Hu Bing, Wang Dingjiang, Xia Zhinan, Yang Aijun, Zhang Jingsong, Shi Qianqian, Dai Hao
1Department of Applied Mathematics, Zhejiang University of Technology, Hangzhou, 310023 China.
2Key Laboratory of Systems Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031 China.
Cogn Neurodyn. 2020 Feb;14(1):137-154. doi: 10.1007/s11571-019-09559-4. Epub 2019 Oct 8.
Absence epileptiform activities are traditionally considered to be primarily induced by abnormal interactions between the cortical and thalamic neurons, which form the thalamocortical circuit in the brain. The basal ganglia, as an organizational unit in the brain, has close input and output relationships with the thalamocortical circuit. Although several studies report that the basal ganglia may participate in controlling and regulating absence epileptiform activities, to date, there have been no studies regarding whether the basal ganglia directly cause absence epileptiform activities. In this paper, we built a basal ganglia-corticothalamic network model to determine the role of basal ganglia in this disease. We determined that absence epileptiform activities might be directly induced by abnormal coupling strengths on certain pivotal pathways in the basal ganglia. These epileptiform activities can be well controlled by the coupling strengths of three major pathways that project from the thalamocortical network to the basal ganglia. The results implied that the substantia nigra pars compacta (SNc) can be considered to be the effective treatment target area for inhibiting epileptiform activities, which supports the observations of previous studies. Particularly, as a major contribution of this paper, we determined that the final presentation position of the epileptic slow spike waves is not limited to the cerebral cortex; these waves may additionally appear in the thalamus, striatal medium spiny neurons, striatal fast spiking interneuron, the SNc, subthalamic nucleus, substantia nigra pars reticulata and globus pallidus pars externa. In addition, consistent with several previous studies, the delay in the network was observed to be a critical factor for inducing transitions between different types of absence epileptiform activities. Our new model not only explains the onset and control mechanism but also provides a unified framework to study similar problems in neuron systems.
失神癫痫样活动传统上被认为主要是由大脑中形成丘脑皮质回路的皮质和丘脑神经元之间的异常相互作用所诱发的。基底神经节作为大脑中的一个组织单位，与丘脑皮质回路有着密切的输入和输出关系。尽管有几项研究报告称基底神经节可能参与控制和调节失神癫痫样活动，但迄今为止，尚无关于基底神经节是否直接导致失神癫痫样活动的研究。在本文中，我们构建了一个基底神经节 - 皮质丘脑网络模型来确定基底神经节在这种疾病中的作用。我们确定失神癫痫样活动可能是由基底神经节中某些关键通路的异常耦合强度直接诱发的。这些癫痫样活动可以通过从丘脑皮质网络投射到基底神经节的三条主要通路的耦合强度得到很好的控制。结果表明，黑质致密部（SNc）可被视为抑制癫痫样活动的有效治疗靶点区域，这支持了先前研究的观察结果。特别地，作为本文的一项主要贡献，我们确定癫痫性慢棘波的最终呈现位置并不局限于大脑皮层；这些波可能还会出现在丘脑、纹状体中等棘状神经元、纹状体快速发放中间神经元、黑质致密部、底丘脑核、黑质网状部和苍白球外侧部。此外，与先前的几项研究一致，观察到网络延迟是诱导不同类型失神癫痫样活动之间转换的关键因素。我们的新模型不仅解释了发病和控制机制，还为研究神经元系统中的类似问题提供了一个统一的框架。
