Special Issue on Epilepsy and Neural Engineering

Objectives. People with refractory epilepsy are overwhelmed by the uncertainty of their next seizures. Accurate prediction of future seizures could greatly improve the quality of life for these patients. New evidence suggests that seizure occurrences can have cyclical patterns for some patients. Even though these cyclicalities are not intuitive, they can be identified by machine learning (ML), to identify patients with predictable vs unpredictable seizure patterns. Approach. Self-reported seizure logs of 153 patients from the Human Epilepsy Project with more than three reported seizures (totaling 8337 seizures) were used to obtain inter-seizure interval time-series for training and evaluation of the forecasting models. Two classes of prediction methods were studied: (1) statistical approaches using Bayesian fusion of population-wise and individual-wise seizure patterns; and (2) ML-based algorithms including least squares, least absolute shrinkage and selection operator, support vector machine (SVM) regression, and long short-term memory regression. Leave-one-person-out cross-validation was used for training and evaluation, by training on seizure diaries of all except one subject and testing on the left-out subject. Main results. The leading forecasting models were the SVM regression and a statistical model that combined the median of population-wise seizure time-intervals with a test subject's prior seizure intervals. SVM was able to forecast 50%, 70%, 81%, 84%, and 87% of seizures of unseen subjects within 0, 1, 2, 3 to 4 d of mean absolute forecasting error, respectively. The subject-wise performances show that patients with more frequent seizures were generally better predicted. Significance. ML models can leverage non-random patterns within self-reported seizure diaries to forecast future seizures. While diary-based seizure forecasting alone is only one of many aspects of clinical care of patients with epilepsy, studying the level of predictability across seizures and patients paves the path towards a better understanding of predictable vs unpredictable seizures on individualized and population-wise bases.

Introduction. Epileptic seizures are common neurological disorders in the world, impacting 65 million people globally. Around 30% of patients with seizures suffer from refractory epilepsy, where seizures are not controlled by medications. The unpredictability of seizures makes it essential to have a continuous seizure monitoring system outside clinical settings for the purpose of minimizing patients' injuries and providing additional pathways for evaluation and treatment follow-up. Autonomic changes related to seizure events have been extensively studied and attempts made to apply them for seizure detection and prediction tasks. This scoping review aims to depict current research activities associated with the implementation of portable, wearable devices for seizure detection or prediction and inform future direction in continuous seizure tracking in ambulatory settings. Methods. Overall methodology framework includes 5 essential stages: research questions identification, relevant studies identification, selection of studies, data charting and summarizing the findings. A systematic searching strategy guided by systematic reviews and meta-analysis (PRISMA) was implemented to identify relevant records on two databases (PubMed, IEEE). Results. A total of 30 articles were included in our final analysis. Most of the studies were conducted off-line and employed consumer-graded wearable device. ACM is the dominant modality to be used in seizure detection, and widely deployed algorithms entail Support Vector Machine, Random Forest and threshold-based approach. The sensitivity ranged from 33.2% to 100% for single modality with a false alarm rate (FAR) ranging from 0.096 to 14.8 d⁻¹. Multimodality has a sensitivity ranging from 51% to 100% with FAR ranging from 0.12 to 17.7 d⁻¹. Conclusion. The overall performance in seizure detection system based on non-cerebral physiological signals is promising, especially for the detection of motor seizures and seizures accompanied with intense ictal autonomic changes.

Objective. Epileptic seizures are relatively common in critically-ill children admitted to the pediatric intensive care unit (PICU) and thus serve as an important target for identification and treatment. Most of these seizures have no discernible clinical manifestation but still have a significant impact on morbidity and mortality. Children that are deemed at risk for seizures within the PICU are monitored using continuous-electroencephalogram (cEEG). cEEG monitoring cost is considerable and as the number of available machines is always limited, clinicians need to resort to triaging patients according to perceived risk in order to allocate resources. This research aims to develop a computer aided tool to improve seizures risk assessment in critically-ill children, using an ubiquitously recorded signal in the PICU, namely the electrocardiogram (ECG). Approach. A novel data-driven model was developed at a patient-level approach, based on features extracted from the first hour of ECG recording and the clinical data of the patient. Main results. The most predictive features were the age of the patient, the brain injury as coma etiology and the QRS area. For patients without any prior clinical data, using one hour of ECG recording, the classification performance of the random forest classifier reached an area under the receiver operating characteristic curve (AUROC) score of 0.84. When combining ECG features with the patients clinical history, the AUROC reached 0.87. Significance. Taking a real clinical scenario, we estimated that our clinical decision support triage tool can improve the positive predictive value by more than 59% over the clinical standard.

Objective. While it is well-known that epilepsy has a clear impact on the activity of both the central nervous system (CNS) and the autonomic nervous system (ANS), its role on the complex interplay between CNS and ANS has not been fully elucidated yet. In this work, pairwise and higher-order predictability measures based on the concepts of Granger Causality (GC) and partial information decomposition (PID) were applied on time series of electroencephalographic (EEG) brain wave amplitude and heart rate variability (HRV) in order to investigate directed brain-heart interactions associated with the occurrence of focal epilepsy. Approach. HRV and the envelopes of δ and α EEG activity recorded from ipsilateral (ipsi-EEG) and contralateral (contra-EEG) scalp regions were analyzed in 18 children suffering from temporal lobe epilepsy monitored during pre-ictal, ictal and post-ictal periods. After linear parametric model identification, we compared pairwise GC measures computed between HRV and a single EEG component with PID measures quantifying the unique, redundant and synergistic information transferred from ipsi-EEG and contra-EEG to HRV. Main results. The analysis of GC revealed a dominance of the information transfer from EEG to HRV and negligible transfer from HRV to EEG, suggesting that CNS activities drive the ANS modulation of the heart rhythm, but did not evidence clear differences between δ and α rhythms, ipsi-EEG and contra-EEG, or pre- and post-ictal periods. On the contrary, PID revealed that epileptic seizures induce a reorganization of the interactions from brain to heart, as the unique predictability of HRV originated from the ipsi-EEG for the δ waves and from the contra-EEG for the α waves in the pre-ictal phase, while these patterns were reversed after the seizure. Significance. These results highlight the importance of considering higher-order interactions elicited by PID for the study of the neuro-autonomic effects of focal epilepsy, and may have neurophysiological and clinical implications.

Objective. Electroencephalography is a technique for measuring normal or abnormal neuronal activity in the human brain, but its low spatial resolution makes it difficult to locate the precise locations of neurons due to the volume conduction effect of brain tissue. Approach. The acoustoelectric (AE) effect has the advantage of detecting electrical signals with high temporal resolution and focused ultrasound with high spatial resolution. In this paper, we use dipoles to simulate real single and double neurons, and further investigate the localization and decoding of single and double dipoles based on AE effects from numerical simulations, brain tissue phantom experiments, and fresh porcine brain tissue experiments. Main results. The results show that the localization error of a single dipole is less than 0.3 mm, the decoding signal is highly correlated with the source signal, and the decoding accuracy is greater than 0.94; the location of double dipoles with an interval of 0.4 mm or more can be localized, the localization error tends to increase as the interval of dipoles decreases, and the decoding accuracy tends to decrease as the frequency of dipoles decreases. Significance. This study localizes and decodes dipole signals with high accuracy, and provides a technical method for the development of EEG.

Objective. Focal cortical dysplasia type IIIa (FCD IIIa) is a highly prevalent temporal lobe epilepsy but the seizure outcomes are not satisfactory after epilepsy surgery. Hence, quantitative neuroimaging, epileptogenic alterations, as well as their values in guiding surgery are worth exploring. Approach. We examined 69 patients with pathologically verified FCD IIIa using multimodal neuroimaging and stereoelectroencephalography (SEEG). Among them, 18 received postoperative imaging which showed the extent of surgical resection and 9 underwent SEEG implantation. We also explored neuroimaging gradient alterations along with the distance to the temporal pole. Subsequently, the machine learning regression model was employed to predict whole-brain epileptogenicity. Lastly, the correlation between neuroimaging or epileptogenicity and surgical cavities was assessed. Main results. FCD IIIa displayed neuroimaging gradient alterations on the temporal neocortex, morphology-signal intensity decoupling, low similarity of intra-morphological features and high similarity of intra-signal intensity features. The support vector regression model was successfully applied at the whole-brain level to calculate the continuous epileptogenic value at each vertex (mean-squared error = 13.8 ± 9.8). Significance. Our study investigated the neuroimaging gradient alterations and epileptogenicity of FCD IIIa, along with their potential values in guiding suitable resection range and in predicting postoperative seizure outcomes. The conclusions from this study may facilitate an accurate presurgical examination of FCD IIIa. However, further investigation including a larger cohort is necessary to confirm the results.