Right uncinate fasciculus supports socioemotional sensitivity in health and neurodegenerative disease
Open accessAbstract
The uncinate fasciculus (UF) connects fronto-insular and temporal gray matter regions involved in visceral emotional reactivity and semantic appraisal, but the precise role of this tract in socioemotional functioning is not well-understood. Using the Revised-Self Monitoring (RSMS) informant questionnaire, we examined whether fractional anisotropy (FA) in the right UF corresponded to socioemotional sensitivity during face-to-face interactions in 145 individuals (40 healthy older adults [NC], and 105 patients with frontotemporal lobar degeneration [FTLD] syndromes in whom this tract is selectively vulnerable, including 31 behavioral variant frontotemporal dementia [bvFTD], 39 semantic variant primary progressive aphasia [svPPA], and 35 nonfluent variant primary progressive aphasia [nfvPPA]). Voxelwise and region-of-interest-based DWI analyses revealed that FA in the right but not left UF significantly predicted RSMS score in the full sample, and in NC and svPPA subgroups alone. Right UF integrity did not predict RSMS score in the bvFTD group, but gray matter volume in the right orbitofrontal cortex adjacent to the UF was a significant predictor. Our results suggest that better socioemotional sensitivity is specifically supported by right UF white matter, highlighting a key neuro-affective relationship found in both healthy aging and neurologically affected individuals. The finding that poorer socioemotional sensitivity corresponded to right UF damage in svPPA but was more robustly influenced by gray matter atrophy adjacent to the UF in bvFTD may have important implications for endpoint selection in clinical trial design for patients with FTLD.
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In a cross-sectional study, grey matter volumes of the right orbitofrontal cortex, not white matter tract pathology (DWI), predicted socioemotional impairment.
“GM volumes of the right orbitofrontal cortex, not WM tract pathology (DWI), predicted socioemotional impairment (Toller et al., 2022)”
From The pursuit for markers of disease progression in behavioral variant frontotemporal dementia: a scoping review to optimize outcome measures for clinical trials (2024) · cites this paper as Toller et al., 2022
Correlations between RSMS and social network abnormalities were not supportive, suggesting the true brain-behavior relationship requires further investigation.
“Yet, correlations between RSMS and social network abnormalities were not supportive, suggesting the true brain-behavior relationship requires further investigation (Toller et al., 2022).”
From The pursuit for markers of disease progression in behavioral variant frontotemporal dementia: a scoping review to optimize outcome measures for clinical trials (2024) · cites this paper as Toller et al., 2022
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Fieldhouse, J. L. P., van Paassen, D. N., van Engelen, M.-P. E., De Boer, S. C. M., Hartog, W. L., Braak, S., Schoonmade, L. J., Schouws, S. N. T. M., Krudop, W. A., Oudega, M. L., et al. (2024) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2024.1382593 · Cited by 8 · see citing works
- Authors
- Toller, G., Mandelli, M. L., Cobigo, Y., Rosen, H. J., Kramer, J. H., Miller, B. L., Gorno-Tempini, M. L., & Rankin, K. P.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Toller, Gianina
- ORCID
- Venue
- NeuroImage: Clinical
- Publisher
- Elsevier BV
- Published
- 2022
- Volume
- 34
- Pages
- 102994
- ISSN
- 2213-1582 (ISSN-L)
- PMC
- PMC9125782
- OpenAlex
- W4220669537
- Cited by
- 23
- References
- 78
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 7 · 2023: 1 · 2022: 2
- FWCI
- 2.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- NeuroImage Clinical (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- National Institutes of Health (2002/2J, 2014-A-004-NET)
- Larry L. Hillblom Foundation (P2ZHP1_165073)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- uncinate fasciculus, frontotemporal lobar degeneration, behavioral variant frontotemporal dementia, semantic dementia, white matter integrity, fractional anisotropy, orbitofrontal cortex, gray matter atrophy, healthy aging, face-to-face social interaction, clinical trial endpoints
- MeSH terms
- Uncinate Fasciculus, Aged, Humans, Neurodegenerative Diseases, Frontotemporal Lobar Degeneration, Primary Progressive Nonfluent Aphasia, Frontotemporal Dementia, White Matter
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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