Midbrain structure volume, estimated myelin and functional connectivity in idiopathic generalised epilepsy

Background: Structural and functional neuroimaging studies often overlook lower basal ganglia struc-tures located in and adjacent to the midbrain due to poor contrast on clinically acquired T1-weighted scans. Here, we acquired T1-weighted, T2-weighted, and resting-state fMRI scans to investigate differ-ences in volume, estimated myelin content and functional connectivity of the substantia nigra (SN), sub -thalamic nuclei (SubTN) and red nuclei (RN) of the midbrain in IGE.Methods: Thirty-three patients with IGE (23 refractory, 10 non-refractory) and 39 age and sex-matched healthy controls underwent MR imaging. Midbrain structures were automatically segmented from T2 -weighted images and structural volumes were calculated. The estimated myelin content for each struc-ture was determined using a T1-weighted/T2-weighted ratio method. Resting-state functional connectiv-ity analysis of midbrain structures (seed-based) was performed using the CONN toolbox.Results: An increased volume of the right RN was found in IGE and structural volumes of the right SubTN differed between patients with non-refractory and refractory IGE. However, no volume findings survived corrections for multiple comparisons. No myelin alterations of midbrain structures were found for any subject groups. We found functional connectivity alterations including significantly decreased connectiv-ity between the left SN and the thalamus and significantly increased connectivity between the right SubTN and the superior frontal gyrus in IGE.Conclusions: We report volumetric and functional connectivity alterations of the midbrain in patients with IGE. We postulate that potential increases in structural volumes are due to increased iron deposition that impacts T2-weighted contrast. These findings are consistent with previous studies demonstrating pathophysiological abnormalities of the lower basal ganglia in animal models of generalised epilepsy.(c) 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

This study investigated the differences in volume, estimated myelin content, and functional connectivity of midbrain structures in patients with idiopathic generalized epilepsy (IGE). The results revealed increased volume in the right red nucleus and differences in structural volumes of the right subthalamic nucleus between non-refractory and refractory IGE patients. Functional connectivity alterations were also observed, including decreased connectivity between the left substantia nigra and thalamus, and increased connectivity between the right subthalamic nucleus and superior frontal gyrus in IGE patients.