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In fact, very few publications have actually addressed the problem, thus making tolerance a typical example of science based on \u201ceminence rather than evidence.\u201d The underpinnings of the phenomena associated with the progressive loss of DBS benefit are not fully elucidated, although the interplay of different\u2014not mutually exclusive\u2014factors has been advocated. In this viewpoint, we gathered the evidence explaining the progressive loss of benefit observed after DBS. We grouped these factors in three categories: disease\u2010related factors (tremor etiology and progression); surgery\u2010related factors (electrode location, microlesional effect and placebo); and stimulation\u2010related factors (not optimized stimulation, stimulation\u2010induced side effects, habituation, and tremor rebound). We also propose possible pathophysiological explanations for the phenomenon and define a nomenclature of the associated features: early versus late DBS failure; tremor rebound versus habituation (to be preferred over tolerance). Finally, we provide a practical approach for preventing and treating this loss of DBS benefit, and we draft a possible roadmap for the research to come. \u00a9 2019 International Parkinson and Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.27821","type":"journal-article","created":{"date-parts":[[2019,8,21]],"date-time":"2019-08-21T16:41:56Z","timestamp":1566405716000},"page":"1761-1773","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":105,"title":["Tremor habituation to deep brain stimulation: Underlying mechanisms and solutions"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5346-0180","authenticated-orcid":false,"given":"Alfonso","family":"Fasano","sequence":"first","affiliation":[{"name":"Edmond J. 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