Abstract
BACKGROUND AND OBJECTIVES: Epilepsy is increasingly conceptualized as a network disorder, and advancing methods for its diagnosis and treatment requires characterizing both the epileptic generator and related networks. Previous research has highlighted alterations in cortical structure and hemodynamics in epilepsy, but it remains unknown whether these alterations concentrate in areas generating epileptic activity. The aim of this study was to interrogate alterations in microstructure, morphology, and intrinsic local function within and beyond spiking tissue in focal epilepsy, combining multimodal MRI and high-density EEG (HD-EEG). METHODS: In this cross-sectional study, we recruited patients with focal epilepsy from the Montreal Neurological Institute's epilepsy monitoring unit. Age-matched and sex-matched control participants were recruited from the community. The 3T MRI acquisitions included T1-weighted, diffusion, quantitative T1 relaxometry, and resting-state functional MRI. Open-access processing tools derived cortex-wide maps of morphology and microstructure (cortical thickness, mean diffusivity, and quantitative T1 relaxometry) and intrinsic local function (timescales, connectivity distance, and node strength). Multivariate approaches generated structural and functional alteration scores for each cortical location. Using HD-EEG electrical source imaging, the most prominent spike type was localized and we quantified MRI alterations within spike sources, as well as in proximal and connected networks. RESULTS: We included 25 patients with focal epilepsy (48% female, mean ± SD age = 31.28 ± 9.30 years) and 55 control participants: 30 for imaging feature normalization (50% female, 31.40 ± 8.74 years) and 25 for computing normative connectivity (48% female, 31.04 ± 5.65 years). Regions harboring spike sources showed increased structural MRI alterations compared with the rest of the brain (mean ± SE: 27.98% ± 6.37% vs 17.67% ± 3.32%; t = 2.28; p = 0.036; d = 0.446). Structural compromise extended to all regions with close functional coupling to spike sources, but not to anatomical neighbors. DISCUSSION: In a modest sample, spiking regions contained more marked alterations in microstructure and morphology than the remaining cortex. There were nevertheless broader network effects, which may relate to a cascading of structural changes to connected cortices. These results underscore the utility of combining quantitative MRI and EEG for characterizing epileptogenic tissue and assessing network effects.