Direction-Dependent Effects of White-Matter Conductivity Anisotropy on Modulation Depth and Spatial Extent in Transcranial Interference Stimulation: A Simulation Study.

Transcranial interference stimulation (TIS) is a non-invasive neuromodulation technique designed to modulate deep brain structures. Although most TIS simulation studies assume isotropic tissue conductivity, white-matter (WM) conductivity is direction dependent. This study investigated how diffusion-tensor-imaging-derived, volume-normalized WM conductivity anisotropy affects the magnitude and spatial distribution of the maximum low-frequency envelope amplitude, here termed maximum modulation depth (MDmax), in individualized TIS models. Six individualized head models were constructed from structural and diffusion MRI data. Isotropic and anisotropic conductivity models were compared under two manually selected proof-of-concept TIS montages designed to produce contrasting modulation-depth directions relative to the dominant fibre orientation of the corpus callosum. For each voxel, MDmax and the corresponding unit modulation-depth direction vector were calculated. Directionality was evaluated in the corpus callosum by comparing this vector with the principal diffusion eigenvector, v₁. To assess whether these effects extended beyond the corpus callosum, additional target-specific analyses were performed in the left M1 and left hippocampus using montages selected in the isotropic model and held fixed between conductivity models. Anisotropic conductivity altered both the magnitude and spatial distribution of the simulated TIS envelope. Whole-brain MDmax was higher in the anisotropic than in the isotropic model under both montages, whereas threshold-defined high-MD volume showed montage-dependent differences. In the corpus callosum body, regional peak modulation depth was higher when the modulation-depth direction vector was more collinear with v₁, but lower when the two directions were approximately orthogonal. Under the target-specific montages, regional peak modulation depth increased modestly in the left primary motor cortex but decreased in the left hippocampus. These findings indicate that anisotropy-related changes are direction- and region-dependent and vary across target-specific montage configurations. Local fibre orientation should therefore be considered when interpreting individualized TIS field models.