Electroencephalography is the tool of choice for the diagnosis of epilepsy. Its use is increasing in the clinic, especially in its high-density form (HD-EEG), because it can be used as a neuroimaging tool, supporting the process of identifying the epileptogenic network (NE) and monitoring the evolution of brain connectivity over time in relation to the epileptic process.In particular, the reorganization of the functional connectome following pharmacological and/or surgical treatment of epilepsy is an aspect that is still little studied, but it could represent a useful prognostic factor that can improve the clinical management of the affected person. In addition, high-density EEG can be applied for the purpose of characterizing functional brain connectivity in some rare neurodevelopmental diseases, particularly Angelman syndrome and Dup15q syndrome, pathological increasingly being studied as a model of neurodevelopmental, cognitive and behavioral alterations in addition to epilepsy. Relatively to recent developments of potentially "disease modifying" therapies for these pathologies, there is indeed a need for markers of brain functioning useful to objectively monitor clinical development.

The present study involves the systematization of data from noninvasive clinical-instrumental assessments such as EEG and structural MRI, acquired during the diagnosis process in drug-resistant epilepsies and rare neurodevelopmental syndromes associated with epilepsy, in order to analyze the relationship between functional-structural organization of the brain system and clinical aspects, including cognitive and behavioral functioning. In the context of epilepsy, a data collection will be carried out to which recent analytical approaches related to the study of the functional connectome will be applied, with the aim of characterizing the reorganization of brain networks over time, hypothesizing a process of progressive "normalization" of these in subjects who present, after the course of treatment (pharmacological and/or surgical), total freedom or a significant reduction of seizures. In parallel, the relationship between the organization of functional networks and cognitive/behavioral functioning pre- and post-treatment will be analyzed, in order to obtain a dynamic and longitudinal view of the patients' clinical evolution. With this in mind, it is important to understand that functional activity is intrinsically linked to brain structures, and in fact the project takes into account the anatomo-functional relationship of the connectome. This relationship is crucial in rare neurodevelopmental syndromes, such as Angelman syndrome and Dup15q, where the use of the structural-functional connectome is a relevant novel element for the purpose of characterizing a highly complex picture that disrupts the global development of the affected child/person. Indeed, the relationship between changes in functional relationships between brain areas and underlying physical connections, as well as the relationship between these and neurodevelopment, are still poorly understood. The second goal of the project is therefore to generalize the use of these patient-friendly methods, starting with data collected with noninvasive instrumentation, in order to improve the characterization of the neurocognitive profile, as well as a useful tool to identify syndrome-specific biomarkers to be used in monitoring clinical development.