IC‐O3–04: <i>In vivo</i> characterization of glutamatergic vulnerability in behavioral variant FTD: An [11C]ABP688 PET/ VBM /DBM study
Bibliographic record
Abstract
Behavioral variant frontotemporal dementia (bvFTD) is a progressive neurodegenerative syndrome characterized by atrophy in frontal, limbic, and temporal brain regions. Although glutamatergic projection neurons are highly affected in bvFTD, such abnormalities have yet to be systemically characterized, chiefly due the lack of suitable molecular probes. Using [11 C]ABP688-a novel Positron Emission Tomography (PET) radiopharmaceutical for in-vivo quantification of mGluR5-and voxel based/deformation based morphometry (VBM/DBM), we sought to determine the magnitude of receptor decrements and the overlap between the topography of such declines and atrophy within frontal, limbic, and temporal brain regions. We analyzed a sample of 5 bvFTD and 7 cognitively normal (CN) subjects who had [11 C]ABP688/MRI data collected in the course of a two-week period. Diagnosis of bvFTD was issued on the basis of the revised Neary criteria. PET binding potential maps (BPND) were calculated using the cerebellum as a reference region. PET images were subsequently registered to ICBM152 space non-linearly. For VBM, T1 MRIs were registered to ICBM152 space nonlinearly, and segmented into gray matter (GM), white matter (GM), and cerebrospinal fluid (CSF). GM maps were then blurred with a 10mm Gaussian kernel. For DBM, the magnitude of each vector of the Jacobian deformation field was computed. Voxel-based group differences were obtained by comparing bvFTD and CN using RMINC. No significant between group differences were found in terms of age, gender, and handedness though educational attainment/MMSE were found to be higher among controls (p < 0.05). Decrements in mGluR5 were widespread throughout cortical and subcortical areas, with maxima in the orbitofrontal cortex, superior frontal gyrus, anterior insula, and temporal lobe. Maxima for structural changes were confined to the basal ganglia, insula, left frontal operculum, anterior/posterior cingulate, precuneus, and temporal lobe. In addition to confirming the vulnerability of the glutamatergic system in bvFTD, we here provide the first results demonstrating declines of mGluR5 in bvFTD. The minimal topographical overlap between our findings, and the greater magnitude of declines in mGluR5 suggests that declines in mGluR5 are independent of brain atrophy or may precede structural changes in bvFTD. t-test comparing [11C]ABP688 BPND between bvFTD and CN. t-test comparing VBM between bvFTD and CN. t-test comparing DBM between bvFTD and CN.
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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 | 0.000 |
| 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) | 0.002 | 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".