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dc.contributor.advisorEmery N. Brown.en_US
dc.contributor.authorLewis, Laura D. (Laura Diane)en_US
dc.contributor.otherMassachusetts Institute of Technology. Department of Brain and Cognitive Sciences.en_US
dc.date.accessioned2014-05-23T19:33:35Z
dc.date.available2014-05-23T19:33:35Z
dc.date.copyright2014en_US
dc.date.issued2014en_US
dc.identifier.urihttp://hdl.handle.net/1721.1/87460
dc.descriptionThesis: Ph. D., Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2014.en_US
dc.descriptionCataloged from PDF version of thesis.en_US
dc.descriptionIncludes bibliographical references.en_US
dc.description.abstractDuring sleep and general anesthesia, the brain enters a state of decreased arousal and consciousness is transiently suspended. How this transition occurs is a fundamental and unsolved question in neuroscience. The neural dynamics that disrupt consciousness have not been identified, and the circuit mechanisms that generate these dynamics remain unknown. Furthermore, understanding the neural basis of sleep and anesthesia is key to improving clinical monitoring of patients undergoing general anesthesia and to advancing treatments of sleep disorders and neurological conditions such as coma. In this thesis, I combine intracranial electrophysiology in human subjects with optogenetic manipulation of thalamocortical circuits in mice to identify the neural dynamics underlying sleep and anesthesia. I first show that loss of consciousness during propofol general anesthesia is associated with the abrupt onset of slow oscillations that disrupt cortical networks. I then demonstrate that activation of the thalamic reticular nucleus generates slow wave activity and decreases arousal state, identifying a causal mechanism that generates physiological and behavioral signs of sleep. Finally, I study patients undergoing deep general anesthesia at levels corresponding to medically induced coma, and show that this state is marked by local cortical dynamics consistent with impaired cerebral metabolism. Taken together, these results identify a set of neural dynamics associated with unconscious states, and demonstrate specific mechanisms for how they disrupt brain function. These findings provide new insight into the neuroscience of arousal states, and suggest clinical approaches that could improve patient care.en_US
dc.description.statementofresponsibilityby Laura D. Lewis.en_US
dc.format.extent138 pagesen_US
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsM.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582en_US
dc.subjectBrain and Cognitive Sciences.en_US
dc.titleBrain states and circuit mechanisms underlying sleep and general anesthesiaen_US
dc.typeThesisen_US
dc.description.degreePh. D.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciences.en_US
dc.identifier.oclc879661658en_US


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