Temporally irregular electrical stimulation to the epileptogenic focus delays epileptogenesis in rats

Background: Variation in the temporal patterns of electrical pulses in stimulation trains has opened a new field of opportunity for the treatment of neurological disorders, such as pharmacoresistant temporal lobe epilepsy. Whether this novel type of stimulation affects epileptogenesis remains to be investigated. Objective: The purpose of this study was to analyze the effects of temporally irregular deep brain stimulation on kindling-induced epileptogenesis in rats. Methods: Temporally irregular deep brain stimulation was delivered at different times with respect to the kindling stimulation. Behavioral and electrographic changes on kindling acquisition were compared with a control group and a temporally regular deep brain stimulation-treated group. The propagation of epileptiform activity was analyzed with wavelet cross-correlation analysis, and interictal epileptiform discharge ratios were obtained. Results: Temporally irregular deep brain stimulation delivered in the epileptogenic focus during the interictal period shortened the daily afterdischarge duration, slowed the progression of seizure stages, diminished the generalized seizure duration and interfered with the propagation of epileptiform activity from the seizure onset zone to the ipsi- and contralateral motor cortex. We also found a negative correlation between seizure severity and interictal epileptiform discharges in rats stimulated with temporally irregular deep brain stimulation. Conclusion: These results provide evidence that temporally irregular deep brain stimulation interferes with the establishment of epilepsy by delaying epileptogenesis by almost twice as long in kindling animals. Thus, temporally irregular deep brain stimulation could be a preventive approach against epilepsy. (C) 2019 Elsevier Inc. All rights reserved.