{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T15:07:51Z","timestamp":1764688071436,"version":"3.41.2"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T00:00:00Z","timestamp":1699488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To characterize how the proximity of deep brain stimulation (DBS) active contact locations relative to the cerebellothalamic tract (CTT) affect clinical outcomes in patients with essential tremor (ET).<\/jats:p><\/jats:sec><jats:sec><jats:title>Background<\/jats:title><jats:p>DBS is an effective treatment for refractory ET. However, the role of the CTT in mediating the effect of DBS for ET is not well characterized. 7-Tesla (T) MRI-derived tractography provides a means to measure the distance between the active contact and the CTT more precisely.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective review was conducted of 12 brain hemispheres in 7 patients at a single center who underwent 7T MRI prior to ventral intermediate nucleus (VIM) DBS lead placement for ET following failed medical management. 7T-derived diffusion tractography imaging was used to identify the CTT and was merged with the post-operative CT to calculate the Euclidean distance from the active contact to the CTT. We collected optimized stimulation parameters at initial programing, 1- and 2-year follow up, as well as a baseline and postoperative Fahn-Tolosa-Marin (FTM) scores.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The therapeutic DBS current mean (SD) across implants was 1.8\u2009mA (1.8) at initial programming, 2.5\u2009mA (0.6) at 1\u2009year, and 2.9\u2009mA (1.1) at 2-year follow up. Proximity of the clinically-optimized active contact to the CTT was 3.1\u2009mm (1.2), which correlated with lower current requirements at the time of initial programming (R<jats:sup>2<\/jats:sup>\u2009=\u20090.458, <jats:italic>p<\/jats:italic>\u2009=\u20090.009), but not at the 1- and 2-year follow up visits. Subjects achieved mean (SD) improvement in tremor control of 77.9% (14.5) at mean follow-up time of 22.2 (18.9) months. Active contact distance to the CTT did not predict post-operative tremor control at the time of the longer term clinical follow up (R<jats:sup>2<\/jats:sup>\u2009=\u2009-0.073, <jats:italic>p<\/jats:italic>\u2009=\u20090.58).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Active DBS contact proximity to the CTT was associated with lower therapeutic current requirement following DBS surgery for ET, but therapeutic current was increased over time. Distance to CTT did not predict the need for increased current over time, or longer term post-operative tremor control in this cohort. Further study is needed to characterize the role of the CTT in long-term DBS outcomes.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2023.1258895","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T04:26:16Z","timestamp":1699849576000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Active contact proximity to the cerebellothalamic tract predicts initial therapeutic current requirement with DBS for ET: an application of 7T MRI"],"prefix":"10.3389","volume":"14","author":[{"given":"Salman S.","family":"Ikramuddin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annemarie K.","family":"Brinda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca D.","family":"Butler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meghan E.","family":"Hill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajiv","family":"Dharnipragada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua E.","family":"Aman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren E.","family":"Schrock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott E.","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tara","family":"Palnitkar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R\u00e9mi","family":"Patriat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noam","family":"Harel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerrold L.","family":"Vitek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew D.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"28","DOI":"10.5334\/tohm.632","article-title":"How Common is Essential Tremor? Update on the Worldwide Prevalence of Essential Tremor","volume":"11","author":"Louis","year":"2021","journal-title":"Tremor Other Hyperkinet Mov"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"3635","DOI":"10.1093\/brain\/awq267","article-title":"Gait ataxia in essential tremor is differentially modulated by thalamic stimulation","volume":"133","author":"Fasano","year":"2010","journal-title":"Brain"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1002\/mds.27121","article-title":"Consensus Statement on the classification of tremors. from the task force on tremor of the International Parkinson and Movement Disorder Society","volume":"33","author":"Bhatia","year":"2018","journal-title":"Mov Disord"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1136\/jnnp-2018-318240","article-title":"Outcomes from stereotactic surgery for essential tremor","volume":"90","author":"Dallapiazza","year":"2019","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1002\/mds.20884","article-title":"Quality of life and personality in essential tremor patients","volume":"21","author":"Lorenz","year":"2006","journal-title":"Mov Disord"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"e580","DOI":"10.1016\/j.wneu.2017.11.064","article-title":"Deep Brain Stimulation for Essential Tremor: A Comparison of Targets","volume":"110","author":"Holslag","year":"2018","journal-title":"World Neurosurg"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1007\/s00429-007-0170-0","article-title":"Human pallidothalamic and cerebellothalamic tracts: anatomical basis for functional stereotactic neurosurgery","volume":"212","author":"Gallay","year":"2008","journal-title":"Brain Struct Funct"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1093\/brain\/awt304","article-title":"Physiological and anatomical decomposition of subthalamic neurostimulation effects in essential tremor","volume":"137","author":"Groppa","year":"2014","journal-title":"Brain"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"376","DOI":"10.3171\/2019.12.Jns192219","article-title":"MR-guided focused ultrasound cerebellothalamic tractotomy for chronic therapy-resistant essential tremor: anatomical target reappraisal and clinical results","volume":"134","author":"Gallay","year":"2020","journal-title":"J Neurosurg"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/j.brs.2023.02.002","article-title":"Lateral cerebellothalamic tract activation underlies DBS therapy for Essential Tremor","volume":"16","author":"Brinda","year":"2023","journal-title":"Brain Stimul"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"046005","DOI":"10.1088\/1741-2560\/9\/4\/046005","article-title":"Improved spatial targeting with directionally segmented deep brain stimulation leads for treating essential tremor","volume":"9","author":"Keane","year":"2012","journal-title":"J Neural Eng"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1002\/mds.27821","article-title":"Tremor habituation to deep brain stimulation: Underlying mechanisms and solutions","volume":"34","author":"Fasano","year":"2019","journal-title":"Mov Disord"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1016\/j.brs.2017.12.015","article-title":"Thalamic Directional Deep Brain Stimulation for tremor: Spend less, get more","volume":"11","author":"Rebelo","year":"2018","journal-title":"Brain Stimul"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1007\/s00415-010-5773-3","article-title":"Deep brain stimulation in the nucleus ventralis intermedius in patients with essential tremor: habituation of tremor suppression","volume":"258","author":"Barbe","year":"2011","journal-title":"J Neurol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1089\/brain.2011.0033","article-title":"Tractography: where do we go from here?","volume":"1","author":"Jbabdi","year":"2011","journal-title":"Brain Connect"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"118649","DOI":"10.1016\/j.neuroimage.2021.118649","article-title":"Clinical applications of magnetic resonance imaging based functional and structural connectivity","volume":"244","author":"Wu","year":"2021","journal-title":"NeuroImage"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e0201469","DOI":"10.1371\/journal.pone.0201469","article-title":"Patient-specific anatomical model for deep brain stimulation based on 7 Tesla MRI","volume":"13","author":"Duchin","year":"2018","journal-title":"PLoS One"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/j.neuroimage.2016.09.023","article-title":"Individualized parcellation of the subthalamic nucleus in patients with Parkinson's disease with 7T MRI","volume":"168","author":"Plantinga","year":"2018","journal-title":"NeuroImage"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1109\/tmi.2009.2035616","article-title":"elastix: a toolbox for intensity-based medical image registration","volume":"29","author":"Klein","year":"2010","journal-title":"IEEE Trans Med Imaging"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1159\/000494738","article-title":"DiODe: Directional Orientation Detection of Segmented Deep Brain Stimulation Leads: A Sequential Algorithm Based on CT Imaging","volume":"96","author":"Hellerbach","year":"2018","journal-title":"Stereotact Funct Neurosurg"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1002\/mds.28566","article-title":"High-Frequency Oscillations in the Pallidum: A Pathophysiological Biomarker in Parkinson's Disease?","volume":"36","author":"Johnson","year":"2021","journal-title":"Mov Disord"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1016\/j.mri.2012.05.001","article-title":"3D Slicer as an image computing platform for the Quantitative Imaging Network","volume":"30","author":"Fedorov","year":"2012","journal-title":"Magn Reson Imaging"},{"volume-title":"Atlas of the Human Brain","year":"2007","author":"Mai","key":"ref23"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"264","DOI":"10.3389\/fnins.2016.00264","article-title":"Multimodal 7T Imaging of Thalamic Nuclei for Preclinical Deep Brain Stimulation Applications","volume":"10","author":"Xiao","year":"2016","journal-title":"Front Neurosci"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1038\/nn1075","article-title":"Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging","volume":"6","author":"Behrens","year":"2003","journal-title":"Nat Neurosci"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1002\/mrm.10609","article-title":"Characterization and propagation of uncertainty in diffusion-weighted MR imaging","volume":"50","author":"Behrens","year":"2003","journal-title":"Magn Reson Med"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/j.neuroimage.2011.09.015","article-title":"FSL","volume":"62","author":"Jenkinson","year":"2012","journal-title":"NeuroImage"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/s1361-8415(01)00036-6","article-title":"A global optimisation method for robust affine registration of brain images","volume":"5","author":"Jenkinson","year":"2001","journal-title":"Med Image Anal"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1002\/mds.22641","article-title":"Micro lesion effect of the globus pallidus internus and outcome with deep brain stimulation in patients with Parkinson disease and dystonia","volume":"24","author":"Cersosimo","year":"2009","journal-title":"Mov Disord"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.nicl.2015.08.008","article-title":"Resting-state functional magnetic resonance imaging of the subthalamic microlesion and stimulation effects in Parkinson's disease: Indications of a principal role of the brainstem","volume":"9","author":"Holiga","year":"2015","journal-title":"Neuroimage Clin"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"16661","DOI":"10.1038\/s41598-020-73714-9","article-title":"Cerebello-thalamo-cortical network is intrinsically altered in essential tremor: evidence from a resting state functional MRI study","volume":"10","author":"Nicoletti","year":"2020","journal-title":"Sci Rep"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"102026","DOI":"10.1016\/j.nicl.2019.102026","article-title":"White matter tracing combined with electric field simulation\u2014A patient-specific approach for deep brain stimulation","volume":"24","author":"Nordin","year":"2019","journal-title":"Neuroimage Clin"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2023.1258895\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T04:26:19Z","timestamp":1699849579000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2023.1258895\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,9]]},"references-count":32,"alternative-id":["10.3389\/fneur.2023.1258895"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2023.1258895","relation":{},"ISSN":["1664-2295"],"issn-type":[{"type":"electronic","value":"1664-2295"}],"subject":[],"published":{"date-parts":[[2023,11,9]]},"article-number":"1258895"}}