Source-level EEG and graph theory reveal widespread functional network alterations in focal epilepsy

Abstract Objective The hypersynchronous neuronal activity associated with epilepsy causes widespread functional network disruptions extending beyond the epileptogenic zone. This altered functional network topology is considered a mediator from which non-seizure symptoms arise, such as cognitive impairment. The aim of the present study was to demonstrate the presence of functional network alterations in focal epilepsy patients with good seizure control and high quality of life. Methods We compared twenty-two focal epilepsy patients and sixteen healthy controls on graph metrics derived from functional connectivity (phase-locking value) of source reconstructed resting-state EEG. Graph metrics were calculated over a predefined range of network densities in five frequency bands. Results In terms of global network topology alterations, we observed a significantly increased small world index in epilepsy patients relative to the healthy controls. On the local level, two left-hemisphere regions displayed a shift towards greater alpha band “hubness”. Conclusions Subtle widespread functional network alterations are evident in focal epilepsy, even in a cohort characterised by successful anti-seizure medication therapy and high quality of life. These findings suggest a possible clinical relevance of functional network analysis in epilepsy. Significance Focal epilepsy is accompanied by global and local functional network aberrancies which might be implied in the sustenance of non-seizure symptoms. Highlights Focal epilepsies are associated with widespread interictal functional network alterations, extending beyond the epilepsy focus. Global and local graph theoretical analyses of source-space EEG functional connectivity networks capture these network changes, and might thus be of clinical relevance. Group-level differences in network metrics are relatively stable across network analysis parameters.