Biomedical Engineering - Research Publications

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    Ensembling crowdsourced seizure prediction algorithms using long-term human intracranial EEG
    Reuben, C ; Karoly, P ; Freestone, DR ; Temko, A ; Barachant, A ; Li, F ; Titericz, G ; Lang, BW ; Lavery, D ; Roman, K ; Broadhead, D ; Jones, G ; Tang, Q ; Ivanenko, I ; Panichev, O ; Proix, T ; Nahlik, M ; Grunberg, DB ; Grayden, DB ; Cook, MJ ; Kuhlmann, L (Wiley, 2020-02)
    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 example, 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.
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    Seizure likelihood varies with day-to-day variations in sleep duration in patients with refractory focal epilepsy: A longitudinal electroencephalography investigation
    Dell, KL ; Payne, DE ; Kremen, V ; Maturana, MI ; Gerla, V ; Nejedly, P ; Worrell, GA ; Lenka, L ; Mivalt, F ; Boston, RC ; Brinkmann, BH ; D'Souza, W ; Burkitt, AN ; Grayden, DB ; Kuhlmann, L ; Freestone, DR ; Cook, MJ (ELSEVIER, 2021-07)
    BACKGROUND: While the effects of prolonged sleep deprivation (≥24 h) on seizure occurrence has been thoroughly explored, little is known about the effects of day-to-day variations in the duration and quality of sleep on seizure probability. A better understanding of the interaction between sleep and seizures may help to improve seizure management. METHODS: To explore how sleep and epileptic seizures are associated, we analysed continuous intracranial electroencephalography (EEG) recordings collected from 10 patients with refractory focal epilepsy undergoing ordinary life activities between 2010 and 2012 from three clinical centres (Austin Health, The Royal Melbourne Hospital, and St Vincent's Hospital of the Melbourne University Epilepsy Group). A total of 4340 days of sleep-wake data were analysed (average 434 days per patient). EEG data were sleep scored using a semi-automated machine learning approach into wake, stages one, two, and three non-rapid eye movement sleep, and rapid eye movement sleep categories. FINDINGS: Seizure probability changes with day-to-day variations in sleep duration. Logistic regression models revealed that an increase in sleep duration, by 1·66 ± 0·52 h, lowered the odds of seizure by 27% in the following 48 h. Following a seizure, patients slept for longer durations and if a seizure occurred during sleep, then sleep quality was also reduced with increased time spent aroused from sleep and reduced rapid eye movement sleep. INTERPRETATION: Our results suggest that day-to-day deviations from regular sleep duration correlates with changes in seizure probability. Sleeping longer, by 1·66 ± 0·52 h, may offer protective effects for patients with refractory focal epilepsy, reducing seizure risk. Furthermore, the occurrence of a seizure may disrupt sleep patterns by elongating sleep and, if the seizure occurs during sleep, reducing its quality.
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    Identifying seizure risk factors: A comparison of sleep, weather, and temporal features using a Bayesian forecast
    Payne, DE ; Dell, KL ; Karoly, PJ ; Kremen, V ; Gerla, V ; Kuhlmann, L ; Worrell, GA ; Cook, MJ ; Grayden, DB ; Freestone, DR (WILEY, 2021-02)
    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.
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    Forecasting cycles of seizure likelihood
    Karoly, PJ ; Cook, MJ ; Maturana, M ; Nurse, ES ; Payne, D ; Brinkmann, BH ; Grayden, DB ; Dumanis, SB ; Richardson, MP ; Worrell, GA ; Schulze-Bonhage, A ; Kuhlmann, L ; Freestone, DR (Wiley, 2020-03-27)
    Objective 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. Methods Forecasts based on circadian and multiday seizure cycles were tested pseudoprospectively using data from 50 app users (mean of 109 seizures per subject). Individuals' 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. Results The validation dataset showed that forecasts of seizure likelihood based on self‐reported cycles were predictive of electrographic seizures for approximately half the cohort. Forecasts using only mobile app diaries allowed users to spend an average of 67.1% of their time in a low‐risk state, with 14.8% of their time in a high‐risk warning state. On average, 69.1% of seizures occurred during high‐risk states and 10.5% of seizures occurred in low‐risk states. Significance 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.
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    Critical slowing down as a biomarker for seizure susceptibility.
    Maturana, MI ; Meisel, C ; Dell, K ; Karoly, PJ ; D'Souza, W ; Grayden, DB ; Burkitt, AN ; Jiruska, P ; Kudlacek, J ; Hlinka, J ; Cook, MJ ; Kuhlmann, L ; Freestone, DR (Nature Research (part of Springer Nature), 2020-05-01)
    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.