During much of sleep, the cerebral cortex is rippled by slow waves, which appear in the electroen... more During much of sleep, the cerebral cortex is rippled by slow waves, which appear in the electroencephalogram as oscillations between 0.5 and 4.5 Hz. Slow waves are regulated as a function of previous wakefulness, being maximal at the beginning of sleep and then progressively returning to a baseline level. This paper discusses a hypothesis about the significance of slow-wave activity and its homeostatic regulation. The hypothesis is as follows: 1. Wakefulness is associated with synaptic potentiation in several cortical circuits; 2. Synaptic potentiation is tied to the homeostatic regulation of slow-wave activity; 3. Slow-wave activity is associated with synaptic downscaling; 4. Synaptic downscaling is tied to the beneficial effects of sleep on performance. The hypothesized link between sleep and synaptic homeostasis is supported by several lines of evidence and leads to testable predictions.
Sleep offers a unique opportunity to relate changes in brain activity to changes in consciousness... more Sleep offers a unique opportunity to relate changes in brain activity to changes in consciousness. Indeed, if it were not for sleep, when consciousness fades in and out on a regular basis, it might be hard to imagine that consciousness is not a given but depends somehow on the way our brain is functioning. At the same time as changes in consciousness occur, brain activity undergoes major changes through an orderly progression of sleep stages, which can be identi fi ed by recording the electroencephalogram (EEG), eye movements (EOG), and muscle tone (EMG). Within each sleep stage, there are frequent, short-lasting electrophysiological phenomena, such as slow oscillations and spindles representing moments at which brain activity undergoes important fl uctuations. There are also orderly spatial changes in the activation of many brain regions, as indicated by imaging studies. Importantly, similar brain activities occur in animals, and this has spearheaded detailed studies of the underlying neural mechanisms. This chapter will fi rst examine how sleep is traditionally subdivided into different stages that alternate in the course of the night. It will then review the dreaming events we experience across sleep. Next, it will consider the neural
Knowledge of the molecular correlates of sleep and wakefulness is essential if we are to understa... more Knowledge of the molecular correlates of sleep and wakefulness is essential if we are to understand the restorative processes occurring during sleep and the cellular mechanisms underlying sleep regulation. In order to determine what molecular changes occur during the sleep-waking cycle, we have recently performed a systematic screening of gene expression in the brain of sleeping, sleep deprived and spontaneously awake rats. Out of the >10 000 genes screened so far, a small minority (>0.5%) was differentially expressed in the cerebral cortex across behavioral states. Most genes were upregulated in wakefulness and sleep deprivation relative to sleep, while only a few had higher expression in sleep relative to wakefulness and sleep deprivation. Almost all the genes upregulated in sleep, and several genes upregulated in wakefulness and sleep deprivation, did not match any known sequence. Known genes that were upregulated in wakefulness and sleep deprivation could be grouped into functional categories: immediate early genes/transcription factors, genes related to energy metabolism, growth factors/adhesion molecules, chaperones/heat shock proteins, vesicle-and synapse-related genes, neurotransmitter/hormone receptors, neurotransmitter transporters, enzymes, and others. Although the characterization of the molecular correlates of sleep, wakefulness and sleep deprivation is still in progress, it is already apparent that the transition from sleep to waking can affect basic cellular functions such as RNA and protein synthesis, neural plasticity, neurotransmission, and metabolism.
Recent studies using microarrays have shown that changes in behavioral states are associated with... more Recent studies using microarrays have shown that changes in behavioral states are associated with rapid and extensive changes in brain gene expression. Sleep, spontaneous wakefulness, short-term (3–8 h), and long-term (1 week) sleep deprivation are each associated with the upregulation of hundreds of genes in the cerebral cortex and other brain areas. In flies, mice, and rats, three categories of genes are consistently upregulated during spontaneous waking or short-term sleep deprivation and downregulated during sleep. They include genes involved in energy metabolism, the cellular stress response, and memory formation and long-term potentiation. The sleep-related transcripts identified in the rat cerebral cortex suggest that sleep may favor protein synthesis, memory consolidation, and synaptic depression, as well as membrane trafficking and glial function. Long-term sleep deprivation in rats is associated with unique changes in brain gene expression, which differ to some extent from those seen after acute sleep loss. Gene expression profiling is a work in progress, and more studies using DNA and protein arrays are needed to characterize the molecular correlates of sleep and wakefulness in different species and in different brain regions.
Effects of intracortical microinjections of nicotinic agonists on sleep regulation
Strong conceptual and theoretical connections have been made between meditation practice, mindful... more Strong conceptual and theoretical connections have been made between meditation practice, mindfulness and lucid dreaming. However, only a handful of empirical studies have evaluated the relationship between lucid dreaming and meditation, and conclusions remain tempered by methodological limitations. Here we evaluate the relationship between meditation, mindfulness and lucid dream frequency using several complementary methods. First, using a cross-sectional design, we evaluate differences in lucid dream frequency between long-term meditators and meditation naïve individuals. Second, we evaluate the relationship between lucid dream frequency and specific facets of trait mindfulness in both meditators and non-meditators. Third, using a blinded randomized-controlled design, we evaluate the impact of an 8-week mindfulness course on lucid dreaming frequency. Our results show that lucid dreaming is more frequent in long-term meditators compared to meditation naïve individuals. Additionally, lucid dream frequency in meditation-naïve individuals was associated with a capacity to verbalize experience, while lucid dream frequency in long-term meditators was associated with observational and decentering facets of trait mindfulness. However, an 8-week mindfulness course did not increase the frequency of lucid dreams. Together these results support a continuity between increased awareness of waking and sleeping states, provide a novel form of evidence linking meditation training to metaawareness, and support an association between meditation practice and lucid dreaming, but leave open the specific nature of this connection.
Sleep is present in all species in which it has been studied, but its functions remain unknown. I... more Sleep is present in all species in which it has been studied, but its functions remain unknown. Identification of the molecular correlates of sleep and wakefulness is essential if we are to understand the restorative processes that occur during sleep, the cellular mechanisms that underlie sleep regulation, and the functional consequences of sleep loss and poor quality sleep. To address the questions of how we know whether sleep has performed its functions and whether treatment has improved sleep quality, we have proposed a synaptic homeostasis hypothesis about the significance of slow wave activity (SWA) during sleep and its homeostatic regulation. Briefly, the hypothesis states that (1) wakefulness is associated with potentiation in several cortical circuits; (2) synaptic potentiation is then tied to the homeostatic regulation of SWA; (3) SWA is associated with synaptic downscaling; and (4) synaptic downscaling is tied to the beneficial effects of sleep on performance. According to this hypothesis, the potentiation of neural circuits that results from synaptic plasticity during alert wakefulness is responsible for SWA homeostasis. Increasing noradrenergic activity increases the expression of long-term potentiation (LTP)-related genes, and interference with these changes block the induction of markers of synaptic potentiation during alert wakefulness. Inducing local LTP-like changes during alert wakefulness also results in increased local slow wave homeostasis. Thus, as SWA homeostasis can be induced on a local level or can be triggered by a learning task, and is strongly correlated with postsleep performance enhancement, plasticity during alert wakefulness depends on good sleep, which, in turn, depends on efficient synaptic downscaling.
Transcriptomic studies have shown that hundreds of genes change their expression levels across th... more Transcriptomic studies have shown that hundreds of genes change their expression levels across the sleep/waking cycle, and found that waking-related and sleep-related mRNAs belong to different functional categories. Proteins, however, rather than DNA or RNA, carry out most of the cellular functions, and direct measurements of protein levels and activity are required to assess the effects of behavioral states on the overall functional state of the cell. Here we used surface-enhanced laser desorption-ionization (SELDI), followed by time-of-flight mass spectrometry, to obtain a large-scale profiling of the proteins in the rat cerebral cortex whose expression is affected by sleep, spontaneous waking, short (6 hours) and long (7 days) sleep deprivation. Each of the 94 cortical samples was profiled in duplicate on 4 different ProteinChip Array surfaces using 2 different matrix molecules. Overall, 1055 protein peaks were consistently detected in cortical samples and 15 candidate biomarkers were selected for identification based on significant changes in multiple conditions (conjunction analysis): 8 "sleep" peaks, 4 "waking" peaks, and 4 "long sleep deprivation" peaks. Four candidate biomarkers were purified and positively identified. The 3353 Da candidate sleep marker was identified as the 30 amino acid C-terminal fragment of rat histone H4. This region encompasses the osteogenic growth peptide, but a possible link between sleep and this peptide remains highly speculative. Two peaks associated with short and long sleep deprivation were identified as hemoglobin alpha1/2 and beta, respectively, while another peak associated with long sleep deprivation was identified as cytochrome C. The upregulation of hemoglobins and cytochrome C may be part of a cellular stress response triggered by even short periods of sleep loss.
The Integrated Information Theory of Consciousness
The integrated information theory (IIT) starts from phenomenology and makes a critical use of tho... more The integrated information theory (IIT) starts from phenomenology and makes a critical use of thought experiments, to claim that consciousness is integrated information. Specifically: (1) the quantity of consciousness is given by the amount of integrated information generated by a complex of elements, and (2) the quality of experience is given by the set of informational relationships within that complex. Integrated information (Φ) is defined as the amount of information generated by causal interactions within a complex of elements, above and beyond the information generated independently by its parts. Qualia space (Q) is a space where each axis represents a possible state of the complex, each point is a probability distribution of its states, and arrows between points represent the informational relationships generated by causal interactions among its elements. Together, the set of informational relationships within a complex specifies a shape in Q that in turn specifies a particular experience. Several observations concerning the neural substrate of consciousness fall naturally into place within the IIT framework. Among them are the association of consciousness with certain neural systems rather than with others; the fact that neural processes underlying consciousness can influence or be influenced by neural processes that remain unconscious; the reduction of consciousness during dreamless sleep and generalized seizures and the distinct role of different cortical architectures in affecting the quality of experience.
A proper understanding of cognitive functions cannot be achieved without an understanding of cons... more A proper understanding of cognitive functions cannot be achieved without an understanding of consciousness, both at the empirical and at the theoretical level. This paper argues that consciousness has to do with a system's capacity for information integration. In this approach, every causal mechanism capable of choosing among alternatives generates information, and information is integrated to the extent that it is generated by a system above and beyond its parts. The set of integrated informational relationships generated by a complex of mechanisms--its quale--specify both the quantity and the quality of experience. As argued below, depending on the causal structure of a system, information integration can reach a maximum value at a particular spatial and temporal grain size. It is also argued that changes in information integration reflect a system's ability to match the causal structure of the world, both on the input and the output side. After a brief review suggesting that this approach is consistent with several experimental and clinical observations, the paper concludes with some prospective remarks about the relevance of understanding information integration for analyzing cognitive function, both normal and pathological.
This article presents an updated account of integrated information theory of consciousness (liT) ... more This article presents an updated account of integrated information theory of consciousness (liT) and some of its implications. /IT stems from thought experiments that lead to phenomenological axioms (existence, compositionality, information, integration, exclusion) and corresponding ontological postulates. The information axiom asserts that every experience is spec~fic - it is what it is by differing in its particular way from a large repertoire of alternatives. The integration axiom asserts that each experience is unified- it cannot be reduced to independent components. The exclusion axiom asserts that every experience is definite - it is limited to particular things and not others and flows at a particular speed and resolution. /IT formalizes these intuitions with postulates. The information postulate states that only "differences that make a difference" from the intrinsic perpective of a system matter: a mechanism generates cause-effect information if its present state has selective past causes and selective future effects within a system. The integration postulate states that only information that is irreducible matters: mechanisms generate integrated information only to the extent that the information they generate cannot be partitioned into that generated within independent components. The exclusion postulate states that only maxima of integrated information matter: a mechanism specifies only one maximally irreducible set of past causes and future effects - a concept. A complex is a set of elements specifying a maximally irreducible constellation of concepts, where the maximum is evaluated over elements and at the optimal spatiatemporal scale. Its concepts specify a maximally integrated conceptual information structure or quale, which is identical with an experience. Finally, changes in information integration upon exposure to the environment reflect a system's ability to match the causal structure of the world. After introducing an updated definition of information integration and related quantities, the article presents some theoretical considerations about the relationship between information and causation and about the relational structure of concepts within a qua/e. It also explores the relationship between the temporal grain size of information integration and the dynamic of metastable states in the corticothalamic complex. Finally, it summarizes how liT accounts for empirical findings about the neural substrate of consciousness, and how various aspects of phenomenology may in principle be addressed in terms of the geometry of information integration.
Clinical observations have established that certain parts of the brain are essential for consciou... more Clinical observations have established that certain parts of the brain are essential for consciousness whereas other parts are not. For example, different areas of the cerebral cortex contribute different modalities and submodalities of consciousness, whereas the cerebellum does not, despite having even more neurons. It is also well established that consciousness depends on the way the brain functions. For example, consciousness is much reduced during slow wave sleep and generalized seizures, even though the levels of neural activity are comparable or higher than in wakefulness. To understand why this is so, empirical observations on the neural correlates of consciousness need to be complemented by a principled theoretical approach. Otherwise, it is unlikely that we could ever establish to what extent consciousness is present in neurological conditions such as akinetic mutism, psychomotor seizures, or sleepwalking, and to what extent it is present in newborn babies and animals. A principled approach is provided by the information integration theory of consciousness. This theory claims that consciousness corresponds to a system's capacity to integrate information, and proposes a way to measure such capacity. The information integration theory can account for several neurobiological observations concerning consciousness, including: (i) the association of consciousness with certain neural systems rather than with others; (ii) the fact that neural processes underlying consciousness can influence or be influenced by neural processes that remain unconscious; (iii) the reduction of consciousness during dreamless sleep and generalized seizures; and (iv) the time requirements on neural interactions that support consciousness.
Background: Consciousness poses two main problems. The first is understanding the conditions that... more Background: Consciousness poses two main problems. The first is understanding the conditions that determine to what extent a system has conscious experience. For instance, why is our consciousness generated by certain parts of our brain, such as the thalamocortical system, and not by other parts, such as the cerebellum? And why are we conscious during wakefulness and much less so during dreamless sleep? The second problem is understanding the conditions that determine what kind of consciousness a system has. For example, why do specific parts of the brain contribute specific qualities to our conscious experience, such as vision and audition? Presentation of the hypothesis: This paper presents a theory about what consciousness is and how it can be measured. According to the theory, consciousness corresponds to the capacity of a system to integrate information. This claim is motivated by two key phenomenological properties of consciousness: differentiation -the availability of a very large number of conscious experiences; and integration -the unity of each such experience. The theory states that the quantity of consciousness available to a system can be measured as the Φ value of a complex of elements. Φ is the amount of causally effective information that can be integrated across the informational weakest link of a subset of elements. A complex is a subset of elements with Φ>0 that is not part of a subset of higher Φ. The theory also claims that the quality of consciousness is determined by the informational relationships among the elements of a complex, which are specified by the values of effective information among them. Finally, each particular conscious experience is specified by the value, at any given time, of the variables mediating informational interactions among the elements of a complex. Testing the hypothesis: The information integration theory accounts, in a principled manner, for several neurobiological observations concerning consciousness. As shown here, these include the association of consciousness with certain neural systems rather than with others; the fact that neural processes underlying consciousness can influence or be influenced by neural processes that remain unconscious; the reduction of consciousness during dreamless sleep and generalized seizures; and the time requirements on neural interactions that support consciousness. The theory entails that consciousness is a fundamental quantity, that it is graded, that it is present in infants and animals, and that it should be possible to build conscious artifacts.
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