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II 型局灶性皮质发育不良中形态异常神经元作为相位-幅度耦合的细胞来源。

Dysmorphic neurons as cellular source for phase-amplitude coupling in Focal Cortical Dysplasia Type II.

机构信息

Department of Neurosurgery, University Hospital Erlangen, Germany; Department of Neurosurgery, University Hospital Halle, Germany.

Department of Neurosurgery, University Hospital Erlangen, Germany; Department of Neurosurgery, University Hospital Vienna, Austria.

出版信息

Clin Neurophysiol. 2021 Mar;132(3):782-792. doi: 10.1016/j.clinph.2021.01.004. Epub 2021 Jan 20.

DOI:10.1016/j.clinph.2021.01.004
PMID:33571886
Abstract

OBJECTIVE

Reliable localization of the epileptogenic zone is necessary for successful epilepsy surgery. Neurophysiological biomarkers include ictal onsets and interictal spikes. Furthermore, the epileptic network shows oscillations with potential localization value and pathomechanistic implications. The cellular origin of such markers in invasive EEG in vivo remains to be clarified.

METHODS

In the presented pilot study, surgical brain samples and invasive EEG recordings of seven patients with surgically treated Focal Cortical Dysplasia (FCD) type II were coregistered using a novel protocol. Dysmorphic neurons and balloon cells were immunohistochemically quantified. Evaluated markers included seizure onset, spikes, and oscillatory activity in delta, theta, gamma and ripple frequency bands, as well as sample entropy and phase-amplitude coupling between delta, theta, alpha and beta phase and gamma amplitude.

RESULTS

Correlations between histopathology and neurophysiology provided evidence for a contribution of dysmorphic neurons to interictal spikes, fast gamma activity and ripples. Furthermore, seizure onset and phase-amplitude coupling in areas with dysmorphic neurons suggests preserved connectivity is related to seizure initiation. Balloon cells showed no association.

CONCLUSIONS

Phase-amplitude coupling, spikes, fast gamma and ripples are related to the density of dysmorphic neurons and localize the seizure onset zone.

SIGNIFICANCE

The results of our pilot study provide a new powerful tool to address the cellular source of abnormal neurophysiology signals to leverage current and novel biomarkers for the localization of epileptic activity in the human brain.

摘要

目的

可靠的致痫区定位对于成功的癫痫手术至关重要。神经生理学生物标志物包括发作起始和发作间期棘波。此外,癫痫网络显示出具有潜在定位价值和病理生理意义的振荡。这些标记物在体内侵入性 EEG 中的细胞起源仍有待阐明。

方法

在本研究中,使用新的方案对 7 名接受手术治疗的局灶性皮质发育不良(FCD)II 型患者的手术脑样本和侵入性 EEG 记录进行了配准。对畸形神经元和气球细胞进行了免疫组织化学定量。评估的标记物包括发作起始、棘波和 delta、theta、gamma 和涟漪频带中的振荡活动,以及样本熵和 delta、theta、alpha 和 beta 相位与 gamma 幅度之间的相位-振幅耦合。

结果

组织病理学与神经生理学之间的相关性为畸形神经元与发作间期棘波、快 gamma 活动和涟漪有关提供了证据。此外,畸形神经元区域的发作起始和相位-振幅耦合表明保留的连接性与发作起始有关。气球细胞没有相关性。

结论

相位-振幅耦合、棘波、快 gamma 和涟漪与畸形神经元的密度有关,并定位发作起始区。

意义

我们的初步研究结果提供了一种新的强大工具,用于解决异常神经生理学信号的细胞源问题,以利用当前和新的生物标志物来定位人类大脑中的癫痫活动。

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