Department of Mathematics and Center for the Neural Basis of Cognition, University of Pittsburgh, 301 Thackeray Hall, Pittsburgh, PA 15260, USA.
Eur J Neurosci. 2012 Jul;36(2):2213-28. doi: 10.1111/j.1460-9568.2012.08108.x.
The availability of suitable animal models and the opportunity to record electrophysiologic data in movement disorder patients undergoing neurosurgical procedures has allowed researchers to investigate parkinsonism-related changes in neuronal firing patterns in the basal ganglia and associated areas of the thalamus and cortex. These studies have shown that parkinsonism is associated with increased activity in the basal ganglia output nuclei, along with increases in burst discharges, oscillatory firing and synchronous firing patterns throughout the basal ganglia. Computational approaches have the potential to play an important role in the interpretation of these data. Such efforts can provide a formalized view of neuronal interactions in the network of connections between the basal ganglia, thalamus, and cortex, allow for the exploration of possible contributions of particular network components to parkinsonism, and potentially result in new conceptual frameworks and hypotheses that can be subjected to biological testing. It has proven very difficult, however, to integrate the wealth of the experimental findings into coherent models of the disease. In this review, we provide an overview of the abnormalities in neuronal activity that have been associated with parkinsonism. Subsequently, we discuss some particular efforts to model the pathophysiologic mechanisms that may link abnormal basal ganglia activity to the cardinal parkinsonian motor signs and may help to explain the mechanisms underlying the therapeutic efficacy of deep brain stimulation for Parkinson's disease. We emphasize the logical structure of these computational studies, making clear the assumptions from which they proceed and the consequences and predictions that follow from these assumptions.
在进行神经外科手术的运动障碍患者中，合适的动物模型的可用性和记录电生理数据的机会，使研究人员能够研究与帕金森病相关的基底神经节和相关丘脑和皮层区域神经元放电模式的变化。这些研究表明，帕金森病与基底神经节输出核的活动增加有关，伴随着爆发放电、振荡放电和整个基底神经节的同步放电模式的增加。计算方法有可能在解释这些数据方面发挥重要作用。这些努力可以为基底神经节、丘脑和皮层之间的连接网络中的神经元相互作用提供一个形式化的观点，允许探索特定网络组件对帕金森病的可能贡献，并可能导致新的概念框架和假设，可以进行生物测试。然而，将丰富的实验发现整合到疾病的连贯模型中非常困难。在这篇综述中，我们概述了与帕金森病相关的神经元活动异常。随后，我们讨论了一些特定的建模努力，这些努力可能将异常的基底神经节活动与帕金森病的主要运动症状联系起来，并有助于解释深部脑刺激治疗帕金森病的机制。我们强调了这些计算研究的逻辑结构，明确了它们所依据的假设以及这些假设所带来的后果和预测。
