In recent years there has been increasing interest in applying network science tools to EEG data. At the 2018 American Epilepsy Society conference in New Orleans, LA, the yearly session of the Engineering and Neurostimulation Special Interest Group focused on emerging, translational technologies to analyze seizure networks. Each speaker demonstrated practical examples of how network tools can be utilized in clinical care and provide additional data to help care for patients with intractable epilepsy. The groups presented advances using tools from functional connectivity, control theory, and graph theory to analyze human EEG data. These tools have great potential to augment clinical interpretation of EEG signals.

Over the past ten years, the drive to improve outcomes from epilepsy surgery has stimulated widespread interest in methods to quantitatively guide epilepsy surgery from intracranial EEG (iEEG). Many patients fail to achieve seizure freedom, in part due to the challenges in subjective iEEG interpretation. To address this clinical need, quantitative iEEG analytics have been developed using a variety of approaches, spanning studies of seizures, interictal periods, and their transitions, and encompass a range of techniques including electrographic signal analysis, dynamical systems modeling, machine learning and graph theory. Unfortunately, many methods fail to generalize to new data and are sensitive to differences in pathology and electrode placement. Here, we critically review selected literature on computational methods of identifying the epileptogenic zone from iEEG. We highlight shared methodological challenges common to many studies in this field, and propose ways that they can be addressed. One fundamental common pitfall is a lack of open-source, high-quality data, which we specifically address by sharing a centralized high-quality, well-annotated, multicenter dataset consisting of >100 patients to support larger and more rigorous studies. Ultimately, we provide a roadmap to help these tools reach clinical trials and hope to improve the lives of future patients.

Over 15 million epilepsy patients worldwide have drug-resistant epilepsy. Successful surgery is a standard of care treatment but can only be achieved through complete resection or disconnection of the epileptogenic zone, the brain region(s) where seizures originate. Surgical success rates vary between 20% and 80%, because no clinically validated biological markers of the epileptogenic zone exist. Localizing the epileptogenic zone is a costly and time-consuming process, which often requires days to weeks of intracranial EEG (iEEG) monitoring. Clinicians visually inspect iEEG data to identify abnormal activity on individual channels occurring immediately before seizures or spikes that occur interictally (i.e. between seizures). In the end, the clinical standard mainly relies on a small proportion of the iEEG data captured to assist in epileptogenic zone localization (minutes of seizure data versus days of recordings), missing opportunities to leverage these largely ignored interictal data to better diagnose and treat patients. IEEG offers a unique opportunity to observe epileptic cortical network dynamics but waiting for seizures increases patient risks associated with invasive monitoring. In this study, we aimed to leverage interictal iEEG data by developing a new network-based interictal iEEG marker of the epileptogenic zone. We hypothesized that when a patient is not clinically seizing, it is because the epileptogenic zone is inhibited by other regions. We developed an algorithm that identifies two groups of nodes from the interictal iEEG network: those that are continuously inhibiting a set of neighbouring nodes (‘sources’) and the inhibited nodes themselves (‘sinks’). Specifically, patient-specific dynamical network models were estimated from minutes of iEEG and their connectivity properties revealed top sources and sinks in the network, with each node being quantified by source-sink metrics. We validated the algorithm in a retrospective analysis of 65 patients. The source-sink metrics identified epileptogenic regions with 73% accuracy and clinicians agreed with the algorithm in 93% of seizure-free patients. The algorithm was further validated by using the metrics of the annotated epileptogenic zone to predict surgical outcomes. The source-sink metrics predicted outcomes with an accuracy of 79% compared to an accuracy of 43% for clinicians’ predictions (surgical success rate of this dataset). In failed outcomes, we identified brain regions with high metrics that were untreated. When compared with high frequency oscillations, the most commonly proposed interictal iEEG feature for epileptogenic zone localization, source-sink metrics outperformed in predictive power (by a factor of 1.2), suggesting they may be an interictal iEEG fingerprint of the epileptogenic zone.

Electrocorticography (ECoG) and stereotactic electroencephalography (SEEG) are popular tools for studying neural mechanisms governing behavior and neural disorders, such as epilepsy. In particular, clinicians are interested in identifying brain regions that start seizures, i.e., the epileptogenic zone (EZ) from such invasive recordings. Currently, they visually inspect signals from each electrode to locate abnormal activity, and are not informed by predictive models that can characterize such recordings and potentially increase accuracy in localizing the EZ. In this paper, we test whether a simple linear time varying (LTV) model is sufficient to characterize both ECoG and SEEG activity. Specifically, we construct linear time invariant models in consecutive time windows before, during and after seizure events creating an LTV model from data collected in one ECoG and one SEEG patient. We find that these LTV models accurately reconstruct both ECoG and SEEG time series measured suggesting that these LTV models can be used for EZ localization.

Over 15 million epilepsy patients worldwide have medically refractory epilepsy (MRE), i.e., they do not respond to anti-epileptic drugs. Successful surgery is a hopeful alternative for seizure freedom but can only be achieved through complete resection or disconnection of the epileptogenic zone (EZ), the brain region(s) where seizures originate. Unfortunately, surgical success rates vary between 30%-70% because no clinically validated biological markers of the EZ exist. Localizing the EZ has thus become a costly and time-consuming process during which a team of clinicians obtain non-invasive neuroimaging data, which is often followed by invasive monitoring involving days-to-weeks of EEG recordings captured intracranially (iEEG). Clinicians visually inspect iEEG data, looking for abnormal activity (e.g., low-voltage high frequency activity) on individual channels occurring immediately before seizures. They also look for abnormal spikes that occur on iEEG between seizures ("resting-state"). In the end, clinicians use <1% of the iEEG data captured to assist in EZ localization (minutes of seizure data versus days of recordings), missing opportunities to leverage these largely ignored data to better diagnose and treat patients. Intracranial EEG offers a unique opportunity to observe rich epileptic cortical network dynamics but waiting for seizures to occur increases patient risks associated invasive monitoring. In this study, we aim to leverage iEEG data in between seizures by developing a new networked-based resting-state iEEG marker of the EZ. We hypothesize that when a patient is not seizing, it is because the EZ is inhibited by neighboring nodes. We develop an algorithm that identifies two groups of nodes from the resting-state iEEG network: those that are continuously inhibiting a set of neighboring nodes ("sources") and the inhibited nodes themselves ("sinks"). Specifically, patient-specific dynamical network models (DNMs) are estimated from minutes of iEEG and their connectivity properties reveal top sources and sinks in the network, with each node being quantified by a source-sink index (SSI). We validate the SSI index in a retrospective analysis of 65 patients by using the SSI of the annotated EZ as a metric to predict surgical outcomes. SSI predicts with an accuracy of 79%, compared to the accuracy of clinicians being 43% (successful outcomes). In failed outcomes, we identify regions of the brain with high SSIs that were untreated. When compared to high frequency oscillations, the most common resting-state iEEG feature proposed for EZ localization, SSI outperformed in predictive power (by a factor of 1.2) suggesting SSI as a resting-state EEG fingerprint of the EZ.