Brain Modulation Lab, Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA 15213, United States.
Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, United States; University of Pittsburgh Comprehensive Epilepsy Center, Pittsburgh, PA 15213, United States.
Exp Neurol. 2017 Aug;294:68-77. doi: 10.1016/j.expneurol.2017.05.003. Epub 2017 May 7.
Individuals with pharmacoresistant epilepsy remain a large and under-treated patient population. Continued technologic advancements in implantable neurostimulators have spurred considerable research efforts directed towards the development of novel antiepileptic stimulation therapies. However, the lack of adequate preclinical experimental platforms has precluded a detailed understanding of the differential effects of stimulation parameters on neuronal activity within seizure networks. In order to chronically monitor seizures and the effects of stimulation in a freely-behaving non-human primate with idiopathic epilepsy, we employed a novel simultaneous video-intracranial EEG recording platform using a state-of-the-art sensing-enabled, rechargeable clinical neurostimulator with real-time seizure detection and wireless data streaming capabilities. Using this platform, we were able to characterize the electrographic and semiologic features of the focal-onset, secondarily generalizing tonic-clonic seizures stably expressed in this animal. A series of acute experiments exploring low-frequency (2Hz) hippocampal stimulation identified a pulse width (150μs) and current amplitude (4mA) combination which maximally suppressed local hippocampal activity. These optimized stimulation parameters were then delivered to the seizure onset-side hippocampus in a series of chronic experiments. This long-term testing revealed that the suppressive effects of low-frequency hippocampal stimulation 1) diminish when delivered continuously but are maintained when stimulation is cycled on and off, 2) are dependent on circadian rhythms, and 3) do not necessarily confer seizure protective effects.
个体患有耐药性癫痫仍然是一个庞大且治疗不足的患者群体。植入式神经刺激器的技术不断进步，促使人们大力研究开发新型抗癫痫刺激疗法。然而，缺乏足够的临床前实验平台，使得我们无法详细了解刺激参数对癫痫网络中神经元活动的差异影响。为了在患有特发性癫痫的自由活动非人类灵长类动物中慢性监测癫痫发作和刺激效果，我们采用了一种新颖的同时视频-颅内 EEG 记录平台，该平台使用了具有实时癫痫检测和无线数据传输功能的最先进的感应式可充电临床神经刺激器。使用该平台，我们能够描述局灶性起始、继发全身性强直-阵挛性癫痫发作的电描记和半定量特征，这种癫痫发作在该动物中稳定表达。一系列探索低频（2Hz）海马刺激的急性实验确定了一种最大程度抑制局部海马活动的脉冲宽度（150μs）和电流幅度（4mA）组合。然后，在一系列慢性实验中，将这些优化的刺激参数输送至癫痫起始侧海马。这种长期测试表明，低频海马刺激的抑制作用 1）在连续输送时会减弱，但在刺激循环开启和关闭时会保持，2）依赖于昼夜节律，3）不一定能提供抗癫痫作用。
