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Journal of Neuroscience Methods Oct 2023Characterization of normal arousal states has been achieved by fitting predictions of corticothalamic neural field theory (NFT) to electroencephalographic (EEG) spectra...
BACKGROUND
Characterization of normal arousal states has been achieved by fitting predictions of corticothalamic neural field theory (NFT) to electroencephalographic (EEG) spectra to yield relevant physiological parameters.
NEW METHOD
A prior fitting method is extended to distinguish conscious and unconscious states in healthy and brain injured subjects by identifying additional parameters and clusters in parameter space.
RESULTS
Fits of NFT predictions to EEG spectra are used to estimate neurophysiological parameters in healthy and brain injured subjects. Spectra are used from healthy subjects in wake and sleep and from patients with unresponsive wakefulness syndrome, in a minimally conscious state (MCS), and emerged from MCS. Subjects cluster into three groups in parameter space: conscious healthy (wake and REM), sleep, and brain injured. These are distinguished by the difference X-Y between corticocortical (X) and corticothalamic (Y) feedbacks, and by mean neural response rates α and β to incoming spikes. X-Y tracks consciousness in healthy individuals, with smaller values in wake/REM than sleep, but cannot distinguish between brain injuries. Parameters α and β differentiate deep sleep from wake/REM and brain injury.
COMPARISON WITH EXISTING METHODS
Other methods typically rely on laborious clinical assessment, manual EEG scoring, or evaluation of measures like Φ from integrated information theory, for which no efficient method exists. In contrast, the present method can be automated on a personal computer.
CONCLUSION
The method provides a means to quantify consciousness and arousal in healthy and brain injured subjects, but does not distinguish subtypes of brain injury.
Topics: Humans; Consciousness; Arousal; Brain; Wakefulness; Electroencephalography; Brain Injuries
PubMed: 37661056
DOI: 10.1016/j.jneumeth.2023.109958 -
ENeuro 2020Decades of research have implicated the ventral tegmental area (VTA) in motivation, learning and reward processing. We and others recently demonstrated that it also...
Decades of research have implicated the ventral tegmental area (VTA) in motivation, learning and reward processing. We and others recently demonstrated that it also serves as an important node in sleep/wake regulation. Specifically, VTA-dopaminergic neuron activation is sufficient to drive wakefulness and necessary for the maintenance of wakefulness. However, the role of VTA-GABAergic neurons in arousal regulation is not fully understood. It is still unclear whether VTA-GABAergic neurons predictably alter their activity across arousal states, what is the nature of interactions between VTA-GABAergic activity and cortical oscillations, and how activity in VTA-GABAergic neurons relates to VTA-dopaminergic neurons in the context of sleep/wake regulation. To address these, we simultaneously recorded population activity from VTA subpopulations and electroencephalography/electromyography (EEG/EMG) signals during spontaneous sleep/wake states and in the presence of salient stimuli in freely-behaving mice. We found that VTA-GABAergic neurons exhibit robust arousal-state-dependent alterations in population activity, with high activity and transients during wakefulness and REM sleep. During wakefulness, population activity of VTA-GABAergic neurons, but not VTA-dopaminergic neurons, was positively correlated with EEG γ power and negatively correlated with θ power. During NREM sleep, population activity in both VTA-GABAergic and VTA-dopaminergic neurons negatively correlated with δ, θ, and σ power bands. Salient stimuli, with both positive and negative valence, activated VTA-GABAergic neurons. Together, our data indicate that VTA-GABAergic neurons, like their dopaminergic counterparts, drastically alter their activity across sleep-wake states. Changes in their activity predicts cortical oscillatory patterns reflected in the EEG, which are distinct from EEG spectra associated with dopaminergic neural activity.
Topics: Animals; Arousal; GABAergic Neurons; Mice; Sleep; Ventral Tegmental Area; Wakefulness
PubMed: 32054621
DOI: 10.1523/ENEURO.0356-19.2020 -
Sleep Dec 2022The pedunculopontine tegmental (PPT) nucleus is implicated in many brain functions, ranging from sleep/wake control and locomotion, to reward mechanisms and learning....
STUDY OBJECTIVES
The pedunculopontine tegmental (PPT) nucleus is implicated in many brain functions, ranging from sleep/wake control and locomotion, to reward mechanisms and learning. The PPT contains cholinergic, GABAergic, and glutamatergic neurons with extensive ascending and descending axonal projections. Glutamatergic PPT (PPTvGlut2) neurons are thought to promote wakefulness, but the mechanisms through which this occurs are unknown. In addition, some researchers propose that PPTvGlut2 neurons promote locomotion, yet even though the PPT is a target for deep brain stimulation in Parkinson's disease, the role of the PPT in locomotion is debated. We hypothesized that PPTvGluT2 neurons drive arousal and specific waking behaviors via certain projections and modulate locomotion via others.
METHODS
We mapped the axonal projections of PPTvGlut2 neurons using conditional anterograde tracing and then photostimulated PPTvGlut2 soma or their axon terminal fields across sleep/wake states and analyzed sleep/wake behavior, muscle activity, and locomotion in transgenic mice.
RESULTS
We found that stimulation of PPTvGlut2 soma and their axon terminals rapidly triggered arousals from non-rapid eye movement sleep, especially with activation of terminals in the basal forebrain (BF) and lateral hypothalamus (LH). With photoactivation of PPTvGlut2 terminals in the BF and LH, this wakefulness was accompanied by locomotion and other active behaviors, but stimulation of PPTvGlut2 soma and terminals in the substantia nigra triggered only quiet wakefulness without locomotion.
CONCLUSIONS
These findings demonstrate the importance of the PPTvGluT2 neurons in driving various aspects of arousal and show that heterogeneous brain nuclei, such as the PPT, can promote a variety of behaviors via distinct axonal projections.
Topics: Animals; Mice; Wakefulness; Neurons; Sleep; Axons; Basal Forebrain
PubMed: 36170177
DOI: 10.1093/sleep/zsac242 -
Neurology India Jan 2024
Topics: Humans; Wakefulness
PubMed: 38442991
DOI: 10.4103/neurol-india.neurol-india_78_24 -
Journal of Sleep Research Feb 2019Many studies investigating sleep and memory consolidation have evaluated full-night sleep rather than alternative sleep periods such as daytime naps. This multi-centre...
Many studies investigating sleep and memory consolidation have evaluated full-night sleep rather than alternative sleep periods such as daytime naps. This multi-centre study followed up on, and was compared with, an earlier full-night study (Schabus et al., 2004) investigating the relevance of daytime naps for the consolidation of declarative and procedural memory. Seventy-six participants were randomly assigned to a nap or wake group, and performed a declarative word-pair association or procedural mirror-tracing task. Performance changes from before to after a 90-min retention interval filled with sleep or quiet wakefulness were evaluated between groups. Associations between performance changes, sleep architecture, spindles, and slow oscillations were investigated. For the declarative task we observed a trend towards stronger forgetting across a wake period compared with a nap period, and a trend towards memory increase over the full-night. For the procedural task, accuracy was significantly decreased following daytime wakefulness, showed a trend to increase with a daytime nap, and significantly increased across full-night sleep. For the nap protocol, neither sleep stages, spindles, nor slow oscillations predicted performance changes. A direct comparison of day and nighttime sleep revealed that daytime naps are characterized by significantly lower spindle density, but higher spindle activity and amplitude compared with full-night sleep. In summary, data indicate that daytime naps protect procedural memories from deterioration, whereas full-night sleep improves performance. Given behavioural and physiological differences between day and nighttime sleep, future studies should try to characterize potential differential effects of full-night and daytime sleep with regard to sleep-dependent memory consolidation.
Topics: Adult; Female; Humans; Male; Polysomnography; Sleep; Wakefulness; Young Adult
PubMed: 29271015
DOI: 10.1111/jsr.12649 -
Comparative Biochemistry and... Feb 2022Balance between sleep, wakefulness and arousal is important for survival of organisms and species as a whole. While, the benefits of sleep both in terms of quantity and...
Balance between sleep, wakefulness and arousal is important for survival of organisms and species as a whole. While, the benefits of sleep both in terms of quantity and quality is widely recognized across species, sleep has a cost for organismal survival and reproduction. Here we focus on how sleep duration, sleep depth and sleep pressure affect the ability of animals to engage in courtship and egg-laying behaviors critical for reproductive success. Using isogenic lines from the Drosophila Genetic Reference Panel with variable sleep phenotypes we investigated the relationship between sleep and reproductive behaviors, courtship and oviposition. We found that three out of five lines with decreased sleep and increased arousal phenotypes, showed increased courtship and decreased latency to court as compared to normal and long sleeping lines. However, the male courtship phenotype is dependent on context and genotype as some but not all long sleeping-low courting lines elevate their courtship in the presence of short sleeping-high courting flies. We also find that unlike courtship, sleep phenotypes were less variable and minimally susceptible to social experience. In addition to male courtship, we also investigated egg-laying phenotype, a readout of female reproductive output and find oviposition to be less sensitive to sleep length and parameters that are indicative of switch between sleep and wake states. Taken together our extensive behavioral analysis here shows complex bidirectional interactions between genotype and environment and add to the growing evidence linking sleep duration and sleep-wake switch parameters to behavioral decision making critical to reproductive output.
Topics: Animals; Arousal; Courtship; Decision Making; Drosophila melanogaster; Female; Male; Oviposition; Phenotype; Reproduction; Sexual Behavior, Animal; Sleep; Video Recording; Wakefulness
PubMed: 34785379
DOI: 10.1016/j.cbpa.2021.111114 -
Frontiers in Neural Circuits 2018Sedatives target just a handful of receptors and ion channels. But we have no satisfying explanation for how activating these receptors produces sedation. In particular,... (Review)
Review
Sedatives target just a handful of receptors and ion channels. But we have no satisfying explanation for how activating these receptors produces sedation. In particular, do sedatives act at restricted brain locations and circuitries or more widely? Two prominent sedative drugs in clinical use are zolpidem, a GABA receptor positive allosteric modulator, and dexmedetomidine (DEX), a selective α2 adrenergic receptor agonist. By targeting hypothalamic neuromodulatory systems both drugs induce a sleep-like state, but in different ways: zolpidem primarily reduces the latency to NREM sleep, and is a controlled substance taken by many people to help them sleep; DEX produces prominent slow wave activity in the electroencephalogram (EEG) resembling stage 2 NREM sleep, but with complications of hypothermia and lowered blood pressure-it is used for long term sedation in hospital intensive care units-under DEX-induced sedation patients are arousable and responsive, and this drug reduces the risk of delirium. DEX, and another α2 adrenergic agonist xylazine, are also widely used in veterinary clinics to sedate animals. Here we review how these two different classes of sedatives, zolpidem and dexmedetomideine, can selectively interact with some nodal points of the circuitry that promote wakefulness allowing the transition to NREM sleep. Zolpidem enhances GABAergic transmission onto histamine neurons in the hypothalamic tuberomammillary nucleus (TMN) to hasten the transition to NREM sleep, and DEX interacts with neurons in the preoptic hypothalamic area that induce sleep and body cooling. This knowledge may aid the design of more precise acting sedatives, and at the same time, reveal more about the natural sleep-wake circuitry.
Topics: Animals; Brain; Histamine; Humans; Hypnotics and Sedatives; Norepinephrine; Sleep; Wakefulness
PubMed: 29434539
DOI: 10.3389/fncir.2018.00004 -
Nature Communications Apr 2023Despite extensive research on astrocytic Ca in synaptic transmission, its contribution to the modulation of sensory transmission during different brain states remains...
Despite extensive research on astrocytic Ca in synaptic transmission, its contribution to the modulation of sensory transmission during different brain states remains largely unknown. Here, by using two-photon microscopy and whole-cell recordings, we show two distinct astrocytic Ca signals in the murine barrel cortex: a small, long-lasting Ca increase during sleep and a large, widespread but short-lasting Ca spike when aroused. The large Ca wave in aroused mice was inositol trisphosphate (IP3)-dependent, evoked by the locus coeruleus-norepinephrine system, and enhanced sensory input, contributing to reliable sensory transmission. However, the small Ca transient was IP3-independent and contributed to decreased extracellular K, hyperpolarization of the neurons, and suppression of sensory transmission. These events respond to different pharmacological inputs and contribute to distinct sleep and arousal functions by modulating the efficacy of sensory transmission. Together, our data demonstrate an important function for astrocytes in sleep and arousal states via astrocytic Ca waves.
Topics: Mice; Animals; Wakefulness; Astrocytes; Calcium Signaling; Arousal; Sleep
PubMed: 37069258
DOI: 10.1038/s41467-023-37974-z -
Chest Jun 2021
Topics: Humans; Wakefulness
PubMed: 34099134
DOI: 10.1016/j.chest.2020.12.066 -
Neuron Oct 2022Sensory areas are spontaneously active in the absence of sensory stimuli. This spontaneous activity has long been studied; however, its functional role remains largely... (Review)
Review
Sensory areas are spontaneously active in the absence of sensory stimuli. This spontaneous activity has long been studied; however, its functional role remains largely unknown. Recent advances in technology, allowing large-scale neural recordings in the awake and behaving animal, have transformed our understanding of spontaneous activity. Studies using these recordings have discovered high-dimensional spontaneous activity patterns, correlation between spontaneous activity and behavior, and dissimilarity between spontaneous and sensory-driven activity patterns. These findings are supported by evidence from developing animals, where a transition toward these characteristics is observed as the circuit matures, as well as by evidence from mature animals across species. These newly revealed characteristics call for the formulation of a new role for spontaneous activity in neural sensory computation.
Topics: Animals; Wakefulness
PubMed: 35863344
DOI: 10.1016/j.neuron.2022.06.019