Whole-brain modelling identifies distinct but convergent paths to unconsciousness in anaesthesia and disorders of consciousness

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Luppi, Andrea I 
Mediano, Pedro AM 
Rosas, Fernando E 
Allanson, Judith 

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.


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)

Article, /631/378/116/2392, /631/378/116/2393, /631/378/116/1925, /631/378/2649/1398, /59/36, /59/78, /59/57, article
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Communications Biology
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Nature Publishing Group UK
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)