Slow-wave Sleep States Research Articles

The temporal asymmetry of cortical dynamics as a signature of brain states

The brain is a complex non-equilibrium system capable of expressing many different dynamics as well as the transitions between them. We hypothesized that the level of non-equilibrium can serve as a signature of a given brain state, which was quantified using the arrow of time (the level of irreversibility). Using this thermodynamic framework, the irreversibility of emergent cortical activity was quantified from local field potential recordings in male Lister-hooded rats at different anesthesia levels and during the sleep-wake cycle. This measure was carried out on five distinct brain states: slow-wave sleep, awake, deep anesthesia–slow waves, light anesthesia–slow waves, and microarousals. Low levels of irreversibility were associated with synchronous activity found both in deep anesthesia and slow-wave sleep states, suggesting that slow waves were the state closest to the thermodynamic equilibrium (maximum symmetry), thus requiring minimum energy. Higher levels of irreversibility were found when brain dynamics became more asynchronous, for example, in wakefulness. These changes were also reflected in the hierarchy of cortical dynamics across different cortical areas. The neural dynamics associated with different brain states were characterized by different degrees of irreversibility and hierarchy, also acting as markers of brain state transitions. This could open new routes to monitoring, controlling, and even changing brain states in health and disease.

Aberrant slow waves in the hippocampus during activation in mice with low cholinergic tone.

The effects of acetylcholine on cortical activation were studied in wild-type (WT) mice, compared to knockout (KO) mice depleted of the vesicular acetylcholine transporter (VAChT) gene in the basal forebrain, and knockdown (KD) mice with heterogeneous depletion of VAChT gene in the brain. Cortical activation was assessed by comparing power spectra of local field potentials (LFPs) during activated states of rapid-eye-movement sleep (REM) or walk (WLK), with those during non-activated states of slow-wave sleep (SWS) or awake-immobility (IMM). Activation-induced suppression of delta (1-4Hz) and beta (13-30 Hz) power in the hippocampus, and delta power in frontal cortex, were reduced in KO and KD mice compared to WT mice. Mean theta frequency was higher in KD than KO mice during WLK and REM, but not different between WT and KO mice. Peak theta (4-12 Hz) and integrated gamma (30-150 Hz) power were not significantly different among mouse groups. However, theta-peak-frequency selected gamma2 (62-100 Hz) power was lower in KO than WT or KD mice during WLK, and theta-peak-frequency selected theta power during REM decreased faster with high theta frequency in KO than WT/ KD mice. Theta power increase during REM compared to WLK was lower in KO and KD mice compared to WT mice. Theta-gamma cross-frequency coherence, a measure of synchronization of gamma with theta phase, was not different among mouse groups. However, during REM, SWS, and IMM, delta-gamma coherence was significantly higher and proximal-distal delta coherence in CA1 was lower in KO than WT/KD mice. We conclude that a deficiency in basal forebrain acetylcholine release not only enhances slow waves and suppresses theta-associated gamma waves during activation, but also increases delta-gamma cross-frequency coherence during nonactivated states, with a possible effect of disrupting cognitive processing during any brain state.

Investigação das correlações existentes entre o ciclo vigília-sono e a dor num modelo experimental de fibromialgia

Os distúrbios do sono são altamente prevalentes em pacientes portadores de fibromialgia. Muitos dos sintomas diurnos, como sonolência excessiva diurna e fadiga, podem estar relacionados a padrões de sono não restaurador, que, associados aos quadros álgicos típicos da doença, se retroalimentam. Neste contexto, objetivamos estudar as possíveis correlações existentes entre o ciclo vigília-sono e os comportamentos álgicos em um modelo animal de fibromialgia induzido por injeções repetidas de reserpina. Foram utilizados ratos Wistar machos e fêmeas adultos que receberam implantes crônicos de eletrodos bipolares encefálicos e de EMG. Injeções de reserpina provocaram aumento na resposta à estimulação mecânica, detectada através do emprego do teste de von Frey. Nos ratos tratados com reserpina observou-se fragmentação do ciclo vigília-sono. Adicionalmente, observou-se a presença de comportamentos aberrantes acompanhados de modificações eletroencefalográficas notáveis quando comparados aos animais controle. Destaca-se, também, alterações em bandas de frequências específicas dos traçados de EEG correspondentes aos estados comportamentais de vigília atenta e de sono de ondas lentas. Por conta desses achados suspeita-se que o modelo de fibromialgia produzido por injeções de reserpina pode servir como modelo aplicável para esta doença em humanos.

Neocortical Slow Oscillations Implicated in the Generation of Epileptic Spasms.

Epileptic spasms are a hallmark of severe seizure disorders. The neurophysiological mechanisms and the neuronal circuit(s) that generate these seizures are unresolved and are the focus of studies reported here. In the tetrodotoxin model, we used 16-channel microarrays and microwires to record electrophysiological activity in neocortex and thalamus during spasms. Chemogenetic activation was used to examine the role of neocortical pyramidal cells in generating spasms. Comparisons were made to recordings from infantile spasm patients. Current source density and simultaneous multiunit activity analyses indicate that the ictal events of spasms are initiated in infragranular cortical layers. A dramatic pause of neuronal activity was recorded immediately prior to the onset of spasms. This preictal pause is shown to share many features with the down states of slow wave sleep. In addition, the ensuing interictal up states of slow wave rhythms are more intense in epileptic than control animals and occasionally appear sufficient to initiate spasms. Chemogenetic activation of neocortical pyramidal cells supported these observations, as it increased slow oscillations and spasm numbers and clustering. Recordings also revealed a ramp-up in the number of neocortical slow oscillations preceding spasms, which was also observed in infantile spasm patients. Our findings provide evidence that epileptic spasms can arise from the neocortex and reveal a previously unappreciated interplay between brain state physiology and spasm generation. The identification of neocortical up states as a mechanism capable of initiating epileptic spasms will likely provide new targets for interventional therapies. ANN NEUROL 2021;89:226-241.

Astrocytic Ca2+ signaling is reduced during sleep and is involved in the regulation of slow wave sleep

Astrocytic Ca2+ signaling has been intensively studied in health and disease but has not been quantified during natural sleep. Here, we employ an activity-based algorithm to assess astrocytic Ca2+ signals in the neocortex of awake and naturally sleeping mice while monitoring neuronal Ca2+ activity, brain rhythms and behavior. We show that astrocytic Ca2+ signals exhibit distinct features across the sleep-wake cycle and are reduced during sleep compared to wakefulness. Moreover, an increase in astrocytic Ca2+ signaling precedes transitions from slow wave sleep to wakefulness, with a peak upon awakening exceeding the levels during whisking and locomotion. Finally, genetic ablation of an important astrocytic Ca2+ signaling pathway impairs slow wave sleep and results in an increased number of microarousals, abnormal brain rhythms, and an increased frequency of slow wave sleep state transitions and sleep spindles. Our findings demonstrate an essential role for astrocytic Ca2+ signaling in regulating slow wave sleep.

Intercorrelation of the Activity of Close-Lying Neurons in the Cat Cerebral Cortex During Slow-Wave Sleep

Cross-correlation analysis of baseline spike activity was performed for 184 pairs of close-lying neurons in the car cortex in the state of slow-wave sleep. Recordings were made in the associative zones of the visual-somatosensory cortex. The activity of individual elements was extracted using the program Spike-2. About half of cases showed no significant coupling. Among 93 pairs showing cross-correlation, 66 were characterized by wide (80–800 msec) peaks in the correlation function centered close to zero delay. Sixteen of these pairs showed not only wide peaks, but also narrow peaks (<50 msec), also centered around the zero point. Fourteen pairs displayed only a narrow peak. The remaining 13 pairs showed either inversion of cross-correlation and/or sharp displacement of the position of the correlation function peak. Crosscorrelations were seen with high probability in pairs of cells showing volley-type baseline activity. correlation of individual neurons in the state of slow-wave sleep was not significantly different from that described previously in the state of waking.

Reciprocal Interactions between Medial Septum and Hippocampus in Theta Generation: Granger Causality Decomposition of Mixed Spike-Field Recordings.

The medial septum (MS) plays an essential role in rhythmogenesis in the hippocampus (HIPP); theta-rhythmic bursts of MS neurons are believed to drive theta oscillations in rats’ HIPP. The MS theta pacemaker hypothesis has solid foundation but the MS-hippocampal interactions during different behavioral states are poorly understood. The MS and the HIPP have reciprocal connections and it is not clear in particular what role, if any, the strong HIPP to MS projection plays in theta generation. To study the functional interactions between MS and HIPP during different behavioral states, this study investigated the relationship between MS single-unit activity and HIPP field potential oscillations during theta states of active waking and REM sleep and non-theta states of slow wave sleep (SWS) and quiet waking (QW), i.e., sleep-wake states that comprise the full behavioral repertoire of undisturbed, freely moving rats. We used non-parametric Granger causality (GC) to decompose the MS-HIPP synchrony into its directional components, MS→HIPP and HIPP→MS, and to examine the causal interactions between them within the theta frequency band. We found a significant unidirectional MS→HIPP influence in non-theta states which switches to bidirectional theta drive during theta states with MS→HIPP and HIPP→MS GC being of equal magnitude. In non-theta states, unidirectional MS→HIPP influence was accompanied by significant MS-HIPP coherence, but no signs of theta oscillations in the HIPP. In theta states of active waking and REM sleep, sharp theta coherence and strong theta power in both structures was associated with a rise in HIPP→MS to the level of the MS→HIPP drive. Thus, striking differences between waking and REM sleep theta states and non-theta states of SWS and QW were primarily observed in activation of theta influence carried by the descending HIPP→MS pathway associated with more regular rhythmic bursts in the MS and sharper MS→HIPP GC spectra without a significant increase in MS→HIPP GC magnitude. The results of this study suggest an essential role of descending HIPP to MS projections in theta generation.

Slow-wave oscillations in a corticothalamic model of sleep and wake

A physiologically-based corticothalamic neural field model is used to study slow wave oscillations including cortical UP and DOWN states in deep sleep by extending it to incorporate bursting dynamics of neurons in the thalamic reticular nucleus. The interplay of local bursting dynamics and network interactions produces the cortical UP and DOWN states of slow wave sleep while preserving previously verified model predictions in the wake state. Results show that EEG spectral features in wake and sleep are reproduced. The bursting is subthreshold but acts to intensify the amplitude of oscillations in slow wave sleep with deep UP/DOWN oscillations on the cortex emerging naturally. Furthermore, there is a continuous cycle between the two regimes, rather than a flip-flop between discrete states.

Characterization of Scale-Free Properties of Human Electrocorticography in Awake and Slow Wave Sleep States

Like many complex dynamic systems, the brain exhibits scale-free dynamics that follow power-law scaling. Broadband power spectral density (PSD) of brain electrical activity exhibits state-dependent power-law scaling with a log frequency exponent that varies across frequency ranges. Widely divergent naturally occurring neural states, awake and slow wave sleep (SWS), were used to evaluate the nature of changes in scale-free indices of brain electrical activity. We demonstrate two analytic approaches to characterizing electrocorticographic (ECoG) data obtained during awake and SWS states. A data-driven approach was used, characterizing all available frequency ranges. Using an equal error state discriminator (EESD), a single frequency range did not best characterize state across data from all six subjects, though the ability to distinguish awake and SWS ECoG data in individual subjects was excellent. Multi-segment piecewise linear fits were used to characterize scale-free slopes across the entire frequency range (0.2–200 Hz). These scale-free slopes differed between awake and SWS states across subjects, particularly at frequencies below 10 Hz and showed little difference at frequencies above 70 Hz. A multivariate maximum likelihood analysis (MMLA) method using the multi-segment slope indices successfully categorized ECoG data in most subjects, though individual variation was seen. In exploring the differences between awake and SWS ECoG data, these analytic techniques show that no change in a single frequency range best characterizes differences between these two divergent biological states. With increasing computational tractability, the use of scale-free slope values to characterize ECoG and EEG data will have practical value in clinical and research studies.

Exploring the spectrum of dynamical regimes and timescales in spontaneous cortical activity

Rhythms at slow (<1Hz) frequency of alternating Up and Down states occur during slow-wave sleep states, under deep anaesthesia and in cortical slices of mammals maintained in vitro. Such spontaneous oscillations result from the interplay between network reverberations nonlinearly sustained by a strong synaptic coupling and a fatigue mechanism inhibiting the neurons firing in an activity-dependent manner. Varying pharmacologically the excitability level of brain slices we exploit the network dynamics underlying slow rhythms, uncovering an intrinsic anticorrelation between Up and Down state durations. Besides, a non-monotonic change of Down state duration is also observed, which shrinks the distribution of the accessible frequencies of the slow rhythms. Attractor dynamics with activity-dependent self-inhibition predicts a similar trend even when the system excitability is reduced, because of a stability loss of Up and Down states. Hence, such cortical rhythms tend to display a maximal size of the distribution of Up/Down frequencies, envisaging the location of the system dynamics on a critical boundary of the parameter space. This would be an optimal solution for the system in order to display a wide spectrum of dynamical regimes and timescales.

Sleep-Like States Modulate Functional Connectivity in the Rat Olfactory System

The present study was an examination of state-dependent functional connectivity during spontaneous activity between the piriform cortex and its upstream and downstream connections. Rats were anesthetized with urethan and allowed to spontaneously cycle between fast- and slow-wave states similar to fast- and slow-wave sleep states. Local field potential recordings were made from the olfactory bulb, piriform cortex, dorsal hippocampus, amygdala, and primary visual cortex. The results demonstrate that during slow-wave sleep-like states, when the piriform cortex shows reduced sensitivity to odor input via the olfactory bulb, there is enhanced coherence with other forebrain structures. Granger causality analyses suggest that the link between piriform cortical and hippocampal activity during slow-wave state is in the direction of the hippocampus to the piriform cortex rather than the reverse. The results suggest that slow-wave sleep-like states may provide an opportunity for the transfer and/or consolidation of information related to odor memories, specifically at a time when the piriform cortex is less sensitive to sensory input.

Single-Unit Activity in Piriform Cortex during Slow-Wave State Is Shaped by Recent Odor Experience

Memory and its underlying neural plasticity play important roles in sensory discrimination and cortical pattern recognition in olfaction. Given the reported function of slow-wave sleep states in neocortical and hippocampal memory consolidation, we hypothesized that activity during slow-wave states within the piriform cortex may be shaped by recent olfactory experience. Rats were anesthetized with urethane and allowed to spontaneously shift between slow-wave and fast-wave states as recorded in local field potentials within the anterior piriform cortex. Single-unit activity of piriform cortical layer II/III neurons was recorded simultaneously. The results suggest that piriform cortical activity during slow-wave states is shaped by recent (several minutes) odor experience. The temporal structure of single-unit activity during slow waves was modified if the animal had been stimulated with an odor within the receptive field of that cell. If no odor had been delivered, the activity of the cell during slow-wave activity was stable across the two periods. The results demonstrate that piriform cortical activity during slow-wave state is shaped by recent odor experience, which could contribute to odor memory consolidation.

Practitioners of vipassana meditation exhibit enhanced slow wave sleep and REM sleep states across different age groups

Intense meditation practices influence brain functions in different ways and at different levels. Earlier studies have shown that meditation practices help to organize sleep-wake behavior. In the present study, we evaluated the sleep architecture of vipassana meditators across different age groups. Whole-night polysomnography was carried out in healthy male subjects between 30 and 60 years of age from control (n = 46) and meditation (n = 45) groups. They were further divided into younger-(30–39 years), middle- (40–49 years), and older-aged (50–60 years) groups. Sleep variables were evaluated from subjects who had a sleep efficiency index more than 85%. The sleep architecture of vipassana meditators was different from that of control groups. Vipassana meditators showed enhanced slow wave sleep and rapid eye movement sleep states with an enhanced number of sleep cycles across all age groups. When compared to meditators, the control groups exhibited pro-nounced age-associated decrease in slow wave sleep states. Our study suggests that vipassana meditation helps to establish a proper sleep structure in old age, probably through its capacity to induce neuronal plasticity events leading to stronger network synchronization and cortical synaptic strengthening.

Behavioral State Regulation of Dendrodendritic Synaptic Inhibition in the Olfactory Bulb

Behavioral states regulate how information is processed in local neuronal circuits. Here, we asked whether dendrodendritic synaptic interactions in the olfactory bulb vary with brain and behavioral states. To examine the state-dependent change of the dendrodendritic synaptic transmission, we monitored changes in field potential responses in the olfactory bulb of urethane-anesthetized and freely behaving rats. In urethane-anesthetized rats, granule-to-mitral dendrodendritic synaptic inhibition was larger and longer when slow waves were present in the electroencephalogram (slow-wave state) than during the fast-wave state. The state-dependent alternating change in the granule-to-mitral inhibition was regulated by the cholinergic system. In addition, the frequency of the spontaneous oscillatory activity of local field potentials and periodic discharges of mitral cells in the olfactory bulb shifted in synchrony with shifts in the neocortical brain state. Freely behaving rats showed multilevel changes in dendrodendritic synaptic inhibition that corresponded to diverse behavioral states; the inhibition was the largest during slow-wave sleep state, and successively smaller during light sleep, awake immobility, and awake moving states. These results provide evidence that behavioral state-dependent global changes in cholinergic tone modulate dendrodendritic synaptic inhibition and the information processing mode in the olfactory bulb.

Going Beyond a Mean-field Model for the Learning Cortex: Second-Order Statistics

Mean-field models of the cortex have been used successfully to interpret the origin of features on the electroencephalogram under situations such as sleep, anesthesia, and seizures. In a mean-field scheme, dynamic changes in synaptic weights can be considered through fluctuation-based Hebbian learning rules. However, because such implementations deal with population-averaged properties, they are not well suited to memory and learning applications where individual synaptic weights can be important. We demonstrate that, through an extended system of equations, the mean-field models can be developed further to look at higher-order statistics, in particular, the distribution of synaptic weights within a cortical column. This allows us to make some general conclusions on memory through a mean-field scheme. Specifically, we expect large changes in the standard deviation of the distribution of synaptic weights when fluctuation in the mean soma potentials are large, such as during the transitions between the "up" and "down" states of slow-wave sleep. Moreover, a cortex that has low structure in its neuronal connections is most likely to decrease its standard deviation in the weights of excitatory to excitatory synapses, relative to the square of the mean, whereas a cortex with strongly patterned connections is most likely to increase this measure. This suggests that fluctuations are used to condense the coding of strong (presumably useful) memories into fewer, but dynamic, neuron connections, while at the same time removing weaker (less useful) memories.

Circadian desynchronization of core body temperature and sleep stages in the rat

Proper functioning of the human circadian timing system is crucial to physical and mental health. Much of what we know about this system is based on experimental protocols that induce the desynchronization of behavioral and physiological rhythms within individual subjects, but the neural (or extraneural) substrates for such desynchronization are unknown. We have developed an animal model of human internal desynchrony in which rats are exposed to artificially short (22-h) light-dark cycles. Under these conditions, locomotor activity, sleep-wake, and slow-wave sleep (SWS) exhibit two rhythms within individual animals, one entrained to the 22-h light-dark cycle and the other free-running with a period >24 h (tau(>24 h)). Whereas core body temperature showed two rhythms as well, further analysis indicates this variable oscillates more according to the tau(>24 h) rhythm than to the 22-h rhythm, and that this oscillation is due to an activity-independent circadian regulation. Paradoxical sleep (PS), on the other hand, shows only one free-running rhythm. Our results show that, similarly to humans, (i) circadian rhythms can be internally dissociated in a controlled and predictable manner in the rat and (ii) the circadian rhythms of sleep-wake and SWS can be desynchronized from the rhythms of PS and core body temperature within individual animals. This model now allows for a deeper understanding of the human timekeeping mechanism, for testing potential therapies for circadian dysrhythmias, and for studying the biology of PS and SWS states in a neurologically intact model.

呼吸波形を用いた徐波睡眠期の推定

In this study, we proposed a method for predicting state of slow-wave sleep based on respiratory waveforms. In our tests, we derived CV values for the amplitude of breathing movement for 5-minute periods, and evaluated three sleep states: REM (Rapideye movement) sleep, WAKE (static supine position, eyes closed), and SWS (Slow-wave sleep), and found that there was a large difference in these amplitude values. Next, we used entire night data for the same subjects, and predicted the SWS periods using the CVvalues. Comparing these results with the results of sleep depth as judged from a sleep polygraph, we confirmed that SWS periods could be predicted with a high level of accuracy. The above results indicate that it is possible to predict state of slow-wave using onlybreathing waveforms during sleep.

Evaluation of sleep architecture in practitioners of Sudarshan Kriya yoga and Vipassana meditation

Yoga is an ancient Indian science and way of life that has been described in the traditional texts as a systematic method of achieving the highest possible functional harmony between body and mind. Yogic practices are claimed to enhance the quality of sleep. Electrophysiological correlates associated with the higher states of consciousness have been reported in long-term practitioners of transcendental meditation during deep sleep states. The present study was carried out to assess sleep architecture in Sudarshan Kriya Yoga (SKY) and Vipassana meditators. This was to ascertain the differences, if any, in sleep architecture following yogic practices. Whole night polysomnographic recordings were carried out in 78 healthy male subjects belonging to control and yoga groups. The groups studied were aged between 20 and 30-years-old (younger) and 31 to 55-years-old (middle-aged). The sleep architecture was comparable among the younger control and yoga groups. While slow wave sleep (non-REM (rapid eye movement) S3 and S4) had reduced to 3.7 percent in the middle-aged control group, participants of the middle-aged yoga groups (both SKY and Vipassana) showed no such decline in slow wave sleep states, which was experienced by 11.76 and 12.76 percent, respectively, of the SKY and Vipassana groups. However, Vipassana practitioners showed a significant enhancement (P < 0.001) in their REM sleep state from that of the age-matched control subjects and also from their SKY counterparts. Yoga practices help to retain slow wave sleep and enhance the REM sleep state in the middle age; they appear to retain a younger biological age as far as sleep is concerned. Overall, the study demonstrates the possible beneficial role of yoga in sleep-wakefulness behavior.

State-Dependent Sensory Gating in Olfactory Cortex

Sensory systems show behavioral state-dependent gating of information flow that largely depends on the thalamus. Here we examined whether the state-dependent gating occurs in the central olfactory pathway that lacks a thalamic relay. In urethane-anesthetized rats, neocortical EEG showed a periodical alternation between two states: a slow-wave state (SWS) characterized by large and slow waves and a fast-wave state (FWS) characterized by faster waves. Single-unit recordings from olfactory cortex neurons showed robust spike responses to adequate odorants during FWS, whereas they showed only weak responses during SWS. The state-dependent change in odorant-evoked responses was observed in a majority of olfactory cortex neurons, but in only a small percentage of olfactory bulb neurons. These findings demonstrate a powerful state-dependent gating of odor information in the olfactory cortex that works in synchrony with the gating of other sensory systems. They suggest a state-dependent switchover of signal processing modes in the olfactory cortex.

Dynamic changes of gamma activities of somatic cortical evoked potentials during wake–sleep states in rats

Somatic evoked potentials (SEPs) from three brain sites elicited by electrical stimulation in 10 rats were recorded throughout wake–sleep states with intrinsic changes in temporal architectures under different vigilance states. Based on the patterns of spontaneous brain and muscle activities, three characteristic vigilance states could be classified: awake, slow-wave sleep (SWS), and paradoxical sleep (PS). Spontaneous gamma activities prominently appeared under awake and PS states, but less under SWS. SEP was filtered out via a zero-phase highpass filter (20 Hz) to extract the gamma activity of the SEP (γSEP). Gamma oscillations of SEPs were clearly observed and were reset by extrinsic electrical stimulation under awake and PS, but not under SWS state. Dynamic changes of γSEPs during wake–sleep states were also confirmed by multiple single-trial spectral analyses. Moreover, gamma oscillations were initiated at the parietal site, and the speed of its propagation in both frontal and occipital directions was significantly different. In addition, a clear two-component architecture of SEPs was observed under awake and PS states, and the gamma rhythmic activity was associated with the second component. Because gamma oscillations are related to feature binding in the waking state, evoked γSEPs in PS may be related to sensory integration analogous to the awake ones. By contrast, a long-lasting biphasic component of SEPs, which might be associated with augmenting response, was observed during SWS. Based on these results, the sleeping brain continuously monitors and selectively processes incoming flow. Our results also strongly support a two-stage information processing taking place in the cortex during sleep.