Selective frontoinsular von Economo neuron and fork cell loss in early behavioral variant frontotemporal dementia
Open accessAbstract
Behavioral variant frontotemporal dementia (bvFTD) erodes complex social-emotional functions as the anterior cingulate cortex (ACC) and frontoinsula (FI) degenerate, but the early vulnerable neuron within these regions has remained uncertain. Previously, we demonstrated selective loss of ACC von Economo neurons (VENs) in bvFTD. Unlike ACC, FI contains a second conspicuous layer 5 neuronal morphotype, the fork cell, which has not been previously examined. Here, we investigated the selectivity, disease-specificity, laterality, timing, and symptom relevance of frontoinsular VEN and fork cell loss in bvFTD. Blinded, unbiased, systematic sampling was used to quantify bilateral FI VENs, fork cells, and neighboring neurons in 7 neurologically unaffected controls (NC), 5 patients with Alzheimer's disease (AD), and 9 patients with bvFTD, including 3 who died of comorbid motor neuron disease during very mild bvFTD. bvFTD showed selective FI VEN and fork cell loss compared with NC and AD, whereas in AD no significant VEN or fork cell loss was detected. Although VEN and fork cell losses in bvFTD were often asymmetric, no group-level hemispheric laterality effects were identified. Right-sided VEN and fork cell losses, however, correlated with each other and with anatomical, functional, and behavioral severity. This work identifies region-specific neuronal targets in early bvFTD.
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Alexithymia is associated with failure to engage the AIC and with degeneration of the AIC and of von Economo neurons in fronto-temporal dementia.
“For example, alexithymia (broadly, deficits in emotional awareness) is associated with failure to engage AIC [81] and with degeneration of AIC and of VENs (Box 2) in the context of fronto-temporal dementia [82,83].”
From Interoceptive inference, emotion, and the embodied self (2013) · cites this paper as [83]
The Introduction and Discussion report frontoinsular degeneration and selective von Economo neuron loss in behavioral-variant frontotemporal dementia, alongside social–emotional deficits. The section on bvFTD symptoms proposes a role for the right frontoinsula in awareness of feelings, but the paper does not specifically establish an association between alexithymia and that degeneration. The separate claim about failure to engage AIC is attributed to citation [81], not this source. (LLM, conf=0.83)
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- Authors
- Kim, E.-J., Sidhu, M., Gaus, S. E., Huang, E. J., Hof, P. R., Miller, B. L., DeArmond, S. J., & Seeley, W. W.
- Affiliations
- University of California, San Francisco (US)
- Icahn School of Medicine at Mount Sinai (US)
- Pusan National University Hospital (KR)
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-06-08
- Volume
- 22
- Issue
- 2
- Pages
- 251-259
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- PMC
- PMC3256403
- OpenAlex
- W2111738120
- Cited by
- 204
- References
- 59
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 14 · 2023: 7 · 2022: 16 · 2021: 11 · 2020: 15 · 2019: 22 · 2018: 12 · 2017: 9 · 2016: 18 · 2015: 11 · 2014: 18 · 2013: 13 · 2012: 12
- FWCI
- 10.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cerebral Cortex (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (P014600538, P50A916573)
- National Institute on Aging (R01AG033017, P50 AG1657303-75271, K08AG027086, P01-AG19724, P01AG019724)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- behavioral variant frontotemporal dementia, von Economo neurons, frontoinsular cortex, neuronal loss, anterior cingulate cortex, Alzheimer's disease, hemispheric lateralization, disease severity
- MeSH terms
- Aged, Cell Count, Cognition Disorders, Female, Gyrus Cinguli, Humans, Functional Laterality, Male, Mental Status Schedule, Middle Aged, Neurons, Statistics as Topic, Cell Death, Frontotemporal Dementia
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