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dc.contributor.authorLuppi, Andrea
dc.contributor.authorMediano, Pedro AM
dc.contributor.authorRosas, Fernando E
dc.contributor.authorAllanson, Judith
dc.contributor.authorPickard, John D
dc.contributor.authorWilliams, Guy
dc.contributor.authorCraig, Michael
dc.contributor.authorFinoia, Paola
dc.contributor.authorPeattie, Alexander
dc.contributor.authorCoppola, Peter
dc.contributor.authorOwen, Adrian M
dc.contributor.authorNaci, Lorina
dc.contributor.authorMenon, David
dc.contributor.authorBor, Daniel
dc.contributor.authorStamatakis, Emmanuel Andreas
dc.date.accessioned2022-05-23T01:02:50Z
dc.date.available2022-05-23T01:02:50Z
dc.date.issued2022-04-20
dc.identifier.issn2399-3642
dc.identifier.other35444252
dc.identifier.otherPMC9021270
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/337387
dc.descriptionFunder: Evelyn Trust
dc.descriptionFunder: James S. McDonnell Foundation
dc.description.abstractThe 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.
dc.description.sponsorshipThe 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.
dc.languageeng
dc.publisherNature Research
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 101719179
dc.sourceessn: 2399-3642
dc.subjectBrain
dc.subjectHumans
dc.subjectUnconsciousness
dc.subjectPropofol
dc.subjectAnesthesia
dc.subjectConsciousness
dc.titleWhole-Brain Modelling Identifies Distinct but Convergent Paths to Unconsciousness in Anaesthesia and Disorders of Consciousness
dc.typeArticle
dc.date.updated2022-05-23T01:02:50Z
prism.issueIdentifier1
prism.publicationNameCommunications Biology
prism.volume5
dc.identifier.doi10.17863/CAM.84801
dcterms.dateAccepted2022-03-08
rioxxterms.versionofrecord10.1038/s42003-022-03330-y
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidLuppi, Andrea I [0000-0002-3461-6431]
dc.contributor.orcidMediano, Pedro AM [0000-0003-1789-5894]
dc.contributor.orcidRosas, Fernando E [0000-0001-7790-6183]
dc.contributor.orcidPickard, John D [0000-0002-5762-6667]
dc.contributor.orcidWilliams, Guy B [0000-0001-5223-6654]
dc.contributor.orcidFinoia, Paola [0000-0002-3908-9255]
dc.contributor.orcidPeattie, Alexander RD [0000-0003-2115-7640]
dc.contributor.orcidCoppola, Peter [0000-0002-8658-7409]
dc.contributor.orcidOwen, Adrian M [0000-0002-5738-3765]
dc.contributor.orcidNaci, Lorina [0000-0001-9630-3978]
dc.contributor.orcidMenon, David K [0000-0002-3228-9692]
dc.contributor.orcidStamatakis, Emmanuel A [0000-0001-6955-9601]
dc.identifier.eissn2399-3642
pubs.funder-project-idMedical Research Council (MR/M009041/1)
pubs.funder-project-idWellcome Trust (210920/Z/18/Z)
cam.issuedOnline2022-04-20


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International