Although the field of anesthesiology has played a leadership role in promoting patient safety, there is still no standard monitor for the target orga of general anesthesia: the brain. The lack of reliable neurophysiologic monitoring can result in patient complications because of insufficient anesthesia (e.g., awareness and post- traumatic stress disorder) as well as excessive anesthesia (e.g., delayed emergence, delirium, neurotoxicity). A number of commercially-available brain monitors are currently used in the operating room, but such devices have shown limited utility and are often based on proprietary or empirical algorithms. Recent advances in neurobiology herald the possibility of a more sophisticated era of brain monitoring and improved patient safety. What is needed is the identification of measurable neurophysiological features of general anesthesia that are informed by the neurobiology of consciousness. We have gathered compelling data in human surgical patients that frontal-to-parietal connectivity in the brain is suppressed by all major classes of anesthetics. However, important questions remain regarding the measurement of information transfer in the brain, the underlying neural mechanisms of this suppressed connectivity and the clinical relevance of the findings. The objective for this application is a deeper understanding of the neurobiological principles of cortical connectivity patterns during consciousness and anesthesia as well as the relevance of such patterns for clinical care. We will achieve this objective by conducting innovative studies with computational brain network models, mechanistic experiments in the non-human primate brain, and a clinical study of surgical patients throughout the perioperative period. These studies will have a positive impact by advancing the neurobiology of anesthetic mechanisms, advancing network science in general, and making a key translational step toward novel brain monitoring strategies for surgical and critical care patients.

Public Health Relevance

This project is relevant to public health because it seeks to understand how general anesthetics affect the brain and how this can best be measured. Gaining a more detailed knowledge of anesthesia and the brain will help improve patient care through better monitoring in the operating room and the development of safer anesthetic drugs.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM098578-08
Application #
9693734
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Justinova, Zuzana
Project Start
2011-07-01
Project End
2021-05-31
Budget Start
2019-06-01
Budget End
2021-05-31
Support Year
8
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Lee, UnCheol; Mashour, George A (2018) Role of Network Science in the Study of Anesthetic State Transitions. Anesthesiology 129:1029-1044
Kim, Hyoungkyu; Moon, Joon-Young; Mashour, George A et al. (2018) Mechanisms of hysteresis in human brain networks during transitions of consciousness and unconsciousness: Theoretical principles and empirical evidence. PLoS Comput Biol 14:e1006424
Mashour, George A; Hudetz, Anthony G (2018) Neural Correlates of Unconsciousness in Large-Scale Brain Networks. Trends Neurosci 41:150-160
Pal, Dinesh; Dean, Jon G; Liu, Tiecheng et al. (2018) Differential Role of Prefrontal and Parietal Cortices in Controlling Level of Consciousness. Curr Biol 28:2145-2152.e5
Mashour, George A; Hudetz, Anthony G (2017) Bottom-Up and Top-Down Mechanisms of General Anesthetics Modulate Different Dimensions of Consciousness. Front Neural Circuits 11:44
Moon, Joon-Young; Kim, Junhyeok; Ko, Tae-Wook et al. (2017) Structure Shapes Dynamics and Directionality in Diverse Brain Networks: Mathematical Principles and Empirical Confirmation in Three Species. Sci Rep 7:46606
Kim, Minkyung; Kim, Seunghwan; Mashour, George A et al. (2017) Relationship of Topology, Multiscale Phase Synchronization, and State Transitions in Human Brain Networks. Front Comput Neurosci 11:55
Pal, Dinesh; Silverstein, Brian H; Lee, Heonsoo et al. (2016) Neural Correlates of Wakefulness, Sleep, and General Anesthesia: An Experimental Study in Rat. Anesthesiology 125:929-942
Hudetz, Anthony G; Mashour, George A (2016) Disconnecting Consciousness: Is There a Common Anesthetic End Point? Anesth Analg 123:1228-1240
Kim, Minkyung; Mashour, George A; Moraes, Stefanie-Blain et al. (2016) Functional and Topological Conditions for Explosive Synchronization Develop in Human Brain Networks with the Onset of Anesthetic-Induced Unconsciousness. Front Comput Neurosci 10:1

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