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Although structural alterations have been reported decades before symptom onset, the longitudinal evolution of socioemotional network dysfunction in premanifest C9RE carriers remains poorly understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this multimodal 2\u2010year longitudinal study, we examined 21 premanifest C9RE carriers and 24 controls using structural magnetic resonance imaging (MRI), resting\u2010state, and task\u2010based functional MRI (fMRI), and multivariate pattern analysis. Participants completed facial emotion processing tasks during fMRI scanning, alongside behavioral assessments. We assessed regional activation, network connectivity, and voxel\u2010wise structural integrity at baseline and follow up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At baseline, premanifest C9RE carriers showed reduced emotion recognition efficiency, accompanied by bilateral thalamic atrophy, decreased activation in the anterior and posterior cingulate cortex, and increased activation in the posterior cerebellum, along with altered multivoxel activity patterns in the anterior cingulate and posterior cerebellum. Resting\u2010state fMRI revealed decreased functional connectivity involving the thalamus, anterior, and posterior cingulate cortex. Longitudinal analyses indicated declining emotion\u2010evoked responses in the posterior cingulate cortex and cerebellum, alongside further thalamic volume loss, whereas functional connectivity showed no significant change over time. Despite these progressive neural alterations, behavioral performance remained stable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Socioemotional circuit dysfunction emerges early in C9RE carriers and progresses over time, preceding overt clinical symptoms. Functional imaging, especially task\u2010based fMRI combined with multivariate pattern analysis, captures early circuit\u2010level alterations that may serve as sensitive biomarkers for premanifest neurodegeneration. ANN NEUROL 2026<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.78355","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:35:31Z","timestamp":1788777331000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tracking Socio\u2010emotional Brain Changes in Premanifest\n                    <i>C9orf72<\/i>\n                    Repeat Expansion Carriers: A Structural and Functional 2\u2010Year Longitudinal\n                    <scp>Magnetic Resonance Imaging<\/scp>\n                    Study"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8256-7574","authenticated-orcid":false,"given":"Jiaze","family":"Sun","sequence":"first","affiliation":[{"name":"Neuropsychiatry, Department of Neurosciences, Leuven Brain Institute KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joke 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