Impact of Brain Anisotropy on Transcranial Temporal Interference Stimulation: Numerical Analysis Toward Reliable Montage Optimization

Background & Aim: Transcranial temporal interference stimulation (TIS) is a novel transcranial electrical stimulation modality that enables focused targeting of deep brain structures. When targeting deep regions, current pathways traverse the highly anisotropic white matter, making anisotropy a potentially critical factor. This study aimed to clarify how anisotropy influences interferential currents in deep brain regions and to assess its impact on TIS montage optimization for the first time. Methods: Anatomical head conductor models with anisotropic and isotropic conductivities were compared to evaluate the role of anisotropy in the intracranial interferential currents distributions and montage optimization. For the anisotropic conductivity, conductivity tensors were derived from diffusion-weighted imaging data for gray matter, white matter, and deep brain structures. Montage optimization was conducted based on Pareto front optimization. Results: In literature-reported TIS montages, anisotropic conductivity significantly altered the interferential electric field intensity, with differences of up to 18% in the white matter, whereas discrepancies in deep brain structures remained below 12%. For TIS-optimized montages, these variations across conductivity models yielded only 50% montage disagreement. However, when constraining differences in focality and target field strength to within 10%, the agreement improved to nearly 90%. Conclusions: Incorporating anisotropic conductivities is important to determine individualized focality and target-field characteristics. Moreover, anisotropy can substantially affect the selection of the optimal montage, but under practical focality and target-field tolerances, montage choices largely converge.