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Two insular regions are differentially involved in behavioral variant FTD and nonfluent/agrammatic variant PPA
Mandelli ML, Vitali P, Santos M, Henry M, Gola K, Rosenberg L, Dronkers N, Miller B et al.. Cortex; a journal devoted to the study of the nervous system and behavior, 2015-11-14
Topic: Brain proteins, microglia and lab models
The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) and the behavioral variant frontotemporal dementia (bvFTD) are focal neurodegenerative disorders belonging to the FTD-spectrum clinical syndromes. NfvPPA is characterized by effortful speech and/or agrammatism and left frontal atrophy, while bvFTD is characterized by social-emotional dysfunction often accompanied by right-lateralized frontal damage. Despite their contrasting clinical presentations, both disorders show prominent left anterior insula atrophy. We investigated differential patterns of insular sub-region atrophy in nfvPPA and bvFTD. Based on knowledge of insular connectivity and physiology, we hypothesized that the left superior precentral region of the dorsal anterior insula (SPGI) would be more atrophic in nvfPPA due to its critical role in motor speech, whereas the ventral anterior region would be more atrophied in bvFTD reflecting its known role in social-emotional-autonomic functions. Early stage nfvPPA and bvFTD patients matched for disease severity, age, gender and education and healthy controls participated in the study. Detailed clinical history, neurological examination, neuropsychological screening evaluation, and high-resolution T1-weighted brain magnetic resonance imaging (MRI) were collected. Voxel-based morphometry (VBM) was applied to perform group comparisons across the whole brain and in bilateral insula region of interest (ROI). Correlation analyses between insular sub-region atrophy and relevant clinical features were performed. Whole brain group comparisons between nfvPPA and bvFTD showed the expected predominantly left or right anterior insular atrophy pattern. ROI analysis of bilateral insula showed that the left SPGI was significantly more atrophied in nfvPPA compared to bvFTD, while the bilateral ventral anterior and right dorsal anterior insula sub-regions were more atrophied in bvFTD than nfvPPA. Only left SPGI volume correlated with speech production abilities, while left and right ventral anterior insula volumes correlated with ratings of aberrant eating behavior. These two FTD clinical variants show different patterns of insular sub-region atrophy in the left precentral dorsal anterior and bilateral ventral anterior regions, providing further evidence for the role of these sub-regions in speech production and social-emotional function.
Key findings
- ROI analysis of bilateral insula showed that the left SPGI was significantly more atrophied in nfvPPA compared to bvFTD, while the bilateral ventral anterior and right dorsal anterior insula sub-regions were more atrophied in bvFTD than nfvPPA.
Why it matters
This study found that different sub-regions of the insula are more atrophied in two types of frontotemporal dementia: the left superior precentral region in nonfluent/agrammatic primary progressive aphasia and the ventral anterior and right dorsal anterior regions in behavioral variant frontotemporal dementia. It is about distinguishing these two disorders, not about treating, curing or preventing Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cortex; a journal devoted to the study of the nervous system and behavior) |
| Journal's citation record | 2 / 4 | Cortex: journal h-index 202 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 70 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.8 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 3 / 6 | Cited 3.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 2 / 4 | Cited 17 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Maria Luisa Gorno‐Tempini: h-index 92 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, San Francisco: institution h-index 1,915 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26673947) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 43 / 100 | — |
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Read the original
- DOI: 10.1016/j.cortex.2015.10.012
- PubMed: 26673947
- Original source →
- Free full text: PubMed Central →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Mandelli, M. L., Vitali, P., Santos, M., Henry, M., Gola, K., Rosenberg, L., et al. (2016). Two insular regions are differentially involved in behavioral variant FTD and nonfluent/agrammatic variant PPA. Cortex; a journal devoted to the study of the nervous system and behavior. https://doi.org/10.1016/j.cortex.2015.10.012
Vancouver
Mandelli ML, Vitali P, Santos M, Henry M, Gola K, Rosenberg L, et al. Two insular regions are differentially involved in behavioral variant FTD and nonfluent/agrammatic variant PPA. Cortex; a journal devoted to the study of the nervous system and behavior. 2016. doi:10.1016/j.cortex.2015.10.012. PMID: 26673947.
BibTeX
@article{mandelli2016-26673947,
author = {Mandelli, M. L. and Vitali, P. and Santos, M. and Henry, M. and Gola, K. and Rosenberg, L. and Dronkers, N. and Miller, B. and others},
title = {{Two insular regions are differentially involved in behavioral variant FTD and nonfluent/agrammatic variant PPA}},
journal = {Cortex; a journal devoted to the study of the nervous system and behavior},
year = {2016},
doi = {10.1016/j.cortex.2015.10.012},
pmid = {26673947},
url = {https://doi.org/10.1016/j.cortex.2015.10.012}
}
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