Investigating sodium homeostasis of structural brain hubs in focal epilepsy using 7 T MRI

Abstract Besides their crucial role in cerebral connectivity, brain hubs are regions vulnerable to the energy deficit associated with various brain disorders. Changes in sodium homeostasis of cortical regions have been observed in focal epilepsy and may reflect energy failure. We investigated whether nodal structural connectivity is differently affected within the hub and non-hub regions by ionic perturbations associated with focal epilepsy. Our hypothesis was that the metabolic demands of hub regions may be associated with a distinct ionic profile detectable by sodium MRI and that this profile is altered in focal epilepsy. We included 39 patients with drug-resistant focal epilepsy and 21 age- and gender-matched healthy controls. Anatomical, diffusion-weighted, and sodium imaging was performed using a 7 Tesla MRI scanner. Patients underwent pre-surgical work-up, including stereo-electroencephalographic recordings for defining the epileptogenic regions. Anatomical parcellation and multimodal coregistration allowed the use of parcels as nodes of whole-brain structural connectomes, linking structural connectivity measures to epileptogenicity and sodium parameters. Sodium parameters in patients were z-scored concerning homologous parcels in controls to allow comparison across regions of interest. Hub regions had higher total sodium concentration (TSC) than non-hub regions in both patients and controls, and this difference was not observed for sodium signal fraction (f, a proxy of intracellular sodium homeostasis). Compared to controls, patients showed increased TSC in both epileptogenic and non-epileptogenic zones, and this increase in TSC was consistent in both hub and non-hub regions. On the contrary, f was increased only within the epileptogenic zones and was not affected by the hubness of a region. Our results also confirm the whole brain increase in TSC and the local increase of the f value within epileptogenic zones previously observed in focal epilepsy patients. Therefore, we propose that sodium imaging can probe distinct tissue properties: TSC appears sensitive to microstructural alterations, while f could reflect homeostatic disruptions specific to epileptogenic regions.