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Executive dysfunction relates to salience network desegregation in behavioural variant frontotemporal dementia
Melanie A. Matyi, Hamsanandini Radhakrishnan, Christopher A. Olm, Jeffrey S. Phillips, Philip A. Cook, Emma Rhodes, James C. Gee, David John Irwin et al.. NeuroImage Clinical, 2025-01-01
Topic: Brain proteins, microglia and lab models
• Executive dysfunction is a key characteristic of bvFTD. • Network de-differentiation reflects loss of specialized networks. • De-differentiation of the salience network relates to executive dysfunction in bvFTD. • Reduced network capacity for specialized processing may mediate emergence of executive dysfunction. The organization of the brain into distinct networks increases (i.e., differentiation) during development and decreases (i.e., de-differentiation) during healthy aging, changes that are associated with improvements and worsening of cognition, respectively. Given that behavioral variant frontotemporal degeneration (bvFTD) is a neurodegenerative disease associated with executive dysfunction and selective vulnerability of the salience network, we tested the hypotheses that bvFTD structural networks are de-differentiated compared to cognitively normal controls (CNC) and that network de-differentiation relates to worse executive function. In a sample of 90 patients with bvFTD and 71 age-matched CNC with diffusion MRI data we generated probabilistic tractography maps and calculated system segregation, a metric that compares within-network to between-network connectivity, to reflect the extent to which brain networks were differentiated. Patients with bvFTD also completed tests of executive function (digit span backwards, phonemic fluency, category fluency) and a control task (lexical retrieval). We assessed group differences in system segregation, reflecting network differentiation, and, within bvFTD, associations between system segregation and neuropsychological test performance. Compared to CNC, patients with bvFTD exhibited lower system segregation of the salience ( p < 0.001) and global brain network ( p = 0.008). In bvFTD, lower salience network system segregation was associated with worse executive function ( p corrected = 0.021) but not lexical retrieval. Results demonstrate associations between executive dysfunction and salience network de-differentiation in patients with bvFTD. Our findings indicate that brain network de-differentiation, reflecting reduced neural capacity for specialized processing, may contribute to the emergence of executive dysfunction in bvFTD.
Key findings
- The organization of the brain into distinct networks increases (i.e., differentiation) during development and decreases (i.e., de-differentiation) during healthy aging, changes that are associated with improvements and worsening of cognition, respectively.
- Given that behavioral variant frontotemporal degeneration (bvFTD) is a neurodegenerative disease associated with executive dysfunction and selective vulnerability of the salience network, we tested the hypotheses that bvFTD structural networks are de-differentiated compared to cognitively normal controls (CNC) and that network de-differentiation relates to worse executive function.
- Compared to CNC, patients with bvFTD exhibited lower system segregation of the salience ( p < 0.001) and global brain network ( p = 0.008).
- In bvFTD, lower salience network system segregation was associated with worse executive function ( p corrected = 0.021) but not lexical retrieval.
- Results demonstrate associations between executive dysfunction and salience network de-differentiation in patients with bvFTD.
Why it matters
In 90 patients with behavioral variant frontotemporal dementia and 71 controls, de-differentiation of the salience network related to worse executive function. This concerns understanding of brain network changes, not treatment, cure or prevention.
Study details
- Participants90
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (NeuroImage Clinical) |
| Journal's citation record | 1 / 4 | NeuroImage Clinical: journal h-index 133 (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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 1 / 4 | 90 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 3 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Lauren M. Massimo: h-index 27 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Pennsylvania: institution h-index 1,859 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40716388) |
| Free to read | 2 / 2 | Free to read |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.nicl.2025.103853
- PubMed: 40716388
- Original source →
- Free full text: NeuroImage Clinical →
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
Matyi, M. A., Radhakrishnan, H., Olm, C. A., Phillips, J. S., Cook, P. A., Rhodes, E., et al. (2025). Executive dysfunction relates to salience network desegregation in behavioural variant frontotemporal dementia. NeuroImage Clinical. https://doi.org/10.1016/j.nicl.2025.103853
Vancouver
Matyi MA, Radhakrishnan H, Olm CA, Phillips JS, Cook PA, Rhodes E, et al. Executive dysfunction relates to salience network desegregation in behavioural variant frontotemporal dementia. NeuroImage Clinical. 2025. doi:10.1016/j.nicl.2025.103853. PMID: 40716388.
BibTeX
@article{matyi2025-40716388,
author = {Matyi, Melanie A. and Radhakrishnan, Hamsanandini and Olm, Christopher A. and Phillips, Jeffrey S. and Cook, Philip A. and Rhodes, Emma and Gee, James C. and Irwin, David John and others},
title = {{Executive dysfunction relates to salience network desegregation in behavioural variant frontotemporal dementia}},
journal = {NeuroImage Clinical},
year = {2025},
doi = {10.1016/j.nicl.2025.103853},
pmid = {40716388},
url = {https://doi.org/10.1016/j.nicl.2025.103853}
}
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