Abstract

The ultimate goal of epileptology is the complete abolishment of epileptic seizures. This might be achieved by a system that predicts seizure onset combined with a system that interferes with the process that leads to the onset of a seizure. Seizure prediction remains, as of yet, unresolved in absence-epilepsy, due to the sudden onset of seizures. We have developed a real-time absence seizure prediction algorithm, evaluated it and implemented it in an on-line, closed-loop brain stimulation system designed to prevent the spike-wave-discharges (SWDs), typical for absence epilepsy, in a genetic rat model. The algorithm corretly predicted 88% of the SWDs while the remaining were quickly detected. A high number of false-positive detections occurred mainly during light slow-wave-sleep. Inclusion of criteria to prevent false-positives greatly reduced the false alarm rate but decreased the sensitivity of the algoritm. Implementation of the latter version into a closed-loop brain-stimulation-system resulted in a 72% decrease in seizure activity. In contrast to long standing beliefs that SWDs are unpredictable, these results demonstrate that they can be predicted and that the development of closed-loop seizure prediction and prevention systems is a feasable step towards interventions to attain control and freedom from epileptic seizures.

Highlights

  • Bilateral generalized spike and wave discharges (SWDs), the electrophysiological hallmark of absence epilepsy, are generated within the cortico-thalamo-cortical network[1,2,3]

  • 5–10 Hz frequency band, which implies that the spectral component of this EEG signal starts to synchronize between cortical layers and between cortex and thalamus

  • A high number of false positive predictions was noticed; they mainly occurred during light slow wave sleep, a state of alertness, in which neurons are slightly hyperpolarized and at high risk for seizure generation[9]

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Summary

Computer Interface

Interactions between the cortical and thalamic channel pairs increased and considering the power W(s, t)= ΠWi(s, t) (Fig. 1c) an isolated pattern (circles in Fig. 1c) corresponding to preictal precursor activity was noticed It showed that momentary changes in each EEG channel, taken for 4 (I) seconds and for ~0.5 seconds (II) before the onset of SWD indicated that an SWD was about to begin. The algorithm’s seizure prediction performance was evaluated with EEG recordings (four hours in duration) of WAG/Rij rats, a well validated genetic animal model of absence epilepsy as they experience several hundreds of spontaneously occuring SWDs per day. The precursors were automatically detected with the help of a set of logical conditions

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