Temporal Rearrangement of Pre-ictal PTZ Induced Spike Discharges by Low Frequency Electrical Stimulation to the Amygdaloid Complex

Abstract Background Epilepsy is a common neurological disease affecting over 40 million people worldwide. The foremost important challenge of epileptologists has been to control and predict the recurrent and spontaneous seizures of epileptic patients. The application of low frequency electrical stimulation (LFS) in deep brain structures has shown promising results in seizure control. However, the use of LFS as a probing strategy for seizure prediction, thus contributing to a closed loop solution, is still poorly explored. Objective To improve seizure prediction by producing gradually increasing phase-locked pre-ictal electrographical responses, due to the short-term plastic changes in epileptogenic neural networks, thus behaving as a "programmed" surrogate marker. Methods Urethane anesthetized rats were divided into 3 groups: the PTZ-noES group was injected with pentylenetetrazole (PTZ 4 mg/ml/min flow rate) i.v. without electrical stimulation (ES); the ES-noPTZ group received ES (0.5 Hz, 0.1 ms pulse width and 0.6 mA) to the amygdaloid complex and the PTZ + ES group received simultaneously i.v. PTZ infusion and ES. After each condition, electrographical parameters and c-Fos expression of regions of interest were evaluated. Results Although the PTZ + ES group had no evident change in the sustained electrographic seizure onset, duration and/or frequency spectrum; c-Fos labeling showed a different expression pattern when compared to the PTZ-noES and ES-noPTZ. Also, PTZ + ES formed a gradually increasing evoked potential; confirming the strong coupling of reverberant neural networks induced by ES – phase locked to stimuli. Conclusion ES induces a detectable temporal rearrangement of pre-ictal activity, which has suggestive applicability to seizure prediction.