Cortical activity can be modulated by endogenous and exogenous electric fields (EFs). Recent experimental and computational data suggested that endogenous EF-mediated effects are compatible with electric dipoles, which contribute to the synchronization of neighboring cortical columns. Consistently, exogenous EFs created by means of transcranial direct-current stimulation (tDCS) have shown that the orientation of current flow determines the effect of the intervention. Here, we investigated the impact of an exogenous EF’s orientation on cortical modulation. We hypothesized that electric dipoles orthogonal to the cortical surface are responsible for the impact of the EF’s orientation on cortical modulation. We tested this hypothesis experimentally in cortical slices and in silico in a mean-field computational model of cortical columns. In the experimental setting, we applied constant exogenous EFs (−/+ 3 V/m) with different orientations (0°, 45° and 90°) to cortical slices expressing spontaneous slow oscillations (ca. 0.3 Hz). We found that DC fields orthogonal to the cortical surface had a maximum modulatory effect, while the efficacy decreased with the rotation of the EF, having a null effect when parallel to the cortical surface. These results were successfully reproduced in a computational model of a cortical column with dipolar properties. The model suggested that the effect of the exogenous EF on neuronal populations is proportional to the cosine of the angle between the direction of the applied EF and the vertical axis of the dipole. Overall, our experiments support the critical role of electric dipoles in understanding the impact of exogenous EFs on cortical activity modulation.

This preprint has been peer-reviewed and published in Neuroscience. Please cite the published version: https://doi.org/10.1016/j.neuroscience.2025.10.019