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

Neurology. 2021 Jul 13;97(2):e166-e177. doi: 10.1212/WNL.0000000000012144. Epub 2021 May 27.

Abstract

Objective: 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.

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 6 frequency bands (1-40 Hz). We further calculated intraclass correlations 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 (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.

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 β band, representing an endophenotype of GGE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain / physiopathology*
  • Cross-Sectional Studies
  • Epilepsy, Generalized / genetics*
  • Epilepsy, Generalized / physiopathology*
  • Female
  • Humans
  • Magnetoencephalography*
  • Male
  • Phenotype
  • Prospective Studies
  • Siblings
  • Young Adult