The brain dynamics of visuospatial perspective-taking captured by intracranial EEG.

Visuospatial perspective-taking (VPT) is the ability to imagine a scene from a position different from the one used in self-perspective judgments (SPJ). We typically use VPT to understand how others see the environment. VPT requires overcoming the self-perspective, and impairments in this process are implicated in various brain disorders, such as schizophrenia and autism. However, the underlying brain areas of VPT are not well distinguished from SPJ-related ones and from domain-general responses to both perspectives. In addition, hierarchical processing theory suggests that domain-specific processes emerge over time from domain-general ones. It mainly focuses on the sensory system, but outside of it, support for this hypothesis is lacking. Therefore, we aimed to spatiotemporally distinguish brain responses domain-specific to VPT from the specific ones to self-perspective, and domain-general responses to both perspectives. In particular, we intended to test whether VPT- and SPJ specific responses begin later than the general ones. We recorded intracranial EEG data from 30 patients with epilepsy who performed a task requiring laterality judgments during VPT and SPJ, and analyzed the spatiotemporal features of responses in the broad gamma band (50-150 Hz). We found VPT-specific processing in a more extensive brain network than SPJ-specific processing. Their dynamics were similar, but both differed from the general responses, which began earlier and lasted longer. Our results anatomically distinguish VPT-specific from SPJ-specific processing. Furthermore, we temporally differentiate between domain-specific and domain-general processes both inside and outside the sensory system, which serves as a novel example of hierarchical processing.

Timing of Allocentric and Egocentric Spatial Processing in Human Intracranial EEG.

Spatial reference frames (RFs) play a key role in spatial cognition, especially in perception, spatial memory, and navigation. There are two main types of RFs: egocentric (self-centered) and allocentric (object-centered). Although many fMRI studies examined the neural correlates of egocentric and allocentric RFs, they could not sample the fast temporal dynamics of the underlying cognitive processes. Therefore, the interaction and timing between these two RFs remain unclear. Taking advantage of the high temporal resolution of intracranial EEG (iEEG), we aimed to determine the timing of egocentric and allocentric information processing and describe the brain areas involved. We recorded iEEG and analyzed broad gamma activity (50-150 Hz) in 37 epilepsy patients performing a spatial judgment task in a three-dimensional circular virtual arena. We found overlapping activation for egocentric and allocentric RFs in many brain regions, with several additional egocentric- and allocentric-selective areas. In contrast to the egocentric responses, the allocentric responses peaked later than the control ones in frontal regions with overlapping selectivity. Also, across several egocentric or allocentric selective areas, the egocentric selectivity appeared earlier than the allocentric one. We identified the maximum number of egocentric-selective channels in the medial occipito-temporal region and allocentric-selective channels around the intraparietal sulcus in the parietal cortex. Our findings favor the hypothesis that egocentric spatial coding is a more primary process, and allocentric representations may be derived from egocentric ones. They also broaden the dominant view of the dorsal and ventral streams supporting egocentric and allocentric space coding, respectively.

Detection of interictal epileptiform discharges using signal envelope distribution modelling: application to epileptic and non-epileptic intracranial recordings.

Interictal epileptiform discharges (spikes, IEDs) are electrographic markers of epileptic tissue and their quantification is utilized in planning of surgical resection. Visual analysis of long-term multi-channel intracranial recordings is extremely laborious and prone to bias. Development of new and reliable techniques of automatic spike detection represents a crucial step towards increasing the information yield of intracranial recordings and to improve surgical outcome. In this study, we designed a novel and robust detection algorithm that adaptively models statistical distributions of signal envelopes and enables discrimination of signals containing IEDs from signals with background activity. This detector demonstrates performance superior both to human readers and to an established detector. It is even capable of identifying low-amplitude IEDs which are often missed by experts and which may represent an important source of clinical information. Application of the detector to non-epileptic intracranial data from patients with intractable facial pain revealed the existence of sharp transients with waveforms reminiscent of interictal discharges that can represent biological sources of false positive detections. Identification of these transients enabled us to develop and propose secondary processing steps, which may exclude these transients, improving the detector's specificity and having important implications for future development of spike detectors in general.

Antagonistic behavior of brain networks mediated by low-frequency oscillations: electrophysiological dynamics during internal-external attention switching.

Antagonistic activity of brain networks likely plays a fundamental role in how the brain optimizes its performance by efficient allocation of computational resources. A prominent example involves externally/internally oriented attention tasks, implicating two anticorrelated, intrinsic brain networks: the default mode network (DMN) and the dorsal attention network (DAN). To elucidate electrophysiological underpinnings and causal interplay during attention switching, we recorded intracranial EEG (iEEG) from 25 epilepsy patients with electrode contacts localized in the DMN and DAN. We show antagonistic network dynamics of activation-related changes in high-frequency (> 50 Hz) and low-frequency (< 30 Hz) power. The temporal profile of information flow between the networks estimated by functional connectivity suggests that the activated network inhibits the other one, gating its activity by increasing the amplitude of the low-frequency oscillations. Insights about inter-network communication may have profound implications for various brain disorders in which these dynamics are compromised.

Automated Identification of Stereoelectroencephalography Contacts and Measurement of Factors Influencing Accuracy of Frame Stereotaxy.

OBJECTIVE: Stereoelectroencephalography (SEEG) is an established invasive diagnostic technique for use in patients with drug-resistant focal epilepsy evaluated before resective epilepsy surgery. The factors that influence the accuracy of electrode implantation are not fully understood. Adequate accuracy prevents the risk of major surgery complications. Precise knowledge of the anatomical positions of individual electrode contacts is crucial for the interpretation of SEEG recordings and subsequent surgery. METHODS: We developed an image processing pipeline to localize implanted electrodes and detect individual contact positions using computed tomography (CT), as a substitute for time-consuming manual labeling. The algorithm automates measurement of parameters of the electrodes implanted in the skull (bone thickness, implantation angle and depth) for use in modeling of predictive factors that influence implantation accuracy. RESULTS: Fifty-four patients evaluated by SEEG were analyzed. A total of 662 SEEG electrodes with 8,745 contacts were stereotactically inserted. The automated detector localized all contacts with better accuracy than manual labeling (p < 0.001). The retrospective implantation accuracy of the target point was 2.4 ± 1.1 mm. A multifactorial analysis determined that almost 58% of the total error was attributable to measurable factors. The remaining 42% was attributable to random error. CONCLUSION: SEEG contacts can be reliably marked by our proposed method. The trajectory of electrodes can be parametrically analyzed to predict and validate implantation accuracy using a multifactorial model. SIGNIFICANCE: This novel, automated image processing technique is a potentially clinically important, assistive tool for increasing the yield, efficiency, and safety of SEEG.

Computational modeling allows unsupervised classification of epileptic brain states across species.

Current advances in epilepsy treatment aim to personalize and responsively adjust treatment parameters to overcome patient heterogeneity in treatment efficiency. For tailoring treatment to the individual and the current brain state, tools are required that help to identify the patient- and time-point-specific parameters of epilepsy. Computational modeling has long proven its utility in gaining mechanistic insight. Recently, the technique has been introduced as a diagnostic tool to predict individual treatment outcomes. In this article, the Wendling model, an established computational model of epilepsy dynamics, is used to automatically classify epileptic brain states in intracranial EEG from patients (n = 4) and local field potential recordings from in vitro rat data (high-potassium model of epilepsy, n = 3). Five-second signal segments are classified to four types of brain state in epilepsy (interictal, preonset, onset, ictal) by comparing a vector of signal features for each data segment to four prototypical feature vectors obtained by Wendling model simulations. The classification result is validated against expert visual assessment. Model-driven brain state classification achieved a classification performance significantly above chance level (mean sensitivity 0.99 on model data, 0.77 on rat data, 0.56 on human data in a four-way classification task). Model-driven prototypes showed similarity with data-driven prototypes, which we obtained from real data for rats and humans. Our results indicate similar electrophysiological patterns of epileptic states in the human brain and the animal model that are well-reproduced by the computational model, and captured by a key set of signal features, enabling fully automated and unsupervised brain state classification in epilepsy.

Distinct patterns of interictal intracranial EEG in focal cortical dysplasia type I and II.

OBJECTIVE: Focal cortical dysplasia (FCD) is the most common malformation causing refractory focal epilepsy. Surgical removal of the entire dysplastic cortex is crucial for achieving a seizure-free outcome. Precise presurgical distinctions between FCD types by neuroimaging are difficult, mainly in patients with normal magnetic resonance imaging findings. However, the FCD type is important for planning the extent of surgical approach and counselling. METHODS: This study included patients with focal drug-resistant epilepsy and definite histopathological FCD type I or II diagnoses who underwent intracranial electroencephalography (iEEG). We detected interictal epileptiform discharges (IEDs) and their recruitment into repetitive discharges (RDs) to compare electrophysiological patterns characterizing FCD types. RESULTS: Patients with FCD type II had a significantly higher IED rate (p < 0.005), a shorter inter-discharge interval within RD episodes (p < 0.003), sleep influence on decreased RD periodicity (p < 0.036), and longer RD episode duration (p < 0.003) than patients with type I. A Bayesian classifier stratified FCD types with 82% accuracy. CONCLUSION: Temporal characteristics of IEDs and RDs reflect the histological findings of FCD subtypes and can differentiate FCD types I and II. SIGNIFICANCE: Presurgical prediction of FCD type can help to plan a more tailored surgical approach in patients with normal magnetic resonance findings.

Distributed brain co-processor for tracking spikes, seizures and behaviour during electrical brain stimulation.

Early implantable epilepsy therapy devices provided open-loop electrical stimulation without brain sensing, computing, or an interface for synchronized behavioural inputs from patients. Recent epilepsy stimulation devices provide brain sensing but have not yet developed analytics for accurately tracking and quantifying behaviour and seizures. Here we describe a distributed brain co-processor providing an intuitive bi-directional interface between patient, implanted neural stimulation and sensing device, and local and distributed computing resources. Automated analysis of continuous streaming electrophysiology is synchronized with patient reports using a handheld device and integrated with distributed cloud computing resources for quantifying seizures, interictal epileptiform spikes and patient symptoms during therapeutic electrical brain stimulation. The classification algorithms for interictal epileptiform spikes and seizures were developed and parameterized using long-term ambulatory data from nine humans and eight canines with epilepsy, and then implemented prospectively in out-of-sample testing in two pet canines and four humans with drug-resistant epilepsy living in their natural environments. Accurate seizure diaries are needed as the primary clinical outcome measure of epilepsy therapy and to guide brain-stimulation optimization. The brain co-processor system described here enables tracking interictal epileptiform spikes, seizures and correlation with patient behavioural reports. In the future, correlation of spikes and seizures with behaviour will allow more detailed investigation of the clinical impact of spikes and seizures on patients.

Novel Paradigm of Subdural Cortical Stimulation Does Not Cause Thermal Damage in Brain Tissue: A Simulation-Based Study.

The thermal effect of a novel effective electrical stimulation mapping (ESM) technique using an Ojemann's stimulation electrode in open craniotomy areas causes a nondestructive local increase in temperature. Another type of stimulating electrode is a subdural strip, routinely used in intraoperative electrocorticography (ECoG), which applies ESM in a covered subdural area over the motor cortex. ECoG electrode geometry produces a different electrical field, causing a different Joule heat distribution in tissue, one that is impossible to measure in subdural space. Therefore, the previous safety control study of the novel ESM technique needed to be extended to include an assessment of the thermal effect of ECoG strip electrodes. We adapted a previously well-validated numerical model and performed coupled complex electro-thermal transient simulations for short-time (28.4 ms) high-frequency (500 Hz) and hyperintense (peak 100 mA) ESM paradigm. The risk of heat-induced cellular damage was assessed by applying the Arrhenius equation integral on the computed time-dependent spatial distribution of temperature in the brain tissue during ESM stimulation and during the cooldown period. The results showed increases in temperature in the proximity around ECoG electrode discs in a safe range without destructive effects. As opposed to open craniotomy, subdural space is not cooled by the air; hence a higher - but still safe - induced temperature was observed. The presented simulation agrees with the previously published histopathological examination of the stimulated brain tissue, and confirms the safety of the novel ESM technique when applied using ECoG strip electrodes.

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

OBJECTIVE: Epilepsy 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. METHODS: The 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. RESULTS: Analysis 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). CONCLUSION: The 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. SIGNIFICANCE: Ictogenic nodes localize the critical parts of the epileptogenic tissue and increase the diagnostic yield of intracranial evaluation.

May intraoperative detection of stereotactically inserted intracerebral electrodes increase precision of resective epilepsy surgery?

OBJECT: Epilepsy surgery is an effective treatment for selected patients with focal intractable epilepsy. Complete removal of the epileptogenic zone significantly increases the chances for postoperative seizure-freedom. In complex surgical candidates, delineation of the epileptogenic zone requires a long-term invasive video/EEG from intracranial electrodes. It is especially challenging to achieve a complete resection in deep brain structures such as opercular-insular cortex. We report a novel approach utilizing intraoperative visual detection of stereotactically implanted depth electrodes to inform and guide the extent of surgical resection. METHODS: We retrospectively reviewed data of pediatric patients operated in Motol Epilepsy Center between October 2010 and June 2020 who underwent resections guided by intraoperative visual detection of depth electrodes following SEEG. The outcome in terms of seizure- and AED-freedom was assessed individually in each patient. RESULTS: Nineteen patients (age at surgery 2.9-18.6 years, median 13 years) were included in the study. The epileptogenic zone involved opercular-insular cortex in eighteen patients. The intraoperative detection of the electrodes was successful in seventeen patients and the surgery was regarded complete in sixteen. Thirteen patients were seizure-free at final follow-up including six drug-free cases. The successful intraoperative detection of the electrodes was associated with favorable outcome in terms of achieving complete resection and seizure-freedom in most cases. On the contrary, the patients in whom the procedure failed had poor postsurgical outcome. CONCLUSION: The reported technique helps to achieve the complete resection in challenging patients with the epileptogenic zone in deep brain structures.

Mapping the Scene and Object Processing Networks by Intracranial EEG.

Human perception and cognition are based predominantly on visual information processing. Much of the information regarding neuronal correlates of visual processing has been derived from functional imaging studies, which have identified a variety of brain areas contributing to visual analysis, recognition, and processing of objects and scenes. However, only two of these areas, namely the parahippocampal place area (PPA) and the lateral occipital complex (LOC), were verified and further characterized by intracranial electroencephalogram (iEEG). iEEG is a unique measurement technique that samples a local neuronal population with high temporal and anatomical resolution. In the present study, we aimed to expand on previous reports and examine brain activity for selectivity of scenes and objects in the broadband high-gamma frequency range (50-150 Hz). We collected iEEG data from 27 epileptic patients while they watched a series of images, containing objects and scenes, and we identified 375 bipolar channels responding to at least one of these two categories. Using K-means clustering, we delineated their brain localization. In addition to the two areas described previously, we detected significant responses in two other scene-selective areas, not yet reported by any electrophysiological studies; namely the occipital place area (OPA) and the retrosplenial complex. Moreover, using iEEG we revealed a much broader network underlying visual processing than that described to date, using specialized functional imaging experimental designs. Here, we report the selective brain areas for scene processing include the posterior collateral sulcus and the anterior temporal region, which were already shown to be related to scene novelty and landmark naming. The object-selective responses appeared in the parietal, frontal, and temporal regions connected with tool use and object recognition. The temporal analyses specified the time course of the category selectivity through the dorsal and ventral visual streams. The receiver operating characteristic analyses identified the PPA and the fusiform portion of the LOC as being the most selective for scenes and objects, respectively. Our findings represent a valuable overview of visual processing selectivity for scenes and objects based on iEEG analyses and thus, contribute to a better understanding of visual processing in the human brain.

A novel effective paradigm of intraoperative electrical stimulation mapping in children.

OBJECTIVE: Resective epilepsy surgery is an established treatment method for children with focal intractable epilepsy, but the use of this method introduces the risk of postsurgical motor deficits. Electrical stimulation mapping (ESM), used to define motor areas and pathways, frequently fails in children. The authors developed and tested a novel ESM protocol in children of all age categories. METHODS: The ESM protocol utilizes high-frequency electric cortical stimulation combined with continuous intraoperative motor-evoked potential (MEP) monitoring. The relationships between stimulation current intensity and selected presurgical and surgery-associated variables were analyzed in 66 children (aged 7 months to 18 years) undergoing 70 resective epilepsy surgeries in proximity to the motor cortex or corticospinal tracts. RESULTS: ESM elicited MEP responses in all children. Stimulation current intensity was associated with patient age at surgery and date of surgery (F value = 6.81, p < 0.001). Increase in stimulation current intensity predicted postsurgical motor deficits (F value = 44.5, p < 0.001) without effects on patient postsurgical seizure freedom (p > 0.05). CONCLUSIONS: The proposed ESM paradigm developed in our center represents a reliable method for preventing and predicting postsurgical motor deficits in all age groups of children. This novel ESM protocol may increase the safety and possibly also the completeness of epilepsy surgery. It could be adopted in pediatric epilepsy surgery centers.

Corrigendum: The Sub-Regional Functional Organization of Neocortical Irritative Epileptic Networks in Pediatric Epilepsy.

[This corrects the article DOI: 10.3389/fneur.2018.00184.].

The Sub-Regional Functional Organization of Neocortical Irritative Epileptic Networks in Pediatric Epilepsy.

Between seizures, irritative network generates frequent brief synchronous activity, which manifests on the EEG as interictal epileptiform discharges (IEDs). Recent insights into the mechanism of IEDs at the microscopic level have demonstrated a high variance in the recruitment of neuronal populations generating IEDs and a high variability in the trajectories through which IEDs propagate across the brain. These phenomena represent one of the major constraints for precise characterization of network organization and for the utilization of IEDs during presurgical evaluations. We have developed a new approach to dissect human neocortical irritative networks and quantify their properties. We have demonstrated that irritative network has modular nature and it is composed of multiple independent sub-regions, each with specific IED propagation trajectories and differing in the extent of IED activity generated. The global activity of the irritative network is determined by long-term and circadian fluctuations in sub-region spatiotemporal properties. Also, the most active sub-region co-localizes with the seizure onset zone in 12/14 cases. This study demonstrates that principles of recruitment variability and propagation are conserved at the macroscopic level and that they determine irritative network properties in humans. Functional stratification of the irritative network increases the diagnostic yield of intracranial investigations with the potential to improve the outcomes of surgical treatment of neocortical epilepsy.

Loss of neuronal network resilience precedes seizures and determines the ictogenic nature of interictal synaptic perturbations.

The mechanism of seizure emergence and the role of brief interictal epileptiform discharges (IEDs) in seizure generation are two of the most important unresolved issues in modern epilepsy research. We found that the transition to seizure is not a sudden phenomenon, but is instead a slow process that is characterized by the progressive loss of neuronal network resilience. From a dynamical perspective, the slow transition is governed by the principles of critical slowing, a robust natural phenomenon that is observable in systems characterized by transitions between dynamical regimes. In epilepsy, this process is modulated by synchronous synaptic input from IEDs. IEDs are external perturbations that produce phasic changes in the slow transition process and exert opposing effects on the dynamics of a seizure-generating network, causing either anti-seizure or pro-seizure effects. We found that the multifaceted nature of IEDs is defined by the dynamical state of the network at the moment of the discharge occurrence.