Chinedu-Eneh Ebenezer O, Chiang Sharon, Andrews John P, Tadayon Ehsan, Fan Joline M, Garcia Paul A, Gonzalez-Giraldo Ernesto, Hegde Manu, Hullett Patrick, Rao Vikram R, Knowlton Robert C, Chang Edward F, Kleen Jonathan K
Department of Neurology, University of California San Francisco, San Francisco, CA, USA; Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
EBioMedicine. 2025 Mar;113:105606. doi: 10.1016/j.ebiom.2025.105606. Epub 2025 Mar 3.
Successful seizure onset zone (SOZ) localisation for epilepsy surgery often relies upon intracranial recordings. Accurate delineation requires anatomical detail yet influences of intracranial electrode density on clinical variables have not been systematically studied.
In this experimental study we compared SOZ localisation between spontaneously captured seizures on higher-density depth and grid electrode arrays (4-5 mm inter-electrode spacing) vs. lower-density resampled versions of those same seizures (8-10 mm spacing). Since traditional review of channel traces would reveal density conditions, we instead projected seizure activity data as heatmaps on patient brain reconstructions and hid electrode locations. Using a single-blinded randomised crossover design, six attending-level epileptologists viewed these visualisations from ten patients under both higher-density and lower-density conditions (n = 120 observations) and digitally annotated SOZs.
Inter-rater agreement between epileptologists on annotated margins was moderate (average Cohen's kappa: 0.47) and lower for the lower-density condition (p = 0.021, mixed effects model). Scorer confidence ratings did not differ between higher- and lower-density conditions (p = 0.410). The spatial extents of annotated SOZs for higher-density recordings were 25.4% larger on average (p = 0.011) and always closer to true SOZ extents in computer simulations, relative to lower-density.
Epileptologists using higher-density depth and subdural intracranial EEG recordings had higher inter-rater agreement and identified larger extents of SOZs compared to lower-density recordings. While further studies assessing surgical outcomes in more patients are needed, these results suggest higher densities of electrodes on already-implanted hardware may reveal sub-centimetre extensions and clearer functional contiguity of the SOZ(s) for better appraisals of pathophysiological margins in epilepsy surgery.
This work was supported by the National Institutes of Health through NINDS grant K23NS110920 and through a UCSF Weill Institute for Neurosciences Pilot Award.
癫痫手术中成功定位癫痫发作起始区（SOZ）通常依赖于颅内记录。准确描绘需要解剖细节，但颅内电极密度对临床变量的影响尚未得到系统研究。
在本实验研究中，我们比较了在高密度深度和网格电极阵列（电极间距4 - 5毫米）上自发捕获的癫痫发作与相同癫痫发作的低密度重采样版本（间距8 - 10毫米）之间的SOZ定位情况。由于传统的通道轨迹审查会揭示密度条件，我们改为将癫痫发作活动数据以热图形式投影到患者脑部重建图上，并隐藏电极位置。采用单盲随机交叉设计，六位主治级癫痫专家在高密度和低密度两种条件下查看了来自十名患者的这些可视化图像（n = 120次观察），并对SOZ进行了数字标注。
癫痫专家之间对标注边界的评分者间一致性为中等（平均科恩kappa系数：0.47），在低密度条件下更低（p = 0.021，混合效应模型）。高密度和低密度条件下评分者的信心评级没有差异（p = 0.410）。相对于低密度记录，高密度记录的标注SOZ的空间范围平均大25.4%（p = 0.011），并且在计算机模拟中总是更接近真实SOZ范围。
与低密度记录相比，使用高密度深度和硬膜下颅内脑电图记录的癫痫专家具有更高的评分者间一致性，并且识别出的SOZ范围更大。虽然需要进一步研究评估更多患者的手术结果，但这些结果表明，在已植入的硬件上增加电极密度可能会揭示SOZ的亚厘米级扩展和更清晰的功能连续性，以便更好地评估癫痫手术中的病理生理边界。
这项工作得到了美国国立卫生研究院通过NINDS资助K23NS110920以及UCSF威尔神经科学研究所试点奖的支持。
