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Epilepsy is a chronic condition characterized by recurrent unprovoked seizures with potentially disabling effects. These seizures, even when generated from a single focus, are believed to involve an extensive network of regions across the brain (Norden & Blumenfeld 2002). The propagation across these networks is responsible for the complex events associated with seizures including altered consciousness and motor phenomena. Additionally, repeated seizures can also produce chronic deficits that persist in between seizures, mainly cognitive deficits, primarily of memory and language related functions (Helmstaedter, et al. 2003). It is likely that these cognitive effects can be related to measurable brain network alterations as well. The non-invasive quantification of alterations in brain networks related to epilepsy is critical in determining the mechanisms of epileptogenesis and its treatments. In addition, it may also identify imaging biomarkers of epilepsy which can be used to diagnose and monitor these patients. Electroencephalography (EEG) is the most widely used method to quantify epileptic activity across the brain. The high temporal resolution of EEG measurements is advantageous in detecting the electrophysiological activity that defines the seizure focus and associated network. However, these techniques have relatively low spatial resolution when performed non-invasively, and can be corrupted by attenuation of the signal by bone or other tissue. Invasive EEG monitoring can measure electrical activity directly from the cortex, but the spatial resolution is still relatively low. The recording can only be obtained from preselected regions of the cortex. This method also involves more significant risk than non-invasive methods, but can be useful in detecting limited networks of epileptic activity (Blumenfeld, et al. 2004b, Englot, et al. 2008, Guye, et al. 2006). Imaging methodologies make it possible to investigate networks across the whole brain without the need for identifying predefined regions. Some non-invasive, low spatial resolution techniques to detect epileptic networks include interictal positron emission tomography (PET) with [18F] fluoro-2-deoxy-glucose (FDG) (Cascino & Jack 1996, Spencer & Bautista 2000) and ictal single-photon emission computed tomography (SPECT) imaging (Cascino & Jack 1996, Spencer & Bautista 2000). In general, these methods attempt to detect regions of metabolic (PET) or perfusion (SPECT) changes during the interictal state or ictal events. Studies have detected widespread brain networks associated with seizures using

Investigations of Brain Network Alterations in Epilepsy Using Functional Magnetic Resonance Imaging