OBJECTIVE: Seizure unpredictability can be debilitating and dangerous for people with epilepsy. Accurate seizure forecasters could improve quality of life for those with epilepsy but must be practical for long-term use. This study presents the first validation of a seizure-forecasting system using ultra-long-term, non-invasive wearable data. METHODS: Eleven participants with epilepsy were recruited for continuous monitoring, capturing heart rate and step count via wrist-worn devices and seizures via electroencephalography (average recording duration of 337 days). Two hybrid models-combining machine learning and cycle-based methods-were proposed to forecast seizures at both short (minutes) and long (up to 44 days) horizons. RESULTS: The Seizure Warning System (SWS), designed for forecasting near-term seizures, and the Seizure Risk System (SRS), designed for forecasting long-term risk, both outperformed traditional models. In addition, the SRS reduced high-risk time by 29% while increasing sensitivity by 11%. SIGNIFICANCE: These improvements mark a significant advancement in making seizure forecasting more practical and effective.

• Keywords
• epilepsy, forecasting, machine learning, seizure, wearable,
• MeSH
• Adult MeSH
• Electroencephalography methods   MeSH
• Epilepsy * physiopathology   diagnosis   MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Wearable Electronic Devices * MeSH
• Forecasting methods   MeSH
• Prospective Studies MeSH
• Heart Rate physiology   MeSH
• Machine Learning MeSH
• Seizures * diagnosis   physiopathology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Epilepsy is a neurological disease characterized by epileptic seizures, which commonly manifest with pronounced frequency and amplitude changes in the EEG signal. In the case of focal seizures, initially localized pathological activity spreads from a so-called "onset zone" to a wider network of brain areas. Chimeras, defined as states of simultaneously occurring coherent and incoherent dynamics in symmetrically coupled networks are increasingly invoked for characterization of seizures. In particular, chimera-like states have been observed during the transition from a normal (asynchronous) to a seizure (synchronous) network state. However, chimeras in epilepsy have only been investigated with respect to the varying phases of oscillators. We propose a novel method to capture the characteristic pronounced changes in the recorded EEG amplitude during seizures by estimating chimera-like states directly from the signals in a frequency- and time-resolved manner. We test the method on a publicly available intracranial EEG dataset of 16 patients with focal epilepsy. We show that the proposed measure, titled Amplitude Entropy, is sensitive to the altered brain dynamics during seizure, demonstrating its significant increases during seizure as compared to before and after seizure. This finding is robust across patients, their seizures, and different frequency bands. In the future, Amplitude Entropy could serve not only as a feature for seizure detection, but also help in characterizing amplitude chimeras in other networked systems with characteristic amplitude dynamics.

• MeSH
• Adult MeSH
• Electroencephalography methods   MeSH
• Entropy MeSH
• Epilepsies, Partial * physiopathology   MeSH
• Humans MeSH
• Brain * physiopathology   MeSH
• Seizures * physiopathology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

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.

• MeSH
• Electrocorticography MeSH
• Epilepsy * MeSH
• Rats MeSH
• Humans MeSH
• Brain * MeSH
• Computer Simulation MeSH
• Cardiac Electrophysiology MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Chronic brain recordings suggest that seizure risk is not uniform, but rather varies systematically relative to daily (circadian) and multiday (multidien) cycles. Here, one human and seven dogs with naturally occurring epilepsy had continuous intracranial EEG (median 298 days) using novel implantable sensing and stimulation devices. Two pet dogs and the human subject received concurrent thalamic deep brain stimulation (DBS) over multiple months. All subjects had circadian and multiday cycles in the rate of interictal epileptiform spikes (IES). There was seizure phase locking to circadian and multiday IES cycles in five and seven out of eight subjects, respectively. Thalamic DBS modified circadian (all 3 subjects) and multiday (analysis limited to the human participant) IES cycles. DBS modified seizure clustering and circadian phase locking in the human subject. Multiscale cycles in brain excitability and seizure risk are features of human and canine epilepsy and are modifiable by thalamic DBS.

• MeSH
• Circadian Rhythm MeSH
• Electroencephalography MeSH
• Epilepsy prevention & control   MeSH
• Deep Brain Stimulation methods   MeSH
• Humans MeSH
• Dogs MeSH
• Risk MeSH
• Thalamus physiology   MeSH
• Seizures prevention & control   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Dogs MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH

OBJECTIVE: Most seizure forecasting algorithms have relied on features specific to electroencephalographic recordings. Environmental and physiological factors, such as weather and sleep, have long been suspected to affect brain activity and seizure occurrence but have not been fully explored as prior information for seizure forecasts in a patient-specific analysis. The study aimed to quantify whether sleep, weather, and temporal factors (time of day, day of week, and lunar phase) can provide predictive prior probabilities that may be used to improve seizure forecasts. METHODS: This study performed post hoc analysis on data from eight patients with a total of 12.2 years of continuous intracranial electroencephalographic recordings (average = 1.5 years, range = 1.0-2.1 years), originally collected in a prospective trial. Patients also had sleep scoring and location-specific weather data. Histograms of future seizure likelihood were generated for each feature. The predictive utility of individual features was measured using a Bayesian approach to combine different features into an overall forecast of seizure likelihood. Performance of different feature combinations was compared using the area under the receiver operating curve. Performance evaluation was pseudoprospective. RESULTS: For the eight patients studied, seizures could be predicted above chance accuracy using sleep (five patients), weather (two patients), and temporal features (six patients). Forecasts using combined features performed significantly better than chance in six patients. For four of these patients, combined forecasts outperformed any individual feature. SIGNIFICANCE: Environmental and physiological data, including sleep, weather, and temporal features, provide significant predictive information on upcoming seizures. Although forecasts did not perform as well as algorithms that use invasive intracranial electroencephalography, the results were significantly above chance. Complementary signal features derived from an individual's historic seizure records may provide useful prior information to augment traditional seizure detection or forecasting algorithms. Importantly, many predictive features used in this study can be measured noninvasively.

• Keywords
• circadian, forecasting, seizure, sleep, weather,
• MeSH
• Bayes Theorem MeSH
• Time Factors * MeSH
• Adult MeSH
• Electrocorticography MeSH
• Epilepsy physiopathology   MeSH
• Risk Assessment MeSH
• Middle Aged MeSH
• Humans MeSH
• Weather * MeSH
• Risk Factors MeSH
• Sleep * MeSH
• Seizures epidemiology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH