{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:12:33Z","timestamp":1790813553470,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2019,6,12]],"date-time":"2019-06-12T00:00:00Z","timestamp":1560297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005725","name":"CHDI Foundation","doi-asserted-by":"publisher","award":["A \u2010 3433"],"award-info":[{"award-number":["A \u2010 3433"]}],"id":[{"id":"10.13039\/100005725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001671","name":"Hereditary Disease Foundation","doi-asserted-by":"publisher","award":["Fellowship 2015\u20102016"],"award-info":[{"award-number":["Fellowship 2015\u20102016"]}],"id":[{"id":"10.13039\/100001671","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["606650"],"award-info":[{"award-number":["606650"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["Fellowship 1106533"],"award-info":[{"award-number":["Fellowship 1106533"]}],"id":[{"id":"10.13039\/501100000925","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":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Trans\u2010neuronal propagation of mutant huntingtin protein contributes to the organised spread of cortico\u2010striatal degeneration and disconnection in Huntington's disease (HD). We investigated whether the network diffusion model, which models transneuronal spread as diffusion of pathological proteins via the brain connectome, can determine the severity of neural degeneration and disconnection in HD. We used structural magnetic resonance imaging (MRI) and high\u2010angular resolution diffusion weighted imaging (DWI) data from symptomatic Huntington's disease (HD) (<jats:italic>N<\/jats:italic> = 26) and age\u2010matched healthy controls (<jats:italic>N<\/jats:italic> = 26) to measure neural degeneration and disconnection in HD. The network diffusion model was used to test whether disease spread, via the human brain connectome, is a viable mechanism to explain the distribution of pathology across the brain. We found that an eigenmode identified in the healthy human brain connectome Laplacian matrix, accurately predicts the cortico\u2010striatal spatial pattern of degeneration in HD. Furthermore, the spread of neural degeneration from sub\u2010cortical brain regions, including the accumbens and thalamus, generates a spatial pattern which represents the typical neurodegenerative characteristics in HD. The white matter connections connecting the nodes with the highest amount of disease factors, when diffusion based disease spread is initiated from the striatum, were found to be most vulnerable to disconnection in HD. These findings suggest that trans\u2010neuronal diffusion of mutant huntingtin protein across the human brain connectome may explain the pattern of gray matter degeneration and white matter disconnection that are hallmarks of HD.<\/jats:p>","DOI":"10.1002\/hbm.24695","type":"journal-article","created":{"date-parts":[[2019,6,12]],"date-time":"2019-06-12T09:40:17Z","timestamp":1560332417000},"page":"4192-4201","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Network spread determines severity of degeneration and disconnection in Huntington's disease"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0043-7531","authenticated-orcid":false,"given":"Govinda R.","family":"Poudel","sequence":"first","affiliation":[{"name":"Mary Mackillop Institute for Health Research Australian Catholic University  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian H.","family":"Harding","sequence":"additional","affiliation":[{"name":"School of Psychological Sciences &amp; Monash Institute of Cognitive and Clinical Neurosciences Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary F.","family":"Egan","sequence":"additional","affiliation":[{"name":"School of Psychological Sciences &amp; Monash Institute of Cognitive and Clinical Neurosciences Monash University  Clayton Victoria Australia"},{"name":"Monash Biomedical Imaging (MBI) Monash University  Melbourne VIC Australia"},{"name":"ARC Centre of Excellence for Integrative Brain Function Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0718-6760","authenticated-orcid":false,"given":"Nellie","family":"Georgiou\u2010Karistianis","sequence":"additional","affiliation":[{"name":"School of Psychological Sciences &amp; Monash Institute of Cognitive and Clinical Neurosciences Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2010.208264"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1516217112"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/120.12.2207"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.02.010"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0074131"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2006.05.057"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2016.02.014"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhg087"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2012.10.001"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt222"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv145"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2009.190702"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2016.12.015"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.09.015"},{"issue":"2","key":"e_1_2_8_16_1","first-page":"213","article-title":"Topography of cerebral atrophy in early Huntington's disease: A voxel based morphometric MRI study","volume":"75","author":"Kassubek J.","year":"2004","journal-title":"Journal of Neurology, Neurosurgery and Psychiatry"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-21-08473.2001"},{"key":"e_1_2_8_18_1","doi-asserted-by":"crossref","unstructured":"Ma H. Yang H. Lyu M. R. &King I. (2008).Mining social networks using heat diffusion processes for marketing candidates selection. Paper presented at the Proceedings of the 17th ACM conference on Information and knowledge management Napa Valley California USA.","DOI":"10.1145\/1458082.1458115"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90585-E"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81369-0"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2017.10.019"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.92641"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv259"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(99)00019-2"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00692"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3761"},{"issue":"2","key":"e_1_2_8_27_1","first-page":"87","article-title":"Abnormal synchrony of resting state networks in premanifest and symptomatic Huntington disease: the IMAGE\u2010HD study","volume":"39","author":"Poudel G. R.","year":"2014","journal-title":"Journal of Psychiatry and Neuroscience"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2014.01.013"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2014.12.009"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.12.040"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.12.034"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn025"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2007.116244"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.03.024"},{"key":"e_1_2_8_35_1","first-page":"561","article-title":"White matter microstructure as biomarker for preclinical Huntington's disease","volume":"18","author":"Szabo N.","year":"2011","journal-title":"European Journal of Neurology"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70170-X"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70276-3"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70088-7"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx371"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ima.22005"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-010-5768-0"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3539-11.2011"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn175"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22351"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02416-0"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2010.06.041"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25309"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.03.004"}],"container-title":["Human Brain Mapping"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhbm.24695","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hbm.24695","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hbm.24695","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hbm.24695","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T14:51:55Z","timestamp":1694271115000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hbm.24695"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,12]]},"references-count":47,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["10.1002\/hbm.24695"],"URL":"https:\/\/doi.org\/10.1002\/hbm.24695","archive":["Portico"],"relation":{},"ISSN":["1065-9471","1097-0193"],"issn-type":[{"value":"1065-9471","type":"print"},{"value":"1097-0193","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,12]]},"assertion":[{"value":"2018-12-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}