DAS Anup, Cash Sydney S, Sejnowski Terrence J
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA 94305 USA.
Massachusetts General Hospital, Boston, MA 02114 USA.
IEEE Access. 2020;8:52738-52748. doi: 10.1109/access.2020.2981017. Epub 2020 Mar 16.
It is generally understood that there is a preictal phase in the development of a seizure and this precictal period is the basis for seizure prediction attempts. The focus of this study is the preictal global spatiotemporal dynamics and its intra-patient variability. We analyzed preictal broadband brain connectivity from human electrocorticography (ECoG) recordings of 185 seizures (which included 116 clinical seizures) collected from 12 patients. ECoG electrodes record from only a part of the cortex, leaving large regions of the brain unobserved. Brain connectivity was therefore estimated using the sparse-plus-latent-regularized precision matrix (SLRPM) method, which calculates connectivity from partial correlations of the conditional statistics of the observed regions given the unobserved latent regions. Brain connectivity was quantified using eigenvector centrality (EC), from which a degree of heterogeneity was calculated for the preictal periods of all seizures in each patient. Results from the SLRPM method are compared to those from the sparse-regularized precision matrix (SRPM) and correlation methods, which do not account for the unobserved inputs when estimating brain connectivity. The degree of heterogeneity estimated by the SLRPM method is higher than those estimated by the SRPM and correlation methods for the preictal periods in most patients. These results reveal substantial heterogeneity or desynchronization among brain areas in the preictal period of human epileptic seizures. Furthermore, the SLRPM method identifies more onset channels from the preictal active electrodes compared to the SRPM and correlation methods. Finally, the correlation between the degree of heterogeneity and seizure severity of patients for SLRPM and SRPM methods were lower than that obtained from the correlation method. These results support recent findings suggesting that inhibitory neurons can have anti-seizure effects by inducing variability or heterogeneity across seizures. Understanding how this variability is linked to seizure initiation may lead to better predictions and controlling therapies.
一般认为,癫痫发作的发展过程中存在发作前期,而这个发作前期是进行癫痫发作预测尝试的基础。本研究的重点是发作前期的全脑时空动力学及其患者个体内的变异性。我们分析了从12名患者收集的185次癫痫发作(其中包括116次临床发作)的人类脑电皮层电图(ECoG)记录中的发作前期宽带脑连接性。ECoG电极仅记录部分皮层,大脑的大片区域未被观测到。因此,使用稀疏加潜在正则化精度矩阵(SLRPM)方法估计脑连接性,该方法根据给定未观测到的潜在区域时观测区域的条件统计量的偏相关性来计算连接性。使用特征向量中心性(EC)对脑连接性进行量化,并据此计算每位患者所有癫痫发作前期的异质性程度。将SLRPM方法的结果与稀疏正则化精度矩阵(SRPM)方法和相关性方法的结果进行比较,后两种方法在估计脑连接性时未考虑未观测到的输入。在大多数患者的发作前期,SLRPM方法估计的异质性程度高于SRPM方法和相关性方法估计的程度。这些结果揭示了人类癫痫发作前期脑区之间存在显著的异质性或去同步化。此外,与SRPM方法和相关性方法相比,SLRPM方法从发作前期活跃电极中识别出更多的起始通道。最后,SLRPM方法和SRPM方法中患者异质性程度与癫痫发作严重程度之间的相关性低于相关性方法得到的相关性。这些结果支持了最近的研究发现,即抑制性神经元可通过在癫痫发作间诱导变异性或异质性来产生抗癫痫发作作用。了解这种变异性与癫痫发作起始的关联可能会带来更好的预测和控制疗法。