病理性神经元在“兴奋-抑制”转换时产生涟漪，扰乱信息传递。

Weiss Shennan A, Fried Itzhak, Engel Jerome, Bragin Anatol, Wang Shuang, Sperling Michael R, Wong Robert K S, Nir Yuval, Staba Richard J

Dept. of Neurology.

Dept. of Physiology and Pharmacology, State University of New York Downstate, Brooklyn, New York, 11203 USA.

medRxiv. 2023 Aug 7:2023.08.01.23293365. doi: 10.1101/2023.08.01.23293365.

OBJECTIVE

To confirm and investigate why pathological HFOs (pHFOs), including Ripples [80-200 Hz] and fast ripples [200-600 Hz], are generated during the UP-DOWN transition of the slow wave and if pHFOs interfere with information transmission.

METHODS

We isolated 217 total units from 175.95 iEEG contact-hours of synchronized macro- and microelectrode recordings from 6 patients. Sleep slow oscillation (0.1-2 Hz) epochs were identified in the iEEG recording. iEEG HFOs that occurred superimposed on the slow wave were transformed to phasors and adjusted by the phase of maximum firing in nearby units (i.e., maximum UP). We tested whether, in the seizure onset zone (SOZ), HFOs and associated action potentials (AP) occur more often at the UP-DOWN transition. We also examined ripple temporal correlations using cross correlograms.

RESULTS

At the group level in the SOZ, HFO and HFO-associated AP probability was highest during the UP-DOWN transition of slow wave excitability (p<<0.001). In the non-SOZ, HFO and HFO-associated AP was highest during the DOWN-UP transition (p<<0.001). At the unit level in the SOZ, 15.6% and 20% of units exhibited more robust firing during ripples (Cohen's d=0.11-0.83) and fast ripples (d=0.36-0.90) at the UP-DOWN transition (p<0.05 f.d.r corrected), respectively. By comparison, also in the SOZ, 6.6% (d=0.14-0.30) and 8.5% (d=0.33-0.41) of units had significantly less firing during ripples and fast ripples at the UP-DOWN transition, respectively. Additional data shows ripple temporal correlations, involving global slow waves, between the hippocampus, entorhinal cortex, and parahippocampal gyrus were reduced by ~50-80% in the SOZ compared to the non-SOZ (N=3).

SIGNIFICANCE

The UP-DOWN transition of slow wave excitability facilitates the activation of pathological neurons to generate pHFOs. The pathological neurons and pHFOs disrupt ripple temporal correlations across brain regions that transfer information and may be important in memory consolidation.

目的

确认并研究为何在慢波的上下转换期间会产生包括涟漪[80 - 200赫兹]和快涟漪[200 - 600赫兹]在内的病理性高频振荡（pHFOs），以及pHFOs是否会干扰信息传递。

方法

我们从6名患者的175.95小时同步宏观和微观电极记录的颅内脑电图（iEEG）接触时间中分离出217个总单元。在iEEG记录中识别出睡眠慢振荡（0.1 - 2赫兹）时段。叠加在慢波上出现的iEEG高频振荡被转换为相量，并根据附近单元最大放电的相位（即最大上升期）进行调整。我们测试了在癫痫发作起始区（SOZ），高频振荡和相关动作电位（AP）在上下转换时是否更频繁出现。我们还使用交叉相关图检查了涟漪时间相关性。

结果

在SOZ的组水平上，在慢波兴奋性的上下转换期间，高频振荡和与高频振荡相关的AP概率最高（p << 0.001）。在非SOZ中，高频振荡和与高频振荡相关的AP在下降 - 上升转换期间最高（p << 0.001）。在SOZ的单元水平上，分别有15.6%和20%的单元在上下转换时的涟漪（科恩d = 0.11 - 0.83）和快涟漪（d = 0.36 - 0.90）期间表现出更强的放电（p < 0.05，经错误发现率校正）。相比之下，同样在SOZ中，分别有6.6%（d = 0.14 - 0.30）和8.5%（d = 0.33 - 0.41）的单元在上下转换时的涟漪和快涟漪期间放电明显减少。额外数据显示，与非SOZ相比，SOZ中涉及海马体、内嗅皮质和海马旁回之间包括全局慢波在内的涟漪时间相关性降低了约50 - 80%（N = 3）。