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Our understanding of cingulate cortex function is limited. As a method for locating the epileptogenic zone, direct electrical cortical stimulation (ECS) provides an opportunity to understand the functional localization of the cingulate cortex. This study aimed to learn more about the function of the cingulate cortex by analyzing a large body of data from our center and by reviewing existing literature on cortical mapping. We retrospectively analyzed the ECS data of 124 patients with drug‐resistant epilepsy who had undergone electrode implantation in the cingulate cortex. The standard stimulation parameters included a biphasic pulse and bipolar stimulation at 50 Hz. Furthermore, we reviewed existing studies on cingulate responses elicited by the ECS and compared them with our results. A total of 329 responses were evoked in 276 contacts using ECS. Of these, 196 were physiological functional responses, which included sensory, affective, autonomic, language, visual, vestibular, and motor responses, along with a few other sensations. Sensory, motor, vestibular, and visual responses were concentrated in the cingulate sulcus visual area (CSv). Furthermore, 133 epilepsy‐related responses were evoked, most of which were concentrated in the ventral cingulate cortex. No responses were evoked by 498 contacts. Furthermore, the comparison of our ECS results with those reported in 11 comprehensive reviews revealed that the cingulate cortex is involved in complicated functions. The cingulate cortex is involved in sensory, affective, autonomic, language, visual, vestibular, and motor functions. The CSv is an integrating node of sensory, motor, vestibular, and visual systems. [ABSTRACT FROM AUTHOR]

Background: Vagus nerve stimulation (VNS) is an effective treatment for patients with refractory epilepsy, yet with varied predictive factors and heterogeneous long-term outcomes. Adjustment of VNS parameters is critical for obtaining favorable efficacy. In this study, we aimed to investigate the long-term outcomes and the possible predictive factors of VNS in patients with refractory epilepsy. Methods: Eighty-six patients (59 males and 27 females) who underwent VNS implantation for treatment of refractory epilepsy between May 2016 and May 2017 at five Epilepsy Centers were enrolled. The clinical data, including sex, age at epilepsy onset, VNS implantation, epilepsy duration, seizure type, MRI findings, history of neurosurgical operations, and responder rate (responders were those with ≥50% seizure reduction), were analyzed. Results: Four-year follow-up data were available for 76 patients (53 males and 23 females). The mean current intensity at the last follow-up was 1.8 ± 0.3 mA (range: 0.75–2.5 mA). The mean seizure reduction was 36.2% at 6 months, 38.5% at 1 year, 69.4% at 3 years, and 56.7% at 4 years. A favorable outcome of ≥50% reduction in seizure frequency occurred in 40.0% of the patients at 6 months, 55.9% at 1 year with 4 patients being seizure-free, 63.2% at 3 years with 5 patients being seizure-free, and 68.4% at 4 years with 5 patients being seizure-free. Earlier onset age (P < 0.001) and shorter duration (P = 0.042) were associated with favorable prognosis. Compared with generalized tonic-clonic seizures, tonic seizures had a favorable outcome (P = 0.026). Twenty-three patients underwent neurosurgical operations before VNS implantation, and the responder rate was 60.9% at the last follow-up. Conclusions: VNS is an adjunctive and effective treatment for patients with refractory epilepsy who are not good candidates for surgical resection or have failed to respond to surgical treatment. The stimulation efficacy increases over time after implantation, and earlier exposure to VNS improves the prognosis. [ABSTRACT FROM AUTHOR]

This study aimed to analyze the topological characteristics of brain structural network in pediatric epilepsy patients with vagus nerve stimulation (VNS) by applying graph theoretical approaches. Nine patients with generalized seizures and eight normal controls (NC) were enrolled. Based on diffusion tensor imaging, graph theory analysis was used to characterize the topological properties in preoperative patients (EP-pre), postoperative patients (EP-post) and NC. The global properties included clustering coefficient (Cp), shortest path length (Lp), small-worldness (γ, λ, δ), global network efficiency (Eg) and local network efficiency (Eloc). The regional properties included degree centrality (DC), nodal efficiency (NE), nodal local efficiency (NLE) and nodal shortest path length (Np). Two sample t -test and paired sample t -test were utilized to compare properties difference. All three groups followed small-world characteristics. There was no significant difference in small-worldness, Cp, Lp, Eg or Eloc between EP-pre and EP-post. Compared with EP-pre: DC in EP-post decreased in the right cuneus and right temporal gyri, while increased in the right paracentral lobule; NE in EP-post decreased in the left dorsolateral superior frontal gyrus, right cuneus, right supramarginal gyrus, and right rolandic operculum, while increased in the right paracentral lobule; NLE in EP-post decreased in the left posterior cingulate gyrus and right supramarginal gyrus, while increased in the left parahippocampal gyrus; NP in EP-post decreased in the right paracentral lobule, while increased in the right cuneus. VNS causes topological characteristics changes in pediatric patients with generalized seizures through regulating regional properties in some brain structures. [ABSTRACT FROM AUTHOR]

Background: Cervical vagus nerve stimulation (VNS) is an effective neuromodulation therapy for patients with drug‐resistant epilepsy (DRE). The previous studies reported that VNS may reduce seizures by regulating the functional connectivity (FC) between cortical and subcortical regions. However, no studies on brainstem have been done in responders who achieved ≥50% seizure reduction following VNS. Methods: Eight healthy controls and eight patients who became responders after 3 months of operation were enrolled in this study. Resting‐state functional MRI (rs‐fMRI) was performed, and two sample and paired sample t test were, respectively, used to detect altered FC between brainstem and cortical/subcortical regions between controls and patients, between preoperative and postoperative patients. Results: In the control group, regions with highest FC to brainstem included bilateral anterior cingulate gyri, left basal ganglia, left insula, left cuneus, right precuneus, and bilateral cerebellum. In preoperative patients, right frontal middle gyrus, bilateral basal ganglia, and right cerebellum were showed highest FC to brainstem. Compared with the controls, preoperative patients exhibited increased FC in bilateral inferior frontal gyri, right temporal cortex, while decreased FC in left insula, left postcentral gyrus, right posterior cingulate gyrus, right precuneus, and left superior parietal gyrus. In postoperative patients, regions with increased FC to brainstem were left insula, left precuneus and left cuneus, and those with decreased FC were right inferior occipital gyrus and right cerebellum. Conclusions: Recurrent seizures caused disturbances in brainstem‐cortical/subcortical FC, especially in motor executive function related regions and default mode network. VNS could reorganize the altered FC between brainstem and insula, precuneus, and cerebellum in responders. [ABSTRACT FROM AUTHOR]

• Less than 1.5 mA may not affect hippocampal-thalamic functional connectivity. • Shorter than 3 months may not affect hippocampal-thalamic functional connectivity. • VNS may be suitable for patients with low left hippocampal-left thalamic connections. • VNS may be suitable for patients with low left hippocampal-right thalamic connections. • Current intensity should increase > 1.5 mA to cause functional connectivity changes. Vagal nerve stimulation (VNS) is widely used as an auxiliary treatment for patients with intractable epilepsy. Up to now, the therapeutic mechanisms remain elusive, and no surgical prediction criteria has been proposed. In this study, the resting-state functional magnetic resonance imaging (rs-fMRI) was chosen to explore aberrant intrinsic brain activity and functional connections in 14 epilepsy patients with VNS stimulators between March 2019 and April 2019. Seven patients who ≥ 50 % seizure reduction was defined as responders, and seven non-responders. All patients had got rs-fMRI scan before and after operation. The hippocampal - thalamic connections (hippocampal and thalamus as regions of interest) were detected to evaluate the diversity in all 14 patients and seven responders with stimulation at 0, 0.5, 1.0, and 1.5 mA. The hippocampal-thalamic connections before operation were also examined between responders and non-responders. The preoperative left hippocampal - left thalamic connections and left hippocampal - right thalamic connections in responders were lower than those in non-responders (p < 0.05). While, there was no significant difference in hippocampal - thalamic connections in all epilepsy patients or responders with different current intensities (p > 0.05). VNS may be more suitable for patients with lower left hippocampal - left thalamic connections and/or left hippocampal - right thalamic connections. The current intensity ≤ 1.5 mA and stimulation time ≤ 3 months may not cause significant changes in hippocampal-thalamic functional connectivity. [ABSTRACT FROM AUTHOR]

• VNS may cause thalamus-precentral gyrus FC changes in DRE patients. • Enhanced FC was observed between bilateral thalamus and bilateral precentral gyrus in responders. • Decreased FC was observed between bilateral thalamus and bilateral precentral gyrus in nonresponders. Vagal nerve stimulation (VNS) is an effective treatment for patients with drug-resistant epilepsy who are unsuitable for surgical epilepsy treatment. However, the mechanism of action of VNS remains unclear, and the efficacy of VNS treatment regarding seizure frequency reduction cannot be assessed before surgery. This study measured changes in functional connectivity between thalamus and precentral gyrus which are activated as vital targets of deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS) using resting-state functional MRI to evaluate the effects of VNS. 16 epilepsy patients who underwent VNS were collected and scanned by resting-state functional MRI before and after operation. The functional connections (regions of interest: thalamus, precentral gyrus) were examined. After three months of stimulation, there were eight responders (≥50 % seizure reduction) and eight non-responders to VNS. No significant difference in thalamus-precentral gyrus functional connectivity was found between responders and nonresponders before operation. Enhanced functional connections were observed between bilateral thalamus and bilateral precentral gyrus in responders, which decreased in nonresponders, while functional connections between bilateral thalamus decreased in both responders and nonresponders. Short-term stimulation may cause thalamus-precentral gyrus functional connectivity changes in DRE patients, and control seizures by enhancing functional connections between bilateral thalamus and bilateral precentral gyrus. [ABSTRACT FROM AUTHOR]

• VNS is a valid treatment for DRE patients. • Epilepsy duration is an independent predictor of response to VNS. • VNS is helpful for patients with an epilepsy duration < 12.5 years, especially those with a duration of 5–12.5 years. Vagus nerve stimulation (VNS) is a form of neuromodulation that has been used to treat individuals with drug-resistant epilepsy (DRE). Although many retrospective studies have explored the predictors of VNS treatment efficacy, the data have been inconsistent, and no VNS studies to date have used the 2017 ILAE epilepsy classification system. In this single-center retrospective study, we reviewed data from 77 patients who underwent VNS implantation between 2011 and 2019. Data regarding patient gender, epilepsy duration, age at implantation, numbers of antiepileptic drugs, MRI findings, history of craniotomy, epilepsy classification, stimulation current intensity, stimulation duration, and responder status (responders were those with ≥ 50 % seizure frequency reduction) were analyzed via univariate analysis or receiver operating characteristic (ROC) curves to select possible related factors and classification cutoffs. Then, binary logistic regression analysis was used to identify the variables that significantly predicted responder status. In the inclusion group, the mean stimulation duration, mean seizure reduction, and responder rate was 47.2 months, 42.6 %, and 50.6 %, respectively. The univariate analysis indicated that seizure types and MRI findings might be related categorical variables (P < 0.05). After performing binary logistic regression and creating ROC curves for the continuous variables, epilepsy duration was chosen as a related variable, with 12.5 years as the classification cutoff (P = 0.002). A binary logistic regression of risk factors showed that epilepsy duration was significantly related to responder status (P < 0.05). Epilepsy duration is an independent predictor for responders to VNS. VNS is more likely to be efficacious in those with an epilepsy duration < 12.5 years, especially those with a duration of 5–12.5 years. [ABSTRACT FROM AUTHOR]

To explore the effect of vagal nerve stimulation (VNS) on spontaneous brain activity in patients with drug-resistant epilepsy (DRE). 15 patients and eight healthy controls (HC) were enrolled and scanned by resting-state functional MRI to investigate changes in the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo). A two-sample t -test or paired sample t -test was used to compare activity between the HCs, preoperative patients (EP-pre), and postoperative patients (EP-post). We also performed correlation analyses to examine the seizure improvement ratio. The voxel-level analyses indicated that, compared with the HC, the EP-pre group exhibited decreased or increased fALFF and ReHo in the frontal cortex, temporal cortex, precentral/postcentral gyrus, amygdala, insula, cerebellum, and lingual gyrus. Furthermore, compared with the EP-pre group, the EP-post group exhibited decreased or increased fALFF and ReHo in the frontal cortex, temporal cortex, precentral gyrus, insula, anterior/median cingulate gyri, and cerebellum. The regions of interest-level analyses indicated that, compared with HC, the EP-pre group exhibited decreased fALFF or ReHo in the caudate nucleus, supramarginal gyrus, precuneus and middle temporal gyrus. Furthermore, compared with the EP-pre group, the EP-post group exhibited increased fALFF or ReHo in the olfactory cortex, gyrus rectus, and superior temporal gyrus. Increased ReHo in the right superior or middle temporal gyrus was positively correlated with the improvement ratio. Altered regional activity in DRE patients was reorganized after 3 months of stimulation. Increased ReHo in the right superior or middle temporal gyrus was implicated in VNS-induced improvement in seizure frequency. [ABSTRACT FROM AUTHOR]