{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:42:07Z","timestamp":1790264527071,"version":"4.1.0"},"reference-count":79,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,9,27]],"date-time":"2018-09-27T00:00:00Z","timestamp":1538006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["NMR in Biomedicine"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:p>Recent studies suggest that neurodegenerative diseases could affect brain structure and function in disease\u2010specific network patterns; however, how spontaneous activity affects structural covariance network (SC) is not clear. We hypothesized that hyper\u2010excitability in Huntington disease (HD) disrupts the coordinated structural and functional connectivity, and treatment with memantine helps to reduce excitotoxicity and normalize the connectivity. MRI was conducted to measure somatosensory activation, resting\u2010state functional\u2010connectivity (rsFC), SC, amplitude of low frequency fluctuation (ALFF) and ALFF covariance (ALFFC) in the YAC128 mouse model of HD. We found somatosensory activation was unchanged but the subcortical ALFF was increased in HD mice, indicating subcortical but not cortical hyperactivity. The reduced sensorimotor rsFC but spared hippocampal and default mode networks in the HD mice was consistent with the more pronounced impairment in motor function compared with cognitive performance. The disease suppressed SC globally and reduced ALFFC in the basal ganglia network as well as its anti\u2010correlation with the default mode network. By comparing these connectivity measures, we found that the originally coupled rsFC\u2010SC relationship was impaired whereas SC\u2010ALFFC correlation was increased by HD, suggesting disease facilitated covariation of brain volume and activity amplitude but not neural synchrony. The comparison with mono\u2010synaptic axonal projection supports the hypothesis that rsFC, but not SC or ALFFC, is highly dependent on structural connectivity under healthy conditions. Treatment with memantine had a strong effect on normalizing the SC and reducing ALFF while slightly increasing other connectivity measures and restoring the rsFC\u2010SC coupling, which is consistent with its effect on alleviating hyper\u2010excitability and improving the coordinated neural growth. These results indicate that HD affects the cerebral structure\u2013function relationship which could be partially reverted by NMDA antagonism. These connectivity measures provide unique insights into pathological and pharmaceutical effects in brain circuitry, and could be translatable biomarkers for evaluating drug effect and refining its efficacy.<\/jats:p>","DOI":"10.1002\/nbm.4007","type":"journal-article","created":{"date-parts":[[2018,9,27]],"date-time":"2018-09-27T10:10:10Z","timestamp":1538043010000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Connectomic imaging reveals Huntington\u2010related pathological and pharmaceutical effects in a mouse model"],"prefix":"10.1002","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2918-1752","authenticated-orcid":false,"given":"Wei\u2010Tang","family":"Chang","sequence":"first","affiliation":[{"name":"Singapore BioImaging Consortium, Agency for Science, Technology and Research  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiftarina","family":"Puspitasari","sequence":"additional","affiliation":[{"name":"Singapore BioImaging Consortium, Agency for Science, Technology and Research  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Garcia\u2010Miralles","sequence":"additional","affiliation":[{"name":"Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling Yun","family":"Yeow","sequence":"additional","affiliation":[{"name":"Singapore BioImaging Consortium, Agency for Science, Technology and Research  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui\u2010Chien","family":"Tay","sequence":"additional","affiliation":[{"name":"Singapore BioImaging Consortium, Agency for Science, Technology and Research  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrianne Bethia","family":"Koh","sequence":"additional","affiliation":[{"name":"Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang Juin","family":"Tan","sequence":"additional","affiliation":[{"name":"Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud A.","family":"Pouladi","sequence":"additional","affiliation":[{"name":"Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research  Singapore Singapore"},{"name":"Department of Medicine National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai\u2010Hsiang","family":"Chuang","sequence":"additional","affiliation":[{"name":"Singapore BioImaging Consortium, Agency for Science, Technology and Research  Singapore Singapore"},{"name":"Queensland Brain Institute University of Queensland  Brisbane Australia"},{"name":"Centre for Advanced Imaging University of Queensland  Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60111-1"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0010-9452(87)80037-0"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg169"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3570"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2012.06.026"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp006"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2056"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep31652"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20979"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2016.10.009"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22351"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2013.03.001"},{"key":"e_1_2_8_14_1","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1503\/jpn.120226","article-title":"Abnormal synchrony of resting state networks in premanifest and symptomatic Huntington disease: the IMAGE\u2010HD study","volume":"2","author":"Poudel GR","year":"2014","journal-title":"J Psychiatry Neurosci"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22616"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.03.024"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00615-3"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5599-08.2009"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.01.008"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/currents.RRN1291"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2013.11.013"},{"key":"e_1_2_8_22_1","first-page":"83","article-title":"Altered baseline brain activity in children with ADHD revealed by resting\u2010state functional MRI","volume":"2","author":"Zang YF","year":"2007","journal-title":"Brain Dev"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13186"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.08.013"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.092759.109"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2007.04.042"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2015.06.010"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2015.01.005"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.09.015"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2009.10.080"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4286-09.2009"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2003.08.003"},{"key":"e_1_2_8_33_1","doi-asserted-by":"crossref","unstructured":"Fox M.D. A.Z.Snyder J.L.Vincent M.Corbetta D.C.Van Essen andM.E.Raichle The human brain is intrinsically organized into dynamic anticorrelated functional networks. Proc Natl Acad Sci U S A 2005.27:9673\u20139678.","DOI":"10.1073\/pnas.0504136102"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.23014"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0013-4694(82)90033-5"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2008.12.026"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2010.03.014"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.15288\/jsad.2013.74.245"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn835"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2911"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7091-0579-5_14"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2016.04.017"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2012.02.095"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2015.02.018"},{"key":"e_1_2_8_45_1","first-page":"2332","article-title":"Network topology and functional connectivity disturbances precede the onset of Huntington's disease. Brain, 2015","volume":"8","author":"Harrington DL","journal-title":"Pt"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.08.105"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.2165\/11586440-000000000-00000"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-013-2966-3"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911855107"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1089\/brain.2012.0095"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028817"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3465"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1929-08.2008"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0141-08.2008"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2010.31"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1001006"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhq291"},{"key":"e_1_2_8_58_1","volume-title":"Simultaneous multi\u2010slab acquisition in 3D multi\u2010slab diffusion\u2010weighted readout\u2010segmented echo\u2010planar imaging. in ISMRM 21th Annual Meeting & Exhibition","author":"Frost R","year":"2013"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0438-17.2017"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.229.4714.668"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1558-5646.2012.01656.x"},{"key":"e_1_2_8_62_1","article-title":"The influence of the amplitude of low\u2010frequency fluctuations on resting\u2010state functional connectivity","volume":"118","author":"Di X","year":"2013","journal-title":"Front Hum Neurosci"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1404346111"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhw327"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhn059"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0811168106"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa013128"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911503106"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt036"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24174"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24406"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24428"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.05.035"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.01.040"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2013.08.004"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.12.026"},{"key":"e_1_2_8_77_1","first-page":"546","article-title":"Effect of Memantine on Brain Metabolic Activity and Perfusion in Drug\u2010na\u00efve Moderate Alzheimer's Disease Patients","volume":"2","author":"Iwamoto T","year":"2018","journal-title":"Neuropsychiatry (London)"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2007.00943.x"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.12779\/dnd.2016.15.2.43"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1176\/jnp.23.2.jnp206"}],"container-title":["NMR in Biomedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fnbm.4007","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/nbm.4007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T14:47:05Z","timestamp":1760971625000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/nbm.4007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,27]]},"references-count":79,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["10.1002\/nbm.4007"],"URL":"https:\/\/doi.org\/10.1002\/nbm.4007","archive":["Portico"],"relation":{},"ISSN":["0952-3480","1099-1492"],"issn-type":[{"value":"0952-3480","type":"print"},{"value":"1099-1492","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,27]]},"assertion":[{"value":"2018-01-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e4007"}}