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.

Differences in the distribution of triggers among resting state networks in patients with juvenile myoclonic epilepsy explained by network analysis

“…Combining the node reduction methods, we found that abnormal discharges originating from six brain regions i.e., Tha, Cere, BG, SMC, VC, and PFC are most likely to lead to epileptic seizure symptoms in patients with JME during resting state. The conclusion in the current study is the same as that of the anterior study, but the former is more comprehensive (Vollmar et al, 2012;Lee and Park, 2019;Qin et al, 2019;Ma et al, 2022). After incorporating the independence of white matter fiber tracts and brain interval FC in the network analysis, we found that the core network also had a certain ability to resist abnormal discharges due to their dynamic change and that the three subcortical brain regions, namely, Tha, Cere, and BG formed a highly coupled subnetwork of functional connections.…”

“…Using the first node reduction method, we found that patients with JME have 21 different brain functional connectivity networks in the resting state. After running the code 500 times, we observed that these 21 different types of connection networks were distributed between ( Abe et al, 2007 ; Vollmar et al, 2012 ; Chin and Ratnavelu, 2016 ; Poleon and Szaflarski, 2017 ; Lee and Park, 2019 ; Qin et al, 2019 ; Ma et al, 2022 ; Samandari Bahraseman et al, 2022 ; Huang et al, 2023 ; Ke et al, 2023 ). As the number of runs increased, the probability of each type of connection network appearing gradually approached 1/21.…”

Altered dynamic functional connectivity of motor cerebellar with sensorimotor network and default mode network in Juvenile Myoclonic Epilepsy

“…The cerebellum was found to be involved in the production of several types of myoclonus [7], and its pathological involvement has been demonstrated in benign adult familial myoclonic epilepsy (BAFME) [8], juvenile absence epilepsy [9], and nonconvulsive partial status epileptic [10]. Previous studies suggested that the cerebellum is involved in the pathophysiological mechanisms of JME [11][12][13]. And it has been hypothesized that the increased inhibition effect of the cerebellum on the (basal ganglia related thalamocortical) BTC pathway might potentially contribute to the motor symptoms in patients during seizures [14].…”