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 psyc...

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Główni autorzy: Mindlin, I, Herzog, R, Belloli, L, Manasova, D, Monge-Asensio, M, Vohryzek, J, Escrichs, A, Alnagger, N, Núñez, P, Gosseries, O, Kringelbach, ML, Deco, G, Tagliazucchi, E, Naccache, L, Rohaut, B, Sitt, JD, Sanz Perl, Y
Format: Journal article
Język:English
Wydane: Nature Research 2024
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author Mindlin, I
Herzog, R
Belloli, L
Manasova, D
Monge-Asensio, M
Vohryzek, J
Escrichs, A
Alnagger, N
Núñez, P
Gosseries, O
Kringelbach, ML
Deco, G
Tagliazucchi, E
Naccache, L
Rohaut, B
Sitt, JD
Sanz Perl, Y
author_facet Mindlin, I
Herzog, R
Belloli, L
Manasova, D
Monge-Asensio, M
Vohryzek, J
Escrichs, A
Alnagger, N
Núñez, P
Gosseries, O
Kringelbach, ML
Deco, G
Tagliazucchi, E
Naccache, L
Rohaut, B
Sitt, JD
Sanz Perl, Y
author_sort Mindlin, I
collection OXFORD
description 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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spelling oxford-uuid:b0eb72da-3b76-45fb-bf23-c87f360ce6ee2024-09-19T20:09:29ZWhole brain modelling for simulating pharmacological interventions on patients with disorders of consciousnessJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b0eb72da-3b76-45fb-bf23-c87f360ce6eeEnglishJisc Publications RouterNature Research2024Mindlin, IHerzog, RBelloli, LManasova, DMonge-Asensio, MVohryzek, JEscrichs, AAlnagger, NNúñez, PGosseries, OKringelbach, MLDeco, GTagliazucchi, ENaccache, LRohaut, BSitt, JDSanz Perl, YDisorders 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.
spellingShingle Mindlin, I
Herzog, R
Belloli, L
Manasova, D
Monge-Asensio, M
Vohryzek, J
Escrichs, A
Alnagger, N
Núñez, P
Gosseries, O
Kringelbach, ML
Deco, G
Tagliazucchi, E
Naccache, L
Rohaut, B
Sitt, JD
Sanz Perl, Y
Whole brain modelling for simulating pharmacological interventions on patients with disorders of consciousness
title Whole brain modelling for simulating pharmacological interventions on patients with disorders of consciousness
title_full Whole brain modelling for simulating pharmacological interventions on patients with disorders of consciousness
title_fullStr Whole brain modelling for simulating pharmacological interventions on patients with disorders of consciousness
title_full_unstemmed Whole brain modelling for simulating pharmacological interventions on patients with disorders of consciousness
title_short Whole brain modelling for simulating pharmacological interventions on patients with disorders of consciousness
title_sort whole brain modelling for simulating pharmacological interventions on patients with disorders of consciousness
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