ORCID Profile
0000-0002-9879-5854
Current Organisation
University of Melbourne
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Biological Mathematics | Central Nervous System | Applied Mathematics | Pattern Recognition and Data Mining | Medical Devices | Artificial Intelligence and Image Processing
Nervous System and Disorders | Expanding Knowledge in the Information and Computing Sciences | Health and Support Services not elsewhere classified |
Publisher: Elsevier BV
Date: 08-2021
DOI: 10.1016/J.YEBEH.2019.106556
Abstract: Epilepsy diagnosis can be costly, time-consuming, and not uncommonly inaccurate. The reference standard diagnostic monitoring is continuous video-electroencephalography (EEG) monitoring, ideally capturing all events or concordant interictal discharges. Automating EEG data review would save time and resources, thus enabling more people to receive reference standard monitoring and also potentially heralding a more quantitative approach to therapeutic outcomes. There is substantial research into the automated detection of seizures and epileptic activity from EEG. However, automated detection software is not widely used in the clinic, and despite numerous published algorithms, few methods have regulatory approval for detecting epileptic activity from EEG. This study reports on a deep learning algorithm for computer-assisted EEG review. Deep convolutional neural networks were trained to detect epileptic discharges using a preexisting dataset of over 6000 labelled events in a cohort of 103 patients with idiopathic generalized epilepsy (IGE). Patients underwent 24-hour ambulatory outpatient EEG, and all data were curated and confirmed independently by two epilepsy specialists (Seneviratne et al., 2016). The resulting automated detection algorithm was then used to review diagnostic scalp EEG for seven patients (four with IGE and three with events mimicking seizures) to validate performance in a clinical setting. The automated detection algorithm showed state-of-the-art performance for detecting epileptic activity from clinical EEG, with mean sensitivity of >95% and corresponding mean false positive rate of 1 detection per minute. Importantly, diagnostic case studies showed that the automated detection algorithm reduced human review time by 80%-99%, without compromising event detection or diagnostic accuracy. The presented results demonstrate that computer-assisted review can increase the speed and accuracy of EEG assessment and has the potential to greatly improve therapeutic outcomes. This article is part of the Special Issue "NEWroscience 2018".
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 16-02-2021
DOI: 10.1212/WNL.0000000000011408
Abstract: To determine the utility of high-frequency activity (HFA) and epileptiform spikes as biomarkers for epilepsy, we examined the variability in their rates and locations using long-term ambulatory intracranial EEG (iEEG) recordings. This study used continuous iEEG recordings obtained over an average of 1.4 years from 15 patients with drug-resistant focal epilepsy. HFA was defined as 80- to 170-Hz events with litudes clearly larger than the background, which was automatically detected with a custom algorithm. The automatically detected HFA was compared with visually annotated high-frequency oscillations (HFOs). The variations of HFA rates were compared with spikes and seizures on patient-specific and electrode-specific bases. HFA included manually annotated HFOs and high- litude events occurring in the 80- to 170-Hz range without observable oscillatory behavior. HFA and spike rates had high amounts of intrapatient and interpatient variability. Rates of HFA and spikes had large variability after electrode implantation in most of the patients. Locations of HFA and spikes varied up to weeks in more than one-third of the patients. Both HFA and spike rates showed strong circadian rhythms in all patients, and some also showed multiday cycles. Furthermore, the circadian patterns of HFA and spike rates had patient-specific correlations with seizures, which tended to vary across electrodes. Analysis of HFA and epileptiform spikes should consider postimplantation variability. HFA and epileptiform spikes, like seizures, show circadian rhythms. However, the circadian profiles can vary spatially within patients, and their correlations to seizures are patient-specific.
Publisher: Wiley
Date: 30-12-2020
DOI: 10.1111/EPI.16785
Abstract: 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. 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 in idual 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. 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 in idual feature. 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 in idual'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.
Publisher: Elsevier BV
Date: 04-2020
Publisher: Oxford University Press (OUP)
Date: 2023
DOI: 10.1093/BRAINCOMMS/FCAD205
Abstract: Many biological processes are modulated by rhythms on circadian and multidien timescales. In focal epilepsy, various seizure features, such as spread and duration, can change from one seizure to the next within the same patient. However, the specific timescales of this variability, as well as the specific seizure characteristics that change over time, are unclear. Here, in a cross-sectional observational study, we analysed within-patient seizure variability in 10 patients with chronic intracranial EEG recordings (185-767 days of recording time, 57-452 analysed seizures atient). We characterised the seizure evolutions as sequences of a finite number of patient-specific functional seizure network states. We then compared seizure network state occurrence and duration to (1) time since implantation and (2) patient-specific circadian and multidien cycles in interictal spike rate. In most patients, the occurrence or duration of at least one seizure network state was associated with the time since implantation. Some patients had one or more seizure network states that were associated with phases of circadian and/or multidien spike rate cycles. A given seizure network state’s occurrence and duration were usually not associated with the same timescale. Our results suggest that different time-varying factors modulate within-patient seizure evolutions over multiple timescales, with separate processes modulating a seizure network state’s occurrence and duration. These findings imply that the development of time-adaptive treatments in epilepsy must account for several separate properties of epileptic seizures, and similar principles likely apply to other neurological conditions.
Publisher: Wiley
Date: 26-07-2020
DOI: 10.1111/EPI.16541
Publisher: Wiley
Date: 07-2022
DOI: 10.1111/EPI.17311
Abstract: To date, the unpredictability of seizures remains a source of suffering for people with epilepsy, motivating decades of research into methods to forecast seizures. Originally, only few scientists and neurologists ventured into this niche endeavor, which, given the difficulty of the task, soon turned into a long and winding road. Over the past decade, however, our narrow field has seen a major acceleration, with trials of chronic electroencephalographic devices and the subsequent discovery of cyclical patterns in the occurrence of seizures. Now, a burgeoning science of seizure timing is emerging, which in turn informs best forecasting strategies for upcoming clinical trials. Although the finish line might be in view, many challenges remain to make seizure forecasting a reality. This review covers the most recent scientific, technical, and medical developments, discusses methodology in detail, and sets a number of goals for future studies.
Publisher: Wiley
Date: 28-12-2019
DOI: 10.1111/EPI.16418
Abstract: Seizure prediction is feasible, but greater accuracy is needed to make seizure prediction clinically viable across a large group of patients. Recent work crowdsourced state-of-the-art prediction algorithms in a worldwide competition, yielding improvements in seizure prediction performance for patients whose seizures were previously found hard to anticipate. The aim of the current analysis was to explore potential performance improvements using an ensemble of the top competition algorithms. The results suggest that minor increments in performance may be possible however, the outcomes of statistical testing limit the confidence in these increments. Our results suggest that for the specific algorithms, evaluation framework, and data considered here, incremental improvements are achievable but there may be upper bounds on machine learning-based seizure prediction performance for some patients whose seizures are challenging to predict. Other more tailored approaches that, for ex le, take into account a deeper understanding of preictal mechanisms, patient-specific sleep-wake rhythms, or novel measurement approaches, may still offer further gains for these types of patients.
Publisher: Cold Spring Harbor Laboratory
Date: 28-11-2020
DOI: 10.1101/2020.11.24.20237990
Abstract: Circadian and multiday rhythms are found across many biological systems, including cardiology, endocrinology, neurology, and immunology. In people with epilepsy, epileptic brain activity and seizure occurrence have been found to follow circadian, weekly, and monthly rhythms. Understanding the relationship between these cycles of brain excitability and other physiological systems can provide new insight into the causes of multiday cycles. The brain-heart link is relevant for epilepsy, with implications for seizure forecasting, therapy, and mortality (i.e., sudden unexpected death in epilepsy). We report the results from a non-interventional, observational cohort study, Tracking Seizure Cycles. This study sought to examine multiday cycles of heart rate and seizures in adults with diagnosed uncontrolled epilepsy (N=31) and healthy adult controls (N=15) using wearable smartwatches and mobile seizure diaries over at least four months (M=12.0, SD=5.9 control M=10.6, SD=6.4). Cycles in heart rate were detected using a continuous wavelet transform. Relationships between heart rate cycles and seizure occurrence were measured from the distributions of seizure likelihood with respect to underlying cycle phase. Heart rate cycles were found in all 46 participants (people with epilepsy and healthy controls), with circadian (N=46), about-weekly (N=25) and about-monthly (N=13) rhythms being the most prevalent. Of the participants with epilepsy, 19 people had at least 20 reported seizures, and 10 of these had seizures significantly phase locked to their multiday heart rate cycles. Heart rate cycles showed similarities to multiday epileptic rhythms and may be comodulated with seizure likelihood. The relationship between heart rate and seizures is relevant for epilepsy therapy, including seizure forecasting, and may also have implications for cardiovascular disease. More broadly, understanding the link between multiday cycles in the heart and brain can shed new light on endogenous physiological rhythms in humans.
Publisher: Cold Spring Harbor Laboratory
Date: 26-03-2020
DOI: 10.1101/2020.03.26.999425
Abstract: To assess the variability in the rates and locations of high-frequency activity (HFA) and epileptiform spikes after electrode implantation, and to examine the long-term patterns of HFA using ambulatory intracranial EEG (iEEG) recordings. Continuous iEEG recordings obtained over an average of 1.4 years from 15 patients with drug-resistant focal epilepsy were used in this study. HFA was defined as high-frequency events with litudes clearly larger than the background, which was automatically detected using a custom algorithm. High-frequency oscillations (HFOs) were also visually annotated by three neurologists in randomly s led segments of the total data. The automatically detected HFA was compared with the visually marked HFOs. The variations of HFA rates were compared with spikes and seizures on patient-specific and electrode-specific bases. HFA was a more general event that encompassed HFOs manually annotated by different reviewers. HFA and spike rates had high amounts of intra- and inter-patient variability. The rates and locations of HFA and spikes took up to weeks to stabilize after electrode implantation in some patients. Both HFA and spike rates showed strong circadian rhythms in all patients and some also showed multiday cycles. Furthermore, the circadian patterns of HFA and spike rates had patient-specific correlations with seizures, which tended to vary across electrodes. Analysis of HFA and epileptiform spikes should account for post-implantation variability. Like seizures, HFA and epileptiform spikes show circadian rhythms. However, the circadian profiles can vary spatially within patients and their correlations to seizures are patient-specific.
Publisher: Elsevier BV
Date: 2021
DOI: 10.2139/SSRN.3745167
Publisher: Springer Science and Business Media LLC
Date: 26-11-2018
DOI: 10.1038/S41593-018-0278-Y
Abstract: 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.
Publisher: Elsevier BV
Date: 10-2021
Publisher: Elsevier BV
Date: 11-2017
Publisher: eLife Sciences Publications, Ltd
Date: 21-07-2020
DOI: 10.7554/ELIFE.55632
Abstract: Seizures are a disruption of normal brain activity present across a vast range of species and conditions. We introduce an organizing principle that leads to the first objective Taxonomy of Seizure Dynamics (TSD) based on bifurcation theory. The ‘dynamotype’ of a seizure is the dynamic composition that defines its observable characteristics, including how it starts, evolves and ends. Analyzing over 2000 focal-onset seizures from multiple centers, we find evidence of all 16 dynamotypes predicted in TSD. We demonstrate that patients’ dynamotypes evolve during their lifetime and display complex but systematic variations including hierarchy (certain types are more common), non-bijectivity (a patient may display multiple types) and pairing preference (multiple types may occur during one seizure). TSD provides a way to stratify patients in complement to present clinical classifications, a language to describe the most critical features of seizure dynamics, and a framework to guide future research focused on dynamical properties.
Publisher: Oxford University Press (OUP)
Date: 08-08-2018
DOI: 10.1093/BRAIN/AWY210
Publisher: Elsevier BV
Date: 11-2018
Publisher: Springer Science and Business Media LLC
Date: 05-2020
DOI: 10.1038/S41467-020-15908-3
Abstract: The human brain has the capacity to rapidly change state, and in epilepsy these state changes can be catastrophic, resulting in loss of consciousness, injury and even death. Theoretical interpretations considering the brain as a dynamical system suggest that prior to a seizure, recorded brain signals may exhibit critical slowing down, a warning signal preceding many critical transitions in dynamical systems. Using long-term intracranial electroencephalography (iEEG) recordings from fourteen patients with focal epilepsy, we monitored key signatures of critical slowing down prior to seizures. The metrics used to detect critical slowing down fluctuated over temporally long scales (hours to days), longer than would be detectable in standard clinical evaluation settings. Seizure risk was associated with a combination of these signals together with epileptiform discharges. These results provide strong validation of theoretical models and demonstrate that critical slowing down is a reliable indicator that could be used in seizure forecasting algorithms.
Publisher: Cold Spring Harbor Laboratory
Date: 21-12-2019
DOI: 10.1101/2019.12.19.19015453
Abstract: Seizure unpredictability is rated as one of the most challenging aspects of living with epilepsy. Seizure likelihood can be influenced by a range of environmental and physiological factors that are difficult to measure and quantify. However, some generalizable patterns have been demonstrated in seizure onset. A majority of people with epilepsy exhibit circadian rhythms in their seizure times and many also show slower, multiday patterns. Seizure cycles can be measured using a range of recording modalities, including self-reported electronic seizure diaries. This study aimed to develop personalized forecasts from a mobile seizure diary app. Forecasts based on circadian and multiday seizure cycles were tested pseudo-prospectively using data from 33 app users (mean of 103 seizures per subject). In idual’s strongest cycles were estimated from their reported seizure times and used to derive the likelihood of future seizures. The forecasting approach was validated using self-reported events and electrographic seizures from the Neurovista dataset, an existing database of long-term electroencephalography that has been widely used to develop forecasting algorithms. The validation dataset showed that forecasts of seizure likelihood based on self-reported cycles were predictive of electrographic seizures. Forecasts using only mobile app diaries allowed users to spend an average of 62.8% of their time in a low-risk state, with 16.6% of their time in a high-risk warning state. On average, 64.5% of seizures occurred during high-risk states and less than 10% of seizures occurred in low-risk states. Seizure diary apps can provide personalized forecasts of seizure likelihood that are accurate and clinically relevant for electrographic seizures. These results have immediate potential for translation to a prospective seizure forecasting trial using a mobile diary app. It is our hope that seizure forecasting apps will one day give people with epilepsy greater confidence in managing their daily activities.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2017
Publisher: Cold Spring Harbor Laboratory
Date: 07-10-2020
DOI: 10.1101/2020.10.05.20207407
Abstract: Objective: Video-electroencephalography (vEEG) is an important component of epilepsy diagnosis and management. Nevertheless, inpatient vEEG monitoring fails to capture seizures in up to one third of patients during diagnostic and pre-surgical monitoring. We hypothesized that personalized seizure forecasts could be used to optimize the timing of vEEG and improve diagnostic yield. Methods: We used a database of ambulatory vEEG studies to select a cohort with linked electronic seizure diaries of more than 20 reported seizures over at least 8 weeks. The total cohort included 48 participants. Diary seizure times were used to detect in iduals' multi-day cycles and estimate times of high seizure risk. We then compared whether estimated seizure risk was significantly different between diagnostic and non-diagnostic vEEGs, and between vEEG with and without recorded epileptic activity. Results: Estimated seizure risk was significantly higher for diagnostic vEEGs and vEEGs with epileptic activity. Across all cycle strengths, the average time in high risk during vEEG was 29.1% compared with 14% for the diagnostic/non-diagnostic groups and 32% compared to 18% for the epileptic activity/no epileptic activity groups. On average, 62.5% of the cohort showed increased time in high risk during vEEG when epileptic activity was recorded (compared to 28% of the cohort where epileptic activity was not recorded). For diagnostic vEEGs, 50% of the cohort had increased time in high risk, compared to 21.5% for non-diagnostic vEEGs. Significance: This study provides a proof of principle that scheduling monitoring times based on personalized seizure risk forecasts can improve the yield of vEEG. Importantly, forecasts can be developed at low cost from mobile seizure diaries. A simple scheduling tool to improve diagnostic outcomes has the potential to reduce the significant cost and risks associated with delayed or missed diagnosis in epilepsy.
Publisher: Frontiers Media SA
Date: 13-07-2021
DOI: 10.3389/FNEUR.2021.690404
Abstract: It is a major challenge in clinical epilepsy to diagnose and treat a disease characterized by infrequent seizures based on patient or caregiver reports and limited duration clinical testing. The poor reliability of self-reported seizure diaries for many people with epilepsy is well-established, but these records remain necessary in clinical care and therapeutic studies. A number of wearable devices have emerged, which may be capable of detecting seizures, recording seizure data, and alerting caregivers. Developments in non-invasive wearable sensors to measure accelerometry, photoplethysmography (PPG), electrodermal activity (EDA), electromyography (EMG), and other signals outside of the traditional clinical environment may be able to identify seizure-related changes. Non-invasive scalp electroencephalography (EEG) and minimally invasive subscalp EEG may allow direct measurement of seizure activity. However, significant network and computational infrastructure is needed for continuous, secure transmission of data. The large volume of data acquired by these devices necessitates computer-assisted review and detection to reduce the burden on human reviewers. Furthermore, user acceptability of such devices must be a paramount consideration to ensure adherence with long-term device use. Such devices can identify tonic–clonic seizures, but identification of other seizure semiologies with non-EEG wearables is an ongoing challenge. Identification of electrographic seizures with subscalp EEG systems has recently been demonstrated over long (& month) durations, and this shows promise for accurate, objective seizure records. While the ability to detect and forecast seizures from ambulatory intracranial EEG is established, invasive devices may not be acceptable for many in iduals with epilepsy. Recent studies show promising results for probabilistic forecasts of seizure risk from long-term wearable devices and electronic diaries of self-reported seizures. There may also be predictive value in in iduals' symptoms, mood, and cognitive performance. However, seizure forecasting requires perpetual use of a device for monitoring, increasing the importance of the system's acceptability to users. Furthermore, long-term studies with concurrent EEG confirmation are lacking currently. This review describes the current evidence and challenges in the use of minimally and non-invasive devices for long-term epilepsy monitoring, the essential components in remote monitoring systems, and explores the feasibility to detect and forecast impending seizures via long-term use of these systems.
Publisher: Public Library of Science (PLoS)
Date: 26-06-2015
Publisher: Springer Science and Business Media LLC
Date: 15-03-2021
DOI: 10.1038/S41582-021-00464-1
Abstract: Epilepsy is among the most dynamic disorders in neurology. A canonical view holds that seizures, the characteristic sign of epilepsy, occur at random, but, for centuries, humans have looked for patterns of temporal organization in seizure occurrence. Observations that seizures are cyclical date back to antiquity, but recent technological advances have, for the first time, enabled cycles of seizure occurrence to be quantitatively characterized with direct brain recordings. Chronic recordings of brain activity in humans and in animals have yielded converging evidence for the existence of cycles of epileptic brain activity that operate over erse timescales: daily (circadian), multi-day (multidien) and yearly (circannual). Here, we review this evidence, synthesizing data from historical observational studies, modern implanted devices, electronic seizure diaries and laboratory-based animal neurophysiology. We discuss advances in our understanding of the mechanistic underpinnings of these cycles and highlight the knowledge gaps that remain. The potential clinical applications of a knowledge of cycles in epilepsy, including seizure forecasting and chronotherapy, are discussed in the context of the emerging concept of seizure risk. In essence, this Review addresses the broad question of why seizures occur when they occur.
Publisher: Wiley
Date: 13-01-2017
DOI: 10.1111/EPI.13636
Publisher: Wiley
Date: 19-06-2023
DOI: 10.1111/EPI.17678
Abstract: Previous studies suggested that patients with epilepsy might be able to forecast their own seizures. This study aimed to assess the relationships between premonitory symptoms, perceived seizure risk, and future and recent self‐reported and electroencephalographically (EEG)‐confirmed seizures in ambulatory patients with epilepsy in their natural home environments. Long‐term e‐surveys were collected from patients with and without concurrent EEG recordings. Information obtained from the e‐surveys included medication adherence, sleep quality, mood, stress, perceived seizure risk, and seizure occurrences preceding the survey. EEG seizures were identified. Univariate and multivariate generalized linear mixed‐effect regression models were used to estimate odds ratios (ORs) for the assessment of the relationships. Results were compared with the seizure forecasting classifiers and device forecasting literature using a mathematical formula converting OR to equivalent area under the curve (AUC). Fifty‐four subjects returned 10 269 e‐survey entries, with four subjects acquiring concurrent EEG recordings. Univariate analysis revealed that increased stress (OR = 2.01, 95% confidence interval [CI] = 1.12–3.61, AUC = .61, p = .02) was associated with increased relative odds of future self‐reported seizures. Multivariate analysis showed that previous self‐reported seizures (OR = 5.37, 95% CI = 3.53–8.16, AUC = .76, p .001) were most strongly associated with future self‐reported seizures, and high perceived seizure risk (OR = 3.34, 95% CI = 1.87–5.95, AUC = .69, p .001) remained significant when prior self‐reported seizures were added to the model. No correlation with medication adherence was found. No significant association was found between e‐survey responses and subsequent EEG seizures. Our results suggest that patients may tend to self‐forecast seizures that occur in sequential groupings and that low mood and increased stress may be the result of previous seizures rather than independent premonitory symptoms. Patients in the small cohort with concurrent EEG showed no ability to self‐predict EEG seizures. The conversion from OR to AUC values facilitates direct comparison of performance between survey and device studies involving survey premonition and forecasting.
Publisher: Wiley
Date: 18-01-2017
DOI: 10.1002/EPI4.12038
Publisher: IOP Publishing
Date: 06-2023
Abstract: Objective . Kalman filtering has previously been applied to track neural model states and parameters, particularly at the scale relevant to electroencephalography (EEG). However, this approach lacks a reliable method to determine the initial filter conditions and assumes that the distribution of states remains Gaussian. This study presents an alternative, data-driven method to track the states and parameters of neural mass models (NMMs) from EEG recordings using deep learning techniques, specifically a long short-term memory (LSTM) neural network. Approach . An LSTM filter was trained on simulated EEG data generated by a NMM using a wide range of parameters. With an appropriately customised loss function, the LSTM filter can learn the behaviour of NMMs. As a result, it can output the state vector and parameters of NMMs given observation data as the input. Main results . Test results using simulated data yielded correlations with R squared of around 0.99 and verified that the method is robust to noise and can be more accurate than a nonlinear Kalman filter when the initial conditions of the Kalman filter are not accurate. As an ex le of real-world application, the LSTM filter was also applied to real EEG data that included epileptic seizures, and revealed changes in connectivity strength parameters at the beginnings of seizures. Significance . Tracking the state vector and parameters of mathematical brain models is of great importance in the area of brain modelling, monitoring, imaging and control. This approach has no need to specify the initial state vector and parameters, which is very difficult to do in practice because many of the variables being estimated cannot be measured directly in physiological experiments. This method may be applied using any NMM and, therefore, provides a general, novel, efficient approach to estimate brain model variables that are often difficult to measure.
Publisher: Public Library of Science (PLoS)
Date: 11-10-2018
Publisher: Elsevier BV
Date: 07-2023
Publisher: Oxford University Press (OUP)
Date: 26-07-2017
DOI: 10.1093/BRAIN/AWX173
Abstract: It is now established that epilepsy is characterized by periodic dynamics that increase seizure likelihood at certain times of day, and which are highly patient-specific. However, these dynamics are not typically incorporated into seizure prediction algorithms due to the difficulty of estimating patient-specific rhythms from relatively short-term or unreliable data sources. This work outlines a novel framework to develop and assess seizure forecasts, and demonstrates that the predictive power of forecasting models is improved by circadian information. The analyses used long-term, continuous electrocorticography from nine subjects, recorded for an average of 320 days each. We used a large amount of out-of-s le data (a total of 900 days for algorithm training, and 2879 days for testing), enabling the most extensive post hoc investigation into seizure forecasting. We compared the results of an electrocorticography-based logistic regression model, a circadian probability, and a combined electrocorticography and circadian model. For all subjects, clinically relevant seizure prediction results were significant, and the addition of circadian information (combined model) maximized performance across a range of outcome measures. These results represent a proof-of-concept for implementing a circadian forecasting framework, and provide insight into new approaches for improving seizure prediction algorithms. The circadian framework adds very little computational complexity to existing prediction algorithms, and can be implemented using current-generation implant devices, or even non-invasively via surface electrodes using a wearable application. The ability to improve seizure prediction algorithms through straightforward, patient-specific modifications provides promise for increased quality of life and improved safety for patients with epilepsy.
Publisher: Cold Spring Harbor Laboratory
Date: 09-02-2020
DOI: 10.1101/2020.02.08.940072
Abstract: Seizures are a disruption of normal brain activity present across a vast range of species, diseases, and conditions. Here we introduce an organizing principle that leads to the first objective Taxonomy of Seizure Dynamics (TSD) based on bifurcation theory, and applied it to the analysis of EEG data. The “dynamotype” of a seizure is the part of its dynamic composition that defines its observable characteristics, including how it starts, evolves and terminates. Analyzing over 2000 focal-onset seizures recorded from 7 epilepsy centers on five continents, we find evidence of all 16 dynamotypes predicted in TSD. We demonstrate that patients’ dynamotypes evolve during their lifetime and display complex but systematic variations including hierarchy (certain dynamotypes are more common), non-bijectivity (a patient may display multiple dynamotypes) and pairing preference (multiple dynamotypes may occur during one seizure). TSD not only provides a way to stratify patients in complement to present practical classifications but also guides biophysically based mechanistic approaches and provides a language to describe the most critical features of seizure dynamics. Taxonomy of Seizure Dynamics (TSD) provides a rigorous method for classifying and quantifying seizures and a principled framework for understanding seizure initiation and propagation.
Publisher: Wiley
Date: 06-04-2018
DOI: 10.1111/EPI.14065
Abstract: We report on patient-specific durations of postictal periods in long-term intracranial electroencephalography (iEEG) recordings. The objective was to investigate the relationship between seizure duration and postictal suppression duration. Long-term recording iEEG from 9 patients (>50 seizures recorded) were analyzed. In total, 2310 seizures were recorded during a total of 13.8 years of recording. Postictal suppression duration was calculated as the duration after seizure termination until total signal energy returned to background levels. The relationship between seizure duration and postictal suppression duration was quantified using the correlation coefficient (r). The effects of populations of seizures within patients, on correlations, were also considered. Populations of seizures within patients were distinguished by seizure duration thresholds and k-means clustering along the dimensions of seizure duration and postictal suppression duration. The effects of bursts of seizures were also considered by defining populations based on interseizure interval (ISI). Seizure duration accounted for 40% of postictal suppression duration variance, aggregated across all patients and seizures. Seizure duration accounted for more than 25% of the variance in postictal suppression duration in 2 patients and accounted for less than 25% in the remaining 7. In 3 patients, heat maps showed multiple distinct postictal patterns indicating multiple populations of seizures. When accounting for these populations, seizure duration accounted for less than 25% of the variance in postictal duration in all populations. Variance in postictal suppression duration accounted for less than 10% of ISI variance in all patients. We have previously demonstrated that some patients have multiple seizure populations distinguishable by seizure duration. This article shows that different seizure populations have distinct and consistent postictal behaviors. The existence of multiple populations in some patients has implications for seizure management and forecasting, whereas the distinct postictal behaviors may have implications for sudden unexpected death in epilepsy (SUDEP) prediction and prevention.
Publisher: Wiley
Date: 27-03-2020
DOI: 10.1111/EPI.16485
Publisher: Wiley
Date: 31-08-2019
DOI: 10.1111/EPI.16321
Abstract: In idual seizure rates are highly volatile, with large fluctuations from month-to-month. Nevertheless, changes in in idual mean seizure rates are used to measure whether or not trial participants successfully respond to treatment. This study aims to quantify the challenges in identifying in idual treatment responders in epilepsy. A power calculation was performed to determine the trial duration required to detect a significant 50% decrease in seizure rates (P < .05) for in iduals. Seizure rate simulations were also performed to determine the number of people who would appear to be 50% responders by chance. Seizure rate statistics were derived from long-term seizure counts recorded during a previous clinical trial for an implantable seizure monitoring device. We showed that in idual variance in monthly seizure rates can lead to an unacceptably high false-positive rate in the detection of in idual treatment responders. This error rate cannot be reduced by increasing the trial population however, it can be reduced by increasing the duration of clinical trials. This finding suggests that some drugs may be incorrectly evaluated as effective or, conversely, that helpful drugs could be rejected based on 50% response rates. It is important to pursue more nuanced approaches to measuring in idual treatment response, which consider the patient-specific distributions of seizure rates.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2018
Publisher: Frontiers Media SA
Date: 28-11-2014
Publisher: Wiley
Date: 31-12-2016
DOI: 10.1111/EPI.13291
Abstract: We report on a quantitative analysis of data from a study that acquired continuous long-term ambulatory human electroencephalography (EEG) data over extended periods. The objectives were to examine the seizure duration and interseizure interval (ISI), their relationship to each other, and the effect of these features on the clinical manifestation of events. Chronic ambulatory intracranial EEG data acquired for the purpose of seizure prediction were analyzed and annotated. A detection algorithm identified potential seizure activity, which was manually confirmed. Events were classified as clinically corroborated, electroencephalographically identical but not clinically corroborated, or subclinical. K-means cluster analysis supplemented by finite mixture modeling was used to locate groupings of seizure duration and ISI. Quantitative analyses confirmed well-resolved groups of seizure duration and ISIs, which were either mono-modal or multimodal, and highly subject specific. Subjects with a single population of seizures were linked to improved seizure prediction outcomes. There was a complex relationship between clinically manifest seizures, seizure duration, and interval. These data represent the first opportunity to reliably investigate the statistics of seizure occurrence in a realistic, long-term setting. The presence of distinct duration groups implies that the evolution of seizures follows a predetermined course. Patterns of seizure activity showed considerable variation between in iduals, but were highly predictable within in iduals. This finding indicates seizure dynamics are characterized by subject-specific time scales therefore, temporal distributions of seizures should also be interpreted on an in idual level. Identification of duration and interval subgroups may provide a new avenue for improving seizure prediction.
Publisher: IEEE
Date: 02-2020
Publisher: Wiley
Date: 26-04-2022
DOI: 10.1111/EPI.17253
Abstract: Emerging evidence has shown that ambient air pollution affects brain health, but little is known about its effect on epileptic seizures. This work aimed to assess the association between daily exposure to ambient air pollution and the risk of epileptic seizures. This study used epileptic seizure data from two independent data sources (NeuroVista and Seer App seizure diary). In the NeuroVista data set, 3273 seizures were recorded using intracranial electroencephalography (iEEG) from 15 participants with refractory focal epilepsy in Australia in 2010–2012. In the seizure diary data set, 3419 self‐reported seizures were collected through a mobile application from 34 participants with epilepsy in Australia in 2018–2021. Daily average concentrations of carbon monoxide (CO), nitrogen dioxide (NO 2 ), ozone (O 3 ), particulate matter ≤10 μm in diameter (PM 10 ), and sulfur dioxide (SO 2 ) were retrieved from the Environment Protection Authority (EPA) based on participants’ postcodes. A patient‐time‐stratified case‐crossover design with the conditional Poisson regression model was used to determine the associations between air pollutants and epileptic seizures. A significant association between CO concentrations and epileptic seizure risks was observed, with an increased seizure risk of 4% (relative risk [RR]: 1.04, 95% confidence interval [CI]: 1.01–1.07) for an interquartile range (IQR) increase of CO concentrations (0.13 parts per million), whereas no significant associations were found for the other four air pollutants in the whole study population. Female participants had a significantly increased risk of seizures when exposed to elevated CO and NO 2 , with RRs of 1.05 (95% CI: 1.01–1.08) and 1.09 (95% CI: 1.01–1.16), respectively. In addition, a significant association was observed between CO and the risk of subclinical seizures (RR: 1.20, 95% CI: 1.12–1.28). Daily exposure to elevated CO concentrations may be associated with an increased risk of epileptic seizures, especially for subclinical seizures.
Publisher: Wiley
Date: 20-04-2023
DOI: 10.1111/EPI.17607
Abstract: The factors that influence seizure timing are poorly understood, and seizure unpredictability remains a major cause of disability. Work in chronobiology has shown that cyclical physiological phenomena are ubiquitous, with daily and multiday cycles evident in immune, endocrine, metabolic, neurological, and cardiovascular function. Additionally, work with chronic brain recordings has identified that seizure risk is linked to daily and multiday cycles in brain activity. Here, we provide the first characterization of the relationships between the cyclical modulation of a erse set of physiological signals, brain activity, and seizure timing. In this cohort study, 14 subjects underwent chronic ambulatory monitoring with a multimodal wrist‐worn sensor (recording heart rate, accelerometry, electrodermal activity, and temperature) and an implanted responsive neurostimulation system (recording interictal epileptiform abnormalities and electrographic seizures). Wavelet and filter–Hilbert spectral analyses characterized circadian and multiday cycles in brain and wearable recordings. Circular statistics assessed electrographic seizure timing and cycles in physiology. Ten subjects met inclusion criteria. The mean recording duration was 232 days. Seven subjects had reliable electroencephalographic seizure detections (mean = 76 seizures). Multiday cycles were present in all wearable device signals across all subjects. Seizure timing was phase locked to multiday cycles in five (temperature), four (heart rate, phasic electrodermal activity), and three (accelerometry, heart rate variability, tonic electrodermal activity) subjects. Notably, after regression of behavioral covariates from heart rate, six of seven subjects had seizure phase locking to the residual heart rate signal. Seizure timing is associated with daily and multiday cycles in multiple physiological processes. Chronic multimodal wearable device recordings can situate rare paroxysmal events, like seizures, within a broader chronobiology context of the in idual. Wearable devices may advance the understanding of factors that influence seizure risk and enable personalized time‐varying approaches to epilepsy care.
Publisher: Cold Spring Harbor Laboratory
Date: 11-05-2021
DOI: 10.1101/2021.05.09.21256558
Abstract: Accurate identification of seizure activity, both clinical and subclinical, has important implications in the management of epilepsy. Accurate recognition of seizure activity is essential for diagnostic, management and forecasting purposes, but patient-reported seizures have been shown to be unreliable. Earlier work has revealed accurate capture of electrographic seizures and forecasting is possible with an implantable intracranial device, but less invasive electroencephalography (EEG) recording systems would be optimal. Here, we present preliminary results of seizure detection and forecasting with a minimally invasive sub-scalp device that continuously records EEG. Five participants with refractory epilepsy who experience at least two clinically identifiable seizures monthly have been implanted with sub-scalp devices (Minder™), providing two channels of data from both hemispheres of the brain. Data is continuously captured via a behind-the-ear system, which also powers the device, and transferred wirelessly to a mobile phone, from where it is accessible remotely via cloud storage. EEG recordings from the sub-scalp device were compared to data recorded from a conventional system during a 1-week ambulatory video-EEG monitoring session. Suspect epileptiform activity (EA) was detected using machine learning algorithms and reviewed by trained neurophysiologists. Seizure forecasting was demonstrated retrospectively by utilising cycles in EA and previous seizure times. The procedures and devices were well tolerated, and no significant complications have been reported. Seizures were accurately identified on the sub-scalp system, as confirmed by periods of concurrent conventional scalp EEG recordings. The data acquired also allowed seizure forecasting to be successfully undertaken. The area under the receiver operating characteristic curve (AUC score) achieved (0.88) is comparable to the best score in recent, state-of-the-art forecasting work using intracranial EEG.
Publisher: Cold Spring Harbor Laboratory
Date: 02-07-2019
DOI: 10.1101/689893
Abstract: The human brain has the capacity to rapidly change state, and in epilepsy these state changes can be catastrophic, resulting in loss of consciousness, injury and even death. Theoretical interpretations considering the brain as a dynamical system would suggest that prior to a seizure recorded brain signals may exhibit critical slowing, a warning signal preceding many critical transitions in dynamical systems. Using long-term intracranial electroencephalography (iEEG) recordings from fourteen patients with focal epilepsy, we found key signatures of critical slowing prior to seizures. Signals related to a critically slowing process fluctuated over temporally long scales (hours to days), longer than would be detectable in standard clinical evaluation settings. Seizure risk was associated with a combination of these signals together with epileptiform discharges. These results provide strong validation of theoretical models and demonstrate that critical slowing is a reliable indicator that could be used in seizure forecasting algorithms.
Publisher: Wiley
Date: 09-01-2018
DOI: 10.1002/ACN3.519
Publisher: Wiley
Date: 26-07-2020
DOI: 10.1111/EPI.16555
Publisher: Springer Science and Business Media LLC
Date: 24-09-2015
DOI: 10.1007/S11910-015-0596-3
Abstract: This review highlights recent developments in the field of epileptic seizure prediction. We argue that seizure prediction is possible however, most previous attempts have used data with an insufficient amount of information to solve the problem. The review discusses four methods for gaining more information above standard clinical electrophysiological recordings. We first discuss developments in obtaining long-term data that enables better characterisation of signal features and trends. Then, we discuss the usage of electrical stimulation to probe neural circuits to obtain robust information regarding excitability. Following this, we present a review of developments in high-resolution micro-electrode technologies that enable neuroimaging across spatial scales. Finally, we present recent results from data-driven model-based analyses, which enable imaging of seizure generating mechanisms from clinical electrophysiological measurements. It is foreseeable that the field of seizure prediction will shift focus to a more probabilistic forecasting approach leading to improvements in the quality of life for the millions of people who suffer uncontrolled seizures. However, a missing piece of the puzzle is devices to acquire long-term high-quality data. When this void is filled, seizure prediction will become a reality.
Publisher: Cold Spring Harbor Laboratory
Date: 26-05-2021
DOI: 10.1101/2021.05.20.21257495
Abstract: The unpredictability of epileptic seizures exposes people with epilepsy to potential physical harm, restricts day-to-day activities, and impacts mental well-being. Accurate seizure forecasters would reduce the uncertainty associated with seizures but need to be feasible and accessible in the long-term. Wearable devices are perfect candidates to develop non-invasive, accessible forecasts but are yet to be investigated in long-term studies. We hypothesized that machine learning models could utilize heart rate as a biomarker for well-established cycles of seizures and epileptic activity, in addition to other wearable signals, to forecast high and low risk seizure periods. This feasibility study tracked participants’ (n = 11) heart rates, sleep, and step counts using wearable smartwatches and seizure occurrence using mobile seizure diaries for at least 6 months (mean = 14.6 months, SD = 3.8 months). Eligible participants had a diagnosis of refractory epilepsy and reported at least 20 seizures (mean = 135, SD = 123) during the recording period. An ensembled machine learning and neural network model estimated seizure risk either daily or hourly, with retraining occurring on a weekly basis as additional data was collected. Performance was evaluated retrospectively against a rate-matched random forecast using the area under the receiver operating curve. A pseudo-prospective evaluation was also conducted on a held-out dataset. Of the 11 participants, seizures were predicted above chance in all (100%) participants using an hourly forecast and in ten (91%) participants using a daily forecast. The average time spent in high risk (prediction time) before a seizure occurred was 37 minutes in the hourly forecast and 3 days in the daily forecast. Cyclic features added the most predictive value to the forecasts, particularly circadian and multiday heart rate cycles. Wearable devices can be used to produce patient-specific seizure forecasts, particularly when biomarkers of seizure and epileptic activity cycles are utilized.
Publisher: Elsevier
Date: 2020
Publisher: Frontiers Media SA
Date: 27-02-2019
Publisher: Public Library of Science (PLoS)
Date: 27-03-2018
Publisher: Cold Spring Harbor Laboratory
Date: 28-03-2023
DOI: 10.1101/2023.03.23.23287561
Abstract: Previous studies suggested that patients with epilepsy might be able to fore-cast their own seizures. We sought to assess the relationships of premonitory symptoms and perceived seizure risk with future and recent self-reported and EEG-confirmed seizures in the subjects living with epilepsy in their natural home environments. We collected long-term e-surveys from ambulatory patients with and without concurrent EEG recordings. Information obtained from the e-surveys included medication compliance, sleep quality, mood, stress, perceived seizure risk and seizure occurrences preceding the survey. EEG seizures were identified. Univariate and multivariate generalized linear mixed-effect regression models were used to estimate odds ratios (ORs) for the assessment of the relationships. Results were compared with device seizure forecasting literature using a mathematical formula converting OR to equivalent area under the curve (AUC). Sixty-nine subjects returned 12,590 e-survey entries, with four subjects acquiring concurrent EEG recordings. Univariate analysis revealed increased stress (OR = 2.52, 95% CI = [1.52, 4.14], p 0.001) and decreased mood (0.32, [0.13, 0.82], 0.02) were associated with increased relative odds of future self-reported seizures. On multivariate analysis, previous self-reported seizures (4.24, [2.69, 6.68], 0.001) were most strongly associated with future self-reported seizures, and high perceived seizure risk (3.30, [1.97, 5.52], 0.001) remained significant when prior self-reported seizures were added to the model. No significant association was found between e-survey responses and subsequent EEG seizures. It appears that patients may tend to self-forecast seizures that occur in sequential groupings. Our results suggest that low mood and increased stress may be the result of previous seizures rather than independent premonitory symptoms. Patients in the small cohort with concurrent EEG showed no ability to self-predict EEG seizures. The conversion from OR to AUC values facilitates direct comparison of performance between survey and device studies involving survey premonition and forecasting. Long-term e-surveys data and concurrent EEG signals were collected across three study sites to assess the ability of the patients to self-forecast their seizures. Patients may tend to self-forecast self-reported seizures that occur in sequential groupings. Factors, such as mood and stress, may not be independent premonitory symptoms but may be the consequence of recent seizures. No ability to self-forecast EEG confirmed seizures was observed in a small cohort with concurrent EEG validation. A mathematic relation between OR and AUC provides a means to compare forecasting performance between survey and device studies.
Publisher: Wiley
Date: 28-01-2021
DOI: 10.1111/EPI.16809
Abstract: Video‐electroencephalography (vEEG) is an important component of epilepsy diagnosis and management. Nevertheless, inpatient vEEG monitoring fails to capture seizures in up to one third of patients. We hypothesized that personalized seizure forecasts could be used to optimize the timing of vEEG. We used a database of ambulatory vEEG studies to select a cohort with linked electronic seizure diaries of more than 20 reported seizures over at least 8 weeks. The total cohort included 48 participants. Diary seizure times were used to detect in iduals' multiday seizure cycles and estimate times of high seizure risk. We compared whether estimated seizure risk was significantly different between conclusive and inconclusive vEEGs, and between vEEG with and without recorded epileptic activity. vEEGs were conducted prior to self‐reported seizures hence, the study aimed to provide a retrospective proof of concept that cycles of seizure risk were correlated with vEEG outcomes. Estimated seizure risk was significantly higher for conclusive vEEGs and vEEGs with epileptic activity. Across all cycle strengths, the average time in high risk during vEEG was 29.1% compared with 14% for the conclusive/inconclusive groups and 32% compared to 18% for the epileptic activity/no epileptic activity groups. On average, 62.5% of the cohort showed increased time in high risk during their previous vEEG when epileptic activity was recorded (compared to 28% of the cohort where epileptic activity was not recorded). For conclusive vEEGs, 50% of the cohort had increased time in high risk, compared to 21.5% for inconclusive vEEGs. Although retrospective, this study provides a proof of principle that scheduling monitoring times based on personalized seizure risk forecasts can improve the yield of vEEG. Forecasts can be developed at low cost from mobile seizure diaries. A simple scheduling tool to improve diagnostic outcomes may reduce cost and risks associated with delayed or missed diagnosis in epilepsy.
Publisher: Elsevier BV
Date: 2018
Publisher: Oxford University Press (OUP)
Date: 17-02-2016
DOI: 10.1093/BRAIN/AWW019
Abstract: We report on a quantitative analysis of electrocorticography data from a study that acquired continuous ambulatory recordings in humans over extended periods of time. The objectives were to examine patterns of seizures and spontaneous interictal spikes, their relationship to each other, and the nature of periodic variation. The recorded data were originally acquired for the purpose of seizure prediction, and were subsequently analysed in further detail. A detection algorithm identified potential seizure activity and a template matched filter was used to locate spikes. Seizure events were confirmed manually and classified as either clinically correlated, electroencephalographically identical but not clinically correlated, or subclinical. We found that spike rate was significantly altered prior to seizure in 9 out of 15 subjects. Increased pre-ictal spike rate was linked to improved predictability however, spike rate was also shown to decrease before seizure (in 6 out of the 9 subjects). The probability distribution of spikes and seizures were notably similar, i.e. at times of high seizure likelihood the probability of epileptic spiking also increased. Both spikes and seizures showed clear evidence of circadian regulation and, for some subjects, there were also longer term patterns visible over weeks to months. Patterns of spike and seizure occurrence were highly subject-specific. The pre-ictal decrease in spike rate is not consistent with spikes promoting seizures. However, the fact that spikes and seizures demonstrate similar probability distributions suggests they are not wholly independent processes. It is possible spikes actively inhibit seizures, or that a decreased spike rate is a secondary symptom of the brain approaching seizure. If spike rate is modulated by common regulatory factors as seizures then spikes may be useful biomarkers of cortical excitability.
Publisher: Frontiers Media SA
Date: 23-08-2021
DOI: 10.3389/FNEUR.2021.713794
Abstract: Accurate identification of seizure activity, both clinical and subclinical, has important implications in the management of epilepsy. Accurate recognition of seizure activity is essential for diagnostic, management and forecasting purposes, but patient-reported seizures have been shown to be unreliable. Earlier work has revealed accurate capture of electrographic seizures and forecasting is possible with an implantable intracranial device, but less invasive electroencephalography (EEG) recording systems would be optimal. Here, we present preliminary results of seizure detection and forecasting with a minimally invasive sub-scalp device that continuously records EEG. Five participants with refractory epilepsy who experience at least two clinically identifiable seizures monthly have been implanted with sub-scalp devices (Minder ® ), providing two channels of data from both hemispheres of the brain. Data is continuously captured via a behind-the-ear system, which also powers the device, and transferred wirelessly to a mobile phone, from where it is accessible remotely via cloud storage. EEG recordings from the sub-scalp device were compared to data recorded from a conventional system during a 1-week ambulatory video-EEG monitoring session. Suspect epileptiform activity (EA) was detected using machine learning algorithms and reviewed by trained neurophysiologists. Seizure forecasting was demonstrated retrospectively by utilizing cycles in EA and previous seizure times. The procedures and devices were well-tolerated and no significant complications have been reported. Seizures were accurately identified on the sub-scalp system, as visually confirmed by periods of concurrent conventional scalp EEG recordings. The data acquired also allowed seizure forecasting to be successfully undertaken. The area under the receiver operating characteristic curve (AUC score) achieved (0.88), which is comparable to the best score in recent, state-of-the-art forecasting work using intracranial EEG.
Start Date: 02-2020
End Date: 12-2023
Amount: $420,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 06-2018
End Date: 12-2024
Amount: $4,133,659.00
Funder: Australian Research Council
View Funded Activity