{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T06:08:42Z","timestamp":1783836522905,"version":"3.55.0"},"reference-count":80,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The clinical diagnosis of tremor disorders depends on the interpretation of subtle movement characteristics, signs, and symptoms. Given the absence of a universally accepted biomarker, differentiation between essential tremor (ET) and tremor\u2010dominant Parkinson's disease (PD) frequently proves to be non\u2010trivial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To identify generalizable tremor characteristics to differentiate ET and PD using feature extraction and machine learning (ML).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Hand accelerometer recordings from 414 patients, clinically diagnosed at six academic centers, formed an exploratory (158 ET, 172 PD) and a validation dataset (30 ET, 54 PD). Established, standardized tremor characteristics were assessed for their cross\u2010center accuracy and validity. Supervised ML was applied to massive higher\u2010order feature extraction of the same recordings to achieve optimal stratification and mechanistic exploration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>While classic tremor characteristics did not consistently differentiate between conditions across centers, the feature combination identified via our ML approach was successfully validated. In comparison with the tremor stability index (TSI), feature\u2010based analysis provided better classification accuracy (81.8% vs. 70.4%), sensitivity (86.4% vs. 70.8%), and specificity (76.6% vs. 70.2%), substantially improving disease stratification. The interpretation of identified features indicates fundamentally different dynamics in tremor\u2010generating circuits: while different discrete but stable signal states in PD indicate several central oscillators, signal characteristics in ET point towards a singular pacemaker.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study establishes the use of feature\u2010based ML as a powerful method to explore accelerometry\u2010derived tremor signals. The combination of hypothesis\u2010free, data\u2010driven analyses and a large, multicenter dataset represents a relevant step towards big data analysis in tremor disorders. \u00a9 2025 The Author(s).\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70032","type":"journal-article","created":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T06:36:47Z","timestamp":1757140607000},"page":"2628-2640","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Phenotypical Differentiation of Tremor Using Time Series Feature Extraction and Machine Learning"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7543-7540","authenticated-orcid":false,"given":"Verena","family":"H\u00e4ring","sequence":"first","affiliation":[{"name":"Department of Neurology University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3209-9360","authenticated-orcid":false,"given":"Veronika","family":"Selzam","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1392-8775","authenticated-orcid":false,"given":"Juan Francisco","family":"Martin\u2010Rodriguez","sequence":"additional","affiliation":[{"name":"Unidad de Trastornos del Movimiento, Servicio de Neurologia y Neurofisiologia Clinica, Instituto de Biomedicina de Sevilla Hospital Universitario Virgen del Rocio\/CSIC\/Universidad de Sevilla  Seville Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III  Madrid Spain"},{"name":"Departamento de Psicolog\u00eda Experimental, Facultad de Psicolog\u00eda Universidad de Sevilla  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3294-6824","authenticated-orcid":false,"given":"Petra","family":"Schwingenschuh","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8054-3678","authenticated-orcid":false,"given":"Gertr\u00fad","family":"Tam\u00e1s","sequence":"additional","affiliation":[{"name":"Department of Neurology Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6375-467X","authenticated-orcid":false,"given":"Linda","family":"K\u00f6hler","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9812-1115","authenticated-orcid":false,"given":"Jan","family":"Raethjen","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital Schleswig\u2010Holstein, Campus Kiel, Christian Albrechts University  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9306-8332","authenticated-orcid":false,"given":"Steffen","family":"Paschen","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital Schleswig\u2010Holstein, Campus Kiel, Christian Albrechts University  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7146-2857","authenticated-orcid":false,"given":"Franziska","family":"Goltz","sequence":"additional","affiliation":[{"name":"Department of Neurology, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3057-0592","authenticated-orcid":false,"given":"Eoin","family":"Mulroy","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7103-5209","authenticated-orcid":false,"given":"Anna","family":"Latorre","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1656-302X","authenticated-orcid":false,"given":"Pablo","family":"Mir","sequence":"additional","affiliation":[{"name":"Unidad de Trastornos del Movimiento, Servicio de Neurologia y Neurofisiologia Clinica, Instituto de Biomedicina de Sevilla Hospital Universitario Virgen del Rocio\/CSIC\/Universidad de Sevilla  Seville Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III  Madrid Spain"},{"name":"Departamento de Medicina, Facultad de Medicina Universidad de Sevilla  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4035-6573","authenticated-orcid":false,"given":"Rick C.","family":"Helmich","sequence":"additional","affiliation":[{"name":"Department of Neurology, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8185-286X","authenticated-orcid":false,"given":"Kailash P.","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9570-593X","authenticated-orcid":false,"given":"Jens","family":"Volkmann","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8738-5825","authenticated-orcid":false,"given":"Robert","family":"Peach","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"},{"name":"Department of Brain Sciences Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4129-5808","authenticated-orcid":false,"given":"Sebastian R.","family":"Schreglmann","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22838"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2012.06.011"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.5334\/tohm.660"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv171"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy098"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00314-w"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2022.08.030"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12683"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1353-8020(11)70027-x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.67.5.646"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.13806"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000005215"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.0854-21.2021"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws023"},{"key":"e_1_2_9_16_1","first-page":"31","volume-title":"Current Concepts of Parkinson Disease and Related Disorders","author":"Marsden CD","year":"1983"},{"key":"e_1_2_9_17_1","volume-title":"Handbook of Tremor Disorders","author":"Findley LJ","year":"1995"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870131303"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27121"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23579"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/wco.0000000000000582"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.8.1100"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004150070053"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26671"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.680011"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2021.07.033"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004691-200411000-00009"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cnp.2019.06.002"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx104"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/s19194301"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.1181-20.2020"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23672"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2014.04.021"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29376"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.13418"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmc1906060"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/practneurol-2020-002688"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41746-021-00438-z"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-022-11293-7"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.701632"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-88919-9"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-58912-9"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1109\/EMBC.2016.7590791"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2017.10.001"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20581-7"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23019"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26525"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26424"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2016.06.008"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2013.0048"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2025.02.255"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.13941"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004691-199603000-00002"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2004.04.006"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23922"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu250"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12938-015-0098-1"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29506"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2022.120196"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0306-4522(99)00583-7"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn270"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2008.06.087"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcaa074"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26663"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870120621"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29584"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.00172"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.14802\/jmd.23020"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.3988\/jcn.2022.18.2.127"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(19)30398-9"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(19)30442-9"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2018-318455"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2017.04.1333"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2012-304113"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26919"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2017.07.006"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2015.02.015"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23289"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2022.03.020"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww286"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2022.04.019"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70032","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mds.70032","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70032","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T06:00:10Z","timestamp":1783836010000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.70032"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,5]]},"references-count":80,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/mds.70032"],"URL":"https:\/\/doi.org\/10.1002\/mds.70032","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,5]]},"assertion":[{"value":"2025-05-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}