{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:35:34Z","timestamp":1760060134324,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Congenital anosmia (CA) is a rare condition characterized by a lifelong inability to perceive odors, which significantly affects daily life and may be linked to broader neurodevelopmental alterations. This study aimed to investigate structural brain differences in patients with CA using MRI, focusing on gray matter (GM) and white matter (WM) changes and their implications for neurodevelopment. Methods: This retrospective study included 28 patients with CA and 28 age- and gender-matched healthy controls. Patients with CA were diagnosed at a single medical center between 1 January 2001 and 30 August 2024. Controls were randomly selected from an imaging database and had no history of olfactory dysfunction. Brain Magnetic Resonance Imaging (MRI)was analyzed using volumetric analysis in SPM12.GM and WM volumes were quantified across 11 anatomical brain regions based on theWFU_PickAtlas toolbox, including frontal, temporal, parietal, occipital, limbic, sub-lobar, cerebellum (anterior\/posterior), midbrain, the pons, and the frontal\u2013temporal junction. Left\u2013right hemispheric comparisons were also conducted. Results: Patients with CA exhibited significantly smaller GM volumes compared to healthy controls (560.6 \u00b1 114.7 cc vs. 693.7 \u00b1 96.3 cc, p &lt; 0.001) but larger WM volumes (554.2 \u00b1 75.4 cc vs. 491.1 \u00b1 79.7 cc, p = 0.015). Regionally, GM reductions were observed in the frontal (131.9 \u00b1 33.7 cc vs. 173.7 \u00b1 27.0 cc, p &lt; 0.001), temporal (81.1 \u00b1 18.4 cc vs. 96.5 \u00b1 14.1 cc, p = 0.001), parietal (52.4 \u00b1 15.2 cc vs. 77.2 \u00b1 12.4 cc, p &lt; 0.001), sub-lobar (57.8 \u00b1 9.7 cc vs. 68.2 \u00b1 10.2 cc, p = 0.001), occipital (39.1 \u00b1 13.0 cc vs. 57.8 \u00b1 8.9 cc, p &lt; 0.001), and midbrain (2.0 \u00b1 0.5 cc vs. 2.3 \u00b1 0.4 cc, p = 0.006) regions. Meanwhile, WM increases were notable in the frontal(152.0 \u00b1 19.9 cc vs. 139.2 \u00b1 24.0 cc, p = 0.027), temporal (71.5 \u00b1 11.5 cc vs. 60.8 \u00b1 9.5 cc, p = 0.001), parietal (75.8 \u00b1 12.4 cc vs. 61.9 \u00b1 11.5 cc, p &lt; 0.001), and occipital (58.7 \u00b1 10.3 cc vs. 41.9 \u00b1 7.9 cc, p &lt; 0.001) lobes. A separate analysis of the left and right hemispheres revealed similar patterns of reduced GM and increased WM volumes in patients with CA across both sides. An exception was noted in the right cerebellum-posterior, where patients with CA showed significantly greater WM volume (5.625 \u00b1 1.667 cc vs. 4.666 \u00b1 1.583 cc, p = 0.026). Conclusions: This study demonstrates widespread structural brain differences in individuals with CA, including reduced GM and increased WM volumes across multiple cortical and sub-lobar regions. These findings suggest that congenital olfactory deprivation may impact brain maturation beyond primary olfactory pathways, potentially reflecting altered synaptic pruning and increased myelination during early neurodevelopment. The involvement of the cerebellum further implies potential adaptations beyond motor functions. These structural differences may serve as potential neuroimaging markers for monitoring CA-associated cognitive or emotional comorbidities.<\/jats:p>","DOI":"10.3390\/diagnostics15151927","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T08:51:41Z","timestamp":1754038301000},"page":"1927","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structural Brain Changes in Patients with Congenital Anosmia: MRI-Based Analysis of Gray- and White-Matter Volumes"],"prefix":"10.3390","volume":"15","author":[{"given":"Shun-Hung","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, Taichung Veterans General Hospital, Taichung 407219, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsian-Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Quantitative Imaging in Medicine (CQUIM), Department of Medical Research, Taichung Veterans General Hospital, Taichung 407219, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8280-6029","authenticated-orcid":false,"given":"Rong-San","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Tungs\u2019 Taichung MetroHarbor Hospital, Taichung 435403, Taiwan"},{"name":"Department of Medical Research, Taichung Veterans General Hospital, Taichung 407219, Taiwan"},{"name":"School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/ajmg.a.30025","article-title":"Isolated congenital anosmia with morphologically normal olfactory bulb in two Iranian families: A new clinical entity?","volume":"127a","author":"Ghadami","year":"2004","journal-title":"Am. 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