Characterization of brain network supporting episodic memory in the absence of one medial temporal lobe.

How the brain supports normal episodic memory function without medial temporal lobe (MTL) structures has not been well characterized, which could provide clues for new therapeutic targets for people with MTL dysfunction-related memory impairment. To characterize brain network supporting effective episodic memory function in the absence of unilateral MTL, we investigated the whole-brain cortical interactions during functional magnetic resonance imaging memory encoding paradigms of words and figures in patients who showed a normal range of memory capacity following unilateral MTL resection and healthy controls (HC). Compared to the HC, the patients showed less activation in the left inferior frontal areas and right thalamus together with greater activation in the many cortical areas including the medial prefrontal cortex (mPFC). Task-based functional connectivity (FC) analysis revealed that the mPFC showed stronger interactions with widespread brain areas in both patient groups, including the hippocampus contralateral to the resection. Moreover, the strength of the mPFC FC predicts the individual memory capacity of the patients. Our data suggest that hyperconnectivity of distributed brain areas, especially the mPFC, is a neural mechanism for memory function in the absence of one MTL.

Mesial temporal lobe epilepsy with hippocampal sclerosis is a network disorder with altered cortical hubs.

OBJECTIVE: Electrophysiologic hubs within the large-scale functional networks in mesial temporal lobe epilepsy (mTLE) with hippocampal sclerosis (HS) have not been investigated. We hypothesized that mTLE with HS has different resting-state network hubs in their large-scale functional networks compared to the hubs in healthy controls (HC). We also hypothesized that the hippocampus would be a functional hub in mTLE patients with HS. METHODS: Resting-state functional networks, identified by using magnetoencephalography (MEG) signals in the theta, alpha, beta, and gamma frequency bands, were evaluated. Networks in 44 mTLE patients with HS (left mTLE = 22; right mTLE = 22) were compared with those in 46 age-matched HC. We investigated betweenness centrality at the source-level MEG network. RESULTS: The main network hubs were at the pole of the left superior temporal gyrus in the beta band, the pole of the left middle temporal gyrus in the beta and gamma bands, left hippocampus in the theta and alpha bands, and right posterior cingulate gyrus in all four frequency bands in mTLE patients; all of which were different from the main network hubs in HC. Only patients with left mTLE showed profound differences from HC at the left hippocampus in the alpha band. SIGNIFICANCE: Our analysis of resting-state MEG signals shows that altered electrophysiologic functional hubs in mTLE patients reflect pathophysiologic brain network reorganization. Because we detected network hubs in both hippocampal and extrahippocampal areas, it is probable that mTLE is a large-scale network disorder rather than a focal disorder. The hippocampus was a network hub in left mTLE but not in right mTLE patients, which may be due to intrinsic functional and structural asymmetries between left and right mTLE patients. The evaluation of cortical hubs, even in the spike-free resting-state, could be a clinical diagnostic marker of mTLE with HS.

Preserved high-centrality hubs but efficient network reorganization during eyes-open state compared with eyes-closed resting state: an MEG study.

A question to be addressed in the present study is how different the eyes-closed (EC) and eyes-open (EO) resting states are across frequency bands in terms of efficiency and centrality of the brain functional network. We investigated both the global and nodal efficiency and betweenness centrality in the EC and EO resting states from 39 volunteers. Mutual information was used to obtain the functional connectivity for each of the four frequency bands (theta, alpha, beta, and gamma). We showed that the cortical hubs with high betweenness centrality were maintained in the EC and EO resting states. We further showed that these hubs were associated with more than three frequency bands, suggesting that these hubs play an important role in the brain functional network at multiple temporal scales in the resting states. Enhanced global efficiency values were found in the theta and alpha bands in the EO state compared with those in the EC state. Moreover, it turned out that in the EO state the functional network was reorganized to enhance nodal efficiency at the nodes related to both the default mode and the dorsal attention networks and sensory-related resting-state networks. This result suggests that in the EO state the brain functional network was efficiently reorganized, facilitating the adaptation of the brain network to the change in state, which could help in understanding brain disorders that have a disturbance in communication with external environments by using the adaptation ability of brain functional networks.

Localization value of magnetoencephalography interictal spikes in adult nonlesional neocortical epilepsy.

Few studies have included magnetoencephalography (MEG) when assessing the diagnostic value of presurgical modalities in a nonlesional epilepsy population. Here, we compare single photon emission computed tomography (SPECT), positron emission tomography (PET), video-EEG (VEEG), and MEG, with intracranial EEG (iEEG) to determine the value of individual modalities to surgical decisions. We analyzed 23 adult epilepsy patients with no abnormal MRI findings who had undergone surgical resection. Localization of individual presurgical tests was determined for hemispheric and lobar locations based on visual analysis. Each localization result was compared with the ictal onset zone (IOZ) defined by using iEEG. The highest to the lowest hemispheric concordance rates were MEG (83%) > ictal VEEG (78%) > PET (70%) > ictal SPECT (57%). The highest to lowest lobar concordance rates were ictal VEEG = MEG (65%) > PET (57%) > ictal SPECT (52%). Statistical analysis showed MEG to have a higher hemispheric concordance than that of ictal SPECT (P = 0.031). We analyzed the effects of MEG clustered-area resection on surgical outcome. Patients who had resection of MEG clusters showed a better surgical outcome than those without such resection (P = 0.038). It is suggested that MEG-based localization had the highest concordance with the iEEG-defined IOZ. Furthermore, MEG cluster resection has prognostic significance in predicting surgical outcome.

Magnetoencephalography in pediatric lesional epilepsy surgery.

This study was performed to assess the usefulness of magnetoencephalography (MEG) as a presurgical evaluation modality in Korean pediatric patients with lesional localization-related epilepsy. The medical records and MEG findings of 13 pediatric patients (6 boys and 7 girls) with localization-related epilepsy, who underwent epilepsy surgery at Seoul National University Children's Hospital, were retrospectively reviewed. The hemispheric concordance rate was 100% (13/13 patients). The lobar or regional concordance rate was 77% (10/13 patients). In most cases, the MEG spike sources were clustered in the proximity of the lesion, either at one side of the margin (nine patients) or around the lesion (one patient); clustered spike sources were distant from the lesion in one patient. Among the patients with clustered spike sources near the lesion, further extensions (three patients) and distal scatters (three patients) were also observed. MEG spike sources were well lateralized and localized even in two patients without focal epileptiform discharges in the interictal scalp electroencephalography. Ten patients (77%) achieved Engel class I postsurgical seizure outcome. It is suggested that MEG is a safe and useful presurgical evaluation modality in pediatric patients with lesion localization-related epilepsy.

Dynamic Functional Connectivity Change-Point Detection With Random Matrix Theory Inference.

To study the dynamic nature of brain activity, functional magnetic resonance imaging (fMRI) data is useful including some temporal dependencies between the corresponding neural activity estimates. Recent studies have shown that the functional connectivity (FC) varies according to time and location which should be incorporated into the model. Modeling this dynamic FC (DFC) requires time-varying measures of spatial region of interest (ROI) sets. To know about the DFC, change-point detection in FC is of particular interest. In this paper, we propose a method of detecting a change-point based on the maximum of eigenvalues via random matrix theory (RMT). From covariance matrices for FC of all ROI's, the temporal change-point of FC is decided by an RMT approach. Simulation results show that our proposed method can detect meaningful FC change-points. We also illustrate the effectiveness of our FC detection approach by applying our method to epilepsy data where change-points detected are explained by the changes in memory capacity. Our study shows the possibility of RMT based approach in DFC change-point problem and in studying the complex dynamic pattern of functional brain interactions.

Single-Trial EEG Connectivity of Default Mode Network Before and During Encoding Predicts Subsequent Memory Outcome.

The successful memory process produces specific activity in the brain network. As the brain activity of the prestimulus and encoding phases has a crucial effect on subsequent memory outcomes (e.g., remembered or forgotten), previous studies have tried to predict the memory performance in this period. Conventional studies have used the spectral power or event-related potential of specific regions as the classification feature. However, as multiple brain regions work collaboratively to process memory, it could be a better option to use functional connectivity within the memory-related brain network to predict subsequent memory performance. In this study, we acquired the EEG signals while performing an associative memory task that remembers scene-word pairs. For the connectivity analysis, we estimated the cross-mutual information within the default mode network with the time-frequency spectra at the prestimulus and encoding phases. Then, we predicted the success or failure of subsequent memory outcome with the connectivity features. We found that the classifier with support vector machine achieved the highest classification accuracy of 80.83% ± 12.65% (mean ± standard deviation) using the beta (13-30 Hz) connectivity at encoding phase among the multiple frequency bands and task phases. Using the prestimulus beta connectivity, the classification accuracy of 72.45% ± 12.52% is also achieved. Among the features, the connectivity related to the dorsomedial prefrontal cortex was found to contribute to successful memory encoding. The connectivity related to the posterior cingulate cortex was found to contribute to the failure of memory encoding. The present study showed for the first time the successful prediction with high accuracy of subsequent memory outcome using single-trial functional connectivity.

Critical area for memory decline after mesial temporal resection in epilepsy patients.

OBJECTIVE: Mesial temporal lobe epilepsy (MTLE) surgery is associated with a risk of memory decline after surgery, but the effect of the extent and locus of temporal resection on postoperative memory function are controversial. The authors' aim in this study was to confirm if selective resection is effective in preserving memory function and identify critical areas for specific memory decline after temporal resection. METHODS: In this single-center retrospective study, the authors investigated data from patients who underwent unilateral MTLE surgery between 2005 and 2015. Data from 74 MTLE patients (60.8% of whom were female; mean [SD] age at surgery 32 years [8.91 years] and duration of epilepsy 16 years [9.65 years]) with histologically proven hippocampal sclerosis were included. Forty-two patients underwent left-sided surgery. The resection area was manually delineated on each patient's postoperative T1-weighted images. Mapping was performed to see if the resected group, compared with the nonresected group, had worse postoperative memory in various memory domains, including verbal item, verbal associative, and figural memory. RESULTS: Overall, 95.9% had a favorable epilepsy outcome. In verbal item memory, resection of the left lateral temporal area was related to postoperative decline in immediate and delayed recall scores of word lists. In verbal associative memory, resection of the anterior part of the left hippocampus, left parahippocampal area, and left lateral temporal area was related to postoperative decline in immediate recall scores of word pairs. Resection of the posterior part of the left hippocampus, left parahippocampal area, and left lateral temporal area was related to delayed recall scores of the same task. Similarly, in the figural memory, postoperative decline of immediate recall scores was associated with the resection of the anterior part of the right hippocampus, amygdala, parahippocampal area, and superior temporal area, and decline of delayed recall scores was related to resection of the posterior part of the right hippocampus and parahippocampal area. CONCLUSIONS: Using voxel-based analysis, which accounts for the individual differences in the resection, the authors found a critical region for postoperative memory decline that is not revealed in the region-of-interest or groupwise comparison. Particularly, resection of the hippocampus was related to associative memory. In both verbal and visual memory, resection of the anterior part of the hippocampus was associated with immediate recall, and resection of the posterior part of the hippocampus was associated with delayed recall. Therefore, the authors' results suggest that selective resection may be effective in preserving postoperative memory decline.

Task-dependent effects of intracranial hippocampal stimulation on human memory and hippocampal theta power.

BACKGROUND: Despite its potential to revolutionize the treatment of memory dysfunction, the efficacy of direct electrical hippocampal stimulation for memory performance has not yet been well characterized. One of the main challenges to cross-study comparison in this area of research is the diversity of the cognitive tasks used to measure memory performance. OBJECTIVE: We hypothesized that the tasks that differentially engage the hippocampus may be differentially influenced by hippocampal stimulation and the behavioral effects would be related to the underlying hippocampal activity. METHODS: To investigate this issue, we recorded intracranial EEG from and directly applied stimulation to the hippocampus of 10 epilepsy patients while they performed two different verbal memory tasks - a word pair associative memory task and a single item memory task. RESULTS: Hippocampal stimulation modulated memory performance in a task-dependent manner, improving associative memory performance, while impairing item memory performance. In addition, subjects with poorer baseline cognitive function improved much more with stimulation. iEEG recordings from the hippocampus during non-stimulation encoding blocks revealed that the associative memory task elicited stronger theta oscillations than did item memory and that stronger theta power was related to memory performance. CONCLUSIONS: We show here for the first time that stimulation-induced associative memory enhancement was linked to increased theta power during retrieval. These results suggest that hippocampal stimulation enhances associative memory but not item memory because it engages more hippocampal theta activity and that, in general, increasing hippocampal theta may provide a neural mechanism for successful memory enhancement.

Clinical Relevance of Interictal Spikes in Tumor-Related Epilepsy: An Electrocorticographic Study.

BACKGROUND AND PURPOSE: Although some surgeons utilize interictal spikes recorded via electrocorticography (ECoG) when planning extensive peritumoral resection in patients with tumor-related epilepsy, the association between interictal spikes and epileptogenesis has not been fully described. We investigated whether the resection of interictal spikes recorded by ECoG is associated with more favorable surgical outcomes in tumor-related epilepsy. METHODS: Of 132 patients who underwent epilepsy surgery for tumor-related epilepsy from 2006 to 2013, seven patients who underwent extraoperative ECoG were included in this study. In each patient, ECoG interictal spike sources were localized using standardized low-resolution brain electromagnetic tomography and were co-registered into a reconstructed brain model. Correspondence to the resection volume was estimated by calculating the percentage of interictal spike sources in the resection volume. RESULTS: All patients achieved gross total resection without oncological recurrence. Five patients achieved favorable surgical outcomes, whereas the surgical outcomes of two patients were unfavorable. Correspondence rates to the resection volume in the favorable and unfavorable surgical outcome groups were 44.6%±27.8% and 43.5%±22.8%, respectively (p=0.96). All patients had interictal spike source clusters outside the resection volume regardless of seizure outcome. CONCLUSIONS: In these cases of tumor-related epilepsy, the extent of the resection of ECoG interictal spikes was not associated with postoperative seizure outcomes. Furthermore, the presence of interictal spike sources outside of the resection area was not related to seizure outcomes. Instead, concentrating more on the complete removal of the brain tumor appears to be a rational approach.

Neural basis of episodic memory in the intermediate term after medial temporal lobe resection.

OBJECTIVE: How the brain supports intermediate-term preservation of memory in patients who have undergone unilateral medial temporal lobe resection (MTLR) has not yet been demonstrated. To understand the neural basis of episodic memory in the intermediate term after surgery for temporal lobe epilepsy (TLE), the authors investigated the relationship between the activation of the hippocampus (HIP) during successful memory encoding and individual memory capacity in patients who had undergone MTLR. They also compared hippocampal activation with other parameters, including structural volumes of the HIP, duration of illness, and age at seizure onset. METHODS: Thirty-five adult patients who had undergone unilateral MTLR at least 1 year before recruiting and who had a favorable seizure outcome were enrolled (17 left MTLR, 18 right MTLR; mean follow-up 6.31 ± 2.72 years). All patients underwent a standardized neuropsychological examination of memory function and functional MRI scanning with a memory-encoding paradigm of words and figures. Activations of the HIP during successful memory encoding were calculated and compared with standard neuropsychological memory scores, hippocampal volumes, and other clinical variables. RESULTS: Greater activation in the HIP contralateral to the side of the resection was related to higher postoperative memory scores and greater postoperative memory improvement than the preoperative baseline in both patient groups. Specifically, postoperative verbal memory performance was positively correlated with contralateral right hippocampal activation during word encoding in the left-sided surgery group. In contrast, postoperative visual memory performance was positively correlated with contralateral left hippocampal activation during figure encoding in the right-sided surgery group. Activation of the ipsilateral remnant HIP was not correlated with any memory scores or volumes of the HIP; however, it had a negative correlation with the seizure-onset age and positive correlation with the duration of illness in both patient groups. CONCLUSIONS: For the first time, a neural basis that supports effective intermediate-term episodic memory after unilateral MTLR has been characterized. The results provide evidence that engagement of the HIP contralateral rather than ipsilateral to the side of resection is responsible for effective memory function in the intermediate term (> 1 year) after surgery in patients who have undergone left MTLR and right MTLR. Engagement of the material-specific contralesional HIP, verbal memory in the left-sided surgery group, and visual memory in the right-sided surgery group were observed.

Predicting epileptic seizures from scalp EEG based on attractor state analysis.

BACKGROUND AND OBJECTIVE: Epilepsy is the second most common disease of the brain. Epilepsy makes it difficult for patients to live a normal life because it is difficult to predict when seizures will occur. In this regard, if seizures could be predicted a reasonable period of time before their occurrence, epilepsy patients could take precautions against them and improve their safety and quality of life. In this paper, we investigate a novel seizure precursor based on attractor state analysis for seizure prediction. METHODS: We analyze the transition process from normal to seizure attractor state and investigate a precursor phenomenon seen before reaching the seizure attractor state. From the result of an analysis, we define a quantified spectral measure in scalp EEG for seizure prediction. From scalp EEG recordings, the Fourier coefficients of six EEG frequency bands are extracted, and the defined spectral measure is computed based on the coefficients for each half-overlapped 20-second-long window. The computed spectral measure is applied to seizure prediction using a low-complexity methodology. RESULTS: Within scalp EEG, we identified an early-warning indicator before an epileptic seizure occurs. Getting closer to the bifurcation point that triggers the transition from normal to seizure state, the power spectral density of low frequency bands of the perturbation of an attractor in the EEG, showed a relative increase. A low-complexity seizure prediction algorithm using this feature was evaluated, using ∼583h of scalp EEG in which 143 seizures in 16 patients were recorded. With the test dataset, the proposed method showed high sensitivity (86.67%) with a false prediction rate of 0.367h-1 and average prediction time of 45.3min. CONCLUSIONS: A novel seizure prediction method using scalp EEG, based on attractor state analysis, shows potential for application with real epilepsy patients. This is the first study in which the seizure-precursor phenomenon of an epileptic seizure is investigated based on attractor-based analysis of the macroscopic dynamics of the brain. With the scalp EEG, we first propose use of a spectral feature identified for seizure prediction, in which the dynamics of an attractor are excluded, and only the perturbation dynamics from the attractor are considered.

Usefulness of multiple frequency band source localizations in ictal MEG.

OBJECTIVE: We evaluated the diagnostic value of multiple frequency band MEG source localization within a wide time window during the preictal period. METHODS: Data for 13 epilepsy patients who showed an ictal event during MEG were analyzed. Several seconds of preictal data were localized in the theta, alpha, beta, and gamma bands by using wavelet transformation and the sLORETA algorithm. The same analysis was performed with narrow time and frequency band. Localization concordances to the surgically resected area were compared. RESULTS: Source localization in the gamma band for a 10s window before ictal onset showed best concordance to the resection cavity. Eight of 13 patients showed sub-lobar concordance in the 10s gamma band localization, whereas 3 showed concordance in the narrow time and frequency analysis. Four of 7 patients with focal cortical dysplasia (FCD) achieved seizure-free outcome, and all 4 showed sub-lobar concordance. CONCLUSIONS: A 10s time window gamma source localization method can be used to delineate the epileptogenic zone. SIGNIFICANCE: The use of a long period during preictal gamma source localization has the potential to become a localizing biomarker of the epileptogenic zone in candidates for surgical intervention, especially in MRI-suspected FCD.

Focal cortical dysplasia alters electrophysiological cortical hubs in the resting-state.

OBJECTIVE: To test the hypothesis that epilepsy patients with focal cortical dysplasia (FCD) have different electrophysiological functional cortical hubs from those of healthy controls. METHODS: Resting-state functional networks in the theta, alpha, beta and gamma frequency bands were evaluated in 35 epilepsy patients with histopathologically verified FCD as a single pathology and in 46 age-matched healthy controls. Using magnetoencephalography (MEG), we investigated the network differences between the two groups by comparing the nodal efficiency (Enodal) and betweenness centrality (BC) values at the source level. RESULTS: The FCD patients had significant Enodal increases in the functional cortical hubs in the left anterior, middle, and posterior cortices and the medial orbital superior frontal cortex in the beta band. The left posterior cingulate cortex showed significant BC increases in the theta, alpha, and beta bands. There was a negative correlation between Enodal and age at seizure onset. CONCLUSIONS: Cortical dysplasia alters whole brain functional cortical hubs compared to healthy controls. The age at seizure onset was negatively correlated with Enodal in the beta band in FCD patients. SIGNIFICANCE: Our study for the first time investigated the functional cortical hubs and their alteration in the resting-state functional network in epilepsy patients with FCD using noninvasive MEG signals.

Episodic memory in aspects of large-scale brain networks.

Understanding human episodic memory in aspects of large-scale brain networks has become one of the central themes in neuroscience over the last decade. Traditionally, episodic memory was regarded as mostly relying on medial temporal lobe (MTL) structures. However, recent studies have suggested involvement of more widely distributed cortical network and the importance of its interactive roles in the memory process. Both direct and indirect neuro-modulations of the memory network have been tried in experimental treatments of memory disorders. In this review, we focus on the functional organization of the MTL and other neocortical areas in episodic memory. Task-related neuroimaging studies together with lesion studies suggested that specific sub-regions of the MTL are responsible for specific components of memory. However, recent studies have emphasized that connectivity within MTL structures and even their network dynamics with other cortical areas are essential in the memory process. Resting-state functional network studies also have revealed that memory function is subserved by not only the MTL system but also a distributed network, particularly the default-mode network (DMN). Furthermore, researchers have begun to investigate memory networks throughout the entire brain not restricted to the specific resting-state network (RSN). Altered patterns of functional connectivity (FC) among distributed brain regions were observed in patients with memory impairments. Recently, studies have shown that brain stimulation may impact memory through modulating functional networks, carrying future implications of a novel interventional therapy for memory impairment.

Usefulness of interictal spike source localization in temporal lobe epilepsy: electrocorticographic study.

The success of epilepsy surgery depends on delineation of the suspected epileptogenic zone. The gold standard to delineate it is to use the ictal onset zone from an electrocorticography (ECoG). Although interictal spikes are also associated with the epileptogenic zone, their clinical significance has been under-evaluated. The aim of this study was to evaluate the source localization of interictal spikes in terms of the association with epileptogenic zone in surgical temporal lobe epilepsy patients. The proposition is that the resection volume in patients with favorable outcomes includes the epileptogenic zone. The association with the epileptogenic zone was assessed as follows: (1) how many of the interictal spike sources are within the resection volume in patients with favorable outcomes and (2) how many of the interictal spike sources are outside the resection volume in patients with unfavorable outcomes. Thirty-eight temporal lobe epilepsy (TLE) patients who underwent both ECoG monitoring and epilepsy surgery were recruited and their 10min of ECoG recordings were analyzed. Six tumor-related TLE patients were excluded in the analysis. Of the remaining 32 patients, 20 patients achieved favorable surgical outcomes (Engel I and II), while the surgical outcomes of 12 patients were unfavorable (Engel III and IV). In each patient, interictal spike sources were localized using sLORETA and co-registered into a reconstructed brain model. The correspondence rate with the resection volume was estimated by counting the percentage of interictal spike sources in the resection volume. The correspondence rate in patients with favorable outcomes was 72.8±22.1, which was significantly higher than that (41.2±28.8) of the patients with unfavorable outcomes (p=0.002). Nine out of twelve patients (75%) with unfavorable outcomes had multiple interictal spike source clusters both interior and exterior to the resection volume, while 4 of the 20 patients with favorable outcomes (20%) had such multiple clusters (p=0.021). In conclusion, interictal spike sources are highly associated with the epileptogenic zone. ECoG interictal spike source localization could help in the delineation of the potential resection volume.

Abnormal functional brain network in epilepsy patients with focal cortical dysplasia.

PURPOSE: Focal cortical dysplasia (FCD) is the second most common pathological entity in surgically treated neocortical focal epilepsy. Despite the recent increase of interest in network approaches derived from graph theory on epilepsy, resting state network analysis of the FCD brain has not been adequately investigated. In this study, we investigated the difference in the resting state functional network between epilepsy patients with FCD and healthy controls using whole-brain magnetoencephalography (MEG) recordings. METHODS: Global mutual information (MIglob) and global efficiency (Eglob) were calculated for theta (4-7 Hz), alpha (8-12 Hz), beta (13-30 Hz), and gamma (31-45 Hz) bands in 35 epilepsy patients with FCD and 23 healthy controls. RESULTS: Resting state FCD brains had stronger functional connectivity (MIglob) in the beta and gamma bands and higher functional efficiency (Eglob) in the beta and gamma bands than those of the controls (p<0.05). The MIglob and Eglob values of FCD type I and II brains in the beta band were higher than those of healthy control brains (p<0.05). In the gamma band, the values of FCD type II brains were higher than those of control and FCD type I brains (p<0.05). CONCLUSIONS: FCD brains had increased functional connectivity in the beta and gamma frequency bands at the resting state compared with those in healthy controls. In addition, patients exhibited different network characteristics depending on the type of FCD. The resting state network analysis could be useful in a clinical setting because we observed network differences even when there was no prominent interictal spike activity.

Localization of MEG pathologic gamma oscillations in adult epilepsy patients with focal cortical dysplasia.

We aimed to evaluate the clinical value of gamma oscillations in MEG for intractable neocortical epilepsy patients with cortical dysplasia by comparing gamma and interictal spike events. A retrospective analysis of MEG recordings of 30 adult neocortical epilepsy patients was performed. Gamma (30-70 Hz) and interictal spike events were independently identified, their independent or concurrent presence determined, and their source localization rates compared. Of 30 patients, gamma activities were detected in 28 patients and interictal spikes in 24 patients. Gamma events alone appeared in 5 patients, interictal spikes alone in 1 patient, and no events in 1 patient. Gamma co-occurred with interictal spikes in 20.1 ± 22.1% and interictal spikes co-occurred with gamma in 15.0 ± 19.2%. Rates of event localization within the resection cavity were significantly different (p = 0.042) between gamma (63.3 ± 32.6%) and interictal spike (47.0 ± 41.3%) events. In 4 of the 5 gamma-only patients the mean localization rate was 42.5%. Compared with the interictal spike localization rate, 4 of 9 seizure-free patients had higher gamma localization rates, 4 had the same rate, and 1 had a lower rate. Individual gamma events can be detected independently from interictal spike presence. Gamma can be localized to the resection cavity at least comparably to or more frequently than that from interictal spikes. Even when interictal spikes were undetected, gamma sources were localized to the resection cavity. Gamma oscillations may be a useful indicator of epileptogenic focus.

Information source in multiple MEG spike clusters can be identified by effective connectivity in focal cortical dysplasia.

It has been reported that patients with a single MEG spike cluster have better postoperative outcomes compared to patients with multiple clusters. However, the problem of identifying a genuine source in the multiple MEG spike clusters remains unsolved. The aim of this study was to determine the focus of the epileptic activity in a situation with multiple MEG spike clusters. Five patients with intractable epilepsy with multiple MEG spike clusters were retrospectively investigated. They had pathologically proven type IA focal cortical dysplasia (FCD) with discordant multimodal presurgical evaluations, and showed a favorable postoperative outcome. MEG spikes were localized and clustered using a hierarchical clustering method. Then, effective connectivity (a phase-slope index method) referring to the causal interaction between distant structures in the brain was applied to the source waveforms extracted from the multiple MEG spike clusters. Finally, the information source, that is, the driver region between multiple clusters, could be identified. We found that 4 of the 5 FCD patients exhibited the driver regions were coincident with the resection area, which was also quite consistent at different epochs. Our results suggest that effective connectivity analysis has a potential value as a presurgical evaluation when multiple MEG spike clusters are found.

Functional cortical hubs in the eyes-closed resting human brain from an electrophysiological perspective using magnetoencephalography.

It is not clear whether specific brain areas act as hubs in the eyes-closed (EC) resting state, which is an unconstrained state free from any passive or active tasks. Here, we used electrophysiological magnetoencephalography (MEG) signals to study functional cortical hubs in 88 participants. We identified several multispectral cortical hubs. Although cortical hubs vary slightly with different applied measures and frequency bands, the most consistent hubs were observed in the medial and posterior cingulate cortex, the left dorsolateral superior frontal cortex, and the left pole of the middle temporal cortex. Hubs were characterized as connector nodes integrating EC resting state functional networks. Hubs in the gamma band were more likely to include midline structures. Our results confirm the existence of multispectral cortical cores in EC resting state functional networks based on MEG and imply the existence of optimized functional networks in the resting brain.