Altered dynamic effective connectivity of the default mode network in newly diagnosed drug-naïve juvenile myoclonic epilepsy

Zhang

et al. 2022

Brain Sciences

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(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.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Zhang

et al. 2022

Brain Sciences

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“…Another study showed generalized spike and wave discharge (GSWD)-related deactivations in the DMN, suggesting that GSWDs may interrupt the functions of the DMN [25]. Dynamic effective connectivity and independent component analyses showed complex alterations of DMN and its components in drug-naïve JME patients, indicating DMN dysfunction in the early stage of JME [26]. Interestingly, another study found significantly reduced DMN connectivity in VPA-resistant IGE patients with uncontrolled seizures, compared with responsive patients and HCs [20].…”

Section: Discussionmentioning

confidence: 99%

Altered brain activity in juvenile myoclonic epilepsy with a monotherapy: a resting-state fMRI study

Qin

Zhang

Ren

et al. 2022

Acta Epileptologica

Background Juvenile myoclonic epilepsy (JME) is the most common syndrome of idiopathic generalized epilepsy. Although resting-state functional magnetic resonance imaging (rs-fMRI) studies have found thalamocortical circuit dysfunction in patients with JME, the pathophysiological mechanism of JME remains unclear. In this study, we used three complementary parameters of rs-fMRI to investigate aberrant brain activity in JME patients in comparison to that of healthy controls. Methods Rs-fMRI and clinical data were acquired from 49 patients with JME undergoing monotherapy and 44 age- and sex-matched healthy controls. After fMRI data preprocessing, the fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and degree centrality (DC) were calculated and compared between the two groups. Correlation analysis was conducted to explore the relationship between local brain abnormalities and clinical features in JME patients. Results Compared with the controls, the JME patients exhibited significantly decreased fALFF, ReHo and DC in the cerebellum, inferior parietal lobe, and visual cortex (including the fusiform and the lingual and middle occipital gyri), and increased DC in the right orbitofrontal cortex. In the JME patients, there were no regions with reduced ReHo compared to the controls. No significant correlation was observed between regional abnormalities of fALFF, ReHo or DC, and clinical features. Conclusions We demonstrated a wide range of abnormal functional activity in the brains of patients with JME, including the prefrontal cortex, visual cortex, default mode network, and cerebellum. The results suggest dysfunctions of the cerebello-cerebral circuits, which provide a clue on the potential pathogenesis of JME.

“…Hence, the dynamic FC, which describes the time‐varying patterns of co‐activations among brain regions, is a more efficient way for uncovering specific properties of functional communication in health and disease (Allen et al, 2014 ; Calhoun & Adali, 2016 ; Fiorenzato et al, 2019 ; F. Liu et al, 2017 ; Sun, Collinson, Suckling, & Sim, 2019 ; Tu et al, 2020 ). For patients with JME, previous studies have revealed that the dynamic FC was reduced and linked to disease severity (Wang, Berglund, Uppman, & Li, 2019 ; Zhang et al, 2018 , 2020 ). However, to our knowledge, no prior study has explored the time‐varying characteristics of SC–FC coupling in JME, and it is still unclear how anatomical connectivity constraint supports dynamic functional interaction in the rich‐club organization.…”

Section: Introductionmentioning

confidence: 95%

“…Liu et al, 2017;Sun, Collinson, Suckling, & Sim, 2019;Tu et al, 2020). For patients with JME, previous studies have revealed that the dynamic FC was reduced and linked to disease severity (Wang, Berglund, Uppman, & Li, 2019;Zhang et al, 2018Zhang et al, , 2020. However, to our knowledge, no prior study has explored the time-varying characteristics of SC-FC coupling in JME, and it is still unclear how anatomical connectivity constraint supports dynamic functional interaction in the rich-club organization.…”

Section: Introductionmentioning

confidence: 99%

Aberrant dynamic structure–function relationship of rich‐club organization in treatment‐naïve newly diagnosed juvenile myoclonic epilepsy

Zheng

et al. 2022

Human Brain Mapping

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Neuroimaging studies have shown that juvenile myoclonic epilepsy (JME) is characterized by impaired brain networks. However, few studies have investigated the potential disruptions in rich-club organization-a core feature of the brain networks. Moreover, it is unclear how structure-function relationships dynamically change over time in JME. Here, we quantify the anatomical rich-club organization and dynamic structural and functional connectivity (SC-FC) coupling in 47 treatment-naïve newly diagnosed patients with JME and 40 matched healthy controls. Dynamic functional network efficiency and its association with SC-FC coupling were also calculated to examine the supporting of structure-function relationship to brain information transfer. The results showed that the anatomical rich-club organization was disrupted in the patient group, along with decreased connectivity strength among rich-club hub nodes. Furthermore, reduced SC-FC coupling in rich-club organization of the patients was found in two functionally independent dynamic states, that is the functional segregation state (State 1) and the strong somatomotor-cognitive control interaction state (State 5); and the latter was significantly associated with disease severity. In addition, the relationships between SC-FC coupling of hub nodes connections and functional network efficiency in State 1 were found to be absent in patients. The Guangyao Liu and Weihao Zheng contributed equally to this study.