Mindlin, IvanHerzog, RubénBelloli, LaouenManasova, DraganaMonge-Asensio, MartíVohzyzek, JakubEscrichs, AniraAlnagger, NajiNúñez, Paul L.Gosseries, Oliviakringelbach, Morten L.Deco, GustavoTagliazucchi, Enzo RodolfoNaccache, LionelRohaut, BenjaminSitt, Jacobo DiegoSanz Perl, Yonatan2025-05-212025-05-212024Mindlin I, Herzog R, Belloli L, Manasova D, Monge-Asensio M, Vohzyzek J, et al. Whole brain modelling for simulating pharmacological interventions on patients with disorders of consciousness. Commun Biol. 2024;7:1176. DOI: 10.1038/s42003-024-06852-92399-3642http://hdl.handle.net/10230/70444Disorders 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.application/pdfeng© The Author(s) 2024. This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, 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 you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. 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-nc-nd/4.0/.ConsciènciaCervell -- ModelsFarmacologiainfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s42003-024-06852-9info:eu-repo/semantics/openAccess