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. 2025 Jan-Feb;18(1):77-93.
doi: 10.1016/j.brs.2024.12.1192. Epub 2024 Dec 20.

Enabling electric field model of microscopically realistic brain

Zhen Qi  1 , Gregory M Noetscher  2 , Alton Miles  1 , Konstantin Weise  3 , Thomas R Knösche  4 , Cameron R Cadman  1 , Alina R Potashinsky  1 , Kelu Liu  1 , William A Wartman  1 , Guillermo Nunez Ponasso  1 , Marom Bikson  5 , Hanbing Lu  6 , Zhi-De Deng  7 , Aapo R Nummenmaa  8 , Sergey N Makaroff  9
Affiliations

Enabling electric field model of microscopically realistic brain

Zhen Qi et al. Brain Stimul. 2025 Jan-Feb.

Abstract

Background: Modeling brain stimulation at the microscopic scale may reveal new paradigms for various stimulation modalities.

Objective: 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.

Methods: 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.

Result: 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.

Conclusion: 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.

Keywords: Biophysical modeling; Boundary element fast multipole method (BEM-FMM); Brain modeling at the microscopic scale; Brain stimulation; Electric field spatial noise; Multiscale brain modeling; Significance statement.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sergey N. Makaroff reports financial support was provided by National Institute of Mental Health. Sergey N. Makaroff reports was provided by National Institute of Biomedical Imaging and Bioengineering. Aapo R. Nummenmaa reports financial support was provided by National Institute on Deafness and Other Communication Disorders. Zhi-De Deng reports financial support was provided by National Institute of Mental Health. Hanbing Lu reports was provided by National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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