Whole brain modelling for simulating pharmacological interventions on patients with disorders of consciousness.
Iván Mindlin, Rubén Herzog, Laouen Belloli, Dragana Manasova, M Monge-Asensio, Jakub Vohryzek, Anira Escrichs, Naji Alnagger, Pablo Núñez, Olivia Gosseries, M L Kringelbach, Gustavo Deco, Enzo Tagliazucchi, Lionel Naccache, Benjamin Rohaut, J D Sitt, Yonatan Sanz Perl
Communications Biology September 19, 2024 DOI: 10.1038/s42003-024-06852-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Computational modeling study Peer reviewed |
|---|---|
| Population | Biologically plausible whole-brain models of patients with disorders of consciousness |
| Citations | 18 |
| Key points | Simulated activation of serotonergic and opioid receptors shifted whole-brain models of disorders of consciousness toward dynamics associated with healthier states, with improvements correlated to mean receptor density. |
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.