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Specifically, the pulvinar, a high\u2010order thalamic nucleus and timekeeper for large\u2010scale cortical networks, has been hypothesized to be involved in <jats:italic>C9orf72<\/jats:italic>\u2010related neurodegenerative diseases. We investigated whether pulvinar volume can be useful for differential diagnosis in ALS <jats:italic>C9orf72<\/jats:italic> mutation carriers and noncarriers and how underlying functional connectivity changes affect this region.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied 19 ALS <jats:italic>C9orf72<\/jats:italic> mutation carriers (<jats:italic>ALSC9+<\/jats:italic>) accurately matched with wild\u2010type ALS (<jats:italic>ALSC9<\/jats:italic>\u2212) and ALS mimic (<jats:italic>ALSmimic<\/jats:italic>) patients using structural and resting\u2010state functional magnetic resonance imaging data. Pulvinar volume was computed using automatic segmentation. Seed\u2010to\u2010voxel functional connectivity analyses were performed using seeds from a pulvinar functional parcellation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pulvinar structural integrity had high discriminative values for <jats:italic>ALSC9+<\/jats:italic> patients compared to <jats:italic>ALSmimic<\/jats:italic> (area under the curve [AUC]\u2009=\u20090.86) and <jats:italic>ALSC9<\/jats:italic>\u2212 (AUC\u2009=\u20090.77) patients, yielding a volume cutpoint of approximately 0.23%. Compared to <jats:italic>ALSmimic<\/jats:italic>, <jats:italic>ALSC9<\/jats:italic>\u2212 showed increased anterior, inferior, and lateral pulvinar connections with bilateral occipital\u2013temporal\u2013parietal regions, whereas <jats:italic>ALSC9+<\/jats:italic> showed no differences. <jats:italic>ALSC9+<\/jats:italic> patients when compared to <jats:italic>ALSC9<\/jats:italic>\u2212 patients showed reduced pulvinar\u2013occipital connectivity for anterior and inferior pulvinar seeds.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Pulvinar volume could be a differential biomarker closely related to the <jats:italic>C9orf72<\/jats:italic> mutation. A pulvinar\u2013cortical circuit dysfunction might play a critical role in disease progression and development, in both the genetic phenotype and ALS wild\u2010type patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.16266","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T11:35:19Z","timestamp":1710243319000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Distinct neural signatures of pulvinar in <i>C9orf72<\/i> amyotrophic lateral sclerosis mutation carriers and noncarriers"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1197-5458","authenticated-orcid":false,"given":"Anna","family":"Nigri","sequence":"first","affiliation":[{"name":"Neuroradiology Unit Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan 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