{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:20:27Z","timestamp":1791274827442,"version":"4.1.0"},"reference-count":87,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T00:00:00Z","timestamp":1651190400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T00:00:00Z","timestamp":1651190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["T32NS091006"],"award-info":[{"award-number":["T32NS091006"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01\u2010NS065980"],"award-info":[{"award-number":["R01\u2010NS065980"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1\u2010NS096606"],"award-info":[{"award-number":["RO1\u2010NS096606"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH\u201019\u20102\u20100002"],"award-info":[{"award-number":["W81XWH\u201019\u20102\u20100002"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH1910861"],"award-info":[{"award-number":["W81XWH1910861"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Brain Mapping"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Traumatic brain injury (TBI) is a major public health problem. Caused by external mechanical forces, a major characteristic of TBI is the shearing of axons across the white matter, which causes structural connectivity disruptions between brain regions. This diffuse injury leads to cognitive deficits, frequently requiring rehabilitation. Heterogeneity is another characteristic of TBI as severity and cognitive sequelae of the disease have a wide variation across patients, posing a big challenge for treatment. Thus, measures assessing network\u2010wide structural connectivity disruptions in TBI are necessary to quantify injury burden of individuals, which would help in achieving personalized treatment, patient monitoring, and rehabilitation planning. Despite TBI being a disconnectivity syndrome, connectomic assessment of structural disconnectivity has been relatively limited. In this study, we propose a novel connectomic measure that we call network normality score (NNS) to capture the integrity of structural connectivity in TBI patients by leveraging two major characteristics of the disease: diffuseness of axonal injury and heterogeneity of the disease. Over a longitudinal cohort of moderate\u2010to\u2010severe TBI patients, we demonstrate that structural network topology of patients is more heterogeneous and significantly different than that of healthy controls at 3\u2009months postinjury, where dissimilarity further increases up to 12\u2009months. We also show that NNS captures injury burden as quantified by posttraumatic amnesia and that alterations in the structural brain network is not related to cognitive recovery. Finally, we compare NNS to major graph theory measures used in TBI literature and demonstrate the superiority of NNS in characterizing the disease.<\/jats:p>","DOI":"10.1002\/hbm.25894","type":"journal-article","created":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T09:57:19Z","timestamp":1651226239000},"page":"3944-3957","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Connectomic assessment of injury burden and longitudinal structural network alterations in moderate\u2010to\u2010severe traumatic brain injury"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9997-9479","authenticated-orcid":false,"given":"Yusuf","family":"Osmanl\u0131o\u011flu","sequence":"first","affiliation":[{"name":"Department of Computer Science, College of Computing and Informatics Drexel University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drew","family":"Parker","sequence":"additional","affiliation":[{"name":"Department of Radiology, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob A.","family":"Alappatt","sequence":"additional","affiliation":[{"name":"Speech and hearing, bioscience and technology program, Harvard Medical School Harvard University  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Gugger","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon R.","family":"Diaz\u2010Arrastia","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Center for Brain Injury and Repair University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Whyte","sequence":"additional","affiliation":[{"name":"Moss Rehabilitation Research Institute, TBI Rehabilitation Research LaboratoryEinstein Medical Center  Elkins Park Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5729-8993","authenticated-orcid":false,"given":"Junghoon J.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Biomedical Sciences CUNY School of Medicine, The City College of New York  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ragini","family":"Verma","sequence":"additional","affiliation":[{"name":"Department of Radiology, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Center for Brain Injury and Repair University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Neurosurgery University of Pennsylvania, Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,4,29]]},"reference":[{"issue":"6","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1002\/ana.410120610","article-title":"Diffuse axonal injury due to nonmissile head injury in humans: An analysis of 45 cases","volume":"12","author":"Adams J. H.","year":"1982","journal-title":"Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2021.117927"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.media.2007.06.004"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v067.i01"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1516"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2006.0153"},{"key":"e_1_2_10_8_1","volume-title":"Controlled oral word association test, multilingual aphasia examination","author":"Benton A. L.","year":"1994"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-012-0494-2"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2010.12.046"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq174"},{"key":"e_1_2_10_12_1","unstructured":"Centers for Disease Control and Prevention(2019).Surveillance Report of Traumatic Brain Injury\u2010related Emergency Department Visits Hospitalizations and Deaths\u2014United States 2014. Centers for Disease Control and Prevention U.S. Department of Health and Human Services."},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11940-010-0085-6"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43588-021-00126-8"},{"issue":"1","key":"e_1_2_10_15_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.47102\/annals-acadmedsg.V36N1p31","article-title":"A brief review of traumatic brain injury rehabilitation","volume":"36","author":"Chua K. S.","year":"2007","journal-title":"Annals\u2010Academy of Medicine Singapore"},{"key":"e_1_2_10_16_1","volume-title":"Delis\u2010Kaplan executive function system (D\u2010KEFS) San Antonio","author":"Delis D. C.","year":"2001"},{"key":"e_1_2_10_17_1","doi-asserted-by":"crossref","unstructured":"Dennis E.L. Rashid F. Jahanshad N. Babikian T. Mink R. Babbitt C. Johnson J. Giza C.C. Asarnow R.F.andThompson p.M. 2017.A network approach to examining injury severity in pediatric TBI. In 2017 IEEE 14th international symposium on biomedical imaging (ISBI 2017) (pp. 105\u2010108). IEEE.","DOI":"10.1109\/ISBI.2017.7950479"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2006.01.021"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3171\/2017.10.JNS17352"},{"key":"e_1_2_10_20_1","unstructured":"Dhollander T. Raffelt D.andConnelly A. 2016.Unsupervised 3\u2010tissue response function estimation from single\u2010shell or multi\u2010shell diffusion MR data without a co\u2010registered T1 image. In ISMRM workshop on breaking the barriers of diffusion MRI (Vol. 5 no. 5). ISMRM."},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv075"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1355617712000835"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1037\/0894-4105.18.3.564"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.01.021"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1142\/S0218001414500013"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2017-317557"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/1545968319868710"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1355617715000740"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0104021"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2019.6762"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A3395"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.2147\/CEOR.S44625"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24065"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2019.01.002"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2016.06.012"},{"issue":"3","key":"e_1_2_10_36_1","first-page":"129","article-title":"Structural and connectomic neuroimaging for the personalized study of longitudinal alterations in cortical shape, thickness and connectivity after traumatic brain injury","volume":"58","author":"Irimia A.","year":"2014","journal-title":"Journal of Neurosurgical Sciences"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-9993(98)90051-X"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2014.07.061"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws322"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa067"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.2217\/iim.10.21"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1355617714000812"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.24713"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/nav.3800020109"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v082.i13"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000304108.32283.aa"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjtee.2016.01.001"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.62"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A0970"},{"issue":"3","key":"e_1_2_10_50_1","first-page":"47","article-title":"Neurorehabilitation of traumatic brain injury (TBI): A clinical review","volume":"7","author":"Oberholzer M.","year":"2019","journal-title":"Medical Science"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1080\/13854046.2019.1598501"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2021.118642"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhu023"},{"key":"e_1_2_10_54_1","unstructured":"Osmanl\u0131o\u011flu Y. 2016.On the applications of metric trees and metric labeling to hard combinatorial optimization problems. (Doctoral dissertation Drexel University)."},{"key":"e_1_2_10_55_1","first-page":"189","volume-title":"International MICCAI Brainlesion Workshop","author":"Osmanl\u0131o\u011flu Y.","year":"2018"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1088\/1741-2552\/ab947b"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.05.064"},{"key":"e_1_2_10_58_1","unstructured":"PinheiroJ BatesD DebRoyS SarkarD RCore Team(2021).nlme: Linear and nonlinear mixed effects models. R package version 3.1\u2010152 https:\/\/CRAN.R-project.org\/package=nlme."},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2016.167"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001199-200501000-00008"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1355617717000996"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-65948-4"},{"key":"e_1_2_10_63_1","volume-title":"The Halstead\u2010Reitan neuropsychological test battery: Theory and clinical interpretation","author":"Reitan R. M.","year":"1985"},{"key":"e_1_2_10_64_1","volume-title":"Memorisation d'une serie de 15 mots en 5 repetitions","author":"Rey A.","year":"1958"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2009.10.003"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.3.418"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2020.117502"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-60365-6_13"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2009.05.049"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.06.005"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2013.00031"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.23561"},{"key":"e_1_2_10_73_1","volume-title":"Translational research in traumatic brain injury","author":"Sophie Su Y. R.","year":"2016"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.0010042"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30118-7"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2007.02.016"},{"key":"e_1_2_10_77_1","volume-title":"Proceedings of the international society for magnetic resonance in medicine, ISMRM","author":"Tournier J. D.","year":"2010"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.116137"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1186\/1749-7922-4-7"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2021.0057"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31822c61d7"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2018.1428089"},{"key":"e_1_2_10_83_1","first-page":"498","volume-title":"Wechsler adult intelligence scale\u2010fourth edition (WAIS\u2010IV)","author":"Wechsler D.","year":"2008"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30279-X"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11682-013-9288-2"},{"key":"e_1_2_10_86_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22664"},{"key":"e_1_2_10_87_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2013.2970"},{"key":"e_1_2_10_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3045"}],"container-title":["Human Brain Mapping"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hbm.25894","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hbm.25894","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hbm.25894","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hbm.25894","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T15:28:19Z","timestamp":1692718099000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hbm.25894"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,29]]},"references-count":87,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2022,9]]}},"alternative-id":["10.1002\/hbm.25894"],"URL":"https:\/\/doi.org\/10.1002\/hbm.25894","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.04.20.440635","asserted-by":"object"}]},"ISSN":["1065-9471","1097-0193"],"issn-type":[{"value":"1065-9471","type":"print"},{"value":"1097-0193","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,29]]},"assertion":[{"value":"2022-01-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}