Qi Zhen, Noetscher Gregory M, Miles Alton, Weise Konstantin, Knösche Thomas R, Cadman Cameron R, Potashinsky Alina R, Liu Kelu, Wartman William A, Ponasso Guillermo Nunez, Bikson Marom, Lu Hanbing, Deng Zhi-De, Nummenmaa Aapo R, Makaroff Sergey N
Department of Electrical and Computer Eng., Worcester Polytechnic Inst., Worcester, MA, USA.
Department of Electrical and Computer Eng., Worcester Polytechnic Inst., Worcester, MA, USA.
Brain Stimul. 2025 Jan-Feb;18(1):77-93. doi: 10.1016/j.brs.2024.12.1192. Epub 2024 Dec 20.
Modeling brain stimulation at the microscopic scale may reveal new paradigms for various stimulation modalities.
We present the largest map to date of extracellular electric field distributions within a layer L2/L3 mouse primary visual cortex brain sample. This was enabled by the automated analysis of serial section electron microscopy images with improved handling of image defects, covering a volume of 250 × 140 × 90 μm³.
The map was obtained by applying a uniform brain stimulation electric field at three different polarizations and accurately computing microscopic field perturbations using the boundary element fast multipole method. We used the map to identify the effect of microscopic field perturbations on the activation thresholds of individual neurons. Previous relevant studies modeled a macroscopically homogeneous cortical volume.
Our result shows that the microscopic field perturbations - an 'electric field spatial noise' with a mean value of zero - only modestly influence the macroscopically predicted stimulation field strengths necessary for neuronal activation. The thresholds do not change by more than 10 % on average.
Under the stated limitations and assumptions of our method, this result essentially justifies the conventional theory of "invisible" neurons embedded in a macroscopic brain model for transcranial magnetic and transcranial electrical stimulation. However, our result is solely sample-specific and is only relevant to this relatively small sample with 396 neurons. It largely neglects the effect of the microcapillary network. Furthermore, we only considered the uniform impressed field and a single-pulse stimulation time course.
在微观尺度上对脑刺激进行建模可能会揭示各种刺激方式的新范例。
我们展示了迄今为止小鼠初级视觉皮层L2/L3层脑样本中细胞外电场分布的最大图谱。这是通过对连续切片电子显微镜图像进行自动分析实现的，改进了对图像缺陷的处理，覆盖体积为250×140×90μm³。
通过在三种不同极化方向施加均匀的脑刺激电场，并使用边界元快速多极子方法精确计算微观场扰动来获得该图谱。我们用该图谱来确定微观场扰动对单个神经元激活阈值的影响。先前的相关研究对宏观上均匀的皮质体积进行了建模。
我们的结果表明，微观场扰动——一种平均值为零的“电场空间噪声”——仅对神经元激活所需的宏观预测刺激场强产生适度影响。阈值平均变化不超过10%。
在我们方法的既定局限性和假设下，这一结果从本质上证明了传统理论中关于经颅磁刺激和经颅电刺激的宏观脑模型中嵌入“不可见”神经元的合理性。然而，我们的结果仅针对特定样本，仅与这个包含396个神经元的相对小样本相关。它在很大程度上忽略了微毛细血管网络的影响。此外，我们仅考虑了均匀外加场和单脉冲刺激时间过程。
