A predictive epilepsy index based on probabilistic classification of interictal spike waveforms

Quantification of interictal spikes in EEG may provide insight on epilepsy disease burden, but manual quantification of spikes is time-consuming and subject to bias. We present a probability-based, automated method for the classification and quantification of interictal events, using EEG data from kainate- and saline-injected mice (C57BL/6J background) several weeks post-treatment. We first detected high-amplitude events, then projected event waveforms into Principal Components space and identified clusters of spike morphologies using a Gaussian Mixture Model. We calculated the odds-ratio of events from kainate- versus saline-treated mice within each cluster, converted these values to probability scores, P(kainate), and calculated an Hourly Epilepsy Index for each animal by summing the probabilities for events where the cluster P(kainate) > 0.5 and dividing the resultant sum by the record duration. This Index is predictive of whether an animal received an epileptogenic treatment (i.e., kainate), even if a seizure was never observed. We applied this method to an out-of-sample dataset to assess epileptiform spike morphologies in five kainate mice monitored for ~1 month. The magnitude of the Index increased over time in a subset of animals and revealed changes in the prevalence of epileptiform (P(kainate) > 0.5) spike morphologies. Importantly, in both data sets, animals that had electrographic seizures also had a high Index. This analysis is fast, unbiased, and provides information regarding the salience of spike morphologies for disease progression. Future refinement will allow a better understanding of the definition of interictal spikes in quantitative and unambiguous terms.