Epilepsy, one of the most common serious neurological conditions, is characterized by spontaneous recurrent seizures, the catastrophic synchronization of brain activity. While anti-epileptic drugs are used as the first-line treatment, they fail in approximately 20–30% of patients. Further, this failure rate is dependent on the type of epilepsy and its cause. Malformations of the cortex have been highly correlated with epilepsy, with an estimated 75% of patients having a cortical malformation presenting with epilepsy at some point. Further, cortical malformations are typically less responsive to drug therapies. Although estimated to only exist in 14% of epilepsy patients, cortical malformations account for between 25–40% of all medically intractable childhood epilepsies.
While the normally laminated cortex has been studied for over 100 years, only more recently has attention been devoted to the malformed cortex. In order to study the role that cortical malformations play in epileptogenesis, animal models of cortical dysplasia, such as the in utero irradiated rat model, have been employed by researchers. Unfortunately, the bulk of this work has been focused on histological and intrinsic neuron property differences with little consideration given to the emergent network properties in dysplastic slices.
In this work I utilized the in utero irradiated rat model to induce cortical dysplasia and compared electrophysiological differences between normal and dysplastic cortex using microelectrode arrays (MEAs). Several metrics were used in the analysis and were categorized as classic, spatial, and novel. Classic metrics were those used by previous researchers to compare epileptiform activity in dysplastic and normally laminated cortices and included ictal event lengths, ictal event distributions, and number of field potentials per ictal event. Spatial metrics were those used by previous researchers to analyze normally laminated cortical slices but have not been applied to dysplastic slices or used to compare the two. New metrics consisted of the application of Granger Causality methods to the data, which have been used previously in neuroscience, but not to compare functional differences between normal and dysplastic tissue.
Results supported and expanded upon previous counter-intuitive and anecdotal evidence that low dose irradiated subjects are functionally more dissimilar from controls than high dose irradiated subjects. This was evidenced by key classic and spatial metrics, such as mean number of ictal events per recording time, mean event length, mean inter-event interval, bias in LFP extrema peaks during events, and wave speed propagation through cortical layers. Surprisingly, and of most potential clinical relevance, results from novel application of Granger Causality analysis to in vitro slice suggests that localized areas drive ictal activity when a dominant initiation site is absent and do not coincide with dominant initiation sites when present.