Fig. 3: Anatomical localization and cross-validation of the optimal stimulation site.

A K-fold cross-validation (k = 10) demonstrating that DBS E-field locations are significantly associated with clinical outcomes in left-out patients (p = 0.047; two-sided, non-parametric, permutation-based t-test, 10,000 permutations). Box plots show the median (thick line), interquartile range (IQR; 25th–75th percentile), and whiskers extending to 1.5× IQR. Individual patient values are overlaid as jittered dots. B Three-dimensional visualization of the stimulation sweet spot, defined as the center of gravity of the largest suprathreshold cluster (p < 0.05, uncorrected) identified via two-sided, voxel-wise, two-sample t-tests comparing E-field magnitudes between improved and non-improved groups. The sweet spot is displayed relative to the centromedian (CM), parafascicular (Pf), and subparafascicular (sPf) nuclei, as defined by the atlas of Krauth et al.⁹³ based on the histological work of Morel¹⁰⁷. Analyses included patients with successful nonlinear image registration to MNI space (n = 10 improved, n = 18 non-improved). C Orthogonal slices showing the unthresholded t-score map. Positive values indicate voxels where E-field magnitude was higher in the improved group; negative values indicate higher E-field magnitude in the non-improved group. Slice coordinates (X, Y, Z) reflect mm positions in MNI152 ICBM 2009b nonlinear asymmetric template space. The unthresholded map is available in NIfTI format at: https://osf.io/bjah5. The map is displayed on the BigBrain atlas¹⁰⁴ registered to MNI space¹⁰⁵. D Thresholded map (p < 0.05, uncorrected; two-sided, voxel-wise two-sample t-tests) highlighting the peak location associated with clinical improvement. Source data are provided as a Source Data file. A Anterior, CL Central lateral nucleus, I Inferior, L Left, Lat. Lateral, Md Mediodorsal nucleus, Med. Medial, P Posterior, PC Posterior commissure, Pulv Pulvinar nucleus, R Right, RN Red nucleus, S Superior.