@article{5565654124af470293ff5d58a181f23a,
title = "Connectivity correlates to predict essential tremor deep brain stimulation outcome: Evidence for a common treatment pathway",
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.",
keywords = "Cerebellum, Deep brain stimulation, Essential tremor, Thalamus",
author = "Middlebrooks, {Erik H.} and Lela Okromelidze and Wong, {Joshua K.} and Eisinger, {Robert S.} and Burns, {Mathew R.} and Ayushi Jain and Lin, {Hsin Pin} and Jun Yu and Enrico Opri and Andreas Horn and Goede, {Lukas L.} and Foote, {Kelly D.} and Okun, {Michael S.} and Alfredo Qui{\~n}ones-Hinojosa and Uitti, {Ryan J.} and Grewal, {Sanjeet S.} and Takashi Tsuboi",
note = "Funding Information: We would like to thank Harith Akram, M.D. for his contribution of prior study data. Mayo Clinic Florida data [in part] were previously collected from study funded by Mayo Clinic Transform the Practice Award. Additional data were provided [in part] by the Human Connectome Project, WU-Minn Consortium (Principal Investigators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research; and by the McDonnell Center for Systems Neuroscience at Washington University. We acknowledge the Parkinson's Foundation Center of Excellence at the University of Florida and the UF INFORM database. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Funding Information: Dr. Burns receives salary support from the Parkinson{\textquoteright}s Foundation. Funding Information: Dr. Horn was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft, Emmy Noether Stipend 410169619 and 424778381 – TRR 295) as well as Deutsches Zentrum f{\"u}r Luft- und Raumfahrt (DynaSti grant within the EU Joint Programme Neurodegenerative Disease Research, JPND). A.H. is participant in the BIH-Charit{\'e} Clinician Scientist Program funded by the Charit{\'e} –Universit{\"a}tsmedizin Berlin and the Berlin Institute of Health. Funding Information: Dr. Qui{\~n}ones-Hinojosa is supported by the Mayo Clinic Professorship and a Clinician Investigator award, and Florida State Department of Health Research Grant, and the Mayo Clinic Graduate School, as well as the NIH (R43CA221490, R01CA200399, R01CA195503, and R01CA216855). Funding Information: Dr. Foote has served as a consultant for Medtronic and Boston Scientific and has received honoraria for these services. He has received research support from Medtronic, Boston Scientific, Abbott/St. Jude, and Functional Neuromodulation. He has received fellowship support from Medtronic. Funding Information: Dr. Okun serves as a consultant for the National Parkinson Foundation, and has received research grants from NIH, NPF, the Michael J. Fox Foundation, the Parkinson Alliance, Smallwood Foundation, the Bachmann-Strauss Foundation, the Tourette Syndrome Association, and the UF Foundation. Dr. Okun{\textquoteright}s DBS research is supported by: R01 NR014852 and R01NS096008. Dr. Okun has previously received honoraria, but in the past >60 months has received no support from industry. Dr. Okun has received royalties for publications with Demos, Manson, Amazon, Smashwords, Books4Patients, and Cambridge (movement disorders books). Dr. Okun is an associate editor for New England Journal of Medicine Journal Watch Neurology. Dr. Okun has participated in CME and educational activities on movement disorders (in the last 36) months sponsored by PeerView, Prime, QuantiaMD, WebMD, Medicus, MedNet, Henry Stewart, and by Vanderbilt University. The institution and not Dr. Okun receives grants from Medtronic, Abbvie, Allergan, and ANS/St. Jude, and the PI has no financial interest in these grants. Dr. Okun has participated as a site PI and/or co-I for several NIH, foundation, and industry sponsored trials over the years but has not received honoraria. Funding Information: We would like to thank Harith Akram, M.D. for his contribution of prior study data. Mayo Clinic Florida data [in part] were previously collected from study funded by Mayo Clinic Transform the Practice Award. Additional data were provided [in part] by the Human Connectome Project, WU-Minn Consortium (Principal Investigators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research; and by the McDonnell Center for Systems Neuroscience at Washington University. We acknowledge the Parkinson{\textquoteright}s Foundation Center of Excellence at the University of Florida and the UF INFORM database. Funding Information: Dr. Middlebrooks has received research support from Varian Medical Systems, Inc. and Boston Scientific Corp. He has also received institutional research support from Mayo Clinic and as a Site PI, Co-I, and consultant on NIH supported grants unrelated to the current study. He is also a consultant for Boston Scientific Corp. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = jan,
doi = "10.1016/j.nicl.2021.102846",
language = "English (US)",
volume = "32",
journal = "NeuroImage: Clinical",
issn = "2213-1582",
publisher = "Elsevier BV",
}