EEG and Epilepsy, Clinical Neuroscience Department, University Hospital and Faculty of Medicine of Geneva, Switzerland; Functional Brain Mapping Lab, Department of Fundamental Neurosciences, University of Geneva, Switzerland; Neurosurgery, Clinical Neuroscience Department, University Hospital and Faculty of Medicine of Geneva, Switzerland.
Institute of Bioengineering, Center for Neuroprosthetics, Ecole Polytechnique Federale de Lausanne (EPFL), Switzerland; Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland.
Neuroimage Clin. 2020;28:102467. doi: 10.1016/j.nicl.2020.102467. Epub 2020 Oct 14.
Epileptic networks, defined as brain regions involved in epileptic brain activity, have been mapped by functional connectivity in simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) recordings. This technique allows to define brain hemodynamic changes, measured by the Blood Oxygen Level Dependent (BOLD) signal, associated to the interictal epileptic discharges (IED), which together with ictal events constitute a signature of epileptic disease. Given the highly time-varying nature of epileptic activity, a dynamic functional connectivity (dFC) analysis of EEG-fMRI data appears particularly suitable, having the potential to identify transitory features of specific connections in epileptic networks. In the present study, we propose a novel method, defined dFC-EEG, that integrates dFC assessed by fMRI with the information recorded by simultaneous scalp EEG, in order to identify the connections characterised by a dynamic profile correlated with the occurrence of IED, forming the dynamic epileptic subnetwork. Ten patients with drug-resistant focal epilepsy were included, with different aetiology and showing a widespread (or multilobar) BOLD activation, defined as involving at least two distinct clusters, located in two different lobes and/or extended to the hemisphere contralateral to the epileptic focus. The epileptic focus was defined from the IED-related BOLD map. Regions involved in the occurrence of interictal epileptic activity; i.e., forming the epileptic network, were identified by a general linear model considering the timecourse of the fMRI-defined focus as main regressor. dFC between these regions was assessed with a sliding-window approach. dFC timecourses were then correlated with the sliding-window variance of the IED signal (VarIED), to identify connections whose dynamics related to the epileptic activity; i.e., the dynamic epileptic subnetwork. As expected, given the very different clinical picture of each individual, the extent of this subnetwork was highly variable across patients, but was but was reduced of at least 30% with respect to the initially identified epileptic network in 9/10 patients. The connections of the dynamic subnetwork were most commonly close to the epileptic focus, as reflected by the laterality index of the subnetwork connections, reported higher than the one within the original epileptic network. Moreover, the correlation between dFC timecourses and VarIED was predominantly positive, suggesting a strengthening of the dynamic subnetwork associated to the occurrence of IED. The integration of dFC and scalp IED offers a more specific description of the epileptic network, identifying connections strongly influenced by IED. These findings could be relevant in the pre-surgical evaluation for the resection or disconnection of the epileptogenic zone and help in reaching a better post-surgical outcome. This would be particularly important for patients characterised by a widespread pathological brain activity which challenges the surgical intervention.
癫痫网络被定义为与癫痫脑活动相关的脑区,已经通过同步脑电图和功能磁共振成像 (EEG-fMRI) 记录中的功能连接进行了映射。这项技术可以定义与间发性癫痫放电 (IED) 相关的脑血流动力学变化,这些变化由血氧水平依赖 (BOLD) 信号测量,与癫痫发作事件一起构成了癫痫疾病的特征。鉴于癫痫活动具有高度的时变性质,对 EEG-fMRI 数据进行动态功能连接 (dFC) 分析似乎特别合适,具有识别癫痫网络中特定连接瞬态特征的潜力。在本研究中,我们提出了一种新的方法,称为 dFC-EEG,它将 fMRI 评估的 dFC 与同时记录的头皮 EEG 信息相结合,以识别与 IED 发生相关的具有动态特征的连接,从而形成动态癫痫子网。纳入了 10 名药物难治性局灶性癫痫患者,病因不同,表现为广泛(或多叶)BOLD 激活,定义为至少涉及两个不同的簇,位于两个不同的叶区和/或扩展到癫痫灶对侧的半球。癫痫灶是从与 IED 相关的 BOLD 图中定义的。通过考虑 fMRI 定义的焦点的时间过程作为主要回归器,使用广义线性模型识别参与间歇性癫痫活动发生的区域,即形成癫痫网络。使用滑动窗口方法评估这些区域之间的 dFC。然后将 dFC 时间过程与 IED 信号的滑动窗口方差(VarIED)相关联,以识别与癫痫活动相关的动力学连接,即动态癫痫子网。正如预期的那样,鉴于每个个体的临床情况非常不同,子网的范围在患者之间差异很大,但在 9/10 名患者中,与最初确定的癫痫网络相比,子网的范围减少了至少 30%。动态子网的连接通常靠近癫痫灶,这反映在子网连接的侧性指数上,该指数高于原始癫痫网络中的连接。此外,dFC 时间过程与 VarIED 之间的相关性主要为正,表明与 IED 发生相关的动态子网得到了加强。dFC 和头皮 IED 的整合提供了对癫痫网络的更具体描述,确定了受 IED 强烈影响的连接。这些发现对于切除或断开致痫区的术前评估可能具有重要意义,并有助于获得更好的术后结果。对于以广泛的病理性脑活动为特征的患者来说,这一点尤其重要,因为这对手术干预提出了挑战。