Abstracts

Rationale: Previous neuroimaging studies reported functional and structural impairments of the upper basal ganglia in idiopathic generalised epilepsy (IGE). However, these studies often overlook morphometric investigations of lower basal ganglia structures located in the midbrain due to poor visibility on clinically acquired volumetric T1-weighted scans. In this study we acquired 3D isotropic T1-weighted, T2-weighted and resting state functional MR images to investigate volumetric, myelin and functional connectivity alterations in three midbrain structures in patients with IGE: the substantia nigra (SN), subthalamic nuclei (STh) and red nuclei (RN).

Methods: A total of 33 patients with IGE (23 refractory, 10 non-refractory), and 18 age and sex matched healthy controls were recruited and underwent MR imaging. The RN, SN, and STh were automatically segmented from T2-weighted images using pBrain (Manjón et al. 2020). Estimated mean myelin content for each structure was determined using a previously described T1-weighted/T2-weighted ratio method (Ganzetti, Wenderoth, and Mantini 2014). Pairwise t-tests of the myelin and volumetric results were calculated to determine statistical significance. Functional connectivity alterations of the structures of interest between groups were identified using seed based resting state fMRI analysis using the CONN toolbox (Whitfield-Gabrieli and Nieto-Castanon 2012) running in SPM12.

Results: Patients with IGE had significantly increased volumes of the left (p=0.03) and right SN (p=0.02) (Figure 1.A), and significantly increased myelin within the right SN (p=0.04) relative to controls (Figure 1.B). Significant alterations in functional connectivity were observed between the left SN and the cerebellum bilaterally in patients with non-refractory IGE relative to patients with refractory IGE (Figure 1.C). No differences in volume or myelin content of the RN were found bilaterally, however, significantly increased functional connectivity between the left RN and the right supramarginal gyrus and left lateral occipital cortex were discovered in patients relative to controls (Figure 1.C). Further RN connectivity alterations were found with significantly increased functional connectivity between the right RN and precuneus cortex for patients with non-refractory IGE relative to patients with refractory IGE and controls. Despite no significant alterations in volume or myelin in the STh, decreased functional connectivity was observed between the left STh and the right occipital cortex in patients with non-refractory IGE compared to patients with refractory IGE.

Conclusions: We report differential volumetric, myelin, and functional connectivity alterations in midbrain structures in patients with IGE. These findings are consistent with previous experiential work that demonstrate pathophysiological abnormalities of the lower basal ganglia in animal models of generalised epilepsy (Velíšek et al. 2011; Hu et al. 2020).

Funding: Please list any funding that was received in support of this abstract.: UK MRC DiMeN DTP studentship; ERUK project grant (Grant number 1085); UK MRC (Grant Numbers MR/S00355X/1 and MR/K023152/1); the Wellcome Trust (105617/Z/14/ Z and 210109/Z/18/Z) and UKRI (MR/T04294X/1).