SUPPLEMENTARY METHODS AND RESULTS Magnetic Resonance Imaging

3D high-resolution T1-weighted: MPRAGE pulse sequence covering the whole brain was acquired with the following parameters: 160 contiguous slices of 1-mm thickness in sagittal orientation; in plane FOV=256×256 mm2, and matrix size 256×256 yielding a spatial resolution of 1×1×1 mm3. The echo time, repetition time, and inversion time were set to TE/TR/TI=3.93 ms/3000 ms/1100 ms with a flip angle FA=15°. Axial T2-weighted: Turbo spin echo (TSE) pulse sequence: 32 contiguous slices of 2-mm thickness in AC-PC orientation; in plane FOV=180×256 mm2, and matrix size 360×512 yielding a spatial resolution of 0.5×0.5×2 mm3. The echo time and repetition time were set to TE/TR=99 ms/6220 ms with a flip angle FA=150°. Coronal T2-weighted: TSE pulse sequence: 32 contiguous slices of 2-mm thickness, perpendicular to AC-PC plane; in plane FOV=168×224 mm2, and matrix size 384×512 yielding a spatial resolution of 0.44×0.44×2 mm3. The echo time and repetition time were set to TE/TR=99 ms/6220 ms with a flip angle FA=150°. Other routine sequences included whole-brain T2-weighted TSE and Fluid-Attenuated Inversion Recovery (FLAIR), and T1-weighted turbo inversion recovery (TIR) in order to discard others surgery-related brain abnormalities.

Probabilistic maps of lesions

Figure S1. Probabilistic maps of lesion distribution for the three groups as divided according with clinical improvement, drawn on coronal sections of the Schaltenbrand and Wharen atlas. Color scales represent the probability of a voxel to belong to Group 1 (red, upper panel), Group 2 (blue, middle panel) or Group 3 (green, lower panel). The coronal maps are arranged from central (F.p 3.0) to posterior (F.p 5.0) sections of the STN. Star (*) represents the center of mass of lesions.

Figure S2. Probabilistic maps of lesion distribution for the three groups as divided according with clinical improvement, drawn on horizontal sections of the Schaltenbrand and Wharen atlas at dorsal level (H.v 1.0) and other two levels ventral to H.v 1.0 (H.v 1.5 and H.v 3.5). Color scales are identical to Figure S1.

Figure S1.

F.p 3.0 F.p 4.0 F.p 5.0

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Figure S2.

H.v 1.0 H.v 1.5 H.v 3.5

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Diffusion Tensor Fiber Tractography

Acquisition: Diffusion weighted MRI data were acquired using a single shot EPI sequence. Fifty-two slices of 2.5 mm thickness with no distance factor were acquired with the following parameters: b=1000 s/mm2; FOV=206×206 mm2; acquisition matrix=128×128; corresponding to an ‘in plane’ spatial resolution of 1.61×1.61 mm2; TE/TR=160 ms/7000 ms. The aforementioned acquisition was repeated 5 times to improve signal to noise ratio. In order to improve EPI quality, magnitude and phase difference images of a T2 gradient echo field mapping sequence were acquired with TE=7.71 ms and 12.47 ms.

Region of Interest (ROI) definitions: ROI locations were determined on the basis of previous works published in the literature and neuroanatomy atlases. The atlases were mapped to subject space by nonlinear registration between the anisotropy map and the atlas included in the DSI Studio package (Fig 1S-A). The (STN), ventrolateral (VL) and ventroanterior (VA) nuclei of the are available in the internally consistent Canonical Model of Morel’s atlas in the ICBM space [1]. internal (GPi) and external (GPe), and are available in the Harvard-Oxford sub- cortical atlas (http://dsi-studio.labsolver.org/). Cortico-spinal track was reconstructed from the JHU white-matter tractography atlas [2].

Deterministic tractography: tracts were reconstructed using a streamline deterministic tractography (FACT) algorithm implemented in the DSI-Studio software package (http://dsi-studio.labsolver.org/). A maximum of 500 mm trace length and a curvature threshold of ± 90° were imposed as tracking parameters. For each seed region, a maximum of 5000 streamlines was imposed.

Track-based analysis: Figure S3-A shows relevant regions registered to the anisotropy map of a representative patient (patient 32). GPi was used as seed in each patient to track streamlines connecting with thalamus. Subthalamic connections are filtered out using the STN as region of avoidance (ROA). The red nucleus and cortico-spinal track are used with spatial orientation purposes. Figure S3-B shows reconstructed fibres, where ventral and dorso-medial pathways are clearly visualized (i.e. and , respectively), converging dorsal-medial-rostral to the STN. Fibre volume is computed by summing the volume of estimated tensors, corrected for overall hemispheric tract volume (using the hemispheric white matter as seed region).

ROI-based analysis Reconstructed pallido-thalamic tracks are converted into a binary ROI. Based on it and digitized corregistered SW-atlas, a region below the thalamus, medial to the and dorsal- medial to STN was drawn manually for each patient in all slices containing pallido-thalamic connections (Figure S3-C and Figure 4 A,B). Note the heterogeneous region medial-dorsal to STN with no pallido-thalamic connections containing the (ZI). Considering that crossing fibres from the contralateral are not resolvable with our low angular resolution and FACT algorithm, and that our hypothesis points to the effect of the lesion on the region surrounding the STN, we opted for a rough approach including this area. Thus, the area under analysis contains the lenticular and thalamic fasciculus (H2 and H1 ) and dorso-medial ZI (ZI.dm), but also contains the prelemniscal radiations, dentate-rubro-thalamic tracks and the more anterior part of the caudal ZI (ZI.c) (see Figures S1 and S2) [3-5]. Mean fractional anisotropy (FA) in this region was computed for each patient.

Figure S3. Connectivity analysis of an illustrative case (patient 32). A) relevant regions of interest in the ICBM space: subthalamic nucleus (yellow, region of avoidance), ventrolateral nuclei of the thalamus (pink, region of interest), internal (red, seed region) and external (green) globus pallidus, and red nucleus (purple). B) Streamline deterministic tractography. Ventral (ansa lenticularis) and dorso-medial (lenticular fasciculus) pathways are differentiated, converging dorsal-medial-rostral to the STN in the thalamic fasciculus. C) ROI-based analysis. Region of interest was drawn including the voxels of the pff and adjacent ZI.

Visualization.

For visual analysis, probabilistic lesions were projected in a high angular and spatial resolution DTI template in the ICBM space [6]. The HCP-842 atlas was constructed using 842 subjects' DWI data from the Human Connectome Project (sampling directions = 90/90/90, b-values = 1000/2000/3000 s/mm2, in-plane resolution = 1.25 mm, slice thickness = 1.25 mm). HCP-842 data was used for visualization purpose only, in order to facilitate the comprehension of the spatial association between lesions and development of hemichorea-ballism (see Figure 4). Pff and drt were reconstructed using q-space diffeomorphic reconstruction [7].

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