Abstract
Abstract
Objective. Electrical stimulation is the most commonly used modality for neuromodulation, with a number of clinical and scientific applications. Although the basic mechanisms of neural activation by electrical stimulation are well understood, important questions remain regarding neural responses to diffuse electric fields such as those generated by transcranial electrical stimulation. For such diffuse fields, the orientation of the electric field with respect to the neurons being stimulated matters, but previous ex vivo brain slice studies–commonly used to study how neurons respond to external electric fields–have only considered electric fields applied in the plane of the slice. Approach. We used two electrode arrays–one oriented parallel and the other perpendicular to coronal brain slices–to generate electric fields oriented orthogonally to the slice as well as along the cortical column. We measured responses in Layer 5 of the somatosensory cortex using several 2-electrode stimulation configurations, while also varying the distance between the electrodes and the slice. Main results. Electrode patterns generating a large electric field component orthogonal to the slice evoked the largest neural responses at every electrode-slice distance. Moreover, neural thresholds were > 5× lower for electric fields orthogonal to the slice compared to electric fields along the cortical column. Significance. These results provide a better understanding of the brain slice as a model for noninvasive stimulation and could lead to new electrode configurations for efficient transcranial neural stimulation.