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

To assess whether neuronal signals in patients with genetic generalized epilepsy (GGE) are heritable, we examined magnetoencephalography resting-state recordings in patients and their healthy siblings.

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 6 frequency bands (1-40 Hz). We further calculated intraclass correlations to estimate heritability for the imaging patterns within families.

Compared with controls (n = 45), patients with GGE (n = 25) showed widespread increased functional connectivity (θ to γ frequency bands) and power (δ to γ 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 β frequencies, but also for δ and θ 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 at onset, disease duration, or seizure control were not.

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 β band, representing an endophenotype of GGE.