Whole brain modelling for simulating pharmacological interventions on patients with disorders of consciousness
Year: 2024
Type: article
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.
Source: Communications Biology
Institutions: Centre National de la Recherche Scientifique, Inserm, Sorbonne Université, Institut du Cerveau, Consejo Nacional de Investigaciones Científicas y Técnicas, Ministerio de Ciencia, Tecnología e Innovación, Université Paris Cité, Universitat Pompeu Fabra, University of Liège, Centre Hospitalier Universitaire de Liège, Aarhus University, University of Oxford, Institució Catalana de Recerca i Estudis Avançats, Adolfo Ibáñez University, University of San Andrés, Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,890
Funders: European Commission, National Research Foundation, Danmarks Grundforskningsfond, Fonds De La Recherche Scientifique - FNRS, Consejo Nacional de Investigaciones Científicas y Técnicas, Ministerio de Ciencia e Innovación, 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
Awards: G1471086492, G1833454833, G2535781731, G2694737719, G2916232624, G3480869486, G434337789, G4921481610, G5032928781, G6033112984, Center for Music in the Brain (MIB), G6966048999, G7084143925, MAPPING AND MODELING THE HEALTHY AND PATHOLOGICAL AGING TRAJECTORIES OF THE HUMAN BRAIN, Model-based biomarkers for the characterization and quantification of global states of consciousness
OpenAlex ID: W4402650878