(J-395) Optimal gray and white matter activation for thalamic deep brain stimulation in essential tremor

Friday, October 13, 2023

9:30 AM – 10:30 AM PDT

Location: Exhibit Hall - Row J - Poster # 395

Presenting Author(s)

KT

Keeler Thomas

Student
Bucknell University, United States

Primary Investigator(s)

Karlo A. Malaga

Assistant Professor of Biomedical Engineering
Bucknell University
Lewisburg, Pennsylvania, United States

Introduction:: Essential tremor (ET) is a neurological movement disorder characterized by involuntary shaking that manifests primarily in the upper extremities (arms, hands, etc.). ET affects 1% of individuals worldwide, increasing to 5% for those older than 65.1 One treatment option for ET is deep brain stimulation (DBS), a surgical technique where implanted electrodes stimulate local brain tissue. The traditional implantation target for ET is the ventral intermediate nucleus (VIM) of the thalamus, less common being the posterior subthalamic area and caudal zona incerta, all of which are gray matter (GM) structures established as alleviators of tremor when stimulated. Side effects associated with VIM DBS include paresthesia and motor contractions (e.g. dysarthria). Recent studies investigate nearby white matter (WM) structures, such as the dentatorubrothalamic tract (DRTT), as more optimal stimulation targets.2-8 The present study aimed to determine if increased WM tissue activation was associated with tremor reduction without side effects.

Materials and Methods:: 18 ET patients previously received unilateral VIM DBS. Their therapeutic and side effect individualized volumes of tissue activation (VTA), previously modeled using finite element analysis, were analyzed in MATLAB.9 Using diffusion tensor imaging data, k-means clustering was implemented as a classification algorithm of three main tissue types in the brain: cerebrospinal fluid, GM, and WM.10 Tissue activation was calculated for therapeutic and side effect outcomes as the overlap with individualized VTAs. Percent activation (percent of VTA activating WM tissue) was compared across clinical outcomes using Wilcoxon rank sum tests. Activated WM tissue coordinates were compared using an ANOVA test across clinical outcomes after finding patient-specific rigid transformations (translation, rotation) to the Morel stereotactic atlas thalamus.

Results, Conclusions, and Discussions:: All clinical outcomes, therapeutic (THER), motor contraction (MTR), and paresthesia (PAR) had similar percentages of WM activation (Figure 1). The comparison of coordinate location of activated WM tissue found that all outcomes in x, y, and z-directions are significantly different, except between THER and MTR WM in the z-direction (Table 1, Figures 2-4). THER WM is medial to MTR and PAR, with MTR being most lateral. THER WM is most anterior and PAR WM is most posterior with MTR WM inbetween. THER and MTR WM are superior to PAR WM.

It is reported that THER outcomes are associated with DRTT stimulation as evidenced by previously mentioned studies, MTR outcomes are associated with corticospinal tract stimulation,11 and PAR outcomes are associated with medial lemniscus stimulation.12 As this study reviews the activated WM associated with those outcomes, comparisons between the location of these WM fiber tracts and activated WM can be investigated.

Although THER, MTR, and PAR clinical outcomes from ET DBS have similar percentages of WM tissue activation, the spatial location of activated WM corresponding to each clinical outcome differs. The results of a comparison of these activated WM tissues to local underlying fiber tracts associated with the understood clinical outcomes from activation can serve to support or refute the new proposed target pathway (DRTT), as well as delineate its relative location.

Acknowledgements (Optional): : The authors thank their collaborators at University of Michigan for clinical data and data visualization code. This work was funded by the Costa Healthcare Research & Design Fund at Bucknell University.

References (Optional): :

1. Haubenberger, D., & Hallett, M. (2018). Essential Tremor. New England Journal of Medicine, 378(19), 1802–1810. https://doi.org/10.1056/NEJMcp1707928.

2. Schlaier, J., et al. (2015). Deep brain stimulation for essential tremor: Targeting the dentato-rubro-thalamic tract? Neuromodulation, 18(2), 105–112. https://doi.org/10.1111/ner.12238.

3. Coenen, V. A., et al. (2016). One-pass deep brain stimulation of dentato-rubro-thalamic tract and subthalamic nucleus for tremor-dominant or equivalent type Parkinson’s disease. Acta Neurochirurgica, 158(4), 773–781. https://doi.org/10.1007/s00701-016-2725-4.

4. Nordin, T., et al. (2019). White matter tracing combined with electric field simulation – A patient-specific approach for deep brain stimulation. NeuroImage: Clinical, 24. https://doi.org/10.1016/j.nicl.2019.102026.

5. Dembek, T. A., et al. (2020). PSA and VIM DBS efficiency in essential tremor depends on distance to the dentatorubrothalamic tract. NeuroImage: Clinical, 26. https://doi.org/10.1016/j.nicl.2020.102235.

6. Gravbrot, N., et al. (2020). Advanced Imaging and Direct Targeting of the Motor Thalamus and Dentato-Rubro-Thalamic Tract for Tremor: A Systematic Review. In Stereotactic and Functional Neurosurgery (Vol. 98, Issue 4, pp. 220–240). S. Karger AG. https://doi.org/10.1159/000507030.

7. Middlebrooks, E. H., et al. (2021). Connectivity correlates to predict essential tremor deep brain stimulation outcome: Evidence for a common treatment pathway. NeuroImage: Clinical, 32. https://doi.org/10.1016/j.nicl.2021.102846.

8. Middlebrooks, E. H., et al. (2022). Directed stimulation of the dentato-rubro-thalamic tract for deep brain stimulation in essential tremor: a blinded clinical trial. Neuroradiology Journal, 35(2), 203–212. https://doi.org/10.1177/19714009211036689.

9. Malaga, K. A., et al. (2022). Thalamic Segmentation and Neural Activation Modeling Based on Individual Tissue Microstructure in Deep Brain Stimulation for Essential Tremor. Neuromodulation. https://doi.org/10.1016/j.neurom.2022.09.013.

10. Elaff, I. (2016). Brain tissue classification based on diffusion tensor imaging: A comparative study between some clustering algorithms and their effect on different diffusion tensor imaging scalar indices. Iranian Journal of Radiology, 13(2). https://doi.org/10.5812/iranjradiol.23726.

11. Slopsema, J. P., et al. (2018). Clinical deep brain stimulation strategies for orientation-selective pathway activation. Journal of Neural Engineering, 15(5). https://doi.org/10.1088/1741-2552/aad978.

12. Iorio-Morin, C., et al. (2020). Deep-brain stimulation for essential tremor and other tremor syndromes: A narrative review of current targets and clinical outcomes. In Brain Sciences (Vol. 10, Issue 12, pp. 1–17). MDPI AG. https://doi.org/10.3390/brainsci10120925.