Connectivity correlates to predict essential tremor deep brain stimulation outcome: Evidence for a common treatment pathway

Erik H. Middlebrooks, Lela Okromelidze, Joshua K. Wong, Robert S. Eisinger, Mathew R. Burns, Ayushi Jain, Hsin Pin Lin, Jun Yu, Enrico Opri, Andreas Horn, Lukas L. Goede, Kelly D. Foote, Michael S. Okun, Alfredo Quiñones-Hinojosa, Ryan J. Uitti, Sanjeet S. Grewal, Takashi Tsuboi

Research output: Contribution to journalArticlepeer-review


Background and purpose: Deep brain stimulation (DBS) is the most common surgical treatment for essential tremor (ET), yet there is variation in outcome and stimulation targets. This study seeks to consolidate proposed stimulation “sweet spots,” as well as assess the value of structural connectivity in predicting treatment outcomes. Materials and methods: Ninety-seven ET individuals with unilateral thalamic DBS were retrospectively included. Using normative brain connectomes, structural connectivity measures were correlated with the percentage improvement in contralateral tremor, based on the Fahn-Tolosa-Marin tremor rating scale (TRS), after parameter optimization (range 3.1–12.9 months) using a leave-one-out cross-validation in 83 individuals. The predictive feature map was used for cross-validation in a separate cohort of 14 ET individuals treated at another center. Lastly, estimated volumes of tissue activated (VTA) were used to assess a treatment “sweet spot,” which was compared to seven previously reported stimulation sweet spots and their relationship to the tract identified by the predictive feature map. Results: In the training cohort, structural connectivity between the VTA and dentato-rubro-thalamic tract (DRTT) correlated with contralateral tremor improvement (R = 0.41; p < 0.0001). The same connectivity profile predicted outcomes in a separate validation cohort (R = 0.59; p = 0.028). The predictive feature map represented the anatomical course of the DRTT, and all seven analyzed sweet spots overlapped the predictive tract (DRTT). Conclusions: Our results strongly support the possibility that structural connectivity is a predictor of contralateral tremor improvement in ET DBS. The results suggest the future potential for a patient-specific functionally based surgical target. Finally, the results showed convergence in “sweet spots” suggesting the importance of the DRTT to the outcome.

Original languageEnglish (US)
Article number102846
JournalNeuroImage: Clinical
StatePublished - Jan 2021


  • Cerebellum
  • Deep brain stimulation
  • Essential tremor
  • Thalamus

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology
  • Cognitive Neuroscience


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