Development and Application of Functional Magnetic Resonance Imaging in Paediatric Focal Epilepsy

There are two major applications of fMRI in paediatric focal epilepsy. The first is mapping of eloquent cortex. The second is the use of simultaneous EEG-fMRI to map the epileptogenic zone. The main methodological issues faced by these fMRI applications are: motion, physiological noise, quality assurance, and statistical analysis. To address the issues of subject motion and physiological noise we constructed a simple analytical biophysical model of Blood Oxygenation Level Dependent (BOLD) signal capable of identifying and correcting these artefacts (named FIACH). This model was validated in a sample of children performing a language task with high motion levels. FIACH outperformed 6 other competitive methods of noise control. In the second study, we characterized how metrics of quality assurance could predict the clinical utility of EEG-fMRI. We also quantified the impact of a natural stimulus (a cartoon) on reducing subject motion. During this analysis it was noted that the corrections for multiple comparisons employed using Random Field Theory (RFT) at an individual level were overly conservative. This led to an exploration of RFT sensitivity and its relationship to image smoothing and degrees of freedom. By reviewing over 150 papers published in 2016 it was possible to estimate that 80% of studies suffer from a similar loss in sensitivity. Simulations are provided to help identify and prevent this loss in sensitivity. In the final study we sought to use EEG-fMRI to characterize the relationship between the brain’s functional organization and Interictal Epileptiform Discharges (IEDs) in paediatric focal epilepsy. Interestingly, we identified increasing connectivity of the piriform cortex and caudate to the default mode network as a function of IEDs. This suggested a mechanism by which IEDs may propagate through functional networks in the brain