Department of Clinical Neuroscience, Imperial College London, London, UK.
J Neurosci Methods. 2010 Apr 30;188(1):105-12. doi: 10.1016/j.jneumeth.2010.01.026. Epub 2010 Jan 29.
Deep brain stimulation (DBS) is an effective surgical treatment used to alleviate the symptoms of neurological disorders, most commonly movement disorders. However, the mechanism of how the applied stimulus pulses interact with the surrounding neuronal elements is not yet clearly understood, slowing progress and development of this promising therapeutic technology. To extend previous approaches of using isolated, myelinated axon models used to estimate the effect of DBS, we propose that taking into account entire neurons will reveal stimulation induced effects overlooked by previous studies. We compared the DBS induced volume of tissue activated (VTA) using arrays of whole cell models of subthalamic nucleus (STN) excitatory neurons consisting of a cell body and an anatomically accurate dendritic tree, to the common models of axon arrays. Our results demonstrate that STN neurons have a higher excitation threshold than axons, as stimulus amplitudes 10 times as large elicit a VTA range a fifth of the distance from the electrode surface. However, the STN neurons do show a change in background firing rate in response to stimulation, even when they are classified as sub-threshold by the VTA definition. Furthermore the whole neuron models are sensitive to regions of high current density, as the distribution of firing is centred on the electrode contact edges These results demonstrate the importance of accurate neuron models for fully appreciating the spatial effects of DBS on the immediate surrounding brain volume within small distances of the electrode, which are overlooked by previous models of isolated axons and individual neurons.
深部脑刺激（DBS）是一种有效的手术治疗方法，用于缓解神经紊乱的症状，最常见的是运动障碍。然而，应用刺激脉冲如何与周围神经元元素相互作用的机制尚不清楚，这减缓了这项有前途的治疗技术的进展和发展。为了扩展以前使用分离的、有髓鞘的轴突模型来估计 DBS 影响的方法，我们提出考虑整个神经元将揭示以前的研究忽略的刺激诱导效应。我们将由胞体和解剖准确的树突组成的丘脑底核（STN）兴奋性神经元的全细胞模型阵列的 DBS 诱导的组织激活体积（VTA）与常见的轴突阵列模型进行了比较。我们的结果表明，STN 神经元的兴奋阈值高于轴突，因为刺激幅度大 10 倍会产生 VTA 范围，距离电极表面的距离是以前研究的五分之一。然而，即使根据 VTA 定义将 STN 神经元归类为亚阈值，它们也会对刺激产生背景放电率的变化。此外，全神经元模型对高电流密度区域很敏感，因为放电分布集中在电极接触边缘。这些结果表明，对于充分理解 DBS 对电极附近小范围内大脑体积的空间影响，准确的神经元模型很重要，而以前的孤立轴突和单个神经元模型忽略了这一点。
