Abstracts

Rationale: Temporal lobe epilepsy (TLE) is the most frequent drug-resistant focal epilepsy, and is associated with widespread structural and functional changes extending from a temporo-limbic epicenter. Prior work in healthy individuals has shown that the microstructural organization of the cortex follows a sensory-fugal gradient, differentiating sensory/motor regions with clear lamination patterns from agranular/dysgranular paralimbic cortices. Here, we studied whether and how these gradients are altered in TLE.

Methods: A cohort of 20 drug-resistant TLE patients (9 women; mean±S.D. 35.45±11.66 years) and 30 healthy controls (HCs; 12 women; 33.50±7.87 years) underwent high-resolution quantitative T1 relaxometry at 3T. In each subject, we sampled intracortical quantitative T1 (qT1) intensities along 14 equivolumetric surfaces between pial and white matter boundaries, yielding cortex-wide microstructural intensity profiles (Fig1A). Profiles were cross-correlated while controlling for the cortex-wide average, resulting in microstructural similarity matrices. We then derived the principal eigenvector of microstructural similarity with diffusion map embedding (Fig1B). We examined differences of resulting microstructural gradient scores using surface-based models controlling for effects of sex and age. Findings were corrected for multiple comparisons using random field theory.

Results: Both TLEs and HCs showed a robust sensory-fugal gradient of cortical microstructure. Comparing groups, differentiation between sensory/motor and paralimbic anchors was reduced in TLE (Fig1C; all pFWE < 0.025). Gradient reductions in TLE primarily targeted bilateral temporal regions, with peak effects in ipsilateral anterior and mesial temporal cortices. Increases in gradient scores were observed in sensory/motor regions, with strongest effects in the ipsilateral cuneus. Repeating between-group comparison after correction of gradient scores for corresponding cortical thickness revealed similar findings. To explore underlying microstructural changes supporting sensory-fugal gradient reorganizations, statistical moments of qT1 intensity were computed across depths at each vertex (Fig2A). These metrics captured the shape of intracortical microstructural profiles, granting insights into laminar perturbations shifting the principal microstructural gradient. Multivariate changes in microstructural profile shape closely co-localized with gradient reorganizations (Fig2B). Indeed, effect sizes were considerably reduced when repeating analyses while controlling for multivariate profile shape alterations.