Connolly Mark J, Piallat Brigitte, Sendi Mohammad, Mahmoudi Babak, Higgins Melinda K, Gutekunst Claire-Anne, Devergnas Annaelle, Gross Robert E
Emory National Primate Research Center, Emory University, Atlanta, GA, United States.
Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, United States.
Heliyon. 2024 Jul 6;10(14):e34257. doi: 10.1016/j.heliyon.2024.e34257. eCollection 2024 Jul 30.
Asynchronous distributed multielectrode stimulation (ADMES) is a novel approach to deep brain stimulation for medication resistant temporal lobe epilepsy that has shown promise in rodent and seizure models. To further evaluate its effects on a pre-clinical model, we characterized the effect of unilateral ADMES in an NHP model of temporal lobe seizures induced by intra-hippocampal injection of penicillin (PCN). Four non-human primates were used for this study in two contemporaneous cohorts. One cohort (n = 3 hemispheres) was implanted with the Medtronic RC + S stimulation (GIN cohort) and recording system connected to two 4-contact ring electrodes to evaluate three unilateral stimulation patterns: 7 Hz Ring ADMES, 20 Hz Dual Ring, and 125 Hz Dual Ring (analog of clinical stimulation). In an additional cohort (EPC cohort, n = 2), two 12-contact segmented electrodes were implanted in the right hippocampus and connected to an externalized recording and stimulation system to allow more flexibility in the stimulation pattern. In this second cohort, 4 variations of stimulation were evaluated (7 Hz Full ADMES, 7 Hz Ring ADMES, 31 Hz Wide Ring, and 31 Hz Dual Ring). In the GIN cohort, we found an increase in seizure frequency and time spent in seizure during the 7 Hz Ring ADMES stimulation compared to the respective post-stimulation. A similar post-stimulation effect was found in the EPC cohort. We also found an increase in seizure frequency during the 7Hz full ADMES compared to the respective post-stimulation. However, we did not find a difference between pre-stimulation and stimulation conditions suggesting a possible post stimulation effect of the 7Hz hippocampal stimulation. In conclusion, in the NHP PCN model of temporal lobe seizures, acute asynchronous hippocampal stimulation was not therapeutic, however, our findings related to the post-stimulation effect can support future studies using hippocampal stimulation for the treatment of temporal lobe epilepsy.
异步分布式多电极刺激（ADMES）是一种用于治疗耐药性颞叶癫痫的新型深部脑刺激方法，已在啮齿动物和癫痫模型中显示出前景。为了进一步评估其对临床前模型的影响，我们在海马内注射青霉素（PCN）诱导的颞叶癫痫非人类灵长类动物模型中，对单侧ADMES的效果进行了表征。本研究使用了四个非人类灵长类动物，分为两个同期队列。一个队列（n = 3个半球）植入了美敦力RC + S刺激（GIN队列）和记录系统，该系统连接到两个4触点环形电极，以评估三种单侧刺激模式：7Hz环形ADMES、20Hz双环和125Hz双环（临床刺激的模拟）。在另一个队列（EPC队列，n = 2）中，将两个12触点分段电极植入右侧海马，并连接到外部记录和刺激系统，以在刺激模式上提供更大的灵活性。在第二个队列中，评估了4种刺激变化（7Hz全ADMES、7Hz环形ADMES、31Hz宽环和31Hz双环）。在GIN队列中，我们发现与各自的刺激后相比，在7Hz环形ADMES刺激期间癫痫发作频率和癫痫发作时间增加。在EPC队列中也发现了类似的刺激后效应。我们还发现与各自的刺激后相比，在7Hz全ADMES期间癫痫发作频率增加。然而，我们没有发现刺激前和刺激条件之间的差异，这表明7Hz海马刺激可能存在刺激后效应。总之，在颞叶癫痫的非人类灵长类动物PCN模型中，急性异步海马刺激没有治疗效果，然而，我们与刺激后效应相关的发现可以支持未来使用海马刺激治疗颞叶癫痫的研究。
