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

Abstract

SUMMARYObjective: To investigate the abortion of seizure generation using "minimal" intervention in hippocampi using two rat models of human temporal lobe epilepsy. Methods: The recording or stimulation electrodes were implanted into both hippocampi (CA1 area). Using the kainic acid (chronic: experiment duration 24 days) and the 4-aminopyridine (acute: experiment duration 2 h) models of paroxysms in rats, a real-time feedback stimulation paradigm was implemented, which triggered a short periodic electrical stimulus (5 Hz for 5 s) 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. Results: 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. Significance: 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.

Seizure detection and neuromodulation: A summary of data presented at the XIII conference on new antiepileptic drug and devices (EILAT XIII)

“…The stimulation current was chosen according to safety considerations, which was three times lower than the maximum deliverable charge per phase. (Shannon, 1992) This report summarizes key findings previously reported by us (Salam et al, 2015) and expands on the mechanisms of action of the proposed neurostimulation therapy based on early seizure detection.…”

All together now: Analogies between chimera state collapses and epileptic seizures

“…On the other hand, this is in keeping with the hypothesis that methods directed at increasing synchronization might help to control epileptic seizures 34 35 . To exploit the principles of our closed-loop schemes to control epileptic seizures will require identifying and precisely targeting the brain regions corresponding to the low-coherence group, for example by intracranial focal electrical neurostimulation 50 . Notwithstanding these challenges, the prospect of control can have far-reaching implications, beyond epileptic seizures.…”

Neural Synchronization from the Perspective of Non-linear Dynamics

“…This has important implications for seizure control, given that such simple models can be studied using non-linear dynamics both theoretically and in simulations. For example, such models can be used for seizure cancelation in medical settings, through the implementation of feedback control systems that could induce desynchronization of the thalamocortical network as it was recently achieved in other in vivo seizure models using a feedback, or closed-loop, protocol (Salam et al, 2015 ).…”