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

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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.



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Commun Biol

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Springer Science and Business Media LLC
Medical Research Council (MR/M009041/1)
Wellcome Trust (210920/Z/18/Z)
The authors would like to thank all the participants for their contribution to this study. This work was supported by grants from the UK Medical Research Council [U.1055.01.002.00001.01 to AMO and JDP]; The James S. McDonnell Foundation [to AMO and JDP]; and the Canada Excellence Research Chairs program (215063 to AMO); the National Institute for Health Research (NIHR, UK), Cambridge Biomedical Research Centre and NIHR Senior Investigator Awards [to DKM], the Stephen Erskine Fellowship (Queens’ College, Cambridge, to EAS), the Canadian Institute for Advanced Research (CIFAR; grant RCZB/072 RG93193) (to DKM and EAS); the L’Oreal-Unesco for Women in Science Excellence Research Fellowship to LN; the British Oxygen Professorship of the Royal College of Anaesthetists [to DKM]; The Evelyn Trust, Cambridge and the EoE CLAHRC fellowship [JA]; the Gates Cambridge Trust (to AIL); the Cambridge International Trust and the Howard Sidney Sussex Studentship (to MMC); and the Vice-Chancellor Award (to PC). AMO and DKM are Fellows of the CIFAR Brain, Mind, and Consciousness Programme. PAM and DB are funded by the Wellcome Trust (grant no. 210920/Z/18/Z). FR is funded by the Ad Astra Chandaria foundation. Computing infrastructure at the Wolfson Brain Imaging Centre (WBIC-HPHI) was funded by the MRC research infrastructure award (MR/M009041/1). The research was also supported by the NIHR Brain Injury Healthcare Technology Co-operative based at Cambridge University Hospitals NHS Foundation Trust and University of Cambridge.