Structural compromise in spiking cortex and connected networks

Abstract

INTRODUCTIONEpilepsy is increasingly conceptualized as a network disorder, and advancing methods for its diagnosis and treatment requires characterizing both the epileptic generator and related networks. We combined multimodal magnetic resonance imaging (MRI) and high-density electroencephalography (HD-EEG) to interrogate alterations in cortical microstructure, morphology, and local function within and beyond spiking tissue in focal epilepsy.METHODSWe studied 25 patients with focal epilepsy (12F, mean ± SD age = 31.28 ± 9.30 years) and 55 age- and sex-matched healthy controls, subdivided into a group of 30 for imaging feature normalization (15F, 31.40 ± 8.74 years) and a group of 25 for replication (12F, 31.04 ± 5.65 years). The 3T MRI acquisition included T1-weighted, diffusion, quantitative T1 relaxometry, and resting-state functional imaging. Open-access MRI processing tools derived cortex-wide maps of morphology and microstructure (cortical thickness, mean diffusivity, and quantitative T1 relaxometry) and intrinsic local function and connectivity (timescales, connectivity distance, and node strength) for all participants. Multivariate approaches generated structural and functional alteration scores for each cortical location. Using HD-EEG, the predominant spike type was localized and we quantified MRI alterations within spike sources, as well as in proximal and connected networks.RESULTSRegions harboring spike sources showed increased structural MRI alterations (mean: 27.98%) compared to the rest of the brain (mean: 17.67%) in patients. Structural compromise extended to all regions with close functional coupling to spike sources (pairedt-tests; FDR-correctedp< 0.05), but not to anatomical neighbors of spike sources. This finding was replicated using average control functional, structural, and anatomical matrices instead of patient-specific matrices.CONCLUSIONSpiking regions contain more marked alterations in microstructure and morphology than the remaining cortex, which may help localize the epileptogenic zone non-invasively. There are nevertheless broader networks effects, which may relate to a cascading of structural changes to functionally connected cortices. These results underscore the utility of combining high-definition MRI and EEG approaches for characterizing epileptogenic tissue and assessing distributed network effects.