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{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T12:01:33Z","timestamp":1705060893922},"reference-count":49,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000143","name":"Alzheimer Society of Canada","doi-asserted-by":"publisher"},{"DOI":"10.13039\/100012479","name":"Weston Brain Institute","doi-asserted-by":"publisher"},{"DOI":"10.13039\/501100000156","name":"FRQS","doi-asserted-by":"publisher"},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["CoEN015"]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher"},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher"},{"DOI":"10.13039\/501100018956","name":"NIHR Cambridge Biomedical Research Centre","doi-asserted-by":"publisher","award":["BRC\u20101215\u201020014","BRC149\/NS\/MH"]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Brain Mapping"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule\u2010associated protein tau (<jats:italic>MAPT<\/jats:italic>), progranulin (<jats:italic>GRN<\/jats:italic>) and chromosome 9 open reading frame 72 (<jats:italic>C9orf72<\/jats:italic>). However, the cerebello\u2010subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first\u2010degree relatives of known symptomatic carriers. Voxel\u2010wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic <jats:italic>C9orf72<\/jats:italic> expansion carriers, thalamic atrophy was found compared to noncarriers, suggesting the importance of this structure in FTD prodromes. PLS analyses demonstrated that the cerebello\u2010subcortical circuitry is related to neuropsychiatric symptoms, with significant overlap in brain\/behavior patterns, but also specificity for each genetic mutation group. The largest differences were in the cerebellar atrophy (larger extent in <jats:italic>C9orf72<\/jats:italic> expansion group) and more prominent amygdalar volume reduction in the <jats:italic>MAPT<\/jats:italic> group. Brain scores in the <jats:italic>C9orf72<\/jats:italic> expansion carriers and <jats:italic>MAPT<\/jats:italic> carriers demonstrated covariation patterns concordant with atrophy patterns detectable up to 20\u2009years before expected symptom onset. Overall, these results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in <jats:italic>C9orf72<\/jats:italic> and the amygdala in <jats:italic>MAPT<\/jats:italic>\u00a0carriers.<\/jats:p>","DOI":"10.1002\/hbm.26220","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T05:34:59Z","timestamp":1678426499000},"page":"2684-2700","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"http:\/\/orcid.org\/0000-0001-6695-9941","authenticated-orcid":false,"given":"Aur\u00e9lie","family":"Bussy","sequence":"first","affiliation":[{"name":"Computational Brain Anatomy (CoBrA) Laboratory, Cerebral Imaging Centre Douglas Mental Health University Institute Montreal Quebec 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