Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Program in Neuroscience and Mental Health, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
Epilepsia. 2022 Oct;63(10):2583-2596. doi: 10.1111/epi.17357. Epub 2022 Jul 22.
Working memory deficits are prevalent in childhood epilepsy. Working memory processing is thought to be supported by the phase of hippocampal neural oscillations. Disruptions in working memory have previously been linked to the occurrence of transient epileptic activity. This study aimed to resolve the associations between oscillatory neural activity, transient epileptiform events, and working memory in children with epilepsy.
Intracranial recordings were acquired from stereotactically implanted electrodes in the hippocampi, epileptogenic zones, and working memory-related networks of children with drug-resistant epilepsy during a 1-back working memory task. Interictal epileptic activity was captured using automated detectors. Hippocampal phase and interregional connectivity within working memory networks were indexed by Rayleigh Z and the phase difference derivative, respectively. Trials with and without transient epileptiform events were compared.
Twelve children (mean age = 14.3 ± 2.8 years) with drug-resistant epilepsy were included in the study. In the absence of transient epileptic activity, significant delta and theta hippocampal phase resetting occurred in response to working memory stimulus presentation (Rayleigh z-score = 9, Rayleigh z-score = 8). Retrieval trials that were in phase with the preferred phase angle were associated with faster reaction times (p = .01, p = .03). Concurrently, delta and theta coordinated interactions between the hippocampi and working memory-related networks were enhanced (phase difference derivative [PDD] z-scores = 6-11). During retrieval trials with pre-encoding or pre-retrieval transient epileptic activity, phase resetting was attenuated (Rayleigh z-score = 5, Rayleigh z-score = 1), interregional connectivity was altered (PDD z-scores = 1-3), and reaction times were prolonged (p = .01, p = .03).
This work highlights the role of hippocampal phase in working memory. We observe poststimulus hippocampal phase resetting coincident with enhanced interregional connectivity. The precision of hippocampal phase predicts optimal working memory processing, and transient epileptic activity prolongs working memory processing. These findings can help guide future treatments aimed at restoring memory function in this patient population.
工作记忆缺陷在儿童癫痫中很常见。工作记忆处理被认为是由海马神经振荡的相位支持的。工作记忆的破坏以前与短暂性癫痫活动的发生有关。本研究旨在解决癫痫儿童的神经活动、短暂性癫痫样事件和工作记忆之间的关联。
使用立体定向植入的电极在药物难治性癫痫儿童的海马、致痫区和与工作记忆相关的网络中采集颅内记录，在 1 背工作记忆任务期间。使用自动探测器捕获间发性癫痫活动。海马相位和工作记忆网络内的区域间连通性分别由 Rayleigh Z 和相位差导数索引。比较有和无短暂性癫痫样事件的试验。
本研究纳入了 12 名（平均年龄 14.3±2.8 岁）药物难治性癫痫儿童。在没有短暂性癫痫活动的情况下，工作记忆刺激呈现时会出现显著的 delta 和 theta 海马相位重置（Rayleigh z 分数=9，Rayleigh z 分数=8）。与首选相位角同相的检索试验与更快的反应时间相关（p=0.01，p=0.03）。同时，海马和与工作记忆相关的网络之间的 delta 和 theta 协调相互作用增强（相位差导数[PDD]z 分数=6-11）。在有预编码或预检索短暂性癫痫活动的检索试验中，相位重置减弱（Rayleigh z 分数=5，Rayleigh z 分数=1），区域间连通性改变（PDD z 分数=1-3），反应时间延长（p=0.01，p=0.03）。
这项工作强调了海马相位在工作记忆中的作用。我们观察到刺激后海马相位重置与增强的区域间连通性同时发生。海马相位的精度预测了最佳的工作记忆处理，短暂性癫痫活动延长了工作记忆处理。这些发现可以帮助指导未来旨在恢复该患者群体记忆功能的治疗方法。
