Heritability of alpha and sensorimotor network changes in temporal lobe epilepsy

Abstract

Objective: Electroencephalography (EEG) features in the alpha band have been shown to differ between people with epilepsy and healthy controls. Here, in a group of patients with mesial temporal lobe epilepsy (mTLE), we seek to confirm these EEG features, and using simultaneous functional magnetic resonance imaging, we investigate whether brain networks related to the alpha rhythm differ between patients and healthy controls. Additionally, we investigate whether alpha abnormalities are found as an inherited endophenotype in asymptomatic relatives.

Methods: We acquired scalp EEG and simultaneous EEG and functional magnetic resonance imaging in 24 unrelated patients with unilateral mTLE, 23 asymptomatic first-degree relatives of patients with mTLE, and 32 healthy controls. We compared peak alpha power and frequency from electroencephalographic data in patients and relatives to healthy controls. We identified brain networks associated with alpha oscillations and compared these networks in patients and relatives to healthy controls.

Results: Patients had significantly reduced peak alpha frequency (PAF) across all parietal and occipital electrodes. Asymptomatic relatives also had significantly reduced PAF over 14 of 17 parietal and occipital electrodes. Both patients and asymptomatic relatives showed a combination of increased activation and a failure of deactivation in relation to alpha oscillations compared to healthy controls in the sensorimotor network.

Interpretation: Genetic factors may contribute to the shift in PAF and alterations in brain networks related to alpha oscillations. These may not entirely be a consequence of anti-epileptic drugs, seizures or hippocampal sclerosis and deserve further investigation as mechanistic contributors to mTLE.

Figure 1

EEG topographical plots for the alpha band. Group‐averaged EEG topographical plots of (A) peak power and (B) peak frequency in the alpha frequency band. In the patients’ and relatives’ plots, channels that show a significant group difference from healthy controls are indicated by pink dots (P < 0.05, FDR‐corrected across parietal and occipital channels only). “L” indicates the left or ipsilateral side. Pat, patients with mTLE; Rel, asymptomatic relatives; Con, healthy controls; EEG, electroencephalography; FDR, false discovery rate; mTLE, mesial temporal lobe epilepsy.

Figure 2

BOLD fMRI correlates of EEG alpha oscillations. (A) Regions showing positive and negative fMRI correlations with EEG alpha oscillations across all subjects. (B) Regions showing higher correlations with alpha oscillations in (B) patients and (C) asymptomatic relatives compared to healthy controls. Voxels in the sensorimotor region that were significantly different from controls in the relatives group had high overlap with voxels found significantly different from controls in the patient group. Images show Z‐statistics at a cluster threshold of P < 0.05 (FWE‐corrected). Positive values are shown in red/yellow and negative values in blue. MNI coordinates are shown above each slice. “L” represents the left or ipsilateral side. BOLD fMRI, blood‐oxygen‐level‐dependent fMRI; EEG, electroencephalography; MNI, Montreal Neurological Institute.

Figure 3

Mean group difference in correlation with alpha oscillation. (A) Clusters showing significantly higher correlation with alpha oscillation in patients compared to healthy controls. (B) Clusters showing significantly higher correlation with alpha oscillation in relatives compared to healthy controls. The mean parameter estimates are shown on the upper axes and the mean group differences shown on the lower axes as bootstrap sampling distributions. Mean differences are depicted as dots; 95% confidence intervals are indicated by the ends of the vertical error bars. Pat, patients with mTLE; Rel, asymptomatic relatives; Con, healthy controls. Figures created on http://www.estimationstats.com. mTLE, mesial temporal lobe epilepsy.