Tomlinson Samuel B, Davis Patrick, Armstrong Caren, Baumgartner Michael E, Kennedy Benjamin C, Marsh Eric D
Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Front Netw Physiol. 2025 May 30;5:1602124. doi: 10.3389/fnetp.2025.1602124. eCollection 2025.
Interictal epileptiform discharges (IEDs) are pathologic hallmarks of epilepsy which frequently arise and spread through networks of functionally-connected brain regions. Recent studies demonstrate that the sequential recruitment of brain regions by propagating IEDs is highly conserved across repeated discharges, suggesting that IED propagation is spatiotemporally constrained by features of the underlying epileptic network. Understanding how repetitive IED sequences relate to the spatiotemporal organization of the epileptic network may reveal key insights into the pathophysiological role of IEDs during epileptogenesis. Delivery of exogenous electrical current allows for direct experimental probing of epileptic network circuitry and correlation with spontaneous epileptiform activity (e.g., IEDs). In this pilot study of human subjects with refractory epilepsy, we performed cortical stimulation via invasive depth electrodes to test whether spatiotemporal patterns observed during spontaneous IEDs are reproduced by evoked cortical potentials. We found that evoked potentials were accentuated following stimulation of early-activating "upstream" IED regions (anterograde) and attenuated with stimulation of late-activating "downstream" IED regions (retrograde). Concordance between IED latencies and evoked potentials suggests that these distinct network phenomena share common spatiotemporal constraints in the human epileptic brain.
发作间期癫痫样放电（IEDs）是癫痫的病理特征，常出现在功能连接的脑区网络中并在其中传播。最近的研究表明，传播的IEDs对脑区的顺序性募集在多次放电过程中高度保守，这表明IED传播在时空上受潜在癫痫网络特征的限制。了解重复性IED序列与癫痫网络的时空组织之间的关系，可能会揭示IEDs在癫痫发生过程中的病理生理作用的关键见解。施加外源电流可以直接对癫痫网络回路进行实验性探测，并与自发性癫痫样活动（如IEDs）进行关联。在这项针对难治性癫痫患者的初步研究中，我们通过侵入性深度电极进行皮层刺激，以测试在自发性IEDs期间观察到的时空模式是否能通过诱发的皮层电位重现。我们发现，刺激早期激活的“上游”IED区域（顺行）后诱发电位增强，而刺激晚期激活的“下游”IED区域（逆行）后诱发电位减弱。IED潜伏期与诱发电位之间的一致性表明，这些不同的网络现象在人类癫痫脑中共享共同的时空限制。
