Heritability of Magnetoencephalography Phenotypes Among Patients With Genetic Generalized Epilepsy and Their Siblings

Abstract

Objective To assess whether neuronal signals in patients with genetic generalized epilepsy (GGE) are heritable, we examined magnetoencephalography (MEG) resting-state recordings in patients and their healthy siblings. Methods In a prospective, cross-sectional design, we investigated source-reconstructed power and functional connectivity in patients, siblings and controls. We analyzed 5 minutes of cleaned and awake data without epileptiform discharges in six frequency bands (1-40 Hz). We further calculated intraclass correlations (ICC) to estimate heritability for the imaging patterns within families. Results Compared with controls (n = 45), patients with GGE (n = 25) showed widespread increased functional connectivity (theta to gamma frequency bands) and power (delta to gamma frequency bands) across the spectrum. Siblings (n = 18) fell between the levels of patients and controls. Heritability of the imaging metrics was observed in regions, where patients strongly differed from controls, mainly in beta frequencies, but also for delta and theta power. Network connectivity in GGE was heritable in frontal, central and inferior parietal brain areas and power in central, temporo-parietal, and subcortical structures. Presence of generalized spike-wave activity during recordings and medication were associated with the network patterns, whereas other clinical factors such as age of onset, disease duration or seizure control were not. Conclusion Metrics of brain oscillations are well suited to characterize GGE and likely relate to genetic factors rather than the active disease or treatment. High power and connectivity levels co-segregated in patients with GGE and healthy siblings, predominantly in the beta band, representing an endophenotype of GGE.