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      Transcutaneous auricular vagus nerve stimulation induces stabilizing modifications in large-scale functional brain networks: towards understanding the effects of taVNS in subjects with epilepsy

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          Abstract

          Transcutaneous auricular vagus nerve stimulation (taVNS) is a novel non-invasive brain stimulation technique considered as a potential supplementary treatment option for subjects with refractory epilepsy. Its exact mechanism of action is not yet fully understood. We developed an examination schedule to probe for immediate taVNS-induced modifications of large-scale epileptic brain networks and accompanying changes of cognition and behaviour. In this prospective trial, we applied short-term (1 h) taVNS to 14 subjects with epilepsy during a continuous 3-h EEG recording which was embedded in two standardized neuropsychological assessments. From these EEG, we derived evolving epileptic brain networks and tracked important topological, robustness, and stability properties of networks over time. In the majority of investigated subjects, taVNS induced measurable and persisting modifications in network properties that point to a more resilient epileptic brain network without negatively impacting cognition, behaviour, or mood. The stimulation was well tolerated and the usability of the device was rated good. Short-term taVNS has a topology-modifying, robustness- and stability-enhancing immediate effect on large-scale epileptic brain networks. It has no detrimental effects on cognition and behaviour. Translation into clinical practice requires further studies to detail knowledge about the exact mechanisms by which taVNS prevents or inhibits seizures.

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          Complex brain networks: graph theoretical analysis of structural and functional systems.

          Recent developments in the quantitative analysis of complex networks, based largely on graph theory, have been rapidly translated to studies of brain network organization. The brain's structural and functional systems have features of complex networks--such as small-world topology, highly connected hubs and modularity--both at the whole-brain scale of human neuroimaging and at a cellular scale in non-human animals. In this article, we review studies investigating complex brain networks in diverse experimental modalities (including structural and functional MRI, diffusion tensor imaging, magnetoencephalography and electroencephalography in humans) and provide an accessible introduction to the basic principles of graph theory. We also highlight some of the technical challenges and key questions to be addressed by future developments in this rapidly moving field.
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            A note on two problems in connexion with graphs

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              Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies.

              To improve patient care and facilitate clinical research, the International League Against Epilepsy (ILAE) appointed a Task Force to formulate a consensus definition of drug resistant epilepsy. The overall framework of the definition has two "hierarchical" levels: Level 1 provides a general scheme to categorize response to each therapeutic intervention, including a minimum dataset of knowledge about the intervention that would be needed; Level 2 provides a core definition of drug resistant epilepsy using a set of essential criteria based on the categorization of response (from Level 1) to trials of antiepileptic drugs. It is proposed as a testable hypothesis that drug resistant epilepsy is defined as failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom. This definition can be further refined when new evidence emerges. The rationale behind the definition and the principles governing its proper use are discussed, and examples to illustrate its application in clinical practice are provided.
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                Author and article information

                Contributors
                randi.von.wrede@ukbonn.de
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                12 April 2021
                12 April 2021
                2021
                : 11
                : 7906
                Affiliations
                [1 ]GRID grid.15090.3d, ISNI 0000 0000 8786 803X, Department of Epileptology, , University Hospital Bonn, ; Venusberg Campus 1, 53127 Bonn, Germany
                [2 ]GRID grid.10388.32, ISNI 0000 0001 2240 3300, Helmholtz-Institute for Radiation and Nuclear Physics, , University of Bonn, ; Nussallee 14-16, 53115 Bonn, Germany
                [3 ]GRID grid.10388.32, ISNI 0000 0001 2240 3300, Interdisciplinary Center for Complex Systems, , University of Bonn, ; Brühler Straße 7, 53175 Bonn, Germany
                Article
                87032
                10.1038/s41598-021-87032-1
                8042037
                33846432
                38972617-bc25-4c88-8b51-d57e4d19499a
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 14 January 2021
                : 22 March 2021
                Funding
                Funded by: Rheinische Friedrich-Wilhelms-Universität Bonn (1040)
                Categories
                Article
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                © The Author(s) 2021

                Uncategorized
                physics,statistical physics, thermodynamics and nonlinear dynamics,complex networks,neuroscience,diseases of the nervous system,epilepsy

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