Whole brain modelling for simulating pharmacological interventions on patients with disorders of consciousness

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.

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Publication Details

Journal
Communications Biology
Published
2024-09-19
DOI
https://doi.org/10.1038/s42003-024-06852-9
Citations
15
Primary Topic
Psychedelics and Drug Studies
Type
article
Field-Weighted Citation Impact
9.59

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article

Whole brain modelling for simulating pharmacological interventions on patients with disorders of consciousness

Jacobo Diego Sitt, Ruben A Herzog, Lionel Naccache, Olivia Gosseries et al.
15 citations
Communications Biology
Psychedelics and Drug Studies
9.59
article

Whole brain modelling for simulating pharmacological interventions on patients with disorders of consciousness

Jacobo Diego Sitt, Ruben A Herzog, Lionel Naccache, Olivia Gosseries, Anira Escrichs, Iván Mindlin, Morten L. Kringelbach, Gustavo Deco, Pablo Núñez, Enzo Tagliazucchi, Martí Monge-Asensio, Naji Alnagger, Jakub Vohryzek, Benjamin Rohaut, Laouen Belloli, Dragana Manasova, Yonatan Sanz Perl
article en
15 citations

Abstract

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.

Communications BiologyVol. 7(1)
Institució Catalana de Recerca i Estudis Avançats (ES), Centre National de la Recherche Scientifique (FR), Consejo Nacional de Investigaciones Científicas y Técnicas (AR), Inserm (FR), University of Liège (BE), Universitat Pompeu Fabra (ES), Aarhus University (DK), Université Paris Cité (FR), Adolfo Ibáñez University (CL), Sorbonne Université (FR), University of Oxford (GB), University of San Andrés (AR), Centro Científico Tecnológico - San Juan (AR), Assistance Publique – Hôpitaux de Paris (FR), Royal Academy of Music (DK), Pitié-Salpêtrière Hospital (FR), Ministerio de Ciencia, Tecnología e Innovación (AR), Institut du Cerveau (FR)
European Commission, National Research Foundation, Danmarks Grundforskningsfond, Fonds De La Recherche Scientifique - FNRS, Consejo Nacional de Investigaciones Científicas y Técnicas, Assistance publique-Hôpitaux de Paris, Sorbonne Université, Agencia Nacional de Investigación y Desarrollo, HORIZON EUROPE Framework Programme, Agència de Gestió d'Ajuts Universitaris i de Recerca, European Regional Development Fund, Agencia Estatal de Investigación, Fondo para la Investigación Científica y Tecnológica
Openalex Percentile: Top 1%
Psychedelics and Drug Studies
9.59
DOIOpen Access PDFOpenAlex
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