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Thesis

Understanding loss of consciousness under general anaesthesia using multimodal neuroimaging

Abstract:

Despite major advancements in consciousness science over the past few decades, how anaesthesia causes loss of consciousness remains incompletely understood and the translation from basic science to clinical practice has been limited. Recent concurrent electroencephalography (EEG) and functional magnetic resonance imaging (FMRI) evidence indicates that a state of complete perception loss is achieved under general anaesthesia when slow wave activity in the brain reaches saturation. Slow wave activity saturation (SWAS) is therefore a potentially clinically relevant end point for titration of anaesthesia.

We have developed a prototype system for titrating anaesthesia to SWAS within an individual. The system features EEG and anaesthesia data input, modelling of slow wave power and detection of SWAS, and visualisation of the model output in a graphical user interface. The prototype system was applied in a patient pre-surgery study (Study 1) which focused on clinical translation of SWAS, and a healthy volunteer EEG-MRI study (Study 2) which focused on experimental validation of SWAS.

We successfully applied the prototype SWAS system in twelve patients (Study 1) and twenty-three healthy volunteers (Study 2). No subjects in either Study 1 or Study 2 were behaviourally responsive when held at SWAS and none had recall of events from when they were held at SWAS.

In Study 2, we also acquired measures of cerebral blood flow (CBF), and resting and task-related FMRI data during wakefulness and when held at SWAS. When held at the SWAS state, CBF was significantly elevated compared to wakefulness. Furthermore, we found that the brain was unresponsive to external stimulation when held at SWAS even when controlling for the observed CBF changes. Finally, we found that this was accompanied by disruption of functional connectivity in the thalamocortical system and in known resting state networks. Our findings provide further evidence that SWAS is a state of perception loss and a clinically relevant target for surgical anaesthesia.

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Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Sub department:
Clinical Neurosciences
Research group:
WIN
Oxford college:
Keble College
Role:
Author
ORCID:
0000-0002-9066-1165

Contributors

Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Sub department:
Clinical Neurosciences
Research group:
WIN
Oxford college:
St Cross College
Role:
Supervisor
ORCID:
0000-0002-6268-487X
Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Sub department:
Clinical Neurosciences
Research group:
WIN
Oxford college:
St Hilda's College
Role:
Supervisor
ORCID:
0000-0003-3234-5639
Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Sub department:
Clinical Neurosciences
Research group:
WIN
Oxford college:
Merton College
Role:
Supervisor
ORCID:
0000-0003-4134-6115


More from this funder
Funder identifier:
https://ror.org/019w4f821
Funding agency for:
Warnaby, C
Grant:
H2020-FETOPEN-2014-2015-RIA
Programme:
Horizon 2020
More from this funder
Funder identifier:
https://ror.org/03x94j517
Funding agency for:
Warnaby, C
Grant:
MR/R006423/1
Programme:
Development Pathway Funding Scheme
More from this funder
Funding agency for:
Holmgren, J
Grant:
N/A
Programme:
Aker Scholarship


DOI:
Type of award:
DPhil
Level of award:
Doctoral
Awarding institution:
University of Oxford

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