Perturbations in dynamical models of wholebrain activity dissociate between the level and stability of consciousness

Consciousness transiently fades away during deep sleep, more stably under anesthesia, and sometimes permanently due to brain injury. The development of an index to quantify the level of consciousness across these different states is regarded as a key problem both in basic and clinical neuroscience. We argue that this problem is ill-defined since such an index would not exhaust all the relevant information about a given state of consciousness. While the level of consciousness can be taken to describe the actual brain state, a complete characterization should also include its potential behavior against external perturbations. We developed and analyzed whole-brain computational models to show that the stability of conscious states provides information complementary to their similarity to conscious wakefulness. Our work leads to a novel methodological framework to sort out different brain states by their stability and reversibility, and illustrates its usefulness to dissociate between physiological (sleep), pathological (brain-injured patients), and pharmacologically-induced (anesthesia) loss of consciousness.S.L. is supported by the University and University Hospital of Liège, the Belgian National Funds for Scientific Research (https://www.flagera. eu/ourfunders/fund-for-scientific-research-fnrs-f-rs-fnrs/, FRS-FNRS), the European Union’s Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement No. 945539 (https://www.humanbrainproject.eu/en/, Human Brain Project SGA3), the European Space Agency (ESA, https://www.esa.int/) and the Belgian Federal Science Policy Office (BELSPO, https:// www.belspo.be/belspo/index_en.stm) in the framework of the PRODEX Programme, “Fondazione Europea di Ricerca Biomedica”, the Bial Foundation, the Mind Science Foundation and the European Commission, the fund Generet, the King Baudouin Foundation, DOCMA project [EUH2020-MSCA–RISE–778234]. SL is research director at FRS-FNRS. AI is partially supported by grants from CONICET; ANID/FONDECYT Regular (1210195 and 1210176); FONCYT-PICT 2017- 1820; ANID/FONDAP/15150012 [https://www.anid. cl/]; Takeda CW2680521 [https://www.takeda.com/ es-es/]; Sistema General de Regalı´as (BPIN2018000100059), Universidad del Valle (CI 5316) [https://www.univalle.edu.co/]; Alzheimer’s Association GBHI ALZ UK-20-639295 [https:// www.alz.org/global/overview.asp]; and the MULTIPARTNER CONSORTIUM TO EXPAND DEMENTIA RESEARCH IN LATIN AMERICA [ReDLat, supported by National Institutes of Health, National Institutes of Aging (R01 AG057234), Alzheimer’s Association (SG-20-725707), Rainwater Charitable foundation - Tau Consortium, and Global Brain Health Institute), https://www.gbhi.org/projects/ multi-partner-consortium-expand-dementiaresearch-latin-america-redlat]. The contents of this publication are solely the responsibility of the authors and do not represent the official views of these Institutions. G.D. is supported by a Spanish national research project (ref. PID2019-105772GBI00 MCIU AE, https://www.csic.es/en/csic I) funded by the Spanish Ministry of Science, Innovation and Universities (MCIU, https://www.ciencia.gob.es/ portal/site/MICINN?lang_choosen=en), State Research Agency (AEI); HBP SGA3 Human Brain Project Specific Grant Agreement 3 (grant agreement no. 945539, https://www. humanbrainproject.eu/en), funded by the EU H2020 FET Flagship programme; SGR Research Support Group support (ref. 2017 SGR 1545), funded by the Catalan Agency for Management of University and Research Grants (AGAUR, https:/ec.europa.eu/growth/tools-databases/regionalinnovation-monitor/organisation/agaur-agencymanagement-university-and-research-grants); Neurotwin Digital twins for model-driven noninvasive electrical brain stimulation (grant agreement ID: 101017716) funded by the EU H2020 FET Proactive programme; euSNN European School of Network Neuroscience (grant agreement ID: 860563, http://www.eusnn.eu/) funded by the EU H2020 MSCA-ITN Innovative Training Networks; CECH The Emerging Human Brain Cluster (Id. 001-P-001682) within the framework of the European Research Development Fund Operational Program of Catalonia 2014-2020; Brain-Connects: Brain Connectivity during Stroke Recovery and Rehabilitation (id. 201725.33) funded by the Fundacio La Marato TV3 (https:// www.ccma.cat/tv3/marato/fundacio/); Corticity, FLAG–ERA JTC 2017, (ref. PCI2018-092891) funded by the Spanish Ministry of Science, Innovation and Universities (MCIU, https://www. ciencia.gob.es/portal/site/MICINN?lang_choosen= en), State Research Agency (AEI). ET is supported by funding from Agencia Nacional De Promocion Cientifica Y Tecnologica (Argentina, https://www. argentina.gob.ar/ciencia/agencia), grant PICT2018-03103 and by a Mercator Fellowship (https:// www.stiftung-mercator.de/en/tenders/mercatorfellowship-program/) awarded by the DFG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript