EFMouse: a Matlab toolbox to model stimulation-induced electric fields in the mouse brain
Authors: Sanchez-Romero Ruben , Akyuz Sibel , Krekelberg Bart 
Published: July 2024

AbstractCompared to the rapidly growing literature on transcranial electrical stimulation (tES) in humans, research into the mechanisms underlying neuromodulation by tES using in-vivo animal models is growing but still relatively rare. Such research, however, is key to overcome experimental limitations in humans and essential to build a detailed understanding of the in-vivo consequences of tES that can ultimately lead to development of targeted and effective therapeutic applications of non-invasive brain stimulation. The sheer difference in scale and geometry between animal models and the human brain contributes to the complexity of designing and interpreting animal studies. Here, we introduce EFMouse, a toolbox that extends previous approaches to model intracranial electric fields and is optimized to generate predictions that can be tested with in-vivo intracranial recordings in mice. Although the EFMouse toolbox has general applicability and could be used to predict intracranial fields for any electrical stimulation study using mice, we illustrate its usage by comparing fields in a tES high-density multi-electrode montage with a more traditional two-electrode montage. Our simulations show that both montages can produce strong focal homogeneous electric fields in targeted areas. However, the high-density montage produces a field that is more perpendicular to the visual cortical surface, which is expected to result in larger changes in neuronal excitability. The EFMouse toolbox is publicly available athttps://github.com/klabhub/EFMouse.Author summaryTranscranial electrical stimulation offers new opportunities for studying brain activity and developing potential therapies. While this technique has been extensively applied in humans, our understanding of its neural consequences is still limited. Animal models offer an opportunity to bridge this gap. However, due to differences in size and brain structure, designing and interpreting electrical stimulation protocols for animal models is challenging. To address this, we developed EFMouse, an open-source computational toolbox that predicts intracranial electrical fields in the mouse brain during stimulation. This toolbox allows researchers to design experiments by simulating electrode arrangements and quantifying properties of the predicted electric field in specific brain regions. By doing so, EFMouse can guide the optimization of stimulation techniques to achieve targeted and reproducible effects. We illustrate its use by comparing a two-electrode and a five-electrode arrangement, in terms of the strength, focality, and direction of their induced electric field. By making EFMouse publicly available, we hope to advance fundamental neuroscience research and the development of future clinical applications.Data/code availability statementAll code and data to reproduce our analyses are available at the EFMouse toolbox repositoryhttps://github.com/klabhub/EFMouse. EFMouse was implemented in Matlab2023a. For the Allen atlas analysis, FSL 6.7.0 onwards is required (https://fsl.fmrib.ox.ac.uk/fsl/). EFMouse toolbox repository DOIhttps://doi.org/10.5281/zenodo.14777233points to the latest version release.Declaration of interestsThe authors have no conflicts of interest to declare.Author statementRuben Sanchez-RomeroConceptualization, Methodology, Software, Formal Analysis, Writing-original draft, Writing-review & editing, Visualization.Sibel AkyuzConceptualization, Methodology, Writing-review & editing.Bart KrekelbergConceptualization, Methodology, Software, Writing-review & editing, Supervision, Resources, Funding acquisition.Financial DisclosureResearch reported in this publication was supported by the National Institute Of Neurological Disorders And Stroke (https://www.ninds.nih.gov/) and the National Institute on Drug Abuse (https://nida.nih.gov/) of the National Institutes of Health under Award Number R01NS120289, for B.K. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funding institution did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.Highlights-EFMouse is a novel, open-source, Matlab-based electric field simulator for the mouse brain.-EFMouse quantifies induced field focality and homogeneity in regions of the Allen Mouse Brain Atlas.-Focal and strong stimulation can be produced with two- or five-electrode montages.-A high-density montage with a lumbar return generates fields perpendicular to the cortical surface.