The role of magnetoencephalography in preoperative localization and postoperative outcome prediction in patients with posterior cortical epilepsy.

OBJECTIVE: We aimed to explore the value of magnetoencephalography in the presurgical evaluation of patients with posterior cortex epilepsy. METHODS: A total of 39 patients with posterior cortex epilepsy (PCE) and intact magnetoencephalography (MEG) images were reviewed from August 2019 to July 2022. MEG dipole clusters were classified into single clusters, multiple clusters, and scatter dipoles based on tightness criteria. The association of the surgical outcome with MEG dipole classifications was evaluated using Fisher's exact tests. RESULTS: Among the 39 cases, there were 24 cases of single clusters (61.5%), nine cases of multiple clusters (23.1%), and six cases of scattered dipoles (15.4%). Patients with single dipole clusters were more likely to become seizure-free. Among single dipole cluster cases (n = 24), complete MEG dipole resection yielded a more favorable surgical outcome than incomplete resection (83.3% vs. 16.7%, p = 0.007). Patients with concordant MRI and MEG findings achieved a significantly more favorable surgical outcome than discordant patients (66.7% vs. 33.3%, p = 0.044), especially in single dipole cluster patients (87.5% vs. 25.0%, p = 0.005). SIGNIFICANCE: MEG can provide additional valuable information regarding surgical candidate selection, epileptogenic zone localization, electrode implantation schedule, and final surgical planning in patients with posterior cortex epilepsy.

Symptomatic responses elicited by electrical stimulation of the cingulate cortex: Study of a cohort of epileptic patients and literature review.

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.

Deep brain stimulation for patients with refractory epilepsy: nuclei selection and surgical outcome.

Objective: By studying the surgical outcome of deep brain stimulation (DBS) of different target nuclei for patients with refractory epilepsy, we aimed to explore a clinically feasible target nucleus selection strategy. Methods: We selected patients with refractory epilepsy who were not eligible for resective surgery. For each patient, we performed DBS on a thalamic nucleus [anterior nucleus of the thalamus (ANT), subthalamic nucleus (STN), centromedian nucleus (CMN), or pulvinar nucleus (PN)] selected based on the location of the patient's epileptogenic zone (EZ) and the possible epileptic network involved. We monitored the clinical outcomes for at least 12 months and analyzed the clinical characteristics and seizure frequency changes to assess the postoperative efficacy of DBS on the different target nuclei. Results: Out of the 65 included patients, 46 (70.8%) responded to DBS. Among the 65 patients, 45 underwent ANT-DBS, 29 (64.4%) responded to the treatment, and four (8.9%) of them reported being seizure-free for at least 1 year. Among the patients with temporal lobe epilepsy (TLE, n = 36) and extratemporal lobe epilepsy (ETLE, n = 9), 22 (61.1%) and 7 (77.8%) responded to the treatment, respectively. Among the 45 patients who underwent ANT-DBS, 28 (62%) had focal to bilateral tonic-clonic seizures (FBTCS). Of these 28 patients, 18 (64%) responded to the treatment. Out of the 65 included patients, 16 had EZ related to the sensorimotor cortex and underwent STN-DBS. Among them, 13 (81.3%) responded to the treatment, and two (12.5%) were seizure-free for at least 6 months. Three patients had Lennox-Gastaut syndrome (LGS)-like epilepsy and underwent CMN-DBS; all of them responded to the treatment (seizure frequency reductions: 51.6%, 79.6%, and 79.5%). Finally, one patient with bilateral occipital lobe epilepsy underwent PN-DBS, reducing the seizure frequency by 69.7%. Significance: ANT-DBS is effective for patients with TLE or ETLE. In addition, ANT-DBS is effective for patients with FBTCS. STN-DBS might be an optimal treatment for patients with motor seizures, especially when the EZ overlaps the sensorimotor cortex. CMN and PN may be considered modulating targets for patients with LGS-like epilepsy or occipital lobe epilepsy, respectively.

Emotional experience elicited by direct electrical stimulation: Case series and literature review.

OBJECTIVE: The cortical representation of emotions is complex, and cortical mapping of emotional experience is incomplete. We aimed to contribute to cortical mapping of emotional experience. METHODS: Clinical data from 400 patients with medically refractory epilepsy who underwent stereo-electroencephalography implantation for localization of the epileptogenic zone at the Beijing Institute of Functional Neurosurgery between October 2015 and June 2021 were collected retrospectively. Furthermore, we reviewed studies that described cortical mapping of emotional experience through electrical cortical stimulation (ECS). Affective responses similar to ictal aura and electrode contacts located in the SOZ were excluded to investigate emotional experiences in normal brain regions. RESULTS: Emotional experiences were evoked by stimulation at 10 electrode contacts in the seven patients, including five contacts that evoked mirth and excitement, one contact that evoked calmness, three contacts that evoked fear, and one contact that evoked sadness. In addition, 21 studies that evaluated emotional experiences in response to cortical electrical stimulation were reviewed. Emotions were distributed in the amygdala, hippocampus, temporal lobe, frontal lobe, insula, frontal operculum, parietal operculum, and cingulate cortex. SIGNIFICANCE: We provided additional evidence that brain regions including the amygdala, hippocampus, temporal lobe, frontal lobe, insula, frontal operculum, parietal operculum, and cingulate cortex were associated with emotional experience.

The anterior nucleus of the thalamus plays a role in the epileptic network.

OBJECTIVES: We investigated both the metabolic differences and interictal/ictal discharges of the anterior nucleus of the thalamus (ANT) in patients with epilepsy to clarify the relationship between the ANT and the epileptic network. METHODS: Nineteen patients with drug-resistant epilepsy who underwent stereoelectroencephalography were studied. Metabolic differences in ANT were analyzed using [18F] fluorodeoxyglucose-positron emission tomography with three-dimensional (3D) visual and quantitative analyses. Interictal and ictal discharges in the ANT were analyzed using visual and time-frequency analyses. The relationship between interictal discharge and metabolic differences was analyzed. RESULTS: We found that patients with temporal lobe epilepsy (TLE) showed significant metabolic differences in bilateral ANT compared with extratemporal lobe epilepsy in 3D visual and quantitative analyses. Four types of interictal activities were recorded from the ANT: spike, high-frequency oscillation (HFO), slow-wave, and α-rhythmic activity. Spike and HFO waveforms were recorded mainly in patients with TLE. Two spike patterns were recorded: synchronous and independent. In 83.3% of patients, ANT was involved during seizures. Three seizure onset types of ANT were recorded: low-voltage fast activity, rhythmic spikes, and theta band discharge. The time interval of seizure onset between the seizure onset zone and ANT showed two patterns: immediate and delayed. INTERPRETATION: ANT can receive either interictal discharges or ictal discharges which propagate from the epileptogenic zones. Independent epileptic discharges can also be recorded from the ANT in some patients. Metabolic anomalies and epileptic discharges in the ANT indicate that the ANT plays a role in the epileptic network in most patients with epilepsy, especially TLE.

Limb loss experience evoked by electric cortical stimulation.

Limb loss experience is a type of body illusion characterized by the sensation of a missing limb or body part. We aimed to investigate the brain areas involved in this unusual somatosensory experience evoked by electric cortical stimulation with stereo-electroencephalography electrodes. We retrospectively reviewed the data of patients with medical intractable epilepsy, from October 2015 to December 2020, who underwent stereo-electroencephalography implantation and electric cortical stimulation in order to locate the epileptogenic zone and obtain a functional map. We included patients who reported experiences of limb loss during the process of electric cortical stimulation for functional mapping. Three patients reported experiences of limb loss in the process of electric cortical stimulation. Limb loss experience (including the right hand, right upper limb and right side of the body) occurred when the cortex of the left posterior insula, posterior dorsal cingulate and parietal operculum were stimulated. Limb loss experience can be evoked by electric cortical stimulation of the posterior insula, parietal operculum, and posterior cingulate cortex, and provides additional evidence that these cortices play a role in the integration of body sensory perception.

Transformative neural representations support long-term episodic memory.

Memory is often conceived as a dynamic process that involves substantial transformations of mental representations. However, the neural mechanisms underlying these transformations and their role in memory formation and retrieval have only started to be elucidated. Combining intracranial EEG recordings with deep neural network models, we provide a detailed picture of the representational transformations from encoding to short-term memory maintenance and long-term memory retrieval that underlie successful episodic memory. We observed substantial representational transformations during encoding. Critically, more pronounced semantic representational formats predicted better subsequent long-term memory, and this effect was mediated by more consistent item-specific representations across encoding events. The representations were further transformed right after stimulus offset, and the representations during long-term memory retrieval were more similar to those during short-term maintenance than during encoding. Our results suggest that memory representations pass through multiple stages of transformations to achieve successful long-term memory formation and recall.

Grey and white matter microstructure changes in epilepsy patients with vagus nerve stimulators.

OBJECTIVES: Vagus nerve stimulation (VNS) has been widely used as an effective treatment for patients with drug-resistant epilepsy (DRE). However, little is known about grey matter (GM) and white matter (WM) microstructure changes caused by VNS. This study aimed to detect consistent GM and WM alterations in epilepsy patients with vagus nerve stimulators. METHODS: The diffusion tensor imaging data was acquired from 15 patients who underwent VNS implantation. The voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) were used to detect group differences in GM and WM microstructure and explore their correlation with postoperative seizure reduction. RESULTS: After 3 months of stimulation, GM density reduced in right cerebellum, left superior temporal gyrus, right inferior temporal gyrus and left thalamus, and increased in left cerebellum, left inferior parietal lobule, left middle occipital gyrus and left gyrus rectus. No significant volume changes had been found in 14 subcortical nuclei. The fractional anisotropy (FA) values reduced in left superior longitudinal fasciculus and left corticospinal tract, and increased in bilateral cingulum and body of corpus callosum. The mean diffusivity (MD) values reduced in right retrolenticular part of internal capsule, right posterior corona radiata and right superior longitudinal fasciculus. The seizure reduction had positive correlation trends with the volume reduction in left nucleus accumbens and right amygdala, and MD reduction in right medial lemniscus and right posterior corona radiata. CONCLUSIONS: The results showed that VNS could cause changes of GM density, WM FA and MD values in epilepsy patients. The volume and MD reduction in some subcortical structures might participate in the seizure frequency reduction of VNS.

Multiple ictal onset patterns underlie seizure generation in seizure-free patients with temporal lobe epilepsy surgery: an SEEG study.

PURPOSE: Seizure originates from different pathological substrate; however, the same pathologies may have distinct mechanisms underlying seizure generation. We aimed to improve the understanding of such mechanisms in patients with temporal lobe epilepsy (TLE) by investigating the stereoelectroencephalography (SEEG) ictal onset patterns (IOPs). METHODS: We analyzed data from a cohort of 19 consecutive patients explored by SEEG and had 1-3-year seizure-freedom following temporal lobe resection. RESULTS: Six IOPs were identified. They were low voltage fast activity (LVFA) (36.5%), rhythmic spikes or spike-waves at low frequency and with high amplitude (34.1%), runs of spikes (10.6%), rhythmic sharp waves (8.2%), low frequency high amplitude repetitive spiking (LFRS) (7.1%), and delta activity (3.5%). All six patterns were found in patients with mesial temporal onset and only two patterns were found in patients with temporal neocortical onset. The most prevalent patterns for patients with mesial temporal onset were rhythmic spikes or spike-waves, followed by LVFA with a mean discharge rate 74 Hz. For patients with temporal neocortical onset, the most prevalent IOP pattern was LVFA with a mean discharge rate 35 Hz, followed by runs of spikes. Compared with Lateral TLE (LTLE), the duration between the onset of the IOPs to the onset of the symptom was longer for patients with MTLE (Mesial TLE) (MTLE:55.7 ± 50.6 s vs LTLE:19.5 ± 16.4 s). CONCLUSION: Multiple IOPs underlie seizure generation in patients with TLE. However, the mesial and lateral temporal lobes share distinct IOPs.

Altered topological properties of brain functional networks in drug-resistant epilepsy patients with vagus nerve stimulators.

PURPOSE: To explore abnormalities of topological properties in drug-resistant epilepsy (DRE) patients after vagus nerve stimulation (VNS) by analyzing brain functional networks using graph theory. METHODS: Fifteen patients and eight healthy controls (HC) were scanned separately with resting-state functional magnetic resonance imaging (rs-fMRI). Graph theoretical analyses were chosen to compare the global (small-world parameters [γ, λ, σ, Cp, and Lp], and network efficiency [Eg and Eloc]), and nodal (BC, DC, and NE) properties in preoperative patients (EPpre), postoperative patients (EPpost) and HC. RESULTS: HC, EPpre and EPpost all satisfied the criteria for small-world properties (σ > 1) within the sparsity range of 0.05-0.5. Compared with EPpre, EPpost performed higher in λ and Eloc but lower in γ, σ, and Cp. Compared with HC, EPpre exhibited decreased BC, DC or NE in the right inferior frontal gyrus, right superior temporal gyrus, bilateral cingulate gyri, right supplementary motor area, right superior occipital gyrus, right Heschl gyrus, and left calcarine fissure; increased BC in the left postcentral/precentral gyrus, right paracentral lobule, left rolandic operculum, and left supramarginal gyrus, and increased NE in the right caudate nucleus. Compared with EPpre, EPpost showed increased BC, DC or NE in the bilateral inferior frontal gyrus, right middle frontal gyrus, bilateral cingulate gyri, right superior temporal gyrus, and right Heschl gyrus and decreased BC in the left fusiform gyrus. CONCLUSION: VNS downregulated small-world properties in DRE, and caused changes in some key nodes to reorganize the transmission ability of the large-scale network.

Comparison of efficiency between VNS and ANT-DBS therapy in drug-resistant epilepsy: A one year follow up study.

Vagus nerve stimulation (VNS) and anterior thalamic deep brain stimulation (ANT-DBS) have both been used for treatments of drug-resistant epilepsy (DRE). However, there is no comparative study on the effectiveness of two methods from one single center. 17 patients with DRE who underwent VNS therapy and 18 patients who underwent DBS were enrolled. A retrospective study was performed starting from baseline before operation extending to 12 months after operation. The seizure types, duration of epilepsy, age at implantation, failed numbers of antiepileptic drugs (AEDs) before operation, history of craniotomy, stimulation parameters and response rate were described. The analysis of liner regression on the age of onset, duration of epilepsy, numbers of AEDs, and the seizure reduction at 12 months after operation was applied. The mean seizure reduction in patients with DBS at 3, 6, 9 and 12 months after the operation was 57.22%, 61.61%, 63.94% and 65.28%, and that in cases with VNS was 36.06%, 39.94%, 45.24% and 48.35%, respectively. At 1 year after the operation, the patients with older operation age, focal seizures and older age of onset responded better to VNS; and those older operation age, focal generalized seizures, history of craniotomy and longer duration of disease responded better to DBS. The efficiency of ANT-DBS was higher than that of VNS at each follow up time point. Patients can choose the appropriate treatment according to the individual clinical characteristics.

Fluid and White Matter Suppression Imaging and Voxel-Based Morphometric Analysis in Conventional Magnetic Resonance Imaging-Negative Epilepsy.

Purpose: Delineation of subtle lesions in magnetic resonance imaging (MRI)-negative patients is of great importance in preoperative epilepsy evaluation. The aim of our study was to explore the diagnostic value of the novel fluid and white matter suppression (FLAWS) sequence in comparison with a voxel-based MRI postprocessing morphometric analysis program (MAP) in a consecutive cohort of non-lesional patients. Methods: Surgical candidates with a negative finding on an official neuroradiology report were enrolled. High-resolution FLAWS image and MAP maps generated based on high-resolution three-dimensional (3D) T1 image were visually inspected for each patient. The findings of FLAWS or MAP-positive (FLAWS/MAP+) regions were compared with the surgical resection cavity in correlation with surgical outcome and pathology. Results: Forty-five patients were enrolled; the pathological examination revealed focal cortical dysplasia (FCD) in 32 patients and other findings in 13 patients. The positive rate, sensitivity, and specificity were 48.9%, 0.43, and 0.87, respectively, for FLAWS and 64.4%, 0.57, and 0.8, respectively, for MAP. Concordance between surgical resection and FLAWS+ or MAP+ regions was significantly associated with a seizure-free outcome (FLAWS: p = 0.002; MAP: p = 0.0003). A positive finding in FLAWS and MAP together with abnormalities in the same gyrus (FLAWS-MAP gyral+) was detected in 31.1% of patients. FLAWS+ only and MAP+ only were found in 7 (15.5%) and 14 (31.1%) patients, respectively. Conclusions: FLAWS showed a promising value for identifying subtle epileptogenic lesions and can be used as a complement to current MAP in patients with MRI-negative epilepsy.

The thalamus-precentral gyrus functional connectivity changes in epilepsy patients following vagal nerve stimulation.

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.

Voxel-based morphometric MRI post-processing and PET/MRI co-registration reveal subtle abnormalities in cingulate epilepsy.

OBJECTIVE: Diagnostic challenges exist in the presurgical evaluation of patients with magnetic resonance imaging (MRI) negative cingulate epilepsy (CE) because of the heterogeneity in clinical semiology and lack of localizing findings on scalp electroencephalographic (EEG) recordings. We aimed to examine the neuroimaging characteristics in a consecutive cohort of patients with MRI-negative CE with a focus on two image post-processing methods, including the MRI post-processing morphometric analysis program (MAP) and 18F-fluorodeoxyglucose-positron emission tomography-MRI (PET/MRI) co-registration. METHODS: Included in this retrospective study were patients with MRI-negative CE who met the following criteria: negative on preoperative MRI, invasive EEG (iEEG) confirmed cingulate gyrus-onset seizures, surgical resection of the cingulate gyrus with/without adjacent cortex, and seizure-free for more than 12 months. MAP and PET/MRI co-registration were performed and investigated by comparison to ictal intracranial EEG findings. Other characteristics obtained from scalp EEG, magnetoencephalography (MEG), iEEG, and pathological study were also reported. RESULTS: Ten patients were included, of which eight were diagnosed with anterior CE, one with middle CE, and one with posterior CE. The semiology included fear, embarrassment, vocalization, ictal pouting, asymmetric tonic posture, hypermotor, and automatism. Scalp EEG revealed unilateral or bilateral frontal-temporal onset. MEG localized the dipoles correctly in one patient (1/10). MAP detected subtle abnormalities in regions concordant with iEEG onset in seven patients (7/10) while PET/MRI co-registration revealed focal concordant hypometabolism in five patients (5/10). Combining MAP with PET/MRI co-registration improved the detection rate to 90 % in this cohort. The pathology was focal cortical dysplasia (FCD), including FCD type IIA in three, type IIB in three, and type I in four. CONCLUSION: MAP and PET/MRI co-registration show promising results in identifying subtle FCD abnormalities in CE with negative results on conventional MRI, which can be otherwise challenging. More importantly, a combination of MRI post-processing and PET/MRI co-registration can greatly improve the identification of epileptic abnormalities, which can be used as surgical target. MAP and PET/MRI co-registration should be incorporated into the routine presurgical evaluation.

Clinical application of intraoperative trial-free online-based language mapping for patients with refractory epilepsy.

OBJECTIVE: The objective of the study was to develop and clinically test a trial-free online-based language mapping method for localizing the eloquent cortex easily in epilepsy operation. METHODS: Nine patients with refractory epilepsy were included in this study according to the results of preoperative evaluation for their epileptogenic zones (EZs) located adjacent to the eloquent cortex. When patients were awakened up from general anesthesia during operation, the trial-free online-based language-mapping paradigm was performed. All positive points marked on the cortex in each test were labeled and superimposed together as the result of functional mapping for each patient. The eloquent cortex was mapped according to the results obtained both from the intraoperative trial-free task localization method and the traditional electrical cortical stimulation (ECS). RESULTS: All patients completed this paradigms twice within 10 min. Based on the results of mapping, the EZs were tried to fully resected on the premise of preserving the mapped eloquent cortex as much as possible. The postoperative follow-up showed the outcome of Engel I in six patients and Engel II in three patients, whereas only two patients had aphemia after surgery and recovered within one week and three months, respectively. SIGNIFICANCE: The intraoperative trial-free online-based language mapping method was primarily identified to be safe and effective. This novel method seems to be promising and worthy of improvement.

Auras in intractable frontal lobe epilepsy: Clinical characteristics, values, and limitations.

Auras are essential in preoperative evaluation and can provide valuable information for delineating seizure onset zones. Frontal lobe epilepsy (FLE) is the second most common focal epilepsy, while a few studies have focused on auras in FLE. To better understand FLE, we analyzed the clinical characteristics, values, and limitations of auras in FLE. The incidence rate of aura in FLE was 37.9% in our study. We included 54 patients and 76 auras in 11 categories were reported. The rate of auras in the decreasing order are as follows: autonomic aura; emotional aura; somatosensory aura; psychic aura; cephalic aura; abdominal aura; whole-body sensory aura, visual aura; auditory aura; and vestibular and unclassified aura. A significant number of aura types can be reported by FLE patients; autonomic aura was the most frequent category and somatosensory auras are most likely associated with the contralateral motor areas.

Altered amplitude of low-frequency fluctuations and regional homogeneity in drug-resistant epilepsy patients with vagal nerve stimulators under different current intensity.

BACKGROUND: The mechanisms of vagal nerve stimulation (VNS) for the treatment of drug-resistant epilepsy (DRE) remain unclear. This study aimed to measure spontaneous brain activity changes caused by VNS in DRE patients using resting-state functional MRI (rs-fMRI). METHODS: The rs-fMRI scans were performed in 16 DRE patients who underwent VNS surgery. Amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) was generated and examined using paired sample t-test to compare activity changes at different current intensity stage. The preoperative and postoperative ALFF/ReHo were also compared in eight responders (≥50% reduction of seizure frequency three months after surgery) and eight nonresponders using paired sample t-test. RESULTS: The significant ALFF and ReHo changes were shown in various cortical/subcortical structures in patients under different current intensity. After three months of stimulation, responders exhibited increased ALFF in the right middle cingulate gyrus, left parahippocampal gyrus, and left cerebellum, and increased ReHo in the right postcentral gyrus, left precuneus, left postcentral gyrus, right superior parietal gyrus, right precentral gyrus, and right superior frontal gyrus. Nonresponders exhibited decreased ALFF in the left temporal lobe and right cerebellum, increased ALFF in bilateral brainstem, decreased ReHo in bilateral lingual gyri, and increased ReHo in the right middle frontal gyrus and right anterior cingulate gyrus. CONCLUSIONS: The spontaneous neural activity changes in DRE patients caused by VNS were in an ongoing process. Increased ALFF/ReHo in frontal cortex, cingulate gyri, precentral/postcentral gyri, parahippocampal gyri, precuneus, parietal cortex, and cerebellum may implicate in VNS-induced improvement in seizure frequency.

The changes in the topological properties of brain structural network based on diffusion tensor imaging in pediatric epilepsy patients with vagus nerve stimulators: A graph theoretical analysis.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: VNS causes topological characteristics changes in pediatric patients with generalized seizures through regulating regional properties in some brain structures.

Stable maintenance of multiple representational formats in human visual short-term memory.

Visual short-term memory (VSTM) enables humans to form a stable and coherent representation of the external world. However, the nature and temporal dynamics of the neural representations in VSTM that support this stability are barely understood. Here we combined human intracranial electroencephalography (iEEG) recordings with analyses using deep neural networks and semantic models to probe the representational format and temporal dynamics of information in VSTM. We found clear evidence that VSTM maintenance occurred in two distinct representational formats which originated from different encoding periods. The first format derived from an early encoding period (250 to 770 ms) corresponded to higher-order visual representations. The second format originated from a late encoding period (1,000 to 1,980 ms) and contained abstract semantic representations. These representational formats were overall stable during maintenance, with no consistent transformation across time. Nevertheless, maintenance of both representational formats showed substantial arrhythmic fluctuations, i.e., waxing and waning in irregular intervals. The increases of the maintained representational formats were specific to the phases of hippocampal low-frequency activity. Our results demonstrate that human VSTM simultaneously maintains representations at different levels of processing, from higher-order visual information to abstract semantic representations, which are stably maintained via coupling to hippocampal low-frequency activity.

The functional connectivity study on the brainstem-cortical/subcortical structures in responders following cervical vagus nerve stimulation.

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.