Fixel-Based White Matter Correlates of Sentence Comprehension in Post-Stroke Aphasia

Abstract

<p>Background/Objectives: Auditory sentence comprehension often remains impaired in individuals with post-stroke aphasia despite recovery in word-level comprehension. Neuroimaging studies have identified a left perisylvian network, especially temporal regions, as central to sentence comprehension, while the role of left frontal areas and specific white matter tracts remains debated. This study uses advanced fixel-based analysis (FBA) of diffusion MRI to precisely map white matter alterations related to complex sentence comprehension deficits in subacute Mandarin-speaking aphasic patients, addressing gaps from prior voxel-based and English-specific research. Methods: Twenty-three right-handed native Mandarin speakers with subacute (1–6 months post-onset) single left-hemisphere strokes underwent diffusion MRI. Standard preprocessing and FBA were conducted. Whole-brain linear regression assessed associations between fiber density and cross-section (FDC) and non-canonical sentence comprehension, controlling for age, education, time post-stroke, and verb comprehension. Mean FDC was calculated for each tract containing at least one significant fixel identified by FBA. Partial Spearman’s correlations examined relationships between mean FDC values within these tracts and comprehension accuracy for each sentence type, controlling for the same covariates. Results: Canonical sentences were comprehended significantly better than non-canonical sentences. FBA identified significant positive correlations between FDC and non-canonical sentence comprehension in the left superior longitudinal fasciculus (SLF II and SLF III), arcuate fasciculus (AF), middle longitudinal fasciculus, inferior fronto-occipital fasciculus, and the isthmus and splenium of the corpus callosum. Fiber density reduction primarily drove reductions in FDC, whereas reductions in fiber cross-section were limited to dorsal tracts (SLF III and AF). Conclusions: This study highlights a distributed left perisylvian white matter network critical for complex sentence comprehension in Mandarin speakers, refining neurocognitive models by identifying specific white matter substrates and demonstrating FBA’s utility in aphasia research.</p>