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.

中文翻译：

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对致痫灶的时间不规则电刺激延迟了大鼠的癫痫发生

背景技术刺激序列中电脉冲的时间模式的变化为治疗神经系统疾病，例如耐药性颞叶癫痫开辟了新的机会领域。这种新型刺激是否会影响癫痫发生仍有待研究。目的本研究的目的是分析时间不规则的深部脑刺激对大鼠点燃诱发癫痫发生的影响。方法 在点燃刺激的不同时间进行时间不规则的深部脑刺激。将点燃采集的行为和电图变化与对照组和时间规律的深部脑刺激治疗组进行比较。用小波互相关分析分析癫痫样活动的传播，并获得发作间期癫痫样放电率。结果 发作间期在致痫灶内进行的时间不规则深部脑刺激缩短了每日后出院持续时间，减缓了癫痫发作阶段的进展，缩短了全身性发作持续时间，并干扰了癫痫样活动从癫痫发作区向 ipsi 的传播。和对侧运动皮层。我们还发现，在用时间不规则的深部脑刺激刺激的大鼠中，癫痫发作的严重程度与发作间期癫痫样放电之间存在负相关。结论 这些结果提供的证据表明，时间上不规则的深部脑刺激通过将点燃动物的癫痫发生延迟几乎两倍的时间来干扰癫痫的建立。因此，