Epileptic Network Research Articles

SY6.4. EEG and fMRI recordings: Established tool or research topic?

EEG with functional MRI combines the spatial resolution of MRI with the temporal resolution of EEG, to reveal an epileptic focus or network. It images blood flow changes in the brain in response to the epileptic discharges of interest, providing a temporally smoothed, average response to a series of epileptic discharges, displayed as a statistical ‘activation map’. Key advantages of EEG-fMRI include that it is non-invasive and offers whole brain coverage, allowing visualisation of deep epileptic foci, and distributed epilepsy networks. Group EEG- fMRI studies have been particularly useful in revealing the brain networks responsible for epileptic syndromes, such as Benign Epilepsy with Centro-Temporal spikes, Genetic Generalised Epilepsy, and Lennox-Gastaut Syndrome, providing important mechanistic insights. When used as a tool for presurgical localisation in individuals, results have been mixed, with around 50% of studies providing helpful localisation. Practical limitations include difficulty detecting discharges due to the harsh recording environment of the MRI, sensitivity of fMRI to patient motion and insufficient epileptic discharges during the fMRI session. Even with optimal recordings some studies show no significant activation, possibly due to frequent epileptic discharges that are too low in amplitude to penetrate the scalp, contaminating the ‘reference’ periods used in analysis. Many EEG-fMRI studies show networks of brain regions are involved, rather than a single region, frustrating interpretation when seeking a surgical target. However, these patterns likely reflect real network recruitment by interictal discharges, and hence indicate the network through which epilepsy is being expressed. There is some evidence that when there is a network of spike related activation, seizure freedom rates are affected by the extent of removal of the region of greatest fMRI activation. Even when not providing definitive localisation, EEG- fMRI activation maps can provide a starting point for subsequent investigations such as additional structural imaging, or invasive studies.

Deep Learning-Based Localization of EEG Electrodes Within MRI Acquisitions.

The simultaneous acquisition of electroencephalographic (EEG) signals and functional magnetic resonance images (fMRI) aims to measure brain activity with good spatial and temporal resolution. This bimodal neuroimaging can bring complementary and very relevant information in many cases and in particular for epilepsy. Indeed, it has been shown that it can facilitate the localization of epileptic networks. Regarding the EEG, source localization requires the resolution of a complex inverse problem that depends on several parameters, one of the most important of which is the position of the EEG electrodes on the scalp. These positions are often roughly estimated using fiducial points. In simultaneous EEG-fMRI acquisitions, specific MRI sequences can provide valuable spatial information. In this work, we propose a new fully automatic method based on neural networks to segment an ultra-short echo-time MR volume in order to retrieve the coordinates and labels of the EEG electrodes. It consists of two steps: a segmentation of the images by a neural network, followed by the registration of an EEG template on the obtained detections. We trained the neural network using 37 MR volumes and then we tested our method on 23 new volumes. The results show an average detection accuracy of 99.7% with an average position error of 2.24 mm, as well as 100% accuracy in the labeling.

Highly consistent temporal lobe interictal spike networks revealed from foramen ovale electrodes

ObjectiveA major challenge that limits understanding and treatment of epileptic events from mesial temporal structures comes from our inability to detect and map interictal networks reproducibly using scalp electrodes. Here, we developed a novel approach to map interictal spike networks and demonstrate their relationships to seizure onset and lesions in patients with foramen ovale electrode implantations. MethodsWe applied the direct Directed Transfer Function to reveal interictal spike propagation from bilateral foramen ovale electrodes on 10 consecutive patients and co-registered spatially with both seizure onset zones and temporal lobe lesions. ResultsHighly reproducible, yet unique interictal spike networks were seen for each patient (correlation: 0.93 ± 0.13). Interictal spikes spread in both anterior and posterior directions within each temporal lobe, often reverberating between sites. Spikes propagated to the opposite temporal lobe predominantly through posterior pathways. Patients with structural lesions (N = 4), including tumors and sclerosis, developed reproducible spike networks adjacent to their lesions that were highly lateralized compared to patients without lesions. Only 5% of mesial temporal lobe spikes were time-locked with scalp electrode spikes. Our preliminary observation on two lesional patients suggested that along with lesion location, Interictal spike networks also partially co-registered with seizure onset zones suggesting interrelationship between seizure onset and a subset of spike networks. ConclusionsThis is the first demonstration of patient-specific, reproducible interictal spike networks in mesial temporal structures that are closely linked to both temporal lobe lesions and seizure onset zones. SignificanceInterictal spike connectivity is a novel approach to map epileptic networks that could help advance invasive and non-invasive epilepsy treatments.

Electrocorticography and stereo EEG provide distinct measures of brain connectivity: implications for network models.

Brain network models derived from graph theory have the potential to guide functional neurosurgery, and to improve rates of post-operative seizure freedom for patients with epilepsy. A barrier to applying these models clinically is that intracranial EEG electrode implantation strategies vary by centre, region and country, from cortical grid & strip electrodes (Electrocorticography), to purely stereotactic depth electrodes (Stereo EEG), to a mixture of both. To determine whether models derived from one type of study are broadly applicable to others, we investigate the differences in brain networks mapped by electrocorticography and stereo EEG in a cohort of patients who underwent surgery for temporal lobe epilepsy and achieved a favourable outcome. We show that networks derived from electrocorticography and stereo EEG define distinct relationships between resected and spared tissue, which may be driven by sampling bias of temporal depth electrodes in patients with predominantly cortical grids. We propose a method of correcting for the effect of internodal distance that is specific to electrode type and explore how additional methods for spatially correcting for sampling bias affect network models. Ultimately, we find that smaller surgical targets tend to have lower connectivity with respect to the surrounding network, challenging notions that abnormal connectivity in the epileptogenic zone is typically high. Our findings suggest that effectively applying computational models to localize epileptic networks requires accounting for the effects of spatial sampling, particularly when analysing both electrocorticography and stereo EEG recordings in the same cohort, and that future network studies of epilepsy surgery should also account for differences in focality between resection and ablation. We propose that these findings are broadly relevant to intracranial EEG network modelling in epilepsy and an important step in translating them clinically into patient care.

Clinically localized seizure focus maybe not exactly the position of abating seizures: a computational evidence

By modeling the brain as a network, the challenge of abating seizure can be recast as a problem of network control. In the premise of bringing network under control, the minimum number of nodes prerequisite for controlling seizures are thus a natural aim of interest, which is still an outstanding issue. Here, we use the network structural control theory to guide the selection for the optimal control nodes with the aim of fully abating seizures. Firstly, we construct the dynamical complex network of pathological seizure by estimating the synchronicity and directionality of information flows over time between EEG signals from 10 patients with focal epilepsy. Then, based on the controllability and observability principles of complex systems, the minimum key nodes which are effective to fully control the network seizure behaviors are obtained. Results show that the calculated control nodes are distinct with the focus zones from clinic report. This suggests that the full control of epileptic network may not only related to the focus zone, the other non-focus nodes could also play important roles. This finding is validated by using the spatiotemporal neural network model connected with our modeled dynamical adjacent matrix. It successfully reproduces the original EEG signals which can be effectively abated by applying pulse stimulation on the identified key nodes or resecting them, while the partial effects can be obtained when functioning onto the clinically identified focus zones of 60% patients. Interestingly, for another 30% patients lesser nodes than clinic reports are need to fully control seizures. In addition, our work facilitates to identify the evolution paths of information flows, so the non-clinic focus zones identified through controllability principle can be supposed to be the potential seizure foci. In sum, our work propose a general methodology or strategy for seizures focus localizations that could comprehensively consider the time-evolving information flow and the analysis of controllability mechanisms driven by the real seizures data, as well as the computational validation. This may promote to develop the canonical computational framework with the core intent of providing support for clinical treatment decisions.

Graph theoretical analysis of evoked potentials shows network influence of epileptogenic mesial temporal region.

It is now widely accepted that seizures arise from the coordinated activity of epileptic networks, and as a result, traditional methods of analyzing seizures have been augmented by techniques like single‐pulse electrical stimulation (SPES) that estimate effective connectivity in brain networks. We used SPES and graph analytics in 18 patients undergoing intracranial EEG monitoring to investigate effective connectivity between recording sites within and outside mesial temporal structures. We compared evoked potential amplitude, network density, and centrality measures inside and outside the mesial temporal region (MTR) across three patient groups: focal epileptogenic MTR, multifocal epileptogenic MTR, and non‐epileptogenic MTR. Effective connectivity within the MTR had significantly greater magnitude (evoked potential amplitude) and network density, regardless of epileptogenicity. However, effective connectivity between MTR and surrounding non‐epileptogenic regions was of greater magnitude and density in patients with focal epileptogenic MTR compared to patients with multifocal epileptogenic MTR and those with non‐epileptogenic MTR. Moreover, electrodes within focal epileptogenic MTR had significantly greater outward network centrality compared to electrodes outside non‐epileptogenic regions and to multifocal and non‐epileptogenic MTR. Our results indicate that the MTR is a robustly connected subnetwork that can exert an overall elevated propagative influence over other brain regions when it is epileptogenic. Understanding the underlying effective connectivity and roles of epileptogenic regions within the larger network may provide insights that eventually lead to improved surgical outcomes.

FMRI-Based Effective Connectivity in Surgical Remediable Epilepsies: A Pilot Study.

Simultaneous EEG-fMRI can contribute to identify the epileptogenic zone (EZ) in focal epilepsies. However, fMRI maps related to Interictal Epileptiform Discharges (IED) commonly show multiple regions of signal change rather than focal ones. Dynamic causal modeling (DCM) can estimate effective connectivity, i.e. the causal effects exerted by one brain region over another, based on fMRI data. Here, we employed DCM on fMRI data in 10 focal epilepsy patients with multiple IED-related regions of BOLD signal change, to test whether this approach can help the localization process of EZ. For each subject, a family of competing deterministic, plausible DCM models were constructed using IED as autonomous input at each node, one at time. The DCM findings were compared to the presurgical evaluation results and classified as: "Concordant" if the node identified by DCM matches the presumed focus, "Discordant" if the node is distant from the presumed focus, or "Inconclusive" (no statistically significant result). Furthermore, patients who subsequently underwent intracranial EEG recordings or surgery were considered as having an independent validation of DCM results. The effective connectivity focus identified using DCM was Concordant in 7 patients, Discordant in two cases and Inconclusive in one. In four of the 6 patients operated, the DCM findings were validated. Notably, the two Discordant and Invalidated results were found in patients with poor surgical outcome. Our findings provide preliminary evidence to support the applicability of DCM on fMRI data to investigate the epileptic networks in focal epilepsy and, particularly, to identify the EZ in complex cases.

The electroclinical features and surgical outcomes of inferior perisylvian epilepsy

ObjectiveTo summarize the clinical and electrophysiological observations of epilepsy originating from the inferior perisylvian cortex, and analyze the potential epileptic networks underlying the semiological manifestations. MethodsWe retrospectively analyzed patients with refractory inferior perisylvian epilepsy (IPE) who had undergone resective surgery, and then reviewed the demographic, clinical, neuroelectrophysiological, neuroimaging, surgical, histopathological, and follow-up data of the patients from the respective medical records. The selected patients were then categorized in accordance with the results of semiological analysis. Quantitative 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) analysis was performed to investigate the underlying neural network. ResultsOf the 18 IPE patients assessed in this study, ipsilateral frontotemporal epileptic discharges or its onsets were the dominant interictal or ictal scalp EEG observations. In addition, oroalimentary or manual automatism was the most frequently documented manifestation, followed by facial tonic or clonic movements. Moreover, the semiological analysis identified and classified the patients into 2 patterns, and the PET statistical analyses conducted on these 2 groups revealed differences in the neural network between them. ConclusionInferior perisylvian epilepsy possesses semiological manifestations similar to those of mesial temporal lobe epilepsy or rolandic opercular epilepsy, hence these conditions should be carefully differentiated. Performing lesionectomy or cortectomy, sparing the mesial temporal structures, was found to be an effective and safe treatment modality for IPE.

Low-Intensity Focused Ultrasound-Mediated Attenuation of Acute Seizure Activity Based on EEG Brain Functional Connectivity.

(1) Background: Ultrasound has been used for noninvasive stimulation and is a promising technique for treating neurological diseases. Epilepsy is a common neurological disorder, that is attributed to uncontrollable abnormal neuronal hyperexcitability. Abnormal synchronized activities can be observed across multiple brain regions during a seizure. (2) Methods: we used low-intensity focused ultrasound (LIFU) to sonicate the brains of epileptic rats, analyzed the EEG functional brain network to explore the effect of LIFU on the epileptic brain network, and continued to explore the mechanism of ultrasound neuromodulation. LIFU was used in the hippocampus of epileptic rats in which a seizure was induced by kainic acid. (3) Results: By comparing the brain network characteristics before and after sonication, we found that LIFU significantly impacted the functional brain network, especially in the low-frequency band. The brain network connection strength across multiple brain regions significantly decreased after sonication compared to the connection strength in the control group. The brain network indicators (the path length, clustering coefficient, small-worldness, local efficiency and global efficiency) all changed significantly in the low-frequency. (4) Conclusions: These results revealed that LIFU could reduce the network connections of epilepsy circuits and change the structure of the brain network at the whole-brain level.

Ictal gamma-band interactions localize ictogenic nodes of the epileptic network in focal cortical dysplasia

ObjectiveEpilepsy surgery fails in > 30% of patients with focal cortical dysplasia (FCD). The seizure persistence after surgery can be attributed to the inability to precisely localize the tissue with an endogenous potential to generate seizures. In this study, we aimed to identify the critical components of the epileptic network that were actively involved in seizure genesis. MethodsThe directed transfer function was applied to intracranial EEG recordings and the effective connectivity was determined with a high temporal and frequency resolution. Pre-ictal network properties were compared with ictal epochs to identify regions actively generating ictal activity and discriminate them from the areas of propagation. ResultsAnalysis of 276 seizures from 30 patients revealed the existence of a seizure-related network reconfiguration in the gamma-band (25–170 Hz; p < 0.005) – ictogenic nodes. Unlike seizure onset zone, resecting the majority of ictogenic nodes correlated with favorable outcomes (p < 0.012). ConclusionThe prerequisite to successful epilepsy surgery is the accurate identification of brain areas from which seizures arise. We show that in FCD-related epilepsy, gamma-band network markers can reliably identify and distinguish ictogenic areas in macroelectrode recordings, improve intracranial EEG interpretation and better delineate the epileptogenic zone. SignificanceIctogenic nodes localize the critical parts of the epileptogenic tissue and increase the diagnostic yield of intracranial evaluation.

In vivo calcium imaging reveals disordered interictal network dynamics in epileptic stxbp1b zebrafish

SummarySTXBP1 mutations are associated with encephalopathy, developmental delay, intellectual disability, and epilepsy. While neural networks are known to operate at a critical state in the healthy brain, network behavior during pathological epileptic states remains unclear. Examining activity during periods between well-characterized ictal-like events (i.e., interictal period) could provide a valuable step toward understanding epileptic networks. To study these networks in the context of STXBP1 mutations, we combine a larval zebrafish model with in vivo fast confocal calcium imaging and extracellular local field potential recordings. Stxbp1b mutants display transient periods of elevated activity among local clusters of interacting neurons. These network “cascade” events were significantly larger in size and duration in mutants. At mesoscale resolution, cascades exhibit neurodevelopmental abnormalities. At single-cell scale, we describe spontaneous hyper-synchronized neuronal ensembles. That calcium imaging reveals uniquely disordered brain states during periods between pathological ictal-like seizure events is striking and represents a potential interictal biomarker.

Validation of semi-automated anatomically labeled SEEG contacts in a brain atlas for mapping connectivity in focal epilepsy.

ObjectiveStereotactic electroencephalography (SEEG) has been widely used to explore the epileptic network and localize the epileptic zone in patients with medically intractable epilepsy. Accurate anatomical labeling of SEEG electrode contacts is critically important for correctly interpreting epileptic activity. We present a method for automatically assigning anatomical labels to SEEG electrode contacts using a 3D‐segmented cortex and coregistered postoperative CT images.MethodStereotactic electroencephalography electrode contacts were spatially localized relative to the brain volume using a standard clinical procedure. Each contact was then assigned an anatomical label by clinical epilepsy fellows. Separately, each contact was automatically labeled by coregistering the subject's MRI to the USCBrain atlas using the BrainSuite software and assigning labels from the atlas based on contact locations. The results of both labeling methods were then compared, and a subsequent vetting of the anatomical labels was performed by expert review.ResultsAnatomical labeling agreement between the two methods for over 17 000 SEEG contacts was 82%. This agreement was consistent in patients with and without previous surgery (P = .852). Expert review of contacts in disagreement between the two methods resulted in agreement with the atlas based over manual labels in 48% of cases, agreement with manual over atlas‐based labels in 36% of cases, and disagreement with both methods in 16% of cases. Labels deemed incorrect by the expert review were then categorized as either in a region directly adjacent to the correct label or as a gross error, revealing a lower likelihood of gross error from the automated method.SignificanceThe method for semi‐automated atlas‐based anatomical labeling we describe here demonstrates potential to assist clinical workflow by reducing both analysis time and the likelihood of gross anatomical error. Additionally, it provides a convenient means of intersubject analysis by standardizing the anatomical labels applied to SEEG contact locations across subjects.

Wheels Within Wheels: Theory and Practice of Epileptic Networks.

Wheels Within Wheels: Theory and Practice of Epileptic Networks.

Responsive manipulation of neural circuit pathology by fully implantable, front-end multiplexed embedded neuroelectronics

Responsive neurostimulation is increasingly required to probe neural circuit function and treat neuropsychiatric disorders. We introduce a multiplex-then-amplify (MTA) scheme that, in contrast to current approaches (which necessitate an equal number of amplifiers as number of channels), only requires one amplifier per multiplexer, significantly reducing the number of components and the size of electronics in multichannel acquisition systems. It also enables simultaneous stimulation of arbitrary waveforms on multiple independent channels. We validated the function of MTA by developing a fully implantable, responsive embedded system that merges the ability to acquire individual neural action potentials using conformable conducting polymer-based electrodes with real-time onboard processing, low-latency arbitrary waveform stimulation, and local data storage within a miniaturized physical footprint. We verified established responsive neurostimulation protocols and developed a network intervention to suppress pathological coupling between the hippocampus and cortex during interictal epileptiform discharges. The MTA design enables effective, self-contained, chronic neural network manipulation with translational relevance to the treatment of neuropsychiatric disease.

Bilateral epileptic networks in congenital and acquired corpus callosum defects: EEG-fMRI study

ObjectivesElectroencephalography-correlated functional magnetic resonance imaging (EEG-fMRI) allows imaging of brain-wide epileptic networks, and demonstrates that focal interictal epileptic activity is sometimes accompanied by bilateral functional activations. The corpus callosum (CC) facilitates bilateral spread of epileptic activity and at times targeted surgically for drug-resistant epilepsy (DRE). We hypothesized that focal epileptic networks are more unilateral in patients lacking intact CC. MethodsWe included focal DRE patients who underwent pre-surgical EEG-fMRI and had CC agenesis (group A, n = 5), patients who previously underwent anterior callosotomy as treatment for drop attacks and continued having seizures (group B, n = 6), and control group of patients with focal epilepsy and intact CC (group C, n = 9). Blood-oxygenation-level-dependent (BOLD) signal maps were generated for interictal epileptic discharges. To quantify bi-hemispheric distribution of epileptic networks, laterality indices were compared between groups. Anatomical and diffusion-weighted imaging demonstrated white matter pathways. Results96% of studies demonstrated bilateral activations. Laterality indices were similar in groups A and C, whereas group B demonstrated a more bilateral network than group C (p = 0.028). Diffusion-weighted and anatomical imaging showed aberrant white matter pathways and larger anterior commissure in groups A and B. 68% of studies showed maximal activation cluster concordant with the presumed epileptic focus, 28% showed non-maximal activation at presumed focus. SignificanceFocal epileptic activity is associated with bilateral functional activations despite lack of intact CC, and is associated with stronger contralateral activation in patients after anterior callosotomy compared to controls. These findings disprove our initial hypothesis, and combined with white matter structural imaging, may indicate that the CC is not a sole route of propagation of epileptic activity, which might spread via anterior commissure. Our study demonstrates the utility of EEG-fMRI in assessing epileptic networks and potentially aiding in tailoring surgical treatments in DRE patients with callosal anomalies, and in callosal surgeries.

Interictal spike networks predict surgical outcome in patients with drug-resistant focal epilepsy.

ObjectiveTo determine if properties of epileptic networks could be delineated using interictal spike propagation seen on stereo‐electroencephalography (SEEG) and if these properties could predict surgical outcome in patients with drug‐resistant epilepsy.MethodsWe studied the SEEG of 45 consecutive drug‐resistant epilepsy patients who underwent subsequent epilepsy surgery: 18 patients with good post‐surgical outcome (Engel I) and 27 with poor outcome (Engel II–IV). Epileptic networks were derived from interictal spike propagation; these networks described the generation and propagation of interictal epileptic activity. We compared the regions in which spikes were frequent and the regions responsible for generating spikes to the area of resection and post‐surgical outcome. We developed a measure termed source spike concordance, which integrates information about both spike rate and region of spike generation.ResultsInclusion in the resection of regions with high spike rate is associated with good post‐surgical outcome (sensitivity = 0.82, specificity = 0.73). Inclusion in the resection of the regions responsible for generating interictal epileptic activity independently of rate is also associated with good post‐surgical outcome (sensitivity = 0.88, specificity = 0.82). Finally, when integrating the spike rate and the generators, we find that the source spike concordance measure has strong predictability (sensitivity = 0.91, specificity = 0.94).InterpretationsEpileptic networks derived from interictal spikes can determine the generators of epileptic activity. Inclusion of the most active generators in the resection is strongly associated with good post‐surgical outcome. These epileptic networks may aid clinicians in determining the area of resection during pre‐surgical evaluation.

Characterizing the seizure onset zone and epileptic network using EEG-fMRI in a rat seizure model

Accurate epileptogenic zone (EZ) or seizure onset zone (SOZ) localization is crucial for epilepsy surgery optimization. Previous animal and human studies on epilepsy have reported that changes in blood oxygen level-dependent (BOLD) signals induced by epileptic events could be used as diagnostic markers for EZ or SOZ localization. Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) recording is gaining interest as a non-invasive tool for preoperative epilepsy evaluation. However, EEG-fMRI studies have reported inconsistent and ambiguous findings. Therefore, it remains unclear whether BOLD responses can be used for accurate EZ or SOZ localization. In this study, we used simultaneous EEG-fMRI recording in a rat model of 4-aminopyridine-induced acute focal seizures to assess the spatial concordance between individual BOLD responses and the SOZ. This was to determine the optimal use of simultaneous EEG-fMRI recording in the SOZ localization. We observed a high spatial consistency between BOLD responses and the SOZ. Further, dynamic BOLD responses were consistent with the regions where the seizures were propagated. These results suggested that simultaneous EEG-fMRI recording could be used as a noninvasive clinical diagnostic technique for localizing the EZ or SOZ and could be an effective tool for mapping epileptic networks.

Phase-amplitude coupling of interictal fast activities modulated by slow waves on scalp EEG and its correlation with seizure outcomes of disconnection surgery in children with intractable nonlesional epileptic spasms.

Epileptic spasms (ESs) are classified as focal, generalized, or unknown onset ESs. The classification of ESs and surgery in patients without lesions apparent on MRI is challenging. Total corpus callosotomy (TCC) is a surgical option for diagnosis of the lateralization and possible treatment for ESs. This study investigated phase-amplitude coupling (PAC) of fast activity modulated by slow waves on scalp electroencephalography (EEG) to evaluate the strength of the modulation index (MI) before and after disconnection surgery in children with intractable nonlesional ESs. The authors hypothesize that a decreased MI due to surgery correlates with good seizure outcomes. The authors studied 10 children with ESs without lesions on MRI who underwent disconnection surgeries. Scalp EEG was obtained before and after surgery. The authors collected 20 epochs of 3 minutes each during non-rapid eye movement sleep. The MI of the gamma (30-70 Hz) amplitude and delta (0.5-4 Hz) phase was obtained in each electrode. MIs for each electrode were averaged in 4 brain areas (left/right, anterior/posterior quadrants) and evaluated to determine the correlation with seizure outcomes. The median age at first surgery was 2.3 years (range 10 months-9.1 years). Two patients with focal onset ESs underwent anterior quadrant disconnection (AQD). TCC alone was performed in 5 patients with generalized or unknown onset ESs. Two patients achieved seizure freedom. Three patients had residual generalized onset ESs. Disconnection surgeries in addition to TCC consisted of TCC + posterior quadrant disconnection (PQD) (1 patient); TCC + AQD + PQD (1 patient); and TCC + AQD + hemispherotomy (1 patient). Seven patients became seizure free with a mean follow-up period of 28 months (range 5-54 months). After TCC, MIs in 4 quadrants were significantly lower in the 2 seizure-free patients than in the 6 patients with residual ESs (p < 0.001). After all 15 disconnection surgeries in 10 patients, MIs in the 13 target quadrants for each disconnection surgery that resulted in freedom from seizures were significantly lower than in the 26 target quadrants in patients with residual ESs (p < 0.001). In children with nonlesional ESs, PAC for scalp EEG before and after disconnection surgery may be a surrogate marker for control of ESs. The MI may indicate epileptogenic neuronal modulation of the interhemispheric corpus callosum and intrahemispheric subcortical network for ESs. TCC may be a therapeutic option to disconnect the interhemispheric modulation of epileptic networks.

Transcutaneous auricular vagus nerve stimulation induces stabilizing modifications in large-scale functional brain networks: towards understanding the effects of taVNS in subjects with epilepsy

Transcutaneous auricular vagus nerve stimulation (taVNS) is a novel non-invasive brain stimulation technique considered as a potential supplementary treatment option for subjects with refractory epilepsy. Its exact mechanism of action is not yet fully understood. We developed an examination schedule to probe for immediate taVNS-induced modifications of large-scale epileptic brain networks and accompanying changes of cognition and behaviour. In this prospective trial, we applied short-term (1 h) taVNS to 14 subjects with epilepsy during a continuous 3-h EEG recording which was embedded in two standardized neuropsychological assessments. From these EEG, we derived evolving epileptic brain networks and tracked important topological, robustness, and stability properties of networks over time. In the majority of investigated subjects, taVNS induced measurable and persisting modifications in network properties that point to a more resilient epileptic brain network without negatively impacting cognition, behaviour, or mood. The stimulation was well tolerated and the usability of the device was rated good. Short-term taVNS has a topology-modifying, robustness- and stability-enhancing immediate effect on large-scale epileptic brain networks. It has no detrimental effects on cognition and behaviour. Translation into clinical practice requires further studies to detail knowledge about the exact mechanisms by which taVNS prevents or inhibits seizures.

Epilepsy surgery in stroke-related epilepsy

PurposeTo provide a descriptive analysis on the presurgical evaluation and surgical management of a cohort of patients with stroke related epilepsy (SRE). MethodsWe retrospectively examined the clinical characteristics, results of non-invasive and invasive presurgical evaluation, surgical management and outcome of consecutive patients with drug-resistant SRE in our institution from January 1, 2013 to January 1, 2020. ResultsTwenty-one of 420 patients (5%) who underwent intracranial EEG (iEEG), resective epilepsy surgery and/or vagus nerve stimulation (VNS) placement, had SRE. Of 13 patients who had iEEG, the ictal onset (IO) was exclusively within the stroke lesion in only one patient. In five patients the IO was extra-lesional and in the remaining seven patients it included the stroke lesion as well as extra-lesional structures. The IO included the mesial temporal region in 11 of the 13 patients (85%). The posterior margin of the stroke lesion was always involved. Five patients underwent surgery without iEEG. In total, 10 patients underwent resective surgery, four VNS placement and two had both corpus callosotomy and VNS placement. Of the patients who had resective surgery, nine were Engel I or II at last follow up. ConclusionWe found that seizures in patients with drug resistant SRE were more frequently originated in the mesial temporal region than in the stroke lesion itself. Despite the complex epileptic network underlying drug-resistant SRE, a thorough presurgical assessment and adequate use of surgical options can lead to excellent surgical outcomes.