Impact of brain anisotropy on transcranial temporal interference stimulation: numerical analysis toward reliable montage optimization.

Transcranial temporal interference stimulation (TIS) is gaining attention as a non-invasive method for engaging deep brain regions. However, TIS-generated current flow to deep targets necessarily passes through highly anisotropic white-matter pathways, and the extent to which anisotropy alters interferential fields remains insufficiently quantified. This study systematically evaluates how anisotropic conductivity affects deep-brain interferential fields and influences TIS montage optimization. Subject-specific anatomical head models incorporating either anisotropic or isotropic conductivities were constructed. For the anisotropic condition, full conductivity tensors were derived from diffusion-weighted imaging for gray matter, white matter, and deep targets. Interferential fields were examined using Pareto-based optimization to compare montage selection between conductivity models. Anisotropy altered interferential field intensities by up to 18% in white matter and remained below 12% in deep targets. These differences resulted in a 50% divergence in optimized montages. When constraining focality and target-field differences to within 10%, montage agreement increased to nearly 90%. Anisotropic conductivities influence focality and field orientation and optimal montage selection. Nonetheless, under practical tolerance ranges for focality and target-field strength, optimized solutions converge across conductivity models. These results indicate that isotropic models can support routine TIS montage optimization when diffusion data are unavailable, while anisotropy remains essential for accurate deep-brain stimulation modeling. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-026-00575-y.