Joost Wagenaar

Crowdsourcing reproducible seizure forecasting in human and canine epilepsy

See Mormann and Andrzejak (doi:10.1093/brain/aww091) for a scientific commentary on this article.   Seizures are thought to arise from an identifiable pre-ictal state. Brinkmann et al. report the results of an online, open-access seizure forecasting competition using intracranial EEG recordings from canines with naturally occurring epilepsy and human patients undergoing presurgical monitoring. The winning algorithms forecast seizures at rates significantly greater than chance.

Real-time control of hind limb functional electrical stimulation using feedback from dorsal root ganglia recordings

OBJECTIVE Functional electrical stimulation (FES) approaches often utilize an open-loop controller to drive state transitions. The addition of sensory feedback may allow for closed-loop control that can respond effectively to perturbations and muscle fatigue. APPROACH We evaluated the use of natural sensory nerve signals obtained with penetrating microelectrode arrays in lumbar dorsal root ganglia (DRG) as real-time feedback for closed-loop control of FES-generated hind limb stepping in anesthetized cats. MAIN RESULTS Leg position feedback was obtained in near real-time at 50 ms intervals by decoding the firing rates of more than 120 DRG neurons recorded simultaneously. Over 5 m of effective linear distance was traversed during closed-loop stepping trials in each of two cats. The controller compensated effectively for perturbations in the stepping path when DRG sensory feedback was provided. The presence of stimulation artifacts and the quality of DRG unit sorting did not significantly affect the accuracy of leg position feedback obtained from the linear decoding model as long as at least 20 DRG units were included in the model. SIGNIFICANCE This work demonstrates the feasibility and utility of closed-loop FES control based on natural neural sensors. Further work is needed to improve the controller and electrode technologies and to evaluate long-term viability.

Forecasting Seizures Using Intracranial EEG Measures and SVM in Naturally Occurring Canine Epilepsy

Management of drug resistant focal epilepsy would be greatly assisted by a reliable warning system capable of alerting patients prior to seizures to allow the patient to adjust activities or medication. Such a system requires successful identification of a preictal, or seizure-prone state. Identification of preictal states in continuous long- duration intracranial electroencephalographic (iEEG) recordings of dogs with naturally occurring epilepsy was investigated using a support vector machine (SVM) algorithm. The dogs studied were implanted with a 16-channel ambulatory iEEG recording device with average channel reference for a mean (st. dev.) of 380.4 (+87.5) days producing 220.2 (+104.1) days of intracranial EEG recorded at 400 Hz for analysis. The iEEG records had 51.6 (+52.8) seizures identified, of which 35.8 (+30.4) seizures were preceded by more than 4 hours of seizure-free data. Recorded iEEG data were stratified into 11 contiguous, non-overlapping frequency bands and binned into one-minute synchrony features for analysis. Performance of the SVM classifier was assessed using a 5-fold cross validation approach, where preictal training data were taken from 90 minute windows with a 5 minute pre-seizure offset. Analysis of the optimal preictal training time was performed by repeating the cross validation over a range of preictal windows and comparing results. We show that the optimization of feature selection varies for each subject, i.e. algorithms are subject specific, but achieve prediction performance significantly better than a time-matched Poisson random predictor (p<0.05) in 5/5 dogs analyzed.

A multimodal platform for cloud-based collaborative research

The need for sharing and analyzing large-scale data sets in scientific research has increased significantly over the last decade. Despite multiple efforts, there is currently no single platform that is widely used to search for, share, and perform custom data analysis over large numbers of TB-scale datasets using cloud technologies. We present a cloud-based portal and data integration/access platform to fulfill this need. The IEEG-Portal is being developed as a means to share and collaborate on projects containing large EEG datasets. It currently contains over 75 de-identified intracranial EEG datasets as well as imaging and associated meta-information, and a variety of datasets from animals. The IEEG-Portal is modular by design, which results in a highly extensible platform for neural data analysis on the cloud. In this paper, we highlight the current state of the portal infrastructure; its capabilities for fostering collaborative research and data-validation, and the challenges that are inherent to sharing and analyzing datasets using a global collaborative cloud-based platform.

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.

An open-source automated platform for three-dimensional visualization of subdural electrodes using CT-MRI coregistration

Visualizing implanted subdural electrodes in three‐dimensional (3D) space can greatly aid in planning, executing, and validating resection in epilepsy surgery. Coregistration software is available, but cost, complexity, insufficient accuracy, or validation limit adoption. We present a fully automated open‐source application, based on a novel method using postimplant computerized tomography (CT) and postimplant magnetic resonance (MR) images, for accurately visualizing intracranial electrodes in 3D space.

Data integration: Combined imaging and electrophysiology data in the cloud.

There has been an increasing effort to correlate electrophysiology data with imaging in patients with refractory epilepsy over recent years. IEEG.org provides a free-access, rapidly growing archive of imaging data combined with electrophysiology data and patient metadata. It currently contains over 1200 human and animal datasets, with multiple data modalities associated with each dataset (neuroimaging, EEG, EKG, de-identified clinical and experimental data, etc.). The platform is developed around the concept that scientific data sharing requires a flexible platform that allows sharing of data from multiple file formats. IEEG.org provides high- and low-level access to the data in addition to providing an environment in which domain experts can find, visualize, and analyze data in an intuitive manner. Here, we present a summary of the current infrastructure of the platform, available datasets and goals for the near future.

Mining continuous intracranial EEG in focal canine epilepsy: Relating interictal bursts to seizure onsets.

Brain regions are localized for resection during epilepsy surgery based on rare seizures observed during a short period of intracranial electroencephalography (iEEG) monitoring. Interictal epileptiform bursts, which are more prevalent than seizures, may provide complementary information to aid in epilepsy evaluation. In this study, we leverage a long‐term iEEG dataset from canines with naturally occurring epilepsy to investigate interictal bursts and their electrographic relationship to seizures.

Interictal epileptiform activity outside the seizure onset zone impacts cognition

See Kleen and Kirsch (doi:10.1093/awx178) for a scientific commentary on this article.Cognitive deficits are common among epilepsy patients. In these patients, interictal epileptiform discharges, also termed spikes, are seen routinely on electroencephalography and believed to be associated with transient cognitive impairments. In this study, we investigated the effect of spikes on memory encoding and retrieval, taking into account the spatial distribution of spikes in relation to the seizure onset zone as well as anatomical regions of the brain. Sixty-seven patients with medication refractory epilepsy undergoing continuous intracranial electroencephalography monitoring engaged in a delayed free recall task to test short-term memory. In this task, subjects were asked to memorize and recall lists of common nouns. We quantified the effect of each spike on the probability of successful recall using a generalized logistic mixed model. We found that in patients with left lateralized seizure onset zones, spikes outside the seizure onset zone impacted memory encoding, whereas those within the seizure onset zone did not. In addition, spikes in the left inferior temporal gyrus, middle temporal gyrus, superior temporal gyrus, and fusiform gyrus during memory encoding reduced odds of recall by as much as 15% per spike. Spikes also reduced the odds of word retrieval, an effect that was stronger with spikes outside of the seizure onset zone. These results suggest that seizure onset regions are dysfunctional at baseline, and support the idea that interictal spikes disrupt cognitive processes related to the underlying tissue.

Millimeter-scale epileptiform spike propagation patterns and their relationship to seizures

OBJECTIVE Current mapping of epileptic networks in patients prior to epilepsy surgery utilizes electrode arrays with sparse spatial sampling (∼1.0 cm inter-electrode spacing). Recent research demonstrates that sub-millimeter, cortical-column-scale domains have a role in seizure generation that may be clinically significant. We use high-resolution, active, flexible surface electrode arrays with 500 μm inter-electrode spacing to explore epileptiform local field potential (LFP) spike propagation patterns in two dimensions recorded from subdural micro-electrocorticographic signals in vivo in cat. In this study, we aimed to develop methods to quantitatively characterize the spatiotemporal dynamics of epileptiform activity at high-resolution. APPROACH We topically administered a GABA-antagonist, picrotoxin, to induce acute neocortical epileptiform activity leading up to discrete electrographic seizures. We extracted features from LFP spikes to characterize spatiotemporal patterns in these events. We then tested the hypothesis that two-dimensional spike patterns during seizures were different from those between seizures. MAIN RESULTS We showed that spatially correlated events can be used to distinguish ictal versus interictal spikes. SIGNIFICANCE We conclude that sub-millimeter-scale spatiotemporal spike patterns reveal network dynamics that are invisible to standard clinical recordings and contain information related to seizure-state.