{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:10:13Z","timestamp":1753891813388,"version":"3.41.2"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T00:00:00Z","timestamp":1655424000000},"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. Hum. Neurosci."],"abstract":"<jats:p>Deep brain stimulation (DBS) is part of state-of-the-art treatment for medically refractory Parkinson\u2019s disease, essential tremor or primary dystonia. However, there are multiple movement disorders that present after a static brain lesion and that are frequently refractory to medical treatment. Using Holmes tremor (HT) as an example, we discuss the effectiveness of currently available treatments and, performing simulations using a Markov Chain approach, propose that DBS with iterative parameter optimization is expected to be more effective than an approach based on sequential trials of pharmacological agents. Since, in DBS studies for HT, the thalamus is a frequently chosen target, using data from previous studies of lesion connectivity mapping in HT, we compared the connectivity of thalamic and non-thalamic targets with a proxy of the HT network, and found a significantly higher connectivity of thalamic DBS targets in HT. The understanding of brain networks provided by analysis of functional connectivity may thus provide an informed framework for proper surgical targeting of individual patients. Based on these findings, we argue that there is an ethical imperative to at least consider surgical options in patients with uncommon movement disorders, while simultaneously providing consistent information regarding the expected effectiveness and risks, even in a scenario of surgical-risk aversion. An approach based on n-of-1 DBS trials may ultimately significantly improve outcomes while informing on optimal therapeutic targets and parameter settings for HT and other disabling and rare movement disorders.<\/jats:p>","DOI":"10.3389\/fnhum.2022.921523","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T04:43:54Z","timestamp":1655441034000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["An Argument in Favor of Deep Brain Stimulation for Uncommon Movement Disorders: The Case for N-of-1 Trials in Holmes Tremor"],"prefix":"10.3389","volume":"16","author":[{"given":"Marcelo","family":"Mendon\u00e7a","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gon\u00e7alo","family":"Cotovio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel","family":"Barbosa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Grunho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albino J.","family":"Oliveira-Maia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,17]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1093\/neuros\/nyaa536","article-title":"Focused ultrasound thalamotomy for refractory essential tremor: a japanese multicenter single-arm study.","volume":"88","author":"Abe","year":"2021","journal-title":"Neurosurgery"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1136\/jnnp.2003.011874","article-title":"Post-stroke movement disorders: report of 56 patients.","volume":"75","author":"Alarc\u00f3n","year":"2004","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B3","doi-asserted-by":"publisher","first-page":"607.e7","DOI":"10.1016\/j.wneu.2016.09.079","article-title":"Post-traumatic tremor and thalamic deep brain stimulation: evidence for use of diffusion tensor imaging.","volume":"96","author":"Boccard","year":"2016","journal-title":"World Neurosurg."},{"key":"B4","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1177\/1073858415581986","article-title":"Mechanism of deep brain stimulation: inhibition, excitation, or disruption?","volume":"22","author":"Chiken","year":"2016","journal-title":"Neuroscientist"},{"key":"B5","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1176\/appi.ajp.2021.20101429","article-title":"Stanford Neuromodulation Therapy (SNT): a double-blind randomized controlled trial.","volume":"179","author":"Cole","year":"2022","journal-title":"Am. J. Psychiatry"},{"key":"B6","doi-asserted-by":"publisher","first-page":"5209","DOI":"10.1172\/JCI136096","article-title":"Mapping mania symptoms based on focal brain damage.","volume":"130","author":"Cotovio","year":"2020","journal-title":"J. Clin. Invest."},{"key":"B7","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/S1547-4127(04)00016-7","article-title":"Risk acceptance and risk aversion: patients\u2019 perspectives on lung surgery.","volume":"14","author":"Cykert","year":"2004","journal-title":"Thorac. Surg. Clin."},{"key":"B8","doi-asserted-by":"publisher","first-page":"S21","DOI":"10.1016\/j.jclinepi.2013.04.006","article-title":"Single-patient (n-of-1) trials: a pragmatic clinical decision methodology for patient-centered comparative effectiveness research.","volume":"66","author":"Duan","year":"2013","journal-title":"J. Clin. Epidemiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2907","DOI":"10.1002\/hbm.20718","article-title":"Coordinate-based activation likelihood estimation meta-analysis of neuroimaging data: a random-effects approach based on empirical estimates of spatial uncertainty.","volume":"30","author":"Eickhoff","year":"2009","journal-title":"Hum. Brain Mapp."},{"key":"B10","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1212\/WNL.0000000000004268","article-title":"MRI-guided focused ultrasound thalamotomy in non-ET tremor syndromes.","volume":"89","author":"Fasano","year":"2017","journal-title":"Neurology"},{"key":"B11","doi-asserted-by":"publisher","first-page":"132","DOI":"10.3171\/2013.10.JNS131225","article-title":"Risks of common complications in deep brain stimulation surgery: management and avoidance.","volume":"120","author":"Fenoy","year":"2014","journal-title":"J. Neurosurg."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1016\/j.athoracsur.2018.11.025","article-title":"Physician gender differences in processing surgical risk features in videos of standardized patients.","volume":"107","author":"Ferguson","year":"2019","journal-title":"Ann. Thorac. Surg."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2237","DOI":"10.1056\/NEJMra1706158","article-title":"Mapping symptoms to brain networks with the human connectome.","volume":"379","author":"Fox","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"B14","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1001\/jamaneurol.2015.51","article-title":"Brain stimulation for torsion dystonia.","volume":"72","author":"Fox","year":"2015","journal-title":"JAMA Neurol."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26361","article-title":"Converging on a neuromodulation target for tremor.","author":"Fox","year":"2022","journal-title":"Ann. Neurol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1097\/MLR.0b013e318215d90d","article-title":"N-of-1 trials in the medical literature: a systematic review.","volume":"49","author":"Gabler","year":"2011","journal-title":"Med. Care"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1007\/s00702-017-1780-1","article-title":"Is nigrostriatal dopaminergic deficit necessary for Holmes tremor to develop? The DaTSCAN and IBZM SPECT study.","volume":"124","author":"Gajos","year":"2017","journal-title":"J. Neural Transm."},{"key":"B18","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.neuroimage.2013.04.127","article-title":"Consortium. The minimal preprocessing pipelines for the human connectome project.","volume":"80","author":"Glasser","year":"2013","journal-title":"Neuroimage"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1136\/jnnp.2003.023077","article-title":"Combination of thalamic Vim stimulation and GPi pallidotomy synergistically abolishes Holmes\u2019 tremor.","volume":"75","author":"Goto","year":"2004","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B20","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1126\/science.1167093","article-title":"Optical deconstruction of parkinsonian neural circuitry.","volume":"324","author":"Gradinaru","year":"2009","journal-title":"Science"},{"key":"B21","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1001\/jamasurg.2017.3936","article-title":"Comparison of internal medicine and general surgery residents\u2019 assessments of risk of postsurgical complications in surgically complex patients.","volume":"153","author":"Healy","year":"2018","journal-title":"JAMA Surg."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2021.102211","article-title":"Toward personalized medicine in connectomic deep brain stimulation.","volume":"210","author":"Hollunder","year":"2022","journal-title":"Prog. Neurobiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1016\/j.parkreldis.2013.07.022","article-title":"Treating post-traumatic tremor with deep brain stimulation: report of five cases.","volume":"19","author":"Issar","year":"2013","journal-title":"Parkinsonism Relat. Disord."},{"key":"B24","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1002\/ana.25618","article-title":"Mapping holmes tremor circuit using the human brain connectome.","volume":"86","author":"Joutsa","year":"2019","journal-title":"Ann. Neurol."},{"key":"B25","doi-asserted-by":"crossref","first-page":"263","DOI":"10.2307\/1914185","article-title":"Prospect theory: an analysis of decision under risk.","volume":"4","author":"Kahneman","year":"1979","journal-title":"Econometrica"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.3171\/2015.2.JNS141098","article-title":"Pallidal stimulation for Holmes tremor: clinical outcomes and single-unit recordings in 4 cases.","volume":"122","author":"Kilbane","year":"2015","journal-title":"J. Neurosurg."},{"key":"B27","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.parkreldis.2019.10.008","article-title":"Decision under risk: argument against early deep brain stimulation in Parkinson\u2019s disease.","volume":"69","author":"Kim","year":"2019","journal-title":"Parkinsonism Relat. Disord."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.3171\/2014.1.JNS12392","article-title":"Multitarget, dual-electrode deep brain stimulation of the thalamus and subthalamic area for treatment of Holmes\u2019 tremor.","volume":"120","author":"Kobayashi","year":"2014","journal-title":"J. Neurosurg."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1002\/mds.27860","article-title":"Deep brain stimulation in movement disorders: from experimental surgery to evidence-based therapy.","volume":"34","author":"Krack","year":"2019","journal-title":"Mov. Disord."},{"key":"B30","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/B978-0-444-63521-1.00030-3","article-title":"Movement disorders secondary to craniocerebral trauma.","volume":"128","author":"Krauss","year":"2015","journal-title":"Handb. Clin. Neurol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1212\/wnl.47.6.1488","article-title":"Post-traumatic movement disorders in survivors of severe head injury.","volume":"47","author":"Krauss","year":"1996","journal-title":"Neurology"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.7916\/tohm.v0.640","article-title":"Treatment with botulinum neurotoxin improves activities of daily living and quality of life in patients with upper limb tremor.","volume":"9","author":"Kreisler","year":"2019","journal-title":"Tremor Other Hyperkinet. Mov."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1935","DOI":"10.1007\/s10072-015-2285-z","article-title":"Botulinum toxin type A for Holmes tremor secondary to thalamic hemorrhage.","volume":"36","author":"Latino","year":"2015","journal-title":"Neurol. Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1136\/jnnp.2007.126219","article-title":"Deep brain stimulation activation volumes and their association with neurophysiological mapping and therapeutic outcomes.","volume":"80","author":"Maks","year":"2009","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebr.2019.100336","article-title":"Making the switch: from case studies to N-of-1 trials.","volume":"12","author":"Margolis","year":"2019","journal-title":"Epilepsy Behav. Rep."},{"key":"B36","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.parkreldis.2017.12.014","article-title":"Deep brain stimulation for lesion-related tremors: a systematic review and meta-analysis.","volume":"47","author":"Mendon\u00e7a","year":"2018","journal-title":"Parkinsonism Relat. Disord."},{"key":"B37","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1001\/2013.jamaneurol.45","article-title":"History, applications, and mechanisms of deep brain stimulation.","volume":"70","author":"Miocinovic","year":"2013","journal-title":"JAMA Neurol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/j.parkreldis.2011.03.009","article-title":"Rescue leads: a salvage technique for selected patients with a suboptimal response to standard DBS therapy.","volume":"17","author":"Oyama","year":"2011","journal-title":"Parkinsonism Relat. Disord."},{"key":"B39","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1212\/WNL.0000000000002440","article-title":"Holmes tremor: clinical description, lesion localization, and treatment in a series of 29 cases.","volume":"86","author":"Raina","year":"2016","journal-title":"Neurology"},{"key":"B40","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1212\/wnl.45.3.472","article-title":"Peduncular \u2018rubral\u2019 tremor and dopaminergic denervation: a PET study.","volume":"45","author":"Remy","year":"1995","journal-title":"Neurology"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.7916\/D82C0FFN","article-title":"Holmes tremor partially responsive to topiramate: a case report.","volume":"8","author":"Rojas","year":"2018","journal-title":"Tremor Other Hyperkinet. Mov."},{"key":"B42","doi-asserted-by":"publisher","first-page":"888","DOI":"10.3171\/jns.2003.98.4.0888","article-title":"Thalamic deep brain stimulation for disabling tremor after excision of a midbrain cavernous angioma. Case report.","volume":"98","author":"Samadani","year":"2003","journal-title":"J. Neurosurg."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1002\/wsbm.1421","article-title":"Systems approaches to optimizing deep brain stimulation therapies in Parkinson\u2019s disease.","volume":"20","author":"Santaniello","year":"2018","journal-title":"Wiley Interdiscip. Rev. Syst. Biol. Med."},{"key":"B44","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1136\/jnnp.2008.146324","article-title":"Disruption of nigrostriatal and cerebellothalamic pathways in dopamine responsive Holmes\u2019 tremor.","volume":"80","author":"Seidel","year":"2009","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B45","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1177\/0272989X9301300409","article-title":"Markov models in medical decision making: a practical guide.","volume":"13","author":"Sonnenberg","year":"1993","journal-title":"Med. Decis. Making"},{"key":"B46","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1136\/jnnp.2006.103275","article-title":"Dramatic response to levetiracetam in post-ischaemic Holmes\u2019 tremor.","volume":"78","author":"Striano","year":"2007","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B47","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1056\/NEJMoa042187","article-title":"Bilateral deep-brain stimulation of the globus pallidus in primary generalized dystonia.","volume":"352","author":"Vidailhet","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1111\/ner.13220","article-title":"Therapeutic advances in the treatment of holmes tremor: systematic review.","author":"Wang","year":"2020","journal-title":"Neuromodulation"}],"container-title":["Frontiers in Human Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnhum.2022.921523\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T04:44:01Z","timestamp":1655441041000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnhum.2022.921523\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,17]]},"references-count":48,"alternative-id":["10.3389\/fnhum.2022.921523"],"URL":"https:\/\/doi.org\/10.3389\/fnhum.2022.921523","relation":{},"ISSN":["1662-5161"],"issn-type":[{"type":"electronic","value":"1662-5161"}],"subject":[],"published":{"date-parts":[[2022,6,17]]},"article-number":"921523"}}