Bruder Jonas Christian, Wagner Kathrin, Lachner-Piza Daniel, Klotz Kerstin Alexandra, Schulze-Bonhage Andreas, Jacobs Julia
Clinic of Neuropediatrics and Muscle Disorders, Freiburg University Medical Center, Breisgau, Germany.
Abteilung Epileptologie Epilepsiezentrum, Klinik Für Neurochirurgie, Universitätsklinikum Freiburg, Breisgau, Germany.
Front Neurol. 2022 Jun 3;13:876024. doi: 10.3389/fneur.2022.876024. eCollection 2022.
High frequency oscillations (HFO; ripples = 80-200, fast ripples 200-500 Hz) are promising epileptic biomarkers in patients with epilepsy. However, especially in temporal epilepsies differentiation of epileptic and physiological HFO activity still remains a challenge. Physiological sleep-spindle-ripple formations are known to play a role in slow-wave-sleep memory consolidation. This study aimed to find out if higher rates of mesial-temporal spindle-ripples correlate with good memory performance in epilepsy patients and if surgical removal of spindle-ripple-generating brain tissue correlates with a decline in memory performance. In contrast, we hypothesized that higher rates of overall ripples or ripples associated with interictal epileptic spikes correlate with poor memory performance.
Patients with epilepsy implanted with electrodes in mesial-temporal structures, neuropsychological memory testing and subsequent epilepsy surgery were included. Ripples and epileptic spikes were automatically detected in intracranial EEG and sleep-spindles in scalp EEG. The coupling of ripples to spindles was automatically analyzed. Mesial-temporal spindle-ripple rates in the speech-dominant-hemisphere (left in all patients) were correlated with verbal memory test results, whereas ripple rates in the non-speech-dominant hemisphere were correlated with non-verbal memory test performance, using Spearman correlation).
Intracranial EEG and memory test results from 25 patients could be included. All ripple rates were significantly higher in seizure onset zone channels ( < 0.001). Patients with pre-surgical verbal memory impairment had significantly higher overall ripple rates in left mesial-temporal channels than patients with intact verbal memory (Mann-Whitney-U-Test: = 0.039). Spearman correlations showed highly significant negative correlations of the pre-surgical verbal memory performance with left mesial-temporal spike associated ripples (r = -0.458; = 0.007) and overall ripples (r = -0.475; = 0.006). All three ripple types in right-sided mesial-temporal channels did not correlate with pre-surgical nonverbal memory. No correlation for the difference between post- and pre-surgical memory and pre-surgical spindle-ripple rates was seen in patients with left-sided temporal or mesial-temporal surgery.
This study fails to establish a clear link between memory performance and spindle ripples. This highly suggests that spindle-ripples are only a small portion of physiological ripples contributing to memory performance. More importantly, this study indicates that spindle-ripples do not necessarily compromise the predictive value of ripples in patients with temporal epilepsy. The majority of ripples were clearly linked to areas with poor memory function.
高频振荡（HFO；涟漪波=80 - 200Hz，快速涟漪波200 - 500Hz）是癫痫患者很有前景的癫痫生物标志物。然而，尤其是在颞叶癫痫中，区分癫痫性和生理性HFO活动仍然是一个挑战。生理睡眠纺锤波 - 涟漪波组合在慢波睡眠记忆巩固中发挥作用。本研究旨在查明内侧颞叶纺锤波 - 涟漪波的较高发生率是否与癫痫患者的良好记忆表现相关，以及手术切除产生纺锤波 - 涟漪波的脑组织是否与记忆表现下降相关。相反，我们假设总体涟漪波或与发作间期癫痫棘波相关的涟漪波的较高发生率与较差的记忆表现相关。
纳入在颞叶内侧结构植入电极、进行神经心理学记忆测试并随后接受癫痫手术的癫痫患者。通过颅内脑电图自动检测涟漪波和癫痫棘波，通过头皮脑电图检测睡眠纺锤波。自动分析涟漪波与纺锤波的耦合情况。使用斯皮尔曼相关性分析，言语优势半球（所有患者均为左侧）的内侧颞叶纺锤波 - 涟漪波发生率与言语记忆测试结果相关，而非言语优势半球的涟漪波发生率与非言语记忆测试表现相关。
可纳入25例患者的颅内脑电图和记忆测试结果。癫痫发作起始区通道的所有涟漪波发生率均显著更高（<0.001）。术前存在言语记忆损害的患者，其左侧内侧颞叶通道的总体涟漪波发生率显著高于言语记忆完好的患者（曼 - 惠特尼U检验：P = 0.039）。斯皮尔曼相关性分析显示，术前言语记忆表现与左侧内侧颞叶棘波相关的涟漪波（r = -0.458；P = 0.007）和总体涟漪波（r = -0.475；P = 0.006）呈高度显著负相关。右侧内侧颞叶通道的所有三种涟漪波类型与术前非言语记忆均无相关性。在接受左侧颞叶或内侧颞叶手术的患者中，未发现术后与术前记忆差异和术前纺锤波 - 涟漪波发生率之间的相关性。
本研究未能确立记忆表现与纺锤波 - 涟漪波之间的明确联系。这强烈表明纺锤波 - 涟漪波只是对记忆表现有贡献的生理涟漪波的一小部分。更重要的是，本研究表明纺锤波 - 涟漪波不一定会损害颞叶癫痫患者中涟漪波的预测价值。大多数涟漪波明显与记忆功能较差的区域相关。
