A fundamental problem in neuroscience and medicine is to understand the mechanisms of general anesthesia. This proposal, """"""""Multimodal Functional Imaging of Auditory Perception Under General Anesthesia"""""""", is submitted in response to the NINDS program announcement for Mentored Quantitative Research Career Development Awards (K25). The candidate seeks to gain training in the neurobiology and clinical pharmacology of anesthesia in order to apply multimodal functional imaging methods to the study of the mechanisms of general anesthesia. Loss of consciousness under general anesthesia is measured clinically by observing the loss of response to external stimuli. However, auditory perception and memory are possible in patients who are clinically unconscious, which may result in post-operative recall of events during anesthesia. Consequences of post-operative recall include sleep disturbances, dreams, nightmares, flashbacks and anxiety, as well as post-traumatic stress disorder. Clinical anesthetic brain monitors are based on empirical relationships between stereotyped anesthesia-related electroencephalographic (EEG) patterns and clinical assessments of patient awareness, but cannot measure activity within functional brain regions responsible for auditory perception under anesthesia. The goal of this project is to characterize anesthesia-induced changes of function in the auditory system using simultaneous EEG and fMRI. FMRI responses to perception of sound temporal envelope will be measured at varying levels of propofol anesthesia, ranging from light sedation to deep anesthesia, with simultaneous EEG. Changes in auditory perceptual processing measured with fMRI will be related to clinical level of consciousness, propofol drug levels, and anesthesia-related EEG patterns. These studies will provide a means to quantify the amount of perceptual processing that occurs after anesthesia-induced loss of consciousness, as well as the EEG patterns that correlate with loss of perceptual processing. Through this research project, as well as didactic courses and tutorials, the candidate will be trained in the neurobiology and clinical pharmacology of anesthesia. The training provided by this Award will help the candidate achieve the long-term career goal of leading an independent biomedical research program to study the systems neuroscience of anesthesia. General anesthesia is administered to over 50,000 patients daily for medical and surgical procedures, but its basic brain mechanisms are not known. Despite safety improvements, anesthesia results in serious side effects such as cardio-respiratory depression or post-operative recall. Through these studies, we hope to begin developing the fundamental neuroscience knowledge necessary to improve anesthetic drugs and monitoring, and to one day solve the problem of anesthesia-related morbidity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Mentored Quantitative Research Career Development Award (K25)
Project #
5K25NS057580-03
Application #
7640739
Study Section
NST-2 Subcommittee (NST)
Program Officer
Babcock, Debra J
Project Start
2007-06-01
Project End
2012-05-31
Budget Start
2009-06-01
Budget End
2010-05-31
Support Year
3
Fiscal Year
2009
Total Cost
$177,012
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Mukamel, Eran A; Pirondini, Elvira; Babadi, Behtash et al. (2014) A transition in brain state during propofol-induced unconsciousness. J Neurosci 34:839-45
Wong, Kin Foon Kevin; Smith, Anne C; Pierce, Eric T et al. (2014) Statistical modeling of behavioral dynamics during propofol-induced loss of consciousness. J Neurosci Methods 227:65-74
Krishnaswamy, Pavitra; Bonmassar, Giorgio; Purdon, Patrick L et al. (2013) Reference-free harmonic regression technique to remove EEG-fMRI ballistocardiogram artifacts. Conf Proc IEEE Eng Med Biol Soc 2013:5426-9
Vijayan, Sujith; Ching, Shinung; Purdon, Patrick L et al. (2013) Thalamocortical mechanisms for the anteriorization of ? rhythms during propofol-induced unconsciousness. J Neurosci 33:11070-5
Brown, Emery N; Purdon, Patrick L (2013) The aging brain and anesthesia. Curr Opin Anaesthesiol 26:414-9
Purdon, Patrick L; Pierce, Eric T; Mukamel, Eran A et al. (2013) Electroencephalogram signatures of loss and recovery of consciousness from propofol. Proc Natl Acad Sci U S A 110:E1142-51
Vijayan, Sujith; Ching, ShiNung; Purdon, Patrick L et al. (2013) Biophysical Modeling of Alpha Rhythms During Halothane-Induced Unconsciousness. Int IEEE EMBS Conf Neural Eng :1104-1107
Brandon Westover, M; Shafi, Mouhsin M; Ching, Shinung et al. (2013) Real-time segmentation of burst suppression patterns in critical care EEG monitoring. J Neurosci Methods 219:131-41
Ching, Shinung; Purdon, Patrick L; Vijayan, Sujith et al. (2012) A neurophysiological-metabolic model for burst suppression. Proc Natl Acad Sci U S A 109:3095-100
Pirondini, E; Babadi, B; Lamus, C et al. (2012) A spatially-regularized dynamic source localization algorithm for EEG. Conf Proc IEEE Eng Med Biol Soc 2012:6752-5

Showing the most recent 10 out of 23 publications