Anatomical correlates of delivered TIS fields across deep and cortical targets

Objective: The objective of this study was to quantify inter-individual variability in target-region TIS envelope amplitude and to examine its associations with anatomical features across deep and cortical targets. Approach: We built individualized finite element head models for 502 healthy HCP participants aged 22-35 years and evaluated five target ROI-montage pairs: hippocampus (two montages), left and right thalamus, and motor cortex. For each target ROI-montage pair, we quantified mean TIS envelope amplitude within target region (EA mean , V/m) and the target-to-brain envelope-amplitude ratio (TBR) as measures of target-field magnitude and spatial selectivity, respectively. Two prespecified global volume ratios were assessed with Pearson correlations, and 20 anatomical features were evaluated using two-stage LASSO-OLS models with an 80:20 internal hold-out split. Bootstrap selection frequencies were calculated for the EA mean models. Main results: EA mean showed substantial inter-individual variability (CV = 28.1-40.0%). Brain-TIV ratio and GM-head ratio were positively correlated with EA mean across all five target ROI-montage pairs (r = 0.281-0.420; all p < 0.001), with directions compatible with CSF-related current shunting. Pairwise EA mean correlations across the five target ROI-montage pairs were high (r = 0.749-0.957). Five two-stage LASSO-OLS models yielded in-sample R 2 values of 0.185-0.282. For TBR, MC1 showed the strongest model fit (R 2 = 0.311; hold-out R 2 = 0.267), while no predictor reached p < 0.05 in either thalamic model. Global predictors appeared repeatedly in the deep-target models. In MC1, the significant set also included skull-head ratio and W-scalp thickness (MC1), neither of which was significant in the deep-target models. The two hippocampal montages (H1 and H2) differed by 31% in EA mean , and their predictor sets reaching OLS p < 0.05 showed modest overlap (Jaccard = 0.33). Significance: This population-scale computational dosimetry analysis quantifies how fixed TIS currents and montages translate into target-field magnitudes across individual head models. The results distinguish the anatomical correlates of delivered amplitude from those of spatial selectivity and provide quantitative information for anatomy-informed TIS planning.