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      Is Open Access

      Slow waves form expanding, memory-rich mesostates steered by local excitability in fading anesthesia

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          Summary

          In the arousal process, the brain restores its integrative activity from the synchronized state of slow wave activity (SWA). The mechanisms underpinning this state transition remain, however, to be elucidated. Here we simultaneously probed neuronal assemblies throughout the whole cortex with micro-electrocorticographic recordings in mice. We investigated the progressive shaping of propagating SWA at different levels of isoflurane. We found a form of memory of the wavefront shapes at deep anesthesia, tightly alternating posterior-anterior-posterior patterns. At low isoflurane, metastable patterns propagated in more directions, reflecting an increased complexity. The wandering across these mesostates progressively increased its randomness, as predicted by simulations of a network of spiking neurons, and confirmed in our experimental data. The complexity increase is explained by the elevated excitability of local assemblies with no modifications of the network connectivity. These results shed new light on the functional reorganization of the cortical network as anesthesia fades out.

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          Highlights

          • Complexity of isoflurane-induced slow waves reliably determines anesthesia level

          • In deep anesthesia, the propagation strictly alternates between front-back-front patterns

          • In light anesthesia, there is a continuum of directions and faster propagation

          • Local excitability underpins the cortical reorganization in fading anesthesia

          Abstract

          Neuroscience; Experimental models in systems biology

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          Most cited references89

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          Principal component analysis: a review and recent developments.

          Large datasets are increasingly common and are often difficult to interpret. Principal component analysis (PCA) is a technique for reducing the dimensionality of such datasets, increasing interpretability but at the same time minimizing information loss. It does so by creating new uncorrelated variables that successively maximize variance. Finding such new variables, the principal components, reduces to solving an eigenvalue/eigenvector problem, and the new variables are defined by the dataset at hand, not a priori, hence making PCA an adaptive data analysis technique. It is adaptive in another sense too, since variants of the technique have been developed that are tailored to various different data types and structures. This article will begin by introducing the basic ideas of PCA, discussing what it can and cannot do. It will then describe some variants of PCA and their application.
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            Breakdown of cortical effective connectivity during sleep.

            When we fall asleep, consciousness fades yet the brain remains active. Why is this so? To investigate whether changes in cortical information transmission play a role, we used transcranial magnetic stimulation together with high-density electroencephalography and asked how the activation of one cortical area (the premotor area) is transmitted to the rest of the brain. During quiet wakefulness, an initial response (approximately 15 milliseconds) at the stimulation site was followed by a sequence of waves that moved to connected cortical areas several centimeters away. During non-rapid eye movement sleep, the initial response was stronger but was rapidly extinguished and did not propagate beyond the stimulation site. Thus, the fading of consciousness during certain stages of sleep may be related to a breakdown in cortical effective connectivity.
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              Consciousness and anesthesia.

              When we are anesthetized, we expect consciousness to vanish. But does it always? Although anesthesia undoubtedly induces unresponsiveness and amnesia, the extent to which it causes unconsciousness is harder to establish. For instance, certain anesthetics act on areas of the brain's cortex near the midline and abolish behavioral responsiveness, but not necessarily consciousness. Unconsciousness is likely to ensue when a complex of brain regions in the posterior parietal area is inactivated. Consciousness vanishes when anesthetics produce functional disconnection in this posterior complex, interrupting cortical communication and causing a loss of integration; or when they lead to bistable, stereotypic responses, causing a loss of information capacity. Thus, anesthetics seem to cause unconsciousness when they block the brain's ability to integrate information.
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                Author and article information

                Contributors
                Journal
                iScience
                iScience
                iScience
                Elsevier
                2589-0042
                12 February 2022
                18 March 2022
                12 February 2022
                : 25
                : 3
                : 103918
                Affiliations
                [1 ]Natl. Center for Radiation Protection and Computational Physics, Istituto Superiore di Sanità, Italian Institute of Health, Viale Regina Elena 299, 00161 Rome, Italy
                [2 ]IDIBAPS (Institut d’Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain
                [3 ]ICREA (Institució Catalana de Recerca i Estudis Avançats), Barcelona, Spain
                Author notes
                []Corresponding author maurizio.mattia@ 123456iss.it
                [4]

                Present address: University of Exeter Medical School, Exeter, UK

                [5]

                Lead contact

                Article
                S2589-0042(22)00188-2 103918
                10.1016/j.isci.2022.103918
                8899414
                35265807
                9419d110-91d8-430b-a05d-68c382ccd017
                © 2022 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 13 September 2021
                : 17 December 2021
                : 9 February 2022
                Categories
                Article

                neuroscience,experimental models in systems biology

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