Distinct Patterns of Temporally Coded Electrical Stimulation Interfere With Long-Range Interhemispheric Coupling in a Focal Model of Epilepsy.

Abstract

OBJECTIVES: This study investigated 1) epileptiform activity propagation triggered by intrahippocampal kainic acid (KA) injections, 2) whether low-frequency probing stimulation applied to the ipsilateral amygdaloid complex (AMY) would affect propagation, and 3) whether distinct temporal patterns of electrical stimulation applied to the contralateral amygdaloid complex interfere with the interhemispheric propagation pattern. MATERIALS AND METHODS: Electrical stimulation (ES) comprised a 100-μs pulse of 500 μA applied to the AMY. The Probing protocol applied a 2000-millisecond interpulse-interval (IPI) ES ipsilateral to KA injection. The Propagation protocol ES was applied contralateral to KA injection using temporally coded ES patterns: periodic stimulation (PS, with fixed 250-millisecond IPI or nonperiodic stimulation [NPS], power-law distributed IPIs constrained by a maximum of 4 pulses/s). Continuous local-field electrophysiologic data were recorded from AMY and hippocampus sites in both hemispheres. RESULTS: Our results show that probing stimulation to the ipsilateral amygdala does not interfere with the seizure propagation pattern; however, independent contralateral seizures were observed. Our data show that NPS treatment, but not PS, interferes with propagation to the contralateral hemisphere even when applied before KA injection: seizure duration, energy, and total number of seizures were significantly reduced. Seizure causality analysis between channels also shows significant differences between PS and NPS treatments. CONCLUSION: These data corroborate that KA injection seizures, even during status epilepticus, are not restricted to injection foci. Our data show promising perspectives on designing a closed-loop solution using 0.5-Hz probing stimulation to predict seizures and temporally coded stimulation to modulate seizure propagation.