General anesthetics are routinely used to induce unconsciousness, and much is known about their effects on receptor function and single neuron activity. Much less is known about how these local effects are manifest at the whole-brain level nor how they influence network dynamics, especially past the point of induced unconsciousness. Using resting-state functional magnetic resonance imaging (fMRI) with nonhuman primates, we investigated the dose-dependent effects of anesthesia on whole-brain temporal modular structure, following loss of consciousness. We found that higher isoflurane dose was associated with an increase in both the number and isolation of whole-brain modules, as well as an increase in the uncoordinated movement of brain regions between those modules. Conversely, we found that higher dose was associated with a decrease in the cohesive movement of brain regions between modules, as well as a decrease in the proportion of modules in which brain regions participated. Moreover, higher dose was associated with a decrease in the overall integrity of networks derived from the temporal modules, with the exception of a single, sensory-motor network. Together, these findings suggest that anesthesia-induced unconsciousness results from the hierarchical fragmentation of dynamic whole-brain network structure, leading to the discoordination of temporal interactions between cortical modules.
Bibliographical noteFunding Information:
Canadian Institutes of Health Research (CIHR) (MOP126158 to J.P.G., MOP89785 to S.E., and PRG-165679 to R.M.); This research has been funded by the European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie grant agreement No 798255. Natural Sciences and Engineering Research Council (NSERC) graduate award (to C.N.A.). NSERC Discovery Grant, as well as funding from the Canadian Foundation for Innovation (to J.P.G.).
© The Author(s) 2020. Published by Oxford University Press. All rights reserved.
Copyright 2020 Elsevier B.V., All rights reserved.
- resting-state functional MRI
- unconsciousnesswhole-brain dynamics
ASJC Scopus subject areas
- Cognitive Neuroscience
- Cellular and Molecular Neuroscience