Based on N = 80 patients from five DBS centers, we mapped deep brain stimulation sites and looked at whether their structural and functional connectivity profiles could inform clinical outcomes in cervical vs. generalized dystonia.
To derive at a testable hypothesis, we looked at microstructure of the internal pallidum (stimulation site) which is made up from two large processing streams that traverse *orthoginally* from each other. i) the pallidofugal bundle and ii) the pallidothalamic tracts.
We hypothesized that we could leverage this anatomical feature of the pallidum to test whether stimulation of either system (panel C) would be associated with optimal outcomes in cervical vs. generalized dystonia.
And indeed, patients with cervical dystonia responded best when modulating the striatopallidofugal bundle entering the internal capsule (the comb system) in its motor domain. Generalized dystonia patients instead responded best when modulating the pallidothalamic tracts.
On a localized level, optimal stimulation sites for cervical dystonia mapped to the head/neck region of the pallidal homunculus, while optimal stimulation sites for generalized dystonia mapped to a broader, more diffuse area within the pallidum.
So does this mean we should modulate distinct networks in cervical vs. generalized dystonia? Well, not really. On a whole brain level, using normative rs-fMRI data, inter alia, things converged on sites in the sensorimotor cortex and cerebellum, as priorly described.
This work was possible based on the great efforts of Martin Reich and @volkmann_jens to pool together a large cohort of DBS patients and all centers that collaborated (list too long – so a picture is attached).
Precision of the analyses was possible due to two methodological advancements: First, the holographic basal ganglia pathway atlas published by the McIntyre lab that they graciously made openly available (@mv_petersen et al. @NeuroCellPress 2019).
First, a lot of fantastic colleagues contributed data for this analysis, resulting in a total of 176 DBS sites from 8 international centers analyzed! @DrPhilipMosley @HarithAkram @DarinDougherty @Martijn_Figee_ @HelenMaybergMD @SameerShethMD @VVV_Cologne @BaldermannJC et al. 🙏
Then, Garance applied a novel sweetspot mapping technique (introduced in ) that uses the Electric Field (instead of VTA) to derive at a detailed definition of optimal stimulation sites in standard space.pnas.org/doi/10.1073/pn…
First, it is impossible to tag everyone that collaborated on this massive effort & it was a great honor to work on the data from the multicenter ADvance trial since ~2018 to make this possible. Big thanks to the Toronto team & Andres Lozano – and of course to all patients! 🙏
Based on electrode localizations made with @leaddbs we were able to register all stimulation sites into MNI space. Here, it was crucial to use @simonoxen’s WarpDrive method since registrations of atrophied brains is tough and millimeters matter.
Advanced imaging sequences allow us to directly visualize anatomical targets for deep brain stimulation and account for interindividual neuroanatomical variability. This could be especially beneficial obscure targets such as the ventral intermediate (Vim) thalamic nucleus.
During surgical planning we identified an oval-shaped hypointensity on fast gray matter acquisition T1 inversion recovery (FGATIR) sequences at the level of Vim. We frequently (but not always) realized that or target coordinate would coincide with this hypointensity.
Delighted to share our review on connectomic DBS for OCD spearheaded by @BaldermannJC out in @BiologicalPsyc1 now. This is likely the most significant clinical-translational achievement I've had the privilege to play a part in, yet.
It all started in Cologne ~2018 where @BaldermannJC was the first to use the novel DBS fiberfiltering technique we had developed for @leaddbs on a dataset of 22 persons with OCD that underwent DBS in their center.