P4‐180: Matrix Reasoning tasks in presymptomatic progranulin carriers
Bibliographic record
Abstract
Functional magnetic resonance imaging (fMRI) has shown differential brain response patterns in several neurodegenerative diseases at their preclinical stage. Progranulin (GRN) mutations have been found to be a cause of familial frontotemporal dementia (FTD). We hypothesized that matrix reasoning tasks could identify a different pattern of fMRI in preclinical GRN mutation carriers from non-carriers. An event-related fMRI study design using matrix reasoning task modeled after Raven's Progressive Matrices was performed in 6 preclinical members of FTD families with confirmed GRN mutations (2 carriers and 4 non-carriers). The task consisted of 0-relational, 1-relational, and 2-relational matrix reasoning, with increasing task complexity from 0- to 2-relational. Response accuracy and speed were compared for each condition with 2-sample t test. A 2X2 full factorial design (SPM8) (group: carrier vs. non-carrier, by task level: 0-relational, 1-relational, 2-relational) was used to compare activation in carriers and non-carriers, with post-hoc contrast p < 0.05 applied to compare intermediate complexity (0- vs. 1-relational) and high complexity (1- vs. 2-relational) within each group separately. Behaviorally, carriers performed less well than non-carriers across all conditions (accuracy: 0-relational 89.2 vs. 98.9% p = 0.005, 1-relational 72.9 vs. 97.9% p = 0.03, 2-relational 45.8 vs. 65.6%, p = 0.0005; speed: 0-relational 3.92s vs. 3.43s p = 0.56, 1-relational 5.09 vs. 4.15s p = 0.015, 2-relational 6.93 vs. 6.07s p = 0.00002). fMRI post-hoc contrast 0- vs. 1-relational showed significantly increased activation of posterior cingulate in carriers without a similar pattern in non-carriers. By contrast, fMRI post-hoc contrast 1- vs. 2-relational showed no change in carriers regardless of response accuracy, but significantly increased activation in anterior cerebellar areas was found in non-carriers. GRN mutation carriers respond to increasing complexity in matrix reasoning differently than non-carriers in their clinical performance as well as in their fMRI brain activation pattern. Carriers appear to significantly recruit posterior brain regions and have declining performance at intermediate complexity, but no change at high complexity. This may suggest a posteriorly located compensatory mechanism in carriers that is functional up to a certain level only, but breaks down with further increases in matrix complexity.
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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 | 0.000 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 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".