Whole-brain modelling identifies distinct but convergent paths to unconsciousness in anaesthesia and disorders of consciousness
Authors
Luppi, Andrea I
Mediano, Pedro AM
Rosas, Fernando E
Allanson, Judith
Williams, Guy B
Craig, Michael M
Finoia, Paola
Peattie, Alexander RD
Coppola, Peter
Owen, Adrian M
Naci, Lorina
Menon, David K
Bor, Daniel
Stamatakis, Emmanuel A
Publication Date
2022-04-20Journal Title
Communications Biology
Publisher
Nature Publishing Group UK
Volume
5
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Luppi, A. I., Mediano, P. A., Rosas, F. E., Allanson, J., Pickard, J., Williams, G. B., Craig, M. M., et al. (2022). Whole-brain modelling identifies distinct but convergent paths to unconsciousness in anaesthesia and disorders of consciousness. Communications Biology, 5 (1) https://doi.org/10.1038/s42003-022-03330-y
Description
Funder: Evelyn Trust; doi: https://doi.org/10.13039/501100004282
Funder: James S. McDonnell Foundation (McDonnell Foundation); doi: https://doi.org/10.13039/100000913
Funder: Canadian Institute for Advanced Research (L'Institut Canadien de Recherches Avancées)
Abstract
Abstract: The human brain entertains rich spatiotemporal dynamics, which are drastically reconfigured when consciousness is lost due to anaesthesia or disorders of consciousness (DOC). Here, we sought to identify the neurobiological mechanisms that explain how transient pharmacological intervention and chronic neuroanatomical injury can lead to common reconfigurations of neural activity. We developed and systematically perturbed a neurobiologically realistic model of whole-brain haemodynamic signals. By incorporating PET data about the cortical distribution of GABA receptors, our computational model reveals a key role of spatially-specific local inhibition for reproducing the functional MRI activity observed during anaesthesia with the GABA-ergic agent propofol. Additionally, incorporating diffusion MRI data obtained from DOC patients reveals that the dynamics that characterise loss of consciousness can also emerge from randomised neuroanatomical connectivity. Our results generalise between anaesthesia and DOC datasets, demonstrating how increased inhibition and connectome perturbation represent distinct neurobiological paths towards the characteristic activity of the unconscious brain.
Keywords
Article, /631/378/116/2392, /631/378/116/2393, /631/378/116/1925, /631/378/2649/1398, /59/36, /59/78, /59/57, article
Sponsorship
Gates Cambridge Trust (OPP1144)
RCUK | MRC | Medical Research Foundation (MR/M009041/1)
University of Cambridge | Sidney Sussex College, University of Cambridge (Howard Sidney Sussex Studentship)
University of Cambridge (Vice-Chancellor Award)
RCUK | Medical Research Council (MRC) (U.1055.01.002.00001.01)
Canadian Institute for Advanced Research (L'Institut Canadien de Recherches Avancées) (Brain, Mind, and Consciousness Programme, RCZB/072 RG93193)
Canada Excellence Research Chairs, Government of Canada (Canada Excellence Research Chairs Program) (215063)
Royal College of Anaesthetists (RCoA) (British Oxygen Professorship)
Identifiers
s42003-022-03330-y, 3330
External DOI: https://doi.org/10.1038/s42003-022-03330-y
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336265
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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