Extracellular neural microstimulation may activate much larger regions than expected by simulations: a combined experimental and modeling study.
Extracellular neural microstimulation may activate much larger regions than expected by simulations: a combined experimental and modeling study.
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DOI：
10.1371/journal.pone.0041324
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Yvert B
中科院分区：
文献类型：
--
作者：
Joucla S;Branchereau P;Cattaert D;Yvert B
几十年来，中枢神经系统的电刺激已被广泛用于基础研究目的或临床治疗应用。然而，关于电刺激的空间范围知之甚少。如果开创性的实验研究报告说，激活阈值电流（TC）随着神经元到电极距离的平方在几百微米以上而增加，那么没有证据表明这种二次定律对更大的距离仍然有效。此外，如今，数值模拟方法已经取代了估计TC的实验研究。然而，模型预测尚未得到验证，直接与实验中的一个共同的范例。在这里，我们提出了一个直接的比较实验测定和建模预测的TC到几毫米的距离。首先，我们结合膜片钳记录和微电极阵列刺激在整个胚胎小鼠脊髓，以确定TC。实验阈值并不遵循二次定律超过1毫米，而是往往保持恒定的距离大于1毫米。接下来，我们建立了相同实验范式的组合有限元-房室模型来预测TC。虽然理论TC在<250微米的距离上与实验TC非常接近，但在更大的距离上被高度高估。这种差异仍然存在，即使修改后的有限元模型的势场，考虑到各向异性，异质性或介电性能的组织。总之，这些结果表明，TC的二次演化并不总是适用于电极和神经元之间的大距离，并且经典模型可能低估了由电刺激激活的组织的体积。
Electrical stimulation of the central nervous system has been widely used for decades for either fundamental research purposes or clinical treatment applications. Yet, very little is known regarding the spatial extent of an electrical stimulation. If pioneering experimental studies reported that activation threshold currents (TCs) increase with the square of the neuron-to-electrode distance over a few hundreds of microns, there is no evidence that this quadratic law remains valid for larger distances. Moreover, nowadays, numerical simulation approaches have supplanted experimental studies for estimating TCs. However, model predictions have not yet been validated directly with experiments within a common paradigm. Here, we present a direct comparison between experimental determination and modeling prediction of TCs up to distances of several millimeters. First, we combined patch-clamp recording and microelectrode array stimulation in whole embryonic mouse spinal cords to determine TCs. Experimental thresholds did not follow a quadratic law beyond 1 millimeter, but rather tended to remain constant for distances larger than 1 millimeter. We next built a combined finite element – compartment model of the same experimental paradigm to predict TCs. While theoretical TCs closely matched experimental TCs for distances <250 microns, they were highly overestimated for larger distances. This discrepancy remained even after modifications of the finite element model of the potential field, taking into account anisotropic, heterogeneous or dielectric properties of the tissue. In conclusion, these results show that quadratic evolution of TCs does not always hold for large distances between the electrode and the neuron and that classical models may underestimate volumes of tissue activated by electrical stimulation.
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影响因子：
4
作者：
Djilas, M.;Oles, C.;Picaud, S.
通讯作者：
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影响因子：
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作者：
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通讯作者：
Yvert B