{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:00:17Z","timestamp":1768568417832,"version":"3.49.0"},"posted":{"date-parts":[[2025,1,15]]},"group-title":"Radiology and Imaging","reference-count":45,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>There are no disease modifying therapies for Huntington\u2019s disease (HD), a rare but fatal genetic neurodegenerative condition. To develop and test new management strategies, a better understanding of the mechanisms underlying HD progression is needed. Aberrant changes in thalamo-cortical and striato-cerebellar circuitry have been observed in asymptomatic HD, along with transient enlargement of the dentate nucleus.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>To evaluate the relationship between thalamo-cerebellar connectivity and HD progression.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Study Type<\/jats:title>\n                  <jats:p>Prospective and retrospective.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Population<\/jats:title>\n                  <jats:p>Patients with HD and healthy controls from a single-center dataset (n=34), and patients from the public TRACK-HD dataset (n=91).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Field strength\/Sequence<\/jats:title>\n                  <jats:p>3T and 7T.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Assessment<\/jats:title>\n                  <jats:p>Thalamo-cerebellar connectivity was compared across patients and controls and related to motor scores and predicted years to symptom onset. Cross-sectional findings were validated within-patient by mapping changes in individual connectivity over time. HD effects on cognitive performance were also explored and related to connectivity.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Statistical Tests<\/jats:title>\n                  <jats:p>\n                    Kruskal-Wallis with post hoc Dunn\u2019s tests and Pearson correlations (p\n                    <jats:sub>significant<\/jats:sub>\n                    &lt;0.05).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    In the 7T cohort, significant premanifest and control group differences in thalamo-dentate connectivity were observed (p\n                    <jats:sub>Dunn<\/jats:sub>\n                    &lt;0.05, \u03b7\n                    <jats:sup>2<\/jats:sup>\n                    =.19-.22), with manifest HD connectivity approaching normative values. Thalamic connectivity with the dentate nucleus and anterior cerebellum also correlated with years to onset (p\n                    <jats:sub>Den<\/jats:sub>\n                    =0.06, r=0.42, p\n                    <jats:sub>Ant<\/jats:sub>\n                    &lt;0.05, r=-0.45), together indicating potential transient functional alterations in premanifest HD. Similar patterns were observed between connectivity (thalamus to dentate nucleus and anterior lobe) and cognitive performance scores across all subjects (p&lt;0.05, r\n                    <jats:sub>Den<\/jats:sub>\n                    =-0.17, r\n                    <jats:sub>Ant<\/jats:sub>\n                    =-0.18). In the premanifest TRACK-HD cohort, connectivity of multiple thalamo-cerebellar connections correlated with years to onset, revealing distinct patterns for patients with low versus high motor scores, again indicative of potential transient alterations. Exploratory non-parametric regression of serial imaging data further supported these findings.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Data conclusion<\/jats:title>\n                  <jats:p>Transient changes in thalamo-cerebellar connectivity are seen in premanifest HD with increasing progression. More studies are needed to validate this potentially useful biomarker.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.01.15.25320232","type":"posted-content","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T21:50:12Z","timestamp":1736977812000},"source":"Crossref","is-referenced-by-count":0,"title":["TRANSIENT ALTERATIONS IN THALAMO-CEREBELLAR FUNCTIONAL CONNECTIVITY IN PREMANIFEST HUNTINGTON\u2019S DISEASE"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5993-0515","authenticated-orcid":false,"given":"Melanie 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B.","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine L.","family":"Possin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher P.","family":"Hess","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janine 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