Integrating multiparametric MRI with intracranial electrophysiology characterizes thalamic pathology in focal epilepsy

The thalamus is increasingly recognized as a key node within epileptogenic networks, yet how recurrent seizure activity shapes its tissue integrity remains poorly understood. Existing evidence has largely relied on individual structural, functional, or electrophysiological modalities, limiting an integrated understanding of thalamic pathology. Here, we combined quantitative sodium, structural, and functional 7 Tesla MRI with stereotactic electroencephalography (SEEG) and clinical characterization to establish a multimodal framework for investigating thalamic involvement in drug-resistant focal epilepsy. Multiparametric MRI revealed widespread increases in total sodium concentration, providing the first evidence of altered thalamic sodium homeostasis in focal epilepsy, together with focal elevations of the short T2* sodium signal fraction within lateral thalamic regions and increased homogeneity of the functional MRI signal. Integrating these complementary measures identified a robust MRI profile that distinguished patients from controls and independently identified patients with SEEG-defined epileptogenic thalami. Reduced thalamic volume was associated with greater ictal thalamic recruitment, whereas multivariate behavioral analyses demonstrated that complementary MRI features differentially reflected the extent of the epileptogenic network, disease chronicity, and demographic characteristics. By integrating measurements spanning tissue pathology, intracranial electrophysiology, and clinical phenotype, this study establishes a framework for characterizing pathological network nodes in focal epilepsy. Such multimodal imaging profiles may support patient stratification and individualized therapeutic strategies, including epilepsy surgery and targeted neuromodulation.