Directed stimulation of the dentato-rubro-thalamic tract for deep brain stimulation in essential tremor: a blinded clinical trial

Erik H. Middlebrooks, Lela Okromelidze, Rickey E. Carter, Ayushi Jain, Chen Lin, Erin Westerhold, Ashley B. Peña, Alfredo Quiñones-Hinojosa, Ryan J. Uitti, Sanjeet S. Grewal

Research output: Contribution to journalArticlepeer-review


Objective: Observational studies utilising diffusion tractography have suggested a common mechanism for tremor alleviation in deep brain stimulation for essential tremor: the decussating portion of the dentato-rubro-thalamic tract. We hypothesised that directional stimulation of the dentato-rubro-thalamic tract would result in greater tremor improvement compared to sham programming, as well as comparable improvement as more tedious standard-of-care programming. Methods: A prospective, blinded crossover trial was performed to assess the feasibility, safety and outcomes of programming based solely on dentato-rubro-thalamic tract anatomy. Using magnetic resonance imaging diffusion-tractography, the dentato-rubro-thalamic tract was identified and a connectivity-based treatment setting was derived by modelling a volume of tissue activated using directional current steering oriented towards the dentato-rubro-thalamic tract centre. A sham setting was created at approximately 180° opposite the connectivity-based treatment. Standard-of-care programming at 3 months was compared to connectivity-based treatment and sham settings that were blinded to the programmer. The primary outcome measure was percentage improvement in the Fahn–Tolosa–Marín tremor rating score compared to the preoperative baseline. Results: Among the six patients, tremor rating scores differed significantly among the three experimental conditions (P=0.030). The mean tremor rating score improvement was greater with the connectivity-based treatment settings (64.6% ± 14.3%) than with sham (44.8% ± 18.6%; P=0.031) and standard-of-care programming (50.7% ± 19.2%; P=0.062). The distance between the centre of the dentato-rubro-thalamic tract and the volume of tissue activated inversely correlated with the percentage improvement in the tremor rating score (R2=0.24; P=0.04). No significant adverse events were encountered. Conclusions: Using a blinded, crossover trial design, we have shown the technical feasibility, safety and potential efficacy of connectivity-based stimulation settings in deep brain stimulation for treatment of essential tremor.

Original languageEnglish (US)
Pages (from-to)203-212
Number of pages10
JournalNeuroradiology Journal
Issue number2
StatePublished - Apr 2022


  • Essential tremor
  • deep brain stimulation
  • dentato-rubro-thalamic tract

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Clinical Neurology


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