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Routes to arousal: a simultaneous EEG-FMRI investigation of pharmacological sedation in humans (Routes to Arousal)
Start date: Sep 15, 2010, End date: Sep 14, 2012 PROJECT  FINISHED 

Functional Magnetic Resonance Imaging studies have progressed from identifying areas of the brain involved in a given task to investigating the temporal correlation or ‘functional connectivity’ between signals from different brain regions. This permits spatial and temporal characterisation of cortical and subcortical functional circuits during the execution of tasks and at rest. Combining information from simultaneous EEG and FMRI measurements affords a still finer physiological fractionation of brain networks. Our main aim is to use simultaneous EEG-FMRI to examine altered functional connectivity during pharmacologically altered arousal in healthy human volunteers. We will focus on thalamo-cortical networks (TCN) and default mode network (DMN), both hypothesized to be involved in alterations in consciousness or arousal. A variety of neurochemical routes lead to reduced arousal. General anaesthetics may act through ligand-gated ion channels of the GABAA and NMDA receptors. In particular, GABAergic cells of the reticular thalamic nucleus may modulate cortical activity. Because vigilance decrements correlate with decreased blood flow in the medial thalamus, and because this reduction significantly covaries with parallel decreases in regions belonging to the DMN, we will study the possible progressive disconnections within each network (TCN and DMN) induced by light sedation (propofol), and the disruption of between-network connectivity. The use of simultaneous EEG to restrict our examination of drug effects in FMRI to those of neuronal origin will provide a robust tool with which to investigate anaesthetic action (reduced arousal) in these networks. By using time-series analysis techniques (phase slope index) we aim to further assess the dynamic changes induced by sedation in the direction of information flow among the nodes of these brain networks. This will improve our understanding of pharmacologically induced sedation at the system-level in the human brain.
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