Figure 3 Anatomical distribution of all implanted electrodes

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Figure 3 Anatomical distribution of all implanted electrodes Figure 3 Anatomical distribution of all implanted electrodes. The anatomical location of all electrodes of 174 leads ... Figure 3 Anatomical distribution of all implanted electrodes. The anatomical location of all electrodes of 174 leads is depicted on the Yelnik Atlas (Yelnik et al., 2007). Inactive contacts are in grey, active contacts are colour-coded, based on stimulation-induced motor score improvement. In horizontal (A) and frontal (B) view contact size is scaled down by 75% with respect to the pallidum for a better overview. The total of 696 electrodes of 174 leads in 87 subjects were classified according to their atlas-based location inside the GPi, GPe or subpallidal white matter (C). A grey colour denotes inactive electrodes. The percentage of motor score improvement associated with an electrode is colour-coded purple (<25%), pink (25–50%), light green (50–80%) and dark green (>80%). Most electrodes were located inside the GPi and subpallidal white matter. Among all available electrode contacts, a significantly larger proportion of activated contacts were located in subpallidal white matter compared to those located inside the GPi (P < 0.001). Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.comThis article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) Brain, awz046, https://doi.org/10.1093/brain/awz046 The content of this slide may be subject to copyright: please see the slide notes for details.

Figure 2 Variability in response of dystonic symptoms to pallidal deep brain stimulation. Improvement indicated on the ... Figure 2 Variability in response of dystonic symptoms to pallidal deep brain stimulation. Improvement indicated on the TWSTRS for cervical or BFMDRS for generalized dystonia compared to baseline. Each patient was grouped into one of the four response categories: non-responder (<25%; purple), average responder (25–50%; pink), good responder (50–80%; light green) and super-responder (>80%; dark green). Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.comThis article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) Brain, awz046, https://doi.org/10.1093/brain/awz046 The content of this slide may be subject to copyright: please see the slide notes for details.

Figure 1 Workflow of sweet spot analysis Figure 1 Workflow of sweet spot analysis. The image analysis workflow that yields the sweet spot is summarized in six ... Figure 1 Workflow of sweet spot analysis. The image analysis workflow that yields the sweet spot is summarized in six consecutive steps. Steps 1–3 are performed using SureTune software. Both the registration of the atlas and detection of lead were performed semi-automatically and were manually validated. Then the data was exported to MATLAB, where steps 4–6 were done with custom built scripts. The volumes of tissue activated (VTAs) were labelled with clinical scores (4) and brought together to a common space (ICBM 2009b NLIN) based on the registered atlases (5). Finally, a statistical analysis for each voxel resulted in a heat map, from which a sweet spot (green) could be distilled. Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.comThis article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) Brain, awz046, https://doi.org/10.1093/brain/awz046 The content of this slide may be subject to copyright: please see the slide notes for details.

Figure 4 Outcome probability of pallidal neurostimulation for dystonia Figure 4 Outcome probability of pallidal neurostimulation for dystonia. The image shows the results of the voxel-wise ... Figure 4 Outcome probability of pallidal neurostimulation for dystonia. The image shows the results of the voxel-wise statistical VTA analysis of 87 dystonia subjects with respect to the dystonia motor score reduction. (A) Heatmap of all dystonia subjects based on signed P-values (a combined t-statistic and P-value; see ‘Materials and methods’ section for details). (B) There was a similar anatomical position of voxels with highest probability of good outcome, with P < 0.05 in cervical (yellow) and generalized (red) and P < 0.01 in all subjects (green). The position of the ‘anti-dystonic sweet spot’ arrogated from 174 different VTAs with different clinical responses (P < 0.01; cluster size threshold >500 voxels) is shown in the axial (C) and sagittal (D) view. Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.comThis article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) Brain, awz046, https://doi.org/10.1093/brain/awz046 The content of this slide may be subject to copyright: please see the slide notes for details.

Figure 5 Correlation of observed clinical improvement with active contact location and VTA-atlas model estimation. The ... Figure 5 Correlation of observed clinical improvement with active contact location and VTA-atlas model estimation. The active contact location was not significantly correlated with clinical improvement provided by pallidal deep brain stimulation (A and B). In contrast, patients with higher scores in the VTA atlas estimation improved significantly more than patients with a low score (C). The atlas estimation used the spatial overlap between the patient specific VTA and the heat map, which results in a distribution of heat-map values for included voxels. This distribution is fed into a linear model and used for training. The trained parameters can then be applied to any new distribution and an individual improvement score will be calculated, which is done here for all patients in a leave-one-out fashion. (D) VTA-atlas-based prediction in an independent dataset of 10 patients with dystonia, forecasting the measured clinical improvement within a mean error of 10.3% (±8.9). Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.comThis article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) Brain, awz046, https://doi.org/10.1093/brain/awz046 The content of this slide may be subject to copyright: please see the slide notes for details.

Figure 6 VTA-atlas prediction modelling in three dystonia patients with pallidal DBS. The image shows the clinical ... Figure 6 VTA-atlas prediction modelling in three dystonia patients with pallidal DBS. The image shows the clinical outcome prediction in individual patients based on the VTA atlas of their stimulation. The current algorithm uses the prediction model, spatial overlap between the patient specific VTA and the heat map, which results in a distribution of heat map- values for included voxels. Clinical response was predicted based on this distribution within a mean error of 15.6 ± 12.5%. Selected examples include a non- and a super-responder with accurate prediction (top and middle), and a good responder (bottom). Interestingly, none of the individual VTAs covered the spot of highest outcome probability (green area, with a P < 0.05), but the prediction model on the whole VTA-atlas map was able to provide an accurate prediction. This illustrates the limitation of a statistical group finding (e.g. the sweet spot) on an individual level. In other words, a stimulation of the sweet spot is not necessary for an individual good motor outcome, but the statistical likelihood is higher. Green dots in the middle column indicate the position of the spot of highest outcome probability in the individual anatomical space of these subjects. Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.comThis article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) Brain, awz046, https://doi.org/10.1093/brain/awz046 The content of this slide may be subject to copyright: please see the slide notes for details.

Figure 7 Exhaustive evaluation of all possible contact positions Figure 7 Exhaustive evaluation of all possible contact positions. Predicted dystonia improvement based on the ... Figure 7 Exhaustive evaluation of all possible contact positions. Predicted dystonia improvement based on the VTA-atlas estimation model (left, middle) compared to the clinically observed outcome (right). In silico testing of all possible monopolar electrode choices with a predefined VTA (3.0 mA; 90 µs) was used to determine the model based prediction of dystonia improvement for the ‘optimal’ computer selected electrode choice. Compared to clinically derived programming choices (middle) the predicted outcome is significantly higher (60.5 ± 21.9% to 76.8 ± 15.3%; P < 0.03). No differences between model based prediction of dystonia improvement for the clinical programming choices to observed clinical outcome (right). Unless provided in the caption above, the following copyright applies to the content of this slide: © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.comThis article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) Brain, awz046, https://doi.org/10.1093/brain/awz046 The content of this slide may be subject to copyright: please see the slide notes for details.