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.

PgDDS Changes the Plant Growth of Transgenic Aralia elata and Improves the Production of Re and Rg3 in Its Leaves.

Aralia elata (Miq.) Seem is a medicinal plant that shares a common pathway for the biosynthesis of triterpenoid saponins with Panax ginseng. Here, we transferred the dammarenediol-II synthase gene from P. ginseng (PgDDS; GenBank: AB122080.1) to A. elata. The growth of 2-year-old transgenic plants (L27; 9.63 cm) was significantly decreased compared with wild-type plants (WT; 74.97 cm), and the leaflet shapes and sizes of the transgenic plants differed from those of the WT plants. Based on a terpene metabolome analysis of leaf extracts from WT, L13, and L27 plants, a new structural skeleton for ursane-type triterpenoid saponins was identified. Six upregulated differentially accumulated metabolites (DAMs) were detected, and the average levels of Rg3 and Re in the leaves of the L27 plants were 42.64 and 386.81 µg/g, respectively, increased significantly compared with the WT plants (15.48 and 316.96 µg/g, respectively). Thus, the expression of PgDDS in A. elata improved its medicinal value.

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.

Activation of brain lactate receptor GPR81 aggravates exercise-induced central fatigue.

Exercise-induced fatigue is a complex physiological phenomenon and is greatly influenced by central mechanisms in brain. As one of the most abundant circulating carbon metabolites, l-lactate in brain has been considered to be an important supplementary fuel during exercise; however, whether it plays a signaling role in fatigue remains largely obscure. In this study, our results initially revealed that brain l-lactate levels were increased after an exhaustive swimming session in several brain regions including motor cortex, hippocampus, and cerebellum. Then, we examined the specific role of brain lactate receptor, also known as hydroxycarboxylic acid receptor 1 (GPR81), in exercise-induced fatigue. We found that intracerebroventricular injection of either d-lactate (an enantiomer that could mediate activation of GPR81 as l-lactate) or a potent GPR81 agonist 3-chloro-5-hydroxybenzoic acid (CHBA), significantly decreased the swimming time to fatigue. After being subjected to the same weight-loaded swimming for 30 min, no obvious changes of blood lactate levels, gastrocnemius pAMPK/AMPK ratio, and glycogen contents were observed between intracerebroventricular CHBA-injected mice and vehicle-treated ones, which suggested a comparable degree of peripheral fatigue. Meanwhile, there were higher extracellular γ-aminobutyric acid (GABA) levels and lower extracellular glutamate levels and glutamate/GABA ratio in motor cortex of the intracerebroventricular CHBA-injected mice than that of vehicle-treated ones, indicating a greater extent of central fatigue in CHBA-injected mice than that in vehicle animals. Collectively, our results suggested that an increased level of brain l-lactate acts as a signaling molecule via activating GPR81, which in turn exacerbates central fatigue during exercise.

Evaluation of Brain Network Properties in Patients with MRI-Negative Temporal Lobe Epilepsy: An MEG Study.

Abnormal functional brain networks of temporal lobe epilepsy (TLE) patients with structural abnormalities may partially reflect structural lesions rather than either TLE per se or functional compensatory processes. In this study, we sought to investigate the brain-network properties of intractable TLE patients apart from the effects of structural abnormalities. The brain network properties of 20 left and 23 right MRI-negative TLE patients and 22 healthy controls were evaluated using magnetoencephalographic recordings in six main frequency bands. A slowing of oscillatory brain activity was observed for the left or right TLE group vs. healthy controls. The TLE groups presented significantly increased functional connectivity in the delta, theta, lower alpha and beta bands, and significantly greater values in the normalized clustering coefficient and path length, and significantly smaller values in the weighted small-world measure in the theta band when compared to healthy controls. Alterations in global and regional band powers can be attributed to spectral slowing in TLE patients. The brain networks of TLE patients displayed abnormally high synchronization in multi-frequency bands and shifted toward a more regular architecture with worse network efficiency in the theta band. Without the contamination of structural lesions, these significant findings can be helpful for better understanding of the pathophysiological mechanism of TLE. The theta band can be considered as a preferred frequency band for investigating the brain-network dysfunction of MRI-negative intractable TLE patients.

Changes in resting-state cerebral blood flow and its connectivity in patients with focal to bilateral tonic-clonic seizures.

Arterial spin labeling (ASL) is an important tool for understanding cerebral perfusion in epilepsy patients. The aim of this study was to explore patterns of change in cerebral blood flow (CBF) and CBF connectivity in patients with focal to bilateral tonic-clonic seizures (FBTCS). High-resolution three-dimensional (3-D) T1-weighted and 3-D pseudo-continuous ASL magnetic resonance imaging (MRI) was collected from 32 patients with FBTCS and 16 healthy volunteers using a 3.0 T MRI scanner. Cerebral blood flow and its connectivity were compared between the FBTCS and control group. Correlation analysis was used to explore relationships of CBF and its connectivity changes with clinical parameters. Cerebral blood flow data of spatial standardization and normalization were used to improve statistical power. Patients with FBTCS exhibited increased CBF in the bilateral thalamus, caudate nucleus, olfactory cortex, and gyrus rectus, but decreased CBF in the bilateral supplementary motor areas (SMA) and middle cingulate cortex (MCC). Patients with FBTCS showed significant positive correlation between CBF and gray matter volume (GMV) in bilateral SMA and MCC. No significant correlations between CBF and clinical parameters were found among FBTCS patients. The anterior cingulate cortex (ACC) showed positive CBF connectivity with the bilateral SMA and MCC, and these CBF connectivity measures differed significantly between groups (cluster-level, FWE-corrected, P < 0.001). These findings suggest that patients with FBTCS have changes in cerebral CBF and CBF connectivity, which may relate to the underlying neuropathology of FBTCS.

Passive Q-switching induced by few-layer MoTe2 in an Yb:YCOB microchip laser.

We report on passive Q-switching action induced by a few-layer MoTe2 saturable absorber in an Yb:YCa4O(BO3)3 (Yb:YCOB) microchip laser. With a sapphire-based few-layer MoTe2 incorporated into the 4 mm long plane-parallel resonator of the Yb:YCOB microchip laser, efficient stable passively Q-switched operation was achieved under output couplings of 40%-70%, producing, at an incident pump power of 5.0 W, an average output power of 1.58 W at a repetition rate of 704 kHz with a slope efficiency of 36%; the pulse energy and peak power were respectively 2.25 µJ and 40.8 W, while the shortest pulse duration obtained was 52 ns.

Few-layer Bi2Te3: an effective 2D saturable absorber for passive Q-switching of compact solid-state lasers in the 1-µm region.

An experimental investigation was carried out to evaluate the potential of few-layer Bi2Te3 topological insulator in use as a saturable absorber for passive Q-switching of compact solid-state lasers in the 1-µm spectral region. By incorporating a sapphire-based few-layer Bi2Te3 sample into a Yb:LuPO4 laser that was formed with a 4-mm plane-parallel resonator, we realized efficient, high-power, high-repetition-rate pulsed laser operation. Depending on the output coupling utilized, single- or dual-wavelength laser action could be achieved. A maximum output power of 5.02 W at 1014.5 nm was produced at a pulse repetition rate of 1.67 MHz, with an optical-to-optical efficiency of 41% and a slope efficiency of 54%; while operating at 1004.9/1012.7 nm, the pulsed laser could produce an output power of 3.94 W at 1.38 MHz, with a pulse duration being as short as 34 ns. The largest pulse energy and highest peak power achieved were 3.0 µJ and 85.3 W. The results demonstrated in our experiment reveal the great potential of the few-layer Bi2Te3 topological insulator in the development of pulsed compact solid-state lasers in the 1-µm region.

Watt-level passively Q-switched Yb:LuPO4 miniature crystal laser with few-layer MoS2 saturable absorber.

We demonstrate a Yb:LuPO4 miniature crystal laser that is formed with a 5 mm long plane-parallel resonator, and is passively Q-switched by a few-layer MoS2 saturable absorber. With 6.53 W of pump power absorbed, an average output power of 2.06 W at 1020.8 nm is generated at a pulse repetition rate of 429 kHz with a slope efficiency of 50%; the resulting pulse energy, duration, and peak power are respectively 4.8 µJ, 83 ns, and 57.8 W. While operating at 1010.5 nm, the laser is capable of producing an average output power of 1.53 W at a repetition rate of 870 kHz, with pulse duration being shortened to 61 ns. These results represent a significant progress in the development of Yb- or Nd-ion lasers passively Q-switched by two-dimensional MoS2.

Multi-watt sub-30 ns passively Q-switched Yb:LuPO4/WS2 miniature laser operating under high output couplings.

We report on a miniature Yb:LuPO4 crystal laser at 1.01 µm that is passively Q-switched with a sapphire-based few-layer WS2 saturable absorber, and that can be operated under very high output couplings (≥80%). With 12.6 W of pump power absorbed, an average output power of 4.35 W is generated at a repetition rate of 1.33 MHz with a slope efficiency of 47%. The maximum pulse energy and highest peak power achieved are 3.41 µJ and 110 W, respectively; while the shortest pulse duration obtained is 28.6 ns. To the best of our knowledge, these results represent the highest output power and shortest pulse duration ever achieved in the 1 µm region from solid-state lasers passively Q-switched by using two-dimensional saturable absorbers.

High-energy passively Q-switched laser operation of Yb:Ca3La2(BO3)4 disordered crystal.

Efficient high-energy passively Q-switched laser operation was demonstrated with Yb:Ca3La2(BO3)4 disordered crystal, producing an average output power of 3.0 W at 1018.7 nm, at a pulse repetition frequency of 5.0 kHz; the resulting pulse energy, duration, and peak power were 600 µJ, 5.3 ns, and 113.2 kW, respectively.

High-energy passively Q-switched operation of Yb:GdCa(4)O(BO(3))(3) laser with a GaAs semiconductor saturable absorber.

High-energy passively Q-switched operation of a Yb:GdCa(4)O(BO(3))(3) laser is demonstrated, with a GaAs crystal plate acting as saturable absorber. An average output power of 1.31 W at 1027 nm is produced at a pulse repetition rate of 1.92 kHz, the resulting pulse energy, duration, and peak power being respectively 0.68 mJ, 9.0 ns, and 75.6 kW. The shortest pulse duration obtained is 4.9 ns; whereas the maximum pulse energy achievable amounts to 0.83 mJ, which proves to be nearly one order of magnitude higher than ever generated from Yb or Nd lasers passively Q-switched by a GaAs saturable absorber.

Acousto-optic Q-switching laser performance of Yb:GdCa(4)O(BO(3))(3)crystal.

We report on the active Q-switching laser performance of Yb:GdCa4O(BO3)3 crystal, demonstrated by employing an acousto-optic Q-switch in a compact plano-concave resonator. Stable repetitively Q-switched operation is achieved with pulse repetition rates varying from 30 to 0.2 kHz, producing an average output power of 10.2 W at 1027.5 nm at 30 kHz of repetition rate, with an optical-to-optical efficiency of 30%. The maximum pulse energy generated at the lowest repetition rate of 0.2 kHz is 4.75 mJ, with a pulse width being 11 ns, gives rise to a peak power that amounts to 432 kW.

High-power passively Q-switched Yb:YCa4O(BO3)3 laser with a GaAs crystal plate as saturable absorber.

We report on efficient high-power passively Q-switched operation of a Yb:YCa4O(BO3)3 laser with a GaAs crystal plate acting as the saturable absorber. An average output power of 5.7 W at 1032 nm is generated at a pulse repetition rate of 166.7 kHz when the incident pump power is 26.8 W, with a slope efficiency determined to be 24.5%. The averaged pulse energy achieved is roughly 30 µJ and is increased to about 40 µJ when the output coupling used changes from 30% to 50%, while the shortest pulse width is measured to be 153 ns.

Passive mode-locking performance of mixed Nd:La(0.11)Y(0.89)VO(4) crystal.

Passive mode locking of a diode pumped Nd:La(0.11)Y(0.89)VO(4) mixed crystal laser with a semiconductor saturable absorber mirror (SESAM) was experimentally investigated for the first time to our knowledge. Stable CW mode-locking has been achieved on both a-cut and c-cut mixed crystals. In case of the a-cut crystal, when a 2% output coupler (OC) was used, the shortest pulse obtained was 4.5 ps and the highest output power was 0.94 W, while when a 6% OC was used, the shortest pulse obtained was 6.8 ps and the highest output power was 5.16 W. In the latter case the optical conversion efficiency is 38% and the slope efficiency is 40.3%, respectively; with the c-cut crystal the shortest pulse achieved was 5.5 ps. Moreover, simultaneous mode locking at two close wavelengths of 1064.3 nm and 1066.2 nm was observed on the c-cut crystal. The mode locked pulse beating generated temporal interference fringe of 0.5 THz repetition rate.

Beyond Growth Hormone: Association of Short Stature Types and Growth Hormones With Scoliosis.

STUDY DESIGN: Cross-sectional and retrospective cohort study. OBJECTIVE: We investigated the effect of 3 types of short stature [partial growth hormone deficiency (GHD), GHD, and idiopathic short stature (ISS)] and recombinant human growth hormone (rhGH) therapy on scoliosis. SUMMARY OF BACKGROUND DATA: In short stature, rhGH is widely used and the concentration of growth hormone varies among types. The epidemiologic characteristics of scoliosis and the role of rhGH in scoliosis remain unclear. PATIENTS AND METHODS: A cross-sectional study was conducted among 3896 patients with short stature (partial GHD, GHD, and ISS), and a 1:1 age and sex-matched control group with preexisting whole-spine radiographs. The cohort study included 2605 subjects who underwent radiography more than twice to assess scoliosis development, progression, and the need for bracing and surgery. Adjusted logistic regression was used to assess differences in the prevalence of scoliosis among patients with partial GHD, GHD, ISS, and controls. The Kaplan-Meier method was used to analyze the time course of scoliosis development and progression. Cox regression was applied to assess the independent factors related to scoliosis development and progression. Mendelian randomization analyses were also performed. RESULTS: Compared with controls, patients with short stature had a higher incidence of scoliosis (34.47% in partial GHD, 31.85% in GHD, 32.94% in ISS vs . 8.83% in control, P < 0.001), a higher risk of scoliosis development [hazard ratio (HR) = 1.964 in partial GHD, P < 0.001; HR = 1.881 in GHD, P = 0.001; HR = 1.706 in ISS, P = 0.001), but not a higher risk of progression, brace, or surgery. Among the 3 types of short stature, there were no differences in the incidence, development, and progression of scoliosis or the need for bracing or surgery. RhGH treatment increased the risk of scoliosis development in each short-stature group (HR = 2.673 in partial GHD, P < 0.001; HR = 1.924 in GHD, P = 0.049; HR = 1.564 in ISS, P = 0.004). Vitamin D supplementation was protective against scoliosis development (HR = 0.456 in partial GHD, P = 0.003; HR = 0.42 in GHD, P = 0.013; HR = 0.838 in ISS, P = 0.257). CONCLUSIONS: More attention should be paid to the spinal curve in patients with partial GHD, GHD, or ISS. For short stature treated with rhGH, the risk of scoliosis development was increased. Vitamin D supplementation may be beneficial for prevention. LEVEL OF EVIDENCE: Level III.

Comparation of differences in the performance of corporate social responsibility between Chinese and American pharmaceutical enterprises-based on corporate social responsibility report.

Objective: We compared Chinese and American pharmaceutical companies' corporate social responsibility (CSR) reports to determine their differences and to analyze the possible reasons for them. Methods: We took as a model the top 500 pharmaceutical companies from Torreya's (a global investment bank) list of the 1,000 most valuable pharmaceutical companies in the world. We then collected the 2020 corporate social responsibility reports of 97 Chinese and 94 American pharmaceutical companies. These reports were analyzed using software such as ROST Content Mining 6.0 and Gephi 0.92. Results: We formed a high-frequency word list, a semantic network diagram, and a high-frequency word centrality scale for the Chinese and American pharmaceutical corporate social responsibility reports. The Chinese pharmaceutical companies' corporate social responsibility reports formed a layout of "double centers and double themes," and the text paid more attention to the disclosure of environmental protection information. The American pharmaceutical companies formed a report presentation form of "three centers and two themes," focusing on corporate social responsibility information disclosures from the perspective of humanistic care. Discussion: The differences in between Chinese and American pharmaceutical companies' corporate social responsibility reports may be due to different corporate development strategies, regulatory requirements, social demands, and the concept of "corporate citizenship." This study makes recommendations for Chinese pharmaceutical companies to better fulfill their CSR at three levels: policy-making, company management, and society.

Expression of PnSS Promotes Squalene and Oleanolic Acid (OA) Accumulation in Aralia elata via Methyl Jasmonate (MeJA) Induction.

Aralia elata is an important herb due to the abundance of pentacyclic triterpenoid saponins whose important precursors are squalene and OA. Here, we found that MeJA treatment promoted both precursors accumulation, especially the latter, in transgenic A. elata, overexpressing a squalene synthase gene from Panax notoginseng(PnSS). In this study, Rhizobium-mediated transformation was used to express the PnSS gene. Gene expression analysis and high-performance liquid chromatography (HPLC) were used to identify the effect of MeJA on squalene and OA accumulation. The PnSS gene was isolated and expressed in A. elata. Transgenic lines showed a very high expression of the PnSS gene and farnesyl diphosphate synthase gene (AeFPS) and a slightly higher squalene content than the wild-type, but endogenous squalene synthase (AeSS), squalene epoxidase (AeSE), and ß-amyrin synthase (Aeß-AS) gene were decreased as well as OA content. Following one day of MeJA treatment, the expression levels of PeSS, AeSS, and AeSE genes increased significantly. On day 3, the maximum content of both products reached 17.34 and 0.70 mg·g-1, which increased 1.39- and 4.90-fold than in the same lines without treatment. Transgenic lines expressing PnSS gene had a limited capability to promote squalene and OA accumulation. MeJA strongly activated their biosynthesis pathways, leading to enhance yield.

Efficacy and safety of perampanel monotherapy in Chinese patients with focal-onset seizures: A single-center, prospective, real-world observational study.

OBJECTIVE: Efficacy and safety of perampanel monotherapy for treating focal-onset seizures (FOS) has been barely studied in China. This observational study aimed to evaluate the efficacy and safety of perampanel monotherapy in treating Chinese patients with FOS. METHODS: This single-center, prospective, real-world observational study enrolled patients aged ≥4 years with FOS who visited the Epilepsy Out-Patient Clinic of Nanjing Brain Hospital affiliated to Nanjing Medical University from January 2020 to December 2021. All patients were treated with perampanel monotherapy. Seizure-freedom rates after 6 and 12 months of treatment were calculated. Adverse events (AEs) were recorded. RESULTS: Seventy patients with FOS were enrolled. The mean maintenance perampanel dose was 4.64 ± 1.55 mg/day. The 6- and 12-month retention rates of perampanel monotherapy were 78.6% (55/70) and 70.0% (49/70), respectively. The 6- and 12-month seizure-freedom rates were 69.84% (44/63) and 65.08% (41/63), respectively. Patients with focal to bilateral tonic-clonic seizures had significantly higher 6-month and numerically higher 12-month seizure freedom rates than patients with focal impaired awareness seizures (P = 0.046 and P = 0.204, respectively). Twenty-six (37.1%) patients experienced treatment-emergent AEs, and the most common AE was dizziness. Four (5.7%) patients withdrew from the study due to AEs. No new safety concern was observed. SIGNIFICANCE: This is the first prospective study on the efficacy and safety of perampanel monotherapy in treating Chinese patients with FOS, and perampanel monotherapy was effective and safe in treating Chinese patients aged ≥4 years with FOS up to 12 months. More multicenter, real-world studies with large sample sizes and longer follow-ups are needed to further evaluate the long-term efficacy and safety of perampanel monotherapy.

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.