Department of Neurological Surgery, University of California, Davis, USA; Center for Neuroscience, University of California, Davis, USA.
Department of Neurological Surgery, University of California, Davis, USA.
Brain Stimul. 2019 May-Jun;12(3):735-742. doi: 10.1016/j.brs.2019.01.005. Epub 2019 Jan 17.
Temporal lobe epilepsy is most prevalent among focal epilepsies, and nearly one-third of patients are refractory to pharmacological intervention. Persistent cognitive and neurobehavioral comorbidities also occur due to the recurrent nature of seizures and medication-related side effects.
Electrical neuromodulation is an effective strategy to reduce seizures both in animal models and clinically, but its efficacy to modulate cognition remains unclear. We hypothesized that theta frequency stimulation of the medial septum would increase septohippocampal oscillations, increase seizure threshold, and improve spatial learning in a rat model of pilocarpine-induced epilepsy.
Sham and pilocarpine rats were implanted with electrodes in the medial septum, hippocampus and prefrontal cortex. EEG was assessed days prior to and following stimulation. Sham and pilocarpine-treated rats received either no stimulation, continuous (throughout each behavior), or pre-task (one minute prior to each behavior) 7.7 Hz septal stimulation during the Barnes maze spatial navigation test and also during assessment of flurothyl-induced seizures.
Both continuous and pre-task stimulation prevented epilepsy-associated reductions in theta oscillations over time. Additionally, both stimulation paradigms significantly improved spatial navigation in the Barnes maze, reducing latency and improving search strategy. Moreover, stimulation led to significant increases in seizure threshold in pilocarpine-treated rats. There was no evidence of cognitive enhancement or increased seizure threshold in stimulated sham rats.
These findings have profound implications as theta stimulation of the septum represents a single frequency and target that has the potential to both improve cognition and reduce seizures for patients with refractory epilepsy.
颞叶癫痫是局灶性癫痫中最常见的一种，近三分之一的患者对药物干预无反应。由于癫痫反复发作和药物相关的副作用，持续性认知和神经行为合并症也会发生。
电神经调节是一种有效的策略，可以减少动物模型和临床中的癫痫发作，但它对调节认知的疗效尚不清楚。我们假设内侧隔区的θ频刺激会增加隔海马振荡，提高癫痫发作阈值，并改善匹罗卡品诱导癫痫大鼠的空间学习能力。
假手术和匹罗卡品大鼠被植入内侧隔、海马和前额皮质电极。在刺激前和刺激后几天评估 EEG。假手术和匹罗卡品处理的大鼠在 Barnes 迷宫空间导航测试期间以及氟烷诱导癫痫发作期间分别接受无刺激、连续（在每次行为过程中）或预任务（每次行为前一分钟）7.7 Hz 隔区刺激。
连续和预任务刺激均能防止癫痫相关的θ振荡随时间的减少。此外，两种刺激方案均显著改善了 Barnes 迷宫的空间导航，降低了潜伏期并改善了搜索策略。此外，刺激导致匹罗卡品处理大鼠的癫痫发作阈值显著增加。刺激假手术大鼠没有表现出认知增强或癫痫发作阈值增加的证据。
这些发现具有深远的意义，因为内侧隔区的θ刺激代表了一种单一的频率和靶点，有可能改善认知和减少耐药性癫痫患者的癫痫发作。
