Coordinated reset stimulation in a large-scale model of the STN-GPe circuit.

Coordinated reset stimulation in a large-scale model of the STN-GPe circuit.
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DOI:
10.3389/fncom.2014.00154
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发表时间:
2014
影响因子:
3.2
通讯作者:
Tass PA
Tass PA
中科院分区:
医学4区
文献类型:
--
作者:
Ebert M;Hauptmann C;Tass PA

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神经元群体的同步是几种脑部疾病的标志。协调复位(CR)刺激是一种基于模型的刺激技术,它通过去同步化专门抵消异常同步。电CR刺激,例如,用于治疗帕金森氏病(PD),通过深部电极给药。为了更深入地了解这种技术,我们扩展了以前研究的自上而下的方法,并构建了相应脑区的大规模计算模型。此外,我们还考虑了模拟大脑结构的空间解剖学特性,并结合了2 · 104个模拟神经元的详细数字表示。我们模拟了丘脑底核(subthalamic nucleus,简称STN)和苍白球(globus pallidus externus,简称GPe)。神经元内的连接受尖峰时间依赖性可塑性(STDP)的支配。通过这种方式,我们模拟了所考虑的大脑结构的生理和病理活动。特别是,我们研究了如何利用可塑性,以及如何通过CR刺激神经元将模型从强同步(病理)活动转移到神经元群体的强去同步(健康)活动。此外,我们研究了特定刺激参数,特别是电极位置对刺激结果的影响。我们的模型提供了一个生物病理学现实模型的大脑区域相关的出现在PD的病理神经元活动向前迈进了一步。此外,我们的模型构成了一个测试台,用于优化刺激参数和新型电极几何形状,以实现有效的CR刺激。
Synchronization of populations of neurons is a hallmark of several brain diseases. Coordinated reset (CR) stimulation is a model-based stimulation technique which specifically counteracts abnormal synchrony by desynchronization. Electrical CR stimulation, e.g., for the treatment of Parkinson's disease (PD), is administered via depth electrodes. In order to get a deeper understanding of this technique, we extended the top-down approach of previous studies and constructed a large-scale computational model of the respective brain areas. Furthermore, we took into account the spatial anatomical properties of the simulated brain structures and incorporated a detailed numerical representation of 2 · 104 simulated neurons. We simulated the subthalamic nucleus (STN) and the globus pallidus externus (GPe). Connections within the STN were governed by spike-timing dependent plasticity (STDP). In this way, we modeled the physiological and pathological activity of the considered brain structures. In particular, we investigated how plasticity could be exploited and how the model could be shifted from strongly synchronized (pathological) activity to strongly desynchronized (healthy) activity of the neuronal populations via CR stimulation of the STN neurons. Furthermore, we investigated the impact of specific stimulation parameters especially the electrode position on the stimulation outcome. Our model provides a step forward toward a biophysically realistic model of the brain areas relevant to the emergence of pathological neuronal activity in PD. Furthermore, our model constitutes a test bench for the optimization of both stimulation parameters and novel electrode geometries for efficient CR stimulation.
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