Humans; Models, Neurological; Deep Learning; Male; Brain/metabolism; Brain/drug effects; Consciousness Disorders/drug therapy; Consciousness Disorders/metabolism; Consciousness Disorders/physiopathology; Brain; Consciousness Disorders; Medicine (miscellaneous); Biochemistry, Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all)
Abstract :
[en] Disorders of consciousness (DoC) represent a challenging and complex group of neurological conditions characterised by profound disturbances in consciousness. The current range of treatments for DoC is limited. This has sparked growing interest in developing new treatments, including the use of psychedelic drugs. Nevertheless, clinical investigations and the mechanisms behind them are methodologically and ethically constrained. To tackle these limitations, we combined biologically plausible whole-brain models with deep learning techniques to characterise the low-dimensional space of DoC patients. We investigated the effects of model pharmacological interventions by including the whole-brain dynamical consequences of the enhanced neuromodulatory level of different neurotransmitters, and providing geometrical interpretation in the low-dimensional space. Our findings show that serotonergic and opioid receptors effectively shifted the DoC models towards a dynamical behaviour associated with a healthier state, and that these improvements correlated with the mean density of the activated receptors throughout the brain. These findings mark an important step towards the development of treatments not only for DoC but also for a broader spectrum of brain diseases. Our method offers a promising avenue for exploring the therapeutic potential of pharmacological interventions within the ethical and methodological confines of clinical research.
Disciplines :
Neurosciences & behavior
Author, co-author :
Mindlin, I ; Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Sorbonne Université, Paris, 75013, France. ivan.mindlin@icm-institute.org
Herzog, R ; Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Sorbonne Université, Paris, 75013, France
Belloli, L; Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Sorbonne Université, Paris, 75013, France ; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ministry of Science, Technology and Innovation, Buenos Aires, Argentina
Manasova, D; Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Sorbonne Université, Paris, 75013, France ; Université Paris Cité, Paris, France
Monge-Asensio, M; Center for Brain and Cognition, Computational Neuroscience Group, Universitat Pompeu Fabra, Barcelona, Spain
Vohryzek, J; Center for Brain and Cognition, Computational Neuroscience Group, Universitat Pompeu Fabra, Barcelona, Spain
Escrichs, A ; Center for Brain and Cognition, Computational Neuroscience Group, Universitat Pompeu Fabra, Barcelona, Spain
Alnagger, Naji ; Université de Liège - ULiège > GIGA > GIGA Neurosciences - Coma Science Group
Núñez, P; Coma Science Group, GIGA Consciousness, University of Liège, Liège, Belgium ; Centre du cerveau, CHU of Liège, Liège, Belgium
Gosseries, Olivia ; Université de Liège - ULiège > GIGA > GIGA Neurosciences - Coma Science Group
Kringelbach, M L ; Centre for Eudaimonia and Human Flourishing, Linacre College, University of Oxford, Oxford, UK ; Department of Psychiatry, University of Oxford, Oxford, UK ; Center for Music in the Brain, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Deco, G ; Center for Brain and Cognition, Computational Neuroscience Group, Universitat Pompeu Fabra, Barcelona, Spain ; Institució Catalana de la Recerca i Estudis Avançats (ICREA), Barcelona, Spain
Tagliazucchi, E; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ministry of Science, Technology and Innovation, Buenos Aires, Argentina ; Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibáñez, Santiago, Chile ; Cognitive Neuroscience Center, Universidad de San Andrés, Buenos Aires, Argentina
Naccache, L ; Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Sorbonne Université, Paris, 75013, France
Rohaut, B; Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Sorbonne Université, Paris, 75013, France ; APHP, Hôpital de la Pitié Salpêtrière, DMU Neurosciences, Neuro ICU, Sorbonne Université, Paris, France
Sitt, J D ; Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Sorbonne Université, Paris, 75013, France. jacobo.sitt@icm-institute.org
Sanz Perl, Y ; Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Sorbonne Université, Paris, 75013, France. yonatan.sanz@upf.edu ; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ministry of Science, Technology and Innovation, Buenos Aires, Argentina. yonatan.sanz@upf.edu ; Center for Brain and Cognition, Computational Neuroscience Group, Universitat Pompeu Fabra, Barcelona, Spain. yonatan.sanz@upf.edu
The authors express gratitude to all the individuals who participated in the studies. Additionally, we extend our thanks to the dedication and support provided by the clinicians at the Neuro ICU, DMU Neurosciences, APHP Sorbonne Universit\u00E9, H\u00F4pital de la Piti\u00E9 Salp\u00EAtri\u00E8re, Paris, France. Moreover, we acknowledge the invaluable contributions of patient families whose consent and understanding significantly contribute to the advancement of the field. We finally thank the financial support of the FLAG-ERA research funding organisation (project ModelDXConsciousness). Y.S.P.is supported by European Union\u2019s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant 896354, and \u2018ERDF A way of making Europe\u2019, ERDF, EU, Project NEurological MEchanismS of Injury, and Sleep-like cellular dynamics (NEMESIS; ref. 101071900) funded by the EU ERC Synergy Horizon Europe. M.L.K. is supported by the Center for Music in the Brain, funded by the Danish National Research Foundation (DNRF117), and Centre for Eudaimonia and Human Flourishing at Linacre College funded by the Pettit and Carlsberg Foundations. ET is supported by grants FONCYT-PICT (2019-02294), CONICET-PIP (11220210100800CO), and ANID/FONDECYT Regular (1220995). O.G. is research associate and N.A. is research fellow at FNRS. G.D. is supported by grant no. PID2022-136216NB-I00 funded by MICIU/AEI/10.13039/501100011033 and by \u2018ERDF A way of making Europe\u2019, ERDF, EU, Project NEurological MEchanismS of Injury, and Sleep-like cellular dynamics (NEMESIS; ref. 101071900) funded by the EU ERC Synergy Horizon Europe, and AGAUR research support grant (ref. 2021 SGR 00917) funded by the Department of Research and Universities of the Generalitat of Catalunya.
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