Identification of abnormal closed-loop pathways in patients with MRI-negative pharmacoresistant epilepsy.

Epilepsy is a disorder of brain networks, that is usually combined with cognitive and emotional impairment. However, most of the current research on closed-loop pathways in epilepsy is limited to the neuronal level or has focused only on known closed-loop pathways, and studies on abnormalities in closed-loop pathways in epilepsy at the whole-brain network level are lacking. A total of 26 patients with magnetic resonance imaging-negative pharmacoresistant epilepsy (MRIneg-PRE) and 26 healthy controls (HCs) were included in this study. Causal brain networks and temporal-lag brain networks were constructed from resting-state functional MRI data, and the Johnson algorithm was used to identify stable closed-loop pathways. Abnormal closed-loop pathways in the MRIneg-PRE cohort compared with the HC group were identified, and the associations of these pathways with indicators of cognitive and emotional impairments were examined via Pearson correlation analysis. The results revealed that the abnormal stable closed-loop pathways were distributed across the frontal, parietal, and occipital lobes and included altered functional connectivity values both within and between cerebral hemispheres. Four abnormal closed-loop pathways in the occipital lobe were associated with emotional and cognitive impairments. These abnormal pathways may serve as biomarkers for the diagnosis and guidance of individualized treatments for MRIneg-PRE patients.

Structural and functional changes in the default mode network in drug-resistant epilepsy.

PURPOSE: To investigate brain network properties and connectivity abnormalities of the default mode network (DMN) in drug-resistant epilepsy (DRE). The study was based on probabilistic fiber tracking and functional connectivity (FC) analysis, to explore the structural and functional connectivity patterns change between frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE). METHODS: A total of 33 DRE patients (18 TLE and 15 FLE) and 30 healthy controls (HCs) were recruited. The volume fraction of the septal brain region of the DMN in DRE was calculated using FreeSurfer. The FC analysis was performed using Data Processing and Analysis for Brain Imaging in MATLAB. The structural connections between brain regions of the DMN were calculated based on probabilistic fiber tracking. RESULTS: The left precuneus (PCUN) volumes in epilepsy groups were lower than that in HCs. Compared with FLE, TLE showed reduced FC between the left hippocampus (HIP) and PCUN/medial frontal gyrus, and between the right inferior parietal lobule (IPL) and right superior temporal gyrus. Compared with HCs, FLE showed increased FCs between the right IPL and occipital lobe, and between the left superior frontal gyrus (SFG) and bilateral superior temporal gyrus. In terms of structural connectivity, TLE exhibited increased connectivity strength between the left SFG and left PCUN, and showed reduced connection strength between the left HIP and left posterior cingulate gyrus/left PCUN, when compared with the FLE. CONCLUSIONS: TLE and FLE patients showed structural and functional changes in the DMN. Compared with FLE patients, the TLE patients showed reduced structural and functional connection strengths between the left HIP and PCUN. These alterations in connection strengths holds promise for the identification of TLE and FLE.

Neurovascular coupling changes in patients with magnetic resonance imaging negative focal epilepsy.

Brain neuron activity is closely related to cerebral blood flow (CBF) changes. Alterations in the regional homogeneity (ReHo) and CBF occur in patients with magnetic resonance imaging negative focal epilepsy (FEP-MRI-). However, the coupling alterations of ReHo and CBF in FEP-MRI- remain unclear. The study aims to explore neurovascular coupling alterations and their clinical implication in FEP-MRI-. We collected resting-state magnetic resonance imaging (MRI) data from 31 healthy controls (HCs) and 48 patients with FEP-MRI-,including three-dimensional (3D) T1-weighted imaging, 3D arterial spin labeling (ASL) imaging,and resting-state functional MRI (rs-fMRI). The CBF and ReHo values were calculated from the ASL and rs-fMRI data, respectively. The CBF/ReHo ratio per voxel and whole-brain CBF-ReHo coupling were compared between the two groups. Correlation analysis involved the CBF/ReHo ratio and clinical indicators in FEP-MRI-. Patients with FEP-MRI- showed significantly increased cross-subject CBF-ReHo and global cross-voxel CBF-ReHo coupling. The CBF/ReHo ratio was higher in the bilateral orbitofrontal gyrus, right parietal lobe, and right middle frontal gyrus of patients with FEP-MRI-. Nevertheless, this ratio was lower in the bilateral supplementary motor areas, the left middle and posterior cingulate gyrus, and the right central sulcus cover. The CBF/ReHo ratio was markedly correlated with cognitive function, memory, intelligence, and epilepsy duration in the above abnormal brain regions. CBF/ReHo ratio may be useful as an indicator of neuropathological mechanisms. These results support the hypothesis that CBF/ReHo ratio relates to the neuropathological mechanisms of FEP-MRI-. Furthermore, it offers new perspectives for studying the mechanisms of MRI-negative epilepsy.

Immediate Effects of Vagal Nerve Stimulation in Drug-Resistant Epilepsy Revealed by Magnetoencephalographic Recordings.

Objective: Vagus nerve stimulation (VNS) has been a neuromodulatory option for treating drug-resistant epilepsy (DRE), but its mechanism remains unclear. To obtain insight into the mechanism by which VNS reduces epileptic seizures, the immediate effects of VNS in brain networks of DRE patients were investigated when the patients' vagal nerve stimulators were turned on. Methods: The brain network properties of 14 DRE patients with a vagal nerve stimulator and 14 healthy controls were evaluated using magnetoencephalography recordings for 6 main frequency bands. Results: Compared with healthy controls, DRE patients exhibited significant increases in functional connectivity in the theta, alpha, beta, and gamma bands and significant reductions in the small-world measure in the theta and beta bands. During periods when patients' vagal nerve stimulators were turned on, DRE patients showed significant reductions in functional connectivity in the theta and alpha bands and a significant increase in the small-world measure in the theta band when compared with periods when patients' vagal nerve stimulators were turned off. Conclusions: Our results indicate that the brain networks of DRE patients were pathologically hypersynchronous and instantaneous VNS can decrease the synchronization of brain networks of epileptic patients, which might play a key role in the mechanism by which VNS reduces epileptic seizures. In the theta band, instantaneous VNS can increase the network efficiency of DRE patients, and the increment in network efficiency may be helpful for improving brain cognitive function in epileptic patients. Impact statement For the first time, we investigated the immediate effects of vagus nerve stimulation (VNS) in the brain networks of drug-resistant epilepsy patients using magnetoencephalography. Our results show that instantaneous VNS can decrease the hypersynchronization of epileptic networks and increase the network efficiency of epileptic patients. Our results are helpful in understanding the mechanism of action by which VNS reduces epileptic seizures and improves the cognitive function in epileptic patients and the brain network reorganization caused by long-term VNS.