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

• Type of Material: Article
• Authors: Erik H Middlebrooks, Mayo Clinic, Jacksonville; Lela Okromelidze, Mayo Clinic, Jacksonville; Joshua K Wong, University of Florida; Robert S Eisinger, University of Florida; Mathew R Burns, University of Florida; Ayushi Jain, Mayo Clinic; Hsin-Pin Lin, University of Florida; Jun Yu, University of Florida; Enrico Opri, Emory University; Andreas Horn, Charité – Universitätsmedizin Berlin; Lukas L Goede, Charité – Universitätsmedizin Berlin; Kelly D Foote, University of Florida; Michael S Okun, University of Florida; Alfredo Quinones-Hinojosa, Mayo Clinic, Jacksonville; Ryan J Uitti, Mayo Clinic, Jacksonville; Sanjeet S Grewal, Mayo Clinic, Jacksonville; Takashi Tsuboi, University of Florida
• Language: English
• Date: 2021-10-05
• Publisher: ELSEVIER SCI LTD
• Publication Version: Final Published Version
• Copyright Statement: © 2021 The Author(s)
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.nicl.2021.102846
• Title of Journal or Parent Work: NEUROIMAGE-CLINICAL
• Volume: 32
• Start Page: 102846
• End Page: 102846
• Grant/Funding Information: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
• Keywords: PARKINSON; VENTRAL INTERMEDIATE NUCLEUS; Neuroimaging; MOTOR; SEGMENTATION; TRACTOGRAPHY; DENTATORUBROTHALAMIC TRACT; Neurosciences & Neurology; Life Sciences & Biomedicine; FUNCTIONAL ACTIVATION; ZONA INCERTA; Science & Technology; MOVEMENT-DISORDER; Deep brain stimulation; Essential tremor; Cerebellum; Thalamus; RUBRO-THALAMIC TRACT
• Research Categories: Health Sciences, Radiology

Abstract

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.