Learn how to interpret and use intracranial EEG findings.

Epilepsy surgery is the therapy of choice for many patients with drug-resistant focal epilepsy. Recognizing and describing ictal and interictal patterns with intracranial electroencephalography (EEG) recordings is important in order to most efficiently leverage advantages of this technique to accurately delineate the seizure-onset zone before undergoing surgery. In this seminar in epileptology, we address learning objective "1.4.11 Recognize and describe ictal and interictal patterns with intracranial recordings" of the International League against Epilepsy curriculum for epileptologists. We will review principal considerations of the implantation planning, summarize the literature for the most relevant ictal and interictal EEG patterns within and beyond the Berger frequency spectrum, review invasive stimulation for seizure and functional mapping, discuss caveats in the interpretation of intracranial EEG findings, provide an overview on special considerations in children and in subdural grids/strips, and review available quantitative/signal analysis approaches. To be as practically oriented as possible, we will provide a mini atlas of the most frequent EEG patterns, highlight pearls for its not infrequently challenging interpretation, and conclude with two illustrative case examples. This article shall serve as a useful learning resource for trainees in clinical neurophysiology/epileptology by providing a basic understanding on the concepts of invasive intracranial EEG.

Entropy in scalp EEG can be used as a preimplantation marker for VNS efficacy.

Vagus nerve stimulation (VNS) is a therapeutic option in drug-resistant epilepsy. VNS leads to ≥ 50% seizure reduction in 50 to 60% of patients, termed "responders". The remaining 40 to 50% of patients, "non-responders", exhibit seizure reduction < 50%. Our work aims to differentiate between these two patient groups in preimplantation EEG analysis by employing several Entropy methods. We identified 59 drug-resistant epilepsy patients treated with VNS. We established their response to VNS in terms of responders and non-responders. A preimplantation EEG with eyes open/closed, photic stimulation, and hyperventilation was found for each patient. The EEG was segmented into eight time intervals within four standard frequency bands. In all, 32 EEG segments were obtained. Seven Entropy methods were calculated for all segments. Subsequently, VNS responders and non-responders were compared using individual Entropy methods. VNS responders and non-responders differed significantly in all Entropy methods except Approximate Entropy. Spectral Entropy revealed the highest number of EEG segments differentiating between responders and non-responders. The most useful frequency band distinguishing responders and non-responders was the alpha frequency, and the most helpful time interval was hyperventilation and rest 4 (the end of EEG recording).

Single-center long-term results of vagus nerve stimulation for pediatric epilepsy: a 10-17-year follow-up study.

PURPOSE: A retrospective study, based on a prospectively built database, presents the results of long-term follow-up care of pediatric vagus nerve stimulation (VNS) patients in terms of seizure outcome, surgical aspects, the potential impact of maturation, and medication changes. METHODS: From a prospectively built database, 16 VNS patients (median age 12.0 years, range 6.0 to 16.0 years; median seizure duration 6.5 years, range 2.0 to 15.5 years) followed for at least 10 years were graded as non-responder - NR (seizure frequency reduction < 50%), responder - R (reduction ≥ 50% and < 80%), and 80% responder - 80R (reduction ≥ 80%). Data about surgical aspects (battery replacement, system complications), seizure dynamics, and medication changes were taken from the database. RESULTS: The early percentages of good results (80R + R) were 43.8% (year 1), 50.0% (year 2), and 43.8% (year 3). These percentages remained stable between years 10 and 12 (50% year 10; 46.7% year 11; 50% year 12) and increased in years 16 (60%) and 17 (75%). Depleted batteries were replaced in ten patients, six of whom were either R or 80R. In the four NR, the indication for replacement was improved quality of life. Three patients had VNS explanted or switched off-one had repeated asystolia and two were NR. The effect of hormonal changes in menarche on seizure was not proven. During the study, antiseizure medication was changed in all patients. CONCLUSIONS: The study proved the efficacy and safety of VNS in pediatric patients over an exceptionally long follow-up period. The demand for battery replacements indicates a positive treatment effect.

The interacting brain: Dynamic functional connectivity among canonical brain networks dissociates cooperative from competitive social interactions.

We spend much our lives interacting with others in various social contexts. Although we deal with this myriad of interpersonal exchanges with apparent ease, each one relies upon a broad array of sophisticated cognitive processes. Recent research suggests that the cognitive operations supporting interactive behaviour are themselves underpinned by several canonical functional brain networks (CFNs) that integrate dynamically with one another in response to changing situational demands. Dynamic integrations among these CFNs should therefore play a pivotal role in coordinating interpersonal behaviour. Further, different types of interaction should present different demands on cognitive systems, thereby eliciting distinct patterns of dynamism among these CFNs. To investigate this, the present study performed functional magnetic resonance imaging (fMRI) on 30 individuals while they interacted with one another cooperatively or competitively. By applying a novel combination of analytical techniques to these brain imaging data, we identify six states of dynamic functional connectivity characterised by distinct patterns of integration and segregation among specific CFNs that differ systematically between these opposing types of interaction. Moreover, applying these same states to fMRI data acquired from an independent sample engaged in the same kinds of interaction, we were able to classify interpersonal exchanges as cooperative or competitive. These results provide the first direct evidence for the systematic involvement of CFNs during social interactions, which should guide neurocognitive models of interactive behaviour and investigations into biomarkers for the interpersonal dysfunction characterizing many neurological and psychiatric disorders.

Pre-implant Heart Activity Differs in Responders and Non-responders to Vagal Nerve Stimulation Therapy in Epileptic Patients.

Vagal Nerve Stimulation (VNS) is used to treat patients with pharmacoresistant epilepsy. However, generally accepted tools to predict VNS response do not exist. Here we examined two heart activity measures - mean RR and pNN50 and their complex behavior during activation in pre-implant measurements. The ECG recordings of 73 patients (38 responders, 36 non-responders) were examined in a 30-sec floating window before (120 sec), during (2x120 sec), and after (120 sec) the hyperventilation by nose and mouth. The VNS response differentiation by pNN50 was significant (min p=0.01) in the hyperventilation by a nose with a noticeable descendant trend in nominal values. The mean RR was significant (p=0.01) in the rest after the hyperventilation by mouth but after an approximately 40-sec delay.Clinical Relevance- Our study shows that pNN50 and mean RR can be used to distinguish between VNS responders and non-responders. However, details of dynamic behavior showed how this ability varies in tested measurement segments.

You took the words right out of my mouth: Dual-fMRI reveals intra- and inter-personal neural processes supporting verbal interaction.

Verbal communication relies heavily upon mutual understanding, or common ground. Inferring the intentional states of our interaction partners is crucial in achieving this, and social neuroscience has begun elucidating the intra- and inter-personal neural processes supporting such inferences. Typically, however, neuroscientific paradigms lack the reciprocal to-and-fro characteristic of social communication, offering little insight into the way these processes operate online during real-world interaction. In the present study, we overcame this by developing a "hyperscanning" paradigm in which pairs of interactants could communicate verbally with one another in a joint-action task whilst both undergoing functional magnetic resonance imaging simultaneously. Successful performance on this task required both interlocutors to predict their partner's upcoming utterance in order to converge on the same word as each other over recursive exchanges, based only on one another's prior verbal expressions. By applying various levels of analysis to behavioural and neuroimaging data acquired from 20 dyads, three principal findings emerged: First, interlocutors converged frequently within the same semantic space, suggesting that mutual understanding had been established. Second, assessing the brain responses of each interlocutor as they planned their upcoming utterances on the basis of their co-player's previous word revealed the engagement of the temporo-parietal junctional (TPJ), precuneus and dorso-lateral pre-frontal cortex. Moreover, responses in the precuneus were modulated positively by the degree of semantic convergence achieved on each round. Second, effective connectivity among these regions indicates the crucial role of the right TPJ in this process, consistent with the Nexus model. Third, neural signals within certain nodes of this network became aligned between interacting interlocutors. We suggest this reflects an interpersonal neural process through which interactants infer and align to one another's intentional states whilst they establish a common ground.

Response to Vagal Stimulation by Heart-rate Features in Drug-resistant Epileptic Patients.

Vagal Nerve Stimulation (VNS) is an option in the treatment of drug-resistant epilepsy. However, approximately a quarter of VNS subjects does not respond to the therapy. In this retrospective study, we introduce heart-rate features to distinguish VNS responders and non-responders. Standard pre-implantation measurements of 66 patients were segmented in relation to specific stimuli (open/close eyes, photic stimulation, hyperventilation, and rests between). Median interbeat intervals were found for each segment and normalized (NMRR). Five NMRRs were significant; the strongest feature achieved significance with p=0.013 and AUC=0.66. Low mutual correlation and independence on EEG signals mean that presented features could be considered as an addition for models predicting VNS response using EEG.

You ≠ me: individual differences in the structure of social cognition.

This study investigated the structure of social cognition, and how it is influenced by personality; specifically, how various socio-cognitive capabilities, and the pattern of inter-relationships and co-dependencies among them differ between divergent personality styles. To measure social cognition, a large non-clinical sample (n = 290) undertook an extensive battery of self-report and performance-based measures of visual perspective taking, imitative tendencies, affective empathy, interoceptive accuracy, emotion regulation, and state affectivity. These same individuals then completed the Personality Styles and Disorders Inventory. Latent Profile Analysis revealed two dissociable personality profiles that exhibited contrasting cognitive and affective dispositions, and multivariate analyses indicated further that these profiles differed on measures of social cognition; individuals characterised by a flexible and adaptive personality profile expressed higher action orientation (emotion regulation) compared to those showing more inflexible tendencies, along with better visual perspective taking, superior interoceptive accuracy, less imitative tendencies, and lower personal distress and negativity. These characteristics point towards more efficient self-other distinction, and to higher cognitive control more generally. Moreover, low-level cognitive mechanisms served to mediate other higher level socio-emotional capabilities. Together, these findings elucidate the cognitive and affective underpinnings of individual differences in social behaviour, providing a data-driven model that should guide future research in this area.

Processing of Emotions in Functional Movement Disorder: An Exploratory fMRI Study.

Background: Affective dysregulation and impaired cognitive control are implicated in the pathology of functional neurological disorders (FNDs). However, voluntary regulation of emotions has seldom been researched in this group of patients. We hypothesized that patients with FNDs use inefficient voluntary emotion regulation strategies and regulate emotional reactions via increased motor activation. Methods: Fifteen patients with functional movement disorder (FMD) and fifteen healthy subjects matched by age, sex, and education underwent an emotion regulation task in fMRI. For stimuli, we used neutral and negative pictures from the International Affective Picture System. There was no restriction on their emotion regulation strategy. Both patients and healthy subjects were asked about the strategies they had used in a post-scanning interview. Participant levels of depression, trait anxiety, and alexithymia were assessed. Results: There were no significant differences in the emotion regulation strategies used by patients and healthy subjects, nor in levels of reported alexithymia and depression. However, patients showed increased activation in several brain areas when observing negative pictures, notably in the post-central gyrus, precuneus, posterior cingulate cortex (PCC) and cerebellar vermis, and also in their emotion regulation condition, particularly in the precuneus and post-central gyrus. Alexithymia was negatively associated with left insular activation during the observation of unpleasant stimuli only in the patient group. Conclusions: Our findings may implicate areas associated with self-referential processing in voluntary emotional regulation and lower emotional awareness as having a role in patients with functional movement disorders. However, our findings must be replicated with larger sample.

Exploiting Graphoelements and Convolutional Neural Networks with Long Short Term Memory for Classification of the Human Electroencephalogram.

The electroencephalogram (EEG) is a cornerstone of neurophysiological research and clinical neurology. Historically, the classification of EEG as showing normal physiological or abnormal pathological activity has been performed by expert visual review. The potential value of unbiased, automated EEG classification has long been recognized, and in recent years the application of machine learning methods has received significant attention. A variety of solutions using convolutional neural networks (CNN) for EEG classification have emerged with impressive results. However, interpretation of CNN results and their connection with underlying basic electrophysiology has been unclear. This paper proposes a CNN architecture, which enables interpretation of intracranial EEG (iEEG) transients driving classification of brain activity as normal, pathological or artifactual. The goal is accomplished using CNN with long short-term memory (LSTM). We show that the method allows the visualization of iEEG graphoelements with the highest contribution to the final classification result using a classification heatmap and thus enables review of the raw iEEG data and interpret the decision of the model by electrophysiology means.

What can be found in scalp EEG spectrum beyond common frequency bands. EEG-fMRI study.

OBJECTIVE: The scalp EEG spectrum is a frequently used marker of neural activity. Commonly, the preprocessing of EEG utilizes constraints, e.g. dealing with a predefined subset of electrodes or a predefined frequency band of interest. Such treatment of the EEG spectrum neglects the fact that particular neural processes may be reflected in several frequency bands and/or several electrodes concurrently, and can overlook the complexity of the structure of the EEG spectrum. APPROACH: We showed that the EEG spectrum structure can be described by parallel factor analysis (PARAFAC), a method which blindly uncovers the spatial-temporal-spectral patterns of EEG. We used an algorithm based on variational Bayesian statistics to reveal nine patterns from the EEG of 38 healthy subjects, acquired during a semantic decision task. The patterns reflected neural activity synchronized across theta, alpha, beta and gamma bands and spread over many electrodes, as well as various EEG artifacts. MAIN RESULTS: Specifically, one of the patterns showed significant correlation with the stimuli timing. The correlation was higher when compared to commonly used models of neural activity (power fluctuations in distinct frequency band averaged across a subset of electrodes) and we found significantly correlated hemodynamic fluctuations in simultaneously acquired fMRI data in regions known to be involved in speech processing. Further, we show that the pattern also occurs in EEG data which were acquired outside the MR machine. Two other patterns reflected brain rhythms linked to the attentional and basal ganglia large scale networks. The other patterns were related to various EEG artifacts. SIGNIFICANCE: These results show that PARAFAC blindly identifies neural activity in the EEG spectrum and that it naturally handles the correlations among frequency bands and electrodes. We conclude that PARAFAC seems to be a powerful tool for analysis of the EEG spectrum and might bring novel insight to the relationships between EEG activity and brain hemodynamics.

Statistical significance of task related deep brain EEG dynamic changes in the time-frequency domain.

We present an off-line analysis procedure for exploring brain activity recorded from intra-cerebral electroencephalographic data (SEEG). The objective is to determine the statistical differences between different types of stimulations in the time-frequency domain. The procedure is based on computing relative signal power change and subsequent statistical analysis. An example of characteristic statistically significant event-related de/synchronization (ERD/ERS) detected across different frequency bands following different oddball stimuli is presented. The method is used for off-line functional classification of different brain areas.

Long-term vagus nerve stimulation in children with focal epilepsy.

OBJECTIVES: The aim of the study was to evaluate the long-term efficacy and hospitalization rates in children with refractory focal epilepsy treated by vagus nerve stimulation. MATERIALS AND METHODS: We retrospectively analyzed 15 children with intractable focal epilepsy treated by vagus nerve stimulation (mean age of 14.6 ± 2.5 years at the time of implantation). We analyzed the treatment effectiveness at 1, 2, and 5 year follow-up visits. We counted the average number of urgent hospitalizations and number of days of urgent hospitalization per year for each patient before and after the VNS implantation. RESULTS: The mean seizure reduction was 42.5% at 1 year, 54.9% at 2 years, and 58.3% at 5 years. The number of responders was 7 (46.7%) at 1 year and 9 (60%) at both 2 and 5 years. The mean number of urgent hospitalizations per patient was 1.0 ± 0.6 per year preoperatively and 0.3 ± 0.5 per year post-operatively (P < 0.0001). The mean number of days of urgent hospitalization per patient was 9.3 ± 6.1 per year preoperatively and 1.3 ± 1.8 per year post-operatively ( < 0.0001). CONCLUSIONS: Vagus nerve stimulation is an effective method of treating children with refractory focal epilepsy. It leads to a substantial decrease in the number and duration of urgent hospitalizations.

[Pharmacoresistant epilepsy after craniocerebral injury]. / Farmakorezistentní epilepsie po kraniocerebrálním poranení.

INTRODUCTION: Posttraumatic epilepsy is one of the possible serious consequencies of both closed and open head injury with clinical manifestation months or years after surgery. In pharmacoresistant patients, surgical therapy should be considered. MATERIAL AND METHODS: The study summarises the results of surgical treatment of pharmacoresistant posttraumatic epilepsy in a group of 13 patients (11 males and 2 females). Average age at the time of injury was 9.6 years in males and 8.8 years in females. The average number of seizures was 10.7-17 seizures/month preoperatively. Invasive EEG monitoring was required in 5 patients in whom non invasive or semiinvasive investigations failed to localize the epileptogenic zone adequately. Temporal lobe resections were performed in 4 patients, 4 patients underwent extratemporal resections and vagus nerve stimulation system was implanted in 5 patients. RESULTS: Three patients (75%) after temporal resections became seizure free (Engel I) and in the remaining patient significant reduction of seizures was achieved (Engel III). There were 2 seizure free patients after extratemporal resections (50%) and significant reduction of seizure rates was achieved (Engel III) in the remaining two. One patient after vagus nerve stimulation met the criteria for > 90% response and there was a 50-90% seizure rate reduction in the remaining 4 patients (vagus nerve stimulation responder). CONCLUSIONS: Although in limited group of patients the study confirms good results of surgical treatment of selected posttraumatic epilepsy patients--mainly temporal epilepsy patients and patients after vagus nerve stimulation. Meticulous presurgical evaluation including invasive encephalography in indicated patients is a precondition for surgical success.

Late divergence of target and nontarget ERPs in a visual oddball task.

Different mental operations were expected in the late phase of intracerebral ERPs obtained in the visual oddball task with mental counting. Therefore we searched for late divergences of target and nontarget ERPs followed by components exceeding the temporal window of the P300 wave. Electrical activity from 152 brain regions of 14 epileptic patients was recorded by means of depth electrodes. Average target and nontarget records from 1800 ms long EEG periods free of epileptic activity were compared. Late divergence preceded by almost identical course of the target and nontarget ERPs was found in 16 brain regions of 6 patients. The mean latency of the divergence point was 570+/-93 ms after the stimulus onset. The target post-divergence section of the ERP differed from the nontarget one by opposite polarity, different latency of the components, or even different number of the components. Generators of post-divergence ERP components were found in the parahippocampal gyrus, superior, middle and inferior temporal gyri, amygdala, and fronto-orbital cortex. Finding of late divergence indicates that functional differences exist even not sooner than during the final phase of the task.

Peri-ictal bed leaving in temporal lobe epilepsy: incidence and lateralizing value.

We analyzed peri-ictal bed leaving (PBL) symptoms in 105 patients with temporal lobe epilepsy (TLE). All patients were classified as Engel I at the 2-year follow-up visit. Histopathological examination revealed hippocampal sclerosis (TLE-HS) in 64 patients and other lesions in 38 patients (TLE-other); 3 patients had no lesions. We reviewed 412 seizures. PBL was defined as lateralized leaving of the bed occurring during the seizure or up to 3 minutes after the end of the seizure. PBL was observed in 28 of 105 patients (26.7%), and in 45 of 412 seizures (10.9%). PBL occurred more frequently in patients with TLE-HS than in patients with TLE-other (32.8% vs 17.1%, P=0.058). PBL was ipsilateral to the seizure onset in 71.4% of patients and 71.2% of seizures (P=0.012 and P<0.001). In patients with TLE-HS, PBL was ipsilateral to seizure onset in 76.2% of patients and 81.2% of seizures (P=0.008 and P<0.001). In patients with TLE-other, PBL was ipsilateral to seizure onset in 42.8% of patients and 46.1% of seizures. There were no differences in the incidence and lateralizing value between patients with right-sided and those with left-sided TLE. PBL is a relatively frequent peri-ictal sign in patients with TLE. The side of PBL in patients with TLE-HS lateralizes the seizure onset to the ipsilateral temporal lobe.

Estimation of neuronal responses from fMRI data.

In this paper we describe a deconvolution technique for estimation of the neuronal signal from an observed hemodynamic responses in fMRI data. Our approach, based on the Rauch-Tung-Striebel smoother for square-root cubature Kalman filter, enables us to accurately infer the hidden states, parameters, and the input of the dynamic system. Additionally, we enhance the cubature Kalman filter with a variational Bayesian approach for adaptive estimation of the measurement noise covariance.

Occurrence and lateralizing value of "rare" peri-ictal vegetative symptoms in temporal lobe epilepsy.

We retrospectively investigated rare peri-ictal vegetative symptoms (PIVS) in 380 seizures of 97 patients with temporal lobe epilepsy (TLE): 234 seizures of 60 patients with TLE with mesiotemporal sclerosis (TLE/MTS) and 146 seizures of 37 patients with TLE with other lesions (TLE/non-MTS) who were at least 2 years after epilepsy surgery and classified as Engel I. We assessed the following PIVS: peri-ictal cough (pC), peri-ictal water drinking (pWD), peri-ictal vomiting (pV), and peri-ictal spitting (pS). We observed pC in 24.7% of patients and 10% of seizures; pWD in 14.4% of patients and 5.9% of seizures; pV and pS occurred more rarely. Both pWD and pC occurred significantly more often in those with TLE of the non- language-dominant hemisphere. The limited occurrence of pV and pS made it impossible to perform statistical analysis for these symptoms. In patients with TLE, pC and pWD were quite frequent; we observed pV and pS less frequently. Both pC and pWD have a significant lateralizing value in TLE.

The level of frontal-temporal beta-2 band EEG synchronization distinguishes anterior cingulate cortex from other frontal regions.

Recent findings indicate that complex cognitive functions are organized at a global level in the brain and rely on large-scale information processing requiring functional integration of multiple disparate neural assemblies. The critical question of the integration of distributed brain activities is whether the essential integrative role can be attributed to a specific structure in the brain or whether this ability is inherent to the cognitive network as a whole. The results of the present study show that mean values of the running correlation function in frontal-temporal EEG pairs with one electrode in the anterior cingulate cortex (ACC) are significantly higher than the same values in other frontal-temporal pairs. These findings indicate a particular role of the ACC in large-scale communication, which could reflect its unique integrative functions in cognitive processing.

Long-term levetiracetam treatment in patients with epilepsy: 3-year follow up.

OBJECTIVES: To assess the long-term efficacy and tolerability of levetiracetam in routine clinical practice. MATERIALS AND METHODS: We retrospectively analysed 218 patients, mostly adults, presenting mostly with localisation-related epilepsy, treated with levetiracetam as adjunctive therapy or monotherapy for up to 36 months. The primary points evaluated were: long-term retention rate, reasons for discontinuing levetiracetam and the percentage of seizure-free patients. RESULTS: The retention rate at 6, 12, 24 and 36 months following the commencement of levetiracetam treatment was 91.7, 75.2, 60.1 and 53.7% respectively. Sixty-seven (30.7%) patients discontinued levetiracetam treatment. During the clinical audit evaluation period, surgical resection or implantation of VNS was performed in 31 (14.3%) patients. In 53 of the 67 patients (79.1%), the treatment was discontinued due to lack of efficacy; in 14 patients (20.9%) treatment was discontinued due to adverse events. In total, 24 of 218 patients (11.0%) were seizure-free for 36 months. CONCLUSIONS: Levetiracetam is an effective and well-tolerated option for long-term treatment of epilepsy in adults.