Department of Pediatrics, University of Chicago, Chicago, IL 60637;
Department of Applied Mathematics, MIRA Institute for Biomedical Engineering and Technical Medicine, University of Twente, Enschede 7500AE, The Netherlands;
Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):10761-10766. doi: 10.1073/pnas.1702490114. Epub 2017 Sep 18.
Small-scale neuronal networks may impose widespread effects on large network dynamics. To unravel this relationship, we analyzed eight multiscale recordings of spontaneous seizures from four patients with epilepsy. During seizures, multiunit spike activity organizes into a submillimeter-sized wavefront, and this activity correlates significantly with low-frequency rhythms from electrocorticographic recordings across a 10-cm-sized neocortical network. Notably, this correlation effect is specific to the ictal wavefront and is absent interictally or from action potential activity outside the wavefront territory. To examine the multiscale interactions, we created a model using a multiscale, nonlinear system and found evidence for a dual role for feedforward inhibition in seizures: while inhibition at the wavefront fails, allowing seizure propagation, feedforward inhibition of the surrounding centimeter-scale networks is activated via long-range excitatory connections. Bifurcation analysis revealed that distinct dynamical pathways for seizure termination depend on the surrounding inhibition strength. Using our model, we found that the mesoscopic, local wavefront acts as the forcing term of the ictal process, while the macroscopic, centimeter-sized network modulates the oscillatory seizure activity.
小规模神经元网络可能对大规模网络动态产生广泛影响。为了揭示这种关系，我们分析了来自四名癫痫患者的八次自发性癫痫发作的多尺度记录。在癫痫发作期间，多单位尖峰活动组织成亚毫米大小的波前，并且这种活动与皮层脑电图记录中的低频节律显著相关，涉及 10 厘米大小的新皮层网络。值得注意的是，这种相关效应是特定于发作波前的，在发作间期或波前区域外的动作电位活动中不存在。为了研究多尺度相互作用，我们使用多尺度非线性系统创建了一个模型，并发现了前馈抑制在癫痫发作中的双重作用的证据：在前馈抑制在波前失效时，允许癫痫发作传播，而通过远程兴奋性连接激活了围绕厘米尺度网络的前馈抑制。分岔分析表明，终止癫痫发作的不同动力学途径取决于周围抑制强度。使用我们的模型，我们发现中尺度局部波前作为发作过程的强迫项，而厘米尺度的宏观网络调制振荡性发作活动。
