Brain Network Mechanism of Fast and Slow Recoveries in Pharmacologically and Pathologically Induced Unconsciousness

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Project Summary/Abstract It is not understood why some patients recover from unconsciousness (anesthesia and coma) at a relatively faster rate while others show prolonged recovery times; or do not recover at all from coma. Traditionally, the approaches to fill this critical gap in our knowledge has focused on the subcortical nuclei linked to the states of arousal (sleep, wake, anesthesia), but recent neuroimaging studies suggest that consciousness, rather than being a product of a localized neural circuit, is likely to be an emergent phenomenon resulting from complex interactions between spatially and temporally distributed activity of neurons across the brain. Accumulating evidences suggest that criticality, an optimal balanced state between order and disorder, in the brain presents highly informative, integrative, and sensitive state such that it has been suggested as a necessary condition for the emergence of consciousness. We recently demonstrated that the level of consciousness during general anesthesia correlates with the degree of brain criticality, and similar findings have been reported from other groups. Therefore, we hypothesize that facilitating the brain networks towards criticality will accelerate the recovery of consciousness from anesthesia and disorders of consciousness. However, controlling criticality is a challenging problem and has not been attempted in the brain networks. Using a novel approach, we will apply explosive synchronization, a phenomenon wherein a small perturbation to a network can lead to an abrupt state transition through global network synchronization, to control brain criticality. By reconceptualizing the mechanism of explosive synchronization as a mechanism of criticality transition, we will be able to systematically study fast and slow transitions in brain criticality and the effect on state transitions. Our long-term goal is to use the principles of physics to develop neuroscientific foundations for the strategies to accelerate the recovery from anesthesia and coma. The objective of the proposed studies is to explore explosive synchronization as a mechanism for the recovery of consciousness. The rationale for the proposed research is that characterization of the relationship between criticality transition and fast/slow recovery of consciousness will provide insights into the fundamental network level mechanisms that govern fast and slow state transitions and will also help inform translational studies aimed at accelerating recovery from unconsciousness. We will pursue the following two specific aims: 1) Determine the relationship between explosive synchronization in the brain networks and the recovery of consciousness from anesthesia and coma. We will use computational modeling to identify the brain network conditions linked to fast and slow state transitions, and test the model predictions using empirical data from anesthesia (human and rat) and coma (human) studies. 2) Determine the causal effect of changes in brain network criticality on the recovery of consciousness from anesthesia in rat. We will use our recently reported rat models of fast and slow recovery of consciousness from anesthesia to investigate a causal relationship between recovery of consciousness and brain criticality.