Evidence map›Paper›PMID 40585235›Full record

ArticleResearch square2025

Fixel-Based Analysis Reveals Detailed White Matter Changes in Semantic Dementia.

Maria Luisa Mandelli, Yann Cobigo, Ilaria Perretti, Dana Leichter, Celina Alba, Rian Bogley, Nick Wellman, Siddarth Ramkrishnan, Zachary A Miller, Bruce L Miller and 3 more

Abstract readPreprint
In one paragraph

Article in Research square, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Maria Luisa MandelliUniversity of California San Francisco.ORCID 0000-0002-2518-2520
Yann CobigoUniversity of California San Francisco.
Ilaria PerrettiUniversity of Pavia.
Dana LeichterUniversity of California San Francisco.
Celina AlbaUniversity of California San Francisco.
Rian BogleyUniversity of California San Francisco.
Nick WellmanUniversity of California San Francisco.
Siddarth RamkrishnanUniversity of California San Francisco.
Zachary A MillerUniversity of California San Francisco.
Bruce L MillerUniversity of California San Francisco.
William W SeeleyUniversity of California San Francisco.
Howard J RosenUniversity of California San Francisco.
Maria Luisa Gorno-TempiniUniversity of California San Francisco.

Funding

TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2M
Primary Progressive Aphasia: Cognition, Anatomy and ProgressionRF1NS050915 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GORNO TEMPINI, MARIA LUISA · 2022 to 2022
$4.7M
Training program in the neurology of language and neurodegenerative aphasiasK24DC015544 · NIDCD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GORNO TEMPINI, MARIA LUISA · 2016 to 2025
$1.9M
NIA NIH HHS P01 AG019724NIDCD NIH HHS K24 DC015544NINDS NIH HHS RF1 NS050915
6 · The paper itself

Abstract

Background and Purpose: Accurately characterizing white matter (WM) microstructure is critical for understanding neurodegenerative diseases such as semantic dementia (SD). Regionally constrained techniques like tract-based spatial statistics (TBSS) rely on diffusion-tensor imaging (DTI) and assume a single fiber population per voxel, limiting their sensitivity to complex architecture. Fixel-based morphometry (FBM) overcomes this by assessing multiple fiber populations (fixels) within a single voxel. In this study, we compared TBSS and Fixel-based analysis (FBA) for detecting WM alterations in SD variants associated with anterior temporal lobe (ATL) atrophy. Methods: Multi-shell diffusion MRI from 16 left-lateralized semantic-variant PPA (svPPA) and 15 right-lateralized semantic-behavioral fronto-temporal dementia (sbvFTD) cases, plus 44 neurologically healthy controls, underwent both TBSS-DTI and whole-brain FBA. Fiber-specific metrics of fiber density and cross-section were contrasted with conventional DTI measures. Results: Both methods confirmed damage to ATL-connected tracts-the uncinate fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and temporal projections of the arcuate fasciculus. FBA, however, revealed additional involvement of juxtacortical and other previously overlooked pathways, including the tapetum and anterior commissure, projections to the parahippocampal gyrus and amygdala, and longer-range parietal connections. Conclusions: By capturing fiber-specific micro- and macrostructural changes, FBA yields a more comprehensive map of WM degeneration in SD than TBSS. The ability to detect early alterations in commissural and mesial-temporal pathways refines our understanding of disease spread and highlights candidate targets for monitoring and intervention aimed at preserving cognitive function.

Indexed as

anterior commissureanterior temporal lobediffusion brain imagingfixel-based analysissemantic dementiatract-based spatial statisticswhite matter changes

Identifiers

PMID40585235
PMCPMC12204362

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.