Department of Neurology, Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Department of Bioengineering, School of Engineering & Applied Science, Philadelphia, Pennsylvania, USA.
Epilepsia. 2023 Apr;64(4):1021-1034. doi: 10.1111/epi.17528. Epub 2023 Feb 22.
Measuring cortico-cortical evoked potentials (CCEPs) is a promising tool for mapping epileptic networks, but it is not known how variability in brain state and stimulation technique might impact the use of CCEPs for epilepsy localization. We test the hypotheses that (1) CCEPs demonstrate systematic variability across trials and (2) CCEP amplitudes depend on the timing of stimulation with respect to endogenous, low-frequency oscillations.
We studied 11 patients who underwent CCEP mapping after stereo-electroencephalography electrode implantation for surgical evaluation of drug-resistant epilepsy. Evoked potentials were measured from all electrodes after each pulse of a 30 s, 1 Hz bipolar stimulation train. We quantified monotonic trends, phase dependence, and standard deviation (SD) of N1 (15-50 ms post-stimulation) and N2 (50-300 ms post-stimulation) amplitudes across the 30 stimulation trials for each patient. We used linear regression to quantify the relationship between measures of CCEP variability and the clinical seizure-onset zone (SOZ) or interictal spike rates.
We found that N1 and N2 waveforms exhibited both positive and negative monotonic trends in amplitude across trials. SOZ electrodes and electrodes with high interictal spike rates had lower N1 and N2 amplitudes with higher SD across trials. Monotonic trends of N1 and N2 amplitude were more positive when stimulating from an area with higher interictal spike rate. We also found intermittent synchronization of trial-level N1 amplitude with low-frequency phase in the hippocampus, which did not localize the SOZ.
These findings suggest that standard approaches for CCEP mapping, which involve computing a trial-averaged response over a .2-1 Hz stimulation train, may be masking inter-trial variability that localizes to epileptogenic tissue. We also found that CCEP N1 amplitudes synchronize with ongoing low-frequency oscillations in the hippocampus. Further targeted experiments are needed to determine whether phase-locked stimulation could have a role in localizing epileptogenic tissue.
测量皮质-皮质诱发电位（CCEPs）是一种用于绘制癫痫网络的有前途的工具，但尚不清楚大脑状态和刺激技术的变化如何影响 CCEPs 用于癫痫定位。我们检验以下两个假设：（1）CCEPs 在试验中表现出系统可变性；（2）CCEP 幅度取决于刺激与内源性低频振荡的时间关系。
我们研究了 11 名患者，他们在立体脑电图电极植入后进行 CCEP 映射，以进行药物难治性癫痫的手术评估。在每个 30 秒、1Hz 双极刺激序列的脉冲后，从所有电极测量诱发电位。我们量化了每个患者的 30 个刺激试验中 N1（刺激后 15-50ms）和 N2（刺激后 50-300ms）幅度的单调趋势、相位依赖性和标准偏差（SD）。我们使用线性回归来量化 CCEP 可变性测量值与临床发作起始区（SOZ）或间发性尖峰率之间的关系。
我们发现 N1 和 N2 波形在整个试验中都表现出正的和负的单调趋势。SOZ 电极和具有高间发性尖峰率的电极在整个试验中具有较低的 N1 和 N2 幅度和较高的 SD。刺激具有较高间发性尖峰率的区域时，N1 和 N2 幅度的单调趋势更为正。我们还发现，试验水平 N1 幅度与海马体中的低频相位间歇性同步，这并不能定位 SOZ。
这些发现表明，涉及在.2-1Hz 刺激序列上计算试验平均响应的标准 CCEP 映射方法可能掩盖了定位致痫组织的试验间可变性。我们还发现，CCEP N1 幅度与海马体中的持续低频振荡同步。需要进一步的靶向实验来确定锁相刺激是否可以在定位致痫组织中发挥作用。
