Increased Thalamic Connectivity in Juvenile Myoclonic Epilepsy Based on Electroencephalography Source-Level Analysis.

Background: This study investigated alterations in the intrinsic thalamic network of patients with juvenile myoclonic epilepsy (JME) based on an electroencephalography (EEG) source-level analysis. Materials and Methods: We enrolled patients newly diagnosed with JME as well as healthy controls. The assessments were conducted in the resting state. We computed sources based on the scalp electrical potentials using a minimum-norm imaging method and a standardized, low-resolution, brain electromagnetic tomography approach. To create a functional connectivity matrix, we used the Talairach atlas to define thalamic nodes and applied the coherence method to measure brain synchronization as edges. We then calculated the intrinsic thalamic network using graph theory. We compared the intrinsic thalamic network of patients with JME with those of healthy controls. Results: This study included 67 patients with JME and 66 healthy controls. EEG source-level analysis revealed significant differences in the intrinsic thalamic networks between patients with JME and healthy controls. The measures of functional connectivity (radius, diameter, and characteristic path length) were significantly lower in patients with JME than in healthy controls (radius: 2.769 vs. 3.544, p = 0.015; diameter: 4.464 vs. 5.443, p = 0.024; and characteristic path length: 2.248 vs. 2.616, p = 0.046). Conclusions: We demonstrated alterations in the intrinsic thalamic network in patients with JME compared with those in healthy controls based on the EEG source-level analysis. These findings indicated increased thalamic connectivity in the JME group. These intrinsic thalamic network changes may be related to the pathophysiology of JME.

Altered dynamic functional connectivity of striatal-cortical circuits in Juvenile Myoclonic Epilepsy.

OBJECTIVE: To investigate whether the dynamic functional connectivity (dFC) of striatal-cortical circuits changes in juvenile myoclonic epilepsy (JME). METHODS: The resting-state EEG-fMRI and the sliding-window approach were adopted to explore the dynamic striatal-cortical circuitry in thirty JME patients compared with 30 well-matched health controls (HCs). Six pairs of striatal seeds were selected as regions of interests. The correlation analysis was performed to reveal the relationship between the altered dFC variability and clinical variables in JME group. RESULTS: JME patients exhibited increased dFC variability mainly involved in fronto-striatal and striatal-thalamic networks; decreased dFC variability between striatum subdivisions and default mode network (DMN) regions compared with HCs (p<0.05, GRF corrected). In addition, the hypervariability between left ventral-rostral putamen and left medial superior frontal gyrus was positively (r= 0.493, p=0.008) correlated with the mean frequency score of myoclonic seizures in JME group. CONCLUSION: JME presented altered dFC variability in striatal-cortical circuits. The pattern of altered circuits showed increased variability in fronto-striatal and striatal-thalamic networks and decreased variability in striatal-DMN. These results provide novel information about the dynamic neural striatal-cortical circuitry of JME.

Functional connectivity disturbances of ascending reticular activating system and posterior thalamus in juvenile myoclonic epilepsy in relation with photosensitivity: A resting-state fMRI study.

OBJECTIVE: Juvenile myoclonic epilepsy (JME) is typified by the occurrence of myoclonic seizures after awakening, though another common trait is myoclonic seizures triggered by photic stimulation. We aimed to investigate the functional connectivity (FC) of nuclei in the ascending reticular activating system (ARAS), thalamus and visual cortex in JME with and without photosensitivity. METHODS: We examined 29 patients with JME (16 photosensitive (PS), 13 non- photosensitive-(NPS)) and 28 healthy controls (HCs) using resting-state functional magnetic resonance imaging (rs-fMRI). Seed-to-voxel FC analyses were performed using 25 seeds, including the thalamus, visual cortex, and ARAS nuclei. RESULTS: Mesencephalic reticular formation seed revealed significant hyperconnectivity between the bilateral paracingulate gyrus and anterior cingulate cortex in JME group, and in both JME-PS and JME-NPS subgroups compared to HCs (pFWE-corr < 0.001; pFWE-corr < 0.001; pFWE-corr = 0.002, respectively). Locus coeruleus seed displayed significant hyperconnectivity with the bilateral lingual gyri, intracalcarine cortices, occipital poles and left occipital fusiform gyrus in JME-PS group compared to HCs (pFWE-corr <0.001). Additionally, locus coeruleus seed showed significant hyperconnectivity in JME-PS group compared to JME-NPS group with a cluster corresponding to the bilateral lingual gyri and right intracalcarine cortex (pFWE-corr < 0.001). Lastly, the right posterior nuclei of thalamus revealed significant hyperconnectivity with the right superior lateral occipital cortex in JME-PS group compared to HCs (pFWE-corr < 0.002). CONCLUSIONS: In JME, altered functional connectivity of the arousal networks might contribute to the understanding of myoclonia after awakening, whereas increased connectivity of posterior thalamus might explain photosensitivity.

Subcortical gray matter changes in pediatric patients with new-onset juvenile myoclonic epilepsy.

OBJECTIVE: The objective of the study was to identify the relationship between subcortical gray matter (GM) volumes and juvenile myoclonic epilepsy (JME). METHODS: We analyzed the brain magnetic resonance imaging (MRI) scans that were performed during the time of the diagnosis of epilepsy by using voxel-based morphometry (VBM) method. The volumetric three-dimensional sequence was used for structural investigation. The volumes of the thalamus, caudate nucleus, pallidum, and putamen were measured in both hemispheres of patients with JME, patients with generalized tonic-clonic seizures alone (GTCS) (as a disease control group) and healthy controls (HCs). All patients were drug-naïve, and treatment had been started after evaluating MRI results. RESULTS: Fifteen patients with JME (9 females, mean age = 16.1 ±â€¯3.2), 18 patients with GTCS (10 females, mean age = 15.5 ±â€¯2.9), and 43 HCs (24 females, mean age = 15.9 ±â€¯2.8) were included in the analysis. No significant difference was found for relative globus pallidus, caudate, and putamen volumes among the groups with JME, GTCS, and the HC group. The relative left and right thalamic volumes were significantly different between groups (Kruskal-Wallis rank test, p = 0.007, p = 0.001). In pairwise comparisons, both right and left relative thalamic volumes were lower in patients with JME than in HCs (right thalamus: means: 0.521 ±â€¯0.066 vs. 0.597 ±â€¯0.058, p < 0.001; left thalamus: means: 0.526 ±â€¯0.088 vs. 0.605 ±â€¯0.057, p < 0.001, Bonferroni post hoc corrections) and in patients with JME than in patients with GTCS (right thalamus: means: 0.521 ±â€¯0.066 vs. 0.578 ±â€¯0.066, p = 0.03; left thalamus: means: 0.526 ±â€¯0.088 vs. 0.592 ±â€¯0.068, p = 0.01, Bonferroni post hoc corrections), whereas there was no significant difference between the HCs and patients with GTCS (right thalamus: means: 0.597 ±â€¯0.058 vs. 0.578 ±â€¯0.066, p = 0.8; left thalamus: means: 0.605 ±â€¯0.057 vs. 0.592 ±â€¯0.068, p = 0.999, Bonferroni post hoc corrections). CONCLUSION: This study allowed us to know that microstructural abnormalities exist from the disease onset, and the thalamus might play a critical role in the pathogenesis of JME.

Alteration of cerebello-thalamocortical spontaneous low-frequency oscillations in juvenile myoclonic epilepsy.

OBJECTIVE: Altered thalamocortical network has been proposed to play a pivotal role in the principal pathophysiology underlying juvenile myoclonic epilepsy (JME). Recently, resting-state fMRI studies have provided converging evidence for thalamocortical dysconnectivity in patients with JME. Herein, we investigated the amplitude and spatial distribution of spontaneous low-frequency oscillations using analysis of fractional amplitude of low-frequency fluctuation (fALFF) in a large group of JME patients in comparison with controls. METHODS: Volumetric MRI and resting-state fMRI were acquired in 75 patients with JME and 62 matched controls. After preprocessing of MRI data, fALFF was computed and then Z-transformed for standardization. fALFF was compared between controls and patients, and correlation analysis between regional fALFF and clinical parameters were performed in patients. RESULTS: Compared with controls, JME patients revealed significant fALFF increases in the bilateral medial thalamus, insular cortex/inferior frontal gyrus, and cerebellum vermis (false discovery rate-corrected P < 0.05). There was no region of fALFF reduction in JME patients relative to controls. No significant correlation was observed between regional fALFF and disease duration or cumulative number of generalized tonic-clonic seizures. CONCLUSIONS: We have shown alterations of low-frequency oscillations in the thalamus, insular cortex/inferior frontal gyrus, and cerebellum in patients with JME, implicating cerebello-thalamocortical network abnormality in the pathophysiology underlying JME. Our results could further support the recent concept that JME is a network epilepsy involving specific cortical and subcortical structures, especially the cerebello-thalamocortical network.

BOLD-fMRI activity informed by network variation of scalp EEG in juvenile myoclonic epilepsy.

Epilepsy is marked by hypersynchronous bursts of neuronal activity, and seizures can propagate variably to any and all areas, leading to brain network dynamic organization. However, the relationship between the network characteristics of scalp EEG and blood oxygenation level-dependent (BOLD) responses in epilepsy patients is still not well known. In this study, simultaneous EEG and fMRI data were acquired in 18 juvenile myoclonic epilepsy (JME) patients. Then, the adapted directed transfer function (ADTF) values between EEG electrodes were calculated to define the time-varying network. The variation of network information flow within sliding windows was used as a temporal regressor in fMRI analysis to predict the BOLD response. To investigate the EEG-dependent functional coupling among the responding regions, modulatory interactions were analyzed for network variation of scalp EEG and BOLD time courses. The results showed that BOLD activations associated with high network variation were mainly located in the thalamus, cerebellum, precuneus, inferior temporal lobe and sensorimotor-related areas, including the middle cingulate cortex (MCC), supplemental motor area (SMA), and paracentral lobule. BOLD deactivations associated with medium network variation were found in the frontal, parietal, and occipital areas. In addition, modulatory interaction analysis demonstrated predominantly directional negative modulation effects among the thalamus, cerebellum, frontal and sensorimotor-related areas. This study described a novel method to link BOLD response with simultaneous functional network organization of scalp EEG. These findings suggested the validity of predicting epileptic activity using functional connectivity variation between electrodes. The functional coupling among the thalamus, frontal regions, cerebellum and sensorimotor-related regions may be characteristically involved in epilepsy generation and propagation, which provides new insight into the pathophysiological mechanisms and intervene targets for JME.

Aberrant Thalamocortical Connectivity in Juvenile Myoclonic Epilepsy.

The purpose of this study was to investigate the functional connectivity (FC) of thalamic subdivisions in patients with juvenile myoclonic epilepsy (JME). Resting state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data were acquired from 22 JME and 25 healthy controls. We first divided the thalamus into eight subdivisions by performing independent component analysis on tracking fibers and clustering thalamus-related FC maps. We then analyzed abnormal FC in each subdivision in JME compared with healthy controls, and we investigated their associations with clinical features. Eight thalamic sub-regions identified in the current study showed unbalanced thalamic FC in JME: decreased FC with the superior frontal gyrus and enhanced FC with the supplementary motor area in the posterior thalamus increased thalamic FC with the salience network (SN) and reduced FC with the default mode network (DMN). Abnormalities in thalamo-prefrontocortical networks might be related to the propagation of generalized spikes with frontocentral predominance in JME, and the network connectivity differences with the SN and DMN might be implicated in emotional and cognitive defects in JME. JME was also associated with enhanced FC among thalamic sub-regions and with the basal ganglia and cerebellum, suggesting the regulatory role of subcortical nuclei and the cerebellum on the thalamo-cortical circuit. Additionally, increased FC with the pallidum was positive related with the duration of disease. The present study provides emerging evidence of FC to understand that specific thalamic subdivisions contribute to the abnormalities of thalamic-cortical networks in JME. Moreover, the posterior thalamus could play a crucial role in generalized epileptic activity in JME.

Juvenile myoclonic epilepsy may be a disorder of cortex rather than thalamus: An effective connectivity analysis.

Although juvenile myoclonic epilepsy has been considered as a disorder of thalamo-cortical circuit, it is not determined the causality relationship between thalamus and cortex. The aim of this study was to evaluate whether juvenile myoclonic epilepsy is a disorder of thalamus or cortex. Twenty-nine patients with juvenile myoclonic epilepsy and 20 normal controls were enrolled in this study. In addition, we included 10 patients with childhood absence epilepsy as a disease control group. Using whole-brain T1-weighted MRIs, we analyzed the volumes of the structures, including hippocampus, thalamus, and total cortex, with FreeSurfer 5.1. We also investigated the effective connectivity among these structures using SPSS Amos 21 based on these volumetric measures. The structural volumes in juvenile myoclonic epilepsy were not different from those in normal controls. There was a statistically significant effective connectivity from the total cortex to the thalamus in the patients with juvenile myoclonic epilepsy. In addition, a significant effective connectivity from the hippocampus to the ipsilateral thalamus was revealed. Unlike the patients with juvenile myoclonic epilepsy, neither the patients with childhood absence epilepsy nor normal controls had a significant effective connectivity from the total cortex to the thalamus or from the thalamus to the cortex. The connectivity of brain in patients with juvenile myoclonic epilepsy could be different from that in patients with childhood absence epilepsy, and the cortex rather than the thalamus might play a critical role in the pathogenesis of juvenile myoclonic epilepsy.

Heterogeneity of anatomic regions by MR volumetry in juvenile myoclonic epilepsy.

OBJECTIVE: To investigate brain volumes in patients with well-characterized juvenile myoclonic epilepsy (JME). MATERIALS AND METHODS: We studied the MRI images of seventeen subjects with EEG and clinically defined JME and seventeen age- and sex-matched controls using voxel-based morphometry (VBM) and automated and manual volumetry. RESULTS: We found no significant group differences in the cortical volumes by automated techniques for all regions or for the whole brain. However, we found a larger pulvinar nucleus in JME using VBM with small volume correction and a larger thalamus with manual volumetry (P = 0.001; corrected two-tailed t-test). By analysing the individual subjects, we determined that considerable heterogeneity exists even in this highly selected group. Histograms of all JME and matched control regions' volumes showed more subjects with JME had smaller hippocampi and larger thalami (P < 0.05; chi-square). Subjects in whom the first seizure was absence were more likely to have smaller hippocampi than their matched control, while those without absences showed no differences (P < 0.05, chi-square). CONCLUSIONS: There is ample evidence for frontal cortical thalamic network changes in JME, but subcortical structural differences were more distinct in this group. Given the heterogeneity of brain volumes in the clinical population, further advancement in the field will require the examination of stringent genetically controlled populations.