Lateral cerebellothalamic tract activation underlies DBS therapy for Essential Tremor

Anne Marie Brinda, Julia P. Slopsema, Rebecca D. Butler, Salman Ikramuddin, Thomas Beall, William Guo, Cong Chu, Remi Patriat, Henry Braun, Mojgan Goftari, Tara Palnitkar, Joshua Aman, Lauren Schrock, Scott E. Cooper, Joseph Matsumoto, Jerrold L. Vitek, Noam Harel, Matthew D. Johnson

Research output: Contribution to journalArticlepeer-review


Background: While deep brain stimulation (DBS) therapy can be effective at suppressing tremor in individuals with medication-refractory Essential Tremor, patient outcome variability remains a significant challenge across centers. Proximity of active electrodes to the cerebellothalamic tract (CTT) is likely important in suppressing tremor, but how tremor control and side effects relate to targeting parcellations within the CTT and other pathways in and around the ventral intermediate (VIM) nucleus of thalamus remain unclear. Methods: Using ultra-high field (7T) MRI, we developed high-dimensional, subject-specific pathway activation models for 23 directional DBS leads. Modeled pathway activations were compared with post-hoc analysis of clinician-optimized DBS settings, paresthesia thresholds, and dysarthria thresholds. Mixed-effect models were utilized to determine how the six parcellated regions of the CTT and how six other pathways in and around the VIM contributed to tremor suppression and induction of side effects. Results: The lateral portion of the CTT had the highest activation at clinical settings (p < 0.05) and a significant effect on tremor suppression (p < 0.001). Activation of the medial lemniscus and posterior-medial CTT was significantly associated with severity of paresthesias (p < 0.001). Activation of the anterior-medial CTT had a significant association with dysarthria (p < 0.05). Conclusions: This study provides a detailed understanding of the fiber pathways responsible for therapy and side effects of DBS for Essential Tremor, and suggests a model-based programming approach will enable more selective activation of lateral fibers within the CTT.

Original languageEnglish (US)
Pages (from-to)445-455
Number of pages11
JournalBrain Stimulation
Issue number2
StatePublished - Mar 1 2023

Bibliographical note

Funding Information:
This work was funded by the NIH ( R01-NS081118 and P41-EB015894 ). AKB and JPS were supported by NSF GRFP awards.

Publisher Copyright:
© 2023 The Authors


  • Cerebellothalamic tract
  • Deep brain stimulation
  • Essential Tremor
  • Pathway activation models

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.


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