Pierce Anne F, Shupe Larry, Bloch Julien, Fetz Eberhard, Yazdan-Shahmorad Azadeh
Department of Bioengineering, University of Washington, Seattle, WA 98195, USA; Washington National Primate Research Center, Seattle, WA 98195, USA.
Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195, USA.
J Neurosci Methods. 2025 Oct;422:110514. doi: 10.1016/j.jneumeth.2025.110514. Epub 2025 Jun 13.
Computational models that predict effects of neural stimulation can serve as a preliminary tool to inform in-vivo research, reducing costs, time, and ethical considerations. However, current models do not support the diverse neural stimulation techniques used in-vivo, including the expanding selection of electrodes, stimulation modalities, and stimulation protocols.
We developed several extensions to The Virtual Electrode Recording Tool for EXtracellular Potentials (VERTEX), the MATLAB-based neural stimulation tool. VERTEX simulates input currents in a large population of multi-compartment neurons within a small cortical slice to model electric field stimulation, while recording local field potentials (LFPs) and spiking activity. Our extensions enhance this framework with support for multiple pairs of parametrically defined electrodes and biphasic, bipolar stimulation delivered at programmable delays. To support the growing use of optogenetic approaches for targeted neural stimulation, we introduced a feature that models optogenetic stimulation through an additional VERTEX input function that converts irradiance to currents at optogenetically responsive neurons. Finally, we added extensions to allow complex stimulation protocols including paired-pulse, spatiotemporal patterned, and closed-loop stimulation.
We demonstrated these novel features using VERTEX's built-in functionalities, with results consistent with other models and experimental work.
Unlike other tools, our extensions enable both electric field and optogenetic stimulation, provide a range of open- and closed-loop protocols, and offer flexible settings within a large-scale cortical network of neurons with realistic biophysical properties.
Our extensions provide an all-in-one platform to efficiently and systematically test diverse, targeted, and individualized stimulation patterns.
预测神经刺激效果的计算模型可作为一种初步工具,为体内研究提供信息,降低成本、节省时间并减少伦理考量。然而,当前模型并不支持体内使用的多种神经刺激技术,包括不断增加的电极选择、刺激方式和刺激方案。
我们对基于MATLAB的神经刺激工具——用于细胞外电位的虚拟电极记录工具(VERTEX)进行了多项扩展。VERTEX在一个小的皮质切片内的大量多节段神经元中模拟输入电流,以对电场刺激进行建模,同时记录局部场电位(LFP)和尖峰活动。我们的扩展通过支持多对参数定义的电极以及以可编程延迟进行的双相、双极刺激来增强这一框架。为了支持越来越多地使用光遗传学方法进行靶向神经刺激,我们引入了一项功能,通过一个额外的VERTEX输入函数对光遗传学刺激进行建模,该函数将光照射强度转换为光遗传学响应神经元处的电流。最后,我们添加了扩展功能,以允许使用复杂的刺激方案,包括配对脉冲、时空模式和闭环刺激。
我们使用VERTEX的内置功能展示了这些新特性,结果与其他模型和实验工作一致。
与其他工具不同,我们的扩展功能既支持电场刺激也支持光遗传学刺激,提供了一系列开环和闭环方案,并在具有现实生物物理特性的大规模神经元皮质网络中提供了灵活的设置。
我们的扩展功能提供了一个一体化平台,可高效、系统地测试各种不同的、靶向的和个性化的刺激模式。