Rapid brief feedback intracerebral stimulation based on real-time desynchronization detection preceding seizures stops the generation of convulsive paroxysms.

Abstract

To investigate the abortion of seizure generation using "minimal" intervention in hippocampi using two rat models of human temporal lobe epilepsy. The recording or stimulation electrodes were implanted into both hippocampi (CA1 area). Using the kainic acid (chronic: experiment duration 24days) and the 4-aminopyridine (acute: experiment duration 2h) models of paroxysms in rats, a real-time feedback stimulation paradigm was implemented, which triggered a short periodic electrical stimulus (5Hz for 5s) upon detecting a seizure precursor. Our seizure precursor detection algorithm relied on the monitoring of the real-time phase synchronization analysis, and detected/anticipated electrographic seizures as early as a few seconds to a few minutes before the behavioral and electrographic seizure onset, with a very low false-positive rate of the detection. The baseline mean seizure frequencies were 5.39 seizures per day (chronic) and 13.2 seizures per hour (acute). The phase synchrony analysis detected 88% (434 of 494) of seizures with a mean false alarm of 0.67 per day (chronic) and 83% (86 of 104) of seizures with a mean false alarm of 0.47 per hour (acute). The feedback stimulation reduced the seizure frequencies to 0.41 seizures per day (chronic) and 2.4 seizures per hour (acute). Overall, the feedback stimulation paradigm reduced seizure frequency by a minimum of 80% to a maximum of 100% in 10 rats, with 83% of the animals rendered seizure-free. This approach represents a simple and efficient manner for stopping seizure development. Because of the short on-demand stimuli, few or no associated side effects are expected in clinical application in patients with epilepsy. Abnormal synchrony patterns are common features in epilepsy and other neurologic and psychiatric syndromes; therefore, this type of feedback stimulation paradigm could be a novel therapeutic modality for use in various neurologic and psychiatric disorders.