Thalamus involvement in genetic frontotemporal dementia assessed using structural and diffusion MRI: a GENFI study
Bibliographic record
Abstract
Abstract Thalamic subregions are commonly, but variably, affected by different forms of frontotemporal dementia. We aimed to better characterize thalamic subregional involvement in genetic frontotemporal dementia with a recently published thalamus segmentation tool that utilizes structural and diffusion MRI, offering additional assessment of mean diffusivity and a more fine-grained analysis of the pulvinar specifically compared to previous studies. Using this tool, we performed thalamus segmentations in MRI scans from C9orf72, GRN and MAPT mutation carriers and mutation non-carriers with suitable 3-Tesla MRI cross-sectional data from the GENetic Frontotemporal dementia Initiative. Mutation carriers were divided according to their genetic group and Clinical Dementia Rating® Dementia Staging Instrument plus National Alzheimer’s Coordinating Center Behaviour and Language Domains global score (0 or 0.5: presymptomatic/prodromal stage, 1 or higher: symptomatic stage). Following stringent quality control and harmonization across sites and scanners, we compared volumes and mean diffusivity values of thalamic subregions in C9orf72 (47 presymptomatic, 10 symptomatic), GRN (57 presymptomatic, 11 symptomatic) and MAPT (31 presymptomatic, 12 symptomatic) mutation carriers to those in 109 mutation non-carriers with analyses of covariance including age and sex (and total intracranial volume for volumetric comparisons) as covariates. Presymptomatic C9orf72 expansion carriers showed smaller volumes (3–8% difference from non-carriers) and higher mean diffusivity (2–5% difference from non-carriers) for several thalamic subregions, including all pulvinar subdivisions. We found subtly larger volumes of the ventral anterior subregion and the non-medial pulvinar (3% difference from non-carriers for both) in presymptomatic GRN mutation carriers, and of the anteroventral subregion (5% difference from non-carriers) in presymptomatic MAPT mutation carriers. Symptomatic mutation carriers in all three genetic groups showed significantly smaller volumes and widespread higher mean diffusivity of thalamic subregions compared with non-carriers, which were overall most prominent in subregions involved in associative and limbic functions (the midline, medial pulvinar, anteroventral, mediodorsal, laterodorsal and lateral posterior subregions). Notably smaller volume (12–23% difference from non-carriers) and higher mean diffusivity (16–23% difference from non-carriers) of the most medial part of the medial pulvinar was a shared feature across the three genetic groups at the symptomatic stage. Overall, our study confirms that thalamic subregions are affected in genetic frontotemporal dementia and identifies prominent involvement of the most medial part of the medial pulvinar as a potential unifying feature in the variable pattern of thalamic subregional involvement across the main genetic groups.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".