CORE B. ADMINISTRATIVE CORE General anesthesia is a fascinating man-made, neurophysiological phenomenon that has been developed empirically over many years to enable safe and humane performance of surgical and non-surgical procedures. Specifically it is a drug-induced condition consisting of unconsciousness, amnesia, analgesia and immobility, along with physiological stability. General anesthesia is administered daily to 60,000 patients in the United States, the mechanisms for how anesthetics act in the brain to create the states of anesthesia are not well understood. Significant progress has been made recently in characterizing the molecular sites that anesthetics target. However, how actions at specific molecular targets lead to the behavioral states is less well understood. Addressing this issue requires a systems neuroscience approach to define how actions of the drugs at specific molecular targets and neural circuits lead to a behavioral state of general anesthesia. In this program project entitled, Integrated Systems Neuroscience Studies of Anesthesia, we will develop an integrated systems neuroscience program consisting of human, non-human primate, rodent and modeling studies of four anesthetics: the GABAA agents, propofol and sevoflurane; the alpha-2 adrenergic agonist, dexmedetomidine; and the NMDA receptor antagonist, ketamine. The program project will also include a DATA ANALYSIS CORE, which will provide assistant with data analysis and conduct research on statistical methods.
The Specific Aims are to understand how the actions of the anesthetics at specific molecular targets and neural circuits produce the oscillatory dynamics (EEG rhythms, changes in LFPs and neural spiking activity) that are likely a primary common mechanism through which anesthetics create altered states of arousal (sedation, hallucination, unconsciousness). This program project will be a unique research collaboration among anesthesiologists, neuroscientists, bioengineers, a neurosurgeon, a neurologist, a statistician and a mathematician at Massachusetts General Hospital and Boston University. The day-to-day management of this program project will require an active team of support staff to accomplish its several goals. The responsibilities of the administrative core will include day-to-day administrative and financial management, along with planning of bi- weekly program project meetings, bi-weekly Executive Committee meetings, and planning of the annual Scientific Advisory Committee meeting.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZGM1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
Cornelissen, L; Kim, S E; Lee, J M et al. (2018) Electroencephalographic markers of brain development during sevoflurane anaesthesia in children up to 3 years old. Br J Anaesth 120:1274-1286
Brown, Emery N; Pavone, Kara J; Naranjo, Marusa (2018) Multimodal General Anesthesia: Theory and Practice. Anesth Analg 127:1246-1258
Sherfey, Jason S; Soplata, Austin E; Ardid, Salva et al. (2018) DynaSim: A MATLAB Toolbox for Neural Modeling and Simulation. Front Neuroinform 12:10
Lewis, Laura D; Piantoni, Giovanni; Peterfreund, Robert A et al. (2018) A transient cortical state with sleep-like sensory responses precedes emergence from general anesthesia in humans. Elife 7:
Walsh, Elisa C; Lee, Johanna M; Terzakis, Kristina et al. (2018) Age-Dependent Changes in the Propofol-Induced Electroencephalogram in Children With Autism Spectrum Disorder. Front Syst Neurosci 12:23
Brown, E N; Purdon, P L; Akeju, O et al. (2018) Using EEG markers to make inferences about anaesthetic-induced altered states of arousal. Br J Anaesth 121:325-327
Akeju, Oluwaseun; Hobbs, Lauren E; Gao, Lei et al. (2018) Dexmedetomidine promotes biomimetic non-rapid eye movement stage 3 sleep in humans: A pilot study. Clin Neurophysiol 129:69-78
Soplata, Austin E; McCarthy, Michelle M; Sherfey, Jason et al. (2017) Thalamocortical control of propofol phase-amplitude coupling. PLoS Comput Biol 13:e1005879
Guidera, Jennifer A; Taylor, Norman E; Lee, Justin T et al. (2017) Sevoflurane Induces Coherent Slow-Delta Oscillations in Rats. Front Neural Circuits 11:36
Akeju, Oluwaseun; Brown, Emery N (2017) Neural oscillations demonstrate that general anesthesia and sedative states are neurophysiologically distinct from sleep. Curr Opin Neurobiol 44:178-185

Showing the most recent 10 out of 12 publications