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

Christoffer Hatlestad-Hall,Ricardo Bruña,Marte Roa Syvertsen,Aksel Erichsen,Vebjørn Andersson,Fabrizio Vecchio,Francesca Miraglia,Paolo M Rossini,Hanna Renvall,Erik Taubøll,Fernando Maestú,Ira H Haraldsen

doi:10.1016/j.clinph.2021.04.008

Abstract

ObjectiveThe hypersynchronous neuronal activity associated with epilepsy causes widespread functional network disruptions extending beyond the epileptogenic zone. This altered network topology is considered a mediator for non-seizure symptoms, such as cognitive impairment. The aim of this study was to investigate functional network alterations in focal epilepsy patients with good seizure control and high quality of life. MethodsWe compared twenty-two focal epilepsy patients and sixteen healthy controls on graph metrics derived from functional connectivity of source-level resting-state EEG. Graph metrics were calculated over a range of network densities in five frequency bands. ResultsWe observed a significantly increased small world index in patients relative to controls. On the local level, two left-hemisphere regions displayed a shift towards greater alpha band “hubness”. The findings were not mediated by age, sex or education, nor by age of epilepsy onset, duration or focus lateralisation. ConclusionsWidespread 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 might support the position that functional network analysis could hold clinical relevance for epilepsy. SignificanceFocal epilepsy is accompanied by global and local functional network aberrancies which might be implied in the sustenance of non-seizure symptoms.

Highlights

MethodsTwenty-two patients diagnosed with uni- or bilateral focal epilepsy (FE; fourteen females, age 55.1 ± 4.3 years) were recruited from neurological outpatient clinics, in connection with routine follow-up visits
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
We investigated a relatively small sample, we have presented evidence that focal epilepsy patients, despite good seizure control and high quality of life, exhibit widespread functional network alterations relative to healthy peers

Summary

Methods

Twenty-two patients diagnosed with uni- or bilateral focal epilepsy (FE; fourteen females, age 55.1 ± 4.3 years) were recruited from neurological outpatient clinics, in connection with routine follow-up visits. Sixteen age-matched healthy control (HC) subjects (twelve females, age 55.9 ± 6.9 years) participated. The HC participants were recruited from the FE patients’ social networks, providing controls with similar socio-economic background to the patients. All FE subjects had used the same anti-seizure medication (ASM) for at least six months prior to their participation in the study. Neither FE nor HC subjects had any history of epilepsy surgery, psychiatric disorders, developmental disorders, nor any other debilitating diseases. All participants provided informed written consent in accordance with the Declaration of Helsinki

Results

Discussion

Conclusion