{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T16:18:21Z","timestamp":1788970701049,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,7]]},"group-title":"Neuroscience","reference-count":44,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["NS127344"],"award-info":[{"award-number":["NS127344"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"publisher"}]},{"award":["NS124084"],"award-info":[{"award-number":["NS124084"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Huntington\u2019s disease (HD) is a neurodegenerative disorder characterized by progressive motor dysfunction. Traditional open-field tests quantify spontaneous locomotor parameters; however, fine mouse motor signatures, particularly disease stage-specific changes in HD motor symptoms and pharmacodynamic responses to therapeutic treatments. Here, we employed a computer vision-aided behavioral flow analysis designed to quantify fine, HD-relevant motor dysfunction in the zQ175DN HD mouse model, ranging from early HD-like motor signatures to well-defined motor deficits. Markerless pose estimation and Keypoint-MoSeq segmented standard top-view open-field recordings into recurrent behavioral syllables, which were then organized into higher-order clusters and transition networks. Disease stage-dependent changes in syllable occurrence, syllable duration, behavioral-state composition, and transition structure were identified. These analyses are not possible with traditional open-field assays. Syllable-duration features provided the strongest genotype discrimination, and HD-like motor features were also characterized by hub remodeling and transition-network disorganization. These features were integrated into an HD motor dysfunction (HDMD) score based on age- or HD progress-matched wild-type (WT) - standardized absolute deviations. The HDMD score distinguished HD mice from WT across multiple symptomatic stages and correlated with HD pathology and disease severity. Effect-size and power analyses suggested improved efficiency for detecting potential therapeutic effects. This framework requires only standard top-view recordings and may also support retrospective analysis of existing open-field video datasets. Overall, the HDMD framework provides a practical strategy for identifying fine motor changes in HD mice, aiding study design and preclinical efficacy assessment in HD drug development.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Abstract Figure<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"749147v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Bullet Points<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Computer-aided behavioral analysis identifies stage-specific HD motor signatures in mice.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>The HDMD score provides clinically relevant motor assessment.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>HDMD improves power to detect therapeutic effects.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Standard top-view videos may support retrospective HDMD analysis.<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.03.749147","type":"posted-content","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:55:17Z","timestamp":1788782117000},"source":"Crossref","is-referenced-by-count":0,"title":["Computer vision-aided locomotor behavioral analysis identifies therapeutic motor signatures in a mouse model of Huntington\u2019s disease"],"prefix":"10.64898","author":[{"given":"Lida","family":"Du","sequence":"first","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287"},{"name":"Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21218"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongshuai","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aadhya","family":"Bavkar","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287"},{"name":"Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21218"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287"},{"name":"Department of Neuroscience, Yale University, New Haven, CT 06510"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukuan","family":"Shi","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren A","family":"Lim","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Guo","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287"},{"name":"Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21218"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqi","family":"Qin","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287"},{"name":"The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A","family":"Ross","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhen","family":"Duan","sequence":"additional","affiliation":[{"name":"Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287"},{"name":"The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026090909000811000_2026.09.03.749147v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90585-E"},{"key":"2026090909000811000_2026.09.03.749147v1.2","doi-asserted-by":"publisher","DOI":"10.7759\/CUREUS.28484"},{"key":"2026090909000811000_2026.09.03.749147v1.3","doi-asserted-by":"publisher","DOI":"10.1186\/S13024-026-00960-2"},{"key":"2026090909000811000_2026.09.03.749147v1.4","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-012-0112-2"},{"key":"2026090909000811000_2026.09.03.749147v1.5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2210719120"},{"key":"2026090909000811000_2026.09.03.749147v1.6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049838"},{"key":"2026090909000811000_2026.09.03.749147v1.7","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab190"},{"key":"2026090909000811000_2026.09.03.749147v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2025.102984"},{"key":"2026090909000811000_2026.09.03.749147v1.9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0148839"},{"key":"2026090909000811000_2026.09.03.749147v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2009.05.007"},{"key":"2026090909000811000_2026.09.03.749147v1.11","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-024-01919-9"},{"key":"2026090909000811000_2026.09.03.749147v1.12","doi-asserted-by":"publisher","DOI":"10.1186\/S13041-023-01054-6"},{"key":"2026090909000811000_2026.09.03.749147v1.13","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw212"},{"key":"2026090909000811000_2026.09.03.749147v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-17956-5"},{"key":"2026090909000811000_2026.09.03.749147v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0209-y"},{"key":"2026090909000811000_2026.09.03.749147v1.16","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-022-01426-1"},{"key":"2026090909000811000_2026.09.03.749147v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2281"},{"key":"2026090909000811000_2026.09.03.749147v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25420-x"},{"key":"2026090909000811000_2026.09.03.749147v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/S42003-022-04080-7"},{"key":"2026090909000811000_2026.09.03.749147v1.20","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-024-02318-2"},{"key":"2026090909000811000_2026.09.03.749147v1.21","doi-asserted-by":"publisher","DOI":"10.1038\/S41596-024-01015-W"},{"key":"2026090909000811000_2026.09.03.749147v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.04.019"},{"key":"2026090909000811000_2026.09.03.749147v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-026-02651-2"},{"key":"2026090909000811000_2026.09.03.749147v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-67559-x"},{"key":"2026090909000811000_2026.09.03.749147v1.25","doi-asserted-by":"publisher","DOI":"10.3389\/FPSYT.2026.1749543\/TEXT"},{"key":"2026090909000811000_2026.09.03.749147v1.26","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-48792-2"},{"key":"2026090909000811000_2026.09.03.749147v1.27","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0209-y"},{"key":"2026090909000811000_2026.09.03.749147v1.28","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-024-02318-2"},{"key":"2026090909000811000_2026.09.03.749147v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22970-y"},{"key":"2026090909000811000_2026.09.03.749147v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2025.115461"},{"key":"2026090909000811000_2026.09.03.749147v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2017.05.011"},{"key":"2026090909000811000_2026.09.03.749147v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2025.11.021"},{"key":"2026090909000811000_2026.09.03.749147v1.33","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2215230120"},{"key":"2026090909000811000_2026.09.03.749147v1.34","doi-asserted-by":"publisher","DOI":"10.1126\/SCIADV.ADT0854;PAGEGROUP:STRING:PUBLICATION"},{"key":"2026090909000811000_2026.09.03.749147v1.35","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04894-9"},{"key":"2026090909000811000_2026.09.03.749147v1.36","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3556"},{"key":"2026090909000811000_2026.09.03.749147v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33584-3"},{"key":"2026090909000811000_2026.09.03.749147v1.38","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0014-23.2023"},{"key":"2026090909000811000_2026.09.03.749147v1.39","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-022-00552-x"},{"key":"2026090909000811000_2026.09.03.749147v1.40","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-024-02500-6"},{"key":"2026090909000811000_2026.09.03.749147v1.41","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PCBI.1009439"},{"key":"2026090909000811000_2026.09.03.749147v1.42","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-022-01615-y"},{"key":"2026090909000811000_2026.09.03.749147v1.43","doi-asserted-by":"publisher","DOI":"10.1002\/MDS.28489;WGROUP:STRING:PUBLICATION"},{"key":"2026090909000811000_2026.09.03.749147v1.44","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abc2888"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.03.749147","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T16:00:18Z","timestamp":1788969618000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.03.749147"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":44,"URL":"https:\/\/doi.org\/10.64898\/2026.09.03.749147","relation":{},"subject":[],"published":{"date-parts":[[2026,9,7]]},"subtype":"preprint"}}