lasting forms of synaptic plasticity in output regions of the hippocampus and in the neocortex. In summary, synchronization of neural assemblies in different frequency ranges induces specific forms of cellular plasticity during subsequent stages of memory formation.     

Sleep stage II contributes to the consolidation of declarative memories

Various studies suggest that non-rapid eye movement (NREM) sleep, especially slow-wave sleep (SWS), is vital to the consolidation of declarative memories. However, sleep stage 2 (S2), which is the other NREM sleep stage besides SWS, has gained only little attention. The current study investigated whether S2 during an afternoon nap contributes to the consolidation of declarative memories. Participants learned associations between faces and cities prior to a brief nap. A cued recall test was administered before and following the nap. Spindle, delta and slow oscillation activity was recorded during S2 in the nap following learning and in a control nap. Increases in spindle activity, delta activity, and slow oscillation activity in S2 in the nap following learning compared to the control nap were associated with enhanced retention of face-city associations. Furthermore, spindles tended to occur more frequently during up-states than down-states within slow oscillations during S2 following learning versus S2 of the control nap. These findings suggest that spindles, delta waves, and slow oscillations might promote memory consolidation not only during SWS, as shown earlier, but also during S2.     

Correlation between EEG rhythms during sleep: surface versus mediotemporal EEG

We compared surface and intracranial electroencephalogram recordings of mediotemporal structures. These structures are critically involved in declarative memory formation and memory consolidation during sleep. As memory processing is suggested to involve the interplay between fast and slow oscillations, we hypothesized different correlations between frequency bands in surface versus mediotemporal electroencephalogram recordings. Polysomnographic recordings obtained in 10 patients with unilateral temporal lobe epilepsy were analyzed. In accordance with earlier studies, we observed that power density in surface electroencephalogram is organized reciprocally between delta/theta and fast frequencies above 16 Hz during non-rapid-eye-movement sleep (negative correlations). In contrast, we found that within the hippocampus delta/theta power alternated in parallel with fast oscillations above 16 Hz during non-rapid-eye-movement sleep (positive correlations).     

Slow fluctuations of single unit activities of hippocampal and thalamic neurons in cats. I. Relation to natural sleep and alert states

Spontaneous unit discharges during the natural sleep-wakefulness cycle in two different neuronal groups, the hippocampal pyramidal cells and thalamic ventrobasal neurons, have been analyzed. The results show that both neurons fire with white-noise-like fluctuations during the slow-wave sleep, and with slow fluctuations with power spectral densities inversely proportional to the frequency in the frequency range of 0.02-1.0 Hz, during the paradoxical sleep. This confirms that the characteristics of fluctuations in neuronal activities of the mesencephalic reticular formation observed in our previous study are more general phenomena in the cat's brain. Partly similar behavior of spectral densities is also observed during the alert state. These observations are quantitatively confirmed by the statistical time series analysis of the spike density processes of spontaneous activities.     

Periods of rest in fMRI contain individual spontaneous events which are related to slowly fluctuating spontaneous activity

fMRI studies of brain activity at rest study slow (<0.1 Hz) intrinsic fluctuations in the blood‐oxygenation‐level‐dependent (BOLD) signal that are observed in a temporal scale of several minutes. The origin of these fluctuations is not clear but has previously been associated with slow changes in rhythmic neuronal activity resulting from changes in cortical excitability or neuronal synchronization. In this work, we show that individual spontaneous BOLD events occur during rest, in addition to slow fluctuations. Individual spontaneous BOLD events were identified by deconvolving the hemodynamic impulse response function for each time point in the fMRI time series, thus requiring no information on timing or a‐priori spatial information of events. The patterns of activation detected were related to the motor, visual, default‐mode, and dorsal attention networks. The correspondence between spontaneous events and slow fluctuations in these networks was assessed using a sliding window, seed‐correlation analysis, where seed regions were selected based on the individual spontaneous event BOLD activity maps. We showed that the correlation varied considerably over time, peaking at the time of spontaneous events in these networks. By regressing spontaneous events out of the fMRI signal, we showed that both the correlation strength and the power in spectral frequencies <0.1 Hz decreased, indicating that spontaneous activation events contribute to low‐frequency fluctuations observed in resting state networks with fMRI. This work provides new insights into the origin of signals detected in fMRI studies of functional connectivity. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Modulation of local field potentials and neuronal activity in primate hippocampus during saccades

Primates use saccades to gather information about objects and their relative spatial arrangement, a process essential for visual perception and memory. It has been proposed that signals linked to saccades reset the phase of local field potential (LFP) oscillations in the hippocampus, providing a temporal window for visual signals to activate neurons in this region and influence memory formation. We investigated this issue by measuring hippocampal LFPs and spikes in two macaques performing different tasks with unconstrained eye movements. We found that LFP phase clustering (PC) in the alpha/beta (8–16 Hz) frequencies followed foveation onsets, while PC in frequencies lower than 8 Hz followed spontaneous saccades, even on a homogeneous background. Saccades to a solid grey background were not followed by increases in local neuronal firing, whereas saccades toward appearing visual stimuli were. Finally, saccade parameters correlated with LFPs phase and amplitude: saccade direction correlated with delta (≤4 Hz) phase, and saccade amplitude with theta (4–8 Hz) power. Our results suggest that signals linked to saccades reach the hippocampus, producing synchronization of delta/theta LFPs without a general activation of local neurons. Moreover, some visual inputs co‐occurring with saccades produce LFP synchronization in the alpha/beta bands and elevated neuronal firing. Our findings support the hypothesis that saccade‐related signals enact sensory input‐dependent plasticity and therefore memory formation in the primate hippocampus.     

Interactions between visual and motor areas during the recognition of plausible actions as revealed by magnetoencephalography

Several studies have shown activation of the mirror neuron system (MNS), comprising the temporal, posterior parietal, and sensorimotor areas when observing plausible actions, but far less is known on how these cortical areas interact during the recognition of a plausible action. Here, we recorded neural activity with magnetoencephalography while subjects viewed point‐light displays of biologically plausible and scrambled versions of actions. We were interested in modulations of oscillatory activity and, specifically, in coupling of oscillatory activity between visual and motor areas. Both plausible and scrambled actions elicited modulations of θ (5–7 Hz), α (7–13 Hz), β (13–35 Hz), and γ (55–100 Hz) power within visual and motor areas. When comparing between the two actions, we observed sequential and spatially distinct increases of γ (～65 Hz), β (～25 Hz), and α (～11 Hz) power between 0.5 and 1.3 s in parieto‐occipital, sensorimotor, and left temporal areas. In addition, significant clusters of γ (～65 Hz) and α/β (～15 Hz) power decrease were observed in right temporal and parieto‐occipital areas between 1.3 and 2.0 s. We found β‐power in sensorimotor areas to be positively correlated on a trial‐by‐trial basis with parieto‐occipital γ and left temporal α‐power for the plausible but not for the scrambled condition. These results provide new insights in the neuronal oscillatory activity of the areas involved in the recognition of plausible action movements and their interaction. The power correlations between specific areas underscore the importance of interactions between visual and motor areas of the MNS during the recognition of a plausible action. Hum Brain Mapp 35:581–592, 2014. © 2012 Wiley‐Periodicals, Inc.     

Brain dynamics sustaining rapid rule extraction from speech

Language acquisition is a complex process that requires the synergic involvement of different cognitive functions, which include extracting and storing the words of the language and their embedded rules for progressive acquisition of grammatical information. As has been shown in other fields that study learning processes, synchronization mechanisms between neuronal assemblies might have a key role during language learning. In particular, studying these dynamics may help uncover whether different oscillatory patterns sustain more item-based learning of words and rule-based learning from speech input. Therefore, we tracked the modulation of oscillatory neural activity during the initial exposure to an artificial language, which contained embedded rules. We analyzed both spectral power variations, as a measure of local neuronal ensemble synchronization, as well as phase coherence patterns, as an index of the long-range coordination of these local groups of neurons. Synchronized activity in the gamma band (20-40 Hz), previously reported to be related to the engagement of selective attention, showed a clear dissociation of local power and phase coherence between distant regions. In this frequency range, local synchrony characterized the subjects who were focused on word identification and was accompanied by increased coherence in the theta band (4-8 Hz). Only those subjects who were able to learn the embedded rules showed increased gamma band phase coherence between frontal, temporal, and parietal regions.     

Inhibiting cholesterol degradation induces neuronal sclerosis and epileptic activity in mouse hippocampus

Elevations in neuronal cholesterol have been associated with several degenerative diseases. An enhanced excitability and synchronous firing in surviving neurons are among the sequels of neuronal death in these diseases and also in some epileptic syndromes. Here, we attempted to increase neuronal cholesterol levels, using a short hairpin RNA to suppress expression of the enzyme cytochrome P450 family 46, subfamily A, polypeptide 1 gene (CYP46A1). This protein hydroxylates cholesterol and so facilitates transmembrane extrusion. A short hairpin RNA CYP46A1construction coupled to the adeno‐associated virus type 5 was injected focally and unilaterally into mouse hippocampus. It was selectively expressed first in neurons of the cornu ammonis (hippocampus) (CA)3a region. Cytoplasmic and membrane cholesterol increased, and the neuronal soma volume increased and then decreased before pyramidal cells died. As CA3a pyramidal cells died, interictal electroencephalographic (EEG) events occurred during exploration and non‐rapid eye movement sleep. With time, neuronal death spread to involve pyramidal cells and interneurons of the CA1 region. CA1 neuronal death was correlated with a delayed local expression of phosphorylated tau. Astrocytes were activated throughout the hippocampus and microglial activation was specific to regions of neuronal death. CA1 neuronal death was correlated with distinct aberrant EEG activity. During exploratory behaviour and rapid eye movement sleep, EEG oscillations at 7–10 Hz (theta) could accelerate to 14–21 Hz (beta) waves. They were accompanied by low‐amplitude, high‐frequency oscillations of peak power at ~300 Hz and a range of 250–350 Hz. Although episodes of EEG acceleration were not correlated with changes in exploratory behaviour, they were followed in some animals by structured seizure‐like discharges. These data strengthen links between increased cholesterol, neuronal sclerosis and epileptic behaviour.     

Sleep homeostasis in the rat in the light and dark period

Sleep is regulated by the interaction of a homeostatic (Process S) and a circadian component. The duration of prior wakefulness is the main factor influencing subsequent sleep duration and its intensity. We investigated in the rat whether the sleep-wake history before sleep deprivation (SD) contributes to the effects of sleep loss incurred during the SD. A 24-h baseline recording was followed by 6 h SD at light onset (SD-Light, n=7), or at dark onset (SD-Dark, n=8) and 18 h recovery. Both SDs led to a pronounced increase in slow wave activity (SWA, EEG power between 0.75 and 4.0 Hz) in NREM sleep and increased sleep consolidation. The prolongation of sleep episodes was associated with increased intra-episode SWA. The amount of waking before the SD correlated positively with the SWA increase during recovery, and SWA levels before SD were negatively correlated with their subsequent increase. The time-course of SWA (Process S) as well as of single frequency bins within the SWA band was successfully simulated based on vigilance-state distribution. The time constant of the exponential monotonic decay (Td) was higher for the 0.75-1.0 Hz bin compared to all remaining frequency bins of the SWA band, reflecting a slower process determining the slow EEG component during sleep. The data show that the homeostatic response after SD, consisting of increased sleep intensity and sleep consolidation is determined by a combination of SD and the preceding vigilance-state history. The slower dynamics of low frequency delta power compared to fast delta frequencies point to heterogeneity within the traditionally defined SWA band.     

Acute effects of meditation training on the waking and sleeping brain: Is it all about homeostasis?

Our recent finding of a meditation‐related increase in low‐frequency NREM sleep EEG oscillatory activities peaking in the theta‐alpha range (4–12 Hz) was not predicted. From a consolidated body of research on sleep homeostasis, we would expect a change peaking in slow wave activity (1–4 Hz) following an intense meditation session. Here we compared these changes in sleep with the post‐meditation changes in waking rest scalp power to further characterize their functional significance. High‐density EEG recordings were acquired from 27 long‐term meditators (LTM) on three separate days at baseline and following two 8‐hr sessions of either mindfulness or compassion‐and‐loving‐kindness meditation. Thirty‐one meditation‐naïve participants (MNP) were recorded at the same time points. As a common effect of meditation practice, we found increases in low and fast waking EEG oscillations for LTM only, peaking at eight and 15 Hz respectively, over prefrontal, and left centro‐parietal electrodes. Paralleling our previous findings in sleep, there was no significant difference between meditation styles in LTM as well as no difference between matched sessions in MNP. Meditation‐related changes in wakefulness and NREM sleep were correlated across space and frequency. A significant correlation was found in the EEG low frequencies (<12 Hz). Since the peak of coupling was observed in the theta‐alpha oscillatory range, sleep homeostatic response to meditation practice is not sufficient to explain our findings. Another likely phenomenon into play is a reverberation of meditation‐related processes during subsequent sleep. Future studies should ascertain the interplay between these processes in promoting the beneficial effects of meditation practice.