Altered Cerebro-Cerebellar Effective Connectivity in New-Onset Juvenile Myoclonic Epilepsy

Abstract

(1) Objective: Resting-state fMRI studies have indicated that juvenile myoclonic epilepsy (JME) could cause widespread functional connectivity disruptions between the cerebrum and cerebellum. However, the directed influences or effective connectivities (ECs) between these brain regions are poorly understood. In the current study, we aimed to evaluate the ECs between the cerebrum and cerebellum in patients with new-onset JME. (2) Methods: Thirty-four new-onset JME patients and thirty-four age-, sex-, and education-matched healthy controls (HCs) were included in this study. We compared the degree centrality (DC) between the two groups to identify intergroup differences in whole-brain functional connectivity. Then, we used a Granger causality analysis (GCA) to explore JME-caused changes in EC between cerebrum regions and cerebellum regions. Furthermore, we applied a correlation analysis to identify associations between aberrant EC and disease severity in patients with JME. (3) Results: Compared to HCs, patients with JME showed significantly increased DC in the left cerebellum posterior lobe (CePL.L), the right inferior temporal gyrus (ITG.R) and the right superior frontal gyrus (SFG.R), and decreased DC in the left inferior frontal gyrus (IFG.L) and the left superior temporal gyrus (STG.L). The patients also showed unidirectionally increased ECs from cerebellum regions to the cerebrum regions, including from the CePL.L to the right precuneus (PreCU.R), from the left cerebellum anterior lobe (CeAL.L) to the ITG.R, from the right cerebellum posterior lobe (CePL.R) to the IFG.L, and from the left inferior semi-lunar lobule of the cerebellum (CeISL.L) to the SFG.R. Additionally, the EC from the CeISL.L to the SFG.R was negatively correlated with the disease severity. (4) Conclusions: JME patients showed unidirectional EC disruptions from the cerebellum to the cerebrum, and the negative correlation between EC and disease severity provides a new perspective for understanding the cerebro-cerebellar neural circuit mechanisms in JME.

Keywords: cerebellar; degree centrality; effective connectivity; juvenile myoclonic epilepsy.

Figure 1

(A) Spatial distribution of the degree centrality (DC) in the juvenile myoclonic epilepsy (JME) patients. (B) Spatial distribution of the DC in healthy controls (HCs). (C) Significantly increased DC within the left cerebellum posterior lobe (CePL.L), the right inferior temporal gyrus (ITG.R), and the right superior frontal gyrus (SFG.R) between the JME patients and HCs, and decreased DC in the left inferior frontal gyrus (IFG.L) and the left superior temporal gyrus (STG.L).

Figure 2

Aberrant effective connectivity in juvenile myoclonic epilepsy (JME) patients. (A) Increased effective connectivity from the left cerebellum posterior lobe (CePL.L) to the right precuneus (PreCU.R; p < 0.01, AlphaSim-corrected). (B) Increased effective connectivity from the left cerebellum anterior lobe (CeAL.L) to the right inferior temporal gyrus (ITG.R; p < 0.01, AlphaSim-corrected). (C) Increased effective connectivity from the right cerebellum posterior lobe (CePL.R) to the left inferior frontal gyrus (IFG.L; p < 0.01, AlphaSim-corrected). (D) Increased effective connectivity from the left inferior semi-lunar lobule of cerebellum (CeISL.L) to the right superior frontal gyrus (SFG.R; p < 0.01, AlphaSim-corrected). (E) Summary of the increased effective connectivity and spatial distribution from the cerebellum to the cerebrum.

Figure 3

Correlations between the increased effective connectivity (EC) and the National Hospital Seizure Severity Scale (NHS3) scores. (A) The EC from the left inferior semi-lunar lobule of the cerebellum (CeISL.L) to the right superior frontal gyrus (SFG.R). (B) The NHS3 scores negatively correlated with the increased effective connectivity from the CePL.L to the SFG.R (r = −0.35, p = 0.042).