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Abnormal network connectivity in frontotemporal dementia: evidence for prefrontal isolation
Farb NA, Grady CL, Strother S, Tang-Wai DF, Masellis M, Black S, Freedman M, Pollock BG et al.. Cortex; a journal devoted to the study of the nervous system and behavior, 2012-09-24
Topic: Brain imaging, connectivity and assessment
Introduction Degraded social function, disinhibition, and stereotypy are defining characteristics of frontotemporal dementia (FTD), manifesting in both the behavioral variant of frontotemporal dementia (bvFTD) and semantic dementia (SD) subtypes. Recent neuroimaging research also associates FTD with alterations in the brain's intrinsic connectivity networks. The present study explored the relationship between neural network connectivity and specific behavioral symptoms in FTD. Methods Resting-state functional magnetic resonance imaging was employed to investigate neural network changes in bvFTD and SD. We used independent components analysis (ICA) to examine changes in frontolimbic network connectivity, as well as several metrics of local network strength, such as the fractional amplitude of low-frequency fluctuations, regional homogeneity, and seed-based functional connectivity. For each analysis, we compared each FTD subgroup to healthy controls, characterizing general and subtype-unique network changes. The relationship between abnormal connectivity in FTD and behavior disturbances was explored. Results Across multiple analytic approaches, both bvFTD and SD were associated with disrupted frontolimbic connectivity and elevated local connectivity within the prefrontal cortex. Even after controlling for structural atrophy, prefrontal hyperconnectivity was robustly associated with apathy scores. Frontolimbic disconnection was associated with lower disinhibition scores, suggesting that abnormal frontolimbic connectivity contributes to positive symptoms in dementia. Unique to bvFTD, stereotypy was associated with elevated default network connectivity in the right angular gyrus. The behavioral variant was also associated with marginally higher apathy scores and a more diffuse pattern of prefrontal hyperconnectivity than SD. Conclusions The present findings support a theory of FTD as a disorder of frontolimbic disconnection leading to unconstrained prefrontal connectivity. Prefrontal hyperconnectivity may represent a compensatory response to the absence of affective feedback during the planning and execution of behavior. Increased reliance upon prefrontal processes in isolation from subcortical structures appears to be maladaptive and may drive behavioral withdrawal that is commonly observed in later phases of neurodegeneration.
Key findings
- Results Across multiple analytic approaches, both bvFTD and SD were associated with disrupted frontolimbic connectivity and elevated local connectivity within the prefrontal cortex.
- Even after controlling for structural atrophy, prefrontal hyperconnectivity was robustly associated with apathy scores.
- Frontolimbic disconnection was associated with lower disinhibition scores, suggesting that abnormal frontolimbic connectivity contributes to positive symptoms in dementia.
- Unique to bvFTD, stereotypy was associated with elevated default network connectivity in the right angular gyrus.
- The behavioral variant was also associated with marginally higher apathy scores and a more diffuse pattern of prefrontal hyperconnectivity than SD.
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Study details
- Evidence strengthLow
How this study scored 36/100
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. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 21 of the 58 points we could judge it on, which is 36 out of 100.
| 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 | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 2013 — 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 23092697) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 21 of the 58 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
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APA 7th
Farb, N. A., Grady, C. L., Strother, S., Tang-Wai, D. F., Masellis, M., Black, S., et al. (2013). Abnormal network connectivity in frontotemporal dementia: evidence for prefrontal isolation. Cortex; a journal devoted to the study of the nervous system and behavior. https://doi.org/10.1016/j.cortex.2012.09.008
Vancouver
Farb NA, Grady CL, Strother S, Tang-Wai DF, Masellis M, Black S, et al. Abnormal network connectivity in frontotemporal dementia: evidence for prefrontal isolation. Cortex; a journal devoted to the study of the nervous system and behavior. 2013. doi:10.1016/j.cortex.2012.09.008. PMID: 23092697.
BibTeX
@article{farb2013-23092697,
author = {Farb, N. A. and Grady, C. L. and Strother, S. and Tang-Wai, D. F. and Masellis, M. and Black, S. and Freedman, M. and Pollock, B. G. and others},
title = {{Abnormal network connectivity in frontotemporal dementia: evidence for prefrontal isolation}},
journal = {Cortex; a journal devoted to the study of the nervous system and behavior},
year = {2013},
doi = {10.1016/j.cortex.2012.09.008},
pmid = {23092697},
url = {https://doi.org/10.1016/j.cortex.2012.09.008}
}