High-density electroencephalographic functional networks in genetic generalized epilepsy: Preserved whole-brain topology hides local reorganization.

OBJECTIVE: Genetic generalized epilepsy (GGE) accounts for approximately 20% of adult epilepsy cases and is considered a disorder of large brain networks, involving both hemispheres. Most studies have not shown any difference in functional whole-brain network topology when compared to healthy controls. Our objective was to examine whether this preserved global network topology could hide local reorganizations that balance out at the global network level. METHODS: We recorded high-density electroencephalograms from 20 patients and 20 controls, and reconstructed the activity of 118 regions. We computed functional connectivity in windows free of interictal epileptiform discharges in broad, delta, theta, alpha, and beta frequency bands, characterized the network topology, and used the Hub Disruption Index (HDI) to quantify the topological reorganization. We examined the generalizability of our results by reproducing a 25-electrode clinical system. RESULTS: Our study did not reveal any significant change in whole-brain network topology among GGE patients. However, the HDI was significantly different between patients and controls in all frequency bands except alpha (p < .01, false discovery rate [FDR] corrected, d < -1), and accompanied by an increase in connectivity in the prefrontal regions and default mode network. This reorganization suggests that regions that are important in transferring the information in controls were less so in patients. Inversely, the crucial regions in patients are less so in controls. These findings were also found in delta and theta frequency bands when using 25 electrodes (p < .001, FDR corrected, d < -1). SIGNIFICANCE: In GGE patients, the overall network topology is similar to that of healthy controls but presents a balanced local topological reorganization. This reorganization causes the prefrontal areas and default mode network to be more integrated and segregated, which may explain executive impairment associated with GGE. Additionally, the reorganization distinguishes patients from controls even when using 25 electrodes, suggesting its potential use as a diagnostic tool.

Long-term outcome of alcohol withdrawal seizures.

BACKGROUND AND PURPOSE: Alcohol withdrawal seizures (AWS) are a well-known complication of chronic alcohol abuse, but there is currently little knowledge of their long-term relapse rate and prognosis. The aims of this study were to identify risk factors for AWS recurrence and to study the overall outcome of patients after AWS. METHODS: In this retrospective single-center study, we included patients who were admitted to the Emergency Department after an AWS between January 1, 2013 and August 10, 2021 and for whom an electroencephalogram (EEG) was requested. AWS relapses up until April 29, 2022 were researched. We compared history, treatment with benzodiazepines or antiseizure medications (ASMs), laboratory, EEG and computed tomography findings between patients with AWS relapse (r-AWS) and patients with no AWS relapse (nr-AWS). RESULTS: A total of 199 patients were enrolled (mean age 53 ± 12 years; 78.9% men). AWS relapses occurred in 11% of patients, after a median time of 470.5 days. Brain computed tomography (n = 182) showed pathological findings in 35.7%. Risk factors for relapses were history of previous AWS (p = 0.013), skull fractures (p = 0.004) at the index AWS, and possibly epileptiform EEG abnormalities (p = 0.07). Benzodiazepines or other ASMs, taken before or after the index event, did not differ between the r-AWS and the nr-AWS group. The mortality rate was 2.9%/year of follow-up, which was 13 times higher compared to the general population. Risk factors for death were history of AWS (p < 0.001) and encephalopathic EEG (p = 0.043). CONCLUSIONS: Delayed AWS relapses occur in 11% of patients and are associated with risk factors (previous AWS >24 h apart, skull fractures, and pathological EEG findings) that also increase the epilepsy risk, that is, predisposition for seizures, if not treated. Future prospective studies are mandatory to determine appropriate long-term diagnostic and therapeutic strategies, in order to reduce the risk of relapse and mortality associated with AWS.

Antiseizure medication ≤48 hours portends better prognosis in new-onset epilepsy.

BACKGROUND: Several studies found that patients with new-onset epilepsy (NOE) have higher seizure recurrence rates if they presented already prior seizures. These observations suggest that timing of antiseizure medication (ASM) is crucial and should be offered immediately after the first seizure. Here, we wanted to assess whether immediate ASM is associated with improved outcome. METHODS: Single-center study of 1010 patients (≥16 years) who presented with a possible first seizure in the emergency department between 1 March 2010 and 1 March 2017. A comprehensive workup was launched upon arrival, including routine electroencephalography (EEG), brain computed tomography/magnetic resonance imaging, long-term overnight EEG and specialized consultations. We followed patients for 5 years comparing the relapse rate in patients treated within 48 h to those with treatment >48 h. RESULTS: A total of 487 patients were diagnosed with NOE. Of the 416 patients (162 female, age: 54.6 ± 21.1 years) for whom the treatment start could be retrieved, 80% (333/416) were treated within 48 h. The recurrence rate after immediate treatment (32%; 107/333) was significantly lower than in patients treated later (56.6%; 47/83; p < 0.001). For patients for whom a complete 5-year-follow-up was available (N = 297, 123 female), those treated ≤48 h (N = 228; 76.8%) had a significantly higher chance of remaining seizure-free compared with patients treated later (N = 69; 23.2%; p < 0.001). CONCLUSIONS: In this retrospective study, immediate ASM therapy (i.e., within 48 h) was associated with better prognosis up to 5 years after the index event. Prospective studies are required to determine the value of immediate workup and drug therapy in NOE patients.

Frequency-specific gaze modulation of emotional face processing in the human amygdala.

Determining the social significance of emotional face expression is of major importance for adaptive behavior, and gaze direction provides critical information in this process. The amygdala is implicated in both emotion and gaze processing, but how and when it integrates expression and gaze cues remains unresolved. We tackled this question using intracranial electroencephalography in epileptic patients to assess both amygdala (n = 12) and orbitofrontal cortex (OFC; n = 11) time-frequency evoked responses to faces with different emotional expressions and different gaze directions. As predicted, self-relevant threat signals (averted fearful and directed angry faces) elicited stronger amygdala activity than self-irrelevant threat (directed fearful and averted angry faces). Fear effects started at early latencies in both amygdala and OFC (~110 and 160 ms, respectively), while gaze direction effects and their interaction with emotion occurred at later latencies. Critically, the amygdala showed differential gamma band increases to fearful averted gaze (starting ~550 ms) and to angry directed gaze (~470 ms). Moreover, when comparing the 2 self-relevant threat conditions among them, we found higher gamma amygdala activity for averted fearful faces and higher beta OFC activity for angry directed faces. Together, these results reveal for the first time frequency-specific effects of emotion and gaze on amygdala and OFC neural activity.

Prestimulus amygdala spectral activity is associated with visual face awareness.

Alpha cortical oscillations have been proposed to suppress sensory processing in the visual, auditory, and tactile domains, influencing conscious stimulus perception. However, it is unknown whether oscillatory neural activity in the amygdala, a subcortical structure involved in salience detection, has a similar impact on stimulus awareness. Recording intracranial electroencephalography (EEG) from 9 human amygdalae during face detection in a continuous flash suppression task, we found increased spectral prestimulus power and phase coherence, with most consistent effects in the alpha band, when faces were undetected relative to detected, similarly as previously observed in cortex with this task using scalp-EEG. Moreover, selective decreases in the alpha and gamma bands preceded face detection, with individual prestimulus alpha power correlating negatively with detection rate in patients. These findings reveal for the first time that prestimulus subcortical oscillations localized in human amygdala may contribute to perceptual gating mechanisms governing subsequent face detection and offer promising insights on the role of this structure in visual awareness.

Added value of advanced workup after the first seizure: A 7-year cohort study.

OBJECTIVE: This study was undertaken to establish whether advanced workup including long-term electroencephalography (LT-EEG) and brain magnetic resonance imaging (MRI) provides an additional yield for the diagnosis of new onset epilepsy (NOE) in patients presenting with a first seizure event (FSE). METHODS: In this population-based study, all adult (≥16 years) patients presenting with FSE in the emergency department (ED) between March 1, 2010 and March 1, 2017 were assessed. Patients with obvious nonepileptic or acute symptomatic seizures were excluded. Routine EEG, LT-EEG, brain computed tomography (CT), and brain MRI were performed as part of the initial workup. These examinations' sensitivity and specificity were calculated on the basis of the final diagnosis after 2 years, along with the added value of advanced workup (MRI and LT-EEG) over routine workup (routine EEG and CT). RESULTS: Of the 1010 patients presenting with FSE in the ED, a definite diagnosis of NOE was obtained for 501 patients (49.6%). Sensitivity of LT-EEG was higher than that of routine EEG (54.39% vs. 25.5%, p < .001). Similarly, sensitivity of MRI was higher than that of CT (67.98% vs. 54.72%, p = .009). Brain MRI showed epileptogenic lesions in an additional 32% compared to brain CT. If only MRI and LT-EEG were considered, five would have been incorrectly diagnosed as nonepileptic (5/100, 5%) compared to patients with routine EEG and MRI (25/100, 25%, p = .0001). In patients with all four examinations, advanced workup provided an overall additional yield of 50% compared to routine workup. SIGNIFICANCE: Our results demonstrate the remarkable added value of the advanced workup launched already in the ED for the diagnosis of NOE versus nonepileptic causes of seizure mimickers. Our findings suggest the benefit of first-seizure tracks or even units with overnight EEG, similar to stroke units, activated upon admission in the ED.

Advances in human intracranial electroencephalography research, guidelines and good practices.

Since the second-half of the twentieth century, intracranial electroencephalography (iEEG), including both electrocorticography (ECoG) and stereo-electroencephalography (sEEG), has provided an intimate view into the human brain. At the interface between fundamental research and the clinic, iEEG provides both high temporal resolution and high spatial specificity but comes with constraints, such as the individual's tailored sparsity of electrode sampling. Over the years, researchers in neuroscience developed their practices to make the most of the iEEG approach. Here we offer a critical review of iEEG research practices in a didactic framework for newcomers, as well addressing issues encountered by proficient researchers. The scope is threefold: (i) review common practices in iEEG research, (ii) suggest potential guidelines for working with iEEG data and answer frequently asked questions based on the most widespread practices, and (iii) based on current neurophysiological knowledge and methodologies, pave the way to good practice standards in iEEG research. The organization of this paper follows the steps of iEEG data processing. The first section contextualizes iEEG data collection. The second section focuses on localization of intracranial electrodes. The third section highlights the main pre-processing steps. The fourth section presents iEEG signal analysis methods. The fifth section discusses statistical approaches. The sixth section draws some unique perspectives on iEEG research. Finally, to ensure a consistent nomenclature throughout the manuscript and to align with other guidelines, e.g., Brain Imaging Data Structure (BIDS) and the OHBM Committee on Best Practices in Data Analysis and Sharing (COBIDAS), we provide a glossary to disambiguate terms related to iEEG research.

Crossmodal Phase Reset and Evoked Responses Provide Complementary Mechanisms for the Influence of Visual Speech in Auditory Cortex.

Natural conversation is multisensory: when we can see the speaker's face, visual speech cues improve our comprehension. The neuronal mechanisms underlying this phenomenon remain unclear. The two main alternatives are visually mediated phase modulation of neuronal oscillations (excitability fluctuations) in auditory neurons and visual input-evoked responses in auditory neurons. Investigating this question using naturalistic audiovisual speech with intracranial recordings in humans of both sexes, we find evidence for both mechanisms. Remarkably, auditory cortical neurons track the temporal dynamics of purely visual speech using the phase of their slow oscillations and phase-related modulations in broadband high-frequency activity. Consistent with known perceptual enhancement effects, the visual phase reset amplifies the cortical representation of concomitant auditory speech. In contrast to this, and in line with earlier reports, visual input reduces the amplitude of evoked responses to concomitant auditory input. We interpret the combination of improved phase tracking and reduced response amplitude as evidence for more efficient and reliable stimulus processing in the presence of congruent auditory and visual speech inputs.SIGNIFICANCE STATEMENT Watching the speaker can facilitate our understanding of what is being said. The mechanisms responsible for this influence of visual cues on the processing of speech remain incompletely understood. We studied these mechanisms by recording the electrical activity of the human brain through electrodes implanted surgically inside the brain. We found that visual inputs can operate by directly activating auditory cortical areas, and also indirectly by modulating the strength of cortical responses to auditory input. Our results help to understand the mechanisms by which the brain merges auditory and visual speech into a unitary perception.

Slow oscillations open susceptible time windows for epileptic discharges.

OBJECTIVE: In patients with epilepsy, interictal epileptic discharges are a diagnostic hallmark of epilepsy and represent abnormal, so-called "irritative" activity that disrupts normal cognitive functions. Despite their clinical relevance, their mechanisms of generation remain poorly understood. It is assumed that brain activity switches abruptly, unpredictably, and supposedly randomly to these epileptic transients. We aim to study the period preceding these epileptic discharges, to extract potential proepileptogenic mechanisms supporting their expression. METHODS: We used multisite intracortical recordings from patients who underwent intracranial monitoring for refractory epilepsy, the majority of whom had a mesial temporal lobe seizure onset zone. Our objective was to evaluate the existence of proepileptogenic windows before interictal epileptic discharges. We tested whether the amplitude and phase synchronization of slow oscillations (.5-4 Hz and 4-7 Hz) increase before epileptic discharges and whether the latter are phase-locked to slow oscillations. Then, we tested whether the phase-locking of neuronal activity (assessed by high-gamma activity, 60-160 Hz) to slow oscillations increases before epileptic discharges to provide a potential mechanism linking slow oscillations to interictal activities. RESULTS: Changes in widespread slow oscillations anticipate upcoming epileptic discharges. The network extends beyond the irritative zone, but the increase in amplitude and phase synchronization is rather specific to the irritative zone. In contrast, epileptic discharges are phase-locked to widespread slow oscillations and the degree of phase-locking tends to be higher outside the irritative zone. Then, within the irritative zone only, we observe an increased coupling between slow oscillations and neuronal discharges before epileptic discharges. SIGNIFICANCE: Our results show that epileptic discharges occur during vulnerable time windows set up by a specific phase of slow oscillations. The specificity of these permissive windows is further reinforced by the increased coupling of neuronal activity to slow oscillations. These findings contribute to our understanding of epilepsy as a distributed oscillopathy and open avenues for future neuromodulation strategies aiming at disrupting proepileptic mechanisms.

Brain Recording, Mind-Reading, and Neurotechnology: Ethical Issues from Consumer Devices to Brain-Based Speech Decoding.

Brain reading technologies are rapidly being developed in a number of neuroscience fields. These technologies can record, process, and decode neural signals. This has been described as 'mind reading technology' in some instances, especially in popular media. Should the public at large, be concerned about this kind of technology? Can it really read minds? Concerns about mind-reading might include the thought that, in having one's mind open to view, the possibility for free deliberation, and for self-conception, are eroded where one isn't at liberty to privately mull things over. Themes including privacy, cognitive liberty, and self-conception and expression appear to be areas of vital ethical concern. Overall, this article explores whether brain reading technologies are really mind reading technologies. If they are, ethical ways to deal with them must be developed. If they are not, researchers and technology developers need to find ways to describe them more accurately, in order to dispel unwarranted concerns and address appropriately those that are warranted.

Neuroprosthetic Speech: The Ethical Significance of Accuracy, Control and Pragmatics.

Neuroprosthetic speech devices are an emerging technology that can offer the possibility of communication to those who are unable to speak. Patients with 'locked in syndrome,' aphasia, or other such pathologies can use covert speech-vividly imagining saying something without actual vocalization-to trigger neural controlled systems capable of synthesizing the speech they would have spoken, but for their impairment.We provide an analysis of the mechanisms and outputs involved in speech mediated by neuroprosthetic devices. This analysis provides a framework for accounting for the ethical significance of accuracy, control, and pragmatic dimensions of prosthesis-mediated speech. We first examine what it means for the output of the device to be accurate, drawing a distinction between technical accuracy on the one hand and semantic accuracy on the other. These are conceptual notions of accuracy.Both technical and semantic accuracy of the device will be necessary (but not yet sufficient) for the user to have sufficient control over the device. Sufficient control is an ethical consideration: we place high value on being able to express ourselves when we want and how we want. Sufficient control of a neural speech prosthesis requires that a speaker can reliably use their speech apparatus as they want to, and can expect their speech to authentically represent them. We draw a distinction between two relevant features which bear on the question of whether the user has sufficient control: voluntariness of the speech and the authenticity of the speech. These can come apart: the user might involuntarily produce an authentic output (perhaps revealing private thoughts) or might voluntarily produce an inauthentic output (e.g., when the output is not semantically accurate). Finally, we consider the role of the interlocutor in interpreting the content and purpose of the communication.These three ethical dimensions raise philosophical questions about the nature of speech, the level of control required for communicative accuracy, and the nature of 'accuracy' with respect to both natural and prosthesis-mediated speech.

Low-Frequency Cortical Oscillations Entrain to Subthreshold Rhythmic Auditory Stimuli.

Many environmental stimuli contain temporal regularities, a feature that can help predict forthcoming input. Phase locking (entrainment) of ongoing low-frequency neuronal oscillations to rhythmic stimuli is proposed as a potential mechanism for enhancing neuronal responses and perceptual sensitivity, by aligning high-excitability phases to events within a stimulus stream. Previous experiments show that rhythmic structure has a behavioral benefit even when the rhythm itself is below perceptual detection thresholds (ten Oever et al., 2014). It is not known whether this "inaudible" rhythmic sound stream also induces entrainment. Here we tested this hypothesis using magnetoencephalography and electrocorticography in humans to record changes in neuronal activity as subthreshold rhythmic stimuli gradually became audible. We found that significant phase locking to the rhythmic sounds preceded participants' detection of them. Moreover, no significant auditory-evoked responses accompanied this prethreshold entrainment. These auditory-evoked responses, distinguished by robust, broad-band increases in intertrial coherence, only appeared after sounds were reported as audible. Taken together with the reduced perceptual thresholds observed for rhythmic sequences, these findings support the proposition that entrainment of low-frequency oscillations serves a mechanistic role in enhancing perceptual sensitivity for temporally predictive sounds. This framework has broad implications for understanding the neural mechanisms involved in generating temporal predictions and their relevance for perception, attention, and awareness.SIGNIFICANCE STATEMENT The environment is full of rhythmically structured signals that the nervous system can exploit for information processing. Thus, it is important to understand how the brain processes such temporally structured, regular features of external stimuli. Here we report the alignment of slowly fluctuating oscillatory brain activity to external rhythmic structure before its behavioral detection. These results indicate that phase alignment is a general mechanism of the brain to process rhythmic structure and can occur without the perceptual detection of this temporal structure.

Electroencephalography, magnetoencephalography and source localization: their value in epilepsy.

PURPOSE OF REVIEW: Source localization of cerebral activity using electroencephalography (EEG) or magnetoencephalography (MEG) can reveal noninvasively the generators of the abnormal signals recorded in epilepsy, such as interictal epileptic discharges (IEDs) and seizures. Here, we review recent progress showcasing the usefulness of these techniques in treating patients with drug-resistant epilepsy. RECENT FINDINGS: The source localization of IEDs by high-density EEG and MEG has now been proved in large patient cohorts to be accurate and clinically relevant, with positive and negative predictive values rivaling those of structural MRI. Localizing seizure onsets is an emerging technique that seems to perform similarly well to the localization of interictal spikes, although there remain questions regarding the processing of signals for reliable results. The localization of somatosensory cortex using EEG/MEG is well established. The localization of language cortex is less reliable, although progress has been made regarding hemispheric lateralization. Source localization is also able to reveal how epilepsy alters the dynamics of neuronal activity in the large-scale networks that underlie cerebral function. SUMMARY: Given the high performance of EEG/MEG source localization, these tools should find a place similar to that of established techniques like MRI in the assessment of patients for epilepsy surgery.

Evaluation of cortical local field potential diffusion in stereotactic electro-encephalography recordings: A glimpse on white matter signal.

While there is a strong interest in meso-scale field potential recording using intracranial electroencephalography with penetrating depth electrodes (i.e. stereotactic EEG or S-EEG) in humans, the signal recorded in the white matter remains ignored. White matter is generally considered electrically neutral and often included in the reference montage. Moreover, re-referencing electrophysiological data is a critical preprocessing choice that could drastically impact signal content and consequently the results of any given analysis. In the present stereotactic electroencephalography study, we first illustrate empirically the consequences of commonly used references (subdermal, white matter, global average, local montage) on inter-electrode signal correlation. Since most of these reference montages incorporate white matter signal, we next consider the difference between signals recorded in cortical gray matter and white matter. Our results reveal that electrode contacts located in the white matter record a mixture of activity, with part arising from the volume conduction (zero time delay) of activity from nearby gray matter. Furthermore, our analysis shows that white matter signal may be correlated with distant gray matter signal. While residual passive electrical spread from nearby matter may account for this relationship, our results suggest the possibility that this long distance correlation arises from the white matter fiber tracts themselves (i.e. activity from distant gray matter traveling along axonal fibers with time lag larger than zero); yet definitive conclusions about the origin of the white matter signal would require further experimental substantiation. By characterizing the properties of signals recorded in white matter and in gray matter, this study illustrates the importance of including anatomical prior knowledge when analyzing S-EEG data.

Tuning face perception with electrical stimulation of the fusiform gyrus.

The fusiform gyrus (FG) is an important node in the face processing network, but knowledge of its causal role in face perception is currently limited. Recent work demonstrated that high frequency stimulation applied to the FG distorts the perception of faces in human subjects (Parvizi et al. []: J Neurosci 32:14915-14920). However, the timing of this process in the FG relative to stimulus onset and the spatial extent of FG's role in face perception are unknown. Here, we investigate the causal role of the FG in face perception by applying precise, event-related electrical stimulation (ES) to higher order visual areas including the FG in six human subjects undergoing intracranial monitoring for epilepsy. We compared the effects of single brief (100 µs) electrical pulses to the FG and non-face-selective visual areas on the speed and accuracy of detecting distorted faces. Brief ES applied to face-selective sites did not affect accuracy but significantly increased the reaction time (RT) of detecting face distortions. Importantly, RT was altered only when ES was applied 100ms after visual onset and in face-selective but not place-selective sites. Furthermore, ES applied to face-selective areas decreased the amplitude of visual evoked potentials and high gamma power over this time window. Together, these results suggest that ES of face-selective regions within a critical time window induces a delay in face perception. These findings support a temporally and spatially specific causal role of face-selective areas and signify an important link between electrophysiology and behavior in face perception. Hum Brain Mapp 38:2830-2842, 2017. © 2017 Wiley Periodicals, Inc.

Seeing scenes: topographic visual hallucinations evoked by direct electrical stimulation of the parahippocampal place area.

In recent years, functional neuroimaging has disclosed a network of cortical areas in the basal temporal lobe that selectively respond to visual scenes, including the parahippocampal place area (PPA). Beyond the observation that lesions involving the PPA cause topographic disorientation, there is little causal evidence linking neural activity in that area to the perception of places. Here, we combined functional magnetic resonance imaging (fMRI) and intracranial EEG (iEEG) recordings to delineate place-selective cortex in a patient implanted with stereo-EEG electrodes for presurgical evaluation of drug-resistant epilepsy. Bipolar direct electrical stimulation of a cortical area in the collateral sulcus and medial fusiform gyrus, which was place-selective according to both fMRI and iEEG, induced a topographic visual hallucination: the patient described seeing indoor and outdoor scenes that included views of the neighborhood he lives in. By contrast, stimulating the more lateral aspect of the basal temporal lobe caused distortion of the patient's perception of faces, as recently reported (Parvizi et al., 2012). Our results support the causal role of the PPA in the perception of visual scenes, demonstrate that electrical stimulation of higher order visual areas can induce complex hallucinations, and also reaffirm direct electrical brain stimulation as a tool to assess the function of the human cerebral cortex.

Baclofen-Associated Onset of Central Sleep Apnea in Alcohol Use Disorder: A Case Report.

A 61-year-old patient with alcohol use disorder (AUD) was referred for suspicion of sleep apnea syndrome (SAS). He had incurred three road accidents attributed to sleepiness over the previous year, shortly after initiation of high-dose (100 mg b.i.d.) treatment with baclofen, a molecule increasingly used in the management of AUD. Polysomnography revealed a severe central SAS (CSAS) with an apnea-hypopnea index (AHI) of 81.6/h. Baclofen was suggested as a possible cause of the CSAS, and after its withdrawal, a second polysomnography was done, showing the disappearance of the central apneas and a shift to severe obstructive SAS (AHI 43.9/h), for which a positive airway pressure (CPAP) treatment was initiated. A third polysomnography was performed under CPAP after reintroduction of baclofen (50 mg b.i.d.) by the patient, showing reappearance of the CSAS (AHI 42.1/h). This case report illustrates the deleterious effect of baclofen on breathing physiology during sleep. Since it is typically prescribed off label at high doses to a population of patients potentially using other substances that inhibit the ventilatory drive, this possible adverse effect is a major concern. When considering the use of baclofen in patients with AUD, the potential for sleep-disordered breathing should be weighed and carefully monitored.

Electric source imaging of interictal activity accurately localises the seizure onset zone.

OBJECTIVE: It remains controversial whether interictal spikes are a surrogate of the seizure onset zone (SOZ). Electric source imaging (ESI) is an increasingly validated non-invasive approach for localising the epileptogenic focus in patients with drug-resistant epilepsy undergoing evaluation for surgery, using high-density scalp EEG and advanced source localisation algorithms that include the patient's own MRI. Here we investigate whether localisation of interictal spikes by ESI provides valuable information on the SOZ. METHODS: In 38 patients with focal epilepsy who later underwent intracranial EEG monitoring, we performed ESI of interictal spikes recorded with 128-256-channel EEG. We measured the distance between the ESI maximum and the nearest intracranial electrodes in the SOZ and irritative zone (IZ, the source of interictal spikes). The resection of the region harbouring the ESI maximum was correlated to surgical outcome. RESULTS: The median distance from the ESI maximum to the nearest electrode involved in the SOZ was 17 mm (IQR 8-27). The IZ and SOZ colocalised in most patients (median distance 0 mm, IQR 0-14), supporting the notion that localising interictal spikes is a valid surrogate for the SOZ. There was no difference in accuracy among patients with temporal or extratemporal epilepsy. In the 32 patients who underwent resective surgery, including the ESI maximum in the resection correlated with favourable outcome (p=0.03). CONCLUSIONS: Localisation of interictal spikes provides an excellent estimate of the SOZ in the majority of patients. ESI should be taken into account for the management of patients undergoing intracranial recordings.

Voxeloc: A time-saving graphical user interface for localizing and visualizing stereo-EEG electrodes.

BACKGROUND: Thanks to its unrivalled spatial and temporal resolutions and signal-to-noise ratio, intracranial EEG (iEEG) is becoming a valuable tool in neuroscience research. To attribute functional properties to cortical tissue, it is paramount to be able to determine precisely the localization of each electrode with respect to a patient's brain anatomy. Several software packages or pipelines offer the possibility to localize manually or semi-automatically iEEG electrodes. However, their reliability and ease of use may leave to be desired. NEW METHOD: Voxeloc (voxel electrode locator) is a Matlab-based graphical user interface to localize and visualize stereo-EEG electrodes. Voxeloc adopts a semi-automated approach to determine the coordinates of each electrode contact, the user only needing to indicate the deep-most contact of each electrode shaft and another point more proximally. RESULTS: With a deliberately streamlined functionality and intuitive graphical user interface, the main advantages of Voxeloc are ease of use and inter-user reliability. Additionally, oblique slices along the shaft of each electrode can be generated to facilitate the precise localization of each contact. Voxeloc is open-source software and is compatible with the open iEEG-BIDS (Brain Imaging Data Structure) format. COMPARISON WITH EXISTING METHODS: Localizing full patients' iEEG implants was faster using Voxeloc than two comparable software packages, and the inter-user agreement was better. CONCLUSIONS: Voxeloc offers an easy-to-use and reliable tool to localize and visualize stereo-EEG electrodes. This will contribute to democratizing neuroscience research using iEEG.