Investigating resting-state functional connectivity in health and epilepsy using magnetonencephalography

It is now widely accepted that different areas of the brain are functionally connected even in the absence of explicit task demands, the so-called 'resting-state'. Differences in resting-state connectivity between groups are increasingly used as a marker of pathology in a number of neurological diseases and neuropsychiatric disorders. However, in order for a specific pattern of functional connectivity to represent a valid biomarker, it must be proven to be stable and reliably measurable in the absence of disease or disorder. Further, much is still unknown about the biological basis and purpose of resting-state activity, that may help to elucidate the functional relevance in patient groups. Magnetoencephalography (MEG) is a technique that is well suited to the study of resting-state connectivity because it provides a direct inference of synchronised neuronal activity. In chapter two of this thesis, the test-retest repeatability of two different approaches to assessing functional coupling of brain areas using MEG is examined. Having established a preferential analysis pipeline, chapter three compares frequency band-limited MEG connectivity with functional connectivity derived from BOLD-fMRI data. The connectivity pipeline is then used for two different applications. First, the approach is combined with pharmacological intervention in healthy subjects in order to investigate the role of AMPA receptors in the glutamate system on the MEG signal and functional connectivity (chapter four). The final experimental chapter focuses on comparing functional connectivity in a group of generalised epilepsy patients with age- and gender-matched healthy control subjects. Taken together, the results of this thesis have implications for the study of functional connectivity in the resting-state using MEG, particularly the sensitivity of the technique to microscale as well as macroscale change