Direction of TIS envelope electric field: Perpendicular to the longitudinal axis of the hippocampus

Temporal Interference Stimulation (TIS) is a non-invasive approach to deep brain stimulation. However, most research has focused on the intensity of modulation, with limited attention given to the directional properties of the induced electric fields, despite their potential importance for precise stimulation.

A novel analytical framework was developed to analyze TIS-induced electric field directions using individual imaging data. For each voxel, the direction corresponding to the maximal modulation depth was calculated. The consistency of these directions within regions of interest (ROIs) and their alignment with the ROI principal axes, derived from principal component analysis (PCA), were assessed.

Simulations revealed complex spatial and temporal trajectories of the electric field at the voxel level. In the left putamen, the maximal modulation depth reached 0.241 ± 0.041 V/m, whereas in the target region, the left hippocampus, it was lower (0.15 ± 0.032 V/m). Notably, in the left hippocampus, the directions of maximal modulation depth were predominantly perpendicular to its longitudinal axis (84.547 ± 8.776°), reflecting structural specificity across its anterior, middle, and posterior regions.

Unlike previous approaches, this study integrates directional analysis into TIS modeling, providing a foundation for precise stimulation by exploring structural alignment.

Our analysis revealed that the orientations of maximal modulation depth in the left hippocampus were perpendicular to its longitudinal axis under the current electrode configuration, but they shifted to parallel alignment when the electrode pairs were swapped. This directional specificity offers insights for optimizing TIS by aligning with structural features, presenting a potential strategy to enhance stimulation precision and broaden its clinical and research applications.