Use this URL to cite or link to this record in EThOS:
Title: Investigating the role of Gamma-aminobutyric acid (GABA) in sedation : a combined electrophysiological, haemodynamic and spectroscopic study in humans
Author: Saxena, Neeraj
ISNI:       0000 0004 7224 1639
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2018
Availability of Full Text:
Access from EThOS:
Access from Institution:
A better understanding of the mechanisms of anaesthesia and sedation are expected not only to improve the understanding of the neural correlates of consciousness but also to help improve safety from the complications of anaesthesia/sedation and develop safer drugs and objective brain function monitoring systems. Neuroimaging modalities such as functional MRI, magnetoencephalography and MR spectroscopy provide complimentary information about brain functions and can help interrogate brain activity in a living human brain. Most anaesthetic drugs act by enhancing the inhibitory actions of GABA in the brain. Most neuroimaging research has focused on anaesthetic-induced unconsciousness, with only few investigating the earliest levels of sedation-induced altered consciousness. The work in this thesis used a range of advanced neuroimaging modalities to investigate the role of GABA (through a GABA-ergic drug, propofol), during mild sedation, in humans. This was performed as a series of experiments within two, sequential, scanning sessions, MEG followed by fMRI, in the same participants. Propofol resulted in a dissociation of the visual gamma band response (decreased evoked, increased induced power). This was related to a reduced BOLD fMRI response but there were no changes in MRS detectable GABA concentration. Response to multisensory stimulation also revealed interesting changes with MEG and fMRI. Functional connectivity analyses showed changes in connectivities of the posterior cingulate cortex (key hub of default-mode network) and thalamus with each other and other key brain regions. Resting state networks were identified with MEG too, which revealed interesting increases in connectivity in certain band- limited networks while motor networks showed no change. Perfusion fMRI using arterial spin labelling revealed a global and regional reduction in perfusion, highlighting some of the key regions (frontal cortex, precuenus, PCC and thalamus) involved in sedation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available