Neuro-vascular coupling patterns during wakefulness and sleep in Genetic Generalized Epilepsies: a novel endophenotyping approach for genotype-phenotype correlation

REFINE proposal aims to identify new endophenotypes of generalized epilepsies (GGE) and explore their genetic associations. The core approach combines advanced EEG-fMRI functional imaging with whole-exome sequencing in well-characterized GGE patients. GGE, accounting for 15-20% of epilepsies, includes various syndromes with overlapping features and diverse responses to treatment. This diversity suggests a need for measurable biomarkers to distinguish GGE phenotypes and guide medication choices. The proposal highlights the heritability of GGE, often involving multiple genes. A key focus is understanding the relationship between electro-clinical features and genotype, especially concerning combinations of genetic variants rather than rare monogenic mutations. Project steps include: (a) analyzing EEG-fMRI networks during different brain states and pathological discharges; (b) correlating these findings with detailed clinical profiles to identify endophenotypes; (c) using these endophenotypes to guide whole-exome sequencing; (d) associating clinical and neurophysiological data with genetic findings through correlation analysis. Goals are: (a) determine if EEG-fMRI-derived endophenotypes can differentiate patients from controls and categorize them into clinically relevant subgroups for better epilepsy management; (b) explore whether these endophenotypes can reveal new genetic variants linked to GGE; (c) establish correlations between genotype and phenotype, reflected in EEG and BOLD measures.