Mining Biomarkers Of Epilepsy From Large-Scale Intracranial Electroencephalography

Epilepsy is a chronic neurological disorder characterized by seizures. Affecting over 50 million people worldwide, the quality of life of a patient with uncontrolled epilepsy is degraded by medical, social, cognitive, and psychological dysfunction. Fortunately, two-thirds of these patients can achieve adequate seizure control through medications. Unfortunately, one-third cannot. Improving treatment for this patient population depends upon improving our understanding of the underlying epileptic network. Clinical therapies modulate this network to some degree of success, including surgery to remove the seizure onset zone or neuromodulation to alter the brain\u27s dynamics. High resolution intracranial EEG (iEEG) is often employed to study the dynamics of cortical networks, from interictal patterns to more complex quantitative features. These interictal patterns include epileptiform biomarkers whose detection and mapping, along with seizures and neuroimaging, form the mainstay of data for clinical decision making around drug therapy, surgery, and devices. They are also increasingly important to assess the effects of epileptic physiology on brain functions like behavior and cognition, which are not well characterized. In this work, we investigate the significance and trends of epileptiform biomarkers in animal and human models of epilepsy. We develop reliable methods to quantify interictal patterns, applying state of the art techniques from machine learning, signal processing, and EEG analysis. We then validate these tools in three major applications: 1. We study the effect of interictal spikes on human cognition, 2. We assess trends of interictal epileptiform bursts and their relationship to seizures in prolonged recordings from canines and rats, and 3. We assess the stability of long-term iEEG spanning several years. These findings have two main impacts: (1) they inform the interpretation of interictal iEEG patterns and elucidate the timescale of post-implantation changes. These findings have important implications for research and clinical care, particularly implantable devices and evaluating patients for epilepsy surgery. (2) They provide an analytical framework to enable others to mine large-scale iEEG datasets. In this way we hope to make a lasting contribution to accelerate collaborative research not only in epilepsy, but also in the study of animal and human electrophysiology in acute and chronic conditions

Decoding Neural Signals with Computational Models: A Systematic Review of Invasive BMI

There are significant milestones in modern human's civilization in which mankind stepped into a different level of life with a new spectrum of possibilities and comfort. From fire-lighting technology and wheeled wagons to writing, electricity and the Internet, each one changed our lives dramatically. In this paper, we take a deep look into the invasive Brain Machine Interface (BMI), an ambitious and cutting-edge technology which has the potential to be another important milestone in human civilization. Not only beneficial for patients with severe medical conditions, the invasive BMI technology can significantly impact different technologies and almost every aspect of human's life. We review the biological and engineering concepts that underpin the implementation of BMI applications. There are various essential techniques that are necessary for making invasive BMI applications a reality. We review these through providing an analysis of (i) possible applications of invasive BMI technology, (ii) the methods and devices for detecting and decoding brain signals, as well as (iii) possible options for stimulating signals into human's brain. Finally, we discuss the challenges and opportunities of invasive BMI for further development in the area.Comment: 51 pages, 14 figures, review articl

Epileptic Seizure Detection And Prediction From Electroencephalogram Using Neuro-Fuzzy Algorithms

This dissertation presents innovative approaches based on fuzzy logic in epileptic seizure detection and prediction from Electroencephalogram (EEG). The fuzzy rule-based algorithms were developed with the aim to improve quality of life of epilepsy patients by utilizing intelligent methods. An adaptive fuzzy logic system was developed to detect seizure onset in a patient specific way. Fuzzy if-then rules were developed to mimic the human reasoning and taking advantage of the combination in spatial-temporal domain. Fuzzy c-means clustering technique was utilized for optimizing the membership functions for varying patterns in the feature domain. In addition, application of the adaptive neuro-fuzzy inference system (ANFIS) is presented for efficient classification of several commonly arising artifacts from EEG. Finally, we present a neuro-fuzzy approach of seizure prediction by applying the ANFIS. Patient specific ANFIS classifier was constructed to forecast a seizure followed by postprocessing methods. Three nonlinear seizure predictive features were used to characterize changes prior to seizure. The nonlinear features used in this study were similarity index, phase synchronization, and nonlinear interdependence. The ANFIS classifier was constructed based on these features as inputs. Fuzzy if-then rules were generated by the ANFIS classifier using the complex relationship of feature space provided during training. In this dissertation, the application of the neuro-fuzzy algorithms in epilepsy diagnosis and treatment was demonstrated by applying the methods on different datasets. Several performance measures such as detection delay, sensitivity and specificity were calculated and compared with results reported in literature. The proposed algorithms have potentials to be used in diagnostics and therapeutic applications as they can be implemented in an implantable medical device to detect a seizure, forecast a seizure, and initiate neurostimulation therapy for the purpose of seizure prevention or abortion

Expert and deep learning model identification of iEEG seizures and seizure onset times

Hundreds of 90-s iEEG records are typically captured from each NeuroPace RNS System patient between clinic visits. While these records provide invaluable information about the patient’s electrographic seizure and interictal activity patterns, manually classifying them into electrographic seizure/non-seizure activity, and manually identifying the seizure onset channels and times is an extremely time-consuming process. A convolutional neural network based Electrographic Seizure Classifier (ESC) model was developed in an earlier study. In this study, the classification model is tested against iEEG annotations provided by three expert reviewers board certified in epilepsy. The three experts individually annotated 3,874 iEEG channels from 36, 29, and 35 patients with leads in the mesiotemporal (MTL), neocortical (NEO), and MTL + NEO regions, respectively. The ESC model’s seizure/non-seizure classification scores agreed with the three reviewers at 88.7%, 89.6%, and 84.3% which was similar to how reviewers agreed with each other (92.9%–86.4%). On iEEG channels with all 3 experts in agreement (83.2%), the ESC model had an agreement score of 93.2%. Additionally, the ESC model’s certainty scores reflected combined reviewer certainty scores. When 0, 1, 2 and 3 (out of 3) reviewers annotated iEEG channels as electrographic seizures, the ESC model’s seizure certainty scores were in the range: [0.12–0.19], [0.32–0.42], [0.61–0.70], and [0.92–0.95] respectively. The ESC model was used as a starting-point model for training a second Seizure Onset Detection (SOD) model. For this task, seizure onset times were manually annotated on a relatively small number of iEEG channels (4,859 from 50 patients). Experiments showed that fine-tuning the ESC models with augmented data (30,768 iEEG channels) resulted in a better validation performance (on 20% of the manually annotated data) compared to training with only the original data (3.1s vs 4.4s median absolute error). Similarly, using the ESC model weights as the starting point for fine-tuning instead of other model weight initialization methods provided significant advantage in SOD model validation performance (3.1s vs 4.7s and 3.5s median absolute error). Finally, on iEEG channels where three expert annotations of seizure onset times were within 1.5 s, the SOD model’s seizure onset time prediction was within 1.7 s of expert annotation

Automatic Detection and Classification of Neural Signals in Epilepsy

The success of an epilepsy treatment, such as resective surgery, relies heavily on the accurate identification and localization of the brain regions involved in epilepsy for which patients undergo continuous intracranial electroencephalogram (EEG) monitoring. The prolonged EEG recordings are screened for two main biomarkers of epilepsy: seizures and interictal spikes. Visual screening and quantitation of these two biomarkers in voluminous EEG recordings is highly subjective, labor-intensive, tiresome and expensive. This thesis focuses on developing new techniques to detect and classify these events in the EEG to aid the review of prolonged intracranial EEG recordings. It has been observed in the literature that reliable seizure detection can be made by quantifying the evolution of seizure EEG waveforms. This thesis presents three new computationally simple non-patient-specific (NPS) seizure detection systems that quantify the temporal evolution of seizure EEG. The first method is based on the frequency-weighted-energy, the second method on quantifying the EEG waveform sharpness, while the third method mimics EEG experts. The performance of these new methods is compared with that of three state-of-the-art NPS seizure detection systems. The results show that the proposed systems outperform these state-of-the-art systems. Epilepsy therapies are individualized for numerous reasons, and patient-specific (PS) seizure detection techniques are needed not only in the pre-surgical evaluation of prolonged EEG recordings, but also in the emerging neuro-responsive therapies. This thesis proposes a new model-based PS seizure detection system that requires only the knowledge of a template seizure pattern to derive the seizure model consisting of a set of basis functions necessary to utilize the statistically optimal null filters (SONF) for the detection of the subsequent seizures. The results of the performance evaluation show that the proposed system provides improved results compared to the clinically-used PS system. Quantitative analysis of the second biomarker, interictal spikes, may help in the understanding of epileptogenesis, and to identify new epileptic biomarkers and new therapies. However, such an analysis is still done manually in most of the epilepsy centers. This thesis presents an unsupervised spike sorting system that does not require a priori knowledge of the complete spike data

Seizure Detection, Seizure Prediction, and Closed-Loop Warning Systems in Epilepsy

Nearly one-third of patients with epilepsy continue to have seizures despite optimal medication management. Systems employed to detect seizures may have the potential to improve outcomes in these patients by allowing more tailored therapies and might, additionally, have a role in accident and SUDEP prevention. Automated seizure detection and prediction require algorithms which employ feature computation and subsequent classification. Over the last few decades, methods have been developed to detect seizures utilizing scalp and intracranial EEG, electrocardiography, accelerometry and motion sensors, electrodermal activity, and audio/video captures. To date, it is unclear which combination of detection technologies yields the best results, and approaches may ultimately need to be individualized. This review presents an overview of seizure detection and related prediction methods and discusses their potential uses in closed-loop warning systems in epilepsy

From Fuzzy Expert System to Artificial Neural Network: Application to Assisted Speech Therapy

This chapter addresses the following question: What are the advantages of extending a fuzzy expert system (FES) to an artificial neural network (ANN), within a computer‐based speech therapy system (CBST)? We briefly describe the key concepts underlying the principles behind the FES and ANN and their applications in assisted speech therapy. We explain the importance of an intelligent system in order to design an appropriate model for real‐life situations. We present data from 1‐year application of these concepts in the field of assisted speech therapy. Using an artificial intelligent system for improving speech would allow designing a training program for pronunciation, which can be individualized based on specialty needs, previous experiences, and the child\u27s prior therapeutical progress. Neural networks add a great plus value when dealing with data that do not normally match our previous designed pattern. Using an integrated approach that combines FES and ANN allows our system to accomplish three main objectives: (1) develop a personalized therapy program; (2) gradually replace some human expert duties; (3) use “self‐learning” capabilities, a component traditionally reserved for humans. The results demonstrate the viability of the hybrid approach in the context of speech therapy that can be extended when designing similar applications

Slow-wave activity in the S1HL cortex is contributed by different layer-specific field potential sources during development

Spontaneous correlated activity in cortical columns is criticalfor postnatal circuit refinement.We used spatial discriminationtechniques to explore the late maturation of synaptic pathways through the laminar distribution of the field potential (FP) generators underlying spontaneous and evoked activities ofthe S1HL cortex in juvenile (P14 –P16) and adult anesthetized rats. Juveniles exhibit an intermittent FP pattern resembling Up/Down states in adults, but with much reduced power and different laminar distribution. Whereas FPs in active periods are dominated by a layer VI generator in juveniles, in adults a developing multipart generatortakes over, displaying current sinks in middle layers (III–V). The blockade of excitatory transmission in upper and middle layers of adults recovered the juvenile-like FP profiles. In additiontothe layer VI generator, a gamma-specific generator in supragranular layers wasthe same in both age groups.While searching for dynamical coupling among generators in juveniles we found significant cross-correlation in one-half of the tested pairs, whereas excessive coherence hindered their efficient separation in adults. Also, potentials evoked by tactile and electrical stimuli showed different short-latency dipoles between the two age groups, and the juveniles lacked the characteristic long latency UP state currents in middle layers. In addition, the mean firing rate of neurons was lower in juveniles. Thus, cortical FPs originate from different intracolumnar segments as they become active postnatally. We suggest that although some cortical segments are active early postnatally, a functional sensory-motor control relies on a delayed maturation and network integration of synaptic connections in middle layers

UNSUPERVISED CLASSIFICATION OF HIGH-FREQUENCY OSCILLATIONS IN NEOCORTICAL EPILEPSY AND CONTROL PATIENTS

Quality of life for the more than 15 million people with drug-resistant epilepsy is tied to how precisely the brain areas responsible for generating their seizures can be localized. High-frequency (100-500 Hz) field-potential oscillations (HFOs) are emerging as a candidate biomarker for epileptogenic networks, but quantitative HFO studies are hampered by selection bias arising out of the need to reduce large volumes of data in the absence of capable automated processing methods. In this thesis, I introduce and evaluate an algorithm for the automatic detection and classification of HFOs that can be deployed without human intervention across long, continuous data records from large numbers of patients. I then use the algorithm in analyzing unique macro- and microelectrode intracranial electroencephalographic recordings from human neocortical epilepsy patients and controls. A central finding is that one class of HFOs discovered by the algorithm (median bandpassed spectral centroid ~140 Hz) is more prevalent in the seizure onset zone than outside. The outcomes of this work add to our understanding of epileptogenic networks and are suitable for near-term translation into improved surgical and device-based treatments