EFMouse: a toolbox to model stimulation-induced electric fields in the mouse brain

Abstract

Research into the mechanisms underlying neuromodulation by tES using in-vivo animal models is key to overcoming experimental limitations in humans and essential to building a detailed understanding of the in-vivo consequences of tES. Insights from such animal models are needed to develop targeted and effective therapeutic applications of non-invasive brain stimulation in humans. 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 generate predictions that can be tested with in-vivo recordings in mice. Novel functionality includes the ability to capture typical surgical approaches in the mouse (e.g., cranial recording windows), the placement of stimulation electrodes anywhere in or on the animal, and novel ways to report field predictions, including some refined measures of focality and direction homogeneity, and quantification based on regions defined in the Allen Mouse Brain Atlas. Although the EFMouse toolbox is generally applicable to planning and designing tES studies in mice, we illustrate its use by posing questions about transcranial direct current stimulation (tDCS) experiments with the goal of targeting the left visual cortex of the mouse. The EFMouse toolbox is publicly available at https://github.com/klabhub/EFMouse. Author summaryTranscranial electrical stimulation offers opportunities for studying brain activity and developing neuromodulation therapies. Even though this technique is used extensively in humans, understanding its neural consequences is still limited. Mouse models offer an opportunity to bridge this gap. However, major differences between human and mouse brains, such as brain size and cortical folding, pose a challenge to the design of appropriate stimulation protocols in mice. 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 series of electrode arrangements, 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. HighlightsEFMouse 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. Montages with a return on the mouses back generate homogeneous fields perpendicular to the cortical surface. Montages with a small distance between stimulation and return electrodes on the mouses head can generate focal, but relatively weak fields.