PT  - JOURNAL ARTICLE
AU  - Dominic Standage
AU  - Corson N. Areshenkoff
AU  - Joseph Y. Nashed
AU  - R. Matthew Hutchison
AU  - Melina Hutchison
AU  - Dietmar Heinke
AU  - Ravi S. Menon
AU  - Stefan Everling
AU  - Jason P. Gallivan
TI  - Dynamic reconfiguration, fragmentation and integration of whole-brain modular structure across depths of unconsciousness
AID  - 10.1101/783175
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 783175
4099  - http://biorxiv.org/content/early/2019/09/27/783175.short
4100  - http://biorxiv.org/content/early/2019/09/27/783175.full
AB  - 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 anaesthesia-induced unconsciousness results from the hierarchical fragmentation of dynamic whole-brain network structure, leading to the discoordination of temporal interactions between cortical modules.