In vivo hippocampal cornu ammonis 1–3 glutamatergic abnormalities are associated with temporal lobe epilepsy surgery outcomes
Bibliographic record
Abstract
Abstract Objective Previous positron emission tomography (PET) studies using [11C]ABP688 show reduced metabotropic glutamate receptor type 5 (mGluR5) allosteric binding site availability in the epileptogenic hippocampus of mesial temporal lobe epilepsy (MTLE) patients. However, the link between mGluR5 abnormalities and postsurgical outcomes remains unclear. Here, we test whether reduced PET [11C]ABP688 binding in cornu ammonis (CA) sectors more vulnerable to glutamatergic excitotoxicity relates to surgical outcomes. Methods We obtained magnetic resonance imaging (MRI) and [11C]ABP688‐PET from 31 unilateral MTLE patients and 30 healthy controls. MRI hippocampal subfields were segmented using FreeSurfer. To respect the lower PET special resolution, MRI‐derived anatomical subfields were combined into CA1–3, CA4/dentate gyrus, and Subiculum. Partial volume corrected [11C]ABP688 nondisplaceable binding potential (BPND) values were averaged across each subfield, and Z‐scores were calculated. Subfield [11C]ABP688‐BPND was compared between seizure‐free and non‐seizure‐free patients. In addition, we also assessed subfield volumes and [18F]fluorodeoxyglucose (FDG) uptake in each clinical group. Results MTLE [11C]ABP688‐BPND was reduced in ipsilateral (epileptogenic) CA1–3 and CA4/dentate‐gyrus (p < .001, 95% confidence interval [CI] = .29–.51) compared to controls, with no difference in Subiculum. [11C]ABP688‐BPND and subfield volumes were compared between seizure‐free (Engel IA, n = 13) and non‐seizure‐free patients (Engel IC–III, n = 10). In ipsilateral CA1–3 only, [11C]ABP688‐BPND was lower in seizure‐free patients than in non‐seizure‐free patients (p = .012, 95% CI = 1.46–11.0) independently of volume. A subset analysis of 12 patients with [11C]ABP688‐PET+[18F]FDG‐PET showed no between‐group significant difference in [18F]FDG uptake, whereas CA1–3 [11C]ABP688‐BPND remained significantly lower in the seven of 12 seizure‐free patients (p = .03, 95% CI = −3.13 to −.21). Significance Reduced mGluR5 allosteric site availability in hippocampal CA1–3, measured in vivo by [11C]ABP688‐PET, is associated with postsurgery seizure freedom independent of atrophy or hypometabolism. Information derived from hippocampal CA1–3 [11C]ABP688‐PET is a promising imaging biomarker potentially impactful in surgical decisions for MRI‐negative/PET‐negative MTLE patients.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 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 | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".