Annu Int Conf IEEE Eng Med Biol Soc. 2022 Jul;2022:4374-4376. doi: 10.1109/EMBC48229.2022.9871670.
Epilepsy is characterized by recurrent, unprovoked seizures which involve transient neuronal hyperexcitability or hypersynchrony. Focal seizures with impaired awareness (FIAS) are commonly related to mesial temporal lobe epilepsy (mTLE) with hippocampal sclerosis and potentially status epilepticus. How seizures terminate spontaneously remains an unanswered question fundamental to epileptology. To study seizure termination, we induced FIAS in a nonhuman primate (NHP) model with electrical kindling. Kindling stimulation was delivered to the basolateral amygdala once weekly for 30 weeks. Chronic linear microelectrode arrays were implanted in NHP mesial temporal lobe targets: the hippocampus, amygdala and entorhinal cortex. Daily electrophysiologic recordings were obtained from all targets before, during and after stimulation to monitor changes to local field potential activity. We detect prominent changes in electrophysiologic dynamics before after-discharge (AD; subclinical, electrographic seizures which begin after a stimulus) self-termination. Specifically, at seizure termination the power of the extra-focal theta rhythm increased, and the theta phase was shown to couple with the gamma rhythm within the seizure focus. The electrical current threshold for eliciting an after-discharge decreased from >700µA to 15µA. The refractory period, which prevents the induction of seizure events at threshold, was initially 3 minutes in duration. At 30 weeks after FIAS induction the refractory period increased to over 5 minutes in duration. Understanding the electrophysiologic dynamics that reflect endogenous seizure termination mechanisms may be a valuable consideration for refining intervention strategies for treatment of epilepsy. Clinical Relevance- Our findings provide further electrophysiologic description of the endogenous mechanisms behind seizure termination in a healthy brain. This work specifically highlights the importance of considering targets outside the epileptogenic zone for therapeutic intervention.
癫痫的特征是反复发作、无诱因的发作，涉及短暂的神经元过度兴奋或过度同步。伴有意识障碍的局灶性发作（FIAS）通常与内侧颞叶癫痫（mTLE）伴海马硬化和潜在的癫痫持续状态有关。发作如何自发终止仍然是癫痫学中一个未解决的基本问题。为了研究发作终止，我们在电点燃的非人类灵长类动物（NHP）模型中诱导 FIAS。每周对基底外侧杏仁核进行一次点燃刺激，共进行 30 周。在 NHP 内侧颞叶目标（海马体、杏仁核和内嗅皮层）中植入慢性线性微电极阵列。在刺激前后的每一天，从所有目标中获取电生理记录，以监测局部场电位活动的变化。我们在发作后放电（AD；刺激后开始的亚临床、电发作）自行终止前后检测到电生理动力学的显著变化。具体来说，在发作终止时，额外焦点的θ节律功率增加，并且在焦点内的γ节律与θ相位耦合。诱发 AD 的电流阈值从>700µA 降低到 15µA。防止在阈值下诱发发作事件的不应期最初持续 3 分钟。在 FIAS 诱导后 30 周，不应期增加到超过 5 分钟。了解反映内源性发作终止机制的电生理动力学可能是改进癫痫治疗干预策略的重要考虑因素。临床相关性-我们的发现为健康大脑中发作终止的内源性机制提供了进一步的电生理描述。这项工作特别强调了考虑癫痫灶外目标对治疗干预的重要性。
