{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:38:31Z","timestamp":1790671111148,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001472","name":"Singapore Police Force","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001472","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010414","name":"Health Research Board","doi-asserted-by":"publisher","award":["HRBEIA\u20102017\u2010019"],"award-info":[{"award-number":["HRBEIA\u20102017\u2010019"]}],"id":[{"id":"10.13039\/100010414","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010414","name":"Health Research Board","doi-asserted-by":"publisher","award":["JPND\u2010Cofund\u20102\u20102019\u20101"],"award-info":[{"award-number":["JPND\u2010Cofund\u20102\u20102019\u20101"]}],"id":[{"id":"10.13039\/100010414","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003840","name":"Irish Institute of Clinical Neuroscience","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003840","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000406","name":"Motor Neurone Disease Association","doi-asserted-by":"publisher","award":["898\u2010792"],"award-info":[{"award-number":["898\u2010792"]}],"id":[{"id":"10.13039\/501100000406","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013278","name":"EU Joint Programme \u2013 Neurodegenerative Disease Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013278","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["17\/CDA\/4737"],"award-info":[{"award-number":["17\/CDA\/4737"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Primary lateral sclerosis (PLS) is a progressive upper motor neuron disorder associated with considerable clinical disability. Symptoms are typically exclusively linked to primary motor cortex degeneration and the contribution of pre\u2010motor, supplementary motor, cortico\u2010medullary and inter\u2010hemispheric connectivity alterations are less well characterized.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a single\u2010centre, prospective, longitudinal neuroimaging study 41 patients with PLS were investigated. Patients underwent standardized neuroimaging, genetic profiling with whole exome sequencing, and comprehensive clinical assessments including upper motor neuron scores, tapping rates, mirror movements, spasticity assessment, cognitive screening and evaluation for pseudobulbar affect. Longitudinal neuroimaging data from 108 healthy controls were used for image interpretation. A standardized imaging protocol was implemented including 3D T1\u2010weighted structural, diffusion tensor imaging and resting\u2010state functional magnetic resonance imaging. Following somatotopic segmentation, cortical thickness analyses, probabilistic tractography, blood oxygenation level dependent signal analyses and brainstem volumetry were conducted to evaluate cortical, brainstem, cortico\u2010medullary and inter\u2010hemispheric connectivity alterations both cross\u2010sectionally and longitudinally.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our data confirm progressive primary motor cortex degeneration, considerable supplementary motor and pre\u2010motor area involvement, progressive brainstem atrophy, cortico\u2010medullary and inter\u2010hemispheric disconnection, and close associations between clinical upper motor neuron scores and somatotopic connectivity indices in PLS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Primary lateral sclerosis is associated with relentlessly progressive motor connectome degeneration. Clinical disability in PLS is likely to stem from a combination of intra\u2010 and inter\u2010hemispheric connectivity decline and primary, pre\u2010 and supplementary motor cortex degeneration. Simple \u2018bedside\u2019 clinical tools, such as tapping rates, are excellent proxies of the integrity of the relevant fibres of the contralateral corticospinal tract.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15725","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T00:17:25Z","timestamp":1675642645000},"page":"1232-1245","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Not a benign motor neuron disease: longitudinal imaging captures relentless motor connectome disintegration in primary lateral sclerosis"],"prefix":"10.1111","volume":"30","author":[{"given":"Marlene","family":"Tahedl","sequence":"first","affiliation":[{"name":"Computational Neuroimaging Group (CNG), Biomedical Sciences Institute Trinity College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ee Ling","family":"Tan","sequence":"additional","affiliation":[{"name":"Computational Neuroimaging Group (CNG), Biomedical Sciences Institute Trinity College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey Li Hi","family":"Shing","sequence":"additional","affiliation":[{"name":"Computational Neuroimaging Group (CNG), Biomedical Sciences Institute Trinity College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rangariroyashe H.","family":"Chipika","sequence":"additional","affiliation":[{"name":"Computational Neuroimaging Group (CNG), Biomedical Sciences Institute Trinity College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"We Fong","family":"Siah","sequence":"additional","affiliation":[{"name":"Computational Neuroimaging Group (CNG), Biomedical Sciences Institute Trinity College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer C.","family":"Hengeveld","sequence":"additional","affiliation":[{"name":"Smurfit Institute of Genetics Trinity College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Doherty","sequence":"additional","affiliation":[{"name":"Smurfit Institute of Genetics Trinity College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell L.","family":"McLaughlin","sequence":"additional","affiliation":[{"name":"Smurfit Institute of Genetics Trinity College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orla","family":"Hardiman","sequence":"additional","affiliation":[{"name":"Computational Neuroimaging Group (CNG), Biomedical Sciences Institute Trinity College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eoin","family":"Finegan","sequence":"additional","affiliation":[{"name":"Computational Neuroimaging Group (CNG), Biomedical Sciences Institute Trinity College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0492-4772","authenticated-orcid":false,"given":"Peter","family":"Bede","sequence":"additional","affiliation":[{"name":"Computational Neuroimaging Group (CNG), Biomedical Sciences Institute Trinity College Dublin  Dublin Ireland"},{"name":"Department of Neurology St James's Hospital  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.NXG.0000464294.88607.dd"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2009.19"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22286"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2019.102089"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2018.1517180"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2020.117039"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-006-0482-7"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.09.041"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2020.1837176"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2018.1562554"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr178"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2018.10.005"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2021.120079"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2018.03.018"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3109\/21678421.2015.1051989"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-020-01366-z"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2020.1790607"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.26765"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2021.04.008"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2019-322541"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2016.1249887"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(99)00211-7"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.2196\/mhealth.2706"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2015.02.017"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70014-5"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2021-326854"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2006.02.004"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhw157"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.02.065"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fninf.2011.00004"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.02.064"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fninf.2016.00027"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/156869"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.26059"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.26054"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2004.07.051"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1109\/TMI.2010.2046908"},{"key":"e_1_2_11_39_1","unstructured":"TournierJD CalamanteF ConnellyA.Improved probabilistic streamlines tractography by 2nd order integration over fibre orientation distributions.Proceedings of the International Society for Magnetic Resonance in Medicine (ISMRM). 2010;18."},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2021.117584"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-018-8964-y"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dib.2020.105115"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.27335"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.14042"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000260065.57832.87"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.01148"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.31083\/j.jin2103087"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-021-10801-5"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2017.06.010"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2020.117052"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dib.2020.106247"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.15725","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ene.15725","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.15725","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T08:36:53Z","timestamp":1692693413000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.15725"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3]]},"references-count":50,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,5]]}},"alternative-id":["10.1111\/ene.15725"],"URL":"https:\/\/doi.org\/10.1111\/ene.15725","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"value":"1351-5101","type":"print"},{"value":"1468-1331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3]]},"assertion":[{"value":"2022-12-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}