{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:44:55Z","timestamp":1789706695742,"version":"4.0.1"},"reference-count":54,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft","award":["DFG CA 893\/22-1"],"award-info":[{"award-number":["DFG CA 893\/22-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: Olfactory dysfunction (OD)\u2014including anosmia and hyposmia\u2014is a common and often persistent outcome of viral infections. This systematic review consolidates findings from structural and functional MRI studies to explore how COVID-19 SARS-CoV-2-induced smell loss alters the brain. Considerable heterogeneity was observed across studies, influenced by differences in methodology, population characteristics, imaging timelines, and OD classification. Methods: Following PRISMA guidelines, we conducted a systematic search of PubMed\/MEDLINE, Scopus, and Web of Science to identify MRI-based studies examining COVID-19\u2019s SARS-CoV-2 OD. Twenty-four studies were included and categorized based on imaging focus: (1) olfactory bulb (OB), (2) olfactory sulcus (OS), (3) grey and white matter changes, (4) task-based brain activation, and (5) resting-state functional connectivity. Demographic and imaging data were extracted and analyzed accordingly. Results: Structural imaging revealed consistent reductions in olfactory bulb volume (OBV) and olfactory sulcus depth (OSD), especially among individuals with OD persisting beyond three months, suggestive of inflammation and neurodegeneration in olfactory-associated regions like the orbitofrontal cortex and thalamus. Functional MRI studies showed increased connectivity in early-stage OD within regions such as the piriform and orbitofrontal cortices, possibly reflecting compensatory activity. In contrast, prolonged OD was associated with reduced activation and diminished connectivity, indicating a decline in olfactory processing capacity. Disruptions in the default mode network (DMN) and limbic areas further point to secondary cognitive and emotional effects. Diffusion tensor imaging (DTI) findings\u2014such as decreased fractional anisotropy (FA) and increased mean diffusivity (MD)\u2014highlight white matter microstructural compromise in individuals with long-term OD. Conclusions: COVID-19\u2019s SARS-CoV-2 olfactory dysfunction is associated with a range of cerebral alterations that evolve with the duration and severity of smell loss. Persistent dysfunction correlates with greater neural damage, underscoring the need for longitudinal neuroimaging studies to better understand recovery dynamics and guide therapeutic strategies.<\/jats:p>","DOI":"10.3390\/brainsci15070690","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T07:42:06Z","timestamp":1751355726000},"page":"690","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Mapping the Olfactory Brain: A Systematic Review of Structural and Functional Magnetic Resonance Imaging Changes Following COVID-19 Smell Loss"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6769-0603","authenticated-orcid":false,"given":"Hanani","family":"Abdul Manan","sequence":"first","affiliation":[{"name":"Smell and Taste Clinic, Department of Otorhinolaryngology, Technische Universit\u00e4t Dresden, Fetscherstrasse 74, 01307 Dresden, Germany"},{"name":"Makmal Pemprosesan Imej Kefungsian (Functional Image Processing Laboratory), Department of Radiology, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Kuala Lumpur 56000, Malaysia"},{"name":"Department of Radiology and Intervention, Hospital Pakar Kanak-Kanak (Children Specialist Hospital), Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaela","family":"de Jesus","sequence":"additional","affiliation":[{"name":"Smell and Taste Clinic, Department of Otorhinolaryngology, Technische Universit\u00e4t Dresden, Fetscherstrasse 74, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6434-3342","authenticated-orcid":false,"given":"Divesh","family":"Thaploo","sequence":"additional","affiliation":[{"name":"Smell and Taste Clinic, Department of Otorhinolaryngology, Technische Universit\u00e4t Dresden, Fetscherstrasse 74, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Hummel","sequence":"additional","affiliation":[{"name":"Smell and Taste Clinic, Department of Otorhinolaryngology, Technische Universit\u00e4t Dresden, Fetscherstrasse 74, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1007\/s00441-020-03367-7","article-title":"The importance of the olfactory system in human well-being, through nutrition and social behavior","volume":"383","author":"Boesveldt","year":"2021","journal-title":"Cell Tissue Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"eadn3028","DOI":"10.1126\/sciadv.adn3028","article-title":"Nature and human well-being: The olfactory pathway","volume":"10","author":"Bratman","year":"2024","journal-title":"Sci. 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