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Cortical folding alterations in ALS remain largely unexplored despite growing interest in neuroimaging markers of the disease. This study is the first whole\u2010brain investigation of sulcal morphometry in ALS. A total of 222 individuals diagnosed with ALS and 194 healthy controls (HC) were recruited through the Canadian ALS Neuroimaging Consortium (CALSNIC) for a longitudinal investigation. Using T1\u2010weighted MRI processed with FreeSurfer and BrainVISA, we extracted cortical thickness and four sulcal features: width, mean depth, surface area, and length, across 123 sulci. We identified widespread alterations in ALS, with 19 sulci showing increased width and length alongside reduced depth and surface area, primarily in frontal and parietal regions surrounding the motor strip. The central sulcus (CS) emerged as the most consistently affected region, displaying bilateral widening and reduced depth, changes that closely tracked motor decline. Longitudinal analyses revealed progressive widening and reduced depth and surface area of the CS. These alterations closely tracked the progression of motor symptoms over the course of the disease and aligned with regional cortical thickness alterations. Our findings demonstrate that brain folding patterns, and in particular CS, are altered in ALS and correlate with clinical progression, resembling the neurodegenerative pattern of the disease. By revealing complementary and sensitive changes, sulcal\u2010based metrics may offer promising neuroimaging biomarkers for early detection, prognosis, and patient stratification in ALS.<\/jats:p>","DOI":"10.1002\/hbm.70449","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T21:38:53Z","timestamp":1773005933000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Brain Folding Trajectories in Amyotrophic Lateral Sclerosis"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6961-0374","authenticated-orcid":false,"given":"Mahan","family":"Shafie","sequence":"first","affiliation":[{"name":"Department of Neuroscience \u201cRita Levi Montalcini\u201d University of Turin  Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Tamba","sequence":"additional","affiliation":[{"name":"Department of Neuroscience \u201cRita Levi Montalcini\u201d University of Turin  Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harpreet","family":"Bhinder","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine University of Alberta  Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Canadian ALS Neuroimaging Consortium (CALSNIC)","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay","family":"Kalra","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine University of Alberta  Edmonton Alberta Canada"},{"name":"Neuroscience and Mental Health Institute University of Alberta  Edmonton Alberta 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