Abstracts

Rationale: Intractable epilepsy that remains resistant to drug treatment is a significant public health problem with very few alternative therapeutic options besides surgery. Our laboratory has been exploring protocols by which electrical stimulation applied to a seizure focus could modulate an epileptic seizure and, ideally, terminate it. We have previously reported (Epilepsia, 2007) that control stimulation using a proportional feedback algorithm with variable feedback gain can be used to suppress although not revert epileptic seizures in the in vivo rat brain. We have more recently begun to investigate the use of feedback stimulation utilizing a phase resetting protocol to stop the progression of a seizure following induction in the in vivo rat hippocampus. Methods: The phase-resetting algorithm uses precisely timed current-neutral pulses whose timing is based upon real-time analysis of electrical activity measured proximal to the seizure focus. Recording and stimulation occurs using separate electrodes implanted in the CA3 region of rat hippocampus. Seizure induction occurs via focal injection of kainic acid proximal to the electrodes. A major element of the hypothesis for applying such phase resetting protocols is that neuronal activity at or near a focus during a seizure sees a significant elevation in synchronous behavior. Precisely timed current stimuli may provide an effective means at disrupting the highly coherent neural activation. Dominant neural frequencies of the intracranial EEG are first determined using Fourier analysis.Results: The effectiveness of several stimulation parameters on reverting seizure activity are currently being examined. These parameters include: phase relationship (Φ) during stimulation application, number of stimulus pulses, pulse duration and profile, and dominant vs. harmonic frequencies. Changes in phase coherence, Teager energy, and EEG amplitude variance are being used to assess the effects of different stimulation parameters on seizure disruption. Conclusions: The use of a control feedback protocol provides a means to adjust stimulation based upon the real-time behavior of the epileptic focus so that different seizure etiologies and system nonstationarities can be adequately addressed. Furthermore, such stimulation would only be applied acutely on demand. If successful, this technique could provide an alternative therapy for seizure control in cases of intractable epilepsy.