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

Perturbations in a large-scale whole-brain model suggest that anesthesia and injury may be imparting functionally similar effects in terms of brain dynamics. 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.

Automated summary

Perturbations in a large-scale whole-brain model reveal that anesthesia and injury can have similar effects on brain dynamics. A computational model incorporating PET and diffusion MRI data shows that spatially-specific local inhibition and connectome perturbation play key roles in reproducing the brain activity observed during anesthesia and disorders of consciousness. These findings suggest common neurobiological mechanisms underlying these conditions.